研究者詳細 - 齋藤　豪

論文 - 齋藤　豪

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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年05月

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年04月 [査読有り]

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年04月

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年04月

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年03月 [国際誌]

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

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年03月

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年03月

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年03月

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)

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年01月 [査読有り]

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年 [査読有り]

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年 [査読有り]

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年12月 [国際誌]

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年12月 [査読有り]

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年10月

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年08月 [査読有り]

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年08月

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年08月

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年08月

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年07月 [査読有り]

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年07月 [査読有り]

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

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