Updated on 2022/11/01

写真a

 
KOYA Yoshihiro
 
Organization
Graduate School of Medicine Laboratory of Bell Research Center-Department of Obstetrics and Gynecology collaborative research Industry-Academia Collaborative Chair Designated lecturer
Title
Designated lecturer

Degree 1

  1. 博士(医学) （ 東京医科歯科大学 ） 

To the head of Degree.▲

Research Interests 3

  1. Oncology

  2. Tumor immunology

  3. Gynecologic oncology

To the head of Research Interests.▲

Research Areas 3

  1. Life Science / Tumor biology

  2. Life Science / Immunology

  3. Life Science / Virology

To the head of Research Areas.▲
 

Papers 48

  1. Microphthalmia-Associated Transcription Factor-Dependent Melanoma Cell Adhesion Molecule Activation Promotes Peritoneal Metastasis of Ovarian Cancer. International journal

    Kazuhisa Kitami, Masato Yoshihara, Yoshihiro Koya, Mai Sugiyama, Shohei Iyoshi, Kaname Uno, Kazumasa Mogi, Sho Tano, Hiroki Fujimoto, Akihiro Nawa, Fumitaka Kikkawa, Hiroaki Kajiyama

    International journal of molecular sciences   Vol. 21 ( 24 ) page： 1 - 15   2020.12

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    Publishing type：Research paper (scientific journal)  

    Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.

    DOI： 10.3390/ijms21249776

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  2. Folate-appended cyclodextrin carrier targets ovarian cancer cells expressing the proton-coupled folate transporter. Reviewed International journal

    Shinichi Saito, Yoshihiro Koya, Hiroaki Kajiyama, Mamoru Yamashita, Fumitaka Kikkawa, Akihiro Nawa

    Cancer science   Vol. 111 ( 5 ) page： 1794 - 1804   2020.5

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    Publishing type：Research paper (scientific journal)  

    Folate receptor alpha (FRα) is overexpressed in >80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as a first-line chemotherapeutic agent in combination with platinum-based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor-EL, a traditional formulation vehicle that causes significant side effects, including neutropenia. Several years ago, folate-appended β-CyD (Fol-c1 -β-CyD) was developed as an FRα-targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol-c1 -β-CyD (PTX/Fol-c1 -β-CyD) in EOC-derived cell lines. We found that PTX/Fol-c1 -β-CyD killed not only FRα-expressing cells but also FRα-negative cells. In the FRα-negative A2780 cells, knockdown of proton-coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol-c1 -β-CyD, whereas knockdown of FRα did not. By contrast, knockdown of either FRα or proton-coupled folate transporter (PCFT) decreased the cytotoxicity of PTX/Fol-c1 -β-CyD in FRα-expressing SK-OV-3 cells. Furthermore, the cytotoxicity of PTX/Fol-c1 -β-CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRα-expressing or PCFT-expressing EOC cells, intraperitoneal administration of PTX/Fol-c1 -β-CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol-c1 -β-CyD targets not only FRα but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity.

    DOI： 10.1111/cas.14379

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  3. Hematopoietic lineage cell-specific protein 1 (HS1), a hidden player in migration, invasion, and tumor formation, is over-expressed in ovarian carcinoma cells. Reviewed

    Koya Y, Liu W, Yamakita Y, Senga T, Shibata K, Yamashita M, Nawa A, Kikkawa F, Kajiyama H

    Oncotarget   Vol. 9 ( 66 ) page： 32609 - 32623   2018.8

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  4. Molecular hydrogen has a positive impact on pregnancy maintenance through enhancement of mitochondrial function and immunomodulatory effects on T cells

    Aoki Chieko, Imai Kenji, Mizutani Teruyuki, Sugiyama Daisuke, Miki Rika, Koya Yoshihiro, Kobayashi Tomoko, Ushida Takafumi, Iitani Yukako, Nakamura Noriyuki, Owaki Taro, Nishikawa Hiroyoshi, Toyokuni Shinya, Kajiyama Hiroaki, Kotani Tomomi

    LIFE SCIENCES   Vol. 308   page： 120955   2022.11

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    Language：Japanese   Publisher：Life Sciences  

    Aims: Molecular hydrogen (H2) has attracted growing interest because of its implications in various diseases. However, the molecular mechanisms underlying the remarkable effect of a small amount of H2 remain elusive. No knowledge has been available on the role of H2 in the etiology of pregnancy disorders or its direct influence on human immune cells. Since maternal immunity, T cells in particular, plays a critical role in pregnancy maintenance. We investigated the effects of H2 on T cells and its relation to preterm birth (PTB). Main methods: Exhaled H2 concentrations in pregnant women were measured and correlated with cytokine concentrations in maternal and umbilical cord blood. H2 was added to T cells collected from healthy donors, and differentiation and proliferation were examined. Energy metabolism was also examined. H2 was administered to mice and cytokine expression was compared. Key findings: Our prospective observational study revealed that maternal production of H2 is significantly lower in pregnant women with PTB, suggesting its potential as a biomarker for predicting PTB. We found that H2 has clear associations with several maternal cytokines, and acts as an immunomodulator by exerting mitochondrial function in human T cells. Moreover, in vivo administration of H2 to pregnant mice regulated inflammatory responses and reduced PTB caused by T cell activation, which further supports the notion that H2 may contribute to prolonged gestation through its immunomodulatory effect. Significance: Measuring maternal H2-production could be a potential clinical tool in the management of PTB, and H2 may have positive impact on pregnancy maintenance.

    DOI： 10.1016/j.lfs.2022.120955

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  5. Regulation of Mesothelial Cell Fate during Development and Human Diseases

    Taniguchi Toshiaki, Tomita Hiroyuki, Kanayama Tomohiro, Mogi Kazumasa, Koya Yoshihiro, Yamakita Yoshihiko, Yoshihara Masato, Kajiyama Hiroaki, Hara Akira

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 23 ( 19 )   2022.10

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    Language：Japanese   Publisher：International Journal of Molecular Sciences  

    Mesothelial cells (MCs) play a classic role in maintaining homeostasis in pleural, peritoneal, and pericardial cavities. MCs work as lubricants to reduce friction between organs, as regulators of fluid transport, and as regulators of defense mechanisms in inflammation. MCs can differentiate into various cells, exhibiting epithelial and mesenchymal characteristics. MCs have a high potential for differentiation during the embryonic period when tissue development is active, and this potential decreases through adulthood. The expression of the Wilms’ tumor suppressor gene (Wt1), one of the MC markers, decreased uniformly and significantly from the embryonic period to adulthood, suggesting that it plays a major role in the differentiation potential of MCs. Wt1 deletion from the embryonic period results in embryonic lethality in mice, and even Wt1 knockout in adulthood leads to death with rapid organ atrophy. These findings suggest that MCs expressing Wt1 have high differentiation potential and contribute to the formation and maintenance of various tissues from the embryonic period to adulthood. Because of these properties, MCs dynamically transform their characteristics in the tumor microenvironment as cancer-associated MCs. This review focuses on the relationship between the differentiation potential of MCs and Wt1, including recent reports using lineage tracing using the Cre-loxP system.

    DOI： 10.3390/ijms231911960

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  6. Peritoneal restoration by repurposing vitamin D inhibits ovarian cancer dissemination via blockade of the TGF-β1/thrombospondin-1 axis. International journal

    Kazuhisa Kitami, Masato Yoshihara, Satoshi Tamauchi, Mai Sugiyama, Yoshihiro Koya, Yoshihiko Yamakita, Hiroki Fujimoto, Shohei Iyoshi, Kaname Uno, Kazumasa Mogi, Yoshiki Ikeda, Akira Yokoi, Nobuhisa Yoshikawa, Kimihiro Nishino, Kaoru Niimi, Akihiro Nawa, Atsushi Enomoto, Hiroaki Kajiyama

    Matrix biology : journal of the International Society for Matrix Biology   Vol. 109   page： 70 - 90   2022.5

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    Ovarian cancer (OvCa), a lethal gynecological malignancy, disseminates to the peritoneum. Mesothelial cells (MCs) act as barriers in the abdominal cavity, preventing the adhesion of cancer cells. However, in patients with OvCa, they are transformed into cancer-associated mesothelial cells (CAMs) via mesenchymal transition and form a favorable microenvironment for tumors to promote metastasis. However, attempts for restoring CAMs to their original state have been limited. Here, we investigated whether inhibition of mesenchymal transition and restoration of MCs by vitamin D suppressed the OvCa dissemination in vitro and in vivo. The effect of vitamin D on the mutual association of MCs and OvCa cells was evaluated using in vitro coculture models and in vivo using a xenograft model. Vitamin D restored the CAMs, and thrombospondin-1 (component of the extracellular matrix that is clinically associated with poor prognosis and is highly expressed in peritoneally metastasized OvCa) was found to promote OvCa cell adhesion and proliferation. Mechanistically, TGF-β1 secreted from OvCa cells enhanced thrombospondin-1 expression in CAMs via Smad-dependent TGF-β signaling. Vitamin D inhibited mesenchymal transition in MCs and suppressed thrombospondin-1 expression via vitamin D receptor/Smad3 competition, contributing to the marked reduction in peritoneal dissemination in vivo. Importantly, vitamin D restored CAMs from a stabilized mesenchymal state to the epithelial state and normalized thrombospondin-1 expression in preclinical models that mimic cancerous peritonitis in vivo. MCs are key players in OvCa dissemination and peritoneal restoration and normalization of thrombospondin-1 expression by vitamin D may be a novel strategy for preventing OvCa dissemination.

    DOI： 10.1016/j.matbio.2022.03.003

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  7. Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components. International journal

    Kaname Uno, Shohei Iyoshi, Masato Yoshihara, Kazuhisa Kitami, Kazumasa Mogi, Hiroki Fujimoto, Mai Sugiyama, Yoshihiro Koya, Yoshihiko Yamakita, Akihiro Nawa, Tomohiro Kanayama, Hiroyuki Tomita, Atsushi Enomoto, Hiroaki Kajiyama

    International journal of molecular sciences   Vol. 23 ( 8 )   2022.4

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-β can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.

    DOI： 10.3390/ijms23084383

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  8. Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy. International journal

    Kaname Uno, Nobuhisa Yoshikawa, Akira Tazaki, Shoko Ohnuma, Kazuhisa Kitami, Shohei Iyoshi, Kazumasa Mogi, Masato Yoshihara, Yoshihiro Koya, Mai Sugiyama, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Fumitaka Kikkawa, Masashi Kato, Hiroaki Kajiyama

    Scientific reports   Vol. 12 ( 1 ) page： 4513 - 4513   2022.3

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with "platinum-resistant recurrence". Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.

    DOI： 10.1038/s41598-022-08503-7

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  9. Adipose-mesothelial crosstalk regulates peritoneal tumor microenvironment and accelerates metastasis of ovarian cancer

    Mogi Kazumasa, Yoshihara Masato, Uno Kaname, Iyoshi Shohei, Kitami Kazuhisa, Sugiyama Mai, Koya Yoshihiro, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 113   page： 735 - 735   2022.2

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    Language：Japanese  

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  10. NGFR contributes the malignancy of ovarian carcinoma cells

    Koya Yoshihiro, Sugiyama Mai, Yoshihara Masato, Kitami Kazuhisa, Uno Kaname, Mogi Kazumasa, Iyoshi Shohei, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 113   page： 1033 - 1033   2022.2

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  11. Vitamin D inhibits mesothelial-mesenchymal-transition accelerating peritoneal dissemination in ovarian cancer via THBS1

    Kitami Kazuhisa, Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Yamakita Yoshihiko, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 113   page： 729 - 729   2022.2

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  12. Notch-dependent intra-tumoral heterogeneity mediates cell-fate dynamics and development of peritoneal dissemination

    Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Mogi Kazumasa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 113   page： 1405 - 1405   2022.2

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  13. Notch signaling contributes to drug resistance acquisition through metabolic alteration in advanced ovarian cancer

    Sugiyama Mai, Yoshihara Masato, Koya Yoshihiro, Kitami Kazuhisa, Uno Kaname, Iyoshi Shohei, Mogi Kazumasa, Yokoi Akira, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 113   page： 1280 - 1280   2022.2

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  14. Pro-tumoral behavior of omental adipocyte-derived fibroblasts in tumor microenvironment at the metastatic site of ovarian cancer Reviewed International journal

    Iyoshi Shohei, Yoshihara Masato, Nakamura Kae, Sugiyama Mai, Koya Yoshihiro, Kitami Kazuhisa, Uno Kaname, Mogi Kazumasa, Tano Sho, Tomita Hiroyuki, Kajiwara Keiji, Taki Masayasu, Yamaguchi Shigehiro, Nawa Akihiro, Kajiyama Hiroaki

    INTERNATIONAL JOURNAL OF CANCER   Vol. 149 ( 11 ) page： 1961 - 1972   2021.12

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Journal of Cancer  

    Adipocyte-rich omentum offers “good soil” for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.

    DOI： 10.1002/ijc.33770

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  15. ビタミンDによる卵巣癌腹膜播種を亢進する腹膜中皮細胞のEMTを標的とした治療

    北見 和久, 吉原 雅人, 杉山 麻衣, 小屋 美博, 山北 由彦, 伊吉 祥平, 宇野 枢, 茂木 一将, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 那波 明宏, 梶山 広明

    日本癌学会総会記事   Vol. 80回   page： [E14 - 4]   2021.9

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  16. 脂肪-中皮細胞により制御される卵巣がん微小環境と腹膜播種

    茂木 一将, 吉原 雅人, 宇野 枢, 伊吉 祥平, 北見 和久, 杉山 麻衣, 小屋 美博, 玉内 学志, 横井 暁, 芳川 修久, 那波 明宏, 梶山 広明

    日本癌学会総会記事   Vol. 80回   page： [E10 - 4]   2021.9

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  17. 卵巣癌腹膜播種においてNotchシグナルは代謝変容を通して薬剤抵抗性獲得に寄与する

    杉山 麻衣, 吉原 雅人, 小屋 美博, 北見 和久, 宇野 枢, 伊吉 祥平, 茂木 一将, 横井 暁, 那波 明宏, 梶山 広明

    日本癌学会総会記事   Vol. 80回   page： [J5 - 4]   2021.9

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  18. Primate-specific POTE-actin gene could play a role in human folliculogenesis by controlling the proliferation of granulosa cells Reviewed International journal

    Kasahara Yukiyo, Osuka Satoko, Takasaki Nobuyoshi, Bayasula, Koya Yoshihiro, Nakanishi Natsuki, Murase Tomohiko, Nakamura Tomoko, Goto Maki, Iwase Akira, Kajiyama Hiroaki

    CELL DEATH DISCOVERY   Vol. 7 ( 1 ) page： 186   2021.7

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cell Death Discovery  

    Patients with primary ovarian insufficiency (POI) often have a high prevalence of autoimmune disorders. To identify antigenic molecules associated with ovarian autoimmunity, we performed immunoprecipitation (IP) screening using serum from patients with POI and the established human granulosa cell line (HGrC1). POTE ankyrin domain family member E (POTEE) and POTE ankyrin domain family member F (POTEF), proteins specific to primates, were identified as candidate antigens. Using immunohistochemistry (IHC) with human ovarian tissue, POTEE or POTEF was weakly seen in the granulosa cells (GCs) of primordial follicles and primary follicles, and strongly in large antral follicles and luteal cells. Interestingly, no signals were detected in growing GCs in secondary, preantral, and small antral follicles. Thus, to explore the function of POTEE and POTEF in human folliculogenesis, we established HGrC1 cell lines with drug-inducible expression of POTEF. Expression of POTEF significantly suppressed cell proliferation in HGrC1 cells. Furthermore, chaperonin containing TCP-1 complex (CCT) components, which affect folding proteins required for cell proliferation, was bound to the actin domain of POTEF protein. Although CCT is normally localized only around the Golgi apparatus, TCP-1α, a component of CCT, co-migrated closer to the cell membrane when POTEF expression was induced. These data suggest that the interaction between POTEF and CCT components impairs the usual function of CCT during cell growth. In addition, over-accumulation of POTEF in HGrC1 cells leads to autophagic failure. It was recently reported that knockout of an autophagic gene in mice leads to a phenotype similar to human POI. These results suggested that a proper amount of POTEF is required for the maintenance of GCs in follicle pools, whereas POTEF overaccumulation might be involved in follicle atresia and the development of POI. We also showed the possibility that POTEF could be an antigen involved in ovarian autoimmunity.

    DOI： 10.1038/s41420-021-00566-1

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  19. 活性型ビタミンDによる中皮間葉系移行の抑制 卵巣癌の腹膜播種を加速させる(Active Vitamin D Inhibits Mesothelial-mesenchymal-transition: Accelerating Peritoneal Dissemination in Ovarian Cancer)

    北見 和久, 吉原 雅人, 杉山 麻衣, 小屋 美博, 伊吉 祥平, 宇野 枢, 茂木 一将, 玉内 学志, 池田 芳紀, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 那波 明宏, 梶山 広明

    日本婦人科腫瘍学会学術講演会プログラム・抄録集   Vol. 63回   page： 231 - 231   2021.7

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    Language：English   Publisher：(公社)日本婦人科腫瘍学会  

  20. Ovarian Cancer-Associated Mesothelial Cells: Transdifferentiation to Minions of Cancer and Orchestrate Developing Peritoneal Dissemination

    Mogi Kazumasa, Yoshihara Masato, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Tano Sho, Koya Yoshihiro, Sugiyama Mai, Yamakita Yoshihiko, Nawa Akihiro, Tomita Hiroyuki, Kajiyama Hiroaki

    CANCERS   Vol. 13 ( 6 ) page： 1 - 13   2021.3

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  21. 卵巣癌腹膜播種においてNotchシグナルは腫瘍内不均一性の形成と細胞増殖亢進に寄与する

    杉山 麻衣, 吉原 雅人, 小屋 美博, 北見 和久, 横井 暁, 伊吉 祥平, 宇野 枢, 山下 守, 吉川 史隆, 那波 明宏, 梶山 広明

    日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page： S - 485   2021.3

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    Language：Japanese   Publisher：(公社)日本産科婦人科学会  

  22. Active vitamin D inhibits mesothelial-mesenchymal-transition accelerating peritoneal dissemination in ovarian cancer

    Kitami Kazuhisa, Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page： 351 - 351   2021.2

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  23. Visualization of platinum resistance through mapping trace elements

    Uno Kaname, Yoshikawa Nobuhisa, Yoshihara Masato, Tazaki Kei, Kato Masashi, Kitami Kazuhisa, Iyoshi Shohei, Tamauchi Satoshi, Sugiyama Mai, Koya Yoshihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page： 906 - 906   2021.2

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  24. Intra-tumoral polarity induced by Notch signaling can be a novel therapeutic target for advanced ovarian cancer

    Yoshihara Masato, Sugiyama Mai, Koya Yoshihiro, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Mogi Kazumasa, Tano Sho, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page： 363 - 363   2021.2

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  25. How do peritoneal mesothelial cells on adipose tissue attract ovarian cancer cells?

    Mogi Kazumasa, Yoshihara Masato, Kitami Kazuhisa, Iyoshi Shohei, Uno Kaname, Tano Sho, Sugiyama Mai, Koya Yoshihiro, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page： 341 - 341   2021.2

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  26. Anti-tumor effect of 9-oxo-10,12-ODA on human cervical cancer cells

    Koya Yoshihiro, Sugiyama Mai, Yoshihara Masato, Shibata Kiyosumi, Nawa Akihiro, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 112   page： 826 - 826   2021.2

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  27. Macrophage-derived extracellular vesicles regulate concanavalin A-induced hepatitis by suppressing macrophage cytokine production. Reviewed International journal

    Reo Kawata, Shingo Oda, Yoshihiro Koya, Hiroaki Kajiyama, Tsuyoshi Yokoi

    Toxicology   Vol. 443   page： 152544 - 152544   2020.10

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    Publishing type：Research paper (scientific journal)  

    Acute liver failure is a clinical syndrome of severe hepatic dysfunction. Immune cells play an important role in acute liver failure. In recent years, the immunoregulatory function of extracellular vesicles (EVs) has been reported; therefore, it is inferred that EVs play a role in immune-mediated hepatitis. In this study, we investigated the immunoregulatory function of EVs in concanavalin A (Con A)-induced hepatitis. The mouse model was prepared by a single intravenous administration of 15 mg/kg Con A, in which there was a significant increase in the serum EVs number. In an in vitro study, the number of secreted EVs was also significantly increased in Con A-treated RAW264.7 cells, a mouse macrophage cell line, but not in Hepa1-6 cells, a mouse hepatoma cell line. In an in vitro EVs treatment study, EVs from Con A-treated mouse serum and Con A-treated RAW264.7 cells suppressed inflammatory cytokine production in Con A-stimulated RAW264.7 cells. miRNA sequencing analysis showed that the expression of mmu-miR-122-5p and mmu-miR-148a-3p was commonly increased in these EVs and EVs-treated cells. The pathways enriched in the predicted miRNA target genes included inflammatory response pathways. The mRNA levels of the target genes in these pathways (mitogen-activated protein kinase, phosphoinositide 3-kinase/Akt and Rho/Rho-associated coiled-coil containing protein kinase pathways) were decreased in the EVs-treated cells. In an in vivo RNA interference study, the knockdown of liver RAB27A, an EVs secretion regulator, significantly exacerbated Con A-induced hepatitis. These data suggest that macrophage-derived EVs play an important role in Con A-induced hepatitis through immunoregulation.

    DOI： 10.1016/j.tox.2020.152544

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  28. 卵巣癌の腹膜播種における腹膜中皮と脂肪組織の影響

    茂木 一将, 吉原 雅人, 北見 和久, 伊吉 祥平, 宇野 枢, 田野 翔, 杉山 麻衣, 小屋 美博, 玉内 学志, 横井 暁, 芳川 修久, 那波 明宏, 梶山 広明

    日本癌学会総会記事   Vol. 79回   page： OE10 - 2   2020.10

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    Language：English   Publishing type：Research paper (other academic)   Publisher：(一社)日本癌学会  

  29. 進行卵巣癌におけるNotchシグナルを介した腫瘍内細胞極性の解明と標的化

    吉原 雅人, 杉山 麻衣, 小屋 美博, 伊吉 祥平, 北見 和久, 宇野 枢, 茂木 一将, 田野 翔, 玉内 学志, 横井 暁, 芳川 修久, 那波 明宏, 梶山 広明

    日本癌学会総会記事   Vol. 79回   page： OE11 - 2   2020.10

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    Language：English   Publishing type：Research paper (other academic)   Publisher：(一社)日本癌学会  

  30. 活性型ビタミンDは腹膜の中皮間葉転換を阻害し、卵巣癌腹膜播種を抑制する

    北見 和久, 吉原 雅人, 杉山 麻衣, 小屋 美博, 伊吉 祥平, 宇野 枢, 茂木 一将, 玉内 学志, 横井 暁, 芳川 修久, 那波 明宏, 梶山 広明

    日本癌学会総会記事   Vol. 79回   page： OE10 - 1   2020.10

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    Language：English   Publishing type：Research paper (other academic)   Publisher：(一社)日本癌学会  

  31. Filopodia play an important role in the trans-mesothelial migration of ovarian cancer cells. Reviewed International journal

    Masato Yoshihara, Yoshihiko Yamakita, Hiroaki Kajiyama, Takeshi Senga, Yoshihiro Koya, Mamoru Yamashita, Akihiro Nawa, Fumitaka Kikkawa

    Experimental cell research   Vol. 392 ( 2 ) page： 112011 - 112011   2020.7

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    Publishing type：Research paper (scientific journal)  

    Ovarian cancer cells shed from primary tumors can spread easily to the peritoneum via the peritoneal fluid. To allow further metastasis, the cancer cells must interact with the mesothelial cell layer, which covers the entire surface of the peritoneal organs. Although the clinical importance of this interaction between cancer and mesothelial cells has been increasingly recognized, the molecular mechanisms utilized by cancer cells to adhere to and migrate through the mesothelial cell layer are poorly understood. To investigate the molecular mechanisms of cancer cell trans-mesothelial migration, we set up an in vitro trans-mesothelial migration assay using primary peritoneal mesothelial cells. Using this method, we found that downregulation of filopodial protein fascin-1 or myosin X expression in ES-2 cells significantly inhibited the rate of trans-mesothelial migration of cancer cells, whereas upregulation of fascin-1 in SK-OV-3 cells enhanced this rate. Furthermore, downregulation of N-cadherin or integrin β1 inhibited the rate of cancer cell trans-mesothelial migration. Conversely, downregulation of cortactin or TKS5 or treatment with the MMP inhibitor GM6001 or the N-WASP inhibitor wiskostatin did not have any effect on cancer cell trans-mesothelial migration. These results suggest that filopodia, but not lamellipodia or invadopodia, play an important role in the trans-mesothelial migration of ovarian cancer cells.

    DOI： 10.1016/j.yexcr.2020.112011

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  32. Exploration of small RNA biomarkers for testicular injury in the serum exosomes of rats. Reviewed International journal

    Reo Kawata, Takumi Kagawa, Yoshihiro Koya, Hiroaki Kajiyama, Shingo Oda, Tsuyoshi Yokoi

    Toxicology   Vol. 440   page： 152490 - 152490   2020.7

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    Publishing type：Research paper (scientific journal)  

    Testicular injury is often observed in drug development. Serum hormones are usually used as noninvasive biomarkers for testicular injury; however, their sensitivities are low. Therefore, it is difficult to monitor testicular injury in drug development. In recent years, molecules in body fluid exosomes have attracted attention as biomarkers for diseases. In this study, small RNAs in serum exosomes were analyzed to identify noninvasive biomarkers of testicular injury in rats, which are often used in preclinical drug development. The rat models of testicular injury were prepared by a single oral administration of 2000 mg/kg ethylene glycol monomethyl ether, in which spermatocyte degeneration and Sertoli cell vacuolation were observed, or 400 mg/kg carbendazim, in which Sertoli cell vacuolation and seminiferous tubule dilation were observed. Serum exosomal small RNA-seq analysis of these models was performed. The analysis identified 3 small RNAs that fluctuated in common between the models, and miR-423-5p and miR-128-3p were selected as candidate markers. For evaluating these candidate markers in other testicular injury models, the models were prepared by a single oral administration of 60 mg/kg 1,3-dinitrobenzene or 500 mg/kg nitrofurazone, and spermatocyte degeneration and Sertoli cell vacuolation were observed. In qPCR analysis, these exosomal miRNAs were upregulated in all models except for the 1,3-dinitrobenzene model, in which severe hemolysis was observed. By contrast, these miRNAs in whole serum extracts did not significantly change in any of the models. In conclusion, we identified miR-423-5p and miR-128-3p in serum exosomes as noninvasive biomarkers for testicular injury in rats.

    DOI： 10.1016/j.tox.2020.152490

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  33. Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway

    Yoshihara Masato, Kajiyama Hiroaki, Yokoi Akira, Sugiyama Mai, Koya Yoshihiro, Yamakita Yoshihiko, Liu Wenting, Nakamura Kae, Moriyama Yoshinori, Yasui Hiroaki, Suzuki Shiro, Yamamoto Yusuke, Ricciardelli Carmela, Nawa Akihiro, Shibata Kiyosumi, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CANCER   Vol. 146 ( 8 ) page： 2268-2280   2020.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/ijc.32854

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  34. Interleukin‑33 expression in ovarian cancer and its possible suppression of peritoneal carcinomatosis. Reviewed

    Sekiya A, Suzuki S, Tanaka A, Hattori S, Shimizu Y, Yoshikawa N, Koya Y, Kajiyama H, Kikkawa F

    International journal of oncology   Vol. 55 ( 3 ) page： 755 - 765   2019.9

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  35. MITF contributes to cell migration/invasion in ovarian carcinoma cells

    Koya Yoshihiro, Ryu Buntei, Sugiyama Mai, Yoshihara Masato, Senga Takeshi, Nawa Akihiro, Kikkawa Fumitaka, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 109   page： 503-503   2018.12

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    Web of Science

  36. Notch signaling enhances the mutual association with epithelial ovarian cancer and mesothelial cells

    Sugiyama Mai, Yoshihara Masato, Koya Yoshihiro, Yokoi Akira, Ryu Buntei, Kikkawa Fumitaka, Kajiyama Hiroaki

    CANCER SCIENCE   Vol. 109   page： 864-864   2018.12

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    Web of Science

  37. Cancer-associated mesothelial cells as a potential therapeutic target in epithelial ovarian cancer Reviewed

    Masato Yoshihara, Hiroaki Kajiyama, Mai Sugiyama, Yoshihiro Koya, Buntei Ryu, Akira Yokoi, Yusuke Yamamoto, Fumitaka Kikkawa

    CANCER SCIENCE   Vol. 109   page： 247 - 247   2018.12

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    Language：English   Publisher：WILEY  

    Web of Science

  38. Mesothelial cells create invasion frontier in peritoneal metastasis of epithelial ovarian cancer

    Iyoshi Shohei, Kajiyama Hiroaki, Yoshihara Masato, Yamakita Yoshihiko, Sugiyama Mai, Koya Yoshihiro, Ryu Buntei, Kikkawa Fumitaka

    CANCER SCIENCE   Vol. 109   page： 282 - 282   2018.12

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  39. Cancer-associated mesothelial cells as a potential therapeutic target in epithelial ovarian cancer

    Yoshihara Masato, Kajiyama Hiroaki, Sugiyama Mai, Koya Yoshihiro, Ryu Buntei, Yokoi Akira, Yamamoto Yusuke, Kikkawa Fumitaka

    CANCER SCIENCE   Vol. 109   page： 247 - 247   2018.12

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  40. CANCER-ASSOCIATED MESOTHELIAL CELLS IN PERITONEAL METASTASIS OF EPITHELIAL OVARIAN CANCER AS A NOVEL THERAPEUTIC TARGET: 3D CO-CULTURE MODELS AND MULTI-OMICS ANALYSIS

    Masato Y., Kajiyama H., Yoshihiko Y., Mai S., Koya Y., Ryu B., Akira Y., Shiro S., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page： 187 - 188   2018.9

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  41. Hematopoietic lineage cell-specific protein 1 immunoreactivity indicates an increased risk of poor overall survival in patients with ovarian carcinoma. Reviewed International journal

    Wenting Liu, Hiroaki Kajiyama, Kiyosumi Shibata, Yoshihiro Koya, Takeshi Senga, Fumitaka Kikkawa

    Oncology letters   Vol. 15 ( 6 ) page： 9406 - 9412   2018.6

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    Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

    Hematopoietic lineage cell-specific protein 1 (HS1) is a 75-kDa intracellular protein that is expressed primarily in hematopoietic cells. Several previous studies have demonstrated the association between HS1 expression and a poor prognosis in hematopoietic malignancies; however, in solid tumors, no studies not been reported. The present study examined the distribution and expression of HS1 in human epithelial ovarian carcinoma (EOC) to determine its clinical significance. Paraffin sections were obtained from EOC tissues and immunostained with HS1 antibody, and then the staining intensities were evaluated. Overall survival (OS) was determined using the Kaplan-Meier estimator method, and multivariate analysis was performed using the Cox proportional hazards analysis. In total, 195 patients with EOC (median age, 56 years) were enrolled into the present study. HS1 immunoreactivity was categorized based on expression levels: Low (89/195; 45.6%) and high (106/195; 54.4%). Results demonstrated no association between expression level(s) and any clinicopathological parameter including age, International Federation of Gynecology and Obstetrics (FIGO) staging, type of chemotherapy or type of surgery received. The 5-year OS rates of patients who demonstrated low (n=89) and high (n=106) HS1 expression were 90.4 and 66.7%, respectively. The OS times for patients with high HS1 expression were significantly shorter compared with those for patients exhibiting low HS1 expression (P=0.0065). Results obtained from the multivariate analysis demonstrated that the FIGO stage and the amount of HS1 expressed were significant independent prognostic markers for poorer OS (hazard ratio, 3.539; 95% confidence interval, 1.221-12.811; P=0.0187). High HS1 expression levels may serve as a useful biomarker in patients with EOC who are likely to exhibit an unfavorable clinical outcome.

    DOI： 10.3892/ol.2018.8493

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  42. Notch signaling enhances the mutual association with epithelial ovarian cancer and mesothelial cells

    Sugiyama Mai, Kajiyama Hiroaki, Yoshihara Masato, Yasui Hiroaki, Ryu Buntei, Koya Yoshihiro, Ymakita Yoshihiko, Kikkawa Fumitaka

    CANCER SCIENCE   Vol. 109   page： 1043-1043   2018.1

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    Web of Science

  43. Carcinoma-associated mesothelial cells promote dissemination and platinum resistance in epithelial ovarian cancer. Reviewed

    Masato Yoshihara, Hiroaki Kajiyama, Mai Sugiyama, Hiroaki Yasui, Yoshihiro Koya, Yoshihiko Yamakita, Buntei Ryu, Akira Yokoi, Yusuke Yamamoto, Fumitaka Kikkawa

    CANCER SCIENCE   Vol. 109   page： 118 - 118   2018.1

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    Language：English   Publisher：WILEY  

    Web of Science

  44. HS1 immunoreactivity indicates increased risk of poor overall survival in ovarian carcinoma

    Liu Wenting, Kajiyama Hiroaki, Shibata Kiyosumi, Koya Yoshihiro, Senga Takeshi, Kikkawa Fumitaka

    CANCER SCIENCE   Vol. 109   page： 307 - 307   2018.1

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  45. HS1 immunoreactivity indicates increased risk of poor overall survival in ovarian carcinoma Reviewed

    Wenting Liu, Hiroaki Kajiyama, Kiyosumi Shibata, Yoshihiro Koya, Takeshi Senga, Fumitaka Kikkawa

    CANCER SCIENCE   Vol. 109   page： 307 - 307   2018.1

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    Language：English   Publisher：WILEY  

    Web of Science

  46. HS1 contributes cell migration/invasion and tumor formation in ovarian carcinoma

    Koya Yoshihiro, Liu Wenting, Yamakita Yoshihiko, Kajiyama Hiroaki, Senga Takeshi, Shibata Kiyosumi, Nawa Akihiro, Kikkawa Fumitaka

    CANCER SCIENCE   Vol. 109   page： 308 - 308   2018.1

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  47. HS1 contributes cell migration/invasion and tumor formation in ovarian carcinoma Reviewed

    Yoshihiro Koya, Wenting Liu, Yoshihiko Yamakita, Hiroaki Kajiyama, Takeshi Senga, Kiyosumi Shibata, Akihiro Nawa, Fumitaka Kikkawa

    CANCER SCIENCE   Vol. 109   page： 308 - 308   2018.1

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    Language：English   Publisher：WILEY  

    Web of Science

  48. Carcinoma-associated mesothelial cells promote dissemination and platinum resistance in epithelial ovarian cancer.

    Yoshihara Masato, Kajiyama Hiroaki, Sugiyama Mai, Yasui Hiroaki, Koya Yoshihiro, Yamakita Yoshihiko, Ryu Buntei, Yokoi Akira, Yamamoto Yusuke, Kikkawa Fumitaka

    CANCER SCIENCE   Vol. 109   page： 118 - 118   2018.1

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To the head of Papers.▲

MISC 8

  1. 9-oxo-10,12-ODAのヒト子宮頸癌細胞に対する抗腫瘍効果の解析

    小屋 美博, 梶山 広明, 吉原 雅人, 杉山 麻衣, 三木 梨可, 友田 豊, 山下 守, 柴田 清住, 那波 明宏, 吉川 史隆

    日本産科婦人科学会雑誌   Vol. 72 ( 臨増 ) page： S - 299   2020.3

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    Language：Japanese   Publisher：(公社)日本産科婦人科学会  

  2. 9-oxo-10,12-ODAのヒト子宮頸癌細胞に対する抗腫瘍効果の解析(Anti-tumor effect of 9-oxo-10,12-ODA on human cervical cancer cells)

    小屋 美博, 杉山 麻衣, 吉原 雅人, 柴田 清住, 千賀 威, 那波 明宏, 吉川 史隆, 梶山 広明

    日本癌学会総会記事   Vol. 78回   page： P - 1147   2019.9

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    Language：English   Publisher：日本癌学会  

  3. 上皮性卵巣癌におけるMITFの機能的役割(Function analysis of MITF in epithelial ovarian cancer)

    北見 和久, 小屋 美博, 梶山 広明, 杉山 麻衣, 伊吉 祥平, 宇野 枢, 吉原 雅人, 那波 明宏, 吉川 史隆

    日本癌学会総会記事   Vol. 78回   page： P - 1061   2019.9

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    Language：English   Publisher：日本癌学会  

  4. がん研究における女性研究者(第6回) 腹膜中皮細胞はNotchシグナルを介して卵巣がん細胞の増殖を亢進する(Women scientists in cancer research Mesothelial cells promote ovarian cancer proliferation through Notch signaling pathway)

    杉山 麻衣, 梶山 広明, 吉原 雅人, 小屋 美博, 横井 暁, 那波 明宏, 吉川 史隆

    日本癌学会総会記事   Vol. 78回   page： SS - 1   2019.9

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    Language：English   Publishing type：Research paper, summary (national, other academic conference)   Publisher：日本癌学会  

  5. MITFは卵巣癌細胞において浸潤に寄与している(MITF contributes to cell migration/invasion in ovarian carcinoma cells)

    小屋 美博, 劉 文亭, 杉山 麻衣, 吉原 雅人, 千賀 威, 那波 明宏, 吉川 史隆, 梶山 広明

    日本癌学会総会記事   Vol. 77回   page： 750 - 750   2018.9

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  6. 上皮性卵巣癌における治療標的としての癌関連腹膜中皮細胞(Cancer-associated mesothelial cells as a potential therapeutic target in epithelial ovarian cancer)

    吉原 雅人, 梶山 広明, 杉山 麻衣, 小屋 美博, 劉 文亭, 横井 暁, 山本 雄介, 吉川 史隆

    日本癌学会総会記事   Vol. 77回   page： 271 - 271   2018.9

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    Language：English   Publishing type：Research paper, summary (national, other academic conference)   Publisher：日本癌学会  

  7. Notch経路を介したS1PレセプターのスイッチがEVTの浸潤を制御する

    三木 梨可, 小谷 友美, 澤田 雅子, 小屋 美博, 山下 守, 伊藤 由美子, 牛田 貴文, 今井 健史, 中野 知子, 炭竈 誠二, 吉川 史隆, 那波 明宏

    日本産科婦人科学会雑誌   Vol. 70 ( 2 ) page： 881 - 881   2018.2

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  8. HS1卵巣がんにおける生存不良のリスクが高いことを示す

    劉 文亭, 梶山 広明, 柴田 清住, 小屋 美博, 千賀 威, 吉川 史隆

    日本癌学会総会記事   Vol. 76回   page： P - 1278   2017.9

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To the head of MISC.▲

Presentations 42

  1. 9-oxo-10,12-ODAのヒト子宮頸癌細胞に対する抗腫瘍効果の解析

    小屋 美博, 梶山 広明, 吉原 雅人, 杉山 麻衣, 三木 梨可, 友田 豊, 山下 守, 柴田 清住, 那波 明宏, 吉川 史隆

    日本産科婦人科学会雑誌  2020.3  (公社)日本産科婦人科学会

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    Event date： 2020.3

    Language：Japanese  

  2. 隣接細胞間コミュニケーションによる卵巣癌腹膜播種微小環境の形成

    杉山 麻衣, 梶山 広明, 吉原 雅人, 小屋 美博, 横井 暁, 山下 守, 那波 明宏, 吉川 史隆

    日本産科婦人科学会雑誌  2020.3  (公社)日本産科婦人科学会

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    Event date： 2020.3

    Language：Japanese  

  3. 接着関連因子TJP1はEVTの浸潤を抑制する

    三木 梨可, 小谷 友美, 澤田 雅子, 小屋 美博, 山下 守, 森山 佳則, 牛田 貴文, 今井 健史, 小林 知子, 炭竈 誠二, 吉川 史隆, 那波 明宏

    日本産科婦人科学会雑誌  2020.3  (公社)日本産科婦人科学会

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    Event date： 2020.3

    Language：Japanese  

  4. 9-oxo-10,12-ODAのヒト子宮頸癌細胞に対する抗腫瘍効果の解析(Anti-tumor effect of 9-oxo-10,12-ODA on human cervical cancer cells)

    小屋 美博, 杉山 麻衣, 吉原 雅人, 柴田 清住, 千賀 威, 那波 明宏, 吉川 史隆, 梶山 広明

    日本癌学会総会記事  2019.9  日本癌学会

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    Event date： 2019.9

    Language：English  

  5. 婦人科がんの発生・病態・治療に関する最新の知見 癌関連中皮細胞の卵巣癌腹膜播種進展における役割(Recent advances in generation, biology, and treatment of gynecologic cancer Carcinoma-associated mesothelial cells as a novel therapeutic target in epithelial ovarian cancer)

    吉原 雅人, 梶山 広明, 杉山 麻衣, 小屋 美博, 横井 暁, 伊吉 祥平, 吉川 史隆

    日本癌学会総会記事  2019.9  日本癌学会

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    Event date： 2019.9

    Language：English  

  6. 大網脂肪細胞由来線維芽細胞の卵巣癌腹膜播種微小環境における役割(The roles of omental adipocyte-derived fibroblast in tumor microenvironment at metastatic sites of ovarian cancer)

    伊吉 祥平, 梶山 広明, 吉原 雅人, 中村 香江, 杉山 麻衣, 小屋 美博, 宇野 枢, 吉川 史隆

    日本癌学会総会記事  2019.9  日本癌学会

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    Event date： 2019.9

    Language：English  

  7. 卵巣癌においてCSPG4は細胞浸潤に大きく寄与している(CSPG4 highly contributes to cell invasion in ovarian carcinoma cells)

    宇野 枢, 小屋 美博, 梶山 広明, 杉山 麻衣, 伊吉 祥平, 北見 和久, 吉原 雅人, 那波 明宏, 吉川 史隆

    日本癌学会総会記事  2019.9  日本癌学会

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    Event date： 2019.9

    Language：English  

  8. 上皮性卵巣癌におけるMITFの機能的役割(Function analysis of MITF in epithelial ovarian cancer)

    北見 和久, 小屋 美博, 梶山 広明, 杉山 麻衣, 伊吉 祥平, 宇野 枢, 吉原 雅人, 那波 明宏, 吉川 史隆

    日本癌学会総会記事  2019.9  日本癌学会

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    Event date： 2019.9

    Language：English  

  9. がん研究における女性研究者(第6回) 腹膜中皮細胞はNotchシグナルを介して卵巣がん細胞の増殖を亢進する(Women scientists in cancer research Mesothelial cells promote ovarian cancer proliferation through Notch signaling pathway)

    杉山 麻衣, 梶山 広明, 吉原 雅人, 小屋 美博, 横井 暁, 那波 明宏, 吉川 史隆

    日本癌学会総会記事  2019.9  日本癌学会

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    Event date： 2019.9

    Language：English  

  10. 卵巣がん腹膜播種形成時における腹膜の変化と役割

    杉山 麻衣, 梶山 広明, 吉原 雅人, 小屋 美博, 横井 暁, 山下 守, 那波 明宏, 吉川 史隆

    日本産科婦人科学会雑誌  2019.2  (公社)日本産科婦人科学会

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    Event date： 2019.2

    Language：Japanese  

  11. 転写因子E2F8のEVTにおける役割

    三木 梨可, 小谷 友美, 澤田 雅子, 小屋 美博, 山下 守, 森山 佳則, 牛田 貴文, 今井 健史, 中野 知子, 炭竈 誠二, 那波 明宏, 吉川 史隆

    日本産科婦人科学会雑誌  2019.2  (公社)日本産科婦人科学会

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    Event date： 2019.2

    Language：Japanese  

  12. 葉酸修飾シクロデキストリンによるFOLR1陽性卵巣癌細胞の標的化

    斉藤 伸一, 小屋 美博, 梶山 広明, 山下 守, 吉川 史隆, 那波 明宏

    日本産科婦人科学会雑誌  2019.2  (公社)日本産科婦人科学会

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    Event date： 2019.2

    Language：Japanese  

  13. 卵巣癌においてMITFはCD146を介して細胞浸潤に寄与している

    小屋 美博, 梶山 広明, 杉山 麻衣, 吉原 雅人, 山下 守, 那波 明宏, 吉川 史隆

    日本産科婦人科学会雑誌  2019.2  (公社)日本産科婦人科学会

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    Event date： 2019.2

    Language：Japanese  

  14. MITFは卵巣癌細胞において浸潤に寄与している(MITF contributes to cell migration/invasion in ovarian carcinoma cells)

    小屋 美博, 劉 文亭, 杉山 麻衣, 吉原 雅人, 千賀 威, 那波 明宏, 吉川 史隆, 梶山 広明

    日本癌学会総会記事  2018.9  日本癌学会

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    Event date： 2018.9

    Language：English  

  15. 卵巣癌腹膜播種における腹膜中皮細胞による浸潤フロンティアの形成(Mesothelial cells create invasion frontier in peritoneal metastasis of epithelial ovarian cancer)

    伊吉 祥平, 梶山 広明, 吉原 雅人, 山北 由彦, 杉山 麻衣, 小屋 美博, 劉 文亭, 吉川 史隆

    日本癌学会総会記事  2018.9  日本癌学会

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    Event date： 2018.9

    Language：English  

  16. 上皮性卵巣癌における治療標的としての癌関連腹膜中皮細胞(Cancer-associated mesothelial cells as a potential therapeutic target in epithelial ovarian cancer)

    吉原 雅人, 梶山 広明, 杉山 麻衣, 小屋 美博, 劉 文亭, 横井 暁, 山本 雄介, 吉川 史隆

    日本癌学会総会記事  2018.9  日本癌学会

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    Event date： 2018.9

    Language：English  

  17. Notch経路を介したS1PレセプターのスイッチがEVTの浸潤を制御する

    三木 梨可, 小谷 友美, 澤田 雅子, 小屋 美博, 山下 守, 伊藤 由美子, 牛田 貴文, 今井 健史, 中野 知子, 炭竈 誠二, 吉川 史隆, 那波 明宏

    日本産科婦人科学会雑誌  2018.2  (公社)日本産科婦人科学会

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    Event date： 2018.2

    Language：Japanese  

  18. 表層上皮性卵巣癌におけるNotchシグナルを介した腹膜中皮細胞の役割

    杉山 麻衣, 梶山 広明, 吉原 雅人, 小屋 美博, 横井 暁, 山下 守, 那波 明宏, 吉川 史隆

    日本産科婦人科学会雑誌  2018.2  (公社)日本産科婦人科学会

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    Event date： 2018.2

    Language：Japanese  

  19. 卵巣癌においてCSPG4は細胞浸潤に大きく寄与している

    小屋 美博, 吉原 雅人, 梶山 広明, 山下 守, 吉川 史隆, 那波 明宏

    日本産科婦人科学会雑誌  2018.2  (公社)日本産科婦人科学会

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    Event date： 2018.2

    Language：Japanese  

  20. HS1卵巣がんにおける生存不良のリスクが高いことを示す

    劉 文亭, 梶山 広明, 柴田 清住, 小屋 美博, 千賀 威, 吉川 史隆

    日本癌学会総会記事  2017.9  日本癌学会

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    Event date： 2017.9

    Language：English  

  21. 表層上皮性卵巣癌における癌関連中皮細胞と腫瘍進展およびプラチナ耐性獲得機構

    吉原 雅人, 梶山 広明, 杉山 麻衣, 安井 啓晃, 小屋 美博, 山北 由彦, 劉 文亭, 横井 暁, 山本 雄介, 吉川 史隆

    日本癌学会総会記事  2017.9  日本癌学会

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    Event date： 2017.9

    Language：English  

  22. 表層上皮性卵巣癌におけるNocthシグナルが及ぼす腹膜中皮細胞との微小環境形成への影響

    杉山 麻衣, 梶山 広明, 吉原 雅人, 安井 啓晃, 劉 文亭, 小屋 美博, 山北 由彦, 吉川 史隆

    日本癌学会総会記事  2017.9  日本癌学会

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    Event date： 2017.9

    Language：English  

  23. 卵巣癌細胞におけるHS1の浸潤および腫瘍形成への寄与

    小屋 美博, 劉 文亭, 山北 由彦, 梶山 広明, 千賀 威, 柴田 清住, 那波 明宏, 吉川 史隆

    日本癌学会総会記事  2017.9  日本癌学会

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    Event date： 2017.9

    Language：English  

  24. マウス卵巣がんにおけるGlypican 3の影響(Effect of Glypican 3 overexpression on mouse ovarian cancer)

    駱 晨虹, 柴田 清住, 梶山 広明, 千賀 威, 小屋 美博, 吉川 史隆

    日本癌学会総会記事  2012.8  日本癌学会

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    Event date： 2012.8

    Language：English  

  25. MOLT-4細胞との共培養後のJ22-HL-60細胞におけるHIV-1導入の機序(Mechanism of HIV-1 induction in J22-HL-60 cells after co-culture with MOLT-4 cells)

    斉 曉華, 小屋 美博, 斉藤 達哉, 清水 佐紀, 斉藤 愛記, 大庭 賢二, 山岡 昇司, 山本 直樹

    日本エイズ学会誌  2005.11  (一社)日本エイズ学会

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    Event date： 2005.11

    Language：English  

  26. HIV-1慢性感染細胞株J22HL-60とT細胞株MOLT-4の共培養時におけるHIV-1複製の増強機構

    斉 暁華, 小屋 美博, 清水 佐紀, 和田 学, 大庭 賢二, 山本 直樹

    日本エイズ学会誌  2004.11  (一社)日本エイズ学会

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    Event date： 2004.11

    Language：Japanese  

  27. プロテアソーム阻害剤Bortezomib(VELCADE TM)のATL細胞への効果

    佐藤 賢文, 野坂 生郷, 小屋 美博, 安永 純一郎, 松岡 雅雄

    臨床血液  2003.8  (一社)日本血液学会-東京事務局

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    Event date： 2003.8

    Language：Japanese  

  28. Bortezomib (Velcade (TM)), formerly known as PS-341, inhibits the growth of adult T-cell leukemia cells in vitro and in vivo.

    Y Satou, K Nosaka, Y Koya, J Yasunaga, M Matsuoka

    AIDS RESEARCH AND HUMAN RETROVIRUSES  2003  MARY ANN LIEBERT INC PUBL

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    Event date： 2003

    Language：English  

  29. In vivo effect of humanized anti-Fas antibody against adult T-cell leukemia (ATL).

    M Matsuoka, Y Koya, J Ohsumi, S Yonehara

    AIDS RESEARCH AND HUMAN RETROVIRUSES  2003  MARY ANN LIEBERT INC PUBL

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    Event date： 2003

    Language：English  

  30. In vivo effect of humanized agonistic anti-fas antibody against adult T-cell leukemia (ATL).

    Y Koya, M Maeda, S Takeda, P Miyazato, J Ohsumi, S Yonehara, M Matsuoka

    BLOOD  2002.11  AMER SOC HEMATOLOGY

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    Event date： 2002.11

    Language：English  

  31. ヒト型抗Fas抗体のATL細胞に対するin vivo抗腫瘍効果

    小屋 美博, 前田 道之, 武田 哲, 大隅 潤, 米原 伸, 松岡 雅雄

    日本癌学会総会記事  2002.10  日本癌学会

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    Event date： 2002.10

    Language：Japanese  

  32. ラットHTLV-I腫瘍モデルにおける抗腫瘍免疫の認識抗原解析

    花渕 志野, 大橋 貴, 小屋 美博, 神奈木 真理

    日本免疫学会総会・学術集会記録  2000.11  (NPO)日本免疫学会

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    Event date： 2000.11

    Language：Japanese  

  33. Induction of HTLV-I-infected T-lymphoproliferative disease in animal models and its immunological aspects

    Kannagi M, Ohashi T, Hanabuchi S, Kato H, Koya Y, Yoshiki T

    Leukemia  2000 

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    Event date： 2000

  34. ラットのATLモデル系を用いたHTLV-I Taxに対するDNAワクチンの有効性の解析

    大橋 貴, 竹村 富美代, 花渕 志野, 加藤 大智, 小屋 美博, 塚原 智典, 神奈木 真理

    日本免疫学会総会・学術集会記録  1999.10  (NPO)日本免疫学会

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    Event date： 1999.10

    Language：Japanese  

  35. 組換えワクシニアウイルスを用いた抗HTLV-I腫瘍免疫の検討

    小屋 美博, 大橋 貴, 加藤 大智, 花渕 志野, 竹村 富美代, 鷲山 美樹, 神奈木 真理

    日本免疫学会総会・学術集会記録  1999.10  (NPO)日本免疫学会

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    Event date： 1999.10

    Language：Japanese  

  36. 抗CD80/86抗体を用いたラットATL様疾患誘導

    花渕 志野, 大橋 貴, 小屋 美博, 竹村 富美代, 広川 勝いく, 吉木 敬, 八木田 秀雄, 奥村 康, 神奈木 真理

    日本免疫学会総会・学術集会記録  1999.10  (NPO)日本免疫学会

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    Event date： 1999.10

    Language：Japanese  

  37. ラットモデルにおけるヒトT細胞白血病ウイルスI型(HTLV-I)感染細胞の腫瘍形成と宿主免疫

    神奈木 真理, 大橋 貴, 花渕 志野, 加藤 大智, 小屋 美博, 廣川 勝いく, 松岡 雅雄, 吉木 敬

    日本癌学会総会記事  1999.8  日本癌学会

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    Event date： 1999.8

    Language：Japanese  

  38. HTLV-I経口感染ラットにおいて認められる持続感染と免疫不応答

    加藤 大智, 小屋 美博, 大橋 貴, 花渕 志野, 神奈木 真理

    日本臨床免疫学会会誌  1998.10  日本臨床免疫学会

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    Event date： 1998.10

    Language：Japanese  

  39. 同系ラット生体内における移入HTLV-I感染細胞の長期生存

    小屋 美博, 大橋 貴, 加藤 大智, 花渕 志野, 塚原 智典, 江藤 健一郎, 松岡 雅雄, 神奈木 真理

    日本臨床免疫学会会誌  1998.10  日本臨床免疫学会

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    Event date： 1998.10

    Language：Japanese  

  40. 同系ラット生体内における移入HTL V‐I感染細胞の長期生存

    KOYA YOSHIHIRO, OHASHI TAKASHI, KATO MASATOMO, HANABUCHI SHINO, TSUKAHARA TOMONORI, ETO KEN'ICHIRO, MATSUOKA MASAO, KANNAGI MARI

    日本免疫学会総会・学術集会記録  1998.10  日本臨床免疫学会

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    Event date： 1998.10

    Language：Japanese  

  41. ヌードラットを用いた成人T細胞白血病(ATL)モデルの作出

    大橋 貴, 花渕 志野, 加藤 大智, 小屋 美博, 広川 勝いく, 吉木 敬, 神奈木 真理

    日本臨床免疫学会会誌  1998.10  日本臨床免疫学会

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    Event date： 1998.10

    Language：Japanese  

  42. 【接着分子の全て】細胞機能と接着分子 T細胞の活性化と接着分子

    塚原 智典, 小屋 美博, 久保 誠, 花渕 志野

    臨床免疫  1998.10  (有)科学評論社

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    Event date： 1998.10

    Language：Japanese  

▼display all

To the head of Presentations.▲

KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 腹水中ペプチド・デグラドミクスに注目した進行卵巣癌に対する腹腔内環境戦略の創生

    Grant number：21KK0157  2021.10 - 2025.3

    科学研究費助成事業  国際共同研究加速基金(国際共同研究強化(B))

    梶山 広明, 吉原 雅人, 佐藤 綾人, 横井 暁, 小屋 美博

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    Authorship：Coinvestigator(s) 

    悪性腹水中のジペプチジルペプチダーゼ酵素群を主としたペプチドバランスを、新規の質量分析手法であるTMT-TAILS法を用いたデグラドミクス解析によって明らかにする。また、腹腔内環境を構成する宿主細胞が、腫瘍の「味方」に至る腫瘍側誘導メカニズムに焦点をあて、腹膜中皮、脂肪細胞、および腫瘍随伴マクロファージといった免疫細胞などにおける包括的な機能解析を、「卵巣癌-腹膜間の細胞コミュニケーション」の観点から行う。さらに、アミノペプチダーゼ阻害剤による卵巣癌進行抑制効果を、実験動物モデルを用いて検証し、治療応用への可能性を模索する。

  2. 卵巣癌細胞を貪食した腹膜中皮細胞による抗腫瘍免疫抑制の機序解明と再賦活化法の検討

    Grant number：21K09492  2021.4 - 2024.3

    小屋 美博

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    Authorship：Principal investigator 

    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

  3. Development of new strategic oncolytic virotherapy for advanced ovarian cancer

    Grant number：16K15705  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Nawa Akihiro, KOYA Yoshihiro, YAMAKITA Yoshihiko, MUTOH Yoshifumi

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    Cyclodextrin is readily soluble cyclic oligosaccharides which is also used as the food additive, and are expected to be new carrier of anticancer agents because of their ability to solubilize the hydrophobic compounds by binding at their internal cavity. On the other hand, folate is paid attention as a cancer targeting ligand because folate receptor alpha (FOLR1) is highly expressed in 80% or more of epithelial ovarian cancer. In this study, we examined if the folate-appended cyclodextrin compound (FA-CyD) can specifically target the ovarian cancer cell lines. As a result, it was suggested that FA-CyD targets not only cells expressing FOLR1 but also cells expressing only the proton-coupled folate transporter (PCFT).

To the head of KAKENHI (Grants-in-Aid for Scientific Research).▲