Details of a Researcher - SAITOU Tsuyoshi

Papers - SAITOU Tsuyoshi

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Large number of CD68+/CD163+ Hofbauer cells and characteristic vascular structural alterations in the placental villi of cases with placenta accreta spectrum.

Hazuki Kashiwagi, Kengo Shigehara, Terufumi Kubo, Yoshihiko Hirohashi, Tasuku Mariya, Kazuhiko Matsuo, Tomoyuki Minowa, Shin-Ichi Ishioka, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Toshihiko Torigoe

Medical molecular morphology 2025.03 [Domestic journal]

Placenta accreta spectrum (PAS) is a serious disease leading to complications and maternal death. The objective of the study was to characterize the placental villi and blood vessels of PAS villi histopathologically. We investigated 10 cases of PAS (five cases of placenta increta, two cases of placenta accreta, and three cases of placenta percreta) histologically. Immunohistochemical staining using anti-CD68 or anti-CD163 antibodies was performed to detect and count Hofbauer cells. Immunohistochemical staining with an anti-CD34 antibody was used to detect vascular endothelial cells, and the number and area of vessels were analyzed. The numbers of CD68-positive or CD163-positive Hofbauer cells were larger in PAS cases compared with control cases. The vascular area in villi was smaller in PAS cases compared with control cases. The number of blood vessels in villi was slightly higher in PAS cases than in control cases. The numbers of Hofbauer cells and vessels in villi were larger in PAS cases compared with control cases, whereas the area of vessels in villi was smaller in PAS cases compared with control cases. Although their biological meaning is elusive, these findings provide novel insights into the pathogenesis of PAS, particularly regarding the role of Hofbauer cells in immune-suppressive role and angiogenesis and the alterations in vascular structure and hemodynamics in the chorionic villi.

DOI PubMed

Maternal age and the rising incidence of hypertensive disorders of pregnancy: A comprehensive analysis of national claims data from Japan.

Naomi Maeda, Masayuki Koyama, Shintaro Takatsuka, Keisuke Oyatani, Nobuaki Himuro, Tasuku Mariya, Yoshika Kuno, Shiro Hinotsu, Tsuyoshi Saito, Hirofumi Ohnishi

PloS one 20 ( 2 ) e0319177 2025 [International journal]

BACKGROUND: Hypertensive disorders of pregnancy (HDP) significantly increase the risk of developing hypertension and cardiovascular disease (CVD) later in life and are a major cause of maternal mortality. However, little is known about the nationwide, long-term, all-inclusive status of HDP. OBJECTIVE: To estimate the incidence of HDP from 2011 to 2019 in Hokkaido, Japan, with a focus on age groups. METHODS: Using National Database (NDB) insurance medical data, a retrospective analysis was conducted. Due to the absence of direct pregnancy data, birth numbers were used as a surrogate for the number of pregnant women to calculate the incidence of HDP. RESULTS: The average incidence rate of HDP over 9 years was 6.37%. The incidence rate was lowest among women aged 25-29 years, at 5.58% (95% confidence interval [CI]: 5.43-5.73), and increased with age, peaking at 10.58% (95% CI: 10.10-11.09) among women over 40 years. Notably, the incidence rate for women under 20 years of age was 6.70% (95% CI: 5.97-7.51), which was higher than that for women in their 20s. A mean annual increase of 0.25% in age-adjusted incidence was observed during this period, which was statistically significant (R² = 0.87, p < 0.01). CONCLUSION: This study reveals that the risk of developing HDP is associated with both older childbearing and younger pregnancies and follows a J-curve, suggesting that factors other than maternal aging also contribute to the increased incidence of HDP and that further research on risk factors for HDP, which is on the rise worldwide, is urgently needed.

DOI PubMed

Identification and phenotypic characterization of neoantigen-specific cytotoxic CD4+ T cells in endometrial cancer

Minami Fusagawa, Serina Tokita, Kenji Murata, Tasuku Mariya, Mina Umemoto, Shintaro Sugita, Kazuhiko Matsuo, Yoshihiko Hirohashi, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe

Cancer Immunology Research ( American Association for Cancer Research (AACR) ) 2024.12

Abstract Tumor-reactive CD4+ T cells often accumulate in the tumor microenvironment (TME) in human cancer, but their functions and roles in antitumor responses remain elusive. Here, we investigated the immunopeptidome of HLA class II–positive (HLA-II+) endometrial cancer with an inflamed TME using a proteogenomic approach. We identified HLA-II neoantigens, one of which induced polyclonal CD4+ tumor-infiltrating lymphocyte (TIL) responses. We then experimentally demonstrated that neoantigen-specific CD4+ TILs lyse target cells in an HLA-II–dependent manner. Single cell transcriptomic analysis of the TME coupled with T-cell receptor (TCR) sequencing revealed the presence of CD4+ T-cell clusters characterized by CXCL13 expression. The CXCL13+ clusters contained two subclusters with distinct cytotoxic gene expression patterns. The identified neoantigen-specific CD4+ T cells were found exclusively in one of the CXCL13+ subclusters characterized by granzyme B and CCL5 expression. These results demonstrate the involvement of tumor-reactive CD4+ T cells with cytotoxic function in immune surveillance of endometrial cancer and reveal their transcriptomic signature.

DOI

【エネルギーデバイスアラカルト-知っておきたい使い方の留意点と技術革新】総論モードの特性と使い分け

玉手雅人, 松浦基樹, 齋藤豪

臨床婦人科産科 ( (株)医学書院 ) 78 ( 12 ) 1083 - 1090 2024.12

＜文献概要＞●電気メスのモードと本体の使い分け:電気メスの効果と性能は,モードと出力設定で変化するが,電気メスを接続する本体の種類によっても異なる.●他の手術機器との使い分け,バイポーラ・アドバンスドバイポーラ・バイクランプの使い分け:電気メス,バイポーラ,アドバンスドバイポーラ,超音波凝固切開装置の組み合わせは術式・手技・コストで考慮する.●機械の特性を理解して,術者が自身の技量や手術スタイルに合わせてエネルギーデバイスを扱うことが重要と思われる.

【エネルギーデバイスアラカルト-知っておきたい使い方の留意点と技術革新】各種デバイスの原理・有用性と使用上の注意点シーリングデバイス

松浦基樹, 玉手雅人, 齋藤豪

臨床婦人科産科 ( (株)医学書院 ) 78 ( 12 ) 1104 - 1111 2024.12

＜文献概要＞●シーリングデバイスは直径7mmまでの血管や組織束がシール可能であり,超音波凝固切開装置より太い血管をシールすることができる.●シーリングデバイスは高周波エネルギーを瞬時に供給して血管のシールを行うため,手術効率が向上するだけではなく,熱の拡散を極力抑えることで周囲の組織への影響を最小限に抑えることができる.●外科医は各デバイスの原理や有用性・注意点などを習熟したうえで,これらのデバイスを使用するべきである.

Impact of colposcopy-guided carbon dioxide laser vaporization therapy on peripheral cervical intraepithelial neoplasia lesions.

Tasuku Mariya, Akira Nishikawa, Mina Umemoto, Shiori Ogawa, Tsuyoshi Saito

Taiwanese journal of obstetrics & gynecology 63 ( 6 ) 846 - 852 2024.11 [International journal]

OBJECTIVE: Laser vaporization is less invasive than conization for cervical intraepithelial neoplasia (CIN). The outcome of laser vaporization for CIN is empirically known to depend on the colposcopic findings, especially localization of the lesion. In this study, we sought to identify factors involved in the outcome of laser vaporization. MATERIALS AND METHODS: We retrospectively investigated 290 cases of CIN (CIN2, n = 180; CIN3, n = 110) treated with laser evaporation at Nishikawa Women's Health Clinic between 2018 and 2021. All treatments were performed using a carbon dioxide laser under either colposcopic vision (n = 172) or direct vision using a vaginal speculum (n = 118). Risk factors were statistically examined for cure rate after treatment. RESULTS: Multivariate analysis using a logistic regression model identified independent factors affecting the success of treatment to be high-risk human papillomavirus infection status preoperatively, CIN grade, presence of CIN lesions at the periphery of the cervix, and the surgical method used. Colposcopy-guided laser vaporization reduced the risk of treatment failure by 84% (odds ratio 0.16, 95% confidence interval 0.06-0.46; p = 0.001) compared with direct vision using a vaginal speculum. For lesions at the periphery of the cervix, most of the treatment failures were in the group that was not guided by colposcopy (p = 0.031). CONCLUSION: The presence of a peripheral CIN lesion was suggested to be a risk factor for treatment failure. Laser vaporization under colposcopic vision is recommended for treatment of peripheral CIN lesions.

DOI PubMed

妊娠初期BVスクリーニング・治療による早産予防は、実臨床では、容易な仕事ではない

島野敏司, 山田俊, 長和俊, 千石一雄, 田村保明, 真里谷奨, 齋藤豪

日本性感染症学会誌 ( (一社)日本性感染症学会 ) 35 ( Suppl. ) 118 - 118 2024.11

Human papillomavirus self-sampling and urine-sampling tests and the management and short-term outcomes of cervical intraepithelial neoplasia: A prospective observational study.

Motoki Matsuura, Masato Tamate, Sachiko Nagao, Taishi Akimoto, Fukiko Kasuga, Kimihito Saito, Satoshi Shikanai, Yoko Nishimura, Mizue Teramoto, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 50 ( 10 ) 1801 - 1807 2024.10 [International journal]

AIM: The importance of human papillomavirus (HPV) co-testing using physician-, self-, and urine-collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1-2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1-2 who simultaneously underwent physician-, self-, and urine-collection sampling tests. METHODS: This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1-2 progressions, the percentage of cases with persistent CIN 1-2, and the outcome differences according to the results of physician-, self-, and urine-sampling tests. RESULTS: There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow-up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV-positive physician- and self-collected samples. No significant difference was observed between cases with CIN 2 who had HPV-positive and HPV-negative results using any sampling method. CONCLUSIONS: Physician- and self-testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted.

DOI PubMed

Successful Outcome of Stage IB3 Cervical Cancer Treated With Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy: A Case Report.

Masato Tamate, Motoki Matsuura, Masayuki Someya, Tasuku Mariya, Shinichi Ishioka, Tsuyoshi Saito

Cureus 16 ( 10 ) e71626 2024.10 [International journal]

Vaginal trachelectomy, which involves resecting the cervix and its parametrium, is a fertility-sparing option for the treatment of early-stage cervical cancer. Although no consensus has been reached on whether simple or radical trachelectomy is preferable, the vaginal approach is typically avoided for tumors larger than 2 cm due to concerns about recurrence. However, some evidence suggests that fertility preservation may still be viable for select patients with larger tumors. This case report describes a woman with bulky cervical cancer who wished to preserve her fertility. After undergoing neoadjuvant chemotherapy (NAC) and vaginal radical trachelectomy (VRT), she achieved a favorable oncological and perinatal outcome, successfully giving birth to a near-full-term baby. The report outlines the patient's management before, during, and after the procedure, including perinatal care. While careful selection of candidates is crucial, accumulating case reports and future trials are expected to shed more light on this treatment approach.

DOI PubMed

Risk-reducing salpingo-oophorectomy for hereditary breast and ovarian cancer patients with vaginal natural orifice transluminal endoscopic surgery (vNOTES).

Masato Tamate, Motoki Matsuura, Sachiko Nagao, Shoko Kurokawa, Taishi Akimoto, Tsuyoshi Saito

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2024.09 [International journal]

DOI PubMed

Identification of immunogenic HLA class I and II neoantigens using surrogate immunopeptidomes.

Serina Tokita, Minami Fusagawa, Satoru Matsumoto, Tasuku Mariya, Mina Umemoto, Yoshihiko Hirohashi, Fumitake Hata, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe

Science advances 10 ( 38 ) eado6491 2024.09 [International journal]

Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE). This approach uses an autologous wild-type immunopeptidome as a surrogate for the tumor immunopeptidome and allows human leukocyte antigen (HLA)-agnostic identification of both HLA class I (HLA-I) and HLA class II (HLA-II) neoantigens. We demonstrate the direct identification of highly immunogenic HLA-I and HLA-II neoantigens using NESSIE in patients with colorectal cancer and endometrial cancer. Fresh or frozen tumor samples are not required for analysis, making it applicable to many patients in clinical settings. We also demonstrate tumor prevention by vaccination with selected neoantigens in a preclinical mouse model. This approach may benefit personalized T cell-mediated immunotherapies.

DOI PubMed

Microbiological investigation of pregnancies following vaginal radical trachelectomy using 16S rRNA sequencing of FFPE placental specimens.

Risa Tsunematsu, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Wataru Arai, Suguru E Tanaka, Kyota Ashikawa, Terufumi Kubo, Yoshiyuki Sakuraba, Tsuyoshi Baba, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Saito

FEBS open bio 2024.09 [International journal]

This study examined the risk of intrauterine infection associated with radical trachelectomy (RT) in early-stage cervical cancer patients. This procedure preserves fertility but is linked to increased risk of intrauterine infection due to cervical defects during pregnancy. DNA was extracted from the formalin-fixed paraffin-embedded (FFPE) placental specimens of 23 pregnant post-RT patients and 16S rRNA gene sequencing was used for bacterial identification. The prevalence of Lactobacillus crispatus and Burkholderia stabilis was significantly higher in the non-chorioamnionitis group. In contrast, alpha diversity analysis using the PD index showed significantly higher diversity in the chorioamnionitis group (P = 0.04). The demonstrated relationship between chorioamnionitis and microbial diversity affirms the importance of controlling the genital bacterial flora in pregnancies following RT.

DOI PubMed

Step-by-step demonstration of "sciatic-nerve-preserved beyond-LEER" in a Thiel-embalmed cadaver: a novel salvage surgery for recurrent gynecologic malignancies.

Hiroyuki Kanao, Masato Tamate, Motoki Matsuura, Sachiko Nagao, Miseon Nakazawa, Shutaro Habata, Tsuyoshi Saito

Journal of gynecologic oncology 35 ( 5 ) e112 2024.09 [International journal]

OBJECTIVE: Complete resection is the curative treatment choice for recurrent gynecological malignancies. Laterally extended endopelvic resection (LEER) is an effective surgical salvage therapy for lateral recurrence. However, when a recurrent tumor occupies the ischial spine and sacrum, LEER is not indicated, and surgical salvage therapy is abandoned. Theoretically, complete resection of such a tumor is possible by additional pelvic bone resection along with the standard LEER. Nevertheless, owing to the anatomical complexities of the beyond-LEER procedure, 2 major issues should be solved: sciatic nerve injury and tumor disruption during pelvic bone amputation. To overcome these technical challenges, we applied a multidirectional beyond-LEER approach, a novel salvage surgical procedure, with an aim of demonstrating its technical feasibility. METHODS: We created a simulation model of a laterally recurrent tumor that occupied the right ischial spine and sacrum in a Thiel-embalmed cadaver. RESULTS: Multidirectional approaches, including laparoscopic, perineal, and dorsal phases, were safely applied. We laparoscopically marked the L4-L5-S1 complex and S2 nerve with different colored tapes, and by pulling them out into a dorsal surgical field, the sciatic nerve was safely preserved. The dissection lines of the multidirectional approaches were aligned using tapes as landmarks, and complete tumor clearance without tumor disruption was accomplished. By following the cadaveric training, the first laparoscopic-assisted beyond-LEER procedure was successfully performed in a patient with recurrent ovarian cancer. CONCLUSION: Using a Thiel-embalmed cadaver, we demonstrated the technical feasibility of a sciatic nerve-preserved beyond-LEER procedure, which was successfully performed in a patient with recurrent ovarian cancer.

DOI PubMed

IB3期の子宮頸癌に対して術前化学療法後に広汎子宮頸部摘出術を施行し分娩となった1例

佐藤冴子, 染谷真行, 玉手雅人, 松浦基樹, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 71回 48 - 48 2024.09

ロボット支援子宮全摘出術での発光式尿管カテーテルと子宮トランスイルミネーターの使用経験

幅田周太朗, 黒川晶子, 有元千紘, 長尾沙智子, 玉手雅人, 秋元太志, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 71回 78 - 78 2024.09

【産婦人科領域における情報リテラシー-ビッグデータとバイオインフォマティクスの活用】婦人科腫瘍領域におけるAIの活用

梅本美菜, 真里谷奨, 南部優太, 藤野雄一, 鳥越俊彦, 齋藤豪

産婦人科の実際 ( 金原出版(株) ) 73 ( 8 ) 829 - 833 2024.08

＜文献概要＞AI(人工知能),なかでも深層学習(deep learning)を用いた技術は,医療においても数多くの分野で応用が試みられている。産婦人科領域においてもそれは決して例外ではない。扱う対象データを画像,病理画像や放射線画像,ならびに内視鏡画像に絞ったとしても,多種多様な検討が行われてきた。本稿では,AI全体の潮流についても触れつつ,婦人科腫瘍領域のなかでも特に深層学習を用いた病理診断,細胞診および組織診にまつわるAIの活用について述べる。

【産婦人科領域における情報リテラシー-ビッグデータとバイオインフォマティクスの活用】婦人科腫瘍領域におけるAIの活用

梅本美菜, 真里谷奨, 南部優太, 藤野雄一, 鳥越俊彦, 齋藤豪

産婦人科の実際 ( 金原出版(株) ) 73 ( 8 ) 829 - 833 2024.08

当院における類内膜癌G3症例の細胞診・病理形態学的評価と臨床経過の検討

幅田周太朗, 齋藤晋平, 有元千紘, 野藤五沙, 長尾沙智子, 黒川晶子, 玉手雅人, 真里谷奨, 秋元太志, 松浦基樹, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 66回 327 - 327 2024.07

婦人科HBOC専門外来の設置・運用によるクライエントの意思決定支援への効果の検証

古来愛香, 真里谷奨, 田中佑弥, 小松茅乃, 宮崎幸子, 石川亜貴, 齋藤豪, 櫻井晃洋

日本遺伝カウンセリング学会誌 ( (一社)日本遺伝カウンセリング学会 ) 45 ( 2 ) 120 - 120 2024.07

Analysis of Treatment Response With Proteins Related to Tumor Immunity in Postoperative Irradiated Cervical Cancer Patients.

Shoh Mafune, Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Ryu Okuda, Masahiro Iwasaki, Motoki Matsuura, Terufumi Kubo, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsuyoshi Saito, Koh-Ichi Sakata

Anticancer research 44 ( 7 ) 3077 - 3086 2024.07 [International journal]

BACKGROUND/AIM: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. PATIENTS AND METHODS: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. RESULTS: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. CONCLUSION: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.

DOI PubMed

当院における類内膜癌G3症例の細胞診・病理形態学的評価と臨床経過の検討

幅田周太朗, 齋藤晋平, 有元千紘, 野藤五沙, 長尾沙智子, 黒川晶子, 玉手雅人, 真里谷奨, 秋元太志, 松浦基樹, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 66回 327 - 327 2024.07

当院における再発子宮体癌に対するPembrolizumab+Lenvatinibの使用経験

長尾沙智子, 松浦基樹, 黒川晶子, 玉手雅人, 秋元太志, 幅田周太朗, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 66回 405 - 405 2024.07

The roles of tight junction protein cingulin in human endometrioid endometrial cancer.

Arisa Kura, Kimihito Saito, Takumi Konno, Takayuki Kohno, Hiroshi Shimada, Tadahi Okada, Soshi Nishida, Daichi Ishii, Motoki Matsuura, Tsuyoshi Saito, Takashi Kojima

Tissue barriers 2361976 - 2361976 2024.06 [International journal]

The bicellular tight junction molecule cingulin (CGN) binds to microtubules in centrosomes. Furthermore, CGN contributes to the tricellular tight junction (tTJ) proteins lipolysis-stimulated lipoprotein receptor (LSR) and tricellulin (TRIC). CGN as well as LSR decreased during the malignancy of endometrioid endometrial cancer (EEC). Although tTJ protein LSR is involved in the malignancy of some cancers, including EEC, the role of CGN is unknown. In this study, we investigated the roles of CGN with tTJ proteins in human EEC cells by using the CGN-overexpressing EEC cell line Sawano. In 2D cultures, CGN was colocalized with LSR and TRIC at tTJ or at γ-tubulin-positive centrosomes. In immunoprecipitation with CGN antibodies, CGN directly bound to LSR, TRIC, and β-tubulin. Knockdown of CGN by the siRNA decreased the epithelial barrier and enhanced cell proliferation, migration and invasion, as well as knockdown of LSR. In the Sawano cells cocultured with normal human endometrial stromal cells, knockdown of CGN decreased expression of LSR and TRIC via MAPK and AMPK pathways. In 2.5D cultures, knockdown of CGN induced the formation of abnormal cysts and increased the permeability of FD-4 to the lumen. In 2D and 2.5D cultures, treatment with β-estradiol with or without EGF or TGF-β decreased CGN expression and the epithelial permeability barrier and enhanced cell migration, and pretreatment with EW7197+AG1478, U0126 or an anti-IL-6 antibody prevented this. In conclusion, CGN, with tTJ proteins might suppress the malignancy of human EEC and its complex proteins are sensitive to estrogen and growth factors derived from stromal cells.

DOI PubMed

低置胎盤の分娩管理の変化と,それに伴う周産期転帰の変化について

染谷真行, 古来愛香, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 60 ( Suppl.1 ) P382 - P382 2024.06

妊娠中期に多量出血を伴わずに原因不明の産科DICを発症した2例

齋藤晋平, 染谷真行, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 60 ( Suppl.1 ) P336 - P336 2024.06

妊娠後期に急性腹症と肝酵素上昇を認め,総胆管結石として待機的管理を行った1例

宮下夕稀子, 染谷真行, 真里谷奨, 馬場剛, 石岡伸一, 岡村直樹, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 60 ( Suppl.1 ) P395 - P395 2024.06

hinotoriを用いた婦人科ロボット支援手術

長尾沙智子, 松浦基樹, 黒川晶子, 玉手雅人, 秋元太志, 諸井明仁, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 150 - 150 2024.06

vNOTESの可能性を広げる術式の研究

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 諸井明仁, 秋元太志, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 143 - 143 2024.06

vNOTESを導入する際の諸問題 vNOTES,船頭多くして船海に出るために

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 諸井明仁, 秋元太志, 幅田周太朗, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 137 - 137 2024.06

日本におけるCSTの現状,産婦人科CSTにおける役割

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 秋元太志, 幅田周太朗, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 121 - 121 2024.06

日本におけるCSTの現状,産婦人科CSTにおける役割

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 秋元太志, 幅田周太朗, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 121 - 121 2024.06

vNOTESの可能性を広げる術式の研究

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 諸井明仁, 秋元太志, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 143 - 143 2024.06

vNOTESを導入する際の諸問題 vNOTES,船頭多くして船海に出るために

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 諸井明仁, 秋元太志, 幅田周太朗, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 137 - 137 2024.06

hinotoriを用いた婦人科ロボット支援手術

長尾沙智子, 松浦基樹, 黒川晶子, 玉手雅人, 秋元太志, 諸井明仁, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 35 ) 150 - 150 2024.06

Early outcomes of three new robotic surgical systems in patients undergoing hysterectomy.

Motoki Matsuura, Sachiko Nagao, Shoko Kurokawa, Masato Tamate, Taishi Akimoto, Tsuyoshi Saito

Updates in surgery 2024.05 [International journal]

New robot models, such as hinotori™, da Vinci SP™, and Hugo™, have been introduced in Japan. This study examined the surgical outcomes of these models in patients from the initial stages of their introduction to the present day.We retrospectively reviewed 36 patients with endometrial cancer or benign gynecologic disease, who underwent robotic hysterectomy using da Vinci SP™, hinotori™, or Hugo™ between March 2023 and March 2024.Robotic hysterectomy was performed using hinotori™ in 10 patients, da Vinci SP™ in 16 patients, and Hugo™ in 10 patients. No significant differences were observed in the characteristics of the patients subjected to surgery using these models. The total operative time was 123.0 min (93-144 min) for hinotori™, 95.0 min (79-165 min) for da Vinci SP™, and 98.5 min (74-177 min) for Hugo™. The total operative time of hinotori™ was significantly longer than that of the other two models (p = 0.031). No differences were observed among the robot systems with respect to complications during or after surgery and the intensity of postoperative pain.Differences in the surgical time were noted depending on the model used. It has been proven that surgeons who are already proficient in performing robotic surgery with da Vinci Xi™ can safely perform surgeries with the new models.

DOI PubMed

Surgical Outcomes of da Vinci Xi™ and da Vinci SP™ for Early-Stage Endometrial Cancer in Patients Undergoing Hysterectomy.

Motoki Matsuura, Sachiko Nagao, Shoko Kurokawa, Masato Tamate, Taishi Akimoto, Tsuyoshi Saito

Journal of clinical medicine 13 ( 10 ) 2024.05 [International journal]

Objectives: This study aimed to evaluate and compare the feasibility and outcomes of two robotic hysterectomy (da Vinci Xi™ vs. da Vinci SP™) systems without lymph node dissection in patients with early-stage endometrial cancer, and assess the postoperative recurrence rate and overall survival of patients. Methods: A retrospective review of 84 patients who underwent robotic hysterectomy for endometrial cancer (stage 1A) was conducted. Surgical procedures, patient characteristics, intraoperative measures, and postoperative outcomes were statistically analyzed. A single gynecologist performed all surgeries. Results: Patient characteristics, average age, and body mass index showed no significant differences between the two models. The total operative time was significantly shorter with da Vinci SP™. Recurrence was identified in only one patient operated on with da Vinci Xi™. All patients were alive during analysis, with a median overall survival of 38 and 9 months for da Vinci Xi™ and da Vinci SP™, respectively. Conclusions: Robotic hysterectomy without lymph node dissection appears to be a safe and effective approach for patients with early-stage endometrial cancer. The da Vinci SP offers the advantage of shorter operative times than the da Vinci Xi™. These findings support the consideration of robotic surgery as a viable option for selected patients.

DOI PubMed

Prediction of Mismatch Repair Status in Endometrial Cancer from Histological Slide Images Using Various Deep Learning-Based Algorithms.

Mina Umemoto, Tasuku Mariya, Yuta Nambu, Mai Nagata, Toshihiro Horimai, Shintaro Sugita, Takayuki Kanaseki, Yuka Takenaka, Shota Shinkai, Motoki Matsuura, Masahiro Iwasaki, Yoshihiko Hirohashi, Tadashi Hasegawa, Toshihiko Torigoe, Yuichi Fujino, Tsuyoshi Saito

Cancers 16 ( 10 ) 2024.05 [International journal]

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly for gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

DOI PubMed

北海道における、妊娠初期妊婦、全例での細菌性腟症スクリーニング・治療は早産・超早産を有意に減少させた。

島野敏司, 山田俊, 長和俊, 千石一雄, 田村保明, 真里谷奨, 齋藤豪

日本産婦人科感染症学会誌 ( (一社)日本産婦人科感染症学会 ) 8 ( 1 ) 105 - 105 2024.05

自己採取および尿採取法による腟内HPV検査の患者の受け入れに関する検討

齋藤豪, 松浦基樹, 寺田倫子, 玉手雅人, 高田優子, 西村庸子, 山下真祐子, 諸井明仁

日本女性医学学会雑誌 ( (一社)日本女性医学学会 ) 31 ( 3 ) 404 - 409 2024.04

子宮頸がん検診の受診率向上は喫緊の課題である.自己採取または尿採取腟内HPV検査は複数の介入研究で受診率向上に有効と報告されている.医師採取HPV検査と同等の感度があれば,受診率向上が課題であるわが国において有効な手段となりうる.われわれはこれまで自己採取・尿採取HPV検査の有効性について比較検討研究を行い報告してきたが,本研究ではよりよい自己採取法を目指し,検体採取対象者に対し検査の受け入れに関するアンケート調査を行った.年齢は20～50歳とし,CIN2以上の患者を100名以上含む計300名を対象に研究を行った.アンケート300人中281人が回答し,子宮頸がんについては「知っている」,あるいは,「なんとなく知っている」と答えた人が93.1%,頸がんが検診でがんになる前の段階で見つけることを「知っている」と答えた人は87.9%,頸がんの原因がHPVと言うウイルスの感染であることを「知っている」と答えた人の割合は93.3%といずれも高い割合であった.採取前に38.6%が不安ありと答えたが,すべての患者が採取を完遂し患者にとって受け入れられているものと考えた.頸がんに対する認知度は高いものの検診率の増加に結びついていないことが今後の課題であり,自己採取HPV検査も解決策の一つと考えられた.(著者抄録)

がん患者の妊孕性温存に関する情報提供の現状と課題

古来愛香, 玉手雅人, 馬場剛, 長尾沙智子, 小川万梨絵, 森下美幸, 久野芳佳, 齋藤豪

日本生殖医学会雑誌 ( (一社)日本生殖医学会 ) 69 ( 1-2 ) 121 - 121 2024.04

子宮移植までのマイルストーン

玉手雅人, 馬場剛, 和田渚, 古来愛香, 幅田周太朗, 小川万梨絵, 松浦基樹, 齋藤豪

日本生殖医学会雑誌 ( (一社)日本生殖医学会 ) 69 ( 1-2 ) 122 - 122 2024.04

我々はこうしている～子宮頸癌手術におけるMISの工夫我々が行う子宮頸癌に対する腹腔鏡下広汎子宮全摘術の工夫

松浦基樹, 長尾沙智子, 黒川晶子, 玉手雅人, 秋元太志, 幅田周太朗, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 42 ( 2 ) 114 - 117 2024.04

Placenta Percreta Progression to Resistance Against Uterine Artery Embolization and Penetration Into the Bladder.

Yukiko Miyashita, Tasuku Mariya, Masayuki Someya, Shinichi Ishioka, Tsuyoshi Saito

Cureus 16 ( 3 ) e55651 2024.03 [International journal]

A 31-year-old female sought termination of pregnancy due to a fetal body stalk anomaly diagnosed at 18 weeks of gestation. Despite an anterior placenta previa, successful vaginal delivery occurred. However, placental adhesion over a previous cesarean scar occurred, and part of the placenta could not be removed. Immediate postpartum bleeding prompted imaging studies, revealing extravasation from adherent placental remnants. Uterine artery embolization (UAE) provided initial hemostasis, but recurrent bleeding necessitated re-embolization. Although conservative treatment was initially pursued, significant hematuria prompted reevaluation, revealing extensive uterine wall and bladder penetration. Surgical intervention with total hysterectomy and partial bladder resection was performed, leading to the successful recovery of bladder function following surgical repair. While this case achieved a positive outcome, there is a potential for permanent urinary dysfunction if lesions are more extensive. While achieving a conservative cure is ideal, it is essential to assess the timing for opting for surgical intervention.

DOI PubMed

The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population.

Masashi Idogawa, Tasuku Mariya, Yumi Tanaka, Tsuyoshi Saito, Hiroshi Nakase, Takashi Tokino, Akihiro Sakurai

Journal of human genetics 2024.02 [International journal]

Hereditary breast and ovarian cancer syndrome (HBOC) resulting from pathogenic variants of BRCA1 or BRCA2 is the most common and well-documented hereditary tumor. Although founder variants have been identified in population-based surveys in various countries, the types of variants are not uniform across races and regions. Recently, the Tohoku Medical Megabank Organization (ToMMo) released whole-genome sequence data including approximately 54,000 individuals from the general population of the Tohoku area in Japan. We analyzed these data and comprehensively identified the prevalence of BRCA1/2 pathogenic and truncating variants. We believe that an accurate understanding of the unique distribution and characteristics of pathogenic BRCA1/2 variants in Japan through this analysis will enable better surveillance and intervention for HBOC patients, not only in Japan but also worldwide.

DOI PubMed

当科における最近10年間のCesarean hysterectomy症例の検討

齋藤晋平, 石岡伸一, 新開翔太, 真里谷奨, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 76 ( 臨増 ) S - 592 2024.02

経過観察中に自然軽快した広汎性卵巣浮腫の2症例

馬場剛, 遠藤俊明, 新開翔太, 真里谷奨, 染谷真行, 森下美幸, 岩崎雅宏, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 76 ( 臨増 ) S - 383 2024.02

The interplay between the epithelial permeability barrier, cell migration and mitochondrial metabolism of growth factors and their inhibitors in a human endometrial carcinoma cell line.

Takumi Konno, Takayuki Kohno, Shin Kikuchi, Arisa Kura, Kimihito Saito, Tadahi Okada, Hiroshi Shimada, Yuya Yamazaki, Tomoki Sugiyama, Motoki Matsuura, Yuki Ohsaki, Tsuyoshi Saito, Takashi Kojima

Tissue barriers 2304443 - 2304443 2024.01 [International journal]

It is known that there are abnormalities of tight junction functions, cell migration and mitochondrial metabolism in human endometriosis and endometrial carcinoma. In this study, we investigated the effects of growth factors and their inhibitors on the epithelial permeability barrier, cell migration and mitochondrial metabolism in 2D and 2.5D cultures of human endometrioid endometrial carcinoma Sawano cells. We also investigated the changes of bicellular and tricellular tight junction molecules and ciliogenesis induced by these inhibitors. The growth factors TGF-β and EGF affected the epithelial permeability barrier, cell migration and expression of bicellular and tricellular tight junction molecules in 2D and 2.5D cultures of Sawano cells. EW-7197 (a TGF-β receptor inhibitor), AG1478 (an EGFR inhibitor) and SP600125 (a JNK inhibitor) affected the epithelial permeability barrier, cell migration and mitochondrial metabolism and prevented the changes induced by TGF-β and EGF in 2D and 2.5D cultures. EW-7197 and AG1478 induced ciliogenesis in 2.5D cultures. In conclusion, TGF-β and EGF promoted the malignancy of endometrial cancer via interplay among the epithelial permeability barrier, cell migration and mitochondrial metabolism. EW-7197 and AG1478 may be useful as novel therapeutic treatments options for endometrial cancer.

DOI PubMed

妊孕性温存療法後、胚移植に至った症例に関する検討

久野芳佳, 馬場剛, 齋藤晋平, 古来愛香, 長尾沙智子, 玉手雅人, 小川万梨絵, 森下美幸, 遠藤俊明, 齋藤豪

日本がん・生殖医療学会誌 ( (一社)日本がん・生殖医療学会 ) 7 ( 1 ) 112 - 112 2024.01

Restoration of ARID1A Protein in ARID1A-deficient Clear Cell Carcinoma of the Ovary Attenuates Reactivity to Cytotoxic T Lymphocytes.

Risa Tsunematsu, Aiko Murai, Yuka Mizue, Terufumi Kubo, Tasuku Mariya, Rena Morita, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Tsuyoshi Saito, Toshihiko Torigoe

Cancer genomics & proteomics 21 ( 4 ) 414 - 420 2024 [International journal]

BACKGROUND/AIM: Clear cell carcinoma is a prevalent histological type of ovarian cancer in East Asia, particularly in Japan, known for its resistance to chemotherapeutic agents and poor prognosis. ARID1A gene mutations, commonly found in ovarian clear cell carcinoma (OCCC), contribute to its pathogenesis. Recent data revealed that the ARID1A mutation is related to better outcomes of cancer immunotherapy. Thus, this study aimed to investigate the immunotherapy treatment susceptibility of OCCC bearing ARID1A mutations. MATERIALS AND METHODS: Expression of ARID1A was analyzed using western blotting in ovarian cancer cell lines. OCCC cell lines JHOC-9 and RMG-V were engineered to overexpress NY-ESO-1, HLA-A*02:01, and ARID1A. Sensitivity to chemotherapy and T cell receptor-transduced T (TCR-T) cells specific for NY-ESO-1 was assessed in ARID1A-restored cells compared to ARID1A-deficient wild-type cells. RESULTS: JHOC-9 cells and RMG-V cells showed no expression of ARID1A protein. Overexpression of ARID1A in JHOC-9 and RMG-V cells did not impact sensitivity to gemcitabine. While ARID1A overexpression decreased sensitivity to cisplatin in RMG-V cells, it had no such effect in JHOC-9 cells. ARID1A overexpression reduced the reactivity of NY-ESO-1-specific TCR-T cells, as observed by the IFNγ ESLIPOT assay. CONCLUSION: Cancer immunotherapy is an effective approach to target ARID1A-deficient clear cell carcinoma of the ovary.

DOI PubMed

A Rare Case of Small Intestinal Cancer With Uterine Metastasis After Surgery for Ovarian Metastasis, Diagnosed Using Immunostaining.

Sachiko Nagao, Motoki Matsuura, Shoko Kurokawa, Masato Tamate, Taishi Akimoto, Tsuyoshi Saito

Case reports in oncological medicine 2024 8551816 - 8551816 2024 [International journal]

Uterine metastases from extragenital sites are rare. We present a case of a woman who had undergone surgery for small intestinal cancer and subsequently developed metastases in her left ovary and uterus. A nulliparous woman in her 50s underwent laparoscopic partial small bowel resection with lymph node dissection for small intestinal cancer. Five months later, computed tomography (CT) revealed a left ovarian tumor and ascites. She underwent bilateral adnexectomy and adjuvant chemotherapy, and the ovarian tumor was diagnosed as a small intestinal cancer metastasis. Two years after the small intestinal cancer surgery, a positron emission tomography (PET)-CT scan revealed a uterine accumulation. Cervical cytology was negative for intraepithelial lesion or malignancy. Endometrial histology showed an adenocarcinoma of the uterus. The patient underwent total abdominal hysterectomy followed by adjuvant chemotherapy. Histopathology and immunohistochemistry of the uterine tumor revealed that it was a metastasis of small intestinal cancer (Cytokeratin 7 [CK7] [-], Cytokeratin 20 [CK20] [+], Special AT-Rich Sequence-Binding Protein 2 [SATB2] [+], Paired Box Gene 2 [PAX2] [-], and estrogen receptor [ER] [-]). In patients with cancer, histopathology and immunohistochemistry are important for distinguishing between primary and metastatic tumors and for guiding the choice of treatment.

DOI PubMed

Diagnosis and Methods of Repair for a Uteroperitoneal Fistula (UPF) Formed After Gynecological Surgeries.

Nagisa Wada, Masato Tamate, Motoki Matsuura, Tsuyoshi Saito

Cureus 15 ( 12 ) e51064 2023.12 [International journal]

A uteroperitoneal fistula (UPF) is a rare disorder that can lead to infertility and has never been reported. UPFs can cause infertility and perinatal complications. A 34-year-old woman (gravida 0) with a history of three gynecological surgeries using a uterine manipulator was diagnosed with a UPF using hysteroscopy and hysterosalpingography. She underwent laparoscopic uterine repair as an infertility treatment. The uterine perforation may have been caused by uterine manipulator insertion or suture failure in the myometrium during her previous laparoscopic myomectomy and cystectomy procedures. The UPF disappeared after the current surgical treatment. The complications of UPFs include infection, infertility, ectopic pregnancy, and uterine rupture. We expected that the presence of a fistula would increase the risk of impaired fertilization, implantation failure, and ectopic pregnancy. This case report contributes valuable insights into the diagnosis of UPFs and their laparoscopic repair.

DOI PubMed

婦人科内視鏡技術認定医が不在である当院でのTLHの取り組み

西森貢隆, 嶋田浩志, 藤部佑哉, 鈴木美紀, 玉手雅人, 松浦基樹, 岩崎雅宏, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 67 ( 1 ) 91 - 91 2023.12

分娩後の子宮全摘出術時に発見され,腹膜癌との鑑別が困難であった異所性脱落膜の1例

有元千紘, 長尾沙智子, 山崎智子, 玉手雅人, 高田さくら, 松浦基樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 67 ( 1 ) 85 - 86 2023.12

分娩後の子宮全摘術時に発見され腹膜癌との鑑別が困難であった異所性脱落膜の1例

有元千紘, 長尾沙智子, 堀清貴, 山崎智子, 玉手雅人, 高田さくら, 松浦基樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 67 ( 1 ) 11 - 15 2023.12

異所性脱落膜は,妊娠中の間葉系未分化細胞の化生もしくは子宮内膜症組織などにプロゲステロンが作用することにより生じる。悪性所見と類似した肉眼的所見を呈することがあるため,鑑別や治療方針の決定に難渋することがある。今回我々は,分娩後の子宮全摘術時に偶然発見され,腹膜癌との鑑別が困難であった異所性脱落膜の一例を経験したため,文献的考察とともに報告する。症例は,39歳,2妊1産,妊娠初期に子宮体部後壁に内膜を圧排する粘膜下筋腫を認めていた。妊娠40週0日に陣痛誘発目的に入院し翌日経腟分娩となったが,胎盤娩出後より出血の増加を認めた。経腹超音波検査にて子宮頸部に6cm大の筋腫を認め,筋腫分娩が疑われた。子宮収縮薬投与や子宮用止血バルーン挿入を行ったが止血は得られず,分娩6時間後に子宮全摘術を決定した。術中にダグラス窩,子宮,直腸からS状結腸漿膜面に散在する集簇性小結節を認め,肉眼的には腹膜播種に類似しており腹膜癌などの悪性腫瘍を否定できなかった。子宮全摘術と小結節の一部生検を行い,手術終了とした。病理組織学的検査では異所性脱落膜の診断であり,悪性所見を認めなかった。術後経過問題なく,1週間後に退院となった。異所性脱落膜は悪性腫瘍と類似した所見を呈する場合があるが,確立された鑑別方法はなく,現時点では病理組織学的診断が不可欠である。本邦での報告は稀ではあるが,妊娠中ないし産褥期の女性において悪性腫瘍との鑑別が必要な病態の1つとして異所性脱落膜があることを認識しておくことが重要であると考える。(著者抄録)

内視鏡手術支援ロボット最新事情-開発者と使用者から見た理想と現実、問題点- da Vinci SPが切り拓く婦人科ロボット手術の近未来

松浦基樹, 長尾沙智子, 黒川晶子, 玉手雅人, 秋元太志, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 28 ( 7 ) 981 - 981 2023.12

当科における卵巣組織凍結の報告と北海道内の同技術の認識について

古来愛香, 玉手雅人, 春日芙貴子, 長尾沙智子, 小川万梨絵, 池田桂子, 久野芳佳, 森下美幸, 馬場剛, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 67 ( 1 ) 85 - 85 2023.12

待機療法にて管理したHypervascular RPOCの3例

堀清貴, 山崎智子, 有元千紘, 長尾沙智子, 玉手雅人, 高田さくら, 松浦基樹, 斎藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 67 ( 1 ) 86 - 87 2023.12

腟に発症したPEComaの1例

小谷松紗弓, 松浦基樹, 西村庸子, 秋元太志, 磯山響子, 玉手雅人, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 67 ( 1 ) 89 - 89 2023.12

婦人科良性疾患に対するロボット支援手術の在り方良性婦人科ロボット手術の進むべき道筋

松浦基樹, 長尾沙智子, 黒川晶子, 玉手雅人, 秋元太志, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 28 ( 7 ) 811 - 811 2023.12

子宮内異物・腟閉鎖症例に対して腹腔鏡下子宮全摘術を施行した一例

黒川晶子, 玉手雅人, 西村庸子, 秋元太志, 松浦基樹, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 28 ( 7 ) 3044 - 3044 2023.12

Identification of cancer driver mutations in liquid-based cytology samples for the screening of endometrial diseases

Motoki Matsuura, Kiyoko Takane, Kiyoshi Yamaguchi, Tsuneo Ikenoue, Seira Hatakeyama, Shoko Kurokawa, Masato Tamate, Taishi Akimoto, Masahiro Iwasaki, Shintaro Sugita, Tadashi Hasegawa, Yasunori Ota, Tsuyoshi Saito, Yoichi Furukawa

BJC Reports ( Springer Science and Business Media LLC ) 1 ( 1 ) 2023.11

Abstract Background Endometrial cancer (EC) is one of the leading causes of cancer death among women and early detection is crucial for its successful treatment. We previously showed that cytological examination combined with genetic analysis using liquid-based cytology (LBC) samples improved the diagnostic sensitivity of EC. Methods Among 218 individuals who underwent endometrial screening by LBC, 208 samples were analysed by cancer-panel sequencing. Excluding 13 samples with low sequence coverage, we further analysed 195 samples. Results Among the 195 women analysed, 39 and 15 were eventually shown to suffer from malignant endometrial and non-endometrial neoplasms, respectively. Driver mutation(s) were found in nine of the 15 cytology-negative patients with endometrial malignancy, corroborating that combination of cytological and genetic analyses should increase the sensitivity of the diagnosis of malignant endometrial neoplasms. Importantly, driver alterations were found in 32 of 125 women without malignant or premalignant diseases, which raises caution for the interpretation of genetic alterations detected in the endometrial samples. Comparison between the driver mutations in the 32 subjects and those in the 29 endometrial malignancies unveiled that the number of mutations and mutations in PTEN, CTNNB1, and TP53 may be applied for the assessment and prediction of development of EC. Conclusions The genetic analysis combined with liquid-based cytology is useful to improve the diagnostic sensitivity of endometrial neoplasms. However, caution must be taken when cancer-associated mutation(s) are detected in the genetic analysis. Further investigation may clarify the risk of malignant endometrial neoplasms in women with driver mutation(s).

DOI

【婦人科悪性腫瘍手術-トラブルシューティングとその予防法-】単純外陰切除術

齋藤豪, 松浦基樹, 玉手雅人, 真里谷奨

産婦人科の実際 ( 金原出版(株) ) 72 ( 12 ) 1397 - 1401 2023.11

北海道では、妊娠初期全例での細菌性腟症(BV)スクリーニング・治療により、早産・超早産の有意な減少をみた

島野敏司, 山田俊, 長和俊, 千石一雄, 田村保明, 真里谷奨, 斎藤豪

日本性感染症学会誌 ( (一社)日本性感染症学会 ) 34 ( 2 ) 89 - 89 2023.11

Pregnancy-specific beta-1-glycoprotein 6 is a potential novel diagnostic biomarker of placenta accreta spectrum.

Hazuki Kashiwagi, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Yoshihiko Hirohashi, Yuya Fujibe, Terufumi Kubo, Masayuki Someya, Tsuyoshi Baba, Shinichi Ishioka, Toshihiko Torigoe, Tsuyoshi Saito

Medical molecular morphology 2023.10 [Domestic journal]

Early diagnosis is essential for the safer perinatal management of placenta accreta spectrum (PAS). We used transcriptome analysis to investigate diagnostic maternal serum biomarkers and the mechanisms of PAS development. We analyzed eight formalin-fixed paraffin-embedded placental specimens from two placenta increta and three placenta percreta cases who underwent cesarean hysterectomy at Sapporo Medical University Hospital between 2013 and 2019. Invaded placental regions were isolated from the uterine myometrium and RNA was extracted. The transcriptome difference between normal placenta and PAS was analyzed by microarray analysis. The PAS group showed markedly decreased expression of placenta-specific genes such as LGALS13 and the pregnancy-specific beta-1-glycoprotein (PSG) family. Term enrichment analysis revealed changes in genes related to cellular protein catabolic process, female pregnancy, autophagy, and metabolism of lipids. From the highly dysregulated genes in the PAS group, we investigated the expression of PSG family members, which are secreted into the intervillous space and can be detected in maternal serum from the early stage of pregnancy. The gene expression level of PSG6 in particular was progressively decreased from placenta increta to percreta. The PSG family, especially PSG6, is a potential biomarker for PAS diagnosis.

DOI PubMed

Nationwide trends in and regional factors associated with minimally invasive hysterectomy for benign indications in Japan.

Kyoko Isoyama, Motoki Matsuura, Misa Hayasaka, Sachiko Nagao, Yoko Nishimura, Toshiki Yoshioka, Yuichi Imai, Etsuko Miyagi, Yukio Suzuki, Tsuyoshi Saito

European journal of obstetrics, gynecology, and reproductive biology 289 129 - 135 2023.10 [International journal]

OBJECTIVE: To examine the prevalence trends of minimally invasive hysterectomy for benign indications in Japan and investigate regional disparities. STUDY DESIGN: A retrospective cohort and ecological study using "The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data". SETTING: Nationwide Japan. PATIENTS: Individuals who underwent hysterectomy for benign indications from 2014 to 2020. INTERVENTIONS: Trend analysis of minimally invasive surgery (MIS) rates through laparoscopic hysterectomies (LH) and robotic-assisted laparoscopic hysterectomies (RA-LH) at the national and prefecture levels. Examination of regional factors contributing to the disparity in MIS implementation rates by second medical service area (SMSA). RESULTS: The number of LH has increased from 16,016 in 2014 to 27,755 in 2020. The nationwide MIS hysterectomy rate increased from 29% in 2014 to 55% in 2020 (p less than 0.001). More than 50% of hysterectomies have been performed as MIS since 2019. There was an increasing trend in MIS rates in all age groups. All prefectures except one showed a significant upward trend (p less than 0.05) in the MIS rates, but MIS rates varied widely (23-84%). In a multivariable model, the MIS was more likely to be performed in the SMSAs in western Japan (p = 0.011), in the SMSAs where the number of laparoscopy-qualified gynecologists is 5-10 (p = 0.013), and 11 or higher (p less than 0.001). CONCLUSIONS: This study reveals a shift towards minimally invasive surgery (MIS) in total hysterectomy procedures in Japan. However, significant disparities in the prevalence of MIS hysterectomy exist, potentially influenced by the number of laparoscopy-qualified gynecologists.

DOI PubMed

小腸癌の子宮転移の一例

長尾沙智子, 黒川晶子, 玉手雅人, 幅田周太朗, 秋元太志, 松浦基樹, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 62 ( Suppl.2 ) 525 - 525 2023.10

子宮移植実現に向けた献体トレーニング

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 秋元太志, 馬場剛, 齋藤豪

Organ Biology ( (一社)日本臓器保存生物医学会 ) 30 ( 3 ) 111 - 111 2023.10

卵巣癌に対するPARP阻害薬の中期成績と有害事象・内服アドヒアランスの関係性の検討

萬和馬, 松浦基樹, 有元千紘, 黒川晶子, 玉手雅人, 齋藤豪

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 61回 O65 - 5 2023.10

Endocrinological and Metabolic Heterogeneity is low in Japanese Women with Polycystic Ovary Syndrome.

Tsuyoshi Baba, Toshiaki Endo, Tasuku Mariya, Yoshika Kuno, Hiroyuki Honnma, Mika Kanaya, Tsuyoshi Saito

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 102217 - 102217 2023.09 [International journal]

OBJECTIVE: This study aims to evaluate the endocrine differences among polycystic ovary syndrome (PCOS) phenotypes in Japanese women. METHODS: 118 Japanese women that we diagnosed with PCOS agreed to be included in the study. The study group was classified into the following four phenotypes: A) hyperandrogenism (HA); ovulatory disorder (OvD) and polycystic ovary morphology (PCOM); B) HA and OvD; C) HA and PCOM; and D) OvD and PCOM. We also recruited 66 healthy Japanese women to the study as control participants. Age, body mass index, androgens, luteinizing hormone, follicle-stimulating hormone, and insulin resistance index were evaluated and compared. RESULTS: The proportions of phenotypes A, B, C, and D were 57/120 (47.5%), 4/120 (3.3%), 13/120 (10.8%), and 46/120 (38.3%), respectively. The proportion of phenotype B was too small; therefore, phenotypes A and B were grouped as classical PCOS for intergroup comparisons. The luteinizing hormone/follicle-stimulating hormone ratio in the classical PCOS group was higher than that in the phenotype D group (P < 0.001). Androgen concentrations in the phenotype D group were significantly lower than those in the other groups (P < 0.01). Phenotype D was more common in lean women with PCOS. The surrogate marker of insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) was not different irrespective of PCOS and its phenotypes. CONCLUSION: Except for androgens, endocrine differences by PCOS phenotype are not evident, suggesting that diversity among patients with PCOS is relatively low in Japanese women.

DOI PubMed

子宮原発骨肉腫の1例

南香穂, 嶋田浩志, 今沙織, 鈴木美紀, 玉手雅人, 幅田周太朗, 松浦基樹, 岩崎雅宏, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 70回 65 - 65 2023.09

卵巣移動術後に発生した卵巣腫瘍を腹腔鏡下に摘出した2例の検討

南怜毅, 鹿内智史, 和田渚, 杉田奈穂子, 玉手雅人, 幅田周太朗, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 70回 53 - 53 2023.09

Laparoscopic retrovesical lower uterine segment bypass for hysterectomy with previous caesarean section: Hung Up the Bladder Bypass (HUBB) technique.

Masato Tamate, Motoki Matsuura, Nagisa Wada, Takaki Adachi, Kazuma Yorozu, Chihiro Arimoto, Tsuyoshi Saito

Journal of gynecology obstetrics and human reproduction 102629 - 102629 2023.07 [International journal]

Patients with a history of cesarean section and a highly adherent bladder may have difficulty in bladder dissection and may suffer damage. It may also be difficult to orient the patient for repair in the event of damage. In such cases, dissection from the side between the bladder and cervix is a good way to avoid complication. This video reviews the steps of the HUBB technique procedure, provides tips and tricks for performing a successful adhesiolysis, and illustrates the procedure's adaptability. The first is the identification of the uterine artery and its position. Step2, a Laparoscopic retrovesical lower uterine segment bypass is created. Step3 a Hung Up the Bladder Bypass is created, the bladder is completely dissected. Step4, an adhesiolysis and leak test is performed. In this report, we would like to introduce a technique for creating a retrovesical lower uterine segment bypass using a laparoscope and traction on the bypass to dissect the bladder.

DOI PubMed

Changes in preterm and extremely preterm birth rates in Japan after the introduction of obstetrical practice guidelines in 2008.

Satoshi Shimano, Takashi Yamada, Kazutoshi Cho, Kazuo Sengoku, Tasuku Mariya, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 2023.07 [International journal]

AIM: Obstetrical guidelines were established in Japan in 2008, and obstetrical diagnoses and treatments were subsequently standardized nationally. We examined changes in the preterm birth rate (PTBR) and extremely preterm birth rate (EPTBR) following the introduction of such guidelines. METHODS: Information on 50 706 432 live births in Japan between 1979 and 2021, including Japanese reproductive medicine, the childbearing age of pregnant women, and the employment status of reproductive-age women between 2007 and 2020, were obtained from the Japanese government and academic societies. Regression analysis was used to compare chronological changes nationally and those of eight Japanese regions. Regional and national average PTBRs and EPTBRs from 2007 to 2020 were compared by using a repeated measures analysis of variance. RESULTS: From 1979 to 2007, PTBRs and EPTBRs in Japan increased significantly. However, from 2008, the national PTBR and EPTBR decreased until 2020 (p < 0.001) and 2019 (p = 0.02), respectively. From 2007 to 2020, overall PTBR and EPTBR were 5.68% and 0.255%, respectively. A significant difference in the PTBR and EPTBR existed between the eight Japanese regions. During this period, the number of pregnancies using assisted reproductive technology increased from 19 595 to 60 381, pregnant women became older, the employment rate of those of reproductive age increased, and nonregular employment was 54%, which was 2.5 times higher than for men. CONCLUSIONS: In Japan, after obstetrical guidelines were enacted in 2008, PTRBs decreased significantly even under the pressure of increasing preterm births. Countermeasures may be necessary for regions showing high PTBRs.

DOI PubMed

当院における婦人科癌に対するがん遺伝子パネル検査の現状と課題

野藤五沙, 真里谷奨, 田中佑弥, 室田文子, 寺本瑞絵, 松浦基樹, 岩崎雅宏, 石川亜貴, 高田弘一, 櫻井晃洋, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 65回 288 - 288 2023.07

献体による手術トレーニングの立ち上げと運営のコツ-本邦の手術を今後も安全かつ世界最高水準で続けるために日本の持続的CSTに必要な横断的で多角的な思考とは?

玉手雅人, 松浦基樹, 齋藤豪

医学教育 ( (一社)日本医学教育学会 ) 54 ( Suppl. ) 72 - 72 2023.07

当科における卵巣組織凍結の現状報告と北海道における小児科医の卵巣組織凍結に対する意識調査

長尾沙智子, 玉手雅人, 春日芙貴子, 西村庸子, 松浦基樹, 久野芳佳, 馬場剛, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 65回 387 - 387 2023.07

子宮頸部腺癌の生検組織における間質線維化反応の臨床的意義

秋元太志, 松浦基樹, 玉手雅人, 岩崎雅宏, 幅田周太朗, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 65回 316 - 316 2023.07

【我々はこうしている～子宮頸癌手術におけるMISの工夫】我々が行う子宮頸癌に対する腹腔鏡下広汎子宮全摘術の工夫

松浦基樹, 玉手雅人, 長尾沙智子, 黒川晶子, 秋元太志, 諸井明仁, 幅田周太朗, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 65回 160 - 160 2023.07

プラチナ感受性再発卵巣がんに対するオラパリブ,ニラパリブ維持療法の比較検討

有元千紘, 松浦基樹, 足立岳貴, 萬和馬, 黒川晶子, 西村庸子, 玉手雅人, 磯山響子, 秋元太志, 幅田周太朗, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 65回 350 - 350 2023.07

【AIがもたらす婦人科癌医療の新展開】深層学習を利用したHE染色からの子宮内膜癌MMR status判定の可否に関する検討

梅本美菜, 真里谷奨, 永田舞, 堀米俊弘, 新開翔太, 杉田真太朗, 金関貴幸, 松浦基樹, 岩崎雅宏, 廣橋良彦, 長谷川匡, 藤野雄一, 鳥越俊彦, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 65回 153 - 153 2023.07

Cervical conization with endoCUT mode applying gastrointestinal endoscopic polypectomy technique.

Masato Tamate, Motoki Matsuura, Tsuyoshi Saito

Obstetrics & gynecology science 2023.06 [International journal]

OBJECTIVE: To show how endoCUT (COMPANY, CITY, STATE, COUNTRY) mode can be safely managed with cervical conization. METHODS: Demonstration of the technique and explanation of endoCUT and soft coagulation mode with narrated video footage. Cervical conization is a therapeutic and diagnostic procedure performed for the diagnosis of cervical intraepithelial lesions and cervical cancer. Specific methods include cold scalpel, ultrasonically activated device and laser, and loop electrosurgical excision procedure (LEEP), which involves transpiration and partial excision. The endoCUT mode and soft coagulation in VIO3 (COMPANY, CITY, STATE, COUNTRY) were used to perform cervical conical resection safely and at low cost (Fig. 1). The endoCUT mode was originally developed for polypectomy in gastrointestinal endoscopy, where no counter traction can be applied [1,2]. RESULTS: The endoCUT mode approach to cervical conization with several key strategies to minimize blood loss and ensure safety: 1) incisions can be made in close contact; 2) resection can be performed with minimal contact with the lesion; 3) control of bleeding from the resected transection by soft coagulation; and 4) low running cost of endoCUT mode. CONCLUSION: Conventionally, cervical conical resection has been performed by using a device capable of making a close incision (cold scalpel, ultrasonically activated device and laser, and LEEP etc.), but there have been issues with bleeding control and cost. Here, we present a new technique using the endoCUT mode and several strategies for safe and effective resection.

DOI PubMed

深層学習によるHE染色データを用いた子宮内膜癌プロファイル判定の適否に関する検討

梅本美菜, 真里谷奨, 永田舞, 堀米俊弘, 新開翔太, 杉田真太朗, 金関貴幸, 松浦基樹, 岩崎雅宏, 廣橋良彦, 長谷川匡, 鳥越俊彦, 齋藤豪, 藤野雄一

日本医療情報学会春季学術大会プログラム・抄録集 ( (一社)日本医療情報学会 ) 27回 122 - 123 2023.06

Therapeutic efficacy of a four-year treatment with eribulin in a patient with uterine leiomyosarcoma: A case report.

Motoki Matsuura, Kazuma Yorozu, Sachiko Nagao, Shoko Kurokawa, Masato Tamate, Taishi Akimoto, Tsuyoshi Saito

Gynecologic oncology reports 47 101205 - 101205 2023.06 [International journal]

Uterine leiomyosarcoma (LMS) is a gynecological malignancy with an extremely poor prognosis. Multiple new therapeutic agents, including pazopanib, trabectedin, and eribulin, have been clinically applied to treat uterine LMS, and their therapeutic effects are expected. We encountered one patient with advanced recurrent uterine LMS who achieved a partial response to a four-year treatment with eribulin. A 31-year-old woman was diagnosed with stage 2B LMS. After the first recurrence, Gemcitabine, Docetaxel (GD) therapy was administered, and complete response (CR) was achieved. However, 2 years and 10 months later, recurrence occurred at the vaginal cuff, and GD therapy and doxorubicin hydrochloride were administered, resulting in CR. Five months later, she experienced another recurrence at the same location and was treated with eribulin. To date, 53 courses of eribulin have been administered and are currently ongoing. Maintaining low neutrophil-to-lymphocyte ratio and low platelet-to lymphocyte ratio in this manner is considered to be one of the reasons why eribulin continues to be effective. We encountered a rare case in which eribulin was administered for the longest period of time, and produced an observable effect in uterine LMS.

DOI PubMed

「助手力」の教育助手力を構成する要素とは何か,どのように教育するのか

梅本美菜, 松浦基樹, 足立岳貴, 有本千紘, 黒川晶子, 西村庸子, 玉手雅人, 秋元太志, 幅田周太朗, 岩崎雅弘, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 34 ) 162 - 162 2023.06

深層学習によるHE染色データを用いた子宮内膜癌プロファイル判定の適否に関する検討

梅本美菜, 真里谷奨, 永田舞, 堀米俊弘, 新開翔太, 杉田真太朗, 金関貴幸, 松浦基樹, 岩崎雅宏, 廣橋良彦, 長谷川匡, 鳥越俊彦, 齋藤豪, 藤野雄一

日本医療情報学会春季学術大会プログラム・抄録集 ( (一社)日本医療情報学会 ) 27回 122 - 123 2023.06

TLHにおける非利き手の有効率を検証する

和田渚, 玉手雅人, 有元千紘, 鹿内智史, 杉田奈穂子, 鈴木将裕, 松浦基樹, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 34 ) 163 - 163 2023.06

機能再建手術 Thiel法固定献体における子宮移植トレーニング

玉手雅人, 松浦基樹, 木須伊織, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 34 ) 73 - 78 2023.06

Thiel法固定献体における子宮移植

玉手雅人, 松浦基樹, 和田渚, 足立岳貴, 有元千紘, 黒川晶子, 西村庸子, 秋元太志, 木須伊織, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 34 ) 146 - 146 2023.06

「助手力」の教育助手力を構成する要素とは何か,どのように教育するのか

梅本美菜, 松浦基樹, 足立岳貴, 有本千紘, 黒川晶子, 西村庸子, 玉手雅人, 秋元太志, 幅田周太朗, 岩崎雅弘, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 34 ) 162 - 162 2023.06

巨大腺筋症に対する開腹子宮頸管縫縮術を施行し,救命可能週数まで妊娠継続できた一絨毛膜二羊膜双胎の1例

常松梨紗, 石岡伸一, 馬場剛, 真里谷奨, 染谷真行, 新開翔太, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 59 ( Suppl.1 ) P322 - P322 2023.06

中心核ミオパチーの児出産を契機に発見された1型リアノジン受容体(RYR1)遺伝子の病的バリアントを有する妊婦の一例

古来愛香, 石岡伸一, 真里谷奨, 藤部佑哉, 坂井拓朗, 染谷真行, 齊藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 59 ( 1 ) 111 - 115 2023.05

1型リアノジン受容体(RYR1)をコードする遺伝子の病的バリアントは,いくつかの先天性ミオパチーの発症に関連している.今回,未診断だったRYR1遺伝子の病的バリアントを有する妊婦の2回の妊娠出産を経験したので報告する.症例:29歳G1P0.既往歴なし.当科外来で妊婦健診を行っていたが,妊娠37週で羊水過多傾向,胎動自覚低下を認め,妊娠38週より分娩誘発を開始した.誘発中に胎児遷延徐脈を認め,緊急帝王切開となった.児は2,596gの男児,Apgar score 2/4(1分/5分)で出生し,floppy infantにて人工呼吸管理となった.その後中心核ミオパチーと判明し,母児にRYR1の病的バリアントがヘテロ接合で認められた.2年後に再び妊娠したが妊娠経過で異常は認めず,妊娠38週で選択的帝王切開となった.児は2,588g,女児,Apgar score 8/9(1分/5分)で出生し筋緊張正常であった.非常に稀だが,母体未診断であったRYR1の病的バリアントを有する症例と考えられた.(著者抄録)

腹腔鏡下子宮筋腫核出術後に発生した多発parasitic myomaの1例

岩崎雅宏, 幅田周太朗, 野藤五沙, 松浦基樹, 玉手雅人, 齋藤豪

産婦人科の実際 ( 金原出版(株) ) 72 ( 5 ) 533 - 536 2023.05

＜文献概要＞Parasitic myomaは,筋腫が子宮と遊離した状態で他の臓器からの栄養血管を得て生着する疾患である。症例はモルセレーターを用いた腹腔鏡下子宮筋腫核出術既往がある47歳女性で,子宮筋腫の増大を認めたため腹式単純子宮全摘出術を施行した際,多発性の子宮と連続性のない筋腫parasitic myomaを認めた。モルセレーターを用いた腹腔鏡下子宮全摘出術や腹腔鏡下子宮筋腫核出術ではparasitic myomaを予防するため,組織飛散防止回収袋を用いた回収や十分な腹腔内洗浄を心がける必要がある。

卵巣癌・子宮体癌症例における細胞診検体(LBC検体を含む)を用いたNGSの有用性 LBC検体によるNGSを子宮体癌早期スクリーニングにどう応用するべきか

松浦基樹, 玉手雅人, 秋元太志, 幅田周太朗, 岩崎雅宏, 畠山晴良, 高根希世子, 山口貴世志, 古川洋一, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 62 ( Suppl.1 ) 174 - 174 2023.05

Mailing human papillomavirus self-sampling kits to women under-screened for cervical cancer improved detection in cervical cancer screening in a general population study in Japan.

Yoko Nishimura, Motoki Matsuura, Noriko Terada, Sachiko Nagao, Hiroshi Shimada, Kyoko Isoyama, Masato Tamate, Masahiro Iwasaki, Tsuyoshi Saito

BMC public health 23 ( 1 ) 473 - 473 2023.03 [International journal]

BACKGROUND: One cause of the increase in cervical cancer rates in Japan is the long-term stagnation in the cervical cancer screening consultation rate. Therefore, improving the screening consultation rate is of urgent concern to reduce cervical cancer incidence. Self-collected human papilloma virus (HPV) tests have been successfully adopted in several countries, such as the Netherlands and Australia, as a measure of individuals who have not undergone cervical cancer screening in national programs. This study aimed to verify whether self-collected HPV tests presented an effective countermeasure for individuals who had not undergone the recommended cervical cancer screenings. METHODS: This study was conducted from December 2020 to September 2022 in Muroran City, Japan. The primary evaluated endpoint was the percentage of citizens who underwent cervical cancer screening at a hospital with positive self-collected HPV test results. The secondary endpoint was the percentage of included participants who were diagnosed with cervical intraepithelial neoplasia (CIN) or higher among those who visited a hospital and underwent cervical cancer screening. RESULTS: The included study participants were 7,653 individuals aged 20-50 years with no record of previous cervical cancer examination in the past 5 years. We mailed these participants information on self-administered HPV tests as an alternative screening procedure and sent the kit to 1,674 women who requested the test. Among them, 953 returned the kit. Among the 89 HPV-positive individuals (positive rate, 9.3%), 71 (79.8%) visited the designated hospital for an examination. A closer examination revealed that 13 women (18.3% of hospital visits) had a CIN finding of CIN2 or higher, among whom one each had cervical cancer and vulvar cancer, eight presented with CIN3, and three presented with CIN2; two cases of invasive gynecologic cancer were also identified. CONCLUSIONS: We conclude that the self-collected HPV tests showed a certain efficacy as a measure of individuals who had not undergone the recommended cervical cancer screening. We devised ways to have the unexamined patients undergo HPV testing and ensure that HPV-positive individuals visited the hospital. Despite a few limitations, our findings suggest the effectiveness of this public health intervention.

DOI PubMed

Clinical application of long-read nanopore sequencing in a preimplantation genetic testing pre-clinical workup to identify the junction for complex Xq chromosome rearrangement-related disease.

Tasuku Mariya, Yui Shichiri, Takeshi Sugimoto, Rie Kawamura, Syunsuke Miyai, Hidehito Inagaki, Eiji Sugihara, Keiko Ikeda, Tsuyoshi Baba, Aki Ishikawa, Michiko Ammae, Yoshiharu Nakaoka, Tsuyoshi Saito, Akihiro Sakurai, Hiroki Kurahashi

Prenatal diagnosis 2023.02 [International journal]

OBJECTIVE: Xq chromosome duplication with complex rearrangements is generally acknowledged to be associated with neurodevelopmental disorders such as Pelizaeus-Merzbacher disease (PMD) and MECP2 duplication syndrome. For couples who required a PGT-M (pre-implantation genetic testing for monogenic disease) for these disorders, junction-specific PCR is useful to directly detect pathogenic variants. Therefore, pre-clinical workup for PGT-M requires the identification of the junction of duplicated segments in PMD and MECP2 duplication syndrome, which is generally difficult. METHODS: In this report, we used nanopore long-read sequencing targeting the X chromosome using an adaptive sampling method to identify breakpoint junctions in disease-causing triplications. RESULTS: By long-read sequencing, we successfully identified breakpoint junctions in one PMD case with PLP1 triplication and in another MECP2 triplication case in a single sequencing run. Surprisingly, the duplicated region involving MECP2 was inserted 45 Mb proximal to the original position. This inserted region was confirmed by FISH analysis. With the help of precise mapping of the pathogenic variant, we successfully re-established STR haplotyping for PGT-M and avoided any potential misinterpretation of the pathogenic allele due to recombination. CONCLUSION: Long-read sequencing with adaptive sampling in a PGT-M pre-clinical workup is a beneficial method for identifying junctions of chromosomal complex structural rearrangements. This article is protected by copyright. All rights reserved.

DOI PubMed

Cell-free RNA発現プロファイルを根拠とした新規無侵襲着床前胚染色体異数性検査アルゴリズムの構築について

真里谷奨, 齋藤豪, 倉橋浩樹

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 430 2023.02

Cell-free RNA発現プロファイルを根拠とした新規無侵襲着床前胚染色体異数性検査アルゴリズムの構築について

真里谷奨, 齋藤豪, 倉橋浩樹

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 430 2023.02

深層学習を用いたHE染色からの子宮内膜癌分子生物学的プロファイル推定の適否に関する検討

梅本美菜, 真里谷奨, 新開翔太, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 260 2023.02

深層学習を用いたHE染色からの子宮内膜癌分子生物学的プロファイル推定の適否に関する検討

梅本美菜, 真里谷奨, 新開翔太, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 260 2023.02

中心核ミオパチーの児出産を契機に発見された1型リアノジン受容体(RYR1)遺伝子のバリアントを有する妊婦の一例

古来愛香, 石岡伸一, 新開翔太, 真里谷奨, 常松梨紗, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 459 2023.02

卵巣癌に対するPARP阻害薬の中期成績と有害事象・内服アドヒアランスの関係性に関する検討

萬和馬, 松浦基樹, 有元千紘, 黒川晶子, 玉手雅人, 秋元太志, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 292 2023.02

当科における卵巣組織凍結の現状報告と北海道における小児科医の卵巣組織凍結に対する意識調査

古来愛香, 玉手雅人, 春日芙貴子, 長尾沙智子, 西村庸子, 松浦基樹, 久野芳佳, 馬場剛, 齋藤豪

日本がん・生殖医療学会誌 ( (一社)日本がん・生殖医療学会 ) 6 ( 1 ) 49 - 53 2023.02

【緒言】小児・思春期・若年成人(children,adolescents and young adults:C-AYA)世代のがんサバイバーが増加することにともない、QOL向上の意識が高まり妊孕性温存法も発展しつつある。当科では、小児がん患者の卵巣組織凍結保存を実施してきた。今回、当院での卵巣組織凍結保存の現状報告(研究1)、および北海道内の小児科医における卵巣組織凍結に対する意識調査(研究2)について報告する。【対象と方法】研究1:2012年12月～2021年6月までに当科で卵巣組織凍結保存を目的とした卵巣摘出術手術20例を対象に、年齢、原疾患、コンサルトから手術までの期間、周術期経過、合併症などの背景を集積した。研究2:北海道内の悪性疾患を診療する小児科医に卵巣組織凍結の認識を匿名でアンケート調査した。【結果】研究1:初診時平均年齢は18.8±8.49歳。原疾患は、血液腫瘍13例、脳腫瘍3例、乳癌2例、軟部腫瘍2例であった。手術までの期間は3-99日(平均31.5±21.5日)、全例腹腔鏡手術であった。研究2:アンケートは5施設18名から回収した。卵巣組織凍結について認識している人が18名(100%)、情報提供をしたことがある人が13名(72.2%)であった。卵巣組織凍結の情報提供をしたが治療の同意が得られない理由としては、経済的理由(保険適応外)、手術のリスク、原疾患治療の遅れ、エビデンスが乏しい、などがあげられた。【結語】卵巣組織凍結保存は微小残存がん病巣(MRD:minimal residual disease)のリスクがあるが、月経発来前の女児に対して唯一の妊孕性温存療法である。しかし、社会的要因によって普及には至っていない。今後、凍結卵巣融解移植成績の発信や卵巣組織凍結の説明方法の均てん化などにより一層卵巣組織凍結という選択肢を提示していきたい。症例治療が滞りなく円滑に進むよう、主治医、生殖医、婦人科腫瘍医の連携が重要であり、今後尽力したい。(著者抄録)

化学療法抵抗性再発子宮体癌に対する当院におけるPembrolizumab/Lenvatinibの使用経験

南怜毅, 幅田周太朗, 有元千紘, 堀清貴, 萬和馬, 野藤五沙, 黒川晶子, 玉手雅人, 秋元太志, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 347 2023.02

帝王切開後高度癒着症例に対する腹腔鏡下子宮全摘術における,Retrovesical Lower Uterine Segment Bypassと検討

有元千紘, 玉手雅人, 足立岳貴, 黒川晶子, 西村庸子, 秋元太志, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 278 2023.02

中心核ミオパチーの児出産を契機に発見された1型リアノジン受容体(RYR1)遺伝子のバリアントを有する妊婦の一例

古来愛香, 石岡伸一, 新開翔太, 真里谷奨, 常松梨紗, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 459 2023.02

Letrozole increases preantral follicle growth and decreases estradiol production without impairing follicle survival.

Fukiko Kasuga-Yamashita, Tsuyoshi Baba, Sachiko Nagao, Yuya Fujibe, Miyuki Morishita, Yoshika Kuno, Tasuku Mariya, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

Journal of ovarian research 15 ( 1 ) 136 - 136 2022.12 [International journal]

BACKGROUND: Letrozole has been reported to be effective in treating anovulation, preventing ovarian hyperstimulation syndrome (OHSS), and retrieving oocytes in breast cancer patients. However, the role and mechanism of letrozole in follicular development remain unclear. RESULTS: We treated mouse preantral follicles with various treatments; we found no significant difference in follicle survival rates in the letrozole (LET) group compared with the control group, but the average diameter of follicles in the LET group tended to be larger (CTRL vs. LET 30, p = 0.064; CTRL vs. LET 100, p = 0.025). The estradiol concentrations in culture media of the LET group were significantly lower than those observed in the control group (CTRL vs. LET 30, p = 0.038; CTRL vs. LET 100, p = 0.025). We further found a marked increase in follicle-stimulating hormone receptor (FSHR) gene expression in response to letrozole treatment (CTRL vs. LET 30, p = 0.075; CTRL vs. LET 100, p = 0.034). This result suggested that increased FSHR expression promotes follicle development. Letrozole inhibited aromatase activity, but the effect was limited. Letrozole did not significantly reduce vascular endothelial growth factor (VEGF) gene expression. CONCLUSIONS: Letrozole may promote follicle development by increasing the expression of FSHR. Letrozole may be useful for fertility preservation of patients with estrogen-dependent cancers such as breast cancer and various other cancers. Whether letrozole has a direct effect in reducing OHSS requires further investigation.

DOI PubMed

A mixed-method evaluation of cadaver surgery training for gynecologic oncology.

Masato Tamate, Motoki Matsuura, Hiroyuki Kanao, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 48 ( 12 ) 3252 - 3261 2022.12 [International journal]

AIM: Traditional surgical training techniques with using patients, and new advances with live animals, artificial models, and simulation methods have several shortcomings. There are a few reports on the usefulness of cadaver surgery training (CST) in gynecology. Herein, we used a mixed-method evaluation to qualitatively and quantitatively explore the educational efficacy of CST by conducting CST programs at the Sapporo Medical University, Japan. METHODS: In 2020, we conducted two CST programs with 45 participants-13 residents, 8 specialists recognized by Japan Society of Obstetrics and Gynecology, 23 certified endoscopists recognized by Japan Society of Gynecology and Obstetrics Endoscopy and Minimally Invasive Therapy, 15 specialists recognized by Japan Society of Gynecologic Oncology, and 14 certified endoscopists cum oncology. Three participants observed the procedure virtually and 42 were physically present. Laparoscopic radical hysterectomy and pelvic exenteration were performed on five Thiel-embalmed cadavers. Participants were asked to complete pre- and post-training surveys that included qualitative questions, concerning the purpose and cost of CST, and quantitative questions, testing anatomical knowledge. RESULTS: We observed that the rate of score improvement to the quantitative questions increased from 58.6% pre-CST to 75.6% post-CST. Furthermore, oncology specialists and those who performed more surgeries and faced more complications during surgeries recorded high percentage of correct answers. Multiple regression analysis statistically confirmed these results. CONCLUSIONS: This study confirmed the educational efficacy of CST.

DOI PubMed

vNOTESによる膜解剖理論に基づいた直腸周囲展開

足立岳貴, 松浦基樹, 黒川晶子, 西村庸子, 玉手雅人, 秋元太志, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 27 ( 7 ) 599 - 599 2022.12

Predictive value of an exosomal microRNA-based signature for tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoh Kozuka, Masashi Idogawa, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Medical molecular morphology 56 ( 1 ) 38 - 45 2022.11 [Domestic journal]

Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA (miRNA) expression signatures associated with the outcome of cervical cancer patients treated with CCRT. Exosomes were isolated from the plasma of 45 patients prior to CCRT during 2014-2020, and miRNA analysis was performed by next-generation sequencing. At a median follow-up of 38 months, 26 patients were recurrence free, 15 patients had died of the disease, and 4 patients received salvage chemotherapy due to distant metastasis. Of the 2522 miRNAs detected, 9 (miR-148a-5p, 1915-3p, 3960, 183-5p, 196b-5p, 200c-3p, 182-5p, 374a-5p, and 431-5p) showed differential expression between the recurrence-free and recurrence groups. Patients were divided into high- and low-risk groups according to the cutoff of the miRNAs-based risk score calculated from respective expression levels. The high-risk group had significantly worse disease-specific survival than the low-risk group (p < 0.001). In addition, miR-374a-5p and miR-431-5p expression showed a weak inverse correlation with tumor-infiltrating CD8+ and FOXP3+ T cells, suggesting a potential inhibitory effect on CCRT by suppressing tumor immunity. This miRNA signature could improve non-invasive monitoring and personalized treatment for cervical cancer.

DOI PubMed

Human papillomavirus testing and cytology using physician-collected uterine cervical samples vs. self-collected vaginal samples and urine samples.

Noriko Terada, Motoki Matsuura, Shoko Kurokawa, Yoko Nishimura, Masato Tamate, Kyoko Isoyama, Satoko Yamazaki, Hiroshi Shimada, Masahiro Suzuki, Yuta Tabuchi, Mizue Teramoto, Tsuyoshi Saito

International journal of clinical oncology 27 ( 11 ) 1742 - 1749 2022.11 [Domestic journal]

BACKGROUND: Human papillomavirus (HPV) testing using self-collected vaginal samples and urine samples is convenient and effective for improving the screening rate. But, to serve as an alternative cervical cancer screening technique, such tests must offer sensitivity equivalent to the HPV testing of physician-collected cervical samples. To examine the effectiveness of HPV testing using self-collected samples and urine samples, we compared the results of HPV testing using these samples with those of HPV testing using physician-collected samples and cytological examinations. METHODS: The study population included 300 women (age: 20-50 years) with abnormal cervical cytology. The results of HPV testing using self-collected samples and urine samples and physician-collected samples and cervical cytology were compared. RESULTS: For all HPV types, the κ-value was 0.773 for physician- and self-collected samples and 0.575 for physician-collected and urine samples. The κ-value for HPV type 16-positive samples was 0.988 for physician- and self-collected samples and 0.896 for physician-collected and urine samples. The κ-value for HPV type 18-positive samples was 0.856 for physician- and self-collected samples and 0.831 for physician-collected and urine samples. For other HPV types, the value was 0.809 for physician- and self-collected samples and 0.617 for physician-collected and urine samples. CONCLUSIONS: The obtained results were consistent between physician- and self-collected samples as well as between physician-collected and urine samples. Considering that the agreement rate was particularly high for the high-risk HPV types 16 and 18, HPV testing using physician-collected samples, self-collected samples, and urine samples was equally effective for the types with high carcinogenicity.

DOI PubMed

子宮移植/妊娠中免疫抑制療法/胎児免疫 Thiel法固定献体における子宮移植トレーニング

玉手雅人, 松浦基樹, 木須伊織, 齋藤豪

Organ Biology ( (一社)日本臓器保存生物医学会 ) 29 ( 3 ) 86 - 86 2022.11

細胞診におけるAIの活用子宮頸部細胞診におけるAIの活用

新開翔太, 真里谷奨, 梅本美菜, 南部優太, 永田舞, 淺沼広子, 上野太郎, 廣橋良彦, 鳥越俊彦, 佐藤生馬, 藤野雄一, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 61 ( Suppl.2 ) 447 - 447 2022.10

子宮動脈塞栓術併用の子宮鏡下切除術において子宮内バルーニングが有用であったRPOCの一例

南怜毅, 長尾沙智子, 木嶋紗弓, 小川栞, 山崎智子, 玉手雅人, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 69回 64 - 64 2022.10

巨大嚢胞化し、子宮留膿腫を繰り返した帝王切開瘢痕部症候群の1例

仁木舜一, 嶋田浩志, 玉手雅人, 杉山芽, 今沙織, 鈴木美紀, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 69回 112 - 112 2022.10

巨大嚢胞化し、子宮留膿腫を繰り返した帝王切開瘢痕部症候群の1例

仁木舜一, 嶋田浩志, 玉手雅人, 杉山芽, 今沙織, 鈴木美紀, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 69回 112 - 112 2022.10

帝王切開創のケロイド予防とその修復の取り組み

杉山芽, 嶋田浩志, 玉手雅人, 仁木舜一, 今沙織, 鈴木美紀, 石岡伸一, 斎藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 69回 66 - 66 2022.10

子宮頸がん検診未受診者対策としての自己採取HPV検査の有効性評価

松浦基樹, 寺田倫子, 西村庸子, 玉手雅人, 長尾沙智子, 秋元太志, 幅田周太朗, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 61 ( Suppl.2 ) 477 - 477 2022.10

子宮動脈塞栓術併用の子宮鏡下切除術において子宮内バルーニングが有用であったRPOCの一例

南怜毅, 長尾沙智子, 木嶋紗弓, 小川栞, 山崎智子, 玉手雅人, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 69回 64 - 64 2022.10

子宮悪性軟部腫瘍に対する新規薬剤が効果を認めた症例の検討

萬和馬, 松浦基樹, 足立岳貴, 有元千紘, 黒川晶子, 西村庸子, 玉手雅人, 秋元太志, 幅田周太朗, 岩崎雅宏, 齋藤豪

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 60回 O46 - 2 2022.10

Self-administration of gender-affirming hormones and supratherapeutic dosing are relatively common in Japanese transgender women.

Tsuyoshi Baba, Toshiaki Endo, Utako Ikeda, Hiroshi Ikeda, Koji Ichihara, Naoya Masumori, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 48 ( 8 ) 2208 - 2213 2022.08 [International journal]

AIM: This study was performed to determine the proportion of transgender women with self-adjusted hormone administration and excess dosing. METHODS: The medical records of 87 transgender women who visited our gender clinic from 2010 through 2019 were reviewed. The complete blood count and serum concentrations of D-dimer, gonadotropins, and sex steroids were compared between transgender women who were self-administering gender-affirming hormones and women not using such hormones. RESULTS: Fifty-eight of 87 (66.7%) transgender women had contravened the guideline and self-adjusted their hormone administration. The hormonal data of one woman with hypopituitarism were eliminated from the analyses. The serum gonadotropin and testosterone levels were significantly lower in the self-administration group than in the hormone-naïve group. Gonadotropin levels below the lower limit of normal were found in 32/86 (37.2%) transgender women. The testosterone levels in six transgender women were not analyzed because these women had undergone sex reassignment surgery before visiting our hospital. Testosterone levels below the lower limit of normal men were found in 36/80 (45.0%) transgender women. Unexpectedly, 29/36 (80.6%) transgender women who were classified as having suppressed serum testosterone levels had testosterone levels of <0.6 ng/mL, which corresponds to the levels in cisgender women. The white blood cell count and hemoglobin concentration were significantly different between the groups. CONCLUSION: Self-initiated hormonal treatments seem to affect the serum concentrations of gonadotropin and sex steroids and the complete blood count. The prevalence of transgender women with self-adjusted use of gender-affirming hormones is high, and an excess dose of hormones occasionally occurs.

DOI PubMed

LSR antibody promotes apoptosis and disrupts epithelial barriers via signal pathways in endometrial cancer.

Kimihito Saito, Takumi Konno, Takayuki Kohno, Hiroshi Shimada, Motoki Matsuura, Tadahi Okada, Arisa Kura, Daichi Ishii, Masuo Kondoh, Tsuyoshi Saito, Takashi Kojima

Tissue barriers 2106113 - 2106113 2022.07 [International journal]

Lipolysis-stimulated lipoprotein receptor (LSR), a lipid metabolism-related factor localized in tricellular tight junctions (tTJs), plays an important role in maintaining the epithelial barrier. LSR is highly expressed in well-differentiated endometrial endometrioid carcinoma (EEC), and its expression decreases during malignancy. Angubindin-1, a novel LSR ligand peptide, regulates tTJs without cytotoxicity, enhances paracellular permeability, and regulates epithelial barrier via c-Jun N-terminal kinase (JNK)/cofilin. In this study, we investigated the immune-modulatory roles of an anti-LSR antibody in the treatment of EEC in vitro compared to those of angubindin-1. We prepared an antibody against the extracellular N-terminal domain of human LSR (LSR-N-ab) and angubindin-1. EEC cell-line Sawano cells in 2D and 2.5D cultures were treated with 100 μg/ml LSR-N-ab or 2.5 μg/ml angubindin-1 with or without protein tyrosine kinase 2β inhibitor PF431396 (PF43) and JNK inhibitor SP600125 (SP60) at 10 μM. Treatment with LSR-N-ab and angubindin-1 decreased LSR at the membranes of tTJs and the activity of phosphorylated LSR and phosphorylated cofilin in 2D culture. Treatment with LSR-N-ab and angubindin-1 decreased the epithelial barrier measured as TEER values in 2D culture and enhanced the epithelial permeability of FD-4 in 2.5D culture. Treatment with LSR-N-ab, but not angubindin-1, induced apoptosis in 2D culture. Pretreatment with PF43 and SP60 prevented all the changes induced by treatment with LSR-N-ab and angubindin-1. Treatment with LSR-N-ab and angubindin-1 enhanced the cell metabolism measured as the mitochondrial respiration levels in 2D culture. LSR-N-ab and angubindin-1 may be useful for therapy of human EEC via enhanced apoptosis or drug absorption.

DOI PubMed

Pathological classification of desmoplastic reaction is prognostic factor in cervical adenocarcinoma.

Taishi Akimoto, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Motoki Matsuura, Masato Tamate, Masahiro Iwasaki, Shutaro Habata, Taro Murakami, Makoto Osanai, Tsuyoshi Saito

Medical molecular morphology 2022.07 [Domestic journal]

Desmoplastic reaction (DR) and inflammation are significant pathological manifestations of tumorigenesis in several cancers. However, the correlation between these stromal reactions and cervical adenocarcinoma has been poorly documented. This investigation elucidated whether DR is a prognostic indicator in early cervical adenocarcinoma patients. Fifty-nine patients with early stage cervical adenocarcinoma (stages I/II) were included in the study. DR was divided into three groups, mature, intermediate, and immature, based on the presence of myxoid stroma and hyalinized keloid-like collagen. Inflammatory cell responses were classified as mild, moderate, and severe. Those stromal reactions were separately evaluated in the invasion front stroma and intratumoral stroma. In both the intratumor and invasion front stroma, intermediate/immature DR was correlated with tumor size, T stage, N stage, lymphovascular invasion, and parametrial infiltration (p < 0.001 to p < 0.05). In addition, in the intratumoral stroma, intermediate/immature DR led to short relapse-free survival and overall survival (p < 0.001). In the invasion front stroma, inflammatory cell responses were associated with DR immaturity and FIGO stage (p < 0.01). These results suggest that the classification of DR maturity is a potential prognostic biomarker in early stage cervical adenocarcinoma patients. DR can be evaluated by routine H&E staining without immunohistochemistry, making it convenient and economical in clinical practice.

DOI PubMed

Label Smoothingを併用した2段階CNNによる子宮頸部細胞診断支援アルゴリズムについて

梅本美菜, 真里谷奨, 南部優太, 新開翔太, 永田舞, 淺沼広子, 廣橋良彦, 鳥越俊彦, 佐藤生真, 藤野雄一, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 64回 189 - 189 2022.07

当院における早期子宮体癌再発症例の検討

幅田周太朗, 岩崎雅宏, 萬和馬, 野藤五沙, 玉手雅人, 秋元太志, 松浦基樹, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 64回 246 - 246 2022.07

プラチナ感受性再発卵巣がんに対するオラパリブ,ニラパリブ維持療法の比較検討

有元千紘, 松浦基樹, 足立岳貴, 萬和馬, 和田渚, 篠原由梨, 黒川晶子, 西村庸子, 玉手雅人, 磯山響子, 秋元太志, 幅田周太朗, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 64回 273 - 273 2022.07

妊娠中の脳腫瘍に対し,周期的なテモゾロミド投与を行った一例

齋藤晋平, 古来愛香, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 58 ( Suppl.1 ) 323 - 323 2022.06

児の緩和的対応を前提とした新生児予後不良な妊娠における,適切な医療体制について

染谷真行, 古来愛香, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 58 ( Suppl.1 ) 310 - 310 2022.06

帝王切開瘢痕部妊娠に対する一期的修復術の工夫

齋藤晋平, 玉手雅人, 西村庸子, 磯山響子, 幅田周太郎, 松浦基樹, 岩崎雅宏, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 33 ) 129 - 129 2022.06

失敗から学ぶ手術におけるわれわれの取組みやコツ開腹、腟式帝王切開瘢痕部妊娠に対する一期的修復術の工夫

齋藤晋平, 玉手雅人, 松浦基樹, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 33 ) 13 - 17 2022.06

サードアームを有効活用した後方アプローチによるロボット支援下子宮全摘術

松浦基樹, 西村庸子, 玉手雅人, 磯山響子, 秋元太志, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 33 ) 152 - 152 2022.06

Radiotherapy for HPV-related cancers: prediction of therapeutic effects based on the mechanism of tumor immunity and the application of immunoradiotherapy.

Masanori Someya, Yuki Fukushima, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoh Kozuka, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Japanese journal of radiology 40 ( 5 ) 458 - 465 2022.05 [Domestic journal]

Human papillomavirus (HPV)-related cancer is one of the diseases entities for which the applications of radiotherapy have been increasing. Recently, the process of carcinogenesis from HPV infection and the mechanism of tumor immunity that develops during disease progression have been elucidated. In this review, we will describe the mechanism of tumor immunity and how chemoradiotherapy may overcome and improve the efficacy of tumor immunity. We will also discuss the usefulness of proteins involved with tumor immunity as a predictive marker of radiotherapy response, and present an overview of ongoing clinical trials of combinations of immune checkpoint inhibitors and radiotherapy to demonstrate the promising combination therapy that has been currently emerging.

DOI PubMed

がん・生殖手術の未来図当院における子宮頸がんに対するがん生殖技術の足取りと未来図

玉手雅人, 松浦基樹, 足立岳貴, 有元千紘, 西村庸子, 黒川晶子, 秋元太志, 齋藤豪

日本外科系連合学会誌 ( 日本外科系連合学会 ) 47 ( 3 ) 404 - 404 2022.05

液体クロマトグラフィー・タンデム質量分析(LC-MS/MS)法にて診断した偽性高テストステロン血症の一例

小川万梨絵, 馬場剛, 春日芙貴子, 玉手雅人, 池田桂子, 森下美幸, 久野芳佳, 遠藤俊明, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 66 ( 1 ) 55 - 58 2022.03

日常診療におけるホルモン検査は,主に免疫学的測定法を用いて行われるが,時に臨床所見と検査所見の乖離をみることがある。今回,無月経を主訴に来院された女性で,男性化徴候がないにもかかわらず高テストステロン血症を呈した偽性高テストステロン血症の症例を経験したので報告する。症例は17歳女性,続発性無月経のため前医を受診したところ,高テストステロン血症を認めた。経腹超音波検査で明らかな卵巣腫瘍もなく,また単純MRIでも明らかな副腎腫瘍もないため,精査加療目的に当科に紹介受診となった。当科初診時の免疫学的測定法で遊離テストステロンは基準値内であったが,総テストステロンは前医同様に高値であった。男性化徴候がないことと,総テストステロン値と遊離テストステロン値とに大きな乖離を認めたため,異好抗体による偽性高値を疑い液体クロマトグラフィー-タンデム質量分析(liquid chromatography-tandem mass spectrometry:LC-MS/MS)法にてテストステロン測定を行った。結果は総テストステロンも遊離テストステロンも基準値内であった。今回使用した免疫学的測定法において,総テストステロン検査にはヒツジ由来の抗体が,遊離テストステロン検査にはウサギ由来の抗体が用いられていたため,当患者の血漿中にヒツジの抗体に非特異的に反応する異好抗体の存在が疑われた。無月経の原因として,2年前に減量を行い,BMI:22から16に低下して以来無月経となった経緯があり,体重減少性無月経が第一に考えられた。今回LC-MS/MSにて測定を行うことで,侵襲の高い選択的副腎・卵巣静脈血サンプリングを回避し診断することができた。臨床所見と検査所見に乖離がある場合には,異好抗体の存在を念頭に検査法を検討する必要がある。(著者抄録)

胎児超音波にて屈曲肢骨異形成症を疑い,胎盤絨毛の遺伝子検査で診断確定した一例

小川万梨絵, 寺本瑞絵, 染谷真行, 石堂茉泉, 新開翔太, 真里谷奨, 池田桂子, 森下美幸, 久野芳佳, 馬場剛, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 374 2022.02

当院における妊孕性温存手術後の癒着因子の抽出とアウトカム

和田渚, 玉手雅人, 木島紗弓, 篠原由梨, 西村庸子, 磯山響子, 秋元太志, 幅田周太朗, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 344 2022.02

子宮頸部原発胎児型横紋筋肉腫の一例

小谷松紗弓, 玉手雅人, 篠原由梨, 西村庸子, 磯山響子, 秋元太志, 幅田周太朗, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 297 2022.02

CD138免疫染色と子宮内microbiotaのcombined testに子宮内pH測定を加えた慢性子宮内膜炎の病態整理

遠藤俊明, 池田詩子, 逸見博文, 本間寛之, 木谷保, 真里谷奨, 久野芳佳, 馬場剛, 山田秀人, 東口篤司, 藤井美穂, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 359 2022.02

子宮頸部原発胎児型横紋筋肉腫の一例

小谷松紗弓, 玉手雅人, 篠原由梨, 西村庸子, 磯山響子, 秋元太志, 幅田周太朗, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 297 2022.02

当院における妊孕性温存手術後の癒着因子の抽出とアウトカム

和田渚, 玉手雅人, 木島紗弓, 篠原由梨, 西村庸子, 磯山響子, 秋元太志, 幅田周太朗, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 344 2022.02

Aberrant expression of claudin-6 contributes to malignant potentials and drug resistance of cervical adenocarcinoma.

Yui Ito, Akira Takasawa, Kumi Takasawa, Taro Murakami, Taishi Akimoto, Daisuke Kyuno, Yuka Kawata, Kodai Shano, Kurara Kirisawa, Misaki Ota, Tomoyuki Aoyama, Masaki Murata, Kotaro Sugimoto, Hideki Chiba, Tsuyoshi Saito, Makoto Osanai

Cancer science 2022.01 [Refereed] [International journal]

Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark of various solid tumors and it is recognized as a useful therapeutic target. Claudin-6 (CLDN6), a member of the family of TJ transmembrane proteins, is an ideal therapeutic target because it is not expressed in human adult normal tissues. In this study, we found that CLDN6 is highly expressed in uterine cervical adenocarcinoma and that high CLDN6 expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor. Shotgun proteome analysis revealed that cell-cell adhesion-related proteins and drug metabolism-associated proteins (aldo-keto reductase (AKR) family proteins) were significantly increased in CLDN6-overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell-cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin and cisplatin. Taken together, the results indicate that aberrant expression of CLDN6 enhances malignant potentials and drug resistance of cervical adenocarcinoma, possibly due to increased cell-cell adhesion properties and drug metabolism. Our findings provide an insight into a new therapeutic strategy, a CLDN6-targeting therapy, against cervical adenocarcinoma.

DOI PubMed

A screening assistance system for cervical cytology of squamous cell atypia based on a two-step combined CNN algorithm with label smoothing.

Yuta Nambu, Tasuku Mariya, Shota Shinkai, Mina Umemoto, Hiroko Asanuma, Ikuma Sato, Yoshihiko Hirohashi, Toshihiko Torigoe, Yuichi Fujino, Tsuyoshi Saito

Cancer medicine 11 ( 2 ) 520 - 529 2022.01 [International journal]

BACKGROUND: Although many cervical cytology diagnostic support systems have been developed, it is challenging to classify overlapping cell clusters with a variety of patterns in the same way that humans do. In this study, we developed a fast and accurate system for the detection and classification of atypical cell clusters by using a two-step algorithm based on two different deep learning algorithms. METHODS: We created 919 cell images from liquid-based cervical cytological samples collected at Sapporo Medical University and annotated them based on the Bethesda system as a dataset for machine learning. Most of the images captured overlapping and crowded cells, and images were oversampled by digital processing. The detection system consists of two steps: (1) detection of atypical cells using You Only Look Once v4 (YOLOv4) and (2) classification of the detected cells using ResNeSt. A label smoothing algorithm was used for the dataset in the second classification step. This method annotates multiple correct classes from a single cell image with a smooth probability distribution. RESULTS: The first step, cell detection by YOLOv4, was able to detect all atypical cells above ASC-US without any observed false negatives. The detected cell images were then analyzed in the second step, cell classification by the ResNeSt algorithm, which exhibited average accuracy and F-measure values of 90.5% and 70.5%, respectively. The oversampling of the training image and label smoothing algorithm contributed to the improvement of the system's accuracy. CONCLUSION: This system combines two deep learning algorithms to enable accurate detection and classification of cell clusters based on the Bethesda system, which has been difficult to achieve in the past. We will conduct further research and development of this system as a platform for augmented reality microscopes for cytological diagnosis.

DOI PubMed

Twin pregnancy with untyped Ehlers-Danlos syndrome requiring prompt genetic testing: A case report.

Shiori Ogawa, Tasuku Mariya, Yuya Fujibe, Marie Ogawa, Keiko Ikeda, Miyako Mizukami, Yoshika Kuno, Aki Ishikawa, Shinichi Ishioka, Akihiro Sakurai, Tsuyoshi Saito

Case reports in women's health 33 e00384 2022.01 [International journal]

Ehlers-Danlos syndrome is a rare genetic disorder that presents with a variety of pathologies depending on the disease type. Among them, vascular Ehlers-Danlos syndrome requires extremely careful management as there have been many reports of fatal perinatal complications such as uterine rupture. Although hypermobile Ehlers-Danlos syndrome is less likely to cause fatal complications, symptoms such as arthralgia, hip dislocation, and depression may be seen throughout pregnancy. We report here a case of twin pregnancy in which Ehlers-Danlos syndrome was first suspected at 19 weeks of gestation. Vascular Ehlers-Danlos syndrome could not be ruled out based on family medical history, making it difficult to determine the perinatal management strategy. Prompt genetic testing did however rule out the vascular type and the patient was diagnosed with hypermobile Ehlers-Danlos syndrome from the clinical symptoms, enabling us to manage the pregnancy safely until 34 weeks of gestation.

DOI PubMed

Case of superficial myofibroblastoma protruding from the posterior fornix treated using laparoscopic surgery

Satoshi Shikanai, Motoki Matsuura, Hiroaki Soyama, Nagisa Wada, Mina Umemoto, Ichiro Miura, Tsuyoshi Saito

JAPANESE JOURNAL OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY ( Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy ) 38 ( 2 ) 230 - 234 2022

DOI

Comparative Evaluation of Preoperative Imaging and Postoperative Histopathology in 108 Patients Who Underwent Laparoscopic- or Robot-Assisted Surgery for Endometrial Cancer.

Noriko Terada, Motoki Matsuura, Shoko Kurokawa, Mizue Teramoto, Masamitsu Hanakenaka, Tsuyoshi Saito

Gynecology and minimally invasive therapy 11 ( 4 ) 203 - 208 2022 [International journal]

OBJECTIVES: The aim of this study was to compare preoperative imaging evaluation results and postoperative histopathology examinations of patients who underwent laparoscopic- or robot-assisted surgery for suspected Stage IA endometrial carcinoma. MATERIALS AND METHODS: There were 298 patients diagnosed with endometrial cancer at our institution between April 2014 and March 2019. Preoperative imaging evaluation based on magnetic resonance imaging (MRI) and computed tomography (CT) revealed 180 patients suspected of having Stage IA disease. Of these, 72 underwent open surgery, 12 underwent robot-assisted surgery, and 96 underwent laparoscopic surgery. In this study, preoperative imaging evaluation results and postoperative histopathology examinations of 108 patients who underwent laparoscopic- or robot-assisted surgery were retrospectively compared. RESULTS: Of the 108 patients, who underwent laparoscopic- or robot-assisted surgery for suspected Stage IA disease, 98 had Stage IA, two had Stage IB, and four had Stages II and III disease. The sensitivity of imaging evaluations based on preoperative MRI and CT was 90.7%. CONCLUSION: Utilizing preoperative MRI and CT imaging resulted in a high rate of successful diagnosis of Stage IA endometrial carcinoma.

DOI PubMed

後腟円蓋より発生する腟腫瘍に対し腹腔鏡下手術を行い、表在性筋線維芽細胞腫と判明した1例

鹿内智史, 松浦基樹, 曽山浩明, 和田渚, 梅本美菜, 三浦一郎, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 38 ( 2 ) 230 - 234 2022

The Roles of Tricellular Tight Junction Protein Angulin-1/Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Endometriosis and Endometrioid-Endometrial Carcinoma.

Hiroshi Shimada, Takayuki Kohno, Takumi Konno, Tadahi Okada, Kimihito Saito, Yuma Shindo, Shin Kikuchi, Mitsuhiro Tsujiwaki, Marie Ogawa, Motoki Matsuura, Tsuyoshi Saito, Takashi Kojima

Cancers 13 ( 24 ) 2021.12 [International journal]

Tight junction proteins play roles beyond permeability barriers functions and control cell proliferation and differentiation. The relation between tight junctions and the signal transduction pathways affects cell growth, invasion and migration. Abnormality of tight junction proteins closely contributes to epithelial mesenchymal transition (EMT) and malignancy of various cancers. Angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) forms tricellular contacts that has a barrier function. Downregulation of angulin-1/LSR correlates with the malignancy in various cancers, including endometrioid-endometrial carcinoma (EEC). These alterations have been shown to link to not only multiple signaling pathways such as Hippo/YAP, HDAC, AMPK, but also cell metabolism in ECC cell line Sawano. Moreover, loss of angulin-1/LSR upregulates claudin-1, and loss of apoptosis stimulating p53 protein 2 (ASPP2) downregulates angulin-1/LSR. Angulin-1/LSR and ASPP2 concentrate at both midbody and centrosome in cytokinesis. In EEC tissues, angulin-1/LSR and ASPP2 are reduced and claudin-2 is overexpressed during malignancy, while in the tissues of endometriosis changes in localization of angulin-1/LSR and claudin-2 are seen. This review highlights how downregulation of angulin-1/LSR promotes development of endometriosis and EEC and discusses about the roles of angulin-1/LSR and its related proteins, including claudins and ASPP2.

DOI PubMed

マイクロバイオーム最前線-ヒト常在菌叢と各種疾患との関連- 腟内および子宮内細菌叢Dysbiosisへの真なるアプローチとは?

真里谷奨, 島野敏司, 遠藤俊明, 和田真一郎, 山田秀人, 藤井美穂, 水無瀬昂, 桜庭喜行, 鳥越俊彦, 齋藤豪

日本臨床微生物学会雑誌 ( (一社)日本臨床微生物学会 ) 32 ( Suppl.1 ) 164 - 164 2021.12

Next-generation sequencing of 16S rRNA for identification of invasive bacterial pathogens in a formalin-fixed paraffin-embedded placental specimen: a case report of perinatal fulminant Streptococcus pyogenes infection

Tasuku Mariya, Toyotaka Sato, Yuya Fujibe, Manami Ishido, Hiroshi Shimada, Terufumi Kubo, Yoko Nagai, Wataru Arai, Suguru E. Tanaka, Kyota Ashikawa, Yoshiyuki Sakuraba, Shinichi Ishioka, Shin-ichi Yokota, Tsuyoshi Saito

Medical Molecular Morphology ( Springer Science and Business Media LLC ) 54 ( 4 ) 374 - 379 2021.12 [Refereed] [Domestic journal]

Intrauterine infection is one of the most important causes of maternal death. In perinatal emergency, we often miss an opportunity to obtain culture specimens. In this study, we tried to examine whether we investigated whether bacteria causing infection can be detected from a formalin-fixed paraffin-embedded (FFPE) placental specimen. We examined the placenta from a maternal invasive infection that resulted in infectious abortion at 18 weeks of gestation. The case was diagnosed by acute fever and abdominal pain, and the patient was cured after 3 weeks of intensive antimicrobial treatment. Four Streptococcus pyogenes strains were isolated from vaginal fluid and blood cultures of the patient. All of the strain types were emm1/ST28. We amplified the V1-V2 region of 16S rRNA from an FFPE placental specimen and sequencing was performed using a next-generation sequencer (NGS). Taxonomic analysis was then performed for sequenced data. We succeeded in detecting causative pathogens from the FFPE placenta: 69.1% of the predominantly identified bacteria were S. pyogenes and other small populations of bacteria were detected. Our results revealed the utility of NGS for 16S rRNA analysis of an FFPE placenta. This method may reveal previous perinatal invasive infections of unknown origin retrospectively.

DOI PubMed

Radical Vaginal Trachelectomy.

Tsuyoshi Saito, Motoki Matsuura, Masato Tamate, Masahiro Iwasaki, Tasuku Mariya

Surgery journal (New York, N.Y.) 7 ( Suppl 2 ) S103-S107 2021.12 [International journal]

Recently, radical vaginal hysterectomy (RVH) has developed into laparoscopically assisted radical vaginal hysterectomy (LARVH), which is associated with the laparoscopical procedure, and it is applied as radical vaginal trachelectomy and semi-radical vaginal hysterectomy. LARVH is indicated for patients with stage IB1 and IIA1 cervical carcinoma, especially those with a tumor size of less than 2 cm, because the cardinal ligaments cannot be resected widely. Although RVH that is associated with laparoscopic pelvic lymphadenectomy is the most used surgical procedure, radical trachelectomy may be performed either abdominally or vaginally (laparoscopic or robotic). One report found that the pregnancy rate was higher in patients who underwent minimally invasive or radical vaginal trachelectomy than in those who underwent radical abdominal trachelectomy.

DOI PubMed

マイクロバイオーム最前線-ヒト常在菌叢と各種疾患との関連- 腟内および子宮内細菌叢Dysbiosisへの真なるアプローチとは?

真里谷奨, 島野敏司, 遠藤俊明, 和田真一郎, 山田秀人, 藤井美穂, 水無瀬昂, 桜庭喜行, 鳥越俊彦, 齋藤豪

日本臨床微生物学会雑誌 ( (一社)日本臨床微生物学会 ) 32 ( Suppl.1 ) 164 - 164 2021.12

子宮頸がんに対する鏡視下広汎子宮全摘術の現状と課題-LACC studyから2年- 鏡視下広汎子宮全摘術の一隅を照らすCST教育

玉手雅人, 松浦基樹, 西村庸子, 常松梨紗, 幅田周太朗, 金尾祐之, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 26 ( 7 ) WS9 - 7 2021.12

低侵襲手術時代における子宮体癌に対するリンパ節摘出の意義と方法早期子宮体癌に対するリンパ節郭清の意義と術式の選択

松浦基樹, 玉手雅人, 長尾沙智子, 西村庸子, 秋元太志, 幅田周太朗, 寺田倫子, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 26 ( 7 ) WS10 - 2 2021.12

妊娠女性の頸部細胞診妊娠中施行radical trachelectomy症例における妊娠中細胞診の変化

石岡伸一, 新開翔太, 真里谷奨, 玉手雅人, 幅田周太朗, 松浦基樹, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 60 ( Suppl.2 ) 458 - 458 2021.10

骨髄間葉系間質細胞は子宮内膜症の病態に関与しているか?

幅田周太朗, 玉手雅人, 松浦基樹, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 60 ( Suppl.2 ) 563 - 563 2021.10

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Masanori Someya, Takaaki Tsuchiya, Yuki Fukushima, Tomokazu Hasegawa, Masakazu Hori, Mio Kitagawa, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Yoshihisa Matsumoto, Koh-Ichi Sakata

Medical molecular morphology 54 ( 3 ) 245 - 252 2021.09 [Domestic journal]

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.

DOI PubMed

腹腔鏡下に治療し得た非交通性副角妊娠の一例

和田渚, 春日芙貴子, 磯山響子, 常松梨紗, 玉手雅人, 幅田周太朗, 寺田倫子, 松浦基樹, 岩崎雅宏, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 37 ( Suppl.I ) 225 - 225 2021.09

異所性妊娠破裂による出血性ショックに対して、REBOAを施行し、安全に腹腔鏡下手術をなしえた1例

岩崎雅宏, 古来愛香, 幅田周太朗, 池田桂子, 野藤五沙, 野呂薫, 玉手雅人, 松浦基樹, 秋元太志, 磯山響子, 西村庸子, 和田渚, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 37 ( Suppl.I ) 309 - 309 2021.09

PGT-SRの結果とStengel-R法による主たる不均衡型転座の予測との一致率

遠藤俊明, 馬場剛, 久野芳佳, 池田詩子, 本間寛之, 逸見博文, 稲木誠, 原鐵晃, 尾崎守, 倉橋浩樹, 斎藤豪

日本IVF学会誌 ( (一社)日本IVF学会 ) 24 ( 2 ) 60 - 60 2021.09

腹腔鏡下子宮全摘術中に腟パイプの直腸誤挿入により直腸損傷を生じた1例

伊野善彦, 玉手雅人, 篠原由梨, 西尾空, 阿部秀悦, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 37 ( Suppl.I ) 274 - 274 2021.09

後腟円蓋より突出する腟腫瘍に対し腹腔鏡下手術を行い、表在性筋線維芽細胞腫と判明した1例

鹿内智史, 松浦基樹, 梅本美菜, 杉田奈穂子, 鈴木将裕, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 37 ( Suppl.I ) 376 - 376 2021.09

肉腫成分過剰増殖を伴う子宮腺肉腫の一例

和田渚, 幅田周太朗, 安宅真名美, 野呂薫, 柏木葉月, 野藤五沙, 玉手雅人, 真里谷奨, 池田桂子, 松浦基樹, 岩崎雅宏, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 68回 60 - 60 2021.08

Bevacizumab併用PTX療法が奏功したBevacizumab併用化学療法既往のある再発子宮頸部腺癌の1例

西森貢隆, 嶋田浩志, 杉山芽, 藤部佑哉, 鈴木美紀, 玉手雅人, 松浦基樹, 岩崎雅宏, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 68回 59 - 59 2021.08

最終摘出から16年後に再発した卵巣癌ポート部位転移の1例

杉山芽, 嶋田浩志, 西森貢隆, 藤部佑哉, 鈴木美紀, 玉手雅人, 松浦基樹, 岩崎雅宏, 斎藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 68回 65 - 65 2021.08

分娩後の子宮全摘出術時に発見され、腹膜癌との鑑別が困難であった異所性脱落膜の1例

有元千紘, 長尾沙智子, 堀清貴, 山崎智子, 玉手雅人, 高田さくら, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 68回 73 - 73 2021.08

帝王切開瘢痕部妊娠に対して一期的修復術を施行した一例

齋藤晋平, 玉手雅人, 有元千紘, 長尾沙智子, 山崎智子, 西村庸子, 磯山響子, 幅田周太朗, 松浦基樹, 岩崎雅宏, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 68回 57 - 57 2021.08

待機療法にて管理したHypervascular RPOCの3例

堀清貴, 山崎智子, 有元千紘, 長尾沙智子, 玉手雅人, 高田さくら, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 68回 46 - 46 2021.08

Effectiveness of cross double mcdonald cerclage for intractable bleeding from a cervical varix in pregnant women

Yuya Fujibe, Tasuku Mariya, Masahito Mizuuchi, Shinichi Ishioka, Tsuyoshi Saito

Gynecology and Minimally Invasive Therapy ( Wolters Kluwer Medknow Publications ) 10 ( 3 ) 177 - 180 2021.07

Cervical varix during pregnancy is a rare condition, and standard management for bleeding from a varix has not been established. We performed cross double cervical cerclage and effectively stopped bleeding. A 41-year-old female had a twin pregnancy. The development of a cervical varix was observed during pregnancy and bleeding from ruptured varix started at 20 weeks of gestation. We performed surgical hemostasis by cervical cerclage. In the first cerclage, we could not stop the bleeding from the varix. For further restriction of blood supply to the cervical varix, we performed a second cerclage in a crossed position on a deeper side of the vagina than the first cerclage. Then the bleeding completely stopped and there was no bleeding until delivery. The 'cross double McDonald cerclage' performed in our patient may be a useful modified cerclage method for stopping intractable bleeding from the cervix during pregnancy.

DOI

子宮温存している若年発症子宮体部腺肉腫の2例

寺田倫子, 松浦基樹, 野藤五沙, 西村庸子, 真里谷奨, 玉手雅人, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 292 - 292 2021.07

子宮体癌と大腸癌におけるミスマッチ修復タンパク欠損と免疫逃避機構の差異に関する検討

真里谷奨, 廣橋良彦, 久保輝文, 岩崎雅宏, 鳥越俊彦, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 214 - 214 2021.07

婦人科腫瘍を疑われた乳癌子宮転移の一例

野藤五沙, 西森貢隆, 安宅真名美, 柏木葉月, 真里谷奨, 池田圭子, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 288 - 288 2021.07

子宮温存している若年発症子宮体部腺肉腫の2例

寺田倫子, 松浦基樹, 野藤五沙, 西村庸子, 真里谷奨, 玉手雅人, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 292 - 292 2021.07

子宮体癌と大腸癌におけるミスマッチ修復タンパク欠損と免疫逃避機構の差異に関する検討

真里谷奨, 廣橋良彦, 久保輝文, 岩崎雅宏, 鳥越俊彦, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 214 - 214 2021.07

消化管ポリープ切除技術を応用した子宮頸部円錐切除術とコストの検討

玉手雅人, 松浦基樹, 西村庸子, 寺田倫子, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 330 - 330 2021.07

術前補助化学療法後の子宮頸癌再発に対しheterogeneousな免疫逃避機構が関与している可能性症例報告(Heterogenous Immune Escape Mechanisms Might be Related to Recurrence of Cervical Cancer after the Neoadjuvant Chemotherapy: A Case Report)

常松梨紗, 岩崎雅宏, 廣橋良彦, 阿部秀悦, 小川万梨絵, 郷久晴朗, 西村庸子, 玉手雅人, 磯山響子, 寺田倫子, 松浦基樹, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 320 - 320 2021.07

自己採取および尿採取HPV検査の有効性に関する検討

松浦基樹, 寺田倫子, 西村庸子, 玉手雅人, 磯山響子, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 326 - 326 2021.07

Estimation of Physiologic Ability and Surgical Stress(E-PASS)で評価した後期高齢者の婦人科手術

篠原由梨, 玉手雅人, 岡田匡氷, 春日芙貴子, 阿部秀悦, 伊野善彦, 寺田倫子, 松浦基樹, 岩崎雅宏, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 32 ) 152 - 152 2021.06

手術室の医療安全を考えるサージカルスモークについて

西尾空, 玉手雅人, 松浦基樹, 寺田倫子, 磯山響子, 春日芙貴子, 岡田匡氷, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 32 ) 153 - 153 2021.06

多様化する子宮全摘腟式子宮全摘の視点全アプローチを経験して振り返った腟式

玉手雅人, 松浦基樹, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 32 ) 13 - 19 2021.06

帝王切開術後癒着症例に対する腹腔鏡下子宮全摘術での膀胱剥離の工夫

有元千紘, 長尾沙智子, 山崎智子, 高田さくら, 玉手雅人, 恐神博行, 松浦基樹, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 32 ) 138 - 138 2021.06

多様化する手術教育の実践がんの手術をどう学び、どう伝えるか

松浦基樹, 玉手雅人, 西村庸子, 寺田倫子, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 32 ) 43 - 46 2021.06

Increased cervical Chlamydia trachomatis and syphilis infections in Japanese females of reproductive age in the late 2010s: Possible cause.

Satoshi Shimano, Tasuku Mariya, Tsuyoshi Saito

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2021.05 [International journal]

From 2000 to 2019, Japan's reproductive-age population gradually declined by 24%. In comparison, the Chlamydia trachomatis infection rate increased from 2016, with the syphilis infection rate increasing more sharply from 2014. Since 2013, the numbers of foreign tourists to Japan have also increased. From 2011 to 2018, the rate of increase in tourists was 5.02 times, while the rate of increase in syphilis patients was higher at 22.4 times. The lack of a one-to-one relationship between foreign tourists and syphilis cases suggests that cases of syphilis were transmitted to others. Although the prevalence of syphilis in the tourists' home countries (Korea in 2014 and China in 2013) was 20-30 times higher than that in Japan, the Japanese sex industry did not discriminate against foreign tourists, leading to increased STI infections in Japanese female sex workers. Indeed, from 2017 to 2018, a history of working in the sex industry for six months was identified as a risk factor for syphilis. The rise in Chlamydia trachomatis infections has lagged behind that of syphilis by two years, with the rate of increase lower. We suspect the difference in increasing rates of syphilis and chlamydial infections is due to the different methods of infection: syphilis can be transmitted by light physical contact, such as a kiss, whereas chlamydia requires close sexual contact, such as oral sex or sexual intercourse. Regardless, examinations and infection control are necessary to prevent the spread of STIs in Japan due to inbound tourists.

DOI PubMed

体腔液セルブロックによる免疫染色の検討

玉手雅人, 松浦基樹, 西村庸子, 新開翔太, 真里谷奨, 寺田倫子, 岩崎雅宏, 石岡伸一, 杉田真太朗, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 60 ( Suppl.1 ) 189 - 189 2021.05

医師採取HPV検査と自己採取および尿採取法によるHPV検査の比較研究

寺田倫子, 松浦基樹, 西村庸子, 玉手雅人, 長尾沙智子, 田渕雄大, 寺本瑞絵, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 60 ( Suppl.1 ) 228 - 228 2021.05

進行卵巣癌における腹水細胞診と腹水遺伝子診断

松浦基樹, 西村庸子, 玉手雅人, 寺田倫子, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 60 ( Suppl.1 ) 269 - 269 2021.05

Does Radical trachelectomy (RT) during pregnancy have higher obstetrical and oncological risks than RT before pregnancy?

Shota Shinkai, Shinichi Ishioka, Tasuku Mariya, Yuya Fujibe, Miseon Kim, Masayuki Someya, Tsuyoshi Saito

( Research Square Platform LLC ) 2021.03

Abstract Purpose Radical trachelectomy (RT) with pelvic lymphadenectomy has become a new treatment option for young patients with uterine cervical cancer stages 1A2–1B1 who desire the preservation of their fertility. However, the application of RT for pregnant patients is still controversial. We comparatively studied both obstetrical and oncological outcomes of pregnant patients who underwent vaginal RT during pregnancy and those who underwent vaginal RT before pregnancy. Methods Both obstetrical and oncological results of eight patients who underwent vaginal RT with pelvic lymphadenectomy during pregnancy in our institute between 2010 and 2020 (Group A), and ten pregnant patients who underwent vaginal RT with pelvic lymphadenectomy before pregnancy during the same period (Group B) were reviewed based on their medical charts. Results There were no significant differences in blood loss, surgical time, or surgical completeness between Group A and Group B. Nor were there significant differences in obstetrical outcomes between the two groups. However, two of the eight patients in Group A had recurrence of the cancer. None of the patients in Group B has shown any signs of recurrence thus far. Conclusion Vaginal RT during pregnancy does not affect the obstetrical prognoses of patients with early invasive uterine cervical cancer, and it might be a tolerable treatment modality for them. However, oncologically, it should be performed carefully as there is a risk of recurrence.

DOI

PSGファミリーの異常浸潤性胎盤診断バイオマーカーとしての可能性

柏木葉月, 真里谷奨, 新開翔太, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 73 ( 臨増 ) S - 611 2021.03

高次施設における帝王切開率抑制の試み

染谷真行, 新開翔太, 真里谷奨, 小川万梨絵, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 73 ( 臨増 ) S - 367 2021.03

Less correlation between mismatch repair proteins deficiency and decreased expression of HLA class I molecules in endometrial carcinoma: a different propensity from colorectal cancer.

Tasuku Mariya, Terufumi Kubo, Yoshihiko Hirohashi, Junko Yanagawa, Yuta Tabuchi, Kazuhiko Matsuo, Kiyoshi Furumura, Rena Morita, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Toshihiko Torigoe

Medical molecular morphology 54 ( 1 ) 14 - 22 2021.03 [Domestic journal]

Mismatch repair protein deficiency (dMMR) is a favorable prognostic factor in colorectal cancer. It is also associated with aberrant expression of HLA class I molecules, which are required for cytotoxic T lymphocyte-mediated cancer immunotherapy. Because dMMR is frequently also found in endometrial cancers (ECs), we retrospectively investigated the expression of mismatch repair proteins and HLA class I molecules in 127 EC patients. In this study, EC patients being treated in our hospital were recruited from 2005 to 2009 and observed until December 2017. Lesion specimens were evaluated via immunohistochemistry for MSH6 and PMS2 (mismatch repair proteins) and HLA class I molecules. Expression of these molecules was statistically related to clinical and pathological factors and prognosis. dMMR was detected in 33 patients and did not correlate with the expression level of HLA class I molecules (P = 0.60). On the other hand, unexpectedly, multivariate analysis revealed that intact expression of HLA class I molecules was associated with p53 overexpression (P = 0.004). Neither dMMR nor decreased expression of HLA class I molecules were prognostic factors. These results are inconsistent with previous findings for colorectal cancer. A distinctive local tissue immune microenvironment would underlie the discrepancy in the results between EC and colorectal cancer.

DOI PubMed

Common iliac artery dissection as a complication of common iliac artery balloon occlusion for placenta percreta: A case report.

Kimihito Saito, Tasuku Mariya, Yuya Fujibe, Masato Saito, Naoki Hirokawa, Shinichi Ishioka, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 47 ( 3 ) 1172 - 1177 2021.03 [International journal]

A 37-year-old pregnant woman who had undergone three previous cesarean sections was diagnosed as having placenta percreta. We decided to perform cesarean hysterectomy with bilateral common iliac artery balloon occlusion (CIABO). The duration of surgery was 2 h and 2 min and total estimated blood loss was 2600 mL. Surgery was completed without any surgical complications, but the pulse oximeter waveform of the left leg became undetectable during surgery. We immediately performed angiography after closure of laparotomy and found abnormal pooling of contrast media at the left common iliac artery in the region in which the balloon was positioned. We made a diagnosis of left common iliac artery dissection caused by CIABO. We performed emergent revascularization by intravascular stenting. We conclude that CIABO can cause common iliac artery dissection by mechanical stimulation of the inflated balloon. Careful intraoperative evaluation of limb ischemia and preparation of intravascular treatment is needed for a safe procedure.

DOI PubMed

子宮体がんスクリーニングにおける遺伝子解析併用の有用性

松浦基樹, 玉手雅人, 西尾空, 西村庸子, 磯山響子, 寺田倫子, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 73 ( 臨増 ) S - 400 2021.03

病院全体の医療安全を考えるサージカルスモークについて

西尾空, 玉手雅人, 松浦基樹, 寺田倫子, 磯山響子, 春日芙貴子, 岡田匡氷, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 73 ( 臨増 ) S - 297 2021.03

術前化学療法が奏功し手術療法が可能となった子宮頸癌IV期病変の摘出子宮における腫瘍浸潤リンパ球(TIL)の特徴を検証した1例

常松梨紗, 岩崎雅宏, 郷久晴朗, 阿部秀悦, 小川万梨絵, 黒川晶子, 西村庸子, 玉手雅人, 磯山響子, 寺田倫子, 松浦基樹, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 73 ( 臨増 ) S - 313 2021.03

Cadaver Surgery Trainingの壁と意義

玉手雅人, 松浦基樹, 西尾空, 太田未咲, 佐藤由梨, 野呂薫, 長尾沙智子, 阿部秀悦, 西村庸子, 磯山響子, 寺田倫子, 郷久晴朗, 岩崎雅宏, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 65 ( 1 ) 88 - 89 2021.03

胃原発転移性卵巣腫瘍に対し付属器摘出術を施行した症例の検討

田中綾一, 辻靖, 南妃奈, 清水亜由美, 池田詩子, 逸見博文, 神崇志, 新藤智子, 鈴木善法, 玉手雅人, 松浦基樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 65 ( 1 ) 43 - 48 2021.03

転移性卵巣腫瘍は胃癌または大腸癌からの転移が最も多い。胃癌からの転移性卵巣腫瘍は周囲臓器へ浸潤または癒着を認める症例は比較的少なく低侵襲に摘出可能であることが多い。胃原発転移性卵巣腫瘍に対し付属器摘出術を施行した症例について検討した。対象は2017年から2年間の間に胃癌を原発とした転移性卵巣腫瘍に対し付属器摘出術を施行した6例。周術期合併症,術後化学療法開始までの期間,無増悪期間,生存期間,術前術後のQOLの変化等について検討した。胃癌診断時の年齢の中央値は47.0歳,6例中5例に腹腔鏡下手術を選択し,周術期合併症を認めた症例は無かった。術前に下腹部痛を認めた2例は共に術後の症状の消失が確認できた。化学療法再開までの中央値は18.0日,増悪または再発をみとめた3例の無増悪期間はそれぞれ8,2,8ヵ月,付属器摘出術後12,8,12ヵ月に原病死に至った。他の3例は現在いずれも無病生存している。症状緩和目的または卵巣転移以外の病勢が充分に制御されている症例において胃原発転移性卵巣腫瘍に対する付属器摘出術は検討され得ると考えられた。(著者抄録)

妊娠時に繰り返す脱落膜ポリープを保存的に管理し第1子で死産となるも第2子で生児を得た1例

倉ありさ, 藤部佑哉, 石堂茉泉, 鹿内智史, 野藤五沙, 新開翔太, 嶋田浩志, 鈴木美紀, 石岡伸一, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 65 ( 1 ) 32 - 37 2021.03

Study of laparoscopic monopolar devices and its thermal effects

Motoki Matsuura, Masato Tamate, Sachiko Nagao, Muna Nishio, Tadahi Okada, Yoko Nishimura, Kyoko Isoyama, Noriko Terada, Tsuyoshi Saito

European Journal of Gynaecological Oncology ( IMR Press Limited ) 42 ( 1 ) 118 - 121 2021.02

Objective: Energy devices are frequently used in minimally invasive surgeries (MIS). For MIS involving gynecologic malignancies, energy devices should be used cautiously to prevent thermal injuries to nearby organs. We evaluated monopolar electrosurgery devices and measured increases in temperature in the tissue and device. Methods: Briefly, the surface of a porcine tissue was incised using short and long activation times. Subsequently, the maximum temperature at the tip of the monopolar device, the cooling time required to reach a temperature of 60 ◦C, and the maximum tissue temperature were recorded. Results: Longer activation time was correlated with a higher tip temperature. With all activation times, there was an increase in the tip temperature that exceeded 100 ◦C. The cooling time to reach 60 ◦C was faster with the short activation times than with the long activation times. Even with the same output, the temperature decreased faster in the coagulation mode, suggesting that the cooling times were shorter with lower outputs. The tissue temperature dropped to 60 ◦C or less within 1 s in the cut mode but required approximately 2 s in the coagulation mode at 40 W. The temperature of the dissected tissue increased to 60 ◦C or higher the cooling time was longer with high output and in the coagulation mode. Conclusions: We revealed that the activation of the monopolar device under routine use conditions exceeded a temperature of 100 ◦C. Additionally, the temperatures of the tip and tissue were significantly higher in proportion to the output and time. For MIS involving gynecologic malignancies, careful attention is necessary to avoid thermal injury.

DOI

Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.

Taro Murakami, Akira Takasawa, Kumi Takasawa, Taishi Akimoto, Tomoyuki Aoyama, Kazufumi Magara, Yuki Saito, Misaki Ota, Daisuke Kyuno, Soh Yamamoto, Tadashi Hasegawa, Tsuyoshi Saito, Makoto Osanai

Cancer science 112 ( 2 ) 906 - 917 2021.02 [International journal]

Recent studies have shown that aberrant expression of tight junction proteins (TJP) contributes to malignant potential of various cancers. In the present study, we investigated the expression of junctional adhesion molecule-A (JAM-A), one of the transmembrane TJP, in uterine cervical adenocarcinoma and the significance of its expression for malignancy. Immunohistochemistry on human surgical specimens showed that JAM-A was aberrantly expressed in neoplastic regions including adenocarcinoma in situ (AIS). Knockout of JAM-A significantly suppressed cell proliferation and colony-forming and migration abilities. We also showed that an antibody specific to an extracellular region of JAM-A reduced cell proliferation ability and that loss of JAM-A increased drug sensitivity of cervical adenocarcinoma cells. Based on a comprehensive proteome analysis, we found that poliovirus receptor (PVR/CD155) was regulated by JAM-A and formed a physical interaction with JAM-A. In human surgical specimens, PVR/CD155 expression was significantly correlated with some clinicopathological features and prognosis of cervical adenocarcinoma. Interestingly, most of the PVR/CD155-positive cases expressed a high level of JAM-A, and patients with the expression pattern of PVR/CD155 positive/JAM-A high had significantly shorter periods of relapse-free survival (P = .00964) and overall survival (P = .0204) than those for the other patients. Our observations suggest that aberrant expression of JAM-A promotes malignancy of uterine cervical adenocarcinoma by regulation of PVR/CD155, and JAM-A is therefore a potential therapeutic target for this malignancy.

DOI PubMed

島野敏司, 真里谷奨, 長井陽子, 芦川享大, 荒井渉, 斎藤豪

臨床と微生物 ( (株)近代出版 ) 48 ( 1 ) 041 - 045 2021.01

ERα increases endometrial cancer cell resistance to cisplatin via upregulation of BAG3.

Shuetsu Abe, Masahiro Iwasaki, Shutaro Habata, Tasuku Mariya, Masato Tamate, Motoki Matsuura, Seiro Satohisa, Tsuyoshi Saito

Oncology letters 21 ( 1 ) 20 - 20 2021.01 [International journal]

Endometrial cancer is a leading cause of cancer-associated mortality in women and has a poor prognosis in advanced stages. Our previous study revealed that BCL-2-associated athanogene 3 (BAG3) may contribute to enhancing cell viability through downregulation of microRNA (miR)-29b in endometrial cancer cell lines. In addition, a relationship between estrogen receptor α (ERα) and BAG3 was recently reported in several cancer cell types. The present study investigated the relationship between ERα and BAG3 in endometrial cancer cell lines. The results demonstrated that exogenous ERα overexpression enhanced BAG3 expression in the EMTOKA endometrial cancer cell line, which does not endogenously express ERα, but had no effect on BAG3 expression levels in the Ishikawa cell line, which does endogenously express ERα. In addition, ERα overexpression suppressed miR-29b expression and enhanced the expression of Mcl-1, a mediator situated downstream of BAG3, in EMTOKA cells, but not Ishikawa cells. ERα overexpression also enhanced EMTOKA, but not Ishikawa, endometrial cancer cell viability in the presence of cisplatin. These findings suggested that ERα may contribute to enhancing endometrial cancer cell resistance to anticancer agents through BAG3 overexpression.

DOI PubMed

骨盤解剖学をCadaver Surgery Trainingで理解する混合研究の試み

玉手雅人, 松浦基樹, 阿部秀悦, 西村庸子, 常松梨沙, 寺田倫子, 真里谷奨, 岩崎雅宏, 金尾祐之, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 311 - 311 2021.01

ERα発現および非発現子宮体癌細胞株に於けるBAG3発現および増殖能との関連

阿部秀悦, 岩崎雅宏, 幅田周太朗, 真里谷奨, 小川万梨絵, 郷久晴朗, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 285 - 285 2021.01

Deep Learning(YOLOv3)を用いたリアルタイム婦人科細胞診断支援システム設計の試み

真里谷奨, 新開翔太, 松浦基樹, 郷久晴朗, 岩崎雅宏, 南部優太, 藤野雄一, 淺沼広子, 廣橋良彦, 鳥越俊彦, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 278 - 278 2021.01

ERα発現および非発現子宮体癌細胞株に於けるBAG3発現および増殖能との関連

阿部秀悦, 岩崎雅宏, 幅田周太朗, 真里谷奨, 小川万梨絵, 郷久晴朗, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 285 - 285 2021.01

Deep Learning(YOLOv3)を用いたリアルタイム婦人科細胞診断支援システム設計の試み

真里谷奨, 新開翔太, 松浦基樹, 郷久晴朗, 岩崎雅宏, 南部優太, 藤野雄一, 淺沼広子, 廣橋良彦, 鳥越俊彦, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 278 - 278 2021.01

骨盤解剖学をCadaver Surgery Trainingで理解する混合研究の試み

玉手雅人, 松浦基樹, 阿部秀悦, 西村庸子, 常松梨沙, 寺田倫子, 真里谷奨, 岩崎雅宏, 金尾祐之, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 311 - 311 2021.01

タイト結合分子Cluadin-2をターゲットにした子宮内膜癌治療のin vitroにおける検討

嶋田浩志, 岡田匡氷, 金野匠, 幸野貴之, 松浦基樹, 郷久晴朗, 岩崎雅宏, 小島隆, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 285 - 285 2021.01

婦人科がんにおける腹腔細胞診の意義進行卵巣癌における腹水細胞診の意義

松浦基樹, 西村庸子, 玉手雅人, 磯山響子, 寺田倫子, 岩崎雅宏, 磯部友見子, 畠山晴良, 高根希世子, 山口貴世志, 池上恒雄, 古川洋一, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 185 - 185 2021.01

腹腔鏡下子宮筋腫核出術後に発生したparasitic myomaの1例

岩崎雅宏, 真里谷奨, 阿部秀悦, 松浦基樹, 玉手雅人, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 36 ( Suppl.I ) [O - 196] 2020.11

YOLOv3を用いた子宮頸部細胞診画像クラスタリング手法の提案

南部優太, 真里谷奨, 新開翔太, 淺沼広子, 廣橋良彦, 齋藤豪, 鳥越俊彦, 佐藤生馬, 藤野雄一

医療情報学連合大会論文集 ( (一社)日本医療情報学会 ) 40回 482 - 486 2020.11

Possibility of Targeting Claudin-2 in Therapy for Human Endometrioid Endometrial Carcinoma.

Tadahi Okada, Takumi Konno, Takayuki Kohno, Hiroshi Shimada, Kimihito Saito, Seiro Satohisa, Tsuyoshi Saito, Takashi Kojima

Reproductive sciences (Thousand Oaks, Calif.) 27 ( 11 ) 2092 - 2103 2020.11 [International journal]

Claudin-2 (CLDN-2) is a leaky-type tight junction protein, and its overexpression increases tumorigenesis of some types of cancer cells. In the present study, to examine the possibility of targeting CLDN-2 in the therapy for endometrioid endometrial adenocarcinoma, we investigated the regulation and role of CLDN-2 in endometriosis and endometrioid endometrial adenocarcinoma. In endometrioid endometrial adenocarcinoma tissues, marked upregulation of CLDN-2 was observed together with malignancy, while in endometriosis tissues, a change in the localization of CLDN-2 was observed. In cells of the endometrial adenocarcinoma cell line Sawano, which highly express CLDN-2, downregulation of CLDN-2 induced by the siRNA upregulated the epithelial barrier and inhibited cell migration. Furthermore, the downregulation of CLDN-2 affected the cell cycle and inhibited cell proliferation. In Sawano cells cultured with high-glucose medium, CLDN-2 expression was downregulated at the mRNA and protein levels. The high-glucose medium upregulated the epithelial barrier, cell proliferation, and migration, and inhibited cell invasion. The histone deacetylase (HDAC) inhibitor tricostatin A (TSA), which has antitumor effects, downregulated CLDN-2 expression, cell proliferation, invasion, and migration, and upregulated the epithelial barrier. The mitochondrial respiration level, an indicator of cancer metabolism, was downregulated by CLDN-2 knockdown and upregulated by the high-glucose condition. Taken together, these results indicated that overexpression of CLDN-2 closely contributed to the malignancy of endometrioid endometrial adenocarcinoma. Downregulation of CLDN-2 via the changes of the glucose concentration and treatment with HDAC inhibitors may be important in the therapy for endometrial cancer.

DOI PubMed

胎児期に診断に苦慮した先天性嚢胞状腺腫様形成異常に胸腔外肺分画症を合併した一例

染谷真行, 古来愛香, 新開翔太, 真里谷奨, 石岡伸一, 齋藤豪

超音波医学 ( (公社)日本超音波医学会 ) 47 ( Suppl. ) S418 - S418 2020.11

腹腔鏡下子宮筋腫核出術後に発生したparasitic myomaの1例

岩崎雅宏, 真里谷奨, 阿部秀悦, 松浦基樹, 玉手雅人, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 36 ( Suppl.I ) [O - 196] 2020.11

若手医師に対する腹腔鏡手術の教育原点回帰、Cadaver Surgery Trainingを用いた教育

玉手雅人, 松浦基樹, 篠原由梨, 黒川晶子, 西村庸子, 磯山響子, 寺田倫子, 金尾祐之, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 36 ( Suppl.I ) [SY1 - 4] 2020.11

腹腔鏡下子宮全摘出術施行時に偶発的に副脾を認めた一例

長尾沙智子, 有元千紘, 山崎智子, 玉手雅人, 恐神博行, 高田さくら, 松浦基樹, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 36 ( Suppl.I ) [O - 046] 2020.11

深層学習を用いた子宮頸部細胞診人工知能診断支援システムの有用性について

真里谷奨, 南部優太, 淺沼広子, 廣橋良彦, 岩崎雅宏, 藤野雄一, 鳥越俊彦, 齋藤豪

日本癌学会総会記事 ( (一社)日本癌学会 ) 79回 OJ15 - 7 2020.10

Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy

Masanori Someya, Takaaki Tsuchiya, Yuki Fukushima, Tomokazu Hasegawa, Yu Takada, Masakazu Hori, Katsutoshi Miura, Mio Kitagawa, Toshio Gocho, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-ichi Sakata

Japanese Journal of Clinical Oncology ( Oxford University Press (OUP) ) 2020.08

Abstract Objective To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. Methods We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. Results In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. Conclusion The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.

DOI

ASPP2 suppression promotes malignancy via LSR and YAP in human endometrial cancer.

Takumi Konno, Takayuki Kohno, Tadahi Okada, Hiroshi Shimada, Seiro Satohisa, Shin Kikuchi, Tsuyoshi Saito, Takashi Kojima

Histochemistry and cell biology 154 ( 2 ) 197 - 213 2020.08 [International journal]

Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via binding with p53 and epithelial polarity molecule PAR3. Lipolysis-stimulated lipoprotein receptor (LSR) is an important molecule at tricellular contacts, and loss of LSR promotes cell migration and invasion via Yes-associated protein (YAP) in human endometrial cancer cells. In the present study, to find how ASPP2 suppression promotes malignancy in human endometrial cancer, we investigated its mechanisms including the relationship with LSR. In endometriosis and endometrial cancers (G1 and G2), ASPP2 was observed as well as PAR3 and LSR in the subapical region. ASPP2 decreased in G3 endometrial cancer compared to G1. In human endometrial cancer cell line Sawano, ASPP2 was colocalized with LSR and tricellulin at tricellular contacts and binding to PAR3, LSR, and tricellulin in the confluent state. ASPP2 suppression promoted cell migration and invasion, decreased LSR expression, and induced expression of phosphorylated YAP, claudin-1, -4, and -7 as effectively as the loss of LSR. Knockdown of YAP prevented the upregulation of pYAP, cell migration and invasion induced by the ASPP2 suppression. Treatment with a specific antibody against ASPP2 downregulated ASPP2 and LSR, affected F-actin at tricellular contacts, upregulated expression of pYAP and claudin-1, and induced cell migration and invasion via YAP. In normal human endometrial epithelial cells, ASPP2 was in part colocalized with LSR at tricellular contacts and knockdown of ASPP2 or LSR induced expression of claudin-1 and claudin-4. ASPP2 suppression promoted cell invasion and migration via LSR and YAP in human endometrial cancer cells.

DOI PubMed

Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy.

Takaaki Tsuchiya, Masanori Someya, Yu Takada, Tomokazu Hasegawa, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Masakazu Hori, Kensei Nakata, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsuyoshi Saito, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 196 ( 8 ) 725 - 735 2020.08 [International journal]

PURPOSE: To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters. MATERIALS AND METHODS: We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples. RESULTS: PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy (p = 0.043). CD8+ T cell infiltration (p = 0.002) and FoxP3+ T cell infiltration (p = 0.003) decreased significantly after chemoradiotherapy. Expression of PD‑1, PD-L1-expressing immune cells (PD-L1 IC), and HLA‑1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells (p = 0.001) and FoxP3+ T cells (p = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS (p < 0.001) and was related to a significantly lower probability of out-of-field recurrence (p = 0.005). CONCLUSION: Chemoradiotherapy induced an immunologic shift that increased PD-L1 TC. Chemoradiotherapy has immunological effects that can influence the results of treatment for uterine cervical cancer.

DOI PubMed

Cadaver Surgery Trainingの壁を超える意義

玉手雅人, 松浦基樹, 西村庸子, 真里谷奨, 磯山響子, 寺田倫子, 郷久晴朗, 岩崎雅宏, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 31 ) 189 - 189 2020.08

Aldolase A promotes epithelial-mesenchymal transition to increase malignant potentials of cervical adenocarcinoma.

Yuki Saito, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Taishi Akimoto, Misaki Ota, Kazufumi Magara, Masaki Murata, Yoshihiko Hirohashi, Tadashi Hasegawa, Norimasa Sawada, Tsuyoshi Saito, Makoto Osanai

Cancer science 111 ( 8 ) 3071 - 3081 2020.08 [International journal]

Recent studies have revealed that metabolic reprogramming is closely associated with epithelial-mesenchymal transition (EMT) during cancer progression. Aldolase A (ALDOA) is a key glycolytic enzyme that is highly expressed in several types of cancer. In this study, we found that ALDOA is highly expressed in uterine cervical adenocarcinoma and that high ALDOA expression promotes EMT to increase malignant potentials, such as metastasis and invasiveness, in cervical adenocarcinoma cells. In human surgical specimens, ALDOA was highly expressed in cervical adenocarcinoma and high ALDOA expression was correlated with lymph node metastasis, lymphovascular infiltration, and short overall survival. Suppression of ALDOA expression significantly reduced cell growth, migration, and invasiveness of cervical cancer cells. Aldolase A expression was partially regulated by hypoxia-inducible factor-1α (HIF-1α). Shotgun proteome analysis revealed that cell-cell adhesion-related proteins were significantly increased in ALDOA-overexpressing cells. Interestingly, overexpression of ALDOA caused severe morphological changes, including a cuboidal-to-spindle shape shift and reduced microvilli formation, coincident with modulation of the expression of typical EMT-related proteins. Overexpression of ALDOA increased migration and invasion in vitro. Furthermore, overexpression of ALDOA induced HIF-1α, suggesting a positive feedback loop between ALDOA and HIF-1α. In conclusion, ALDOA is overexpressed in cervical adenocarcinoma and contributes to malignant potentials of tumor cells through modulation of HIF-1α signaling. The feedback loop between ALDOA and HIF-1α could become a therapeutic target to improve the prognosis of this malignancy.

DOI PubMed

ロボット手術におけるPeNのコツ

松浦基樹, 西村庸子, 黒川晶子, 玉手雅人, 磯山響子, 寺田倫子, 郷久晴朗, 岩崎雅宏, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 31 ) 155 - 155 2020.08

Mucinous carcinoma originating in the peritoneum diagnosed by an ascites cell block: a case report.

Sachiko Nagao, Motoki Matsuura, Masato Tamate, Shintaro Sugita, Tsuyoshi Saito

Journal of medical case reports 14 ( 1 ) 99 - 99 2020.07 [International journal]

BACKGROUND: Peritoneal carcinoma is a rare disease that is diagnosed and treated in a manner similar to ovarian cancer. In most cases, the histological type is serous carcinoma, and chemotherapy is effective. However, there are a few case reports of mucinous peritoneal carcinoma. We inferred the histological type before surgery using an ascites cell block sample, which was useful for determining the treatment plan. CASE PRESENTATION: Our patient was a 60-year-old Japanese woman. She presented with a feeling of fullness in the abdomen. A computed tomographic scan showed a large quantity of ascitic fluid and thickening of the greater omentum, as well as thickening of the peritoneum at the pouch of Douglas and diaphragm. Hence, peritoneal carcinoma was suspected. The tumor markers carcinoembryonic antigen, cancer antigen 19-9, and cancer antigen 125 were all increased, and no malignant findings were observed in the uterus or ovaries. Cells suggestive of carcinoma were found in the ascitic fluid, and immunostaining by the cell block method suggested the possibility of mucinous carcinoma. The preoperative chemotherapy strategy was changed to short courses, and tumor reduction surgery was planned. Similar to the suspicion before surgery, the pathology results indicated mucinous carcinoma, and the therapeutic effect of chemotherapy was grade 0. CONCLUSIONS: Determining whether peritoneal carcinoma is serous carcinoma is important for therapy and prognostic prediction. In this case, we encountered a patient for whom surgery was chosen because of drug therapy resistance inferred through histological type estimation using the cell block method. Inferring the histological type by cell block preparation is useful for diagnosis and treatment selection.

DOI PubMed

当院婦人科領域におけるBRCA遺伝子検査状況の変化

真里谷奨, 寺田倫子, 宮崎幸子, 石川亜貴, 岩崎雅宏, 齋藤豪, 櫻井晃洋

日本遺伝カウンセリング学会誌 ( 日本遺伝カウンセリング学会 ) 41 ( 2 ) 75 - 75 2020.06

【専門医はもういらない? せまりくるAI時代】AIによる病理組織診断支援

真里谷奨, 久保輝文, 齋藤豪, 鳥越俊彦

産婦人科の実際 ( 金原出版(株) ) 69 ( 5 ) 463 - 468 2020.05

＜文献概要＞AIによる画像認識は,深層学習による画像特徴の自動解析が実用化して以後,多分野への応用が試みられている。医療画像におけるAI研究も深層学習の登場によりパラダイムシフトが起こっており,わが国が豊富なリソースを有する放射線画像や内視鏡画像,ならびに病理組織画像について多種多様な検討が行われてきた。本稿では,AIによる病理組織診断支援の概要と実際について,特に実臨床における有用性および発展性を主体に述べる。

Transabdominal cerclage (TAC) as a new tool for the treatment of cervical incompetence (CI).

Shinichi Ishioka, Tasuku Mariya, Masayuki Someya, Tsuyoshi Saito

Annals of translational medicine 8 ( 9 ) 571 - 571 2020.05 [International journal]

DOI PubMed

妊娠中の広汎子宮頸部摘出術(RT)後子宮頸部細胞診における異型細胞の出現

石岡伸一, 真里谷奨, 金美善, 新開翔太, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 59 ( Suppl.1 ) 232 - 232 2020.05

Deep Learning(YOLO)を用いた子宮頸部細胞診診断支援の有用性

新開翔太, 真里谷奨, 郷久晴朗, 岩崎雅宏, 南部優太, 藤野雄一, 淺沼広子, 廣橋良彦, 鳥越俊彦, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 59 ( Suppl.1 ) 207 - 207 2020.05

開腹子宮頸部縫縮術(TAC)後妊娠初期流産症例に対するmethotrexate(MTX)療法の一例

石堂茉泉, 石岡伸一, 藤部佑哉, 鈴木美紀, 嶋田浩志, 真里谷奨, 馬場剛, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 56 ( 1 ) 198 - 202 2020.05

34歳。子宮頸癌のため腟式広汎子宮頸部摘出術+骨盤リンパ節郭清術の既往で有った。その2年後に体外受精により妊娠し、妊娠19週で帝王切開による分娩となった。この分娩から3年後にテフロンテープを用いた開腹子宮頸部縫縮術(TAC)を施行し、TAC後6ヵ月で体外受精にて妊娠したが、妊娠8週で稽留流産となった。流産後3ヵ月経過しても子宮内容物が排出されず絨毛組織の筋層内浸潤が疑われ、流産後12週よりMTX投与1日20mg・5日間を2週間毎に開始し、3コース終了後に血清ヒト絨毛性ゴナドトロピン値がほぼ正常化した。治療終了後3ヵ月で月経が再開し、その後に再度妊娠8週相当で流産となったが、子宮内容物は流産判明から1ヵ月以内に自然排出された。さらに6ヵ月後に体外受精で妊娠し、妊娠33週6日に帝王切開にて男児1912g、アプガースコア8/9点を出産し、術後経過順調で8日目に退院した。

早期子宮体癌における腹腔細胞診に関する検討

西村庸子, 松浦基樹, 玉手雅人, 寺田倫子, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 59 ( 3 ) 125 - 128 2020.05

目的:子宮体癌における腹腔細胞診の結果は2008年のFIGO分類において進行期の決定に考慮されなくなった。独立した予後因子になるとするいくつかの報告もあるが、現在のところ腹腔細胞診と予後との関係については、結論が得られていない。今回われわれは、術前1A期の診断で腹腔鏡下手術を行い、術後病理でも1Aと診断された症例の腹腔細胞診に関して検討した。方法:2014年7月〜2018年12月に術前1A期の診断で腹腔鏡下子宮全摘、両側付属器摘出術(症例によっては骨盤リンパ節郭清)を行った82例について検討した。成績:82例のうち、5例(6.1%)は腹腔細胞診が陽性であった。5例のうち、1例は脈管侵襲陽性であり、4例は脈管侵襲陰性で、その他のリスク因子も認めなかった。5例のうち、2例は術後化学療法が行われ、いずれも再発はみられていないが、術後化学療法を行わなかった3例はいずれも再発を認めた。腹腔細胞診が陰性であった77例の中で再発をきたした症例は2例あり、1例は肺転移、もう1例は腹膜播種再発であった。結論:今回の結果はフォローアップ期間も、症例数も限定的なものではあるが、低リスク子宮体癌であっても腹腔細胞診陽性であれば術後補助療法を施行した方が予後が改善する可能性が示唆された。(著者抄録)

Pregnancies after vaginal radical trachelectomy (RT) in patients with early invasive uterine cervical cancer: results from a single institute.

Shota Shinkai, Shinichi Ishioka, Tasuku Mariya, Yuya Fujibe, Miseon Kim, Masayuki Someya, Tsuyoshi Saito

BMC pregnancy and childbirth 20 ( 1 ) 248 - 248 2020.04 [International journal]

BACKGROUND: Radical tracheletomy (RT) with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who desire to maintain their fertility. However, this operative method entails a high risk for the following pregnancy due to its radicality. METHODS: We have performed vaginal RT for 71 patients and have experienced 28 pregnancies in 21 patients. They were followed up carefully according to the follow-up methods we reported previously. Their pregnancy courses and prognoses after the pregnancy were retrospectively reviewed. RESULTS: All the vaginal RTs were performed safely without serious complications, including 6 patients who underwent the operation during pregnancy. The median time to be pregnant after RT was 29.5 months. 13 patients (46%) became pregnant without artificial insemination by husband or assisted reproductive technology. Cesarean section was performed for all of them. The median time of pregnancy was 34 weeks, and emergent cesarean section was performed for 7 pregnancies (25%). The median birth weight was 2156 g. Four patients had trouble with cervical cerclage, and they suffered from sudden premature preterm rupture of the membrane (pPROM) during the second trimester of pregnancy. We underwent transabdominal cerclage (TAC) for all of them and careful management for the prevention of uterine infection was performed. One patient had a recurrence of cancer during pregnancy. CONCLUSIONS: Both the obstetrical prognosis and oncological prognosis after vaginal RT have become favorable for pregnant patients after vaginal RT.

DOI PubMed

妊娠中の広汎子宮頸部全摘出術腟式トラケレクトミー

齋藤豪, 岩崎雅宏, 松浦基樹, 玉手雅人, 真里谷奨, 石岡伸一

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 38 ( 2 ) 145 - 150 2020.04

われわれの教室では従来腟式準広汎性子宮全摘術に取り組んでいたが、平成16年より本術式を応用し腟式トラケレクトミーに取り組んでいる。これまで79例の腟式トラケレクトミーを行ってきたが、このうち2010年以来7例に対し妊娠初期の子宮頸がんに対し本術式を行う機会があったので報告する。症例は妊娠12週から26週で、6例がIB1期で、1例がIB2期であった。手術は腹式に骨盤リンパ郭清術を施行して、腟式に子宮頸部の操作を行い、最終的に子宮動脈本幹起始部レベルで子宮頸部を切断する。その後、頸部をナイロン糸でマクドナルド縫合し腟壁と縫合した。本術式の適応に関する基本方針は腫瘍径2cm以下のIB1期までとしているが、患者の希望が極めて強くリスクを説明してもなお妊娠の継続を望む症例に関して、7例中2例に関してはそれ以上の症例で手術を施行した。IB2期の症例は骨盤リンパ転移を認め、16週で妊娠を中断し子宮全摘・CCRTを施行した。他の1例はリンパ転移を認めたが、妊娠継続の希望が強く、再発リスクを説明した上で妊娠中に化学療法を施行し30週で妊娠を中断、子宮全摘・CCRTを施行した。その他の5例はリンパ転移を認めずtermで帝王切開術にて分娩している。今回の7例すべての症例において再発は認めておらず、破水などの産科合併症も認められなかった。今回の検討で6例の生児を得たが、児には発達の障害は認められていない。これまでの経験を通じ、妊娠中のリンパ郭清および腟式トラケレクトミーに関しては、大きな合併症を引き起こすリスクはそれほど高くはないことが示唆された。しかし、症例の適応、手術の時期、その他の治療法の選択などについては検討の余地は多く、他施設での症例の蓄積が必要と考える。(著者抄録)

Elevated expression of G protein-coupled receptor 30 (GPR30) is associated with poor prognosis in patients with uterine cervical adenocarcinoma.

Yoshihiko Ino, Taishi Akimoto, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Asako Ueda, Misaki Ota, Kazufumi Magara, Yohei Tagami, Masaki Murata, Tadashi Hasegawa, Tsuyoshi Saito, Norimasa Sawada, Makoto Osanai

Histology and histopathology 35 ( 4 ) 351 - 359 2020.04 [International journal]

Uterine cervical adenocarcinoma has a worse prognosis than that of squamous cell carcinoma and useful diagnostic and prognostic markers are needed. Estrogen is one of the key regulators of several cancers, however, the estrogen signaling has not been focused on in cervical adenocarcinoma. Here, we shows expression profile of classical estrogen receptor (ER) and a novel membrane type estrogen receptor, G protein-coupled receptor 30 (GPR30), in surgical specimens (n=53). GPR30 was strongly expressed on the cell membrane and in the cytoplasm in adenocarcinoma in situ (AIS) and adenocarcinoma, and its expression was especially strong at the invasion front in most of the cases of GPR30-positive adenocarcinoma. Nuclear staining of ER was strong in non-neoplastic glands, whereas it was almost absent in most of the AIS and adenocarcinoma cases. There was a weak but statistically significant negative correlation between immunoreactivity of GPR30 and that of ER in cervical AIS and adenocarcinoma lesions (Spearman's correlation, r=-0.324, p=0.017). ROC curve analysis revealed that immunoreactivity of GPR30 successfully distinguished neoplasms from non-neoplastic glands with high specificity (100%) and sensitivity (75.5%). GPR30 positivity was significantly correlated with histological type (p=0.009), tumor diameter (p=0.003), tumor size (p<0.001), lymphovascular infiltration (p=0.005) and UICC stage (p<0.001). ER expression was correlated only with tumor factor (p=0.047). GPR30-high patients had poor prognosis with a significantly shorter overall survival (OS) period (p=0.0309). GPR30 expression is a potential diagnostic and prognostic marker.

DOI PubMed

Epithelial barrier dysfunction and cell migration induction via JNK/cofilin/actin by angubindin-1.

Takumi Konno, Takayuki Kohno, Shin Kikuchi, Hiroshi Shimada, Seiro Satohisa, Tsuyoshi Saito, Masuo Kondoh, Takashi Kojima

Tissue barriers 8 ( 1 ) 1695475 - 1695475 2020.04 [Refereed] [International journal]

Angulin-1/LSR is a tricellular tight junction molecule, that plays an important role in maintaining the epithelial and endothelial barriers. The actin cytoskeleton at tricellular contacts also contributes to the maintenance of the epithelial barrier. Loss of angulin-1/LSR enhances the migration of various cancer cells. Angubindin-1 is a novel binder to angulin-1/LSR and angulin-3. It is a peptide generated from the angulin-1 binding site of Clostridium perfringens iota toxin, which affects the actin cytoskeleton and decreases the epithelial and endothelial barrier functions. However, its regulatory mechanisms are not well understood. To investigate the regulatory mechanisms of the epithelial barrier dysfunction and cell migration induction by angubindin-1, we used human endometrial cancer cell line Sawano, which has high LSR expression and the epithelial barrier function. Angubindin-1 decreased LSR expression and the epithelial barrier function and increased cell migration. It inhibited the recovery of the epithelial barrier function in a Ca-switch model. At tricellular contacts, sinking of the membrane and an increase of actin fibers near the junctions were caused by angubindin-1. It dynamically changed F-actin from lines to dot-like structures at tricellular contacts. Angubindin-1 transiently increased the phosphorylation of cofilin and JNK, which are involved in the regulation of the intracellular actin cytoskeleton. Furthermore, knockdown of JNK and the JNK inhibitor SP600125 prevented the decrease of the epithelial barrier function and the increase of cell migration induced by angubindin-1. These findings suggest that angubindin-1 might reversibly regulate the epithelial barrier and cell migration at tricellular contacts via JNK/cofilin/actin cytoskeleton dynamics.

DOI PubMed

子宮頸がんにおける当院のVaginal Trachelectomyの成績と意義

玉手雅人, 松浦基樹, 黒川晶子, 西村庸子, 磯山響子, 寺田倫子, 真里谷奨, 岩崎雅宏, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 72 ( 臨増 ) S - 359 2020.03

Prune Belly Syndromeの女児が出生後に総排泄腔遺残も疑われた1例

藤部佑哉, 真里谷奨, 蛯谷由真, 水柿祐子, 川俣あかり, 水内将人, 森下美幸, 馬場剛, 石岡伸一, 長岡由修, 石郷岡哲郎, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 108 - 109 2020.03

子宮体癌の化学療法後に治療関連骨髄異形成症候群を発症した1例

小川万梨絵, 岩崎雅宏, 阿部秀悦, 常松梨紗, 郷久晴朗, 黒川晶子, 西村庸子, 玉手雅人, 磯山響子, 寺田倫子, 松浦基樹, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 72 ( 臨増 ) S - 592 2020.03

当院における婦人科悪性腫瘍患者の血栓症治療に関する検討

西村庸子, 松浦基樹, 黒川晶子, 玉手雅人, 磯山響子, 寺田倫子, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 72 ( 臨増 ) S - 528 2020.03

当院で出生した先天性疾患児の出生前診断状況および遺伝学的対応に関する検討

真里谷奨, 斉藤公仁, 水柿祐子, 藤部佑哉, 川俣あかり, 水内将人, 森下美幸, 馬場剛, 水上都, 石川亜貴, 石岡伸一, 櫻井晃洋, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 108 - 108 2020.03

初回術前化学療法後に心肺停止となった卵巣癌の1例

常松梨紗, 岩崎雅宏, 野呂薫, 阿部秀悦, 小川万梨絵, 郷久晴朗, 西村庸子, 玉手雅人, 磯山響子, 寺田倫子, 松浦基樹, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 72 ( 臨増 ) S - 653 2020.03

子宮筋腫に対して腹腔鏡手術後,異型細胞・核分裂像の増加を認めた症例の特徴と傾向

神未央奈, 玉手雅人, 明石祐史, 杉尾明香, 足立英文, 松浦基樹, 森下美幸, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 104 - 104 2020.03

アプローチを横断した子宮全摘術の教育

玉手雅人, 松浦基樹, 神未央奈, 石堂茉泉, 斉藤公仁, 西村庸子, 寺本瑞絵, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 102 - 102 2020.03

再発外陰癌に対する化学療法中に発症した間質性肺炎の1症例

斉藤公仁, 郷久晴朗, 岩崎雅宏, 鹿内智史, 秋元太志, 石堂茉泉, 西村庸子, 玉手雅人, 松浦基樹, 寺本瑞絵, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 100 - 100 2020.03

若手産婦人科医の腹腔鏡手技トレーニングにおけるタイムトライアルの有用性の検討

長尾沙智子, 玉手雅人, 藤部佑哉, 西村庸子, 松浦基樹, 寺本瑞絵, 馬場剛, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 102 - 102 2020.03

難治性尿路感染症に隠れたものは? 女性診療科として考えるライフステージごとの尿路感染症

真里谷奨, 齋藤豪, 高橋聡

日本化学療法学会雑誌 ( (公社)日本化学療法学会 ) 68 ( 2 ) 246 - 246 2020.03

女性診療科として考えるライフステージごとの尿路感染症

真里谷奨, 齋藤豪, 高橋聡

感染症学雑誌 ( (一社)日本感染症学会 ) 94 ( 2 ) 219 - 220 2020.03

Localization of Tricellular Tight Junction Molecule LSR at Midbody and Centrosome During Cytokinesis in Human Epithelial Cells.

Takumi Konno, Takayuki Kohno, Shin Kikuchi, Hiroshi Shimada, Seiro Satohisa, Kenichi Takano, Tsuyoshi Saito, Takashi Kojima

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 68 ( 1 ) 59 - 72 2020.01 [International journal]

Epithelial integrity and barrier function are maintained during cytokinesis in vertebrate epithelial tissues. The changes in localization and the roles of tricellular tight junction molecule lipolysis-stimulated lipoprotein receptor (LSR) during cytokinesis are not well known, although new tricellular tight junctions form at the flank of the midbody during cytokinesis. In this study, we investigated the changes in localization and the role of LSR at the midbody and centrosome during cytokinesis using human endometrial carcinoma cell line Sawano, comparing the tricellular tight junction molecule tricellulin; bicellular tight junction molecules occludin, claudin-7, zonula occludens-1, and cingulin; and the epithelial polarized related molecules apoptosis-stimulating of p53 protein 2, PAR3, and yes-associated protein. During cytokinesis induced by treatment with taxol, the epithelial barrier was maintained and the tricellular tight junction molecules LSR and tricellulin were concentrated at the flank of the acetylated tubulin-positive midbody and in γ-tubulin-positive centrosomes with the dynein adaptor Hook2, whereas the other molecules were localized there as well. All the molecules disappeared by knockdown using small interfering RNAs. Furthermore, by the knockdown of Hook2, the epithelial barrier was maintained and most of the molecules disappeared from the centrosome. These findings suggest that LSR may play crucial roles not only in barrier function but also in cytokinesis.

DOI PubMed

円錐切除後断端陰性の子宮頸部高度異形成(CIN3)に対するTLH後に、SCCが判明した1例

常松梨紗, 岡田匡氷, 長尾沙智子, 黒川晶子, 西村庸子, 玉手雅人, 松浦基樹, 森下美幸, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 24 ( 7 ) MO318 - 3 2019.12

モルセーフを円滑に挿入するための当科での工夫

寺田倫子, 玉手雅人, 西村庸子, 松浦基樹, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 24 ( 7 ) MO316 - 5 2019.12

早期子宮体癌に対する腹腔鏡下手術とロボット支援下手術の比較検討

松浦基樹, 黒川晶子, 西村庸子, 玉手雅人, 寺田倫子, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 24 ( 7 ) MO324 - 5 2019.12

腹腔鏡手術修練におけるCadaver Surgical Trainingの有用性

黒川晶子, 玉手雅人, 長尾沙智子, 西村庸子, 寺田倫子, 松浦基樹, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 24 ( 7 ) MO212 - 6 2019.12

ロボット支援下手術におけるロールインからコンソールまでの定型化の必要性

西村庸子, 松浦基樹, 黒川晶子, 玉手雅人, 寺田倫子, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 24 ( 7 ) MO323 - 5 2019.12

Successful administration of recombinant human antithrombin in a pregnant Japanese woman with hereditary antithrombin deficiency.

Yuya Fujibe, Tasuku Mariya, Masahito Mizuuchi, Shinichi Ishioka, Masahiro Yoshida, Tsuyoshi Saito

Taiwanese journal of obstetrics & gynecology 58 ( 6 ) 849 - 851 2019.11 [International journal]

OBJECTIVE: Hereditary antithrombin (AT) deficiency increases the risk of venous thromboembolism (VTE) in pregnant woman. We report the first case of administration of recombinant human antithrombin (rhAT) to a pregnant Japanese woman with AT deficiency. CASE REPORT: A 30-year-old woman, gravida 2 para 0, was referred to our hospital because of AT deficiency. Unfractionated heparin was administered from 13 weeks of gestation and rhAT was administered from labor onset. A cesarean section was performed and the patient and her baby were healthy, with no sequelae. CONCLUSION: We concluded that rhAT was effective for preventing VTE during delivery, with no potential infection risks.

DOI PubMed

当科において妊娠初期子宮頸部細胞診HSIL/ASC-H以上を認めた症例の検討

真里谷奨, 石岡伸一, 玉手雅人, 郷久晴朗, 松浦基樹, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.2 ) 587 - 587 2019.10

転移性女性生殖器がんにおける臨床像と捺印細胞像

玉手雅人, 松浦基樹, 長尾沙智子, 西村庸子, 真里谷奨, 寺田倫子, 郷久晴朗, 杉田真太朗, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.2 ) 601 - 601 2019.10

当院におけるオラパリブ投与症例の検討

松浦基樹, 黒川晶子, 西村庸子, 玉手雅人, 磯山響子, 寺田倫子, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 57回 P156 - 7 2019.10

術前診断が困難であった早期卵巣癌の一例

松浦基樹, 西村庸子, 玉手雅人, 寺田倫子, 寺本瑞絵, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.2 ) 602 - 602 2019.10

タイト結合による子宮内膜の悪性化制御機序

郷久晴朗, 嶋田浩志, 岩崎雅宏, 染谷真行, 金野匠, 菊池真, 幸野貴之, 玉手雅人, 松浦基樹, 小島隆, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 67回 36 - 36 2019.09

ロボット支援下手術におけるロールインからコンソールまでの定型化の必要性

西村庸子, 松浦基樹, 黒川晶子, 玉手雅人, 寺田倫子, 郷久晴朗, 岩崎雅宏, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 67回 74 - 74 2019.09

若年女性に発症した外陰部Bowen病の一例

太田未咲, 郷久晴朗, 岩崎雅宏, 小川万梨絵, 常松梨紗, 阿部秀悦, 野呂薫, 黒川晶子, 西村庸子, 玉手雅人, 磯山響子, 寺田倫子, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 67回 79 - 79 2019.09

子宮体がんスクリーニングにおける子宮内膜液状化細胞診検体を用いた遺伝子解析の有用性(Evaluation of the utility of liquid-based genetic diagnosis for screening of endometrial cancer)

池上恒雄, 松浦基樹, 高根希世子, 山口貴世志, 齋藤豪, 古川洋一

日本癌学会総会記事 ( (一社)日本癌学会 ) 78回 P - 1144 2019.09

Pioglitazone suppresses excessive follicular development in murine preantral follicles.

Sachiko Nagao, Tsuyoshi Baba, Yuya Fujibe, Sayaka Adachi, Keiko Ikeda, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

Journal of ovarian research 12 ( 1 ) 82 - 82 2019.08 [International journal]

Polycystic ovary syndrome (PCOS) is an endocrine disease that is common in women in their reproductive period. Patients with this disease suffer from anovulation and hyperandrogenism. Ovulation induction with exogenous gonadotropin often causes ovarian hyperstimulation syndrome because many small antral follicles pause in their growth. Treatment with insulin sensitizers is reportedly effective for both anovulation associated with PCOS, and suppression of excessive follicular growth; however, the underlying mechanism of action remains unknown. Although pioglitazone is known as an insulin sensitizer, it also has a potent modulator of cell growth and apoptosis irrespective of insulin resistance. To clarify the effect of pioglitazone on follicular growth, we performed in vitro culture of murine preantral follicles. Secondary follicles (100-160 μm in diameter) isolated from 6-week-old ICR mice were individually cultured for 13 days. Culture conditions were as follows: 1) follicle-stimulating hormone (FSH; 33 mIU/mL; control), 2) FSH plus dihydrotestosterone (DHT; 500 ng/mL), 3) FSH plus pioglitazone (5 ng/mL), and 4) FSH plus DHT/pioglitazone. Survival rate and follicle diameter were evaluated, and concentrations of estradiol (E2) and vascular endothelial growth factor (VEGF) in culture media were measured. mRNA expression of various growth-promoting factors and Vegf within follicles were also assessed. Although no significant differences were observed with regard to survival rate, follicle diameters on day 13 were significantly different.Compared with the control group, the DHT group showed enhanced growth, while groups administered pioglitazone showed stagnation of the accelerated growth induced by DHT. Although DHT treatment enhanced the expression of bone morphogenetic protein 2 (Bmp2) mRNA, pioglitazone exposure suppressed induction of Bmp2 mRNA by DHT. Vegf mRNA and protein expression were also significantly reduced when pioglitazone was added to culture media containing DHT.Administration of pioglitazone negatively affected follicular growth and VEGF levels, which may suppress excessive follicular growth and prevent ovarian hyperstimulation syndrome.

DOI PubMed

術前に良性嚢胞腺腫と診断し、腹腔鏡手術後に卵巣癌と診断された1例

郷久晴朗, 岩崎雅宏, 鹿内智史, 常松梨紗, 阿部秀悦, 小川万梨絵, 西村庸子, 玉手雅人, 寺田倫子, 松浦基樹, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 265 - 265 2019.08

重症子宮内膜症を有する不妊治療における手術とART介入のタイミング

森下美幸, 長尾沙智子, 新開翔太, 久野芳佳, 真里谷奨, 馬場剛, 遠藤俊明, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 252 - 252 2019.08

卵巣移動術後の内膜症性嚢胞に対し腹腔鏡で治療し得た1例

鹿内智史, 玉手雅人, 神未央奈, 伊野善彦, 鈴木将裕, 西村庸子, 松浦基樹, 寺本瑞絵, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 186 - 186 2019.08

腹腔鏡下子宮筋腫核出術後に、ポート挿入部に腫瘍転移した1例

岩崎雅宏, 郷久晴朗, 小川万梨絵, 阿部秀悦, 松浦基樹, 玉手雅人, 西村庸子, 常松梨紗, 黒川晶子, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 246 - 246 2019.08

腹腔鏡下子宮体癌手術を行った95例の術前評価と術後病理組織診の比較検討

寺田倫子, 松浦基樹, 黒川晶子, 西村庸子, 玉手雅人, 寺本瑞絵, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 281 - 281 2019.08

産婦人科卒後後期研修医としてCadaverで学べること

神未央奈, 玉手雅人, 鹿内智史, 伊野善彦, 西村庸子, 秋元太志, 松浦基樹, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 181 - 181 2019.08

Fundamental Use of Surgical Energyを導入した手術教育

玉手雅人, 松浦基樹, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 30 ) 157 - 157 2019.08

早期子宮体癌の診断で腹腔鏡下手術を施行した症例の腹腔細胞診に関する検討

西村庸子, 石堂茉泉, 神未央奈, 長尾沙智子, 玉手雅人, 寺田倫子, 松浦基樹, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 162 - 162 2019.08

Cadaver Surgery Multi Angleな手術教育と研究

玉手雅人, 松浦基樹, 長尾沙智子, 西村庸子, 杉尾明香, 竹中慎, 明石祐史, 林茂徳, 金尾祐之, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 119 - 119 2019.08

疲れにくい腹腔鏡手術男女の身体的特性から

長尾沙智子, 西村庸子, 玉手雅人, 松浦基樹, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 117 - 117 2019.08

男性均衡型相互転座保因者の体外受精胚の第一減数分裂で最も頻度の高い不均衡分離様式の予測は可能か?

遠藤俊明, 馬場剛, 鷹巣祐子, 木谷保, 尾崎守, 加藤武馬, 倉橋浩樹, 斉藤豪

日本遺伝カウンセリング学会誌 ( (一社)日本遺伝カウンセリング学会 ) 40 ( 2 ) 84 - 84 2019.07

Obstetrical prognosis of patients who underwent vaginal radical trachelectomy during pregnancy.

Mina Umemoto, Shinichi Ishioka, Yuko Mizugaki, Yuya Fujibe, Tasuku Mariya, Akari Kawamata, Masahito Mizuuchi, Miyuki Morishita, Tsuyoshi Baba, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 45 ( 6 ) 1167 - 1172 2019.06 [International journal]

AIM: Radical trachelectomy (RT) with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who decide to maintain their fertility. However, this operative method entails a high risk for the following pregnancy due to its radicality. Therefore, RT for pregnant patients can be a challenge both for gynecologic oncologists and obstetricians. METHODS: We have performed vaginal RT for five pregnant patients with uterine cervical cancer stage 1B1 according to the method of Dargent et al. The operations were performed between 16 and 26 weeks of pregnancy, and the patients were followed up carefully according to the follow-up methods we reported previously. RESULTS: Vaginal RT was performed for five patients without any troubles. Four of the patients continued their pregnancies until almost 34 weeks or longer under our previously published follow-up schedule. The pregnancy of one patient was terminated at 26 weeks due to recurrence of the cancer. CONCLUSION: Expansion of vaginal RT for pregnant patients with uterine cervical cancer could be a practical option for pregnant patients with early invasive uterine cervical cancer.

DOI PubMed

リステリア菌血症により流産に至った1例

藤部佑哉, 真里谷奨, 嶋田浩志, 山中郁仁, 水内将人, 寺本瑞絵, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 55 ( 2 ) 530 - 530 2019.06

子宮体部漿液性癌18例の検討

寺田倫子, 松浦基樹, 西村庸子, 玉手雅人, 郷久晴朗, 岩崎雅宏, 寺本瑞絵, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.1 ) 276 - 276 2019.05

子宮内膜癌細胞におけるタイト結合分子claudin-2の関与

郷久晴朗, 嶋田浩志, 玉手雅人, 秋元太志, 西村庸子, 寺田倫子, 松浦基樹, 岩崎雅宏, 小島隆, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.1 ) 320 - 320 2019.05

早期子宮体癌における腹腔細胞診に関する検討

西村庸子, 松浦基樹, 玉手雅人, 寺田倫子, 郷久晴朗, 寺本瑞絵, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.1 ) 225 - 225 2019.05

子宮体癌におけるKRAS変異の意義

松浦基樹, 西村庸子, 玉手雅人, 寺田倫子, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.1 ) 319 - 319 2019.05

子宮頸部原発大細胞神経内分泌癌の細胞像

寺本瑞絵, 西村庸子, 秋元太志, 玉手雅人, 磯山響子, 小川万梨絵, 寺田倫子, 松浦基樹, 郷久晴朗, 岩崎雅宏, 齊藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 58 ( Suppl.1 ) 270 - 270 2019.05

Androgen potentiates the expression of FSH receptor and supports preantral follicle development in mice.

Yuya Fujibe, Tsuyoshi Baba, Sachiko Nagao, Sayaka Adachi, Keiko Ikeda, Miyuki Morishita, Yoshika Kuno, Masahiro Suzuki, Masahito Mizuuchi, Hiroyuki Honnma, Toshiaki Endo, Tsuyoshi Saito

Journal of ovarian research 12 ( 1 ) 31 - 31 2019.04 [International journal]

Hyperandrogenism is one of the cardinal symptoms in polycystic ovary syndrome and plays a key role in the pathogenesis of polycystic ovary syndrome. However, the precise effects and mechanisms of excess androgen during follicular development are still unclear. Here we investigated the effects of androgen on mouse follicle development in vitro. Androgen did not affect the growth of follicles smaller than 160-180 μm in the presence of follicle-stimulating hormone (FSH). However, in the presence of low FSH, androgen supported the growth of follicles larger than 160-180 μm, a size at which growing follicles acquire FSH-dependency. Androgen did not change the mRNA expression of various growth-promoting factors but did increase mRNA expression of the FSH receptor. We suggest that androgen has a positive impact on follicle development by augmentation of the actions of FSH. Therefore, FSH-responsive but FSH-independent follicles grow in the presence of a certain level of FSH or androgen, and androgen compensates for FSH deficiency in FSH-dependent follicles.

DOI PubMed

自然消失した子宮動脈仮性動脈瘤の超音波パワードップラー法所見の変化

嶋田浩志, 野藤五沙, 鈴木美紀, 幅田周太朗, 藤部佑哉, 水内将人, 馬場剛, 石岡伸一, 齋藤豪

超音波医学 ( (公社)日本超音波医学会 ) 46 ( Suppl. ) S719 - S719 2019.04

出血リスクが高い症例における帝王切開術の工夫

岡田匡永, 玉手雅人, 長尾沙智子, 黒川晶子, 鈴木利理, 田渕雄大, 松浦基樹, 水内将人, 岡村直樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 63 ( 1 ) 71 - 71 2019.03

TLHにおいてどうすれば尿管、子宮動脈は簡単に同定できるのか

山下真祐子, 松浦基樹, 玉手雅人, 野呂薫, 寺田倫子, 寺本瑞絵, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 63 ( 1 ) 67 - 67 2019.03

胸郭低形成を契機に診断した6番染色体短腕部分欠失かつ11番染色体部分重複の一例

寺田倫子[竹田], 寺本瑞絵, 長尾沙智子, 玉手雅人, 磯山響子, 染谷真行, 寺田光次郎, 岡村直樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 63 ( 1 ) 33 - 39 2019.03

胸郭低形成は、骨系統疾患や羊水過少が原因となって生じることが多い。骨系統疾患では四肢短縮を認めるが、今回胸郭低形成以外に骨所見はなく、羊水過少もない染色体不均衡型転座の症例を経験したので報告する。症例の母体は30歳、7妊2産。妊娠28週で胎児発育不全(fetal growth restriction:FGR)のため近医産婦人科より紹介となった。胎児エコーでは四肢短縮は認めないものの、ベル型の胸郭のため胸郭低形成が疑われた。羊水インデックス(amniotic fluid index:AFI)は5～7cmであった。他、エコースクリーニングでは心房中隔欠損(Atrial septal defect:ASD)疑いとなったが、致死的疾患は認めなかった。TORCH検索では異常は認められなかった。妊娠38週に帝王切開で2,011gの男児が出生し、アプガースコア4/9点、臍帯動脈血ガスpH=7.039であった。出生後、胸郭低形成、ASD、PDA(patent ductus arteriosus)、埋没陰茎、両側難聴などの診断となり、染色体検査に提出したところ46,XY,add(6)(p25)と診断された。両親の染色体を検査に提出したところ、母親が46,XX,t(6;11)(p25;q21)であり、母親由来の染色体不均衡型転座と判明した。児はPDAに対し開胸手術を必要としたが、術後経過順調であり自宅退院となり、3歳の時点で発達の遅れは伴うものの致死的疾患は生じていない。本症例は、6p25欠失と11q部分重複からなる不均衡型転座である。四肢短縮など他の骨所見のない胸郭低形成の症例は、染色体不均衡型転座も考慮する必要がある。(著者抄録)

Clonal analysis revealed functional heterogeneity in cancer stem-like cell phenotypes in uterine endometrioid adenocarcinoma.

Tabuchi Y, Hirohashi Y, Hashimoto S, Mariya T, Asano T, Ikeo K, Kuroda T, Mizuuchi M, Murai A, Uno S, Kawai N, Kubo T, Nakatsugawa M, Kanaseki T, Tsukahara T, Saito T, Torigoe T

Experimental and molecular pathology 106 78 - 88 2019.02 [Refereed]

DOI PubMed

Recurrent Massive Uterine Bleeding from a Cesarean Scar Treated Successfully by Laparoscopic Surgery.

Tasuku Mariya, Mina Umemoto, Naoko Sugita, Masahiro Suzuki, Tsuyoshi Saito

Gynecology and minimally invasive therapy 8 ( 1 ) 36 - 39 2019 [International journal]

A cesarean scar can cause abnormal uterine bleeding including prolonged menstruation or postmenstrual spotting. Our patient showed massive uterine bleeding from a cesarean scar and needed blood transfusion for hemorrhagic shock. A cesarean section had only been performed once for delivery stop 9 years ago. Recurrent hemorrhage could not be controlled by conservative treatment, and we performed laparoscopic scar resection and repair. The abnormal uterine bleeding was successfully stopped, and the menstrual cycle was normalized after surgical treatment. We should be aware that even an uneventful cesarean section may have a risk of massive hemorrhage postoperatively as in the present case.

DOI PubMed

The roles of metformin and pravastatin on Placental endoplasmic reticulum stress and Placental growth factor in human villous-like trophoblastic BeWo cells

Masahiro Suzuki, Masahito Mizuuchi, Tsuyoshi Baba, Yuya Fujibe, Yoshihiko Ino, Shinichi Ishioka, Tsuyoshi Saito

Sapporo Medical journal ( Sapporo Medical University ) 87 ( 1-6 ) 75 - 84 2018.12

Preeclampsia (PE) is related to an imbalance of angiogenic factors. Placental growth factor (P1GF) is reduced in early onset PE. Recent evidence indicates that metformin and statins may suppress endoplasmic reticulum (ER) stress. We previously reported that the unfolded protein response activated by ER stress down-regulated P1GF protein expression and predicted these drugs could prevent placental ER stress and up-regulate P1GF protein expression in trophoblast-like cells. In this study, we aimed to establish the effects of these drugs on P1GF and activating transcription factor 4 (ATF4) protein expression. We confirmed that P1GF messenger RNA (mRNA) levels were decreased under ER stress induced by thapsigargin and that ATF4 mRNA was increased under the same conditions and then administered metformin to it. Transcript analysis showed increased P1GF mRNA compared with thapsigargin only treatment and that this was dependent on metformin levels. Under ER stress, western blot showed high levels of ATF4 and phosphorylated-eukaryotic initiation factor 2 subunit a (p-eIF2a) but low levels of P1GF protein. By contrast, compared with thapsigargin alone, ATF4 and p-eIF2a levels were low and P1GF levels were high when metformin and thapsigargin were given, but these were again dependent on metformin concentrations. Western blot also confirmed that pravastatin attenuated ER stress and increased P1GF protein expression. In conclusion, metformin and pravastatin suppressed ER stress and restored P1GF levels in trophoblastlike cells. However, although these results indicate that these drugs have a potential for preventing or treating PE, the lack of clarity on the mechanism requires further study.

DOI

Efficacy of liquid-based genetic diagnosis of endometrial cancer.

Matsuura M, Yamaguchi K, Tamate M, Satohisa S, Teramoto M, Iwasaki M, Sugita S, Hasegawa T, Koubo R, Takane K, Ikenoue T, Furukawa Y, Saito T

Cancer science 109 ( 12 ) 4025 - 4032 2018.12 [Refereed]

DOI PubMed

TLHにおけるデバイスの選択について

西村庸子, 松浦基樹, 石堂茉泉, 長尾沙智子, 玉手雅人, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 23 ( 7 ) OS139 - 3 2018.12

子宮体癌に対するロボット支援下子宮全摘術を円滑に行うために

松浦基樹, 石堂茉泉, 長尾沙智子, 西村庸子, 玉手雅人, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 23 ( 7 ) OS142 - 5 2018.12

Cytotoxicity of Clostridium perfringens enterotoxin depends on the conditions of claudin-4 in ovarian carcinoma cells.

Satoshi Tanaka, Tomoyuki Aoyama, Marie Ogawa, Akira Takasawa, Masaki Murata, Makoto Osanai, Tsuyoshi Saito, Norimasa Sawada

Experimental cell research 371 ( 1 ) 278 - 286 2018.10 [International journal]

Currently, Clostridium perfringens enterotoxin (CPE) is being investigated as an anti-cancer drug for tumors expressing the tight junction (TJ) transmembrane proteins claudin-3 and/or claudin-4. However, the optimal conditions for CPE cytotoxicity are still unclear. Our objectives were to determine the optimal conditions for CPE as an anti-cancer drug for treating ovarian cancer in vitro and in vivo. In our experiments, cells at low culture density showed higher sensitivity to CPE, suggesting that claudins at TJs were poorly accessible to CPE compared with those at the edge of cell colonies. Ovarian cancer cells cultured under calcium-depleted pretreatment conditions to disrupt TJs and to knock-down TJ proteins and E-cadherin production altered CPE cytotoxicity, which was mainly dependent on claudin-4 expression. These results suggest that the condition of claudin-4 at the cell surface is important for CPE cytotoxicity. Our in vivo experiments showed that a high dose of CPE is required for the effective treatment of peritoneal dissemination of ovarian cancer cells. Here, we suggest that the accessibility of CPE to claudins is important for its cytotoxicity and depends on the conditions of claudin-4 in vitro. In addition, E-cadherin expression in ovarian cancer cells affects the efficiency of CPE in vivo.

DOI PubMed

Treatment and prognosis of recurrent uterine leiomyosarcomas in last 5 years

Saito Tsuyoshi, Tanaka Rhoichi, Satohisa Seiro, Abe Shuetsu, Iwasaki Masahiro, Teramoto Mizue, Matsuura Motoki, Tamate Masato

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 50 2018.10 [Refereed]

Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression.

Taishi Akimoto, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Masaki Murata, Makoto Osanai, Tsuyoshi Saito, Norimasa Sawada

Neoplasia (New York, N.Y.) 20 ( 10 ) 1083 - 1093 2018.10 [International journal]

Cervical adenocarcinomas are believed to lose estrogen response on the basis of no expression of a nuclear estrogen receptor such as ERα in clinical pathology. Here, we demonstrated that cervical adenocarcinoma cells respond to a physiological concentration of estrogen to upregulate claudin-1, a cell surface molecule highly expressed in cervical adenocarcinomas. Knockout of claudin-1 induced apoptosis and significantly inhibited proliferation, migration, and invasion of cervical adenocarcinoma cells and tumorigenicity in vivo. Importantly, all of the cervical adenocarcinoma cell lines examined expressed a membrane-bound type estrogen receptor, G protein-coupled receptor 30 (GPR30/GPER1), but not ERα. Estrogen-dependent induction of claudin-1 expression was mediated by GPR30 via ERK and/or Akt signaling. In surgical specimens, there was a positive correlation between claudin-1 expression and GPR30 expression. Double high expression of claudin-1 and GPR30 predicts poor prognosis in patients with cervical adenocarcinomas. Mechanism-based targeting of estrogen/GPR30 signaling and claudin-1 may be effective for cervical adenocarcinoma therapy.

DOI PubMed

Multiple part umbilical cord entanglement and neonatal outcomes

Tasuku Mariya, Yuya Fujibe, Shota Shinkai, Naoko Sugita, Masahiro Suzuki, Toshiaki Endo, Tsuyoshi Saito

Taiwanese Journal of Obstetrics and Gynecology ( Elsevier BV ) 57 ( 5 ) 672 - 676 2018.10

DOI

Recurrence after total laparoscopic hysterectomy without morcellation for smooth muscle tumors of uncertain malignant potential: A rare case report

Satohisa Seiro, Abe Shuetsu, Iwasaki Masahiro, Akimoto Taishi, Shikanai Satoshi, Tamate Masato, Matsuura Motoki, Teramoto Mizue, Saito Tsuyoshi

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 84 2018.10 [Refereed]

The role of claudin-2 on the malignancy of human endometrioid carcinoma tissues

Satohisa Seiro, Shimada Hiroshi, Kohno Takayuki, Konno Takumi, Tamate Masato, Matsuura Motoki, Teramoto Mizue, Akimoto Taishi, Iwasaki Masahiro, Kojima Takashi, Saito Tsuyoshi

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 109 2018.10 [Refereed]

Rare case of occult testosterone-producing ovarian tumor that was diagnosed by selective venous hormone sampling.

Yoshika Kuno, Tsuyoshi Baba, Takafumi Kuroda, Mizue Teramoto, Naoki Hirokawa, Toshiaki Endo, Tsuyoshi Saito

Reproductive medicine and biology 17 ( 4 ) 504 - 508 2018.10 [Domestic journal]

CASE: A 32 year old woman was referred because of secondary amenorrhea, hirsutism, and voice deepening. OUTCOME: The blood testosterone level was markedly high. A transvaginal ultrasound revealed a small region in the left ovary, but whether or not it was a tumor was unclear. Therefore, selective ovarian venous sampling was performed. Consequently, the testosterone level was selectively increased in a blood sample that was taken from the left ovarian vein, the tumor was successfully localized, and a laparoscopic left oophorectomy was performed. Although the left ovary appeared to be normal at laparoscopy, the androgen-secreting tumor was located within it. The tumor was diagnosed as a Leydig cell tumor by histopathological analyses. CONCLUSION: This report demonstrates that selective blood sampling from ovarian veins before an operation is effective in localizing an androgen-producing ovarian tumor that is difficult to diagnose by imaging studies.

DOI PubMed

膀胱子宮窩腹膜に発生した悪性孤立性線維性腫瘍の1例

伊野善彦, 松浦基樹, 山本直美, 三浦一郎, 三浦千砂子, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 57 ( Suppl.2 ) 745 - 745 2018.10

マイクロサテライト不安定性およびHLAクラスI分子低発現の子宮内膜癌における臨床的意義(Clinical implications of microsatellite instability and HLA Class I downregulation in endometrial cancer)

真里谷奨, 廣橋良彦, 玉手雅人, 郷久晴朗, 久保輝文, 寺本瑞絵, 岩崎雅宏, 鳥越俊彦, 齋藤豪

日本癌学会総会記事 ( (一社)日本癌学会 ) 77回 518 - 518 2018.09

次世代術者のキャリアとビジョン〜悪性腫瘍手術を見据えて〜守破離現状直視と未来のビジョン

玉手雅人, 松浦基樹, 明石祐史, 寒河江悟, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 34 ( Suppl.I ) 144 - 144 2018.08

妊娠11週の卵管間質部妊娠破裂に対して腹腔鏡下に治療し得た1例

伊野善彦, 玉手雅人, 神未央奈, 野呂薫, 秋元太志, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 34 ( Suppl.I ) 340 - 340 2018.08

既往帝王切開創部子宮筋層癒合不全に対し腹腔鏡下筋層再縫合術を行った1例

阿部秀悦, 玉手雅人, 山下真祐子, 長尾沙智子, 西澤庸子, 杉尾明香, 明石祐史, 郷久晴朗, 寺本瑞絵, 馬場剛, 岩崎雅宏, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 34 ( Suppl.I ) 297 - 297 2018.08

技術認定医取得後に経験したConversion症例から考えるTLHの安全な適応

明石祐史, 杉尾明香, 明石大輔, 西村庸子, 玉手雅人, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 34 ( Suppl.I ) 332 - 332 2018.08

経口抗菌薬を用いた妊娠中の産道Streptococcus agalactiae除菌の試みと腟内細菌叢との関連に関する検討

真里谷奨, 鹿内智史, 嶋田浩志, 杉田奈穗子, 鈴木将裕, 野手健司, 鷲見亮太, 齋藤豪

帯広協会病院医誌 ( (福)北海道社会事業協会帯広病院 ) 3 17 - 27 2018.07

妊娠中の経口抗菌薬による産道Streptococcus agalactiae(Group B streptococcus;GBS)除菌の有効性、ならびに他臨床的因子との関連の有無を後方視的に検討した。2013年1月～2015年12月までに当院で分娩となった妊婦を対象に、産道GBS検出および消失、Nugent Score、GBSに対する抗菌薬の内服状況等について統計学的検討を行った。GBS陽性妊婦124症例中107例に経口抗菌薬が投与され、他17例は非投与であった。投与・非投与群間で、GBSの消失率に有意差は認められなかった。抗菌薬投与後もGBS感染が継続した患者(39例)ではNugent scoreが有意に高く、腟内細菌叢が不良であり、Lactobacillus spp.の存在率も低い経口があった。多変量解析の結果、GBS消失の独立因子はNugent scoreであった。妊娠中の経口抗菌薬投与による産道GBS消失率の有意な上昇は認められなかったが、腟内細菌叢とGBS消失には密接な関連が認められた。

Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study: Design, methods and baseline results in 14 642 women.

Aoyama-Kikawa S, Fujita H, Hanley SJB, Kasamo M, Kikuchi K, Torigoe T, Matsuno Y, Tamakoshi A, Sasaki T, Matsuura M, Kato Y, Dong P, Watari H, Saito T, Sengoku K, Sakuragi N

Cancer science 109 ( 6 ) 2003 - 2012 2018.06 [Refereed]

DOI PubMed

術前の良悪性の診断が困難だった卵巣腫瘍症例の検討

鈴木利理, 玉手雅人, 長尾沙智子, 田渕雄大, 松浦基樹, 齋藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 29 ) 171 - 171 2018.06

2009年IOM指針に基づいた推奨妊娠中体重増加における出生児体重の検討

嶋田浩志, 高田さくら, 恐神博行, 水内将人, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 54 ( 2 ) 717 - 717 2018.06

Bakriバルーンの前置胎盤・低置胎盤帝王切開症例における予防的止血効果の検討

梅本美菜, 黒田敬史, 水内将人, 野呂薫, 柏木葉月, 伊野善彦, 杉田菜穂子, 鈴木将裕, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

日本産婦人科・新生児血液学会誌 ( 日本産婦人科・新生児血液学会 ) 28 ( 1 ) 30 - 31 2018.05

当院前置胎盤・低置胎盤の帝王切開時にBakriバルーンを使用した14例を対象に、予防的止血効果に関する検討を行った。その結果、全例がBakriによる止血奏効例で、Bakri予防使用群は6例、非予防使用群は8例であった。分娩第3期の出血量は2群間で有意差を認めなかったが、分娩第4期の出血量はBakri予防使用群で有意に少なかった。今回の検討から、帝王切開時におけるBakriの予防的使用は、前置・低置胎盤に対する術中および分娩第4期の止血法として有効であることが示唆された。

遺伝性乳癌卵巣癌症候群(HBOC)における子宮頸部・内膜細胞診の検討

寺本瑞絵, 柏木葉月, 秋元太志, 玉手雅人, 寺田倫子, 鈴木美和, 松浦基樹, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 57 ( Suppl.1 ) 220 - 220 2018.04

子宮内膜細胞診の有用性子宮内膜液状化細胞診検体による遺伝子解析研究

松浦基樹, 玉手雅人, 郷久晴朗, 寺本瑞絵, 幸保莉香, 畠山晴良, 山口貴世志, 杉田真太朗, 池上恒雄, 岩崎雅宏, 長谷川匡, 古川洋一, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 57 ( Suppl.1 ) 123 - 123 2018.04

多機能な細胞接着分子が関わるがんの理解診断・治療への応用をめざして 3細胞間タイト結合分子LSRの発現低下によるがん細胞の悪性化機序

金野匠, 嶋田浩志, 郷久晴朗, 齋藤豪, 幸野貴之, 小島隆

日本病理学会会誌 ( (一社)日本病理学会 ) 107 ( 1 ) 242 - 242 2018.04

玉手雅人, 齋藤豪

産科と婦人科 ( (株)診断と治療社 ) 85 ( Suppl ) 174 - 181 2018.04

Pioglitazone is effective for multiple phenotyepes of the Zucker fa/fa rat with polycystc ovary morphology and insulin resistance

Miyuki Morishita, Toshiaki Endo, Tsuyoshi Baba, Yoshika Kuno, Keiko Ikeda, Tamotsu Kiya, Hiroyuki Honnma, Tsuyoshi Saito

Journal of Ovarian Research ( BioMed Central Ltd. ) 11 ( 1 ) 2018.03 [Refereed]

Background: Hyperandrogenism and insulin resistance may be related to the etiology of PCOS. Zucker fa/fa rats with polycystic ovary are obese, have insulin resistance without diabetes mellitus or hyperandrogenism and can be utilized as PCOS model rats without effects of hyperandrogenemia. PCOS patients are reported to have elevated levels of serum anti-Mullerian hormone (AMH), which has an inhibitory action on folliculogenesis, and low levels of serum adiponectin, which blocks apoptosis and induces biological effects in some tissues. Pioglitazone, an insulin sensitizer, is administered to PCOS patients with insulin resistance to induce ovulation but the mechanisms by which this occurs have not been elucidated. Methods: We purchased 4-week-old female fatty Zucker fa/fa rats as well as lean Zucker +/+ rats for use as control rats with normal insulin sensitivity. The Zucker fa/fa rats were administered pioglitazone (2.5 mg/kg body weight/day) or a vehicle every day for 14 days in separate groups. The Zucker +/+ rats were also administered the vehicle. After 2 weeks of treatment, they were euthanized and we obtained serum samples and both ovaries and determined the body weight, ovarian weight, and serum AMH, adiponectin, testosterone, and androstenedione levels. We also examined ovarian histology to check follicle numbers by using hematoxylin-eosin staining, and the number of atretic follicles using Tdt-mediated dUTP nick end labeling (TUNEL) methods. Results: The Zucker fa/fa rats used as PCO model rats and Pioglitazone treated PCO model rats were significantly heavier than the Zucker +/+ control rats (p < 0.05) at 15 day old. Pioglitazone treatment did not influence body weight or ovarian weight in either group. However, the total number of follicles was significantly larger in the PCO model rats than in the control rats (P < 0.05). Although pioglitazone treatment appeared to decrease the total number of follicles in the PCO model rats, the decrease was not statistically significant. However, pioglitazone treatment significantly decreased the total number of atretic follicles and the rate of atreteic follicles in the PCO model rats (P < 0.05). The serum AMH level was significantly higher in the PCO model rats than in the control rats. Pioglitazone treatment significantly decreased the serum AMH level and significantly increased the serum adiponectin level in the PCO model rats (P < 0.05). Serum testosterone and androstenedione levels were quite low or undetectable in the 3 groups of rats, and were not influenced by pioglitazone treatment. Conclusion: In this study, pioglitazone treatment reduced the serum AMH level and increased the serum adiponectin level in PCO model rats. These effects are related to reduction of the total number of atretic follicles and rate of atretic follicles. This proves that pioglitazone treatment improves healthy follicle growth in these PCO model rats with insulin resistance.

DOI

子宮頸部細胞診ASC-US症例における従来法と液状検体法による比較検討

鹿内智史, 真里谷奨, 嶋田浩志, 玉手雅人, 黒田敬史, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 62 ( 1 ) 172 - 172 2018.03

卵巣腫瘍および腸管型GISTとの鑑別に苦慮した非医原性腸管parasitic leiomyoma

鈴木麻由, 嶋田浩志, 阿部秀悦, 鹿内智史, 真里谷奨, 橋本卓, 阿部厚憲, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 62 ( 1 ) 193 - 193 2018.03

非医原性parasitic leiomyomaの一例

嶋田浩志, 阿部秀悦, 鹿内智史, 真里谷奨, 橋本卓, 阿部厚憲, 郷久晴朗, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 62 ( 1 ) 21 - 24 2018.03

近年、子宮筋腫の腹腔鏡手術の普及により、電動式モルセレーターが原因と考えられる医原性Parasitic leiomyoma(PM、寄生筋腫)が問題となっている。しかし、古くから非医原性症例のPMも知られており、診断に苦慮することがある。今回我々は、卵巣腫瘍およびGISTとの鑑別に苦慮した非医原性PMの症例を経験した。症例は68歳、2妊1産、既往歴に虫垂炎手術歴あり。右下腹部の違和感を主訴に当科初診、MRI検査では多発子宮筋腫と子宮右前壁側に子宮との連続性に乏しい65×45×41mm大の腫瘤性病変を認めた。変性筋腫または右卵巣腫瘍の疑いで腹式子宮全摘術および両側付属器摘出術の方針となった。術中所見では両側卵巣は正常であり、回盲部末端より5cm口側に有茎性の充実腫瘍を認めた。小腸Gastrointestinal stromal tumor(GIST)の疑いで小腸部分切除術を実施し終了した。病理所見は細胞増生が密な有棘性細胞像を認め、CD34、S-100は陰性、actin、desminが陽性よりPMの診断となった。術後症状は改善し以後は良好に経過した。筋腫手術既往のない症例においてPMを疑うことはまれである。さらにPMとGISTおよび卵巣腫瘍を鑑別することは困難であり、審査腹腔鏡を行うことが有用である。(著者抄録)

子宮鏡ガイド下に腹腔鏡下子宮体部筋層形成術を施行し出産に至った2症例

明石祐史, 杉尾明香, 西澤庸子, 金美善, 玉手雅人, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 62 ( 1 ) 224 - 224 2018.03

地域周産期施設における腹腔鏡手術の特性と有用性

玉手雅人, 長尾沙智子, 黒川晶子, 染谷真行, 岡村直樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 62 ( 1 ) 222 - 222 2018.03

当院における腹腔鏡下子宮筋腫核出術後の妊娠症例の検討

西村庸子, 杉尾明香, 玉手雅人, 金美善, 森下美幸, 明石祐史, 遠藤俊明, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 62 ( 1 ) 36 - 40 2018.03

目的:近年の晩婚化に伴い、子宮筋腫核出術施行後の妊娠出産が増加している。筋腫核出後の妊娠合併症として子宮破裂や帝王切開施行時に癒着等が問題となる。今回当院で腹腔鏡下子宮筋腫核出術(Laparoscopic myomectomy以下LM)施行後に妊娠出産した症例について、妊娠分娩経過に関し後方視的に検討した。また開腹子宮筋腫核出術(Abdominal myomectomy以下AM)、腹腔鏡補助下子宮筋腫核出術(Laparoscopic assisted myomectomy以下LAM)施行後に当院で帝王切開を施行した群と妊娠経過、子宮筋層の所見、腹腔内癒着等を比較検討した。方法:対象は2012年4月から2015年9月までに当院でLMを施行した196例のうち術後帝王切開術を施行した37例、AM後帝王切開術8例、LAM後帝王切開術9例。それぞれの妊娠合併症、手術時間、癒着率、手術合併症等を比較した。当院の方針として、筋腫核出後の妊娠は全て帝王切開施行とした。結果:子宮筋腫核出部癒着率はAM群、LAM群、LM群の順に高い傾向を認めた。3群とも子宮破裂や癒着胎盤の症例もなかった。結論:LM後の妊娠では、子宮破裂のリスクが高いとする報告もあるが、正確な縫合による子宮筋層の修復や、鉗子操作、過度な電気凝固止血操作を避けるなどの試みによりリスクを軽減できる可能性がある。(著者抄録)

Transabdominal cerclage (TAC) for patients with ultra-short uterine cervix after uterine cervix surgery and its impact on pregnancy

Shinichi Ishioka, Miseon Kim, Yuko Mizugaki, Saori Kon, Kyoko Isoyama, Masahito Mizuuchi, Miyuki Morishita, Tsuyoshi Baba, Takao Sekiya, Tsuyoshi Saito

Journal of Obstetrics and Gynaecology Research ( Blackwell Publishing ) 44 ( 1 ) 61 - 66 2018.01 [Refereed]

Aim: Patients with an ultra-short uterine cervix as a result of large conization, repeated conization or radical trachelectomy (RT), are at high risk of preterm premature rupture of the membrane, which leads to preterm birth. We have commenced performing transabdominal cerclage (TAC) of the uterine cervix for these patients. In this study, we examined the safety of TAC and its impact on pregnancy. Methods: We have performed TAC in 11 patients before pregnancy: in six after large cervical operations, such as repeated conization and in five for difficulties with cervical cerclage after RT. After laparotomy, a Teflon thread was placed in the avascular space between the uterine vessels and the uterine muscle, and tied. The clinical course of the patients after TAC and their pregnancy course were retrospectively reviewed. Results: TAC was performed safely without any complications. The mean operative duration was 53 ± 10 min, and the mean blood loss during the operation was 49 ± 64 mL. Seven women conceived within 2 years after TAC. Their pregnancy courses were favorable. Five of the women underwent scheduled cesarean sections, while two pregnancies are ongoing. Conclusions: Although there are risks of various complications as a result of the use of non-absorbable thread and the need for two extra laparotomies, TAC can be a safe and useful option for patients who show cervical incompetence after large uterine cervical operations, such as RT or large conization.

DOI PubMed

LOSS OF ASPP2 PROMOTES CELL INVASION AND MIGRATION VIA YAP IN HUMAN ENDOMETRIAL CANCER

Shimada, H, Satohisa, S, Konno, T, Matsuura, M, Teramoto, M, Kohno, T, Iwasaki, M, Kojima, T, Saito, T

International Journal of Gynecological Cancer 2018

Downregulation of lipolysis-stimulated lipoprotein receptor promotes cell invasion via claudin-1-mediated matrix metalloproteinases in human endometrial cancer

Hiroshi Shimada, Seiro Satohisa, Takayuki Kohno, Takumi Konno, Ken-Ichi Takano, Syunta Takahashi, Tsubasa Hatakeyama, Chihiro Arimoto, Tsuyoshi Saito, Takashi Kojima

ONCOLOGY LETTERS ( SPANDIDOS PUBL LTD ) 14 ( 6 ) 6776 - 6782 2017.12 [Refereed]

Lipolysis-stimulated lipoprotein receptor (LSR) is a novel molecule present at tricellular contacts which recruits tricellulin (TRIC), a molecular component of tricellular tight junctions (tTJs). LSR and TRIC are colocalized with the bicellular tight junction (bTJ) protein claudin (CLDN)-1-based tight junction strands at tricellular corners. Knockdown of LSR in normal epithelial cells affects tTJ formation and the epithelial barrier function. In cancer cells knockdown of LSR has been demonstrated to increase cell invasion. However, the detailed mechanisms of how the downregulation of LSR enhances cell invasion in cancer remain unclear. In the present study, knockdown of LSR by small interfering RNA (siRNA) in Sawano human endometrial adenocarcinoma cells induced cell invasion. In LSR-knockdown Sawano cells, upregulation of CLDN-1 protein, which contributes to the cell invasion via matrix metalloproteinases (MMPs), was observed compared with the control group by western blotting and immunostaining. Knockdown of LSR significantly induced Sp1 transcription factor activity in the CLDN-1 promoter region. In LSR-knockdown Sawano cells, DNA microarray analysis demonstrated that MMP-1, MMP-2 and MMP-10 mRNA levels were increased, and the protein levels of membrane-type 1-MMP, MMP-2, MMP-9 and MMP-10 were shown to be increased on western blots. Knockdown of CLDN-1 with siRNA prevented the upregulation of cell invasion induced by the knockdown of LSR in Sawano cells. On the invasive front of human endometrial carcinoma tissue samples, a decrease in LSR and increase in CLDN-1 protein levels were observed using immunohistochemical methods. In conclusion, the results indicate that the downregulation of LSR promotes cell invasion of human endometrial cancer via CLDN-1 mediation of MMPs. This mechanism is important for studying the association of tTJs with the cellular invasion of cancer.

DOI

膜を意識して行う腹腔鏡下En bloc骨盤リンパ節郭清

松浦基樹, 玉手雅人, 斎藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 22 ( 7 ) SF113 - 02 2017.12

変性筋腫核出術の工夫

岡田匡氷, 玉手雅人, 田渕雄大, 長尾沙智子, 杉尾明香, 明石祐史, 松浦基樹, 斎藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 22 ( 7 ) SF036 - 06 2017.12

当科での広間膜内筋腫に対する核出術における手術戦略

田渕雄大, 玉手雅人, 長尾沙智子, 杉尾明香, 明石祐史, 松浦基樹, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 22 ( 7 ) SF036 - 05 2017.12

診療、教育、研究の充実にはオフの活動が不可欠!

齋藤豪, 松浦基樹, 玉手雅人, 岩崎雅宏, 郷久晴朗, 寺田倫子

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 22 ( 7 ) 3 - 1 2017.12

急性虫垂炎との鑑別に難渋し診断的腹腔鏡にて卵管留血腫の茎捻転と判明した女児の1例

鹿内智史, 真里谷奨, 嶋田浩志, 郷久晴朗, 高橋徹, 齋藤豪

産科と婦人科 ( (株)診断と治療社 ) 84 ( 12 ) 1513 - 1517 2017.12

細胞質分裂における3細胞間タイト結合分子の局在と役割

金野匠, 幸野貴之, 菊池真, 嶋田浩志, 郷久晴朗, 齋藤豪, 小島隆

生命科学系学会合同年次大会 ( 生命科学系学会合同年次大会運営事務局 ) 2017年度 [2P - 0351] 2017.12

Comprehensive single-cell transcriptome analysis reveals heterogeneity in endometrioid adenocarcinoma tissues

Shinichi Hashimoto, Yuta Tabuchi, Hideaki Yurino, Yoshihiko Hirohashi, Shungo Deshimaru, Takuya Asano, Tasuku Mariya, Kenshiro Oshima, Yuzuru Takamura, Yoshiaki Ukita, Akio Ametani, Naoto Kondo, Norikazu Monma, Tadayuki Takeda, Sadahiko Misu, Toshitugu Okayama, Kazuho Ikeo, Tsuyoshi Saito, Shuich Kaneko, Yutaka Suzuki, Masahira Hattori, Kouji Matsushima, Toshihiko Torigoe

SCIENTIFIC REPORTS ( NATURE PUBLISHING GROUP ) 7 2017.10 [Refereed]

Single cell transcriptome analysis of a cancer tissue can provide objective assessment of subtype population or the activation of each of various microenvironment component cells. In this study, we applied our newly developed technique of single cell analysis to the myometrial infiltration side (M-side) and the endometrial side (E-side) of a human endometrioid adenocarcinoma with squamous differentiation tissues. We also analyzed spherogenic cultures derived from the same tissue to identify putative regulators of stemness in vivo. Cancer cells in the E-side were highly malignant compared with those in the M-side. Many cells on the E-side were positive for spheroid-specific tumorigenesis-related markers including SOX2. In addition, there were higher numbers of epithelial-to-mesenchymal transition (EMT) cells in the E-side compared with the M-side. This study identified a site containing cells with high malignant potential such as EMT and cancer stem-like cells in cancer tissues. Finally, we demonstrate that established endometrioid adenocarcinoma subtype classifiers were variably expressed across individual cells within a tumor. Thus, such intratumoral heterogeneity may be related to prognostic implications.

DOI

子宮体癌における予後因子と子宮頸部細胞診所見の関連性の検討

田中綾一, 鈴木孝浩, 玉手雅人, 寺田倫子, 松浦基樹, 鈴木美和, 高橋円, 郷久晴朗, 寺本瑞絵, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 56 ( Suppl.2 ) 726 - 726 2017.10

Umbilical cord extracts improve diabetic abnormalities in bone marrow-derived mesenchymal stem cells and increase their therapeutic effects on diabetic nephropathy

Kanna Nagaishi, Yuka Mizue, Takako Chikenji, Miho Otani, Masako Nakano, Yusaku Saijo, Hikaru Tsuchida, Shinichi Ishioka, Akira Nishikawa, Tsuyoshi Saito, Mineko Fujimiya

SCIENTIFIC REPORTS ( NATURE PUBLISHING GROUP ) 7 ( 1 ) 8484 2017.08 [Refereed]

Bone marrow-derived mesenchymal stem cells (BM-MSC) has been applied as the most valuable source of autologous cell transplantation for various diseases including diabetic complications. However, hyperglycemia may cause abnormalities in intrinsic BM-MSC which might lose sufficient therapeutic effects in diabetic patients. We demonstrated the functional abnormalities in BM-MSC derived from both type 1 and type 2 diabetes models in vitro, which resulted in loss of therapeutic effects in vivo in diabetic nephropathy (DN). Then, we developed a novel method to improve abnormalities in BM-MSC using human umbilical cord extracts, namely Wharton's jelly extract supernatant (WJs). WJs is a cocktail of growth factors, extracellular matrixes and exosomes, which ameliorates proliferative capacity, motility, mitochondrial degeneration, endoplasmic reticular functions and exosome secretions in both type 1 and type 2 diabetes-derived BM-MSC (DM-MSC). Exosomes contained in WJs were a key factor for this activation, which exerted similar effects to complete WJs. DM-MSC activated by WJs ameliorated renal injury in both type 1 and type 2 DN. In this study, we developed a novel activating method using WJs to significantly increase the therapeutic effect of BM-MSC, which may allow effective autologous cell transplantation.

DOI PubMed

Ovarian high-grade endometrioid stromal sarcoma with YWHAE and NUTM2B rearrangements.

Noriaki Kikuchi, Shintaro Sugita, Katsuya Nakanishi, Taro Sugawara, Keiko Segawa, Yumika Ito, Terufumi Kubo, Hiromi Fujita, Hiroshi Hirano, Ryoichi Tanaka, Tsuyoshi Saito, Tadashi Hasegawa

Pathology international 67 ( 6 ) 327 - 329 2017.06 [International journal]

DOI PubMed

当院における死戦期帝王切開を念頭においた産科救急システムの構築

水内将人, 藤部佑哉, 嶋田浩志, 馬場剛, 石岡伸一, 斎藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 53 ( 2 ) 727 - 727 2017.06

Phosphorylation of HSF1 at serine 326 residue is related to the maintenance of gynecologic cancer stem cells through expression of HSP27.

Kazuyo Yasuda, Yoshihiko Hirohashi, Tasuku Mariya, Aiko Murai, Yuta Tabuchi, Takafumi Kuroda, Hiroki Kusumoto, Akari Takaya, Eri Yamamoto, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Yasuaki Tamura, Hiroshi Hirano, Tadashi Hasegawa, Tsuyoshi Saito, Noriyuki Sato, Toshihiko Torigoe

Oncotarget 8 ( 19 ) 31540 - 31553 2017.05 [International journal]

Cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) are defined by their higher tumor-initiating ability, self-renewal capacity and differentiation capacity. CSCs/CICs are resistant to several therapies including chemotherapy and radiotherapy. CSCs/CICs thus are thought to be responsible for recurrence and distant metastasis, and elucidation of the molecular mechanisms of CSCs/CICs are essential to design CSC/CIC-targeting therapy. In this study, we analyzed the molecular aspects of gynecological CSCs/CICs. Gynecological CSCs/CICs were isolated as ALDH1high cell by Aldefluor assay. The gene expression profile of CSCs/CICs revealed that several genes related to stress responses are preferentially expressed in gynecological CSCs/CICs. Among the stress response genes, a small heat shock protein HSP27 has a role in the maintenance of gynecological CSCs/CICs. The upstream transcription factor of HSP27, heat shock factior-1 (HSF1) was activated by phosphorylation at serine 326 residue (pSer326) in CSCs/CICs, and phosphorylation at serine 326 residue is essential for induction of HSP27. Immunohistochemical staining using clinical ovarian cancer samples revealed that higher expressions of HSF1 pSer326 was related to poorer prognosis. These findings indicate that activation of HSF1 at Ser326 residue and transcription of HSP27 is related to the maintenance of gynecological CSCs/CICs.

DOI PubMed

3細胞間タイト結合蛋白LSRはYAP/AMOT/merlinを介して子宮内膜癌の悪性化へ関与する

阿部秀悦, 嶋田浩志, 郷久晴朗, 金野匠, 齋藤豪, 幸野貴之, 小島隆

日本細胞生物学会大会講演要旨集 ( (一社)日本細胞生物学会 ) 69回 95 - 95 2017.05

Rap1GAP inhibits tumor progression in endometrial cancer.

Tamate M, Tanaka R, Osogami H, Matsuura M, Satohisa S, Iwasaki M, Saito T

Biochemical and biophysical research communications 485 ( 2 ) 476 - 483 2017.04 [Refereed]

DOI PubMed

子宮内膜細胞の悪性化におけるASPP2の役割

郷久晴朗, 嶋田浩志, 岩崎雅宏, 寺田倫子, 鈴木美和, 秋元太志, 寺本瑞絵, 田中綾一, 阿部秀祝, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 56 ( Suppl.1 ) 353 - 353 2017.04

初期子宮体癌の合併が診断しえたポリープ状異型腺筋腫の1例

黒川晶子, 玉手雅人, 長尾沙智子, 染谷真行, 郷久晴朗, 寺本瑞絵, 杉田真太朗, 田中綾一, 岩崎雅宏, 岡村直樹, 齋藤豪

産科と婦人科 ( (株)診断と治療社 ) 84 ( 4 ) 495 - 498 2017.04

ポリープ状異型腺筋腫(atypical polypoid adenomyoma:APAM)は病理組織学的に良性腫瘍に属する。しかし、複雑型子宮内膜異型増殖症や子宮体部類内膜腺癌を合併することも多い。好発年齢が比較的若年であることから、治療に関しては慎重な対応が必要となる。また術前の画像や細胞像から判断することは困難であり、多くは術後に診断される。今回、初回手術でAPAMの診断となり、慎重に経過観察を行った結果、内膜細胞診から子宮体癌の合併を疑い適切に治療を行うことができた1例を経験した。(著者抄録)

Uterine epithelioid leiomyosarcoma with c-kit expression and YWHAE gene rearrangement: a case report of a diagnostic pitfall of uterine sarcoma.

Terufumi Kubo, Shintaro Sugita, Ryuichi Wada, Noriaki Kikuchi, Masahiro Iwasaki, Yumika Ito, Taro Sugawara, Hiromi Fujita, Makoto Emori, Ryoichi Tanaka, Hiroshi Hirano, Tsuyoshi Saito, Tadashi Hasegawa

Diagnostic pathology 12 ( 1 ) 26 - 26 2017.03 [International journal]

BACKGROUND: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. CASE PRESENTATION: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses. The immunophenotype of the tumor featured smooth muscle differentiation and hormone receptor expression. The cell membrane and cytoplasm were positive for c-kit, although no mutation was found in the c-kit or PDGFRA gene. Fluorescence in situ hybridization (FISH) analysis revealed a relatively low frequency of YWHAE rearrangement, whereas there were few NUTM2A and NUTM2B split signals. CONCLUSIONS: In this case, the tumor was not typical of any three of the differential diagnoses mentioned above. However, insufficient frequency of YWHAE, NUTM2A, and NUTM2B gene rearrangement and absence of mutation in both the c-kit and PDGFRA genes suggested that this tumor should be categorized as epithelioid leiomyosarcoma. This is an instructive case showing a potential diagnostic pitfall of uterine sarcoma. Comprehensive approaches including molecular biological techniques are required for definitive diagnosis.

DOI PubMed

Role of dilatation and curettage performed for spontaneous or induced abortion in the etiology of endometrial thinning

Atsushi Azumaguchi, Hirofumi Henmi, Hirofumi Ohnishi, Toshiaki Endo, Tsuyoshi Saito

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 ( 3 ) 523 - 529 2017.03 [Refereed]

DOI PubMed

Conversion症例からTLHの適応を考える

明石祐史, 杉尾明香, 西澤庸子, 玉手雅人, 金美善, 足立英文, 森下美幸, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 61 ( 1 ) 56 - 56 2017.03

子宮頸部原発平滑筋肉腫の1例

竹田倫子[寺田], 玉手雅人, 杉田真太朗, 鈴木孝浩, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 56 ( 2 ) 92 - 95 2017.03

背景:子宮平滑筋肉腫は子宮体部に発生することが多く、子宮頸部原発の平滑筋肉腫はまれである。われわれは、子宮頸部に発生した平滑筋肉腫の症例を経験したので報告する。症例:症例は45歳。不正出血が続くため当科を受診した。子宮頸部に1.5cm大の筋腫様腫瘤を認めた。腫瘍擦過細胞診ではNILM(negative for intraepithelial lesion or malignancy)と診断し、子宮鏡下に腫瘍摘出術を施行したところ平滑筋肉腫との診断にて、初回手術から23日後に準広汎子宮全摘出術+両付属器摘出術を施行した。術後約2年経過したが、今のところ再発の徴候はない。結論:平滑筋肉腫は細胞診で診断することが困難な場合があるため、細胞診で紡錘形細胞を認めた場合は、悪性腫瘍である可能性も考慮しながら診断を進めていく必要がある。(著者抄録)

腹腔鏡下子宮筋腫核出術において、筋腫のバリエーションから考えた術前治療と術後病理

玉手雅人, 長尾沙智子, 染谷真行, 竹田倫子, 杉尾明香, 森下美幸, 明石祐史, 岡村直樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 61 ( 1 ) 55 - 55 2017.03

Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer

Hiroshi Shimada, Shyuetsu Abe, Takayuki Kohno, Seiro Satohisa, Takumi Konno, Syunta Takahashi, Tsubasa Hatakeyama, Chihiro Arimoto, Takuya Kakuki, Yakuto Kaneko, Ken-ichi Takano, Tsuyoshi Saito, Takashi Kojima

SCIENTIFIC REPORTS ( NATURE PUBLISHING GROUP ) 7 2017.01 [Refereed]

Lipolysis-stimulated lipoprotein receptor (LSR) is a unique molecule of tricellular contacts of normal and cancer cells. We investigated how the loss of LSR induced cell migration, invasion and proliferation in endometrial cancer cell line Sawano. mRNAs of amphiregulin (AREG) and TEA domain family member 1 (TEAD1) were markedly upregulated by siRNA-LSR. In endometrial cancer tissues, downregulation of LSR and upregulation of AREG were observed together with malignancy, and Yes-associated protein (YAP) was present in the nuclei. siRNA-AREG prevented the cell migration and invasion induced by siRNA-LSR, whereas treatment with AREG induced cell migration and invasion. LSR was colocalized with TRIC, angiomotin (AMOT), Merlin and phosphorylated YAP (pYAP). siRNA-LSR increased expression of pYAP and decreased that of AMOT and Merlin. siRNA-YAP prevented expression of the mRNAs of AREG and TEAD1, and the cell migration and invasion induced by siRNA-LSR. Treatment with dobutamine and 2-deoxy-D-glucose and glucose starvation induced the pYAP expression and prevented the cell migration and invasion induced by siRNA-LSR. siRNA-AMOT decreased the Merlin expression and prevented the cell migration and invasion induced by siRNA-LSR. The loss of LSR promoted cell invasion and migration via upregulation of TEAD1/AREG dependent on YAP/pYAP and AMOT/Merlin in human endometrial cancer cells.

DOI PubMed

Prognostic significance of the co-expression of EGFR and HER2 in adenocarcinoma of the uterine cervix.

Ueda A, Takasawa A, Akimoto T, Takasawa K, Aoyama T, Ino Y, Nojima M, Ono Y, Murata M, Osanai M, Hasegawa T, Saito T, Sawada N

PLOS ONE 12 ( 8 ) e0184123 2017 [Refereed]

DOI PubMed

Downregulation of LSR promotes cell invasion via claudin-1-mediated MMPs in human endometrial cancer.

Shimada H, Satohisa S, Kohno T, Konno T, Takano K, Takahashi S, Hatakeyama T, Arimoto C, Saito T, Kojima T

Oncology Letters 14(6):6776-6782. 2017 [Refereed]

PubMed

Virological and cytological clearance in laser vaporization and conization for cervical intra-epithelial neoplasia grade 3.

Tasuku Mariya, Akira Nishikawa, Kanae Sogawa, Riri Suzuki, Masae Saito, Akari Kawamata, Ayumi Shimizu, Takehito Nihei, Tomoko Sonoda, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 42 ( 12 ) 1808 - 1813 2016.12 [International journal]

AIM: Cervical intra-epithelial neoplasia (CIN) is the precancerous stage of cervical cancer. Standard treatment for high-grade CIN is conization of the cervix. The risk of preterm birth following conization has been discussed recently. In contrast, laser vaporization is believed not to affect perinatal outcome, but the long-term effectiveness of each surgical procedure is still unclear. The aim of this prospective unmatched-cohort study was therefore to compare virological and cytological clearance and recurrence risk between conization and vaporization for CIN3. METHODS: Subject consisted of CIN3 patients treated at the present hospital between 2007 to 2011 and followed up until December 2014. One hundred and one patients were treated with laser conization, and 137 with vaporization. The surgical procedure was selected on the basis of colposcopy, pathological grade and patient's hope for pregnancy. RESULTS: There were no significant differences in cure rate, human papilloma virus (HPV) clearance rate or recurrence rates between the conization and vaporization groups. Risk ratio of recurrence for each surgical procedure adjusted for age and HPV persistence status were analyzed on Cox proportional hazards modeling. Recurrence risk ratio for patients treated by vaporization was 6.21 (95%CI: 0.65-59.19; P = 0.111) compared with conization and there were no significant differences. No adverse pregnancy outcome was observed in the vaporization group compared with conization. CONCLUSIONS: Laser vaporization is useful for young patients with CIN3 who hope for pregnancy in the future.

DOI PubMed

Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy

Yu Takada, Masanori Someya, Yoshihisa Matsumoto, Masaaki Satoh, Kensei Nakata, Masakazu Hori, Masato Saito, Naoki Hirokawa, Kunihiko Tateoka, Mizue Teramoto, Tsuyoshi Saito, Tadashi Hasegawa, Koh-ichi Sakata

MEDICAL MOLECULAR MORPHOLOGY ( SPRINGER JAPAN KK ) 49 ( 4 ) 210 - 216 2016.12 [Refereed]

DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %, P = 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %, P = 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P = 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %, P = 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.

DOI

腹水セルブロックにおける検討が治療方針決定に有用であった腹膜原発粘液性腺癌の1例

玉手雅人, 長尾沙智子, 竹田倫子, 松浦基樹, 寺本瑞絵, 郷久晴朗, 田中綾一, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 55 ( Suppl.2 ) 494 - 494 2016.10

Analysis of the expression and localization of tight junction transmembrane proteins, claudin-1,-4,-7, occludin and JAM-A, in human cervical adenocarcinoma

Taishi Akimoto, Akira Takasawa, Masaki Murata, Yui Kojima, Kumi Takasawa, Masanori Nojima, Tomoyuki Aoyama, Yutaro Hiratsuka, Yusuke Ono, Satoshi Tanaka, Makoto Osanai, Tadashi Hasegawa, Tsuyoshi Saito, Norimasa Sawada

HISTOLOGY AND HISTOPATHOLOGY ( F HERNANDEZ ) 31 ( 8 ) 921 - 931 2016.08 [Refereed]

Objective. Tight junction proteins have recently been reported to be useful for distinguishing between neoplastic and non-neoplastic tissues. In this study, we evaluated the expression and localization of tight junction transmembrane proteins in human cervical adenocarcinoma and adenocarcinoma in situ (AIS), and we determined whether their expression patterns could distinguish cervical adenocarcinoma from nonneoplastic cervical glands. Methods. Fifty-five patients with cervical adenocarcinoma or AIS were included in this study. Surgical specimens were immunohistochemically stained for claudin (CLDN) -1, -4, -7, occludin, and JAM-A. Results. Significantly higher expression levels of CLDNs and JAM-A were found in cervical AIS and adenocarcinoma than in non-neoplastic glands. In cervical AIS and adenocarcinoma, localization of CLDN-1 and JAM-A was extended throughout the whole cell membranes, whereas they were predominantly expressed at the most apical cell-cell junction in non-neoplastic glands. ROC curve analysis revealed that immunoreactivities of CLDN-1 or JAM-A successfully distinguished neoplasms from nonneoplastic cervical glands with high specificity (CLDN-1, 79.1%; JAM-A, 79.1%) and high sensitivity (CLDN-1, 84.1%; JAM-A, 95.5%). Conclusions. As expected, there were immunohistochemical differences between cervical adenocarcinoma and non-neoplastic cervical glands by using antibodies against tight junction transmembrane proteins. These results suggest that CLDN-1 and JAM-A are potential biomarkers for cervical adenocarcinoma.

DOI

腹腔鏡下に診断し得た女児の左卵管留血腫

鹿内智史, 嶋田浩志, 真里谷奨, 郷久晴朗, 高橋徹, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 32 ( Suppl.I ) 246 - 246 2016.08

子宮全摘出術における腹腔鏡下手術と腟式手術の手術侵襲に関する検討

田中綾一, 明石祐史, 玉手雅人, 杉尾明香, 金美善, 寺田倫子, 森下美幸, 郷久晴朗, 寺本瑞絵, 岩崎雅宏, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 32 ( Suppl.I ) 322 - 322 2016.08

腹腔鏡下手術においてセプラフィルム腹腔内搬入および貼付目的に用いたトロックスガーゼの使用経験

田中綾一, 森下美幸, 寺本瑞絵, 寺田倫子, 玉手雅人, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 32 ( Suppl.I ) 324 - 324 2016.08

Possibility of less radical treatment for patients with early invasive uterine cervical cancer

Miseon Kim, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Masahito Mizuuchi, Sakura Takada, Tsuyoshi Saito

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH ( WILEY-BLACKWELL ) 42 ( 7 ) 876 - 882 2016.07 [Refereed]

AimRadical trachelectomy (RT) with lymphadenectomy has become a standard treatment modality for patients with early invasive uterine cervical cancer who hope to preserve fertility. However, pregnancy after RT has high risks of preterm birth. The possibility of more conservative RT and the application of RT for patients with higher clinical stages were studied. MethodsThe medical charts and specimens of 42 patients who underwent RT and 64 patients who underwent radical hysterectomy were retrospectively studied. Tumor size, distance between the margin of the cancer and the internal orifice of the uterus (os), parametrial invasion, lymph node metastasis and prognoses were investigated. ResultsThe average distances between the inner margin of the cancer and the internal os were 37 mm, 29 mm, 18.7 mm and 14 mm for patients with stage 1 A2, 1B1 ( 2 cm), 1B1 (> 2 cm) and 1B2, respectively. When amputation was performed 10 mm below the internal os, all 10 patients with 1 A2, 57 with 1B1 ( 2 cm), 19 with 1B1 (> 2 cm), and one with 1B2 had a cancer-free margin > 10 mm. Patients with stage 1 A2 had a cancer-free margin > 10 mm even if we amputated the cervix 20 mm below the internal os. Parametrial invasion was detected in two patients with stage 1B1. ConclusionsA simple trachelectomy 20 mm below the internal os with pelvic lymphadenectomy might be possible for stage 1 A2 patients. The present method is best for stage 1B1 patients ( 2 cm). RT for stage 1B1 (>2 cm) or higher stages should be contraindicated.

DOI

BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

Shutaro Habata, Masahiro Iwasaki, Asuka Sugio, Miwa Suzuki, Masato Tamate, Seiro Satohisa, Ryoichi Tanaka, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF ONCOLOGY ( SPANDIDOS PUBL LTD ) 49 ( 1 ) 402 - 410 2016.07 [Refereed]

Paclitaxel in combination with carboplatin improves survival among patients with susceptible ovarian cancers, but no strategy has been established against resistant ovarian cancers. BAG3 (Bcl-2-associated athanogene 3) is one of six BAG family proteins, which are involved in such cellular processes as proliferation, migration and apoptosis. In addition, expression of BAG3 with Mcl-1, a Bcl-2 family protein, reportedly associates with resistance to chemotherapy. Our aim in this study was to evaluate the functional role of BAG3 and Mcl-1 in ovarian cancer chemoresistance and explore possible new targets for treatment. We found that combined expression of BAG3 and Mcl-1 was significantly associated with a poor prognosis in ovarian cancer patients. In vitro, BAG3 knockdown in ES2 clear ovarian cancer cells significantly increased the efficacy of paclitaxel in combination with the Mcl-1 antagonist MIM1, with or without the Bcl-2 family antagonist ABT737. Moreover, BAG3 was found to positively regulate Mcl-1 levels by binding to and inhibiting USP9X. Our data show that BAG3 and Mcl-1 are key mediators of resistance to chemotherapy in ovarian cancer. In BAG3 knockdown ES2 clear ovarian cancer cells, combination with ABT737 and MIM1. enhanced the efficacy of paclitaxel. These results suggest that inhibiting BAG3 in addition to antiapoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers.

DOI

3細胞間タイト結合蛋白LSRはHippo pathwayを介して子宮内膜癌の悪性化に関与している

嶋田浩志, 郷久晴朗, 金野匠, 高橋駿太, 畠山翔翼, 幸野貴之, 田中綾一, 寺本瑞絵, 岩崎雅宏, 小島隆, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 34 ( 3 ) 416 - 416 2016.06

Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer

Tasuku Mariya, Yoshihiko Hirohashi, Toshihiko Torigoe, Yuta Tabuchi, Takuya Asano, Hiroshi Saijo, Takafumi Kuroda, Kazuyo Yasuda, Masahito Mizuuchi, Tsuyoshi Saito, Noriyuki Sato

ONCOTARGET ( IMPACT JOURNALS LLC ) 7 ( 18 ) 26806 - 26822 2016.05 [Refereed]

Epithelial ovarian cancer (EOC) is one of the most lethal cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) have been reported to be origin of primary and recurrent cancers and to be resistant to several treatments. In this study, we identified matrix metalloproteinase-10 (MMP10) is expressed in CSCs/CICs of EOC. An immunohistochemical study revealed that a high expression level of MMP10 is a marker for poor prognosis and platinum resistance in multivariate analysis. MMP10 gene overexpression experiments and MMP10 gene knockdown experiments using siRNAs revealed that MMP10 has a role in the maintenance of CSCs/CICs in EOC and resistance to platinum reagent. Furthermore, MMP10 activate canonical Wnt signaling by inhibiting noncanonical Wnt signaling ligand Wnt5a. Therefore, MMP10 is a novel marker for CSCs/CICs in EOC and that targeting MMP10 is a novel promising approach for chemotherapy-resistant CSCs/CICs in EOC.

DOI

MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation.

Kazuyo Yasuda, Yoshihiko Hirohashi, Takafumi Kuroda, Akari Takaya, Terufumi Kubo, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Noriyuki Sato, Toshihiko Torigoe

Biochemical and biophysical research communications 472 ( 4 ) 643 - 7 2016.04 [International journal]

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH(high)) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH(high) population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

DOI PubMed

子宮体癌初代培養細胞株における癌幹細胞の分離同定とその解析

田渕雄大, 廣橋良彦, 真里谷奨, 浅野拓也, 黒田敬史, 齋藤豪, 鳥越俊彦

日本病理学会会誌 ( (一社)日本病理学会 ) 105 ( 1 ) 397 - 398 2016.04

Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy

Takuya Asano, Yoshihiko Hirohashi, Toshihiko Torigoe, Tasuku Mariya, Ryota Horibe, Takafumi Kuroda, Yuta Tabuchi, Hiroshi Saijo, Kazuyo Yasuda, Masahito Mizuuchi, Akari Takahashi, Hiroko Asanuma, Tadashi Hasegawa, Tsuyoshi Saito, Noriyuki Sato

ONCOTARGET ( IMPACT JOURNALS LLC ) 7 ( 10 ) 11223 - 11237 2016.03 [Refereed]

Cervical cancer is a major cause of cancer death in females worldwide. Cervical cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are resistant to conventional radiotherapy and chemotherapy, and CSCs/CICs are thought to be responsible for recurrence. Eradication of CSCs/CICs is thus essential to cure cervical cancer. In this study, we isolated cervical CSCs/CICs by sphere culture, and we identified a cancer testis (CT) antigen, CTCFL/BORIS, that is expressed in cervical CSCs/CICs. BORIS has 23 mRNA isoform variants classified by 6 subfamilies (sfs), and they encode 17 different BORIS peptides. BORIS sf1 and sf4 are expressed in both CSCs/CICs and non-CSCs/CICs, whereas BORIS sf6 is expressed only in CSCs/CICs. Overexpression of BORIS sf6 in cervical cancer cells increased sphere formation and tumor-initiating ability compared with those in control cells, whereas overexpression of BORIS sf1 and BORIS sf4 resulted in only slight increases. Thus, BORIS sf6 is a cervical CSC/CIC-specific subfamily and has a role in the maintenance of cervical CSCs/CICs. BORIS sf6 contains a specific c-terminal domain (C34), and we identified a human leukocyte antigen (HLA)-A2-restricted antigenic peptide, BORIS C34_24(9) encoded by BORIS sf6. A BORIS C34_24(9)-specific cytotoxic T cell (CTL) clone showed cytotoxicity for BORIS sf6-overexpressing cervical cancer cells. Furthermore, the CTL clone significantly suppressed sphere formation of CaSki cells. Taken together, the results indicate that the CT antigen BORIS sf6 is specifically expressed in cervical CSCs/CICs, that BORIS sf6 has a role in the maintenance of CSCs/CICs, and that BORIS C34_24(9) peptide is a promising candidate for cervical CSC/CIC-targeting immunotherapy.

Obstetrical prognosis of patients with cervical intraepithelial neoplasia (CIN) after "coin-shaped" conization

Miseon Kim, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Tsuyoshi Saito

ARCHIVES OF GYNECOLOGY AND OBSTETRICS ( SPRINGER HEIDELBERG ) 293 ( 3 ) 651 - 657 2016.03 [Refereed]

Purpose Uterine cervical conization is related to adverse pregnancy outcomes in subsequent pregnancies. To deal with this problem, we started conservative coin-shaped conization for reproductive-aged patients with cervical intraepithelial neoplasia (CIN). Here we report both the obstetrical and oncological impacts of this operation in comparison with the standard cone-shaped resection. Methods A total of 401 women 44 years old or younger were treated in our hospital by CO2 laser conization between 2003 and 2012, and subsequently 50 patients became pregnant. The patients were divided into two groups, a standard cone-shaped conization group (until 2008) and a shallow coin-shaped conization group (beginning in 2008). The pregnancy courses and oncological prognoses of these two groups were studied. Results Cone height reduction of about 3 mm was done. However, there were no significant differences between the two groups with regard to the occurrence of oncological complications. In the standard conization group, 18 of the 25 patients delivered at term. In the coin-shaped conization group, 20 of the 25 patients delivered at term. There were no significant differences between the two groups with regard to the occurrence of various obstetrical complications. However, the reduction rate of cervical length over the pregnancy was smaller in the coin-shaped group and the number of patients with a short cervix length of 2 cm or less was smaller in the coin-shaped group. Conclusions Although conservative coin-shaped conization did not markedly improve the obstetrical prognosis, this operative procedure improved the reduction rate of uterine cervical length over the pregnancy without any increase in oncological complications.

DOI

化学療法による血小板減少に対する加味帰脾湯の効果

山下芙貴子, 松浦基樹, 箕輪智幸, 鈴木将裕, 田渕雄大, 高田さくら, 玉手雅人, 寺本瑞絵, 郷久晴朗, 田中綾一, 岩崎雅宏, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 60 ( 1 ) 68 - 68 2016.03

成熟嚢胞性奇形腫の悪性転化が疑われたが、術後に卵巣カルチノイドと診断された1例の後方視的検討

鹿内智史, 玉手雅人, 馬場敦志, 高橋円, 明石祐史, 郷久晴朗, 寺本瑞絵, 田中綾一, 岩崎雅宏, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 60 ( 1 ) 64 - 65 2016.03

一期的手術を施行した血管内平滑筋腫の1例

箕輪智幸, 松浦基樹, 山下芙貴子, 鈴木将裕, 田渕雄大, 高田さくら, 玉手雅人, 寺本瑞絵, 郷久晴朗, 田中綾一, 岩崎雅宏, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 60 ( 1 ) 62 - 63 2016.03

術後20年目に局所再発した子宮体癌の1例

鈴木将裕, 松浦基樹, 山下芙貴子, 箕輪智幸, 田渕雄大, 高田さくら, 玉手雅人, 寺本瑞絵, 郷久晴朗, 田中綾一, 岩崎雅宏, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 60 ( 1 ) 71 - 71 2016.03

BMI66.5kg/m2の高度肥満妊婦における帝王切開の経験

森下美幸, 嶋田浩志, 馬場剛, 石岡伸一, 遠藤俊明, 齋藤豪

産科と婦人科 ( (株)診断と治療社 ) 83 ( 2 ) 226 - 231 2016.02

肥満による子宮内膜癌の悪性化におけるLSR(lipolysis-stimulated lipoprotein receptor)の役割

嶋田浩志, 郷久晴朗, 寺本瑞絵, 田中綾一, 岩崎雅宏, 小島隆, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 68 ( 2 ) 631 - 631 2016.02

子宮体癌3期症例に関する治療成績の検討

伊坂五沙, 玉手雅人, 竹浪奈穂子, 郷久晴朗, 鈴木美和, 寺本瑞絵, 田中綾一, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 68 ( 2 ) 890 - 890 2016.02

腹水セルブロックにおける免疫組織学的検討が組織型・治療方針決定に有用であった腹膜原発粘液性腺癌の1例

長尾沙智子, 玉手雅人, 染谷真行, 竹田倫子, 岡村直樹, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 68 ( 2 ) 887 - 887 2016.02

再発を来した悪性卵巣胚細胞腫瘍の検討

嶋田浩志, 田中綾一, 鈴木美和, 高橋円, 郷久晴朗, 寺本瑞絵, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 34 ( 1 ) 26 - 36 2016.01

2006年1月から2014年8月までに当院で治療を行った悪性卵巣胚細胞腫瘍(Malignant ovarian germ cell tumors:MOGCTs)20症例のうち3例の再発症例について検討および報告する。年齢は20歳、15歳、24歳で、進行期はそれぞれIIIc期(T3bN1M0)、Ic期(T1cNXM0)、Ia期(T1aNXM0)であった。組織型は2例がImmature teratoma(G3)、1例が一部にImmature teratoma(G1)を含むYolk sac tumorであった。全例に初回治療で妊孕性温存手術が実施され、ブレオマイシン、エトポシド、シスプラチンの3剤併用療法(BEP療法)を実施した。全例に再発巣の摘出術(Secondary debulking surgery:SDS)が施行され、術後にパクリタキセル、イソフォスファミド、シスプラチン併用療法(TIP療法)が施行された。再発までの期間は全例4ヵ月、初回治療から2例は12、26ヵ月で死亡、1例は30ヵ月経過し無病生存している。前者はSDS後に早期に再発し死亡に至っており、SDSが予後を改善した可能性は低い。しかし、後者は無病生存しているため、SDSが予後を改善した可能性もあり、今後のさらなる検討が必要である。(著者抄録)

The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.

Shimada H, Satohisa S, Kohno T, Takahashi S, Hatakeyama T, Konno K, Tsujiwaki M, Saito T, Kojima T

Oncotarget 7(19):27735-52. 2016 [Refereed]

PubMed

不妊治療前の治療的腹腔鏡/子宮鏡にて、子宮内膜増殖症を伴う子宮ポリープ状異型腺筋腫(APAM)と診断した1例

玉手雅人, 明石祐史, 長尾沙智子, 西澤庸子, 杉尾明香, 松浦基樹, 齋藤豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 20 ( 7 ) OS217 - 6 2015.12

肥満によるヒト子宮内膜癌の悪性化におけるlipolysis-stimulated lipoprotein receptorの役割

小島隆, 嶋田浩志, 郷久晴朗, 金野匠, 高橋俊太, 畠山翔翼, 有元千尋, 野島伊世里, 齋藤豪, 幸野貴之

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 ( (公社)日本生化学会 ) 88回・38回 [3T18p - 01(3P1048)] 2015.12

Preservation of fertility and subsequent childbirth after methotrexate treatment of placenta percreta: a case report.

Tamate M, Matsuura M, Habata S, Akashi Y, Tanaka R, Ishioka S, Endo T, Saito T

Journal of medical case reports 9 232 2015.10 [Refereed]

DOI PubMed

BORIS variant subfamily 6は癌幹細胞性に関与し免疫療法の標的となりうる

浅野拓也, 廣橋良彦, 真里谷奨, 黒田敬史, 浅沼広子, 鳥越俊彦, 齋藤豪

日本癌学会総会記事 ( (一社)日本癌学会 ) 74回 P - 1233 2015.10

Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following paclitaxel and carboplatin in patients with gynecologic cancers: A randomized, multicenter, phase-II trial.

Matsuura M, Satohisa S, Teramoto M, Tanaka R, Iwasaki M, Nishikawa A, Mizunuma M, Tanaka S, Hayakawa O, Saito T

The journal of obstetrics and gynaecology research 41 ( 10 ) 1607 - 1613 2015.10 [Refereed]

DOI PubMed

腹腔鏡および子宮鏡にて子宮内膜増殖症を伴う子宮ポリープ状異型腺筋腫と診断した1例

玉手雅人, 寺本瑞絵, 竹田倫子, 松浦基樹, 郷久晴朗, 田中綾一, 岩崎雅宏, 齋藤豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 ) 54 ( Suppl.2 ) 561 - 561 2015.10

卵巣原発膠芽腫に対し手術・化学放射線療法を施行後、再々発しCBDCA/VP-16療法が奏効した一例

伊坂五沙, 郷久晴朗, 岩崎雅宏, 竹浪奈穂子, 嶋田浩志, 寺本瑞絵, 田中綾一, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 63回 93 - 93 2015.09

急激に進行し経過不良であった再発粘液性境界悪性卵巣腫瘍の一例

小川俊史, 郷久晴朗, 岩崎雅宏, 田中綾一, 寺本瑞絵, 竹浪奈穂子, 伊坂五沙, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 63回 58 - 58 2015.09

Successful delivery after transabdominal cerclage of uterine cervix for cervical incompetence after radical trachelectomy

Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yushi Akashi, Miyuki Morishita, Asuka Sugio, Naohiro Kanayama, Tsuyoshi Saito

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH ( WILEY-BLACKWELL ) 41 ( 8 ) 1295 - 1299 2015.08 [Refereed]

Pregnancy after radical trachelectomy (RT) has a high risk of prematurity and complications such as pre-termpremature rupture of the membrane and chorioamnionitis. Placing a cervical cerclage at the time of RT plays an important role in preventing such obstetrical complications. In patients who have trouble with the cervical cerclage, miscarriage during the second trimester seems to be inevitable. We have therefore started preconception transabdominal cerclage (TAC) for these patients. A 36-year-old Japanese woman who had a history of miscarriage due to trouble with the nylon thread used for cerclage, successfully delivered after TAC. TAC is a useful treatment modality to prevent miscarriage for patients who have trouble with cerclage after RT.

DOI

妊孕能温存希望で子宮筋腫核出術後、平滑筋種以外の診断となった症例の検討

玉手雅人, 明石祐史, 長尾沙智子, 西澤庸子, 杉尾明香, 森下美幸, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 31 ( Suppl.I ) 199 - 199 2015.08

鏡視下手術の合併症と再発予防偶発合併症から必然的要因を探り予防するために当院合併症例からの検討

明石祐史, 杉尾明香, 西澤庸子, 玉手雅人, 金美善, 森下美幸, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 31 ( Suppl.I ) 102 - 102 2015.08

アイソレーションバッグによるIn bag morcellationのコツとピットフォール

明石祐史, 杉尾明香, 西澤庸子, 玉手雅人, 金美善, 森下美幸, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 31 ( Suppl.I ) 200 - 200 2015.08

当院における腹腔鏡下子宮筋腫核出術後の妊娠症例の検討

西澤庸子, 杉尾明香, 金美善, 玉手雅人, 森下美幸, 明石祐史, 斎藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 31 ( Suppl.I ) 243 - 243 2015.08

腔鏡下卵巣子宮内膜症性嚢胞核出術に対する希釈バソプレッシン注入法の効果と妊孕能への影響 conbined法の積極運用を取り入れて

杉尾明香, 明石祐史, 西澤庸子, 金美善, 玉手雅人, 森下美幸, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 31 ( Suppl.I ) 194 - 194 2015.08

卵巣腫瘍の術前正診率から考える術式の選択

長尾沙智子, 玉手雅人, 西澤庸子, 杉尾明香, 森下美幸, 明石祐史, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 31 ( Suppl.I ) 210 - 210 2015.08

腹腔鏡にて子宮内膜症を発生母地とした低悪性度子宮内膜間質肉腫と診断し得た1例

玉手雅人, 明石祐史, 長尾沙智子, 西澤庸子, 杉尾明香, 森下美幸, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 31 ( Suppl.I ) 254 - 254 2015.08

手術・化学放射線療法を施行後再々発し、CBDCA/VP-16療法が奏効した卵巣原発膠芽腫の一例

郷久晴朗, 岩崎雅宏, 竹浪奈穂子, 阿部秀悦, 嶋田浩志, 玉手雅人, 幅田周太朗, 鈴木美和, 寺本瑞絵, 田中綾一, 斎藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 33 ( 3 ) 609 - 609 2015.06

子宮体がん基礎肥満による子宮内膜癌の悪性化におけるLSR(lipolysis-stimulated lipoprotein receptor)の役割

嶋田浩志, 小島隆, 郷久晴朗, 金野匠, 高橋俊太, 畠山翔翼, 幸野貴之, 寺本瑞絵, 田中綾一, 岩崎雅宏, 斎藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 33 ( 3 ) 535 - 535 2015.06

ヒト子宮内膜癌細胞の悪性化におけるlipolysis-stimulated lipoprotein receptorの役割

嶋田浩志, 郷久晴朗, 金野匠, 高橋俊太, 畠山翔翼, 齋藤豪, 幸野貴之, 小島隆

日本細胞生物学会大会講演要旨集 ( (一社)日本細胞生物学会 ) 67回 167 - 167 2015.06

卵巣がん基礎 BAG3はUSP9Xを介してMcl-1を安定化させることで抗がん剤耐性に関与している

幅田周太朗, 岩崎雅宏, 杉尾明香, 鈴木美和, 玉手雅人, 郷久晴朗, 田中綾一, 斎藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 33 ( 3 ) 534 - 534 2015.06

腹腔鏡下筋腫核出術の筋腫回収におけるBagging法の有用性と限界 PDAの勧告に鑑みて

明石祐史, 玉手雅人, 杉尾明香, 森下美幸, 斎藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 26 ) 201 - 201 2015.06

卵巣上皮性境界悪性腫瘍と診断し再発した症例の検討

鈴木美和, 田中綾一, 寺本瑞絵, 竹浪奈穂子, 玉手雅人, 幅田周太朗, 郷久晴朗, 岩崎雅宏, 斎藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 33 ( 3 ) 603 - 603 2015.06

BAG3 increases the invasiveness of uterine corpus carcinoma cells by suppressing miR-29b and enhancing MMP2 expression

Shutaro Habata, Masahiro Iwasaki, Asuka Sugio, Miwa Suzuki, Masato Tamate, Seiro Satohisa, Ryoichi Tanaka, Tsuyoshi Saito

ONCOLOGY REPORTS ( SPANDIDOS PUBL LTD ) 33 ( 5 ) 2613 - 2621 2015.05 [Refereed]

Approximately 30% of uterine corpus carcinomas are diagnosed at an advanced stage and have a poor prognosis. Our previous study indicated that BCL2-associated athanogene 3 (BAG3) enhances matrix metalloproteinase-2 (MMP2) expression and binds to MMP2 to positively regulate the process of cell invasion in ovarian cancer cells. Recently, altered miRNA expression patterns were observed in several groups of patients with endometrial cancers. One of the altered miRNAs, miR-29b, reportedly reduces tumor invasiveness by suppressing MMP2 expression. Our aim in the present study was to examine the relationships among BAG3, miR-29b and MMP2 in endometrioid adenocarcinoma cells. We found that BAG3 suppresses miR-29b expression and enhances MMP2 expression, which in turn increases. cell motility and invasiveness. Moreover, restoration of miR-29b through BAG3 knockdown reduced MMP2 expression, as well as cell motility and invasiveness. Collectively, our findings indicate that BAG3 enhances MMP2 expression by suppressing miR-29b, thereby increasing the metastatic potential of endometrioid adenocarcinomas.

DOI

HLA class I as a predictor of clinical prognosis and CTL infiltration as a predictor of chemosensitivity in ovarian cancer.

Yoshihiko Hirohashi, Toshihiko Torigoe, Tasuku Mariya, Vitaly Kochin, Tsuyoshi Saito, Noriyuki Sato

Oncoimmunology 4 ( 5 ) e1005507 2015.05 [International journal]

PubMed

HLA class I as a predictor of clinical prognosis and CTL infiltration as a predictor of chemosensitivity in ovarian cancer

Yoshihiko Hirohashi, Toshihiko Torigoe, Tasuku Mariya, Vitaly Kochin, Tsuyoshi Saito, Noriyuki Sato

ONCOIMMUNOLOGY ( TAYLOR & FRANCIS INC ) 4 ( 5 ) 2015.05 [Refereed]

DOI

卵巣癌幹細胞の幹細胞性制御におけるMMP10の作用

真里谷奨, 廣橋良彦, 田渕雄大, 浅野拓也, 黒田敬史, 水内将人, 安田和世, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 104 ( 1 ) 302 - 302 2015.03

癌精巣抗原BORIS sf6は婦人科癌幹細胞性に関与し免疫療法のターゲットになりうる

浅野拓也, 廣橋良彦, 真里谷奨, 黒田敬史, 浅沼広子, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 104 ( 1 ) 301 - 301 2015.03

治療方針に苦慮した急性Stanford A型大動脈解離合併妊娠

嶋田浩志, 遠藤俊明, 山本雅恵, 杉尾明香, 清水亜由美, 森下美幸, 明石祐史, 馬場剛, 石岡伸一, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 59 ( 1 ) 22 - 26 2015.03

周産期の大動脈解離の発症は非常に稀であるが、40歳未満の大動脈解離の発症の半数は妊娠に合併するといわれている。急性のStanford A型大動脈解離は手術治療が原則であるが、妊娠に合併した場合の治療方針は明確に定まっていない。今回我々は帝王切開術と子宮摘出術の決断に苦慮した急性Stanford A型大動脈解離の一例を経験したので報告する。症例は31歳女性。未経妊未経産。妊娠31週に制御不能な胸痛および背部痛を自覚し、前医を受診した。造影CTで急性Stanford A型大動脈解離と診断され、当院に手術目的に緊急搬送された。治療方針に苦慮したが帝王切開を先行させ、胎児を娩出後に人工血管置換術を一期的に行った。人工血管置換術中の産科的出血を予防するために子宮全摘術を実施した。術後経過は良好で合併症もなく、母子ともに術後24日目に退院した。帝王切開術の施行時期と子宮摘出術の選択に議論の余地はあるが、人工血管置換術時の体外循環による胎児への影響と大動脈解離の死亡率を考慮した場合、妥当な選択だったと考えられる。(著者抄録)

腫瘍減量手術が施行された再発卵巣癌の予後因子についての検討

田中綾一, 寺本瑞絵, 西澤庸子, 竹浪奈穂子, 玉手雅人, 幅田周太朗, 鈴木美和, 高橋円, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 67 ( 2 ) 864 - 864 2015.02

Associations of serum isoflavone, adiponectin and insulin levels with risk for epithelial ovarian cancer: Results of a case-control study

Seiko Otokozawa, Ryoichi Tanaka, Hiroshi Akasaka, Eiki Ito, Sumiyo Asakura, Hirofumi Ohnishi, Shigeyuki Saito, Tetsuji Miura, Tsuyoshi Saito, Mitsuru Mori

Asian Pacific Journal of Cancer Prevention ( Asian Pacific Organization for Cancer Prevention ) 16 ( 12 ) 4987 - 4991 2015 [Refereed]

Background: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. Materials and Methods: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. Results: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low (P< inf> trend< /inf> < 0.001). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low (P< inf> trend< /inf> =0.005). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low (P< inf> trend< /inf> =0.004). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low P< inf> trend< /inf> < 0.001). Conclusions: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer.

DOI PubMed

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

Kazuyo Yasuda, Toshihiko Torigoe, Tasuku Mariya, Takuya Asano, Takafumi Kuroda, Junichi Matsuzaki, Kanae Ikeda, Makoto Yamauchi, Makoto Emori, Hiroko Asanuma, Tadashi Hasegawa, Tsuyoshi Saito, Yoshihiko Hirohashi, Noriyuki Sato

LABORATORY INVESTIGATION ( NATURE PUBLISHING GROUP ) 94 ( 12 ) 1355 - 1369 2014.12 [Refereed]

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cells within cancer that contribute to cancer initiation and progression. Cancer-associated fibroblasts (CAFs) are stromal fibroblasts surrounding tumor cells, and they have important roles in tumor growth and tumor progression. It has been suggested that stromal fibroblasts and CSCs/CICs might mutually cooperate to enhance their growth and tunnorigenic capacity. In this study, we investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian CSCs/CICs. CSCs/CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high (ALDH1(high)) population by the ALDEFLUOR assay. Histological examination of tumor tissues derived from ALDH1(high) cells revealed few fibrous stroma, whereas those derived from fibroblast-mixed ALDH1(high) cells showed abundant fibrous stroma formation. In vivo tumor-initiating capacity and in vitro sphere-forming capacity of ALDH1(high) cells were enhanced in the presence of fibroblasts. Gene expression analysis revealed that fibroblast-mixed ALDH1(high) cells had enhanced expression of fibroblast growth factor 4 (FGF4) as well as sternness-associated genes such as SOX2 and POU5F1. Sphere-forming capacity of ALDH1(high) cells was suppressed by small-interfering RNA (siRNA)-mediated knockdown of FGFR2, the receptor for FGF4 which was expressed preferentially in ALDH1(high) cells. Taken together, the results indicate that interaction of fibroblasts with ovarian CSCs/CICs enhanced tumor-initiating capacity and stem-like properties through autocrine and paracrine FGF4-FGFR2 signaling.

DOI PubMed

Prognostic Impact of Human Leukocyte Antigen Class I Expression and Association of Platinum Resistance with Immunologic Profiles in Epithelial Ovarian Cancer

Tasuku Mariya, Yoshihiko Hirohashi, Toshihiko Torigoe, Takuya Asano, Takafumi Kuroda, Kazuyo Yasuda, Masahito Mizuuchi, Tomoko Sonoda, Tsuyoshi Saito, Noriyuki Sato

CANCER IMMUNOLOGY RESEARCH ( AMER ASSOC CANCER RESEARCH ) 2 ( 12 ) 1220 - 1229 2014.12 [Refereed]

Epithelial ovarian cancer (EOC) is one of the most deadly carcinomas in females. Immune systems can recognize EOCs; however, a defect of human leukocyte antigen (HLA) class I expression is known to be a major mechanism for escape from immune systems, resulting in poor prognosis. The purpose of this study is to identify novel correlations between immunologic responses and other clinical factors. We investigated the expression of immunologic components in 122 cases of EOCs for which surgical operations were performed between 2001 and 2011. We immunohistochemically stained EOC specimens using an anti-pan HLA class I monoclonal antibody (EMR8-5) and anti-CD3, -CD4, and -CD8 antibodies, and we analyzed correlations between immunologic parameters and clinical factors. In multivariate analysis that used the Cox proportional hazards model, independent prognostic factors for overall survival in advanced EOCs included low expression level of HLA class I [risk ratio (RR), 1.97; 95% confidence interval (CI), 1.01-3.83; P = 0.046] and loss of intraepithelial cytotoxic T lymphocyte (CTL) infiltration (RR, 2.11; 95% CI, 1.06-4.20; P = 0.033). Interestingly, almost all platinum-resistant cases showed a significantly low rate of intraepithelial CTL infiltration in the x 2 test (positive vs. negative: 9.0% vs. 97.7%; P < 0.001). Results from a logistic regression model revealed that low CTL infiltration rate was an independent factor of platinum resistance in multivariate analysis (OR, 3.77; 95% CI, 1.08-13.12; P = 0.037). Platinum-resistant EOCs show poor immunologic responses. The immune escape system of EOCs may be one of the mechanisms of platinum resistance. (C) 2014 AACR.

DOI

Importance of uterine cervical cerclage to maintain a successful pregnancy for patients who undergo vaginal radical trachelectomy

Miseon Kim, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yushi Akashi, Miyuki Morishita, Hidefumi Adachi, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER JAPAN KK ) 19 ( 5 ) 906 - 911 2014.10 [Refereed]

We have performed 36 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer and experienced 10 deliveries. Pregnancy after RT has far higher risks of prematurity and complications such as preterm premature rupture of the membrane (pPROM) and chorioamnionitis. We report the significance of transabdominal cerclage in the follow-up of pregnancy after vaginal RT. Our operative procedure is based on that of Dargent et al. We amputated the cervix approximately 10 mm below the isthmus. For the removal of the parametrium, we cut at the level of type II hysterectomy. A nylon suture is also placed around the residual cervix. Pregnancy courses after vaginal RT were studied in 9 patients (10 pregnancies) with respect to cervical length and several infectious signs. Obstetric prognosis after RT was improved with our follow-up modality. Four patients who were followed up with this modality were able to continue their pregnancies until late in the third trimester. However, it was not effective for four patients who showed cervical incompetence due to slack cerclage. They suffered from pPROM without any infectious signs and uterine contraction. Though we performed transabdominal uterine cervical cerclage for one patient in her 19th week of pregnancy, it was unsuccessful. Cervical cerclage placed at the time of RT played an important role in preventing dilatation of the uterine cervix and the subsequent occurrence of pPROM. Transabdominal cervical cerclage should be performed earlier in pregnancy or before pregnancy in patients who have experienced problems with cervical cerclage.

DOI PubMed

BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer

Asuka Sugio, Masahiro Iwasaki, Shutaro Habata, Tasuku Mariya, Miwa Suzuki, Hiroyuki Osogami, Masato Tamate, Ryoichi Tanaka, Tsuyoshi Saito

GYNECOLOGIC ONCOLOGY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 134 ( 3 ) 615 - 623 2014.09 [Refereed]

Objective. Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its often late diagnosis and its chemoresistance. We identified a set of microRNAs whose expression is altered upon BAG3 knockdown. Our primary objective was to examine the relationships between BAG3, miR-29b and Mcl-1, an antiapoptotic Bcl-2 family protein, in ovarian cancer cells. Methods. Ovarian cancer cells were cultured and their responsiveness to paclitaxel was tested. Microarray analysis was performed to identify microRNAs differentially expressed in E52 BAG3 knockdown ovarian cancer cells and their control cells. Primary ovarian cancer tissues were obtained from 56 patients operated on for ovarian cancer. The patients' clinical and pathological data were obtained from their medical records. Results. BAG3 knockdown increased the chemosensitivity to paclitaxel of ES2 ovarian clear cell carcinoma cells to a greater degree than AMOC2 serous adenocarcinoma cells. gRT-PCR analysis showed that miR-29b expression was significantly upregulated in primary cancer tissue expressing low levels of BAG3, as compared to tissue expressing high levels. Moreover, levels of miR-29b correlated significantly with progression-free survival. Upregulation of miR-29b also reduced levels of Mcl-1 and sensitized ES2 cells to low-dose paclitaxel. Conclusions. BAG3 knockdown appears to downregulate expression of Mcl-1 through upregulation of miR-29b, thereby increasing the chemosensitivity of ovarian clear cell carcinoma cells. This suggests that BAG3 is a key determinant of the responsiveness of ovarian cancer cells, especially clear cell carcinoma, to paclitaxel and that BAG3 may be a useful therapeutic target for the treatment of ovarian cancer. (C) 2014 Elsevier Inc. All rights reserved.

DOI PubMed

婦人科癌における癌精巣抗原BORISの発現ならびに癌幹細胞性の検討(Expression and characterization of the cancer/testis/stem antigen BORIS in gynecologic cancer stem cells)

浅野拓也, 廣橋良彦, 真里谷奨, 黒田敬史, 浅沼広子, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本癌学会総会記事 ( (一社)日本癌学会 ) 73回 P - 1164 2014.09

卵巣癌幹細胞におけるMMP10による幹細胞性の制御について(MMP10 regulates stemness of ovarian cancer stem cells)

真里谷奨, 廣橋良彦, 浅野拓也, 黒田敬史, 水内将人, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本癌学会総会記事 ( (一社)日本癌学会 ) 73回 P - 1162 2014.09

Rap1GAPの発現と子宮体部類内膜腺癌の分化度(Expression of Rap1GAP and differentiation of endometrioid adenocarcinoma in endometrial cancer)

玉手雅人, 田中綾一, 幅田周太朗, 杉尾明香, 松浦基樹, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本癌学会総会記事 ( (一社)日本癌学会 ) 73回 P - 2080 2014.09

Prediction of the therapeutic effect of dienogest in ovarian endometrial cysts using the apparent diffusion coefficient

Motoki Matsuura, Masato Tamate, Yuta Tabuchi, Sakura Takada, Ryoichi Tanaka, Masahiro Iwasaki, Tsuyoshi Saito

GYNECOLOGICAL ENDOCRINOLOGY ( INFORMA HEALTHCARE ) 30 ( 8 ) 597 - 599 2014.08 [Refereed]

The purpose of this study was to investigate whether apparent diffusion coefficient (ADC) mean values can be used for predicting the treatment response in ovarian endometrial cyst patients with dienogest (DNG) administration. Eighteen patients received DNG (2 mg/day, orally) for 60 days, among whom 26 ovarian endometrial cysts were retrospectively identified. Mean ADC values of individual ovarian endometrial cysts were obtained by ADC maps inside the tumor. There was a significant correlation between ADC values and reduction ratio. When calculating the mean ADC values for three groups; more than 50%, 50-25% and less than 25%, ADC values significantly increased with increasing reduction ratio; 2.05 x 10(-3) mm(2)/s, 1.28 x 10(-3) mm(2)/s and 0.94 x 10(-3) mm(2)/s, respectively (p = 0.0180). Multiple regression analysis by reduction ratio (%), ADC mean values (x 10(-3) mm(2)/s), tumor longest diameter (cm) and CA125 (Wml) revealed that tumor reduction ratio by DNG administration could be predicted by the following equation; R=19.3 + 24.0x - 0.4y + 0.1z (R: Reduction ratio, x: ADC mean, y: Longest diameter, z: CA125). In conclusion, the ADC mean value is useful for the prediction of the treatment response in ovarian endometrial cyst patients with DNG administration.

DOI PubMed

Common hypothetical etiology of excess androgen exposure in female-to-male transsexualism and polycystic ovary syndrome

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Tsuyoshi Saito

Gender Identity: Disorders, Developmental Perspectives and Social Implications ( Nova Science Publishers, Inc. ) 253 - 270 2014.07

Gender identity disorder is recognized as a rare disease. The prevalence of this disorder is different among regions and races. In Japan, the prevalence of female-to-male transsexual (FTM-TS) patients is estimated to be 1 in 12,500 women, which is approximately twice as many as male-to-female transsexual patients. There are two interesting facts in association with FTM-TS: 1) the complication rate of polycystic ovary syndrome (PCOS) is high among FTM-TS patients and 2) natal female patients with congenital adrenal hyperplasia (CAH) tend to have gender identity problems more often than the normal population. PCOS is a common disease and it affects 5-10% of women of reproductive age. PCOS is characterized by ovulation disorder, hyperandrogenism, and polycystic ovarian morphology. Additionally, PCOS is correlated with insulin resistance, and predisposes to type 2 diabetes mellitus, atherosclerosis, and metabolic syndrome. The etiology of PCOS is still obscure, but excess androgen exposure during the fetal period is considered to be a dominant hypothesis. CAH is an autosomal recessive disorder impairing adrenal steroid metabolism, which causes excess androgenemia from the fetal period. A review on 250 natal female cases with CAH showed that 13 (5.2%) of the patients had serious gender identity problems. Surprisingly, the occurrence of FTM-TS in CAH is extremely high. The pathogenesis of FTM-TS is still uncertain. However, excess androgen exposure may be related to FTM-TS according to the above-mentioned findings. In humans, experimental androgen administration to women is impossible. However, cross-sex hormone administration to FTM-TS patients is not associated with any problems because it is a standard tactic for treatment. If excess androgen exposure is a cause of PCOS, androgen-treated FTM-TS patients may be a disease model of PCOS. Assessment of the effects of androgen administration on metabolic parameters is informative because FTM-TS patients with PCOS may have potent insulin resistance. In this chapter, we discuss endocrinological aspects of FTM-TS, the effect of crosssex hormones, and the hypothetical etiology in FTM and PCOS.

Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone

Keiko Ikeda, Tsuyoshi Baba, Miyuki Morishita, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

JOURNAL OF OVARIAN RESEARCH ( BIOMED CENTRAL LTD ) 7 46 2014.04 [Refereed]

Background: Hyperandrogenism is the primary manifestation of polycystic ovary syndrome (PCOS), which appears to be caused by excess exposure to androgen. As such, androgenized animal models have been developed and investigated to study the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with follicle growth, and its levels are two to three times higher in women with PCOS than in those with normal ovaries. We studied how duration of androgen administration affects folliculogenesis and AMH expression. Methods: We divided 30 immature (3-week-old) Sprague Dawley rats into six groups. Three groups were injected each evening with dehydroepiandrosterone (DHEA) (6 mg/100 g body weight/0.2 ml sesame oil) for 7, 15 or 30 days, respectively. The three control groups were injected with 0.2 ml of sesame oil for the corresponding lengths of time. Resected ovaries were sectioned and examined to determine follicle numbers at each developmental stage, and immunostained to assess AMH expression. Results: On day 7, follicle numbers and AMH expression levels at each developmental stage of follicle growth were similar in the respective control and DHEA groups. On day 15, the total follicle number (P = 0.041), the percentage of primordial follicles (P = 0.039) and AMH expression were significantly greater in the DHEA than the control group. On day 30, the percentages of primordial (P = 0.005), primary (P = 0.0002) and atretic (P = 0.03) follicles were significantly greater in the DHEA group, whereas the percentage of intermediary follicles (early pre-antral, late preantral, and early antral follicles) was significantly lower in the DHEA group (P = < 0.0001). AMH expression in DHEA-treated rats on day 30 was seen exclusively in the primordial (P = 0.0413) and late antral follicles (p = 0.028). Conclusions: Androgen administration increases AMH production in a process that regulates the growth of primordial follicles. That is, androgen-induced AMH expression provides local negative feedback to folliculogenesis augmented by androgen.

DOI PubMed

エストロゲン産生を示す低分化型セルトリ・間質細胞腫瘍の一例

恐神博行, 田中綾一, 玉手雅人, 杉尾明香, 鈴木美和, 郷久晴朗, 寺本瑞絵, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 32 ( 2 ) 253 - 256 2014.04

低分化型のセルトリ・間質細胞腫瘍は性索間質細胞腫瘍に分類され、卵巣悪性腫瘍の0.2%を占める非常に稀な腫瘍である。我々は、エストラジオール値の上昇を認めた卵巣低分化型セルトリ・間質細胞腫瘍を経験したので報告する。症例は65歳、1経妊1経産。主訴は不正性器出血で、画像所見から右卵巣原発の性索間質性腫瘍が疑われた。エストラジオール値が57.6pg/mlと上昇していた。腹式単純子宮全摘出術および両側付属器切除術を施行し、低分化型セルトリ・間質細胞腫瘍と診断された。免疫組織染色では、Inhibin-α、calretinin、CD56およびMIN2/CD99が陽性、EMAは陰性であった。現在まで再発徴候は認められていない。(著者抄録)

Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity

Mizue Teramoto, Takahiro Suzuki, Seiro Satohisa, Yushi Akashi, Motoki Matsuura, Miwa Suzuki, Ryoichi Tanaka, Tsuyoshi Saito

MEDICAL MOLECULAR MORPHOLOGY ( SPRINGER JAPAN KK ) 47 ( 1 ) 31 - 37 2014.03 [Refereed]

Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96 h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.

DOI PubMed

婦人科癌における癌精巣抗原BORISの発現ならびに癌幹細胞性の検討

浅野拓也, 廣橋良彦, 真里谷奨, 黒田敬史, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 103 ( 1 ) 266 - 266 2014.03

上皮性卵巣癌122例のHLA Class I発現およびCTL腫瘍内浸潤の臨床的因子との関連

真里谷奨, 廣橋良彦, 浅野拓也, 黒田敬史, 安田和世, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 103 ( 1 ) 371 - 371 2014.03

予後不良であった卵巣悪性胚細胞腫瘍2例の検討

新開翔太, 田中綾一, 山中郁仁, 嶋田浩志, 鈴木美和, 高橋円, 長澤邦彦, 伊東英樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 58 ( 1 ) 112 - 113 2014.03

子宮体癌・発癌と進展子宮体がんの転移、浸潤におけるBAG3の役割 micro RNAとの関連を検討する

幅田周太朗, 岩崎雅宏, 杉尾明香, 玉手雅人, 恐神博行, 鈴木美和, 田中綾一, 斎藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 66 ( 2 ) 459 - 459 2014.02

Excessive androgen exposure as an etiological factor of polycystic ovary syndrome

Tsuyoshi Baba, Toshiaki Endo, Sayaka Adachi, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Tsuyoshi Saito

Journal of Mammalian Ova Research ( Japanese Society of Mammalian Ova Research ) 31 ( 1 ) 23 - 30 2014

Polycystic ovary syndrome (PCOS) is a heterogeneous group of disorders characterized by ovulation disorder, hyperandrogenism, and polycystic ovarian morphology (PCOM). Several diagnostic criteria suggest that hyperandrogenism is a core symptom of PCOS. Androgens are believed to cause preantral follicle growth and arrest the growth of antral follicles. This results in accumulation of small antral follicles in the ovaries, thus forming PCOM. Observational studies of patients with female-to-male transsexualism or congenital adrenal hyperplasia indicate that androgen administration to these patients does not produce typical PCOS-like features. However, endogenous androgen exposure in early life may lead to some traits of PCOS in adulthood. To reveal the association between the timing of excess androgen exposure and reproductive function, various animal models have been investigated using androgen administration. Rhesus monkeys exposed to excess androgen during the early fetal period show a PCOS-like phenotype, including metabolic and hypothalamic- pituitary characteristics. This finding implies that exposure to excess androgen during this critical period programs the hypothalamic-pituitary-ovary axis and metabolic organs. Although findings obtained in animal studies will not necessarily be replicated in humans, prenatal androgen excess is the dominant PCOS hypothesis. ©2014 Japan Society for Ova Research.

DOI

Difficulty in the management of pregnancy after vaginal radical trachelectomy

Sakura Takada, Shin-Ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Miyuki Morishita, Yushi Akashi, Masahito Mizuuchi, Hidefumi Adachi, Miseon Kim, Tsuyoshi Saito

International Journal of Clinical Oncology 18 ( 6 ) 1085 - 1090 2013.12 [Refereed]

Background: We have performed 26 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer since 2003 and, to date, have experienced 8 deliveries. The procedure has a high risk for preterm labor and the subsequent occurrence of preterm premature rupture of membranes (pPROM). We report the present situation and the limits of follow-up of pregnancy after vaginal RT. Methods: Our operative procedure is based on that of Dargent et al. We usually amputate the cervix approximately 10 mm below the isthmus. To remove the parametrium, we cut at the level of type II hysterectomy. Pregnancy courses after vaginal RT were studied in 8 patients with respect to symptoms, cervical length, and several infectious signs. Results: We recommended that patients enter hospital early in their second trimester, and prophylactic daily vaginal disinfection with povidone-iodine and an ulinastatin vaginal suppository were administered. Careful checking for vaginal infectious signs, as well as cervical length and abdominal tension of patients was also performed. Four patients followed up with this modality were able to continue their pregnancies until late in the third trimester. However, this follow-up modality was not effective for patients who showed cervical incompetence due to slack cervical cerclage. They suffered from pPROM at 26 and 19 weeks of gestation. Conclusion: We need a new approach for the management of pregnant patients after vaginal RT with cervical incompetence due to slack cervical cerclage to prevent cervical infection. © 2012 Japan Society of Clinical Oncology.

DOI PubMed

Regulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano

Masayuki Someya, Takashi Kojima, Marie Ogawa, Takafumi Ninomiya, Kazuaki Nomura, Akira Takasawa, Masaki Murata, Satoshi Tanaka, Tsuyoshi Saito, Norimasa Sawada

CELL AND TISSUE RESEARCH ( SPRINGER ) 354 ( 2 ) 481 - 494 2013.11 [Refereed]

The number of patients with uterine endometrial carcinoma, the cause of which involves sex hormones, has recently been growing rapidly because of increases in life expectancy and obesity. Tight junction proteins claudin-3 and -4 are receptors of Clostridium perfringens enterotoxin (CPE) and increase during endometrial carcinogenesis. In the present study of normal human endometrial epithelial (HEE) cells and the uterus cancer cell line Sawano, we investigate changes in the expression of tight junction proteins including claudin-3 and -4, the fence and barrier functions of the tight junction and the cytotoxic effects of CPE by sex hormones. In primary cultured HEE cells, treatment with progesterone (P4) but not estradiol (E2), induced claudin-1, -3, -4 and -7 and occludin, together with the downregulation of the barrier function but not the fence function. In Sawano cells, claudin-3 and -4 were upregulated by E2 but not by P4, together with a disruption of both the barrier and fence function. In primary cultured HEE cells, claudin-3 and -4 were localized at the apicalmost regions (tight junction areas) and no cytotoxicity of CPE was observed. In Sawano cells, claudin-3 and -4 were found not only in the apicalmost regions but also at the basolateral membrane and the cytotoxicity of CPE was enhanced by E2. Thus, tight junctions are physiological regulated by sex hormones in normal HEE cells during the menstrual cycle suggesting that safer and more effective therapeutic methods targeting claudins in uterine cancer can be developed.

DOI PubMed

The Tight-Junction Protein Claudin-6 Induces Epithelial Differentiation from Mouse F9 and Embryonic Stem Cells

Kotaro Sugimoto, Naoki Ichikawa-Tomikawa, Seiro Satohisa, Yushi Akashi, Risa Kanai, Tsuyoshi Saito, Norimasa Sawada, Hideki Chiba

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 8 ( 10 ) e75106 2013.10 [Refereed]

During epithelialization, cell adhesions and polarity must be established to maintain tissue assemblies and separate the biological compartments in the body. However, the molecular basis of epithelial morphogenesis, in particular, a role of cell adhesion molecules in epithelial differentiation from stem cells, remains unclear. Here, we show that the stable and conditional expression of a tight-junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse F9 stem cells. We also demonstrate that Cldn6 induces the expression of other tight-junction and microvillus molecules including Cldn7, occludin, ZO-1 alpha+, and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium Perfringens enterotoxin. Furthermore, similar results were obtained in mouse embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel cue to induce epithelial differentiation.

DOI PubMed

ALDH1-High Ovarian Cancer Stem-Like Cells Can Be Isolated from Serous and Clear Cell Adenocarcinoma Cells, and ALDH1 High Expression Is Associated with Poor Prognosis

Takafumi Kuroda, Yoshihiko Hirohashi, Toshihiko Torigoe, Kazuyo Yasuda, Akari Takahashi, Hiroko Asanuma, Rena Morita, Tasuku Mariya, Takuya Asano, Masahito Mizuuchi, Tsuyoshi Saito, Noriyuki Sato

PLoS ONE ( 6 ) 8 ( 6 ) e65158 2013.06 [Refereed]

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1high) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1high cells. ALDH1high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis. © 2013 Kuroda et al.

DOI PubMed

Assisted reproductive technique increases the risk of placental polyp

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Shin-Ichi Ishioka, Tsuyoshi Saito

Gynecological Endocrinology ( 6 ) 29 ( 6 ) 611 - 614 2013.06 [Refereed]

The purpose of this study was to clarify the risk factors and outcomes of placental polyp. This retrospective study was conducted on 1645 patients delivered or aborted in Sapporo Medical University from 2007 through 2011. Transvaginal color Doppler ultrasonography, hysteroscopy, contrast-enhanced MRI or 3D-CT angiography were performed. There were 1532 deliveries and 113 abortions. Seventy-one (4.3%) were ART-conceived and the remaining 1574 (95.7%) were non-ART pregnancies. Fifteen (0.91%) cases were confirmed as having placental polyp. Nine cases of placental polyp were identified among the 1574 (0.57%) as non-ART-related pregnancies, and 6 were identified among the 71 (8.5%) as ART-related pregnancies. Thus, pregnancies achieved through ART showed 20x greater incidence of complicating placental polyp than pregnancies achieved through without ART (p=9.02×10-6 odds ratio, 19.59 95% confidence interval, 5.27-72.84, logistic regression analysis). Evaluation of blood flow within the polyp showed that in five of seven patients with low blood flow, the polyps spontaneously dropped off 79-115 days postpartum. Thus, ART-related pregnancies may be a risk factor of placental polyp, and spontaneous drop-off of the polyp is often observed in cases with low blood flow within the mass. © 2013 Informa UK Ltd.

DOI PubMed

子宮筋腫合併妊娠の妊娠経過及び分娩への影響に関する検討

竹浪奈穂子, 玉手雅人, 谷垣衣理, 郷久晴朗, 早川修, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 49 ( 2 ) 774 - 774 2013.06

最近経験した鼠径部腫瘍5症例の検討

寺本瑞絵, 岩崎雅宏, 嶋田浩志, 鈴木利理, 竹浪奈穂子, 染谷真行, 田渕雄大, 池田桂子, 鈴木美和, 高橋円, 長澤邦彦, 田中綾一, 伊東英樹, 斉藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 24 ) 159 - 159 2013.05

ヒト上皮性卵巣癌におけるアルデヒド脱水素酵素遺伝子ALDH1の発現とstemnessの検討

黒田敬史, 廣橋良彦, 鳥越俊彦, 安田和世, 浅沼広子, 高橋あかり, 浅野拓也, 真里谷奨, 水内将人, 斉藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 102 ( 1 ) 348 - 348 2013.04

診断に苦慮した卵巣悪性胚細胞腫瘍の1例

嶋田浩志, 田中綾一, 岩見菜々子, 長澤邦彦, 伊東英樹, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 57 ( 1 ) 111 - 112 2013.03

Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology

Keiko Ikeda, Tsuyoshi Baba, Hiroko Noguchi, Kunihiko Nagasawa, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

HUMAN REPRODUCTION ( OXFORD UNIV PRESS ) 28 ( 2 ) 453 - 461 2013.02 [Refereed]

Does administration of androgen to female-to-male transsexual persons (FTMs) of reproductive age induce polycystic ovary (PCO) morphology? Administration of high-dose androgen to women causes pathognomonic changes to the ovarian cortex and stroma that resemble SteinLeventhal syndrome but it does not induce PCO morphology. Androgen is thought to play a key role in follicular development and to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). In several experimental models, animals given high-dose androgen show ovarian changes similar to those in women with PCOS. In previous human studies, the ovaries of FTMs who received androgen for long periods also exhibited PCO morphology. We conducted a retrospective casecontrol study of women, all without PCOS, undergoing salpingo-oophorectomy. The case group consisted of 11 FTMs taking testosterone (duration range: 17 months to 14 years), while the control group consisted of 10 patients with gynaecologic malignancies who did not receive testosterone. Resected ovaries from both groups were compared histologically with respect to changes in the cortex and stroma, and the number of follicles at each maturation stage. Compared with controls, the FTM group had a thicker ovarian cortex (P 0.0001), and more hyperplastic collagen (P 0.001), ovarian stromal hyperplasia (P 0.003) and stromal luteinization, i.e. luteinized stromal cells with a small dark central nucleus surrounded by clear cytoplasm (P 0.004). Isolated clusters of such stromal luteinized cells were found only in the testosterone-treated ovaries of FTMs. The number of primordial follicles was similar in the two groups (P 0.22). The numbers of early stage (primary, pre-antral and early antral) follicles, which are dependent on androgen, were also similar (P 0.81), as were the numbers of antral follicles (P 0.97). In contrast, significantly greater numbers of atretic follicles were seen in the FTM than that in the control group (P 0.01). In addition to the low numbers in the study groups, the histological changes in FTMs were investigated after testosterone administration, therefore it is possible that some of the observed changes were already present, before androgen administration. Our results are at variance with those of earlier studies and suggest that excessive androgen exposure in women of reproductive age may not be a factor in the pathogenesis of PCOS. None.

DOI PubMed

Roles of microRNA-34a in the pathogenesis of placenta accreta

Kota Umemura, Shin-Ichi Ishioka, Toshiaki Endo, Yoshiaki Ezaka, Madoka Takahashi, Tsuyoshi Saito

Journal of Obstetrics and Gynaecology Research 39 ( 1 ) 67 - 74 2013.01

DOI PubMed

Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

Yasuda K, Torigoe T, Morita R, Kuroda T, Takahashi A, Matsuzaki J, Kochin V, Asanuma H, Hasegawa T, Saito T, Hirohashi Y, Sato N

PloS one ( 8 ) 8 e68187 2013 [Refereed]

DOI PubMed

A myotonic dystrophy 1 patient complicated with placental adherence after miscarriage of one dichorionic diamniotic twin following her tenth in vitro fertilization and embryo transfer.

Endo T, Baba T, Sugio A, Morishita M, Takahashi M, Akashi Y, Ishioka S, Tachi N, Imai T, Tamakawa M, Saito T

Archives of gynecology and obstetrics ( 6 ) 286 1605 - 1608 2012.12 [Refereed]

DOI PubMed

Weight reduction and pioglitazone ameliorate polycystic ovary syndrome after removal of a Sertoli-stromal cell tumor

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Shin-Ichi Ishioka, Tsuyoshi Saito

International Journal of Women's Health 4 ( 1 ) 607 - 611 2012.11 [Refereed]

This report presents an unusual case of Sertoli-stromal cell tumor and polycystic ovary syndrome successfully treated with weight reduction and an insulin-sensitizing agent. A 22-year-old woman, gravida 0, para 0, visited our hospital for the first time with a 12-year history of secondary amenorrhea and hypertrichosis. Transvaginal ultrasonography revealed a solid tumor in the right ovary. Right salpingo-oophorectomy was performed and pathological examination confirmed a Sertoli-stromal cell tumor. The patient's serum androgen levels declined postoperatively, but remained above normal. Pioglitazone treatment for 6 months also significantly reduced serum androgen levels, but they still remained above normal. However, after losing 12 kg of body weight, the patient's serum androgen levels declined to normal, and spontaneous menstruation became regular. Weight reduction with pioglitazone is an effective means of treating hyperandrogenism. © 2012 Baba et al, publisher and licensee Dove Medical Press Ltd.

DOI PubMed

母児ともに救命し得た大動脈解離合併妊娠の3例

嶋田浩志, 岡村直樹, 染谷真行, 齋藤雅恵, 竹田倫子, 浅野拓也, 明石祐史, 馬場剛, 石岡伸一, 遠藤俊明, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 60回 90 - 90 2012.09

160kg高度肥満妊婦に対する帝王切開の経験

中嶋千紗, 馬場剛, 森下美幸, 金美善, 足立英文, 明石祐史, 浅野拓也, 嶋田浩志, 杉尾明香, 石岡伸一, 遠藤俊明, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 60回 87 - 87 2012.09

Epidermal growth factor modulates claudins and tight junctional functions in ovarian cancer cell lines.

Ogawa M, Kojima T, Someya M, Nomura K, Takasawa A, Murata M, Tanaka S, Saito T, Sawada N

Histochemistry and cell biology ( 2 ) 138 323 - 338 2012.08 [Refereed]

DOI PubMed

Simultaneous presentation of tubal and primary abdominal pregnancies following clomiphene citrate treatment

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Naoko Takenami, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Hideyuki Ikeda, Tsuyoshi Saito

ARCHIVES OF GYNECOLOGY AND OBSTETRICS ( SPRINGER HEIDELBERG ) 286 ( 2 ) 395 - 398 2012.08 [Refereed]

Abdominal pregnancy is a rare condition that is potentially life-threatening for the mother. We present a case of simultaneous ectopic pregnancies (EPs) in the right fallopian tube and in the vesicouterine pouch. A 26-year-old woman had undergone prior ovulation induction with clomiphene citrate and human chorionic gonadotropin (hCG) at an outside hospital for unexplained infertility. The patient was referred to our hospital for a suspected ectopic pregnancy at 6 weeks gestation. Transvaginal ultrasonography detected a viable fetus at the anterior left side of the uterus; therefore, we suspected a left tubal pregnancy. However, laparoscopic surgery revealed that EPs were located in both the left vesicouterine pouch and in the right fallopian tube. Resection of the right salpinx and abdominal implant were performed. Histopathological examination confirmed the simultaneous presentation of a primary abdominal pregnancy and a right tubal pregnancy. After surgery, the patient's serum hCG level returned to normal. Concurrent EPs and abdominal pregnancy are very rare. However, it should be noted that reproductive technologies sometimes cause unusual clinical situations. A thorough abdominal inspection is needed.

DOI

Trophectoderm morphology significantly affects the rates of ongoing pregnancy and miscarriage in frozen-thawed single-blastocyst transfer cycle in vitro fertilization.

Hiroyuki Honnma, Tsuyoshi Baba, Masahiro Sasaki, Yoshiki Hashiba, Hiroshi Ohno, Takanori Fukunaga, Toshiaki Endo, Tsuyoshi Saito, Yoshimasa Asada

Fertility and sterility 98 ( 2 ) 361 - 7 2012.08 [International journal]

OBJECTIVE: To determine which parameter of blastocyst morphology is the most important predictor of ongoing pregnancy or miscarriage. DESIGN: Retrospective analysis. SETTING: One in vitro fertilization (IVF) center. PATIENT(S): Women who underwent a total of 1,087 frozen-thawed single-blastocyst transfer cycles. INTERVENTION(S): First IVF treatment with blastocysts after frozen-thawed cycle. MAIN OUTCOME MEASURE(S): Ongoing pregnancy and miscarriage rates as related to blastocyst morphology (blastocyst expansion, inner cell mass, and trophectoderm), and interaction tests in unadjusted logistic regression models to assess clinical factors affecting outcomes. RESULT(S): After adjustment for trophectoderm, inner cell mass, and age as confounders, trophectoderm was determined to be statistically significantly related to the rate of ongoing pregnancy. Trophectoderm was also statistically significantly related to the miscarriage rate. By contrast, neither inner cell mass nor blastocyst expansion was statistically significantly related. CONCLUSION(S): In frozen-thawed embryo transfer cycles, trophectoderm morphology is statistically significantly related to the rates of ongoing pregnancy and miscarriage after adjusting for confounders. Trophectoderm morphology may be the most important parameter when selecting a single blastocyst for transfer.

DOI PubMed

[Mechanism of metastasis in endometrial cancer].

Saito T, Tanaka R, Iwasaki M

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 4 317 - 320 2012.06 [Refereed]

PubMed

Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses.

Mizuuchi M, Hirohashi Y, Torigoe T, Kuroda T, Yasuda K, Shimizu Y, Saito T, Sato N

Experimental and molecular pathology ( 1 ) 92 185 - 190 2012.02 [Refereed]

DOI PubMed

Evaluation of cervical conization as a definitive treatment for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3.

Takeda N, Suzuki T, Suzuki M, Matsuura M, Tanaka R, Fujii M, Ito E, Saito T

Archives of gynecology and obstetrics 285 ( 2 ) 453 - 457 2012.02 [Refereed]

DOI PubMed

Continuous follicle-stimulating hormone exposure from pituitary adenoma causes periodic follicle recruitment and atresia, which mimics ovarian hyperstimulation syndrome.

Mika Kanaya, Tsuyoshi Baba, Yoshimitsu Kitajima, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Toshiaki Endo, Tsuyoshi Saito

International journal of women's health 4 427 - 31 2012 [International journal]

CONTEXT: Follicle-stimulating hormone (FSH)-secreting pituitary adenoma is usually a nonfunctioning tumor, but in rare cases it may develop into ovarian hyperstimulation. Several reports have revealed that serum FSH levels are normal to slightly high in patients with combined FSH-secreting pituitary adenoma with ovarian hyperstimulation. This finding is different from iatrogenic ovarian hyperstimulation syndrome (OHSS), which is associated with extremely high levels of FSH. OBJECTIVE: To describe the clinical course of two patients who developed OHSS from FSH-secreting pituitary adenoma. RESULTS: Endocrine studies of the two cases revealed that FSH levels were normal or slightly increased, but luteinizing hormone levels were low to undetectable. Their estradiol (E2) levels were intriguing: levels fluctuated drastically over 6 weeks in Case 1, but stayed flat in Case 2. Ultrasonographic examinations showed bilaterally enlarged multicystic ovaries, and magnetic resonance imaging indicated pituitary tumors. Transsephenoidal resection of the tumors ameliorated the symptoms and pathological diagnosis revealed FSH-secreting pituitary adenomas. CONCLUSION: As is not the case in iatrogenic OHSS, even a small to moderate amount of FSH stimulation, which is continuously secreted by a pituitary adenoma, can cause ovarian hyperstimulation. Although FSH-secreting pituitary adenoma can cause ovarian hyperstimulation, an extremely high amount of E2 biosynthesis from granulosa cells seldom occurs.

DOI PubMed

First case of vaginal radical trachelectomy in a pregnant Japanese woman

Nanako Iwami, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Kunihiko Nagasawa, Madoka Takahashi, Asuka Sugio, Sakura Takada, Tasuku Mariya, Masahiro Mizunuma, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER TOKYO ) 16 ( 6 ) 737 - 740 2011.12 [Refereed]

A diagnosis of cervical cancer during pregnancy poses difficult management and ethical problems. Survival of the patient is the foremost concern, but fetal viability and well-being must also be addressed. Radical trachelectomy (RT) has recently begun to be performed as a possible treatment modality for early stage invasive uterine cervical cancer in pregnant patients who would like to continue their pregnancy. A 32-year-old Japanese woman visited a local hospital for prenatal care, and was diagnosed with a FIGO I B1 adenocarcinoma of the uterine cervix. She had a strong desire to avoid pregnancy termination, so she was admitted to our hospital for fertility-preserving surgery. After extensive counseling, vaginal radical trachelectomy with abdominal pelvic lymphadenectomy was performed in the 16th gestational week. The excised uterine cervix and lymph nodes were pathologically negative for cancer. To maintain her pregnancy, daily vaginal disinfection with povidone iodine, bed rest, and administration of ritodrine and an ulinastatin vaginal suppository were continued until the delivery. At 34 weeks' gestation, an emergency cesarean section was performed because of sudden premature rupture of the membranes. A baby girl was born weighing 2112 g, with Apgar score of 8/9. The mother remains without evidence of recurrence at the time of this report. This is the first case of successful pregnancy and delivery in Japan after vaginal RT.

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p53 negatively regulates the hepatoma growth factor HDGF.

Yasushi Sasaki, Hideaki Negishi, Masashi Idogawa, Ikuko Yokota, Ryota Koyama, Masanobu Kusano, Hiromu Suzuki, Masahiro Fujita, Reo Maruyama, Minoru Toyota, Tsuyoshi Saito, Takashi Tokino

Cancer research 71 ( 22 ) 7038 - 47 2011.11 [Refereed] [International journal]

Hepatoma-derived growth factor (HDGF) is a secreted heparin-binding growth factor that has been implicated in cancer development and progression. Here, we report that HDGF is a critical target for transcriptional repression by the tumor suppressor p53. Endogenous HDGF expression was decreased in cancer cells with introduction of wild-type p53, which also downregulated HDGF expression after DNA damage. In support of the likelihood that HDGF is a critical driver of cancer cell growth, addition of neutralizing HDGF antibodies to culture media was sufficient to block cell growth, migration, and invasion. Similarly, these effects were elicited by conditioned culture medium from p53-expressing cells, and they could be reversed by the addition of recombinant human HDGF. Interestingly, we found that HDGF was overexpressed also in primary gastric, breast, and lung cancer tissues harboring mutant p53 genes. Mechanistic investigations revealed that p53 repressed HDGF transcription by altering HDAC-dependent chromatin remodeling. Taken together, our results reveal a new pathway in which loss of p53 function contributes to the aggressive pathobiological potential of human cancers by elevating HDGF expression.

DOI PubMed

A Remarkably Easy Knot-Tying Technique for Single-Incision Laparoscopic Surgery with the SILS Port for Gynecologic Diseases

Toshiaki Endo, Kunihiko Nagasawa, Kota Umemura, Tsuyoshi Baba, Hirofumi Henmi, Tsuyoshi Saito

JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY ( ELSEVIER SCIENCE INC ) 18 ( 4 ) 500 - 502 2011.07 [Refereed]

Single-incision laparoscopic surgery (SILS) has been quickly accepted, especially for women, because the cosmetic benefits may be greater than with ordinary laparoscopic surgery. In gynecologic disease, SILS is appropriate for diagnostic laparoscopy, oophorectomy, and salpingectomy, among other conditions. In addition, the knot-tying process for intracorporeal suturing during SILS is a major rate-limiting step and a key determinant of the popularity of SILS. Although a roticulator instrument is useful for creating the needed operative angle, knot tying is still believed to be difficult. We have devised a remarkably simple knot-tying technique that can be applied during SILS with a SILS Port with a Roticulator and a straight-type needle driver. We determined that, after transfixing the needle, the long tail of the thread should be grasped at around 90 degrees relative to the long axis of tip of the Roticulator, which is articulated at 80 degrees. This automatically forms an ideal C-loop because of gravitation. The needle attached to the long tail should face the distal side from the tip of Roticulator (from the surgeon's perspective). The apex of the C-loop is then toward the proximal side from the tip of the Roticulator (from the perspective of the surgeon). This thread position is important during the knot-tying process. The upper arm of the C-loop should then be entwined by applying a series of axial spinning movements to the rod of the needle driver. At this time, the jaws of the needle driver should be kept open so the thread does not slip off of the rod. The benefit of this technique is that it does not require any special skills; any surgeon able to perform intracorporeal suturing should also be able to easily tie knots during SILS. Journal of Minimally Invasive Gynecology (2011) 18, 500-502 (C) 2011 AAGL. All rights reserved.

DOI

Distinctive features of female-to-male transsexualism and prevalence of gender identity disorder in Japan.

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Hiroyuki Honnma, Hiroshi Ikeda, Naoya Masumori, Tousei Ohmura, Tamotsu Kiya, Takashi Fujimoto, Motoiki Koizumi, Tsuyoshi Saito

The journal of sexual medicine 8 ( 6 ) 1686 - 93 2011.06 [International journal]

INTRODUCTION: The prevalence of transsexualism is thought to differ among socio-geographic backgrounds, and little is known about its prevalence in Japan. Polycystic ovary syndrome (PCOS), which is known to be associated with insulin resistance and metabolic syndrome, is often seen in female-to-male (FTM) transsexual patients. Consequently, detection of PCOS is an important part of health care for these individuals. AIM: The purpose of this study was to assess the prevalence of transsexuality in Japan, as well as the incidences of PCOS and insulin resistance among Japanese FTM transsexual patients. METHODS: One hundred four male-to-female (MTF) and 238 FTM Japanese transsexual patients were studied. Medical histories, including histories of menstrual cycling and hormone treatment, were taken. To exclude other diseases, such as congenital adrenal hyperplasia and hormone-secreting tumors, thorough medical assessments, including transvaginal or transrectal ultrasonography and measurement of serum hormone levels and insulin resistance indexes, were performed. MAIN OUTCOME MEASURES: The diagnosis of PCOS was based on the Rotterdam 2003 criteria. RESULTS: Based on demographic statistics, the prevalences of MTF and FTM transsexuality are about 3.97 and 8.20 per 100,000 people, respectively, making the MTF-to-FTM ratio about 1:2. Of the FTM transsexual patients studied, 128 had not taken hormones before their initial assessment (untreated group); the remaining 50 self-administered androgen. Among the untreated group, 32.0% were diagnosed with PCOS, 30.1% were insulin-resistant, and 31.1% showed hypoadiponectinemia. CONCLUSIONS: The sex ratio among Japanese transsexuals is different than among Caucasians. PCOS and insulin resistance are common findings in FTM transsexual patients at initial presentation.

DOI PubMed

BAG3 (BCL2-associated athanogene 3) interacts with MMP-2 to positively regulate invasion by ovarian carcinoma cells

Miwa Suzuki, Masahiro Iwasaki, Asuka Sugio, Akinori Hishiya, Ryoichi Tanaka, Toshiaki Endo, Shinichi Takayama, Tsuyoshi Saito

CANCER LETTERS ( ELSEVIER IRELAND LTD ) 303 ( 1 ) 65 - 71 2011.04 [Refereed]

BAG3 (BCL2-associated athanogene 3) is a member of the BAG family proteins, which interact with and regulate Hsp70. Our aim in the present study was to correlate BAG3 expression in ovarian cancer with invasion and progression-free survival. We found that BAG3 interacts with MMP2 in cultured ovarian cancer cells, and that knockdown of BAG3 expression downregulated MMP2 expression and diminished cell motility and invasiveness. The incidence of BAG3 positivity was significantly higher at advanced clinical stages of ovarian cancer than at early stages. We suggest that BAG3 binds to MMP2 to positively regulate the process of cell invasion. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma.

Matsuura M, Suzuki T, Suzuki M, Tanaka R, Ito E, Saito T

Oncology reports 25 ( 1 ) 41 - 47 2011.01 [Refereed]

PubMed

Osteopontin is a new target molecule for ovarian clear cell carcinoma therapy.

Matsuura M, Suzuki T, Saito T

Cancer science 101 ( 8 ) 1828 - 1833 2010.08 [Refereed]

DOI PubMed

Prediction of histologic type and lymph node metastasis for advanced ovarian cancer on uterine cervical and endometrial cytology.

Suzuki M, Suzuki T, Matsuura M, Iwasaki M, Tanaka R, Ito E, Fujii M, Saito T

Acta cytologica 54 ( 4 ) 575 - 581 2010.07 [Refereed]

DOI PubMed

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats.

Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Ayumi Shimizu, Kunihiko Nagasawa, Tsuyoshi Baba, Takashi Fujimoto, Hirofumi Henmi, Yoshimitsu Kitajima, Kengo Manase, Shinichi Ishioka, Eiki Ito, Tsuyoshi Saito

Reproductive biology and endocrinology : RB&E 8 73 - 73 2010.06 [International journal]

BACKGROUND: Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. METHODS: In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). RESULTS: Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. CONCLUSIONS: Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

DOI PubMed

Successful uterus-preserving surgery for treatment of chemotherapy-resistant placenta increta.

Endo T, Hayashi T, Shimizu A, Matsuura M, Mizuuchi M, Nagasawa K, Ezaka Y, Baba T, Ishioka S, Saito T

Gynecologic and obstetric investigation 69 ( 2 ) 112 - 115 2010 [Refereed]

DOI PubMed

Changes of uterine blood flow after vaginal radical trachelectomy (VRT) in patients with early-stage uterine invasive cervical cancer

Kota Umemura, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yoshiaki Ezaka, Kunihiko Nagasawa, Madoka Takahashi, Masahito Mizuuchi, Nanako Iwami, Hidefumi Adachi, Noriko Takeda, Mitsuharu Tamagawa, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES ( IVYSPRING INT PUBL ) 7 ( 5 ) 260 - 266 2010 [Refereed]

Background. Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined. Methods. Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions. Results. New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected. Conclusion. Ligation and cutting of several supplying arteries by RT induces new areterial vascularization and it does not seem to affect fetal growth and placental function.

Outcomes of planned delivery delay in pregnant patients with invasive gynecologic cancer

Shin-ichi Ishioka, Yoshiaki Ezaka, Toshiaki Endo, Kunihiko Nagasawa, Ayumi Shimizu, Akiyasu Sato, Marie Inoue, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER TOKYO ) 14 ( 4 ) 321 - 325 2009.08 [Refereed]

Pregnancy with invasive gynecologic cancer is a rare condition. It is still unclear whether we can choose planned delay in treatment until maturation of the fetus as a treatment modality for this condition. If there are no adverse effects from the cancer and there is improvement of neonatal outcomes, this treatment modality might be an option for patients with this condition. Eight pregnant patients were diagnosed as having invasive gynecologic cancer between January 1998 and December 2007. Five of them, (four with invasive uterine cervical cancer and one with ovarian cancer) chose planned delay in treatment. The pregnancy courses and prognoses of these patients were studied. The period of planned delay in treatment varied from 2 weeks to 19 weeks. The period was shorter for patients who had complications. The pain caused by the cancer was the main obstacle to this treatment modality in two patients (one with advanced ovarian cancer and one with uterine cervical cancer). No apparent tumor growth, elevation of tumor markers, or complications induced by the cancer itself were detected in the remaining three patients. Only the patient with advanced ovarian cancer died of the primary disease after the delivery. Fetal outcome was uniformly good for the delayed-treatment group. All the babies are growing well, and no fetal deaths or neonatal deaths occurred. Planned delay in treatment to allow for fetal maturity is acceptable in pregnant patients with certain types of invasive gynecologic cancers.

DOI

The contributions of resistin and adiponectin gene single nucleotide polymorphisms to the genetic risk for polycystic ovary syndrome in a Japanese population

Tsuyoshi Baba, Toshiaki Endo, Fumihiro Sata, Kunihiko Nagasawa, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Mika Kanaya, Osamu Moriwaka, Hirofumi Kamiya, Hideto Yamada, Hisanori Minakami, Reiko Kishi, Tsuyoshi Saito

GYNECOLOGICAL ENDOCRINOLOGY ( INFORMA HEALTHCARE ) 25 ( 8 ) 498 - 503 2009 [Refereed] [International journal]

Polycystic ovary syndrome (PCOS) is a heterogeneous group of disorders that occur fairly commonly in women of reproductive age and are characterized by a variety of clinical manifestations, including insulin resistance that is independent of obesity. Recent studies suggest that altered adipocytokine gene expression is closely associated with insulin resistance and that single nucleotide polymorphisms (SNPs) modulate the expression and/or function of these genes, thereby affecting insulin sensitivity. With that in mind, we investigated whether SNPs at position 7420 of the resistin gene (RETN) and/or 711377 of the adiponectin gene (ADIPOQ) modulate the susceptibility to PCOS. We evaluated the genotypes of 117 women with PCOS and 380 healthy fertile controls and measured the index of insulin resistance and hormonal profiles in the PCOS women. The RETN 7420G/G homozygous variant genotype occurred significantly more frequently among the PCOS group than among the control group (15.4% vs. 8.4%, p = 0.035). PCOS women with the RETN 7420G/ G genotype also showed significantly higher BMIs and greater insulin resistance than those with RETN 7420 C/C or C/G genotypes. The ADIPOQ SNP at 711377 showed no association with PCOS. We conclude that the RETN G/G at 7420 genotype is associated with PCOS in Japanese women.

DOI PubMed

Analgesic efficacy of controlled-release oxycodone in patients with uterine or ovarian cancer.

Suzuki T, Morishita M, Ito E, Matsuura M, Tanaka R, Saito T

American journal of therapeutics 15 ( 1 ) 31 - 35 2008.01 [Refereed]

DOI PubMed

Advanced epithelial ovarian carcinoma during pregnancy

Shin-ichi Ishioka, Takuhiro Hayashi, Toshiaki Endo, Tsuyoshi Baba, Hiroyuki Honma, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER TOKYO ) 12 ( 5 ) 375 - 378 2007.10 [Refereed]

We report a rare case of advanced ovarian mucinous adenocarcinoma in a pregnant woman. A 28-year-old pregnant Japanese woman was diagnosed with an ovarian tumor 8cm in diameter at a local hospital. She was sent to a private hospital at 25 weeks of gestation because of the growing ovarian tumor. Advanced ovarian carcinoma with widespread intraabdominal dissemination was detected by laparotomy at the hospital and she was referred to our hospital for further management. At 27 weeks of gestation, she underwent cesarean section, followed by abdominal total hysterectomy, and bilateral salpingo-oophorectomy. A girl weighing 879 g was delivered, with Apgar scores of 4 and 6 at 1 and 5 min, respectively. The pathological diagnosis of the tumor was mucinous cystadenocarcinoma grade 2. Although chemotherapy was not effective for her and she died of the disease 4 months after the surgery, her baby grew well and weighed 3750g 3 months after delivery. For the treatment of such patients, we believe we should choose operative therapy as early as possible after the maturation of the fetus, although there are several reports of successful treatment with the administration of chemotherapy during pregnancy. To determine a better approach for such patients, multidisciplinary staff meetings, including gynecological oncologists, obstetricians, neonatologists, psychologists, and the patient are important.

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Pregnancy-related complications after vaginal radical trachelectomy for early-stage invasive uterine cervical cancer

Shin-Ichi Ishioka, Toshiaki Endo, Takuhiro Hayashi, Tsuyoshi Baba, Kota Umemura, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER TOKYO ) 12 ( 5 ) 350 - 355 2007.10 [Refereed]

Background Pregnancy-related complications after vaginal radical trachelectomy (RT) for early-stage invasive uterine cervical cancer were studied in comparison with those occurring after laser conization. The strategy to reduce vaginal RT-related complications during pregnancy is also discussed. Methods. Pregnancy courses after vaginal RT in two patients and those after laser conization in five patients, whose operations were performed during the same period, were studied with respect to symptoms, cervical length, and infectious signs. Results. The cervix shortened progressively both in patients with laser conization and in those with RT. However, throughout the pregnancy, the remaining cervix after the operation was longer in patients who had undergone conization than in those who had undergone vaginal RT. After laser conization, two of the five patients suffered from preterm rupture of the membrane (PROM) at 36 weeks of gestation, and both patients who had undergone vaginal RT had premature PROM (pPROM), at 32 and 24 weeks of gestation, respectively. Conclusion. Prevention of preterm labor and the following occurrence of pPROM is a significant task to be resolved in order to improve pregnancy outcome after vaginal RT for early-stage invasive uterine cervical cancer. Daily vaginal disinfection with povidone iodine and the administration of a ulinastatin vaginal suppository, bed rest, and the use of ritodrine would be the best approach, and a more conservative approach for stage Ia2 also might be taken into consideration.

DOI

Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population

Tsuyoshi Baba, Toshiaki Endo, Fumihiro Sata, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Mika Kanaya, Hideto Yamada, Hisanori Minakami, Reiko Kishi, Tsuyoshi Saito

LIFE SCIENCES ( PERGAMON-ELSEVIER SCIENCE LTD ) 81 ( 10 ) 850 - 854 2007.08 [Refereed]

(PCOS). We hypothesized that insulin receptor substrate-1 (IRS-1) Gly972Arg polymorphism and/or ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Lysl 2 1 Gln polymorphism predisposes women to PCOS and that these polymorphisms also affect anthropometric variables, glucose metabolism and androgen synthesis. To test those ideas, we studied the genotypes, indexes of insulin resistance, and hormone profiles in 123 Japanese women with PCOS and 3 80 healthy Japanese controls. We found that there were significantly more IRS-1 972Arg carriers among the PCOS patients than among the healthy controls (10.6% vs. 4.8%, p=0.029), which is consistent with our finding that women carrying the IRS-1 972Arg allele had a significantly increased risk of developing PCOS (odds ratio: 3.31, 95% confidence interval: 1.49-7.35). By contrast, the ENPPI Lys121Arg polymorphism was distributed equally among PCOS patients and controls. In addition, neither of these polymorphisms studied affected the anthropometric variables, metabolic parameters or androgen levels of women with PCOS. We conclude that the IRS-1 Gly972Arg polymorphism is associated with PCOS in the Japanese population. (c) 2007 Elsevier Inc. All rights reserved.

DOI PubMed

Association between polycystic ovary syndrome and female-to-make transsexuality

Tsuyoshi Baba, Toshiaki Endo, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Hiroshi Ikeda, Naoya Masumori, Hirofumi Kamiya, Osamu Moriwaka, Tsuyoshi Saito

HUMAN REPRODUCTION ( OXFORD UNIV PRESS ) 22 ( 4 ) 1011 - 1016 2007.04 [Refereed]

The aim of this study is to understand the relationship between polycystic ovary syndrome (PCOS), altered hormonal characteristics and insulin resistance in female-to-male (FTM) transsexual patients. METHODS: We studied 69 Japanese FTM cases, aged 17-47 years, who were seen in the Gender Identity Disorder Clinic of Sapporo Medical University Hospital between December 2003 and May 2006. The subjects had never received hormonal treatment or sex re-assignment surgery. Prior to treatment, they received physical examinations entailing measurement of anthropometric, metabolic and endocrine parameters, after which we compared the values obtained according to the presence or absence of PCOS and/or obesity. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Of the 69 participating FTM cases, 40 (58.0%) were found to have PCOS. Of the 49 for whom HOMA-IR was calculated, 15 (30.6 %) also showed insulin resistance, whereas of the 59 for whom adiponectin was measured, 18 (30.5%) showed hypoadiponectinaemia. Of 69 for whom androgens were measured, 29 (39.1 %) showed hyperandrogenaemia. Insulin resistance was associated with obesity but not with PCOS. In contrast, hyperandrogenaemia was associated with both PCOS and obesity. CONCLUSIONS: FTM transsexual patients have a high prevalence of PCOS and hyperandrogenaemia.

DOI

A successful IVF-pregnancy in a patient who underwent conservative surgery followed by a regimen of cisplatin, vinblastine and peplomycin to treat an advanced ovarian mixed germ cell tumour: A Case Report

Y. Kitajima, T. Endo, T. Hayashi, S. Ishioka, T. Baba, H. Honnma, T. Saito

HUMAN REPRODUCTION ( OXFORD UNIV PRESS ) 22 ( 3 ) 850 - 852 2007.03 [Refereed]

Mixed germ cell tumours of the ovary, one type of malignant ovarian germ cell tumours (MOGCTs), are rare gynaecologic cancers usually affecting young women. We report the case of a patient with an advanced ovarian mixed germ cell tumour who underwent fertility-saving surgery followed by a chemotherapy regimen of cisplatin, vinblastine and peplomycin. The patient was disease-free 8 years after initial presentation. She conceived and gestated dichorionic twins after IVF-embryo transfer. To the best of our knowledge, the patient is the first to be treated successfully with the combination chemotherapy regimen and then conceive safely using assisted reproductive technology (ART).

DOI

Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus.

Toshiaki Endo, Tamotsu Kiya, Taeko Goto, Hirofumi Henmi, Kengo Manase, Hiroyuki Honnma, Tsuyoshi Baba, Shinichi Ishioka, Takuhiro Hayashi, Manabu Chida, Kazuyo Arima, Kiyohiro Yamazaki, Mika Kanaya, Atsushi Azumaguchi, Osamu Moriwaka, Hirofumi Kamiya, Tsuyoshi Saito

Reproductive medicine and biology 5 ( 4 ) 235 - 243 2006.12 [Domestic journal]

Matrix metalloproteinases (MMP) are capable of degrading a variety of extracellular matrix (ECM) proteins and are also involved in the processing of a number of bioactive molecules. Our findings indicate that the functions of MMP in the ovary and uterus are organ-specific and time-dependently vary during the reproductive cycle. Prolactin induces structural luteolysis indicated by loss of luteal weight, protein and DNA within 36 h after pretreatment with ergot alkaloid. MMP activation appears crucial for the selective depletion of protein during luteal involution, which entails loss of ECM accompanied by apoptosis. During GnRHagonist-induced luteolysis, this response was also associated with marked increases in MMP-2, which degraded collagen type IV, and MT1-MMP, which in addition to activating MMP-2 also degrades collagen type I, III and V. We also found that the level of MT1-MMP and MMP-2 expression in the human CL is greater during the late luteal phase than during either the early mid luteal phases or during gestation, respectively. That dehydroepiandrosterone (DHEA) treatment caused the formation of cysts from antral follicles in the ovaries of immature rats while depressing MMP-2 collagenolytic activity and enhancing lysyl oxidase expression highlights the importance of collagen degradation in the process of ovulation and suggests that changes in the activities of these enzymes play a key role in ovarian cystogenesis in polycystic ovary syndrome patients. Furthermore, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive apoptotic granulosa cells in rats treated with DHEA, that the Fas/FasL/Caspase-8 (death receptor-dependent) pathway is pivotal for follicular atresia and that increased levels of MT1-MMP likely play an important role in tissue remodeling during follicular atresia. After parturition, the uterus undergoes involution, a conspicuous feature characterized by a rapid reduction in the collagen content mediated by degradation of extracellular collagen bundles. Our findings strongly suggest that MT1-MMP, MMP-2 and MMP-9 are each time-dependently regulated and play important roles in tissue remodeling during postpartum uterine involution. (Reprod Med Biol 2006; 5: 235-243).

DOI PubMed

Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats

Hiroyuki Honnma, Toshiaki Endo, Hirofumi Henmi, Kunihiko Nagasawa, Tsuyoshi Baba, Kiyohiro Yamazaki, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Tsuyoshi Saito

APOPTOSIS ( SPRINGER ) 11 ( 9 ) 1525 - 1533 2006.09 [Refereed]

One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats (P < 0.05), as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis.

DOI

Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells

Kunihiko Nagasawa, Hideki Chiba, Hiroki Fujita, Takashi Kojima, Tsuyoshi Saito, Toshiaki Endo, Norimasa Sawada

Journal of Cellular Physiology 208 ( 1 ) 123 - 132 2006.07

Gap-junction plaques are often observed with tight-junction strands of vascular endothelial cells but the molecular interaction and functional relationships between these two junctions remain obscure. We herein show that gap-junction proteins connexin40 (Cx40) and Cx43 are colocalized and coprecipitated with tight-junction molecules occludin, claudin-5, and ZO-1 in porcine blood-brain barrier (BBB) endothelial cells. Gap junction blockers 18β-glycyrrhetinic acid (18β-GA) and oleamide (OA) did not influence expression of Cx40, Cx43, occludin, claudin-5, junctional adhesion molecule (JAM)-A, JAM-B, JAM-C, or ZO-1, or their subcellular localization in the porcine BBB endothelial cells. In contrast, these gap-junction blocking agents inhibited the barrier function of tight junctions in cells, determined by measurement of transendothelial electrical resistance and paracellular flux of mannitol and inulin. 18β-GA also significantly reduced the barrier property in rat lung endothelial (RLE) cells expressing doxycycline-induced claudin-1, but did not change the interaction between Cx43 and either claudin-1 or ZO-1, nor their expression levels or subcellular distribution. These findings suggest that Cx40- and/or Cx43-based gap junctions might be required to maintain the endothelial barrier function without altering the expression and localization of the tight-junction components analyzed. © 2006 Wiley-Liss, Inc.

DOI PubMed

Coordinated elevation of membrane type I-matrix metalloproteinase and matrix metalloproteinase-2 expression in rat uterus during postpartum involution

Kengo Manase, Toshiaki Endo, Mitunobu Chida, Kunihiko Nagasawa, Hiroyuki Honnma, Kiyohiro Yamazaki, Yoshimitu Kitajima, Taeko Goto, Mika Kanaya, Takuhiro Hayashi, Toshihiro Mitaka, Tsuyoshi Saito

REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY ( BIOMED CENTRAL LTD ) 4 32 2006.06 [Refereed]

Background: The changes occurring in the rodent uterus after parturition can be used as a model of extensive tissue remodeling. As the uterus returns to its prepregnancy state, the involuting uterus undergoes a rapid reduction in size primarily due to the degradation of the extracellular matrix, particularly collagen. Membrane type-I matrix metalloproteinase (MT1- MMP)is one of the major proteinases that degrades collagen and is the most abundant MMP form in the uterus. Matrix metalloproteinase-2(MMP-2) can degrade type I collagen, although its main function is to degrade type IV collagen found in the basement membrane. To understand the expression patterns of matrix metalloproteinases (MMPs) in the rat uterus, we analyzed their activities in postpartum uterine involution. Methods: We performed gelatin zymography, northern blot analysis and immunohistochemistry to compare the expression levels of MT1- MMP, MMP-2, matrix metalloproteinase-9 (MMP-9) and the tissue inhibitors of MMPs-1 and 2 (TIMP-1 and TIMP-2) in the rat uterus 18 h, 36 h and 5 days after parturition with their expression levels during pregnancy ( day 20). Results: We found that both MT1- MMP and MMP-2 localized mainly in the cytoplasm of uterine interstitial cells. The expression levels of MT1- MMP and MMP-2 mRNAs and the catalytic activities of the expressed proteins significantly increased 18 h and 36 h after parturition, but at postpartum day 5, their mRNA expression levels and catalytic activities decreased markedly. The expression levels of MMP-9 increased 18 h and 36 h after parturition as determined by gelatin zymography including the expression levels of TIMP-1 and TIMP-2. Conclusion: These expression patterns indicate that MT1-MMP, MMP-2, MMP- 9, TIMP-1 and TIMP-2 may play key roles in uterine postpartum involution and subsequent functional regenerative processes.

DOI PubMed

Successful delivery after vaginal radical trachelectomy for invasive uterine cervical cancer.

Ishioka S, Endo T, Hayashi T, Kitajima Y, Sugimura M, Sagae S, Saito T

International journal of clinical oncology 11 ( 2 ) 146 - 149 2006.04 [Refereed]

DOI PubMed

Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines.

Terasawa K, Toyota M, Sagae S, Ogi K, Suzuki H, Sonoda T, Akino K, Maruyama R, Nishikawa N, Imai K, Shinomura Y, Saito T, Tokino T

British journal of cancer ( 6 ) 94 914 - 921 2006.03 [Refereed]

DOI PubMed

Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5.

Yoshimitsu Kitajima, Toshiaki Endo, Kunihiko Nagasawa, Kengo Manase, Hiroyuki Honnma, Tsuyoshi Baba, Takuhiro Hayashi, Hideki Chiba, Norimasa Sawada, Tsuyoshi Saito

Endocrinology 147 ( 2 ) 694 - 9 2006.02 [International journal]

We investigated the mechanism by which a GnRH agonist (GnRHa) affects ovarian vascularity, vascular permeability, and expression of the tight junction protein claudin-5 in a rat model of ovarian hyperstimulation syndrome (OHSS). Hyperstimulated rats received excessive doses of pregnant mare serum gonadotropin (PMSG; 50 IU/d) for 4 consecutive days, from d 25 to 28 of life, followed by 25 IU human chorionic gonadotropin (hCG) on d 29. Control rats received 10 IU PMSG on d 27 of life, followed by 10 IU hCG on d 29. GnRHa (leuprolide 100 microg/kg.d) was administered to some hyperstimulated rats either on d 29 and 30 (short-term GnRHa treatment) or from d 25 to 30 (long-term GnRHa treatment). Ovarian vascular density (vessels per 10 mm(2)) and vessel endothelial area (percent) were assessed by immunohistochemical analysis of the distribution of von Willebrand factor, whereas vascular permeability was evaluated based on leakage of Evans blue. High doses of PMSG and hCG significantly increased ovarian weight, vascular permeability, vascular density, and the vessel endothelial area and significantly reduced expression of claudin-5 protein and mRNA. All of these effects were significantly and dose-dependently inhibited by administration of GnRHa. This suggests that reduced expression of claudin-5 plays a crucial role in the increased ovarian vascular permeability seen in OHSS and that its expression can be modulated by GnRHa treatment. Indeed, preventing redistribution of tight junction proteins in endothelial cells and the resultant loss of endothelial barrier architecture might be the key to protecting patients against massive extravascular fluid accumulation in cases of OHSS.

PubMed

Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers

K Maeno, A Masuda, K Yanagisawa, H Konishi, H Osada, T Saito, R Ueda, T Takahashi

ONCOGENE ( NATURE PUBLISHING GROUP ) 25 ( 2 ) 271 - 277 2006.01 [Refereed]

The c-jun oncogene is frequently overexpressed in non-small-cell lung cancers (NSCLC), but its functional involvement in lung cancer development has not been clearly elucidated. In this study, we found that among the immediate-early serum responsible genes, exemplified by c-jun, c-fos and c-myc, induction of c-jun in a human bronchial epithelial cell line, BEAS-2B, was dependent on anchorage, in contrast to clear induction of c-fos and c-myc under both anchorage-dependent and - independent conditions. In fact, forced expression of c-jun in BEAS-2B cells significantly increased cell viability and colony formation in soft agar. Furthermore, we also found that such anchorage-dependent regulation of c-jun was lost in a significant fraction of human lung cancer cell lines. Interestingly, suppressed anchorage-independent but not anchorage-dependent growth was noted by constitutive expression of a dominant-negative c-jun mutant in a lung cancer cell line showing dysregulated and sustained c-jun expression in the absence of anchorage. These findings suggest that dysregulated c-jun expression may be involved in the acquisition of anchorage independence in the process of human lung carcinogenesis.

DOI

Accuracy of magnetic resonance imaging for the evaluation of myometrial invasion in endometrial carcinoma

Takashi Fujimoto, Mitsuharu Tamagawa, Miho Kimura, Ryoichi Tanaka, Kota Umemura, Eiki Ito, Takahiro Suzuki, Masato Hareyama, Tsuyoshi Saito

Tumor Research 41 71 - 76 2006

Endometrial carcinoma is the most common gynecologic malignancy and accounts for 6% of all cancers in women. In patients with endometrial cancer, preoperative knowledge of myometrial tumor extension has important prognostic and therapeutic implications. The aim of this retrospective study is to assess whether magnetic resonance (MR) imaging is useful to assess the depth of myometrial invasion by endometrial carcinoma. Sixty patients between 2003 and 2005 were included in the study. All patients were proven histopathologically endometrial carcinoma and underwent preoperative MR imaging and all data was compared in all cases. The histological results showed no myometrial invasion in 8 cases, myometrial invasion of less than 50% in 35 cases, and myometrial invasion of more than 50% in 17cases. In the cases of no myometrial invasion, MR T2 weighted imaging had a sensitivity of 87.5%, a specificity of 86.5%, a positive predictive Value (PPV) of 50.0% and a negative predictive value (NPV) of 97.8%. In the cases of myometrial invasion of less than 50%, MR T2 weighted imaging had a sensitivity of 82.9%, a specificity of 72.0%, PPV of 80.6% and NPV of 75.0%. By contrast, in the cases of myometrial invasion of more than 50%, the sensitivity, specificity, PPV and NPV of MR T2 weighted imaging were 58.8%, 100%, 100% and 86.0% respectively. Errors in MR findings when determining myometrial tumor spread were more frequently underestimations rather than overestimations. Our results indicate that MR imaging is useful for the preoperative assessment of the depth ofmyometrial invasion in patients with endometrial carcinoma.

Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4α-induced epithelial polarization

Seiro Satohisa, Hideki Chiba, Makoto Osanai, Shigeo Ohno, Takashi Kojima, Tsuyoshi Saito, Norimasa Sawada

Experimental Cell Research ( Academic Press Inc. ) 310 ( 1 ) 66 - 78 2005.10 [Refereed]

We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4α [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4α triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4α-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells. Induced expression of HNF-4α led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4α provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization. © 2005 Elsevier Inc. All rights reserved.

DOI PubMed

Over-expression of heat shock proteins in carcinogenic endometrium

K Wataba, T Saito, K Fukunaka, K Ashihara, M Nishimura, R Kudo

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS ) 91 ( 4 ) 448 - 456 2001.02 [Refereed]

We have previously shown that the subcellular localization of beta -catenin changes according to the cell proliferation status of the human endometrium, suggesting a role of intercellular transduction in cell growth control in human endometrium not only in the physiological but also in the carcinogenic condition. To further study the possible role of heat shock proteins (HSPs) in growth control, we immunohistochemically analyzed 92 endometrial samples, 30 of normal endometrium, 20 of endometrial hyperplasia and 42 of endometrial cancer, for expression of HSP27, HSP70, HSP90, estrogen receptor (ER) and progesterone receptor. HSP27 and HSP90 were detected in endometrial epithelium strongly in the proliferative phase and weakly in the secretory phase during the menstrual cycle according to the serum estradiol level. However, they were over-expressed in endometrial hyperplasia, especially HSP27. In endometrial cancer, HSP27 expression was heterogenic among the glands and lower than that in the proliferative phase and endometrial hyperplasia. HSP27 over-expression was also observed in samples including endometrial cancer and associated hyperplasia. Results of Western blotting followed those of immunohistochemistry, HSP70 was not changed during the menstrual cycle, as HSP27 and HSP90 were, and was rather stably expressed in endometrial hyperplasia and cancer. Our results suggest that HSP27 and HSP90 contribute to cell proliferation in endometrial epithelium and that over-expression of HSP27 in endometrial hyperplasia occurs as a result of the activated condition of ER, though in cancer it decreases according to the loss of function of ER. (C) 2001 Wiley-Liss, Inc.

Usefulness of enucleation of uterine myoma for patients complicated sterility

H. Mizumoto, T. Saito, T. Endo, A. Nishikawa, K. Ashihara, R. Tanaka, R. Kudo

Japanese Journal of Fertility and Sterility 46 ( 3 ) 13 - 16 2001

Though it is still unclear about whether uterine myoma is a cause of sterility and whether enucleation of myoma is a successful therapy for sterility, it is believed that the myoma obstructs implantation. In this study, we analyzed the pregnancy rate (%) after enucleation of myoma in 21 women who were suffering from sterility but did not have a clear cause except the myoma. After the enucleation, 12 of the 21 (57%) women became pregnant, These consisted of 9 of the 17 (53%) who had the abdominal enucleation and 3 of the 4 (75%) with vaginal enucleation. We could not find any correlation between the age and the pregnancy rate. As for the correlation between the pregnancy rate and the location of the myoma, 3 patients with subserosal myoma became pregnant as did 9 with intramural myoma, whereas 2 with submucosal myoma did not. Six of the 12 (50%) patients became pregnant within 12 months and within 18 months 9 (75%) had became pregnant. The mean was 14 months. From these results, we concluded that the enucleation of myoma is a useful procedure as a therapy for sterility.

Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers

K Yanagisawa, K Uchida, M Nagatake, A Masuda, M Sugiyama, T Saito, K Yamaki, T Takahashi, H Osada

ONCOGENE ( STOCKTON PRESS ) 19 ( 19 ) 2305 - 2311 2000.05 [Refereed]

Smad family members are essential intracellular signaling components of the transforming growth factor-beta (TGF-beta) superfamily involved in a range of biological activities. The loss of sensitivity to TGF-beta is frequent in human lung cancers and inactivation of Smad family members are thought to play important roles in disruption of TGF-beta signaling. In the study presented here, we characterized the biological and biochemical functions of six Smad2 and Smad4 mutants, which we previously identified in human lung cancers. All mutant Smad2 and Smad4 were in fact found to be defective in transmitting growth inhibitory signals originating from TGF-beta and incapable of activating Smad/hFAST-1-mediated transcription. Transcriptional activation of plasminogen activator inhibitor type 1 (PAI-1) was impaired in four of the six mutants due to the defects in homo- and/or hetero-oligomerization with wild-type Smads, In contrast, the remaining two Smad mutants showed a modest reduction in the PAI-1 transcriptional activation and apparently retained the ability to oligomerize with wild-type Smads, Significant loss of growth inhibition and Smad/hFAST-1-mediated transcriptional activation by all of the six mutants suggested that Smad mutants are indeed functionally impaired Smad mutations and may play a role in lung tumorigenesis, Moreover, the present findings suggest that in addition to the impairment in the homo- and/or hetero-oligomerization, there may be an alternative mechanism producing disruption of TGF-beta signaling, involving hFAST-1-or possibly other transcriptional cofactor(s)-mediated transcriptional activation.

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