研究者詳細 - 齋藤　豪

論文 - 齋藤　豪

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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

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年12月

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

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

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

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

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

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年06月 [国際誌]

DOI PubMed

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

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

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)

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

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

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

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