研究者詳細 - 齋藤　豪

論文 - 齋藤　豪

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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年03月 [査読有り]

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

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年03月

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年03月

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年03月

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年03月

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年03月

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)

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年03月

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年01月 [査読有り]

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年

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年12月 [査読有り]

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

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年12月

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年12月

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年12月

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年12月

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年12月

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年10月 [査読有り]

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年10月

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年08月 [査読有り]

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

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年06月

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年05月 [国際誌]

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

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