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Researchers Faculty Profiles Home 日本語 English Researchers Menu Japanese Page Nagoya University HP. Back to Home. Personnel Information ▼ ◆ Personnel Information ◆ Degree ◆ Research Interests ◆ Field of expertise (Grants-in-aid for Scientific Research classification) ◆ Research History ◆ Education ◆ Awards Research Activity ▼ ◆ Papers ◆ MISC ◆ Presentations ◆ KAKENHI (Grants-in-Aid for Scientific Research) Education Activity ▼ No achievements Contribution to Society ▼ No achievements × Updated on 2024/04/07  Personnel Information ◆ Profile ◆ Degree ◆ Research Interests ◆ Research Areas ◆ Research History ◆ Education ◆ Awards  Research Activity ◆ Papers ◆ MISC ◆ Presentations ◆ KAKENHI (Grants-in-Aid for Scientific Research)  Education Activity No achievements  Contribution to Society No achievements Updated on 2024/04/07   YOKOI Akira   Organization Nagoya University Hospital Obstetrics and Gynecology Lecturer of hospital Title Lecturer of hospital Degree Degree 1 博士(医学) ( 2017.7   名古屋大学 )  To the head of Degree.▲ Research Interests Research Interests 3 腫瘍生物学 Ovarian cancer リキッドバイオプシー To the head of Research Interests.▲ Research Areas Research Areas 3 Life Science / Tumor diagnostics and therapeutics Life Science / Tumor biology Life Science / Obstetrics and gynecology To the head of Research Areas.▲ Research History Research History 7 名古屋大学高等研究院 講師 2023 名古屋大学医学部附属病院 産科婦人科 講師 2023 名古屋大学高等研究院   助教 2020 - 2023 Nagoya University Hospital   Obstetrics and Gynecology   Assistant Professor 2020 - 2023 Japan Society for Promotion of Science 2018 - 2020 University of Texas, MD Anderson Cancer Center   Postdoctoral Fellow 2018 - 2020   More details Country:United States National Cancer Center, Research Institute 2014 - 2018 ▼display all To the head of Research History.▲ Education Education 1 Nagoya University   Graduate School of Medicine 2014.4 - 2017.7 To the head of Education.▲ Awards Awards 12 医学奨励賞 2024   名古屋大学医学系研究科   JSOG Distinguished Scientific Achievement Award 2023   The Japan Society of Obstetrics and Gynecology   名古屋大学医師会研究奨励賞 2023   一般社団法人 名古屋大学医師会   奨励賞 2022   日本細胞外小胞学会   令和2年度 赤崎賞 2021   名古屋大学   学術奨励賞 2020   尚和会   第九回 名古屋大学石田賞 2020   日本癌学会奨励賞 2020   日本癌学会   Clovis Oncology Post-Doctoral Fellowship Award, USA 2019   Foundation for Women’s Cancer of the Society of Gynecologic Oncology   Research Award 2017 in Global Retreat 2018   Nagoya University Graduate School of Medicine   Best Research Paper Award 2018   Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer 名古屋大学学術奨励賞 2017   名古屋大学   ▼display all To the head of Awards.▲   Papers Papers 94 Spatial exosome analysis using cellulose nanofiber sheets reveals the location heterogeneity of extracellular vesicles. International journal Akira Yokoi, Kosuke Yoshida, Hirotaka Koga, Masami Kitagawa, Yukari Nagao, Mikiko Iida, Shota Kawaguchi, Min Zhang, Jun Nakayama, Yusuke Yamamoto, Yoshinobu Baba, Hiroaki Kajiyama, Takao Yasui Nature communications   Vol. 14 ( 1 ) page: 6915 - 6915   2023.11  More details Language:English   Publishing type:Research paper (scientific journal)   Extracellular vesicles (EVs), including exosomes, are recognized as promising functional targets involved in disease mechanisms. However, the intravital heterogeneity of EVs remains unclear, and the general limitation for analyzing EVs is the need for a certain volume of biofluids. Here, we present cellulose nanofiber (CNF) sheets to resolve these issues. We show that CNF sheets capture and preserve EVs from ~10 μL of biofluid and enable the analysis of bioactive molecules inside EVs. By attaching CNF sheets to moistened organs, we collect EVs in trace amounts of ascites, which is sufficient to perform small RNA sequence analyses. In an ovarian cancer mouse model, we demonstrate that CNF sheets enable the detection of cancer-associated miRNAs from the very early phase when mice did not have apparent ascites, and that EVs from different locations have unique miRNA profiles. By performing CNF sheet analyses in patients, we identify further location-based differences in EV miRNA profiles, with profiles reflecting disease conditions. We conduct spatial exosome analyses using CNF sheets to reveal that ascites EVs from cancer patients exhibit location-dependent heterogeneity. This technique could provide insights into EV biology and suggests a clinical strategy contributing to cancer diagnosis, staging evaluation, and therapy planning. DOI: 10.1038/s41467-023-42593-9 Web of Science Scopus PubMed Identifying high-grade serous ovarian carcinoma-specific extracellular vesicles by polyketone-coated nanowires. International journal Akira Yokoi, Mayu Ukai, Takao Yasui, Yasuhide Inokuma, Kim Hyeon-Deuk, Juntaro Matsuzaki, Kosuke Yoshida, Masami Kitagawa, Kunanon Chattrairat, Mikiko Iida, Taisuke Shimada, Yumehiro Manabe, I-Ya Chang, Eri Asano-Inami, Yoshihiro Koya, Akihiro Nawa, Kae Nakamura, Tohru Kiyono, Tomoyasu Kato, Akihiko Hirakawa, Yusuke Yoshioka, Takahiro Ochiya, Takeshi Hasegawa, Yoshinobu Baba, Yusuke Yamamoto, Hiroaki Kajiyama Science advances   Vol. 9 ( 27 ) page: eade6958   2023.7  More details Language:English   Publishing type:Research paper (scientific journal)   Cancer cell-derived extracellular vesicles (EVs) have unique protein profiles, making them promising targets as disease biomarkers. High-grade serous ovarian carcinoma (HGSOC) is the deadly subtype of epithelial ovarian cancer, and we aimed to identify HGSOC-specific membrane proteins. Small EVs (sEVs) and medium/large EVs (m/lEVs) from cell lines or patient serum and ascites were analyzed by LC-MS/MS, revealing that both EV subtypes had unique proteomic characteristics. Multivalidation steps identified FRα, Claudin-3, and TACSTD2 as HGSOC-specific sEV proteins, but m/lEV-associated candidates were not identified. In addition, for using a simple-to-use microfluidic device for EV isolation, polyketone-coated nanowires (pNWs) were developed, which efficiently purify sEVs from biofluids. Multiplexed array assays of sEVs isolated by pNW showed specific detectability in cancer patients and predicted clinical status. In summary, the HGSOC-specific marker detection by pNW are a promising platform as clinical biomarkers, and these insights provide detailed proteomic aspects of diverse EVs in HGSOC patients. DOI: 10.1126/sciadv.ade6958 Web of Science Scopus PubMed Exosomes and extracellular vesicles: Rethinking the essential values in cancer biology Reviewed International journal Akira Yokoi, Takahiro Ochiya Seminars in Cancer Biology   Vol. 74   page: 79 - 91   2021.9  More details Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV   Extracellular vesicles (EVs) such as exosomes are released by all living cells and contain diverse bioactive molecules, including nucleic acids, proteins, lipids, and metabolites. Accumulating evidence of EV-related functions has revealed that these tiny vesicles can mediate specific cell-to-cell communication. Within the tumor microenvironment, diverse cells are actively interacting with their surroundings via EVs facilitating tumor malignancy by regulating malignant cascades including angiogenesis, immune modulation, and metastasis. This review summarizes the recent studies of fundamental understandings of EVs from the aspect of EV heterogeneity and highlights the role of EVs in the various steps from oncogenic to metastatic processes. The recognition of EV subtypes is necessary to identify which pathways can be affected by EVs and which subtypes can be targeted in therapeutic approaches or liquid biopsies. DOI: 10.1016/j.semcancer.2021.03.032 Web of Science Scopus PubMed Mechanisms of nuclear content loading to exosomes Reviewed International journal Akira Yokoi, Alejandro Villar-Prados, Paul Allen Oliphint, Jianhua Zhang, Xingzhi Song, Peter De Hoff, Robert Morey, Jinsong Liu, Jason Roszik, Karen Clise-Dwyer, Jared K. Burks, Theresa J. O’Halloran, Louise C. Laurent, Anil K. Sood Science Advances   Vol. 5 ( 11 ) page: eaax8849   2019.11  More details Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Association for the Advancement of Science (AAAS)   Exosome cargoes are highly varied and include proteins, small RNAs, and genomic DNA (gDNA). The presence of gDNA suggests that different intracellular compartments contribute to exosome loading, resulting in distinct exosome subpopulations. However, the loading of gDNA and other nuclear contents into exosomes (nExo) remains poorly understood. Here, we identify the relationship between cancer cell micronuclei (MN), which are markers of genomic instability, and nExo formation. Imaging flow cytometry analyses reveal that 10% of exosomes derived from cancer cells and <1% of exosomes derived from blood and ascites from patients with ovarian cancer carry nuclear contents. Treatment with genotoxic drugs resulted in increased MN and nExos both in vitro and in vivo. We observed that multivesicular body precursors and exosomal markers, such as the tetraspanins, directly interact with MN. Collectively, this work provides new insights related to nExos, which have implications for cancer biomarker development. DOI: 10.1126/sciadv.aax8849 PubMed Integrated extracellular microRNA profiling for ovarian cancer screening. Reviewed International journal Akira Yokoi, Juntaro Matsuzaki, Yusuke Yamamoto, Yutaka Yoneoka, Kenta Takahashi, Hanako Shimizu, Takashi Uehara, Mitsuya Ishikawa, Shun-Ichi Ikeda, Takumi Sonoda, Junpei Kawauchi, Satoko Takizawa, Yoshiaki Aoki, Shumpei Niida, Hiromi Sakamoto, Ken Kato, Tomoyasu Kato, Takahiro Ochiya Nature communications   Vol. 9 ( 1 ) page: 4319 - 4319   2018.10  More details Language:English   Publishing type:Research paper (scientific journal)   A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9-10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer. DOI: 10.1038/s41467-018-06434-4 Web of Science Scopus PubMed Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer. Reviewed International journal Akira Yokoi, Yusuke Yoshioka, Yusuke Yamamoto, Mitsuya Ishikawa, Shun-Ichi Ikeda, Tomoyasu Kato, Tohru Kiyono, Fumitaka Takeshita, Hiroaki Kajiyama, Fumitaka Kikkawa, Takahiro Ochiya Nature communications   Vol. 8   page: 14470 - 14470   2017.3  More details Language:English   Publishing type:Research paper (scientific journal)   Advanced ovarian cancers are highly metastatic due to frequent peritoneal dissemination, resulting in dismal prognosis. Here we report the functions of cancer-derived extracellular vesicles (EVs), which are emerging as important mediators of tumour metastasis. The EVs from highly metastatic cells strongly induce metastatic behaviour in moderately metastatic tumours. Notably, the cancer EVs efficiently induce apoptotic cell death in human mesothelial cells in vitro and in vivo, thus resulting in the destruction of the peritoneal mesothelium barrier. Whole transcriptome analysis shows that MMP1 is significantly elevated in mesothelial cells treated with highly metastatic cancer EVs and intact MMP1 mRNAs are selectively packaged in the EVs. Importantly, MMP1 expression in ovarian cancer is tightly correlated with a poor prognosis. Moreover, MMP1 mRNA-carrying EVs exist in the ascites of cancer patients and these EVs also induce apoptosis in mesothelial cells. Our findings elucidate a previously unknown mechanism of peritoneal dissemination via EVs. DOI: 10.1038/ncomms14470 Web of Science Scopus PubMed Serum miRNA as a predictive biomarker for ovarian reserve after endometrioma-cystectomy. International journal Atsushi Yabuki, Ayako Muraoka, Satoko Osuka, Akira Yokoi, Kosuke Yoshida, Masami Kitagawa, Bayasura, Reina Sonehara, Natsuki Miyake, Natsuki Nakanishi, Tomoko Nakamura, Akira Iwase, Hiroaki Kajiyama Reproductive biology   Vol. 24 ( 1 ) page: 100821 - 100821   2024.3  More details Language:English   Publishing type:Research paper (scientific journal)   Ovarian endometrioma (OE) is a common gynecological disease that is often treated with surgery and hormonal treatment. However, ovarian cystectomy can impair the ovarian reserve (OR). Previously, we showed that perioperative administration of dienogest (DNG) is an effective option for OR preservation. However, there were differences in the extent of OR preservation among patients following perioperative DNG treatment. In the current study, we performed a global examination of serum microRNAs (miRNAs) to identify accurate biomarkers that predict post-operative restoration of OR following perioperative DNG treatment. We also sought to identify specific miRNAs related to the anti-Müllerian hormone (AMH). miRNA sequencing was performed on serum samples obtained from twenty-seven patients who received perioperative DNG treatment. Candidate miRNAs were selected by comparing patients whose ORs were restored postoperatively (responder group, n = 7) with those whose ORs were not (non-responder group, n = 7). miR-370-3p and miR-1307-3p were significantly upregulated in the responder group, whereas miR-27b-3p was upregulated in the non-responder group. The pretreatment value of each miRNA could predict DNG responsiveness for OR following ovarian cystectomy (area under the curve [AUC] > 0.8). The quantitative polymerase chain reaction (qPCR) revealed only miR-1307-3p was found to be significantly upregulated in the responder group (P < 0.05). In addition, we identified miR-139-3p, miR-140-3p, and miR-629-5p as AMH-associated miRNAs. The transition of AMH showed a correlation with miR-139-3p (P < 0.05, r = -0.76). The miRNAs identified herein represent potential serum biomarkers of clinical value in predicting OR prior to DNG treatment. DOI: 10.1016/j.repbio.2023.100821 Web of Science Scopus PubMed Small extracellular vesicles in follicular fluids for predicting reproductive outcomes in assisted reproductive technology. International journal Ayako Muraoka, Akira Yokoi, Kosuke Yoshida, Masami Kitagawa, Eri Asano-Inami, Mayuko Murakami, Bayasula, Natsuki Miyake, Natsuki Nakanishi, Tomoko Nakamura, Satoko Osuka, Akira Iwase, Hiroaki Kajiyama Communications medicine   Vol. 4 ( 1 ) page: 33 - 33   2024.2  More details Language:English   Publishing type:Research paper (scientific journal)   BACKGROUND: Assisted reproductive technology accounts for an increasing proportion of infertility treatments, and assessments to predict clinical pregnancy outcomes are desired. Extracellular vesicles exist in follicular fluid, and small non coding RNAs in extracellular vesicles underline the possibility of reflecting pregnancy potential. METHODS: Follicular fluid samples are collected from 20 ovarian follicles of 15 infertile patients undergoing assisted reproductive technology. Extracellular vesicles are isolated by serial centrifugation and small RNA sequencing is performed to investigate the profiles of microRNAs and P-element-induced wimpy testis-interacting RNAs. RESULTS: Small extracellular vesicles with a size range of approximately 100 nm are successfully isolated, and the small non coding RNA profiles of pregnant samples (n = 8) are different from those of non-pregnant samples (n = 12). Fourteen dysregulated small non coding RNAs are selected to identify the independent candidates [mean read count >100, area under the curve >0.8]. Among them, we find that a specific combination of small non coding RNAs (miR-16-2-3p, miR-378a-3p, and miR-483-5p) can predict the pregnant samples more precisely using a receiver operating characteristics curves analysis (area under the curve: 0.96). Furthermore, even in the same patients, the three microRNAs are differentially expressed between pregnant and non-pregnant samples. CONCLUSIONS: Our results demonstrate that small non coding RNAs derived from small extracellular vesicles in follicular fluid can be potential non-invasive biomarkers for predicting pregnancy, leading to their probable application in assisted reproductive technology. Further large-scale studies are required to validate the clinical usefulness of these small non coding RNAs. DOI: 10.1038/s43856-024-00460-8 Web of Science PubMed Uterine leiomyosarcoma cell-derived extracellular vesicles induce the formation of cancer-associated fibroblasts. International journal Yukari Nagao, Akira Yokoi, Kosuke Yoshida, Masami Kitagawa, Eri Asano-Inami, Tomoyasu Kato, Mitsuya Ishikawa, Yusuke Yamamoto, Hiroaki Kajiyama Biochimica et biophysica acta. Molecular basis of disease   Vol. 1870 ( 4 ) page: 167103 - 167103   2024.2  More details Language:English   Publishing type:Research paper (scientific journal)   OBJECTIVE: Uterine leiomyosarcoma (ULMS) is a rare malignant tumor, which is aggressive, and has a poor prognosis even during its early stages. Extracellular vesicles (EVs) carry cargo, such as microRNAs (miRNAs), which are involved in intercellular communication in the tumor microenvironment and other processes. Because there are no studies on EV-related miRNAs in ULMS, we identified EV-related miRNAs in ULMS and examined their function. METHODS: Small EVs (sEVs) and medium/large EVs (m/lEVs) were extracted from ULMS cells by ultracentrifugation and their basic characteristics were evaluated. Then, small RNA sequencing was done to obtain EV-related miRNA profiles. Next, miRNA expression levels in sera and tissues of ULMS patients were compared with those of myoma patients. RESULTS: miR-654-3p and miR-369-3p were indicated to be highly expressed in both sera and tissues of ULMS patients. These two miRNAs are also highly expressed in ULMS cell lines and ULMS-derived EVs. Some cancer-associated fibroblast (CAF) markers were increased when fibroblasts were treated with ULMS-derived EVs. Furthermore, fibroblasts took up EVs derived from ULMS as determined by confocal laser microscopy. In addition, the transfection of the two candidate miRNAs into fibroblasts significantly increased some CAF markers, particularly ACTA2. CONCLUSION: miR-654-3p and miR-369-3p are highly expressed in ULMS-derived EVs, indicating that these EV-related miRNAs induce the formation of cancer-associated fibroblasts. DOI: 10.1016/j.bbadis.2024.167103 Scopus PubMed An update of oncologic and obstetric outcomes of radical trachelectomy for early-stage cervical cancer: The need for further minimally invasive treatment. International journal Satoshi Tamauchi, Shohei Iyoshi, Masato Yoshihara, Kosuke Yoshida, Yoshiki Ikeda, Yusuke Shimizu, Akira Yokoi, Kaoru Niimi, Nobuhisa Yoshikawa, Hiroaki Kajiyama The journal of obstetrics and gynaecology research   Vol. 50 ( 2 ) page: 175 - 181   2024.2  More details Language:English   Publishing type:Research paper (scientific journal)   AIMS: To investigate the oncologic and obstetric outcomes of radical trachelectomy (RT) in patients with early-stage cervical cancer and to evaluate the potential role of fertility-preserving treatments in improving pregnancy outcomes while oncologic status is stable. METHODS: In this single-institution study, we analyzed the oncologic and obstetric outcomes of 67 patients with early-stage cervical cancer who underwent RT at Nagoya University Hospital. RESULTS: The cancer recurrence rate (6.0%) and the mortality rate (1.5%) were comparable with those of previous studies. Of the 46 patients who attempted to conceive after RT, 19 (41.3%) became pregnant, and 16 gave birth. Of these 37.5% delivered at term, and delivery at less than 28 weeks of gestation occurred in 31.3% of pregnancies. CONCLUSIONS: RT is a viable treatment option for selected patients with early-stage cervical cancer. However, the use of less invasive techniques, such as conization/simple trachelectomy and pelvic lymph node dissection, may improve pregnancy outcomes while oncologic status is stable. DOI: 10.1111/jog.15824 Web of Science Scopus PubMed Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. International journal Joshua A Welsh, Deborah C I Goberdhan, Lorraine O&#39;Driscoll, Edit I Buzas, Cherie Blenkiron, Benedetta Bussolati, Houjian Cai, Dolores Di Vizio, Tom A P Driedonks, Uta Erdbrügger, Juan M Falcon-Perez, Qing-Ling Fu, Andrew F Hill, Metka Lenassi, Sai Kiang Lim, Mỹ G Mahoney, Sujata Mohanty, Andreas Möller, Rienk Nieuwland, Takahiro Ochiya, Susmita Sahoo, Ana C Torrecilhas, Lei Zheng, Andries Zijlstra, Sarah Abuelreich, Reem Bagabas, Paolo Bergese, Esther M Bridges, Marco Brucale, Dylan Burger, Randy P Carney, Emanuele Cocucci, Federico Colombo, Rossella Crescitelli, Edveena Hanser, Adrian L Harris, Norman J Haughey, An Hendrix, Alexander R Ivanov, Tijana Jovanovic-Talisman, Nicole A Kruh-Garcia, Vroniqa Ku&#39;ulei-Lyn Faustino, Diego Kyburz, Cecilia Lässer, Kathleen M Lennon, Jan Lötvall, Adam L Maddox, Elena S Martens-Uzunova, Rachel R Mizenko, Lauren A Newman, Andrea Ridolfi, Eva Rohde, Tatu Rojalin, Andrew Rowland, Andras Saftics, Ursula S Sandau, Julie A Saugstad, Faezeh Shekari, Simon Swift, Dmitry Ter-Ovanesyan, Juan P Tosar, Zivile Useckaite, Francesco Valle, Zoltan Varga, Edwin van der Pol, Martijn J C van Herwijnen, Marca H M Wauben, Ann M Wehman, Sarah Williams, Andrea Zendrini, Alan J Zimmerman, Misev Consortium, Clotilde Théry, Kenneth W Witwer Journal of extracellular vesicles   Vol. 13 ( 2 ) page: e12404   2024.2  More details Language:English   Publishing type:Research paper (scientific journal)   Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its &#39;Minimal Information for Studies of Extracellular Vesicles&#39;, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly. DOI: 10.1002/jev2.12404 Scopus PubMed Effect of radical trachelectomy on ovarian reserve: A single-institute prospective study. International journal Atsushi Nakagawa, Satoshi Tamauchi, Mamiko Sato, Masato Yoshihara, Akira Yokoi, Yusuke Shimizu, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kaoru Niimi, Satoko Osuka, Hiroaki Kajiyama The journal of obstetrics and gynaecology research   Vol. 50 ( 2 ) page: 212 - 217   2024.2  More details Language:English   Publishing type:Research paper (scientific journal)   AIM: Reduced responses to controlled ovarian stimulation (COS) after radical trachelectomy (RT) have been previously reported. We aimed to assess the effect of RT on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels before and after the procedure in this prospective study. METHODS: We included 12 patients who underwent RT between September 2019 and December 2021 in this study. Serum AMH levels were measured preoperatively, 1 month postoperatively, and 6 months postoperatively. Differences in the AMH levels were assessed using a paired t-test. RESULTS: The median age of the patients was 30.6 years, and the median follow-up time was 30.1 months. AMH levels at 1 and 6 months postoperatively did not show a consistent trend. At 1 month postoperatively, the average AMH level decreased insignificantly but returned to preoperative levels at 6 months. The differences in AMH levels before and after RT were insignificant. CONCLUSION: Our findings indicate that RT did not affect ovarian reserve as measured by AMH levels. However, the relationship between unchanged ovarian reserve and reduced response to COS remains unclear. Further research with larger sample sizes and additional measures of ovarian function is needed to corroborate these results and investigate the long-term effects of RT on ovarian reserve. Understanding these mechanisms will help guide surgical practices and provide patients with valuable information about their reproductive outcomes after RT. DOI: 10.1111/jog.15828 Web of Science Scopus PubMed Emerging bacterial factors for understanding pathogenesis of endometriosis. International journal Ayako Muraoka, Akira Yokoi, Hiroaki Kajiyama iScience   Vol. 27 ( 1 ) page: 108739 - 108739   2024.1  More details Language:English   Publishing type:Research paper (scientific journal)   The pathogenesis of endometriosis is a complex process, and recent research has introduced novel hypotheses in this field. This review summarizes recent studies on the pathogenesis of endometriosis. We focused on several classical hypotheses, as well as their interactions with the microenvironment of hormonal dependence and immunosuppression. Furthermore, we highlighted the emergence of bacterial factors associated with endometriosis. Recent advances in next-generation sequencing (NGS) have revealed the presence and detailed distribution of these bacteria as well as the involvement of specific bacteria in pathogenesis. These factors alter the microenvironment in the early stages of endometriosis development, leading to lesion formation. Understanding the mechanisms underlying the early development of endometriosis from a new perspective would be helpful for the development of novel therapeutic agents for endometriosis. DOI: 10.1016/j.isci.2023.108739 Web of Science Scopus PubMed Mean platelet volume as a potential biomarker for survival outcomes in ovarian clear cell carcinoma. Nobuhisa Yoshikawa, Tetsuya Matsukawa, Satomi Hattori, Shohei Iyoshi, Kosuke Yoshida, Masato Yoshihara, Satoshi Tamauchi, Yusuke Shimizu, Yoshiki Ikeda, Akira Yokoi, Kaoru Niimi, Michiyasu Kawai, Hiroaki Kajiyama International journal of clinical oncology   Vol. 28 ( 12 ) page: 1680 - 1689   2023.12  More details Language:English   Publishing type:Research paper (scientific journal)   OBJECTIVE: This study aimed to explore the prognostic value of mean platelet volume (MPV) in patients with ovarian clear cell carcinoma (OCCC) and evaluate the predictive performance of a random forest model incorporating MPV and other key clinicopathological factors. METHODS: A total of 204 patients with OCCC treated between January 2004 and December 2019 were retrospectively analyzed. Clinicopathological characteristics and preoperative laboratory data were collected, and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional hazards models. An optimal MPV cutoff was determined by receiver operating characteristic (ROC) curve analysis. A random forest model was then constructed using the identified independent prognostic factors, and its predictive performance was evaluated. RESULTS: The ROC analysis identified 9.3 fL as the MPV cutoff value for predicting 2-year survival. The MPV-low group had lower 5-year overall survival and progression-free survival rates than the MPV-high group (p = 0.003 and p = 0.034, respectively). High MPV emerged as an independent prognostic factor (p = 0.006). The random forest model, incorporating the FIGO stage, residual tumors, peritoneal cytology, and MPV, demonstrated robust predictive performance (area under the curve: 0.905). CONCLUSION: MPV is a promising prognostic indicator in OCCC. Lower MPV correlated with worse survival rates, advocating its potential utility in refining patient management strategies. The commendable predictive performance of the random forest model, integrating MPV and other significant prognostic factors, suggests a pathway toward enhanced survival prediction, thereby warranting further research. DOI: 10.1007/s10147-023-02417-8 Web of Science Scopus PubMed Establishment and characterization of a non-gestational choriocarcinoma patient-derived xenograft model. International journal Yukari Oda, Kaoru Niimi, Kosuke Yoshida, Satoshi Tamauchi, Akira Yokoi, Yuko Yasui, Yuki Nishiko, Mayu Shibata, Yusuke Shimizu, Masato Yoshihara, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kimihiro Nishino, Eiko Yamamoto, Hiroaki Kajiyama BMC cancer   Vol. 23 ( 1 ) page: 1103 - 1103   2023.11  More details Language:English   Publishing type:Research paper (scientific journal)   BACKGROUND: Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. METHODS: Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. RESULTS: The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour. CONCLUSIONS: We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC. DOI: 10.1186/s12885-023-11626-3 Web of Science Scopus PubMed 9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins. International journal Kazumasa Mogi, Yoshihiro Koya, Masato Yoshihara, Mai Sugiyama, Rika Miki, Emiri Miyamoto, Hiroki Fujimoto, Kazuhisa Kitami, Shohei Iyoshi, Sho Tano, Kaname Uno, Satoshi Tamauchi, Akira Yokoi, Yusuke Shimizu, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kaoru Niimi, Yoshihiko Yamakita, Hiroyuki Tomita, Kiyosumi Shibata, Akihiro Nawa, Yutaka Tomoda, Hiroaki Kajiyama Scientific reports   Vol. 13 ( 1 ) page: 19208 - 19208   2023.11  More details Language:English   Publishing type:Research paper (scientific journal)   Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25-50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer. DOI: 10.1038/s41598-023-44365-3 Web of Science Scopus PubMed Small Extracellular Vesicles from adipose-derived stem cells suppress cell proliferation by delivering the let-7 family of microRNAs in ovarian cancer. International journal Hironori Suzuki, Akira Yokoi, Kaname Uno, Kosuke Yoshida, Masami Kitagawa, Eri Asano-Inami, Seiko Matsuo, Yukari Nagao, Kazuhiro Suzuki, Kae Nakamura, Masato Yoshihara, Satoshi Tamauchi, Yusuke Shimizu, Yoshiki Ikeda, Nobuhisa Yoshikawa, Hiroaki Kajiyama, Yusuke Yamamoto Biochemical and biophysical research communications   Vol. 680   page: 211 - 219   2023.11  More details Language:English   Publishing type:Research paper (scientific journal)   INTRODUCTION: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines. MATERIALS AND METHODS: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was investigated using IncuCyte and microRNA sequencing. Moreover, the potential functions of miRNAs were evaluated by gain-of function analysis and in silico analysis. RESULTS: ADSC-EVs suppressed SKOV3 and OV90 cell proliferation. In particular, small EVs (sEVs) from ADSCs exhibited a stronger antitumor effect than ADSC-medium/large EVs (m/lEVs). Comparison of the miRNA profiles between ADSC-sEVs and ADSC-m/lEVs, along with downstream pathway analysis, suggested the involvement of the let-7 family. Overexpression of hsa-let-7b-5p and hsa-let-7e-5p significantly suppressed the proliferation of SKOV3 cells. In silico analysis revealed that four potential target genes of hsa-let-7b-5p and hsa-let-7e-5p were significantly associated with the prognoses of the patients. CONCLUSION: ADSC-sEVs had a stronger antitumor effect than ADSC-m/lEVs. Hsa-let-7b-5p and hsa-let-7e-5p, which are highly abundant in ADSC-sEVs, suppressed cell proliferation. These findings may open up new possibilities for therapeutic approaches using ADSC-sEVs. DOI: 10.1016/j.bbrc.2023.09.022 Web of Science Scopus PubMed The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer. International journal Kaname Uno, Nobuhisa Yoshikawa, Kazuhisa Kitami, Sho Mori, Takahiro Shibata, Shohei Iyoshi, Hiroki Fujimoto, Kazumasa Mogi, Masato Yoshihara, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Kazuyoshi Kato, Tsutomu Hoshiba, Hidenori Oguchi, Hiroaki Kajiyama Japanese journal of clinical oncology   Vol. 53 ( 10 ) page: 942 - 949   2023.10  More details Language:English   Publishing type:Research paper (scientific journal)   OBJECTIVE: The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. METHODS: We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. RESULTS: The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29-5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18-8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31-10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage. CONCLUSIONS: The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage. DOI: 10.1093/jjco/hyad086 Web of Science Scopus PubMed Interleukin-17A stimulation induces alterations in Microglial microRNA expression profiles. International journal Yukako Iitani, Rika Miki, Kenji Imai, Kazuya Fuma, Takafumi Ushida, Sho Tano, Kosuke Yoshida, Akira Yokoi, Hiroaki Kajiyama, Tomomi Kotani Pediatric research   Vol. 95 ( 1 ) page: 167 - 173   2023.9  More details Language:English   Publishing type:Research paper (scientific journal)   BACKGROUND: Increased maternal interleukin (IL)-17A and activated microglia are pivotal factors contributing to the pathological phenotypes of maternal immune activation (MIA), developing neurodevelopmental disorders in offspring. This study aimed to determine whether IL-17A affects the microglial microRNA (miRNA) profiles. METHODS: The miRNA expression profiles of primary cultured microglia stimulated with recombinant IL-17A were examined comprehensively using miRNA sequencing and validated through qRT-PCR. The expressions of miRNAs target genes identified using bioinformatics, were investigated in microglia transfected with mimic miRNA. The target gene&#39;s expression was also examined in the fetal brains of the MIA mouse model induced by maternal lipopolysaccharide (LPS) administration. RESULTS: Primary cultured microglia expressed the IL-17A receptor and increased proinflammatory cytokines and nitric oxide synthase 2 upon treatment with IL-17A. Among the three miRNAs with |log2FC | >1, only mmu-miR-206-3p expression was significantly up-regulated by IL-17A. Transfection with the mmu-miR-206-3p mimic resulted in a significant decrease in the expression of Hdac4 and Igf1, target genes of mmu-miR-206-3p. Hdac4 expression also significantly decreased in the LPS-induced MIA model. CONCLUSIONS: IL-17A affected microglial miRNA profiles with upregulated mmu-miR-206-3p. These findings suggest that targeting the IL-17A/mmu-miR-206-3p pathway may be a new strategy for predicting MIA-related neurodevelopmental deficits and providing preventive interventions. IMPACT: Despite the growing evidence of interleukin (IL)-17A and microglia in the pathology of maternal immune activation (MIA), the downstream of IL-17A in microglia is not fully known. IL-17A altered microRNA profiles and upregulated the mmu-miR-206-3p expression in microglia. The mmu-miR-206-3p reduced autism spectrum disorder (ASD) related gene expressions, Hdac4 and Igf1. The Hdac4 expression was also reduced in the brain of MIA offspring. The hsa-miR-206 sequence is consistent with that of mmu-miR-206-3p. This study may provide clues to pathological mechanisms leading to predictions and interventions for ASD children born to mothers with IL-17A-related disorders. DOI: 10.1038/s41390-023-02825-6 Web of Science Scopus PubMed DDIT4 Facilitates Lymph Node Metastasis via the Activation of NF-κB Pathway and Epithelial-Mesenchymal Transition. International journal Xinxin Lin, Nobuhisa Yoshikawa, Wenting Liu, Tetsuya Matsukawa, Kae Nakamura, Masato Yoshihara, Yoshihiro Koya, Mai Sugiyama, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Yusuke Shimizu, Hiroaki Kajiyama Reproductive sciences (Thousand Oaks, Calif.)   Vol. 30 ( 9 ) page: 2829 - 2841   2023.9  More details Language:English   Publishing type:Research paper (scientific journal)   This study was aimed to identify a novel metastasis-promoting molecule and elucidate its functional and prognostic roles in cervical cancer. DDIT4 (DNA-damage-inducible transcript 4), a hypoxia-inducible gene, was identified by analyzing multiple microarray databases. The correlation between DDIT4 expression in immunohistochemistry and clinicopathological characteristics in the public database and our cohort was evaluated by statistical analysis. Transwell® assay and wound-healing assay to determine cell migration and invasion were performed. DDIT4 was knocked down using siRNA or lentiviral vectors. The potential downstream pathways of DDIT4 were explored and verified by a gene set enrichment analysis and western blotting. The in vivo metastatic capability was determined with the use of an intraperitoneal injection mouse model. In the analysis of the public database and our cohort, DDIT4 high expression was significantly related to short overall survival and lymph node metastasis in patients with early-stage cervical cancer. The knockdown of DDIT4 attenuated the migration and invasion activity of tumor cells in vitro and reduced the expression of epithelial-mesenchymal transition (EMT)-related proteins and the NF-κB pathway in cervical cancer cells. DDIT4 also promoted tumor progression in the mouse model. Our results indicate that DDIT4 can be a prognostic indicator in cervical cancer and promote lymph node metastasis, augmenting malignancy via the EMT and NF-kB pathways. DOI: 10.1007/s43032-023-01230-y Web of Science Scopus PubMed Downregulating vaccinia-related kinase 1 by luteolin suppresses ovarian cancer cell proliferation by activating the p53 signaling pathway. International journal Xuboya Chang, Satoshi Tamauchi, Kosuke Yoshida, Masato Yoshihara, Akira Yokoi, Yusuke Shimizu, Yoshiki Ikeda, Nobuhisa Yoshikawa, Tohru Kiyono, Yusuke Yamamoto, Hiroaki Kajiyama Gynecologic oncology   Vol. 173   page: 31 - 40   2023.6  More details Language:English   Publishing type:Research paper (scientific journal)   OBJECTIVES: Ovarian cancer constitutes one of the most common causes of cancer-related deaths, and preventing chemotherapy resistance and recurrence in patients with ovarian cancer remains a challenge. Herein, we aimed to identify the effect of luteolin, a novel therapeutic agent targeting vaccinia-related kinase 1 (VRK1), on high-grade serous ovarian cancer (HGSOC). METHODS: Phosphokinase array, RNA sequencing, and cell cycle and apoptosis assays were conducted to determine the underlying mechanism of the effect of luteolin on HGSOC cells. The anticancer effects of oral and intraperitoneal luteolin administration were assessed in patient-derived xenograft models via several methods, including the assessment of tumor size and immunohistochemistry of phospho-p53, phosphor-HistoneH3 and cleaved caspase 3. RESULTS: Luteolin reduced HGSOC cell proliferation and increased apoptosis and cell cycle arrest at G2/M. Compared with controls, several genes were dysregulated in luteolin-treated cells, and luteolin activated the p53 signaling pathway. The human phosphokinase array revealed distinct p53 upregulation in luteolin-treated cells, as confirmed by p53 phosphorylation at ser15 and ser46 using western blot analysis. In patient-derived xenograft models, oral or intraperitoneal luteolin administration substantially suppressed tumor growth. Moreover, combination treatment involving luteolin and cisplatin inhibited tumor cell proliferation, especially in cisplatin-resistant HGSOC cell lines. CONCLUSIONS: Luteolin demonstrated considerable anticancer effect on HGSOC cells, reduced VRK1 expression, and activated the p53 signaling pathway, thereby inducing apoptosis and cell cycle arrest in G2/M and inhibiting cell proliferation. Furthermore, luteolin exhibited a synergistic effect with cisplatin both in vivo and in vitro. Thus, luteolin can be considered a promising cotreatment option for HGSOC. DOI: 10.1016/j.ygyno.2023.04.003 Web of Science Scopus PubMed Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach Reviewed Kosuke Yoshida, Akira Yokoi, Masami Kitagawa, Mai Sugiyama, Tomofumi Yamamoto, Jun Nakayama, Hiroshi Yoshida, Tomoyasu Kato, Hiroaki Kajiyama, Yusuke Yamamoto Oncology Reports   Vol. 49 ( 5 )   2023.5  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Spandidos Publications   DOI: 10.3892/or.2023.8523 Web of Science Scopus PubMed Preoperative serum microRNAs as potential prognostic biomarkers in ovarian clear cell carcinoma. Reviewed International journal Kazuhiro Suzuki, Akira Yokoi, Kosuke Yoshida, Tomoyasu Kato, Takahiro Ochiya, Yusuke Yamamoto, Hiroaki Kajiyama Journal of gynecologic oncology   Vol. 34 ( 3 ) page: e34 - 3310   2023.5  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本癌学会   OBJECTIVE: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian carcinoma with poor prognosis. However, no effective biomarkers have been established for predicting unfavorable events, including recurrence and poor prognoses. Serum microRNAs (miRNAs) have been increasingly reported to be useful in predicting a patient&#39;s condition and have been recognized as a potentially less-invasive source for liquid biopsy in cancer. Therefore, this study aimed to evaluate serum miRNA profiles from patients with OCCC and to establish biomarker for predicting the prognoses. METHODS: The GSE106817, which included preoperative serum miRNA profiles of patients with ovarian tumors, was used, and clinical information was investigated. In all, 66 patients with OCCC were included, excluding those with other histological subtypes or insufficient prognostic information. Moreover, miRNA profiles of OCCC tissues were also examined. RESULTS: The median follow-up period was 64.3 (8.0-153.3) months. Based on multivariable Cox regression analyses and the expression of miRNAs in OCCC tissues, miR-150-3p, miR-3195, and miR-7704 were selected as miRNA candidates associated with both progression-free survival (PFS) and overall survival (OS). Then, the prognostic index was calculated based on expression values of 3 serum miRNAs. Kaplan-Meier survival analysis indicated that the prognostic index was significantly predictive of PFS and OS (p=0.004 and p=0.012, respectively). CONCLUSION: Preoperative serum miRNA profiles of miR-150-3p, miR-3195, and miR-7704 can be used to potentially predict the prognosis of patients with OCCC. DOI: 10.3802/jgo.2023.34.e34 Web of Science Scopus PubMed The association of UBAP2L and G3BP1 mediated by small nucleolar RNA is essential for stress granule formation. Reviewed International journal Eri Asano-Inami, Akira Yokoi, Mai Sugiyama, Toshinori Hyodo, Tomonari Hamaguchi, Hiroaki Kajiyama Communications biology   Vol. 6 ( 1 ) page: 415 - 415   2023.4  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Stress granules (SGs) are dynamic, non-membranous structures composed of non-translating mRNAs and various proteins and play critical roles in cell survival under stressed conditions. Extensive proteomics analyses have been performed to identify proteins in SGs; however, the molecular functions of these components in SG formation remain unclear. In this report, we show that ubiquitin-associated protein 2-like (UBAP2L) is a crucial component of SGs. UBAP2L localized to SGs in response to various stresses, and its depletion significantly suppressed SG organization. Proteomics and RNA sequencing analyses found that UBAP2L formed a protein-RNA complex with Ras-GTP-activating protein SH3 domain binding protein 1 (G3BP1) and small nucleolar RNAs (snoRNAs). In vitro binding analysis demonstrated that snoRNAs were required for UBAP2L association with G3BP1. In addition, decreased expression of snoRNAs reduced the interaction between UBAP2L and G3BP1 and suppressed SG formation. Our results reveal a critical role of SG component, the UBAP2L/snoRNA/G3BP1 protein-RNA complex, and provide new insights into the regulation of SG assembly. DOI: 10.1038/s42003-023-04754-w Web of Science Scopus PubMed Novel therapeutic strategies targeting UCP2 in uterine leiomyosarcoma. Reviewed International journal Yukari Nagao, Akira Yokoi, Kosuke Yoshida, Mai Sugiyama, Eri Watanabe, Kae Nakamura, Masami Kitagawa, Eri Asano-Inami, Yoshihiro Koya, Masato Yoshihara, Satoshi Tamauchi, Yusuke Shimizu, Yoshiki Ikeda, Nobuhisa Yoshikawa, Tomoyasu Kato, Yusuke Yamamoto, Hiroaki Kajiyama Pharmacological research   Vol. 189   page: 106693 - 106693   2023.3  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Uterine leiomyosarcoma (ULMS) is a malignant stromal tumor arising from the myometrium with a poor prognosis and very limited response to current chemotherapy. This study aimed to identify novel targets for ULMS through a three-step screening process using a chemical library consisting of 1,271 Food and Drug Administration-approved drugs. First, we evaluated their inhibitory effects on ULMS cells and identified four candidates: proscillaridin A, lanatoside C, floxuridine, and digoxin. Then, we subcutaneously or orthotopically transplanted SK-UT-1 cells into mice to establish mouse models. In vivo analyses showed that proscillaridin A and lanatoside C exerted a superior anti-tumor effect. The results of mRNA sequencing showed that uncoupling protein 2 (UCP2) was suppressed in the sirtuin signaling pathway, increasing reactive oxygen species (ROS) and inducing cell death. Moreover, the downregulation of UCP2 induced ROS and suppressed ULMS cell growth. Furthermore, analyses using clinical samples showed that UCP2 expression was significantly upregulated in ULMS tissues than in myoma tissues both at the RNA and protein levels. These findings suggested that UCP2 is a potential therapeutic target and can contribute to the development of novel therapeutic strategies in patients with ULMS. DOI: 10.1016/j.phrs.2023.106693 Web of Science Scopus PubMed Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma. Reviewed International journal Eri Watanabe, Akira Yokoi, Kosuke Yoshida, Mai Sugiyama, Masami Kitagawa, Kimihiro Nishino, Eiko Yamamoto, Kaoru Niimi, Yusuke Yamamoto, Hiroaki Kajiyama Cancer medicine   Vol. 12 ( 4 ) page: 4543 - 4556   2023.2  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   BACKGROUND: Choriocarcinoma is a rare and aggressive gynecological malignancy. The standard treatment is systemic chemotherapy as choriocarcinoma exhibits high chemosensitivity. However, refractory choriocarcinoma exhibits chemoresistance; thus, the prognosis remains very poor. This study aimed to identify novel therapeutic agents for choriocarcinoma by utilizing a drug repositioning strategy. METHODS: Three choriocarcinoma cell lines (JAR, JEG-3, and BeWo) and a human extravillous trophoblast cell line (HTR-8/SVneo) were used for the analyses. The growth inhibitory effects of 1,271 FDA-approved compounds were evaluated in vitro screening assays and selected drugs were tested in tumor-bearing mice. Functional analyses of drug effects were performed based on RNA sequencing. RESULTS: Muti-step screening identified vorinostat, camptothecin (S, +), topotecan, proscillaridin A, and digoxin as exhibiting an anti-cancer effect in choriocarcinoma cells. Vorinostat, a histone deacetylase inhibitor, was selected as a promising candidate for validation and the IC50 values for choriocarcinoma cells were approximately 1 μM. RNA sequencing and subsequent pathway analysis revealed that the ferroptosis pathway was likely implicated, and key ferroptosis-related genes (i.e., GPX4, NRF2, and SLC3A2) were downregulated following vorinostat treatment. Furthermore, vorinostat repressed tumor growth and downregulated the expression of GPX4 and NRF2 in JAR cell-bearing mice model. CONCLUSION: Vorinostat, a clinically approved drug for the treatment of advanced primary cutaneous T-cell lymphoma, showed a remarkable anticancer effect both in vitro and in vivo by regulating the expression of ferroptosis-related genes. Therefore, vorinostat may be an effective therapeutic candidate for patients with choriocarcinoma. DOI: 10.1002/cam4.5243 Web of Science Scopus PubMed Tumor suppressive miRNAs in small extracellular vesicles derived from ADSCs shows anti-tumor capacity in ovarian cancer Suzuki, H; Yokoi, A; Uekusa, R; Kitagawa, M; Yoshida, K; Uno, K; Kajiyama, H CANCER SCIENCE   Vol. 114   page: 1374 - 1374   2023.2  More details Web of Science Preoperative serum microRNAs as potential prognostic biomarkers in ovarian clear cell carcinoma Suzuki, K; Yokoi, A; Yoshida, K; Kato, T; Ochiya, T; Yamamoto, Y; Kajiyama, H CANCER SCIENCE   Vol. 114   page: 1986 - 1986   2023.2  More details Web of Science Novel exosome analyses for micro volume ascites in ovarian cancer dissemination Yokoi, A; Yasui, T; Yoshida, K; Kitagawa, M; Kajiyama, H CANCER SCIENCE   Vol. 114   page: 20 - 20   2023.2  More details Web of Science Notch signaling can be a new therapeutic target for advanced ovarian cancer Sugiyama, M; Yoshihara, M; Koya, Y; Kitami, K; Uno, K; Iyoshi, S; Mogi, K; Yokoi, A; Nakamura, K; Nawa, A; Kajiyama, H CANCER SCIENCE   Vol. 114   page: 2065 - 2065   2023.2  More details Web of Science Identifying Copy Number Variations in Extracellular Vesicles as a Novel Biomarker of High Grade Serous Ovarian Carcinoma Uekusa, R; Yokoi, A; Kitagawa, M; Yoshida, K; Yoshihara, M; Tamauchi, S; Niimi, K; Matsuzaki, J; Yamamoto, Y; Kajiyama, H CANCER SCIENCE   Vol. 114   page: 1063 - 1063   2023.2  More details Web of Science Aberrant activation of cell cycle-related kinases as novel therapeutic targets for uterine leiomyosarcoma Yoshida, K; Yokoi, A; Kato, T; Kajiyama, H; Yamamoto, Y CANCER SCIENCE   Vol. 114   page: 1457 - 1457   2023.2  More details Web of Science Aberrant activation of cell cycle-related kinases as novel therapeutic targets for uterine leiomyosarcoma Yoshida, K; Yokoi, A; Kato, T; Kajiyama, H; Yamamoto, Y CANCER SCIENCE   Vol. 114   page: 913 - 913   2023.2  More details Web of Science Development of mortality prediction models for infants with isolated, left-sided congenital diaphragmatic hernia before and after birth Yoneda Kota, Amari Shoichiro, Mikami Masashi, Uchida Keiichi, Yokoi Akiko, Okawada Manabu, Furukawa Taizo, Toyoshima Katsuaki, Inamura Noboru, Okazaki Tadaharu, Yamoto Masaya, Masumoto Kouji, Terui Keita, Okuyama Hiroomi, Hayakawa Masahiro, Taguchi Tomoaki, Usui Noriaki, Isayama Tetsuya PEDIATRIC PULMONOLOGY   Vol. 58 ( 1 ) page: 152 - 160   2023.1  More details Language:English   Publisher:Pediatric Pulmonology   Background: Mortality prediction of congenital diaphragmatic hernia (CDH) is essential for developing treatment strategies, including fetal therapy. Several researchers have reported prognostic factors for this rare but life-threatening condition; however, the optimal combination of prognostic factors remains to be elucidated. Objectives: This study aimed to develop the most discriminative prenatal and postnatal models to predict the mortality of infants with an isolated left-sided CDH. Methods: This multi-institutional retrospective cohort study included infants with CDH born at 15 tertiary hospitals of the Japanese CDH Study Group between 2011 and 2016. We developed multivariable logistic models with every possible combination of predictors and identified models with the highest cross-validated area under the receiver operating characteristic curve (AUC) for prenatal and postnatal predictions. Results: Among 302 eligible infants, 44 died before discharge. The prenatal mortality prediction model was based on the observed/expected lung area to head circumference ratio (O/E LHR), liver herniation, and stomach herniation (AUC, 0.830). The postnatal mortality prediction model was based on O/E LHR, liver herniation, and the lowest oxygenation index (AUC, 0.944). Conclusion: Our models can facilitate the prenatal and postnatal mortality prediction of infants with isolated left-sided CDH. DOI: 10.1002/ppul.26172 Web of Science Scopus PubMed The prognostic significance of DDIT4 in endometrial cancer. International journal Nobuhisa Yoshikawa, Kosuke Yoshida, Wenting Liu, Tetsuya Matsukawa, Satomi Hattori, Masato Yoshihara, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Yusuke Shimizu, Kaoru Niimi, Hiroaki Kajiyama Cancer biomarkers : section A of Disease markers   Vol. 37 ( 4 ) page: 217 - 225   2023  More details Language:English   Publishing type:Research paper (scientific journal)   BACKGROUND: Despite extensive research on endometrial cancer and tumor hypoxic microenvironment, there are no reports exploring the role of DDIT4 in endometrial cancer. OBJECTIVE: This study aimed to elucidate the significance of DDIT4, as a prognostic biomarker for endometrial cancer by immunohistochemical staining and statistical analysis. METHODS: Four endometrial cancer cells were cultured under normoxia and hypoxia, and the differentially expressed genes were examined using RNA-seq. Immunohistochemical staining for DDIT4 and HIF1A was performed in 86 patients with type II endometrial cancer treated at our hospital, and their correlation with other clinicopathological factors and the prognostic role was analyzed using statistical methods. RESULTS: The expression analysis of hypoxia-inducible genes using four types of endometrial cancer cells revealed that DDIT4 was among the 28 genes that were upregulated in all cells. Based on our results of immunohistochemistry of DDIT4 expression in endometrial cancer tissues, univariate and multivariate analyses based on COX regression analysis showed that high DDIT4 expression significantly correlated to favorable prognosis in both progression-free survival and overall survival. Limited to recurrent cases, metastasis to only lymph nodes was significantly related to high DDIT4 expression, whereas metastasis to other parenchymal organs was significantly dominant in patients with low DDIT4 expression. CONCLUSIONS: The expression of DDIT4 enables to predict survival and recurrence in type II endometrial cancer. DOI: 10.3233/CBM-220368 Web of Science Scopus PubMed Prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia: a systematic review and meta-analysis Masahata Kazunori, Yamoto Masaya, Umeda Satoshi, Nagata Kouji, Terui Keita, Fujii Makoto, Shiraishi Masayuki, Hayakawa Masahiro, Amari Shoichiro, Masumoto Kouji, Okazaki Tadaharu, Inamura Noboru, Toyoshima Katsuaki, Koike Yuki, Furukawa Taizo, Yazaki Yuta, Yokoi Akiko, Endo Masayuki, Tazuke Yuko, Okuyama Hiroomi, Usui Noriaki PEDIATRIC SURGERY INTERNATIONAL   Vol. 38 ( 12 ) page: 1745 - 1757   2022.12  More details Language:English   Publisher:Pediatric Surgery International   Purpose: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). Methods: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. Results: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65–30.89], 11.14 (95% CI 5.19–23.89), and 10.28 (95% CI 3.38–31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. Conclusions: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH. DOI: 10.1007/s00383-022-05232-w Web of Science Scopus PubMed Hypoalbuminemia for the prediction of survival in patients with stage IVB cervical cancer. International journal Nobuhisa Yoshikawa, Masato Yoshihara, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Hiroaki Kajiyama PloS one   Vol. 17 ( 9 ) page: e0273876   2022.9  More details Language:English   Publishing type:Research paper (scientific journal)   We evaluated the prognostic significance of malnutrition in patients with metastatic cervical cancer. In this study, we retrospectively analyzed the cases of 43 patients with stage IVB (FIGO2018) cervical cancer treated at our institute from December 2004 to December 2017. We determined the correlation between clinicopathological characteristics and survival by performing univariate and multivariate analyses. The serum albumin value at diagnosis was used as an index of malnutrition. The median follow-up period was 16.4 months (range, 0.9-91.4 months). On Kaplan-Meier analysis, the 1- and 2-year overall survival (OS) rates for all patients were 61.6% and 48.6%, respectively. The optimal serum albumin for predicting 1-year survival was 3.3 g/dL, as determined by the receiver operating characteristic curve to maximize the area under the curve. The OS of the patients with albumin >3.3 g/dL (n = 28) was significantly better than that of the patients with albumin ≤3.3 g/dL (n = 15) (p = 0.004). The univariate and multivariate analyses revealed that pretreatment serum albumin and mode of primary treatment were significantly associated with survival in patients with stage IVB cervical cancer. Hypoalbuminemia was an unfavorable prognostic factor for patients with metastatic cervical cancer. DOI: 10.1371/journal.pone.0273876 Web of Science Scopus PubMed 卵巣がん細胞外小胞の機能解析と臨床応用へ向けた基盤研究 横井 暁 日本婦人科腫瘍学会雑誌   Vol. 40 ( 3 ) page: 159 - 166   2022.7  More details Language:Japanese   Publisher:公益社団法人 日本婦人科腫瘍学会   DOI: 10.57291/jsgo.40.3_159 CiNii Research Survival benefits of retroperitoneal lymphadenectomy for optimally-resected advanced ovarian high-grade serous carcinoma: a multi-institutional retrospective study. Reviewed International journal Yoshiki Ikeda, Masato Yoshihara, Satoshi Tamauchi, Akira Yokoi, Nobuhisa Yoshikawa, Hiroaki Kajiyama Journal of gynecologic oncology   Vol. 33 ( 4 ) page: e40   2022.7  More details Language:English   Publishing type:Research paper (scientific journal)   OBJECTIVE: The survival benefits of retroperitoneal lymphadenectomy (RLNA) for epithelial ovarian cancer (EOC) remain controversial because clinical behaviors differ among subtypes. The purpose of the present study was to clarify whether RLNA increases the survival rate of advanced high-grade serous carcinoma (HGSC). METHODS: This was a retrospective cohort analysis of 3,227 patients with EOC treated between 1986 and 2017 at 14 institutions. Among them, 335 patients with stage IIB-IV HGSC who underwent optimal cytoreduction (residual tumor of <1 cm) were included. Patients were divided into the RLNA group (n=170) and non-RLNA group (n=165). All pathological slides were assessed based on a central pathological review. Oncologic outcomes were compared between the two groups in the original and weighted cohorts adjusted with the inverse probability of treatment weighting. RESULTS: The median observation period was 49.8 (0.5-241.5) months. Overall, 219 (65%) out of 335 patients had recurrence or progression, while 146 (44%) died of the disease. In the original cohort, RLNA was a significant prognostic factor for longer progression-free survival (PFS) (hazard ratio [HR]=0.741; 95% confidence interval [CI]=0.558-0.985) and overall survival (OS) (HR=0.652; 95% CI=0.459-0.927). In the weighted cohort in which all variables were well balanced as standardized differences decreased, RLNA was also a significant prognostic factor for more favorable oncologic outcomes (PFS, adjusted HR=0.742; 95% CI=0.613-0.899) and OS, adjusted HR=0.620; 95% CI=0.488-0.787). CONCLUSION: The present study demonstrated that RLNA for stage III-IV HGSC with no residual tumor after primary debulking surgery contributed to better oncologic outcomes. DOI: 10.3802/jgo.2022.33.e40 Web of Science Scopus PubMed CiNii Research Long-Term Outcomes of Congenital Diaphragmatic Hernia: Report of a Multicenter Study in Japan Yamoto Masaya, Nagata Kouji, Terui Keita, Hayakawa Masahiro, Okuyama Hiroomi, Amari Shoichiro, Yokoi Akiko, Masumoto Kouji, Okazaki Tadaharu, Inamura Noboru, Toyoshima Katsuaki, Koike Yuhki, Yazaki Yuta, Furukawa Taizo, Usui Noriaki CHILDREN-BASEL   Vol. 9 ( 6 )   2022.6  More details Language:English   Publisher:Children   Background: Treatment modalities for neonates with congenital diaphragmatic hernia (CDH) have greatly improved in recent years, with a concomitant increase in survival. However, long-term outcomes restrict the identification of optimal care pathways for CDH survivors in adolescence and adulthood. Therefore, we evaluated the long-term outcomes within the Japanese CDH Study Group (JCDHSG). Methods: Participants were born with CDH between 2006 and 2018 according to the JCDHSG. Participants were enrolled in the database at 1.5, 3, 6, and 12 years old. Follow-up items included long-term complications, operations for long-term complication, and home medical care. Results: A total of 747 patients were included in this study, with 626 survivors (83.8%) and 121 non-survivors (16.2%). At 1.5, 3, 6, and 12 years old, 45.4%, 36.5%, 34.8%, and 43.6% developed complications, and 20.1%, 14.7%, 11.5%, and 5.1% of participants required home care, respectively. Recurrence, pneumonia, pneumothorax, gastroesophageal reflux disease, and intestinal obstruction decreased with age, and thoracic deformity increased with age. Conclusions: As CDH survival rates improve, there is a need for continued research and fine-tuning of long-term care to optimize appropriate surveillance and long-term follow-up. DOI: 10.3390/children9060856 Web of Science Scopus PubMed Aberrant activation of cell cycle-related kinases and the potential therapeutic impact of PLK1 or CHEK1 inhibition in uterine leiomyosarcoma. Reviewed International journal Kosuke Yoshida, Akira Yokoi, Tomofumi Yamamoto, Yusuke Hayashi, Jun Nakayama, Tsuyoshi Yokoi, Hiroshi Yoshida, Tomoyasu Kato, Hiroaki Kajiyama, Yusuke Yamamoto Clinical cancer research : an official journal of the American Association for Cancer Research   Vol. 28 ( 10 ) page: 2147 - 2159   2022.5  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   PURPOSE: Uterine leiomyosarcoma is among the most aggressive gynecological malignancies. No effective treatment strategies have been established. This study aimed to identify novel therapeutic targets for uterine leiomyosarcoma based on transcriptome analysis and assess the preclinical efficacy of novel drug candidates. EXPERIMENTAL DESIGN: Transcriptome analysis was performed using fresh-frozen samples of six uterine leiomyosarcomas and three myomas. The Ingenuity Pathway Analysis was used to identify potential therapeutic target genes for uterine leiomyosarcoma. Afterward, our results were validated using three independent datasets, including 40 uterine leiomyosarcomas. Then, the inhibitory effects of several selective inhibitors for the candidate genes were examined using SK-UT-1, SK-LMS-1, and SKN cell lines. RESULTS: We identified 512 considerably dysregulated genes in uterine leiomyosarcoma compared with myoma. The Ingenuity Pathway Analysis revealed that the function of several genes, including CHEK1 and PLK1, were predicted to be activated in uterine leiomyosarcoma. Through an in vitro drug screening, PLK1 or CHEK1 inhibitors (BI-2536 or prexasertib) were found to exert a superior anti-cancer effect against cell lines at low nanomolar concentrations and induce cell cycle arrest. In SK-UT-1 tumor-bearing mice, BI-2536 monotherapy remarkably suppressed tumorigenicity. Moreover, the prexasertib and cisplatin combination therapy inhibited tumor proliferation and prolonged the time to tumor progression. CONCLUSIONS: We identified upregulated expressions of PLK1 and CHEK1; their kinase activity was activated in uterine leiomyosarcoma. BI-2536 and prexasertib demonstrated a significant anti-cancer effect. Therefore, cell cycle-related kinases may present a promising therapeutic strategy for the treatment of uterine leiomyosarcoma. DOI: 10.1158/1078-0432.CCR-22-0100 Web of Science Scopus PubMed CiNii Research Is cystectomy an option as conservative surgery for young patients with borderline ovarian tumor? A multi-institutional retrospective study. International journal Yoshiki Ikeda, Masato Yoshihara, Nobuhisa Yoshikawa, Satoshi Tamauchi, Akira Yokoi, Kimihiro Nishino, Kaoru Niimi, Hiroaki Kajiyama International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics   Vol. 157 ( 2 ) page: 437 - 443   2022.5  More details Language:English   Publishing type:Research paper (scientific journal)   OBJECTIVE: We investigated the impact of cystectomy for borderline ovarian tumor (BOT) on tumor recurrence in comparison with those receiving salpingo-oophorectomy using the inverse probability of treatment weighting (IPTW). METHODS: Between 1986 and 2017, 4,708 women with a malignant ovarian neoplasm were collected after a central pathological review and search of the medical records from 14 collaborating institutions. Among them, a total of 285 young women with stage I BOT were extracted. To compare recurrence-free survival (RFS) between the surgery groups, Cox regression analyses and IPTW-adjusted Kaplan-Meier method were employed. RESULTS: During a median follow-up of 62.0 (1.2-270.4) months, 10 patients (3.5%) developed recurrence. In multivariate analysis, the practice of cystectomy was not a significant prognostic indicator of RFS {hazard ratio (95% confidence interval): 1.276 (0.150-10.864), P=0.823}. In the IPTW-adjusted cohort, the 5-year RFS rates were 95.8 and 96.0% in patients receiving cystectomy and salpingo-oophorectomy, respectively (P=0.378). CONCLUSION: If patients are selected appropriately, cystectomy in itself may not increase tumor recurrence in young women with early-stage BOT. A large-scale prospective clinical study is necessary to validate this finding. DOI: 10.1002/ijgo.13844 Web of Science Scopus PubMed Peritoneal Restoration by Repurposing Vitamin D Inhibits Ovarian Cancer Dissemination via Blockade of the TGF-β1/Thrombospondin-1 Axis. Reviewed 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  More details Language:English   Publishing type:Research paper (scientific journal)   PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 Web of Science Scopus PubMed CiNii Research Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis. Reviewed International journal Yoshiki Ikeda, Masato Yoshihara, Nobuhisa Yoshikawa, Akira Yokoi, Satoshi Tamauchi, Kimihiro Nishino, Kaoru Niimi, Hiroaki Kajiyama BMC women&#39;s health   Vol. 22 ( 1 ) page: 80 - 80   2022.3  More details Language:English   Publishing type:Research paper (scientific journal)   OBJECTIVE: In young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients&#39; survival. METHODS: Between 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts. RESULTS: During 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234-1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330-2.669), P = 0.905}. CONCLUSIONS: Even after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS. DOI: 10.1186/s12905-022-01642-z Web of Science Scopus PubMed CiNii Research Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy. Reviewed 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  More details Language:English   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 Web of Science Scopus PubMed CiNii Research Adjuvant taxane plus platinum chemotherapy for stage I ovarian clear cell carcinoma with complete surgical staging: are more than three cycles necessary? Mayu Ukai, Shiro Suzuki, Masato Yoshihara, Akira Yokoi, Nobuhisa Yoshikawa, Hiroaki Kajiyama, Fumitaka Kikkawa International Journal of Clinical Oncology   Vol. 27 ( 3 ) page: 609 - 618   2022.3  More details Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC   BACKGROUND: Previous studies on adjuvant chemotherapy for patients with ovarian clear cell carcinoma (OCCC) have included a limited number of Asian patients with surgical stage I OCCC, despite differences in OCCC survival by race and stage. The aim of this study was to estimate the survival effect of the number of cycles of adjuvant taxane plus carboplatin chemotherapy in Asian patients with surgical stage I OCCC. METHODS: We retrospectively identified 227 patients with surgical stage I OCCC at 14 institutions from 1995 to 2017. Kaplan-Meier analysis and Cox proportional hazard regression with inverse probability of treatment weighting (IPTW) adjustment were performed to evaluate overall survival (OS) and recurrence-free survival (RFS) in patients receiving ≤ 3 and 4-6 cycles of taxane plus platinum adjuvant chemotherapy. RESULTS: Eighty-nine and 138 patients received ≤ 3 and 4-6 cycles of adjuvant chemotherapy, respectively. There was no between-group difference in OS or RFS with or without IPTW adjustment. In Cox proportional hazards analysis, 4-6 cycles of adjuvant chemotherapy were not associated with improved OS (HR 1.090; 95% CI 0.518-2.291; p = 0.821) or RFS (HR 1.144; 95% CI 0.619-2.114; p = 0.669) compared to ≤ 3 cycles, even with IPTW adjustment. Subgroup analysis in different substages of stage I OCCC showed that the number of cycles of adjuvant chemotherapy had no impact on OS or RFS. CONCLUSION: Three or fewer cycles of taxane plus carboplatin chemotherapy may be a reasonable treatment regime for patients with surgical staging I OCCC. DOI: 10.1007/s10147-021-02075-8 Web of Science Scopus PubMed Other Link: https://link.springer.com/article/10.1007/s10147-021-02075-8/fulltext.html Adipose-mesothelial crosstalk regulates peritoneal tumor microenvironment and accelerates metastasis of ovarian cancer Mogi, K; Yoshihara, M; Uno, K; Iyoshi, S; Kitami, K; Sugiyama, M; Koya, Y; Tamauchi, S; Yokoi, A; Yoshikawa, N; Nawa, A; Kajiyama, H CANCER SCIENCE   Vol. 113   page: 735 - 735   2022.2  More details Web of Science Vitamin D inhibits mesothelial-mesenchymal-transition accelerating peritoneal dissemination in ovarian cancer via THBS1 Kitami, K; Yoshihara, M; Sugiyama, M; Koya, Y; Yamakita, Y; Iyoshi, S; Uno, K; Mogi, K; Tamauchi, S; Yokoi, A; Yoshikawa, N; Nishino, K; Niimi, K; Nawa, A; Kajiyama, H CANCER SCIENCE   Vol. 113   page: 729 - 729   2022.2  More details Web of Science Prognostic impact of extracellular miRNAs in patients with high-grade serous ovarian carcinoma Yoshida, K; Yokoi, A; Matsuzaki, J; Kato, T; Ochiya, T; Kajiyama, H; Yamamoto, Y CANCER SCIENCE   Vol. 113   page: 1788 - 1788   2022.2  More details Web of Science Notch signaling contributes to drug resistance acquisition through metabolic alteration in advanced ovarian cancer Sugiyama, M; Yoshihara, M; Koya, Y; Kitami, K; Uno, K; Iyoshi, S; Mogi, K; Yokoi, A; Nawa, A; Kajiyama, H CANCER SCIENCE   Vol. 113   page: 1280 - 1280   2022.2  More details Web of Science Drug repositioning screening for an inhibitor of EV secretion in ovarian cancer cells Yoshioka, Y; Yokoi, A; Ochiya, T CANCER SCIENCE   Vol. 113   page: 1410 - 1410   2022.2  More details Web of Science Discovering novel therapeutic agents for uterine leiomyosarcoma Nagao, Y; Yokoi, A; Yoshida, K; Watanabe, E; Yoshihara, M; Tamauchi, S; Yoshikawa, N; Yamamoto, Y; Kato, T; Kajiyama, H CANCER SCIENCE   Vol. 113   page: 1181 - 1181   2022.2  More details Web of Science Chemical library-based drug repositioning strategy for choriocarcinoma therapy Watanabe, E; Yokoi, A; Yoshida, K; Yamamoto, Y; Nishino, K; Niimi, K; Kajiyama, H CANCER SCIENCE   Vol. 113   page: 1501 - 1501   2022.2  More details Web of Science Anti-tumor capacity of specific contents in small extracellular vesicles derived from ADSCs in ovarian cancer Yokoi, A; Yoshida, K; Uno, K; Kajiyama, H CANCER SCIENCE   Vol. 113   page: 1408 - 1408   2022.2  More details Web of Science A case of fistula cancer in Crohn&#39;s disease indistinguishable preoperatively from Bartholin&#39;s adenocarcinoma Matsui Mami, Niimi Kaoru, Yoshihara Masato, Tamauchi Satoshi, Yokoi Akira, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Kajiyama Hiroaki Japanese Journal of Gynecological Oncology   Vol. 40 ( 1 ) page: 10 - 16   2022.1  More details Language:Japanese   Publisher:Japan Society of Gynecologic Oncology  

Adenocarcinoma of the vulva is rare. Lesions of the posterior vaginal vestibule are often assumed to be primary lesions of the Bartholin&#39;s glands. We report a case where vulvar adenocarcinoma in a Crohn&#39;s disease patient was diagnosed as cancer arising from an anal fistula following resection. A 48-year-old woman received treatment for Crohn&#39;s disease. Six months prior, she had a tumor of the left vulvar area, close to the vaginal vestibule. Adenocarcinoma was confirmed based on biopsy results. Upper and lower gastrointestinal endoscopy performed was negative. Accordingly, Bartholin&#39;s adenocarcinoma was suspected. On the first visit, a 4 cm mass was found in the left Bartholin&#39;s gland area. CT revealed mild bilateral inguinal lymph node hypertrophy. We performed simple vulvectomy and bilateral inguinal lymph node sampling for biopsy. The pathological diagnosis was moderately different from adenocarcinoma. A continuity was observed between the colonic mucosal epithelium and the adenocarcinoma. Accordingly, anal fistula cancer was confirmed. The excision margin was positive on the deep exfoliated surface of the left vaginal wall. Subsequently, robot-assisted laparoscopic abdominal perineal resection, vaginal perineal resection, colon stoma construction, and inguinal lymph node dissection were performed. Capecitabine plus oxaliplatin (CAPOX) chemotherapy is currently being administered to the patient. Vulvar adenocarcinoma with Crohn&#39;s disease should be scrutinized with suspicion of anal fistula cancer.

DOI: 10.57291/jsgo.40.1_10 CiNii Research Integrative transcriptomics analysis for uterine leiomyosarcoma identifies aberrant activation of cell cycle-dependent kinases and their potential therapeutic significance. Kosuke Yoshida, Akira Yokoi, Tomofumi Yamamoto, Yusuke Hayashi, Jun Nakayama, Tsuyoshi Yokoi, Hiroshi Yoshida, Tomoyasu Kato, Hiroaki Kajiyama, Yusuke Yamamoto     2022.1  More details Publisher:Cold Spring Harbor Laboratory   Purpose: Uterine leiomyosarcoma is among the most aggressive gynecological malignancies. No effective treatment strategies have been established. This study aimed to identify novel therapeutic targets for uterine leiomyosarcoma based on transcriptome analysis and assess the preclinical efficacy of novel drug candidates.Experimental Design: Transcriptome analysis was carried out using fresh-frozen samples of six uterine leiomyosarcomas and three myomas. The Ingenuity Pathway Analysis was then used to identify potential therapeutic target genes for uterine leiomyosarcoma. Moreover, our results were validated using three independent datasets, including 40 uterine leiomyosarcomas. Then, the inhibitory effects of several selective inhibitors for the candidate genes were examined using the SK-UT-1, SK-LMS-1, and SKN cell lines.Results: We identified 512 considerably dysregulated genes in uterine leiomyosarcoma compared with myoma. The Ingenuity Pathway Analysis showed that the function of several genes, including CHEK1 and PLK1, were predicted to be activated in uterine leiomyosarcoma. Through an in vitro drug screening, PLK1 or CHEK1 inhibitors (BI 2536 or prexasertib) were found to exert a superior anti-cancer effect against cell lines at low nanomolar concentrations and induced cell cycle arrest. In SK-UT-1 tumor-bearing mice, BI 2536 monotherapy demonstrated a marked tumor regression. Moreover, the prexasertib and cisplatin combination therapy also reduced tumorigenicity and prolonged survival.Conclusion: We identified the upregulated expression of PLK1 and CHEK1; their kinase activity was considered to be activated in uterine leiomyosarcoma. BI 2536 and prexasertib demonstrate a significant anti-cancer effect; thus, cell cycle-related kinases may represent a promising therapeutic strategy for treating uterine leiomyosarcoma. DOI: 10.1101/2022.01.06.22268775 Clinical effects of cervical conization with positive margins in cervical cancer. Reviewed International journal Yukari Nagao, Akira Yokoi, Kosuke Yoshida, Masanori Sumi, Masato Yoshihara, Satoshi Tamauchi, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kimihiro Nishino, Kaoru Niimi, Hiroaki Kajiyama Scientific reports   Vol. 11 ( 1 ) page: 23288 - 23288   2021.12  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Radical surgery after cervical conization is a common approach for the treatment of cervical cancer. In some cases, disease progression is observed after positive margins at conization, but the effect of conization on disease progression remains unclear. Thus, the aim of this study was to investigate the clinical outcomes of positive margins at conization in cervical cancer. A total of 101 patients who underwent cervical conization before radical hysterectomy and pelvic lymph node dissection were considered eligible by reviewing medical records. The association between the positive margins and patient outcomes, including subsequent lymph node metastasis, was evaluated. The rate of lymphovascular space invasion (LVSI) positivity at radical surgery was significantly higher in patients with positive margins (p = 0.017) than in those with negative margins, although there was no significant difference in the rate of pelvic lymph node metastasis (p = 0.155). Moreover, there was no significant difference in the overall survival or progression-free survival between the two groups (p = 0.332 and 0.200, respectively). A positive margin at conization presented no significant prognostic disadvantage; thus, diagnostic conization is one of the most suitable treatment options for early-stage cervical cancer that is difficult to accurately assess. DOI: 10.1038/s41598-021-02635-y Web of Science Scopus PubMed Extracellular microRNA profiling for prognostic prediction in patients with high‐grade serous ovarian carcinoma Reviewed International journal Kosuke Yoshida, Akira Yokoi, Juntaro Matsuzaki, Tomoyasu Kato, Takahiro Ochiya, Hiroaki Kajiyama, Yusuke Yamamoto Cancer Science   Vol. 112 ( 12 ) page: 4977 - 4986   2021.12  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley   High-grade serous ovarian carcinoma is a leading cause of death in female patients worldwide. MicroRNAs (miRNAs) are stable noncoding RNAs in the peripheral blood that reflect a patient&#39;s condition, and therefore, they have received substantial attention as noninvasive biomarkers in various diseases. We previously reported the usefulness of serum miRNAs as diagnostic biomarkers. Here, we investigated the prognostic impact of the serum miRNA profile. We used the GSE106817 dataset, which included preoperative miRNA profiles of patients with ovarian malignancies. Excluding patients with other malignancy or insufficient prognostic information, we included 175 patients with high-grade serous ovarian carcinoma. All patients except four underwent surgery and received chemotherapy as initial treatment. The median follow-up period was 54.6 months (range, 3.5-144.1 months). Univariate Cox regression analysis revealed that higher levels of miR-187-5p and miR-6870-5p were associated with both poorer progression-free survival (PFS) and overall survival (OS), and miR-1908-5p, miR-6727-5p, and miR-6850-5p were poor prognostic indicators of PFS. The OS and PFS prognostic indices were then calculated using the expression values of three prognostic miRNAs. Multivariate Cox regression analysis showed that both indices were significantly independent poor prognostic factors (hazard ratio for OS and PFS, 2.343 [P = .015] and 2.357 [P = .005], respectively). In conclusion, circulating miRNA profiles can potentially provide information to predict the prognosis of patients with high-grade serous ovarian carcinoma. Therefore, there is a strong demand for early clinical application of circulating miRNAs as noninvasive biomarkers. DOI: 10.1111/cas.15154 Web of Science Scopus PubMed Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.15154 CD63-mediated cloaking of VEGF in small extracellular vesicles contributes to anti-VEGF therapy resistance. International journal Shaolin Ma, Lingegowda S Mangala, Wen Hu, Emine Bayaktar, Akira Yokoi, Wei Hu, Sunila Pradeep, Sanghoon Lee, Paul D Piehowski, Alejandro Villar-Prados, Sherry Y Wu, Michael H McGuire, Olivia D Lara, Cristian Rodriguez-Aguayo, Christopher J LaFargue, Nicholas B Jennings, Karin D Rodland, Tao Liu, Vikas Kundra, Prahlad T Ram, Sundaram Ramakrishnan, Gabriel Lopez-Berestein, Robert L Coleman, Anil K Sood Cell reports   Vol. 36 ( 7 ) page: 109549 - 109549   2021.8  More details Language:English   Publishing type:Research paper (scientific journal)   Despite wide use of anti-vascular endothelial growth factor (VEGF) therapy for many solid cancers, most individuals become resistant to this therapy, leading to disease progression. Therefore, new biomarkers and strategies for blocking adaptive resistance of cancer to anti-VEGF therapy are needed. As described here, we demonstrate that cancer-derived small extracellular vesicles package increasing quantities of VEGF and other factors in response to anti-VEGF therapy. The packaging process of VEGF into small extracellular vesicles (EVs) is mediated by the tetraspanin CD63. Furthermore, small EV-VEGF (eVEGF) is not accessible to anti-VEGF antibodies and can trigger intracrine VEGF signaling in endothelial cells. eVEGF promotes angiogenesis and enhances tumor growth despite bevacizumab treatment. These data demonstrate a mechanism where VEGF is partitioned into small EVs and promotes tumor angiogenesis and progression. These findings have clinical implications for biomarkers and therapeutic strategies for ovarian cancer. DOI: 10.1016/j.celrep.2021.109549 PubMed Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer. International journal Kosuke Yoshida, Nobuhisa Yoshikawa, Kazuhisa Kitami, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Kimihiro Nishino, Kaoru Niimi, Hiroaki Kajiyama Cancer cell international   Vol. 21 ( 1 ) page: 314 - 314   2021.6  More details Language:English   Publishing type:Research paper (scientific journal)   BACKGROUND: Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. The characteristics of metastatic cancer may differ from those of primary ovarian cancer and reflect the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers. METHODS: Patients with advanced epithelial ovarian cancer were eligible for this study. Five patients underwent surgery and resection of paired primary ovarian and omental metastatic cancer at Nagoya University. Metabolome analysis was performed in these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch&#39;s t-test was used for comparisons between two independent groups. RESULTS: Metabolite profiles were all different, which reflects diversity among these cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, in some cases, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers. With regard to histological subtype, the total levels of amino acids, especially the percentage of glutamine, were significantly enriched in serous carcinomas compared with nonserous carcinomas (p = 0.004 and p = 0.001). Moreover, the reduced forms of glutathione and polyamines were also more abundant in serous carcinomas than in nonserous carcinomas (p = 0.025 and 0.048). CONCLUSIONS: The metabolite profiles differed depending on tumor location and histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers. DOI: 10.1186/s12935-021-02014-7 Web of Science Scopus PubMed Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer. Reviewed International journal Satomi Hattori, Nobuhisa Yoshikawa, Kazumasa Mogi, Kosuke Yoshida, Masato Yoshihara, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Kimihiro Nishino, Kaoru Niimi, Shiro Suzuki, Hiroaki Kajiyama Current oncology (Toronto, Ont.)   Vol. 28 ( 3 ) page: 1663 - 1672   2021.6  More details Language:English   Publishing type:Research paper (scientific journal)   (1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer. DOI: 10.3390/curroncol28030155 Web of Science Scopus PubMed ChrXq27.3 miRNA cluster functions in cancer development. Reviewed International journal Kosuke Yoshida, Akira Yokoi, Yusuke Yamamoto, Hiroaki Kajiyama Journal of experimental & clinical cancer research : CR   Vol. 40 ( 1 ) page: 112 - 112   2021.3  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   MicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial-mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888-892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets. DOI: 10.1186/s13046-021-01910-0 Web of Science Scopus PubMed Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance. Reviewed International journal Kosuke Yoshida, Akira Yokoi, Mai Sugiyama, Shingo Oda, Kazuhisa Kitami, Satoshi Tamauchi, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kimihiro Nishino, Kaoru Niimi, Shiro Suzuki, Fumitaka Kikkawa, Tsuyoshi Yokoi, Hiroaki Kajiyama Oncogene   Vol. 40 ( 7 ) page: 1255 - 1268   2021.2  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer and exhibits dismal prognosis due to chemoresistance. Moreover, only few effective therapeutic options exist for patients with recurrent OCCC, and an understanding of its molecular characteristics is essential for the development of novel therapeutic approaches. In the present study, we investigated unique MicroRNAs (miRNA) profiles in recurrent/metastatic OCCC and the role of miRNAs in cisplatin resistance. Comprehensive miRNA sequencing revealed that expression of several miRNAs, including miR-508-3p, miR-509-3p, miR-509-3-5p, and miR-514a-3p was remarkably less in recurrent cancer tissues when compared with that in paired primary cancer tissues. These miRNAs are located in the chrXq27.3 region on the genome. Moreover, its expression was negative in omental metastases in two patients with advanced OCCC. In vitro analyses revealed that overexpression of miR-509-3p and miR-509-3-5p reversed cisplatin resistance and yes-associated protein 1 (YAP1) was partially responsible for the resistance. Immunohistochemistry revealed that YAP1 expression was inversely correlated with the chrXq27.3 miRNA cluster expression. In conclusion, these findings suggest that alteration of the chrXq27.3 miRNA cluster could play a critical role in chemoresistance and miRNAs in the cluster and their target genes can be potential therapeutic targets. DOI: 10.1038/s41388-020-01595-3 Web of Science Scopus PubMed Gain-of-function p53 protein transferred via small extracellular vesicles promotes conversion of fibroblasts to a cancer-associated phenotype. Reviewed International journal Shaolin Ma, Michael H McGuire, Lingegowda S Mangala, Sanghoon Lee, Elaine Stur, Wen Hu, Emine Bayraktar, Alejandro Villar-Prados, Cristina Ivan, Sherry Y Wu, Akira Yokoi, Santosh K Dasari, Nicholas B Jennings, Jinsong Liu, Gabriel Lopez-Berestein, Prahlad Ram, Anil K Sood Cell reports   Vol. 34 ( 6 ) page: 108726 - 108726   2021.2  More details Language:English   Publishing type:Research paper (scientific journal)   Tumor and stromal interactions consist of reciprocal signaling through cytokines, growth factors, direct cell-cell interactions, and extracellular vesicles (EVs). Small EVs (≤200 nm) have been considered critical messengers of cellular communication during tumor development. Here, we demonstrate that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to fibroblasts. GOF p53 protein is selectively bound by heat shock protein 90 (HSP90), a chaperone protein, and packaged into small EVs. Inhibition of HSP90 activity blocks packaging of GOF, but not wild-type, p53 in small EVs. GOF p53-containing small EVs result in their conversion to cancer-associated fibroblasts. In vivo studies reveal that GOF p53-containing small EVs can enhance tumor growth and promote fibroblast transformation into a cancer-associated phenotype. These findings provide a better understanding of the complex interactions between cancer and stromal cells and may have therapeutic implications. DOI: 10.1016/j.celrep.2021.108726 PubMed The role of chrXq27.3 miRNA cluster in advanced ovarian clear cell carcinoma Reviewed International journal Yoshida, K; Yokoi, A; Yoshihara, M; Tamauchi, S; Yoshikawa, N; Nishino, K; Niimi, K; Kikkawa, F; Kajiyama, H CANCER SCIENCE   Vol. 112   page: 291 - 291   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science Luteolin suppresses Ovarian Cancer progression via decrease the expression of VRK1 Reviewed International journal Chang, XY; Kajiyama, H; Yoshikawa, N; Yokoi, A; Tamauchi, S; Yoshihara, M CANCER SCIENCE   Vol. 112   page: 770 - 770   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science Intra-tumoral polarity induced by Notch signaling can be a novel therapeutic target for advanced ovarian cancer Reviewed International journal Yoshihara, M; Sugiyama, M; Koya, Y; Iyoshi, S; Kitami, K; Uno, K; Mogi, K; Tano, S; Tamauchi, S; Yokoi, A; Yoshikawa, N; Nawa, A; Kajiyama, H CANCER SCIENCE   Vol. 112   page: 363 - 363   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science How do peritoneal mesothelial cells on adipose tissue attract ovarian cancer cells? Reviewed International journal Mogi, K; Yoshihara, M; Kitami, K; Iyoshi, S; Uno, K; Tano, S; Sugiyama, M; Koya, Y; Tamauchi, S; Yokoi, A; Yoshikawa, N; Nawa, A; Kajiyama, H CANCER SCIENCE   Vol. 112   page: 341 - 341   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science Extracellular miRNAs as Predictive Biomarkers for Glypican-3-Derived Peptide Vaccine Therapy Response in Ovarian Clear Cell Carcinoma Reviewed International journal Mayu Ukai, Akira Yokoi, Kosuke Yoshida, Shiro Suzuki, Kiyosumi Shibata, Fumitaka Kikkawa, Tetsuya Nakatsura, Hiroaki Kajiyama Cancers   Vol. 13 ( 3 ) page: 550 - 550   2021.2  More details Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG   Ovarian clear cell carcinoma (OCCC) has been treated with surgery and chemotherapy; however, the prognosis remains poor because of chemoresistance. Therefore, immunotherapies are attracting attention, including the GPC3 peptide vaccine, which improves overall survival. However, the response rate is limited and there are no sufficient predictive biomarkers that can identify responders before treatment. Our purpose was to identify circulating serum miRNAs as predictive biomarkers for response to GPC3 peptide vaccine. Eighty-four patients in a phase II trial of a GPC3 peptide vaccine were enrolled and miRNA sequencing was performed on their serum samples. Candidate miRNAs were selected from a group of 14 patients for whom treatment was responsive and validated in an independent group of 10 patients for whom treatment was responsive. Three markedly upregulated miRNAs, miR-375-3p, miR-193a-5p, and miR-1228-5p, were identified, and the combination of those miRNAs demonstrated high value in the prediction of the response. The origin of these miRNAs was assessed by referring to OCCC tissue miRNA profiles, and they were not identified as cancer tissue-related miRNAs. Functional annotation analysis suggested that they were associated with interferon-related pathways. The miRNAs identified herein have great potential to allow the realization of liquid biopsy for predicting the immunotherapy response and precision medicine. DOI: 10.3390/cancers13030550 Web of Science Scopus PubMed Exploring the biological roles of extracellular vesicles carrying nucleic acids in ovarian cancer Reviewed International journal Yokoi, A CANCER SCIENCE   Vol. 112   page: 204 - 204   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science Comprehensive analyses of small extracellular vesicles carrying nucleic acids in ovarian cancer Reviewed International journal Yokoi, A; Ochiya, T CANCER SCIENCE   Vol. 112   page: 973 - 973   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science Active vitamin D inhibits mesothelial-mesenchymal-transition accelerating peritoneal dissemination in ovarian cancer Reviewed International journal Kitami, K; Yoshihara, M; Sugiyama, M; Koya, Y; Iyoshi, S; Uno, K; Mogi, K; Tamauchi, S; Yokoi, A; Yoshikawa, N; Nawa, A; Kajiyama, H CANCER SCIENCE   Vol. 112   page: 351 - 351   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science A novel approach for liquid biopsy by using nuclear derived exosomes in ovarian cancer Reviewed International journal Yokoi, A CANCER SCIENCE   Vol. 112   page: 986 - 986   2021.2  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Web of Science 血液マイクロRNAによる子宮肉腫と変性筋腫の術前鑑別診断 加藤 友康, 横井 暁, 松崎 潤太郎, 山本 雄介, 舘 慶生, 米岡 完, 清水 華子, 植原 貴史, 石川 光也, 滝澤 聡子, 青木 良晃, 加藤 健, 落谷 孝広, 東レ株式会社新事業開発部門DNAチップG 日本婦人科腫瘍学会雑誌   Vol. 39 ( 1 ) page: 297 - 297   2021.1  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   Establishment and characterization of cell lines from human endometrial epithelial and mesenchymal cells from patients with endometriosis Reviewed International journal Ayako Muraoka, Satoko Osuka, Tohru Kiyono, Miho Suzuki, Akira Yokoi, Tomohiko Murase, Kimihiro Nishino, Kaoru Niimi, Tomoko Nakamura, Maki Goto, Hiroaki Kajiyama, Yutaka Kondo, Fumitaka Kikkawa F&S Science   Vol. 1 ( 2 ) page: 195 - 205   2020.11  More details Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV   OBJECTIVE: To establish and characterize cell lines derived from human endometrial epithelial cells (ECs) and mesenchymal cells (MCs) from patients with and without endometriosis. DESIGN: In vitro experimental study. SETTING: University and national cancer center research institute. PATIENT(S): Two women with endometriosis and two women without endometriosis. INTERVENTION(S): Sampling of endometrial ECs and MCs. MAIN OUTCOME MEASURE(S): Establishing immortalized endometrial ECs and MCs with quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunocytochemical analysis, and RNA sequence profiling performed to characterize the immortalized cells and a cell proliferation assay, three-dimensional culture, and assays for hormone responses performed to characterize the features of ECs. RESULT(S): The qRT-PCR, immunocytochemical analysis, and Western blot analysis revealed that the ECs and MCs maintained their original features. Moreover, the immortalized cells were found to retain responsiveness to sex steroid hormones. The ECs formed a gland-like structure in three-dimensional culture, indicating the maintenance of normal EC phenotypes. The RNA sequence profiling, principal component analysis, and clustering analysis showed that the gene expression patterns of the immortalized cells were different from those of cancer cells. Several signaling pathways that were statistically significantly enriched in ECs and MCs with endometriosis were revealed. CONCLUSION(S): We successfully obtained four paired immortalized endometrial ECs and MCs from patients with and without endometriosis. Using these cells could help identify diagnostic and therapeutic targets for endometriosis. The cell lines established in this study will thus serve as powerful experimental tools in the study of endometriosis. DOI: 10.1016/j.xfss.2020.09.001 Scopus PubMed The clinical impact of intra- and extracellular miRNAs in ovarian cancer. Reviewed International journal Kosuke Yoshida, Akira Yokoi, Tomoyasu Kato, Takahiro Ochiya, Yusuke Yamamoto Cancer science   Vol. 111 ( 10 ) page: 3435 - 3444   2020.10  More details Language:English   Publishing type:Research paper (scientific journal)   Ovarian cancer is the most lethal gynecological cancer due to lack of early screening methods and acquired drug resistance. MicroRNAs (miRNAs) are effective post-transcriptional regulators that are transferred by extracellular vesicles, such as exosomes. Numerous studies have revealed that miRNAs are differentially expressed in epithelial ovarian cancer and act either as oncogenes or tumor suppressor genes. Cancer cells secrete exosomes containing miRNAs, which exert various effects on the components of the tumor microenvironment, including cancer-associated fibroblasts, macrophages, and adipocytes. Conversely, cancer cells also receive exosomes from these cells. As a result of cell-to-cell communication, epithelial ovarian cancer acquires a more aggressive phenotype and resistance to multiple drugs. In addition, some circulating miRNAs are protected from RNase degradation in the peripheral blood and can be potential non-invasive biomarkers. In particular, the combination of several circulating miRNAs enhances the accuracy of cancer screening. Likewise, comprehensive analyses revealed specific miRNA signatures in non-epithelial ovarian tumors and several miRNAs contributing to alterations of carcinogenic pathways. Overall, miRNAs play a crucial role in ovarian cancer progression. In this review, we discuss the emerging roles of intra- and extracellular miRNAs in ovarian cancers. In the near future, miRNAs will be practical biomarkers and computational deep learning will help in the clinical application of miRNAs. Moreover, miRNAs are potential therapeutic targets and agents, and there are ongoing clinical trials of miRNA replacement therapy. Therefore, accelerating research on miRNA might improve the prognosis of patients with ovarian cancer. DOI: 10.1111/cas.14599 Web of Science Scopus PubMed Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway. Reviewed International journal Masato Yoshihara, Hiroaki Kajiyama, Akira Yokoi, Mai Sugiyama, Yoshihiro Koya, Yoshihiko Yamakita, Wenting Liu, Kae Nakamura, Yoshinori Moriyama, Hiroaki Yasui, Shiro Suzuki, Yusuke Yamamoto, Carmela Ricciardelli, Akihiro Nawa, Kiyosumi Shibata, Fumitaka Kikkawa International journal of cancer   Vol. 146 ( 8 ) page: 2268 - 2280   2020.4  More details Language:English   Publishing type:Research paper (scientific journal)   Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell-to-cell crosstalk or phenotypic alterations including the acquisition of platinum-resistance in OvCa cells. Herein, we report how OvCa-associated mesothelial cells (OCAMs) induce platinum-resistance in OvCa cells through direct cell-to-cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF-β1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum-sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell-to-cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF-β1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell-to-cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum-resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination. DOI: 10.1002/ijc.32854 Web of Science Scopus PubMed Prognostic impact of pelvic and para-aortic lymphadenectomy on clinically-apparent stage I primary mucinous epithelial ovarian carcinoma: a multi-institutional study with propensity score-weighted analysis. Reviewed International journal Masato Yoshihara, Hiroaki Kajiyama, Satoshi Tamauchi, Shohei Iyoshi, Akira Yokoi, Shiro Suzuki, Michiyasu Kawai, Tetsuro Nagasaka, Kunihiko Takahashi, Shigeyuki Matsui, Fumitaka Kikkawa Japanese journal of clinical oncology   Vol. 50 ( 2 ) page: 145 - 151   2020.2  More details Language:English   Publishing type:Research paper (scientific journal)   BACKGROUND: The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. METHODS: We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. RESULTS: Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P = 0.696) and recurrence-free survival (P = 0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. CONCLUSIONS: The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials. DOI: 10.1093/jjco/hyz163 Web of Science Scopus PubMed Serum microRNA profile enables preoperative diagnosis of uterine leiomyosarcoma. Reviewed International journal Akira Yokoi, Juntaro Matsuzaki, Yusuke Yamamoto, Keisei Tate, Yutaka Yoneoka, Hanako Shimizu, Takashi Uehara, Mitsuya Ishikawa, Satoko Takizawa, Yoshiaki Aoki, Ken Kato, Tomoyasu Kato, Takahiro Ochiya Cancer science   Vol. 110 ( 12 ) page: 3718 - 3726   2019.12  More details Language:English   Publishing type:Research paper (scientific journal)   Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated. DOI: 10.1111/cas.14215 Web of Science Scopus PubMed Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background. Reviewed International journal Kosuke Yoshida, Akira Yokoi, Takumi Kagawa, Shingo Oda, Satomi Hattori, Satoshi Tamauchi, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kimihiro Nishino, Fumi Utsumi, Kaoru Niimi, Shiro Suzuki, Kiyosumi Shibata, Hiroaki Kajiyama, Tsuyoshi Yokoi, Fumitaka Kikkawa Carcinogenesis   Vol. 40 ( 12 ) page: 1435 - 1444   2019.12  More details Language:English   Publishing type:Research paper (scientific journal)   Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including &#39;pathway in cancer&#39; and &#39;cell cycle&#39;. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers. DOI: 10.1093/carcin/bgz135 Web of Science Scopus PubMed COMPREHENSIVE MIRNA SEQUENCING OF SQUAMOUS CELL CARCINOMA ARISING FROM OVARIAN MATURE TERATOMA Reviewed International journal Yoshida, K; Yokoi, A; Tamauchi, S; Ikeda, Y; Yoshikawa, N; Nishino, K; Niimi, K; Suzuki, S; Kajiyama, H; Kikkawa, F INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 29   page: A544 - A545   2019.11  More details Language:Japanese   Publishing type:Research paper (scientific journal)   DOI: 10.1136/ijgc-2019-ESGO.1079 Web of Science Cancer extracellular vesicles contribute to stromal heterogeneity by inducing chemokines in cancer-associated fibroblasts. Reviewed International journal Yutaka Naito, Yusuke Yamamoto, Naoya Sakamoto, Iwao Shimomura, Akiko Kogure, Minami Kumazaki, Akira Yokoi, Masakazu Yashiro, Tohru Kiyono, Kazuyoshi Yanagihara, Ryou-U Takahashi, Kosei Hirakawa, Wataru Yasui, Takahiro Ochiya Oncogene   Vol. 38 ( 28 ) page: 5566 - 5579   2019.7  More details Language:English   Publishing type:Research paper (scientific journal)   Cancer-associated fibroblasts (CAFs), one of the major components of a tumour microenvironment, comprise heterogeneous populations involved in tumour progression. However, it remains obscure how CAF heterogeneity is governed by cancer cells. Here, we show that cancer extracellular vesicles (EVs) induce a series of chemokines in activated fibroblasts and contribute to the formation of the heterogeneity. In a xenograft model of diffuse-type gastric cancer, we showed two distinct fibroblast subpopulations with alpha-smooth muscle actin (α-SMA) expression or chemokine expression. MicroRNAs (miRNAs) profiling of the EVs and the transfection experiment suggested that several miRNAs played a role in the induction of chemokines such as CXCL1 and CXCL8 in fibroblasts, but not for the myofibroblastic differentiation. Clinically, aberrant activation of CXCL1 and CXCL8 in CAFs correlated with poorer survival in gastric cancer patients. Thus, this link between chemokine expression in CAFs and tumour progression may provide novel targets for anticancer therapy. DOI: 10.1038/s41388-019-0832-4 PubMed A landmark in drug discovery based on complex natural product synthesis. Kawano S, Ito K, Yahata K, Kira K, Abe T, Akagi T, Asano M, Iso K, Sato Y, Matsuura F, Ohashi I, Matsumoto Y, Isomura M, Sasaki T, Fukuyama T, Miyashita Y, Kaburagi Y, Yokoi A, Asano O, Owa T, Kishi Y Scientific reports   Vol. 9 ( 1 ) page: 8656   2019.6  More details Language:English   DOI: 10.1038/s41598-019-45001-9 PubMed Drug library screen reveals benzimidazole derivatives as selective cytotoxic agents for KRAS-mutant lung cancer. Reviewed International journal Iwao Shimomura, Akira Yokoi, Isaku Kohama, Minami Kumazaki, Yuji Tada, Koichiro Tatsumi, Takahiro Ochiya, Yusuke Yamamoto Cancer letters   Vol. 451   page: 11 - 22   2019.6  More details Language:English   Publishing type:Research paper (scientific journal)   KRAS is one of the most frequently mutated oncogenes in human non-small cell lung cancer (NSCLC). Mutations in KRAS are detected in 30% of NSCLC cases, with most of them occurring in codons 12 and 13 and less commonly in others. Despite intense efforts to develop drugs targeting mutant KRAS, no effective therapeutic strategies have been successfully tested in clinical trials. Here, we investigated molecular targets for KRAS-activated lung cancer cells using a drug library. A total of 1271 small molecules were screened in KRAS-mutant and wild-type lung cancer cell lines. The screening identified the cytotoxic effects of benzimidazole derivatives on KRAS-mutant lung cancer cells. Treatments with two benzimidazole derivatives, methiazole and fenbendazole-both of which are structurally specific-yielded significant suppression of the RAS-related signaling pathways in KRAS-mutated cells. Moreover, combinatorial therapy with methiazole and trametinib, a MEK inhibitor, induced synergistic effects in KRAS-mutant lung cancer cells. Our study demonstrates that these benzimidazole derivatives play an important role in suppressing KRAS-mutant lung cancer cells, thus offering a novel combinatorial therapeutic approach against such cancer cells. DOI: 10.1016/j.canlet.2019.03.002 PubMed PAI-1 secreted from metastatic ovarian cancer cells triggers the tumor-promoting role of the mesothelium in a feedback loop to accelerate peritoneal dissemination. Reviewed International journal Yang Peng, Hiroaki Kajiyama, Hong Yuan, Kae Nakamura, Masato Yoshihara, Akira Yokoi, Kayo Fujikake, Hiroaki Yasui, Nobuhisa Yoshikawa, Shiro Suzuki, Takeshi Senga, Kiyosumi Shibata, Fumitaka Kikkawa Cancer letters   Vol. 442   page: 181 - 192   2019.2  More details Language:English   Publishing type:Research paper (scientific journal)   The mesothelium, covered by a continuous monolayer of mesothelial cells, is the first protective barrier against metastatic ovarian cancer. However, mesothelial cells release tumor-promoting factors that accelerate the process of peritoneal metastasis. We identified cancer-associated mesothelial cells (CAMs) that had tumor-promoting potential. Here, we found that plasminogen activator inhibitor-1 (PAI-1) induced the formation of CAMs, after which CAMs increasingly secreted the oncogenic factors interleukin-8 (IL-8) and C-X-C motif chemokine ligand 5 (CXCL5), further promoting the metastasis of ovarian cancer cells in a feedback loop. After the formation of CAMs, PAI-1 activated the nuclear factor kappa B (NFκB) pathway in the CAMs, thus transcriptionally upregulating the expression of the downstream NFκB targets IL-8 and CXCL5. Moreover, PAI-1 correlated with peritoneal metastasis in ovarian cancer patients and indicated a poor prognosis. In both ex vivo and in vivo models, after PAI-1 expression was knocked down, the metastasis of ovarian cancer cells decreased significantly. Therefore, targeting PAI-1 may provide a potential target for future therapeutics to prevent the formation of CAMs and alleviate peritoneal metastasis in ovarian cancer patients. DOI: 10.1016/j.canlet.2018.10.027 Web of Science Scopus PubMed Investigation of postpartum hemorrhage related to assisted reproductive technology (ART) pregnancy managed by in-hospital midwife care system OSHIMA Kazumi, YOKOI Akira, SHIBATA Sachiko, MANO Makiko Journal of Japan Academy of Midwifery   Vol. 32 ( 2 ) page: 169 - 177   2018.12  More details Language:Japanese   Publisher:Japan Academy of Midwifery  

Purpose

The authors&#39; birth center is an in-hospital midwifery facility annexed to the Perinatal Medical Center. Even if the course of pregnancy and delivery is uneventful, unexpected massive bleeding can occur after childbirth. Pregnancies conceived via assisted reproductive technology (ART) are said to be a risk factor for placenta accreta; and placenta accreta can cause critical obstetrical hemorrhage. In our facility, if a parturient conceived via ART wishes to give birth in an in-hospital midwifery unit, childbirth is carried out in a birth center with the permission of the obstetrician. We conducted a case-control study about postpartum hemorrhage (PPH) to examine the safety of giving birth of pregnant women conceived via ART (fresh embryo transfer and cryopreserved embryo transfer) in an in-hospital midwifery care.

Subjects and Methods

During the survey period between April 2013 and March 2016, the total number of birth center deliveries was 604, including 567 not conceived through ART and 37 conceived through ART: fresh embryo transfer in 9 cases and cryopreserved embryo transfer (CET) in 28 cases. We carried out a statistical analysis of the amount of postpartum bleeding, the amount of bleeding during the 24 hours following delivery, and the frequency of PPH (postpartum bleeding of 500mL or more, or bleeding of 800mL or more during the 24 hours following delivery) among pregnancies not conceived through ART, pregnancies conceived through fresh embryo transfer, and pregnancies conceived through CET. Multiple linear regression analysis of the amount of postpartum bleeding and the amount of bleeding during the 24 hours following delivery was performed, and the frequency of PPH was determined using multivariate logistic analysis.

Results

The amount of postpartum bleeding and the amount during the 24 hours following delivery were significantly greater among pregnancies conceived through CET than among those not conceived through ART; the frequency of PPH was also significantly higher among pregnancies conceived through CET than among those not conceived through ART. In addition, PPH consisted of critical obstetrical hemorrhage in 4 cases, 3 of which occurred in mothers pregnant with fetuses conceived through ART using CET.

Conclusions

Our study suggested that pregnancy conceived through CET was a risk factor for PPH. Regarding care system and eligibility for giving birth of pregnant women conceived through CET in an in-hospital midwifery unit, further investigations are needed.

DOI: 10.3418/jjam.jjam-2017-0048 CiNii Research Cancer-associated mesothelial cells as a potential therapeutic target in epithelial ovarian cancer Reviewed International journal 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  More details Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY   Web of Science The role of extracellular RNAs in ovarian cancer Reviewed International journal Yokoi, A; Yoshioka, Y; Yamamoto, Y; Matsuzaki, J; Kato, T; Kato, K; Kajiyama, H; Kikkawa, F; Ochiya, T CANCER SCIENCE   Vol. 109   page: 351 - 351   2018.12  More details Publishing type:Research paper (scientific journal)   Web of Science Notch signaling enhances the mutual association with epithelial ovarian cancer and mesothelial cells Reviewed International journal Mai Sugiyama, Masato Yoshihara, Yoshihiro Koya, Akira Yokoi, Buntei Ryu, Fumitaka Kikkawa, Hiroaki Kajiyama CANCER SCIENCE   Vol. 109   page: 864 - 864   2018.12  More details Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY   Web of Science Carcinoma-associated mesothelial cells promote dissemination and platinum resistance in epithelial ovarian cancer. Reviewed International journal 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  More details Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY   Web of Science Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer Reviewed International journal Yokoi, A; Yoshioka, Y; Yamamoto, Y; Ishikawa, M; Kato, T; Kiyono, T; Kajiyama, H; Kikkawa, F; Ochiya, T CANCER SCIENCE   Vol. 109   page: 29 - 29   2018.1  More details Publishing type:Research paper (scientific journal)   Web of Science 既存薬ライブラリーを用いた、活性型Ras変異がんを標的とする分子標的治療の探索 Reviewed International journal 下村 巌, 横井 暁, 山本 雄介, 多田 裕司, 巽 浩一郎, 落谷 孝広 生命科学系学会合同年次大会   Vol. 2017年度   page: [3P - 0974]   2017.12  More details Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:生命科学系学会合同年次大会運営事務局   A combination of circulating miRNAs for the early detection of ovarian cancer. Reviewed International journal Akira Yokoi, Yusuke Yoshioka, Akihiro Hirakawa, Yusuke Yamamoto, Mitsuya Ishikawa, Shun-Ichi Ikeda, Tomoyasu Kato, Kaoru Niimi, Hiroaki Kajiyama, Fumitaka Kikkawa, Takahiro Ochiya Oncotarget   Vol. 8 ( 52 ) page: 89811 - 89823   2017.10  More details Language:English   Publishing type:Research paper (scientific journal)   Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine. DOI: 10.18632/oncotarget.20688 Web of Science Scopus PubMed Diagnostic potential of multiple miRNAs for detecting early ovarian cancer Yokoi Akira, Yoshioka Yusuke, Kato Tomoyasu, Kajiyama Hiroaki, Kikkawa Fumitaka, Ochiya Takahiro Japan Journal of Molecular Tumor Marker Research   Vol. 32 ( 0 ) page: 27   2017  More details Language:Japanese   Publisher:Japanese Society for Molecular Tumor Marker Research   DOI: 10.11241/jsmtmr.32.27 CiNii Research ▼display all To the head of Papers.▲ MISC MISC 193 当院における免疫チェックポイント阻害薬の使用経験について 齋藤 舞, 芳川 修久, 吉田 康将, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 池田 芳紀, 新美 薫, 梶山 広明 愛知産科婦人科学会学術講演会プログラム   Vol. 118回   page: 8 - 8   2023.10  More details Language:Japanese   Publisher:愛知産科婦人科学会   卵巣がんにおける細胞外小胞エクソソームの包括的機能解析 横井 暁 日本産科婦人科学会雑誌   Vol. 75 ( 10 ) page: 1064 - 1071   2023.10  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   外科的治療を要した下大静脈に至る静脈内筋腫の1例 杉原 穂乃花, 吉田 康将, 國島 温志, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 池田 芳紀, 芳川 修久, 新美 薫, 梶山 広明 愛知産科婦人科学会学術講演会プログラム   Vol. 118回   page: 5 - 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28   2023.10  More details Language:Japanese   Publisher:東海産婦人科内視鏡手術研究会   stage I卵巣明細胞癌の術後化学療法は3サイクル以上必要か? 鵜飼 真由, 鈴木 史郎, 吉原 雅人, 横井 暁, 芳川 修久, 岸上 靖幸, 小口 秀紀, 梶山 広明, 吉川 史隆 日本癌治療学会学術集会抄録集   Vol. 61回   page: IJCO - 4   2023.10  More details Language:English   Publisher:(一社)日本癌治療学会   高異型度漿液性卵巣癌におけるPARP阻害薬治療の効果予測としての細胞外小胞中DNA解析(Application of DNA in Extracellular Vesicles to Predict PARP inhibitor Response in High Grade Serous Ovarian Carcinoma) 植草 良輔, 横井 暁, 北川 雅美, 吉田 康将, 松崎 潤太郎, 山本 雄介, 梶山 広明 日本癌学会総会記事   Vol. 82回   page: 2146 - 2146   2023.9  More details Language:English   Publisher:(一社)日本癌学会   高異型度漿液性卵巣癌特異的エクソソーム膜タンパク質同定を目指した包括的プロテオーム解析(Identifying high-grade serous ovarian carcinoma-specific membrane proteins on small extracellular vesicles) 横井 暁, 鵜飼 真由, 安井 隆雄, 北川 雅美, 吉田 康将, 稲見 恵理, 石川 光也, 加藤 友康, 松崎 潤太郎, 山本 雄介, 梶山 広明 日本癌学会総会記事   Vol. 82回   page: 789 - 789   2023.9  More details Language:English   Publisher:(一社)日本癌学会   空間的トランスクリプトーム解析を用いた卵巣成熟奇形腫の悪性転化に関わる機序の解明(Elucidation of mechanisms underlying malignant transformation of ovarian mature teratoma through spatial transcriptomics) 吉田 康将, 横井 暁, 常 続博雅, 玉内 学志, 北川 雅美, 稲見 恵理, 中山 淳, 加藤 友康, 山本 雄介, 梶山 広明 日本癌学会総会記事   Vol. 82回   page: 1236 - 1236   2023.9  More details Language:English   Publisher:(一社)日本癌学会   卵巣癌における新規治療法としての脂肪由来間葉系幹細胞エクソソームの可能性(Therapeutic potential of extracellular vesicles from adipose-derived stem cells in ovarian cancer) 鈴木 公基, 横井 暁, 宇野 枢, 吉田 康将, 稲見 恵理, 北川 雅美, 鈴木 一弘, 長尾 有佳里, 山本 雄介, 梶山 広明 日本癌学会総会記事   Vol. 82回   page: 1011 - 1011   2023.9  More details Language:English   Publisher:(一社)日本癌学会   子宮平滑筋肉腫におけるUCP2を標的とした新規治療戦略(Novel therapeutic strategies targeting UCP2 in uterine leiomyosarcoma) 長尾 有佳里, 横井 暁, 吉田 康将, 杉山 麻衣, 渡邉 絵里, 北川 雅美, 吉原 雅人, 玉内 学志, 加藤 友康, 石川 光也, 山本 雄介, 梶山 広明 日本癌学会総会記事   Vol. 82回   page: 1233 - 1233   2023.9  More details Language:English   Publisher:(一社)日本癌学会   プラチナ抵抗性卵巣癌克服に向けた細胞外小胞関連JAK/STAT経路解析(Overcoming platinum resistance of ovarian cancer regulating the activated JAK/STAT pathways via extracellular vesicles) 鈴木 一弘, 横井 暁, 吉田 康将, 稲見 恵理, 北川 雅美, 山本 雄介, 北井 美穂, 植野 さやか, 須藤 保, 梶山 広明 日本癌学会総会記事   Vol. 82回   page: 129 - 129   2023.9  More details Language:English   Publisher:(一社)日本癌学会   CRISPR-Cas9生体内スクリーニングによる卵巣奇形腫悪性転化の新規治療開発(CRISPR-Cas9 in vivo screening for novel therapy for malignant transformation of mature cystic teratoma of the ovary) 玉内 学志, 常 続博雅, 吉田 康将, 横井 暁, 梶山 広明 日本癌学会総会記事   Vol. 82回   page: 1238 - 1238   2023.9  More details Language:English   Publisher:(一社)日本癌学会   ドラッグリポジショニングを用いた卵巣がん細胞のエクソソーム分泌抑制剤のスクリーニング(Drug repositioning screening for an inhibitor of EV secretion in ovarian cancer cells) 吉岡 祐亮, 竹下 文隆, 横井 暁, 落谷 孝広, 落合 孝広 日本癌学会総会記事   Vol. 82回   page: 791 - 791   2023.9  More details Language:English   Publisher:(一社)日本癌学会   高異型度漿液性卵巣癌に対するPARP阻害薬効果予測としての細胞外小胞DNA上コピー数多型解析 植草 良輔, 横井 暁, 吉田 康将, 北川 雅美, 芳川 修久, 松崎 潤太郎, 山本 雄介, 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. 65回   page: 296 - 296   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   高異型度漿液性卵巣癌に対するPARP阻害薬効果予測としての細胞外小胞DNA上コピー数多型解析 植草 良輔, 横井 暁, 吉田 康将, 北川 雅美, 芳川 修久, 松崎 潤太郎, 山本 雄介, 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. 65回   page: 296 - 296   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   血中循環型マイクロRNA解析による卵巣癌サブタイプ別治療奏功性予測 鈴木 一弘, 横井 暁, 吉田 康将, 北川 雅美, 落谷 孝広, 山本 雄介, 加藤 友康, 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. 65回   page: 296 - 296   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   初回手術と併施した腹壁瘢痕ヘルニア修復術が原因と考えられた子宮体癌IA期早期腹壁再発の1例 國島 温志, 池田 芳紀, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 芳川 修久, 新美 薫, 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. 65回   page: 320 - 320   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   卵巣癌における新規治療法としての脂肪由来間葉系幹細胞エクソソームの可能性 鈴木 公基, 横井 暁, 宇野 枢, 植草 良輔, 松尾 聖子, 長尾 有佳里, 鈴木 一弘, 吉田 康将, 稲見 恵理, 北川 雅美, 芳川 修久, 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. 65回   page: 356 - 356   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   子宮体癌の免疫微小環境をProMisE分類から再考する 服部 諭美, 芳川 修久, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 池田 芳紀, 新美 薫, 鈴木 史朗, 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. 65回   page: 289 - 289   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   子宮肉腫患者予後改善へ向けたトランスレーショナル研究の取り組み 横井 暁, 長尾 有佳里, 吉田 康将, 吉原 雅人, 玉内 学志, 清水 裕介, 池田 芳紀, 芳川 修久, 新美 薫, 梶山 広明 愛知産科婦人科学会学術講演会プログラム   Vol. 117回   page: 6 - 6   2023.7  More details Language:Japanese   Publisher:愛知産科婦人科学会   子宮頸癌術後化学放射線療法中に急性下肢動脈閉塞を発症した一例 池田 芳紀, 柴田 真由, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 芳川 修久, 新美 薫, 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. 65回   page: 383 - 383   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   血中循環型マイクロRNA解析による卵巣癌サブタイプ別治療奏功性予測 鈴木 一弘, 横井 暁, 吉田 康将, 北川 雅美, 落谷 孝広, 山本 雄介, 加藤 友康, 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. 65回   page: 296 - 296   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   ニラパリブが有効だったBRCA1遺伝子生殖細胞変異を有する卵巣癌の髄膜播種の一例 玉内 学志, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 新美 薫, 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. 65回   page: 371 - 371   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   Ovarian clear cell carcinomaにおける腫瘍浸潤リンパ球および腫瘍関連マクロファージの臨床的意義(Clinical Significance of Tumor-infiltrating Lymphocytes and Tumor-associated Macrophages in Ovarian Clear Cell Carcinoma) 芳川 修久, 松川 哲也, 服部 諭美, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 池田 芳紀, 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. 65回   page: 276 - 276   2023.7  More details Language:English   Publisher:(公社)日本婦人科腫瘍学会   2つの婦人科悪性腫瘍に対して妊孕性温存治療を行い,生児を得た一例 中川 敦史, 玉内 学志, 吉原 雅人, 清水 裕介, 横井 暁, 池田 芳紀, 芳川 修久, 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. 65回   page: 387 - 387   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   【卵巣癌維持療法の日本人リアルワールドデータから見えてくるもの】リアルワールドデータからみる卵巣癌化学療法の変遷と維持療法の影響 茂木 一将, 吉原 雅人, 宮本 絵美里, 藤本 裕基, 伊吉 祥平, 宇野 枢, 玉内 学志, 横井 暁, 清水 裕介, 池田 芳紀, 芳川 修久, 新美 薫, 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. 65回   page: 140 - 140   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   【卵巣癌維持療法の日本人リアルワールドデータから見えてくるもの】卵巣癌維持療法としてのPARP阻害剤使用182例におけるReal World Data検証 渡邉 絵里, 横井 暁, 植草 良輔, 芳川 修久, 新美 薫, 鈴木 史朗, 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. 65回   page: 137 - 137   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   【婦人科発癌の謎に迫る~ここまでわかった分子機序】子宮平滑筋肉腫における発癌メカニズム解析と新規治療戦略の同定 長尾 有佳里, 横井 暁, 吉田 康将, 北川 雅美, 山本 雄介, 加藤 友康, 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. 65回   page: 144 - 144   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   【婦人科発癌の謎に迫る~ここまでわかった分子機序】子宮平滑筋肉腫における発癌メカニズム解析と新規治療戦略の同定 長尾 有佳里, 横井 暁, 吉田 康将, 北川 雅美, 山本 雄介, 加藤 友康, 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. 65回   page: 144 - 144   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   【若手産婦人科医がつなぐTR,基礎研究が面白い!】空間的腹水中エクソソーム解析による新しい卵巣がん進展メカニズム解析 横井 暁, 吉田 康将, 北川 雅美, 稲見 恵理, 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. 65回   page: 147 - 147   2023.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   粘液性卵巣癌における臨床パラメーターの検討 鈴木 一弘, 横井 暁, 黒田 啓太, 吉田 康将, 吉原 雅人, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 東海産科婦人科学会雑誌   Vol. 59   page: 445 - 445   2023.3  More details Language:Japanese   Publisher:東海産科婦人科学会   高異型度漿液性卵巣がん特異的エクソソーム膜タンパク質の同定と臨床応用 北川 雅美, 横井 暁, 鵜飼 真由, 吉田 康将, 加藤 友康, 梶山 広明 日本産科婦人科学会雑誌   Vol. 75 ( 臨増 ) page: S - 366   2023.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   機械学習による良性・境界悪性・悪性卵巣腫瘍術前診断の試み 血液検査データを用いた漿液性腫瘍に関する予備実験 池田 芳紀, 國島 温志, 植草 良輔, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 芳川 修久, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 75 ( 臨増 ) page: S - 429   2023.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   卵巣がんにおける細胞外小胞エクソソームの包括的機能解析 横井 暁 日本産科婦人科学会雑誌   Vol. 75 ( 臨増 ) page: S - 84   2023.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   婦人科がん患者への漢方処方の実態調査報告 芳川 修久, 松川 哲也, 吉原 雅人, 玉内 学志, 横井 暁, 清水 裕介, 梶山 広明 日本産科婦人科学会雑誌   Vol. 75 ( 臨増 ) page: S - 491   2023.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   がんゲノムプロファイルに基づく成熟奇形腫悪性転化患者腫瘍由来モデルを用いたPARP阻害薬の有効性の実証 中川 敦史, 玉内 学志, 吉原 雅人, 清水 裕介, 横井 暁, 池田 芳紀, 芳川 修久, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 75 ( 臨増 ) page: S - 370   2023.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   p53オートファジー関連キナーゼを標的とした卵巣癌新規治療化合物の開発 玉内 学志, 吉原 雅人, 横井 暁, 清水 裕介, 芳川 修久, 池田 芳紀, 梶山 広明 日本産科婦人科学会雑誌   Vol. 75 ( 臨増 ) page: S - 369   2023.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   IV期卵巣癌における初回治療時の転移部位別予後比較 國島 温志, 池田 芳紀, 吉原 雅人, 玉内 学志, 清水 裕介, 横井 暁, 芳川 修久, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 75 ( 臨増 ) page: S - 517   2023.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   新たな診断・治療開発に向けた婦人科がん分子機構の解明レビュー 卵巣がん細胞由来核酸搭載エクソソームの機能解析と臨床応用 横井 暁 日本産科婦人科学会雑誌   Vol. 74 ( 10 ) page: 1609 - 1619   2022.10  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   婦人科悪性腫瘍における炎症性マーカーとサルコペニア指数の意義 芳川 修久, 松川 哲也, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 清水 裕介, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 60回   page: P102 - 1   2022.10  More details Language:English   Publisher:(一社)日本癌治療学会   子宮平滑筋肉腫に対するマルチオミクス解析による新規治療標的の同定 吉田 康将, 横井 暁, 加藤 友康, 梶山 広明, 山本 雄介 日本癌治療学会学術集会抄録集   Vol. 60回   page: OF - 4   2022.10  More details Language:English   Publisher:(一社)日本癌治療学会   平均血小板容積は卵巣明細胞癌患者の予後予測マーカーである 松川 哲也, 芳川 修久, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 清水 裕介, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 60回   page: P17 - 3   2022.10  More details Language:English   Publisher:(一社)日本癌治療学会   高異型度漿液性卵巣癌における細胞外小胞エクソソーム中コピー数多型解析(Identifying Copy Number Variations in Extracellular Vesicles as a Novel Biomarker of High Grade Serous Ovarian Carcinoma) 植草 良輔, 横井 暁, 北川 雅美, 吉田 康将, 吉原 雅人, 玉内 学志, 新美 薫, 松崎 潤太郎, 山本 雄介, 梶山 広明 日本癌学会総会記事   Vol. 81回   page: MS5 - 2   2022.9  More details Language:English   Publisher:(一社)日本癌学会   脂肪系幹細胞由来のsmall extracellular vesiclesに含まれる腫瘍抑制性miRNAは卵巣癌において抗腫瘍効果を示す(Tumor suppressive miRNAs in small extracellular vesicles derived from ADSCs shows anti-tumor capacity in ovarian cancer) 鈴木 公基, 横井 暁, 植草 良輔, 北川 雅美, 吉田 康将, 宇野 枢, 梶山 広明 日本癌学会総会記事   Vol. 81回   page: P - 2133   2022.9  More details Language:English   Publisher:(一社)日本癌学会   卵巣がん腹膜播種における革新的微量腹水中エクソソーム解析(Novel exsome analyses for micro volume ascites in ovarian cancer dissemination) 横井 暁, 安井 隆雄, 吉田 康将, 北川 雅美, 梶山 広明 日本癌学会総会記事   Vol. 81回   page: IS1 - 5   2022.9  More details Language:English   Publisher:(一社)日本癌学会   子宮平滑筋肉腫における新規治療標的としての細胞周期関連キナーゼの異常活性化(Aberrant activation of cell cycle-related kinases as novel therapeutic targets for uterine leiomyosarcoma) 吉田 康将, 横井 暁, 加藤 友康, 梶山 広明, 山本 雄介 日本癌学会総会記事   Vol. 81回   page: E - 2067   2022.9  More details Language:English   Publisher:(一社)日本癌学会   Notchシグナルは進行卵巣癌の新規治療標的となり得る(Notch signaling can be a new therapeutic target for advanced ovarian cancer) 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, 中村 香江, 那波 明宏, 梶山 広明 日本癌学会総会記事   Vol. 81回   page: P - 3060   2022.9  More details Language:English   Publisher:(一社)日本癌学会   高悪性度漿液性卵巣癌の新規バイオマーカーとしての細胞外小胞DNAのコピー数多型 植草 良輔, 横井 暁, 鵜飼 真由, 吉田 康将, 北川 雅美, 吉原 雅人, 玉内 学志, 池田 芳紀, 芳川 修久, 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. 64回   page: 211 - 211   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   難治性婦人科がんの克服を目指して 腫瘍促進的腹膜環境の正常化を標的とした難治性卵巣癌に対する新規治療戦略の開発 北見 和久, 吉原 雅人, 山北 由彦, 杉山 麻衣, 小屋 美博, 藤本 裕基, 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, 榎本 篤, 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. 64回   page: 103 - 103   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   若手医師によるTRをつなぐ 卵巣癌腹膜播種におけるNotchシグナルを介した腫瘍内不均一性の解明と新規治療標的化 吉原 雅人, 茂木 一将, 藤本 裕基, 伊吉 祥平, 北見 和久, 宇野 枢, 田野 翔, 玉内 学志, 横井 暁, 池田 芳紀, 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. 64回   page: 116 - 116   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   婦人科がんにおけるliquid biopsyの有用性 卵巣がん細胞外小胞の機能解析と臨床応用へ向けた基盤研究 横井 暁 日本婦人科腫瘍学会雑誌   Vol. 40 ( 3 ) page: 159 - 166   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   子宮体癌および子宮内膜異型増殖症の妊孕性温存後再発に対する再温存治療に関する検討 中川 敦史, 玉内 学志, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 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. 64回   page: 245 - 245   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   子宮平滑筋肉腫に対するRNAシーケンス解析に基づく新規治療薬候補の同定 吉田 康将, 横井 暁, 加藤 友康, 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. 64回   page: 195 - 195   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   新しいエクソソーム解析法による卵巣がんバイオマーカーの新展開 横井 暁, 鵜飼 真由, 北川 雅美, 吉田 康将, 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. 64回   page: 193 - 193   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   細胞分裂期キナーゼVRK1を標的とした新しい卵巣癌治療法の開発 玉内 学志, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 新美 薫, 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. 64回   page: 277 - 277   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   腫瘍微小環境の免疫トレランス克服を目指したキメラ抗原受容体導入養子細胞免疫療法の開発 芳川 修久, 松川 哲也, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 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. 64回   page: 275 - 275   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   腫瘍浸潤リンパ球のパターン別にみた子宮体癌の3分類(Three Classifications of Endometrial Cancer According to the Tumor-infiltrating Patterns of Lymphocytes) 服部 諭美, 鈴木 史朗, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 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. 64回   page: 200 - 200   2022.7  More details Language:English   Publisher:(公社)日本婦人科腫瘍学会   フェロトーシス誘導による絨毛癌新規治療薬戦略 渡邉 絵里, 横井 暁, 吉田 康将, 杉山 麻衣, 北川 雅美, 西野 公博, 新美 薫, 山本 雄介, 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. 64回   page: 195 - 195   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   Stage I期卵巣明細胞癌に対する3サイクル以上の補助化学療法は必要なのか 多施設共同研究(Are More than Three Cycles of Adjuvant Chemotherapy for Surgical Stage I Ovarian Clear Cell Carcinoma Necessary?: A Multi-institutional Study) 大野 真由, 鈴木 史朗, 横井 暁, 吉原 雅人, 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. 64回   page: 198 - 198   2022.7  More details Language:English   Publisher:(公社)日本婦人科腫瘍学会   I期卵巣癌患者に対する妊孕性温存手術後の補助化学療法が予後に与える影響 池田 芳紀, 吉原 雅人, 芳川 修久, 横井 暁, 玉内 学志, 西野 公博, 新美 薫, 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. 64回   page: 191 - 191   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   2型子宮体癌におけるCD47発現の検討 松川 哲也, 芳川 修久, 劉 文亭, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 西野 公博, 新美 薫, 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. 64回   page: 247 - 247   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   がん治療におけるバイオマーカーのnew era Small RNAプロファイルに基づく高異型度漿液性卵巣癌プラチナ感受性の再定義 鈴木 一弘, 横井 暁, 吉田 康将, 北川 雅美, 吉原 雅人, 玉内 学志, 池田 芳紀, 芳川 修久, 須藤 保, 長尾 昌二, 山口 聡, 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. 64回   page: 112 - 112   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   コンディショナルノックインマウスを用いた卵巣がん関連中皮細胞の系譜追跡と機能解析 茂木 一将, 谷口 寿章, 吉原 雅人, 藤本 裕基, 宇野 枢, 伊吉 祥平, 北見 和久, 杉山 麻衣, 小屋 美博, 山北 由彦, 玉内 学志, 池田 芳紀, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 富田 弘之, 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. 64回   page: 194 - 194   2022.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   婦人科腫瘍に対する鏡視下手術を含めた骨盤内臓全摘術23例の検討 新美 薫, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 梶山 広明 東海産科婦人科学会雑誌   Vol. 58   page: 47 - 53   2022.3  More details Language:Japanese   Publisher:東海産科婦人科学会   骨盤内臓全摘術は、周囲臓器に浸潤した進行・再発婦人科悪性腫瘍に対して完全切除を行うことで、長期生存が期待できる方法の一つである。しかし、侵襲が大きい上にストマの造設等でQOLの低下を招くため手術適応が難しい。また、拡大視が可能な腹腔鏡下手術は骨盤手術に有用で術後の早期回復も期待でき、近年腹腔鏡下骨盤内臓全摘術も増えている。今回、当院で2012年から2021年に骨盤内臓全摘術を施行した、骨盤内進行・再発婦人科悪性腫瘍23例を対象として、合併症、予後等を解析した。さらに開腹手術と腹腔鏡下手術を比較検討した。年齢の中央値は54歳で、原発は子宮頸癌8例、腟癌3例、子宮体癌3例、卵巣・卵管癌6例、平滑筋肉腫2例、原発不明癌1例であった。術式は開腹10例、腹腔鏡11例で全例外科および泌尿器科と連携して行った。周術期死亡例はなく、周術期合併症は17例(73.9%)にあり、尿路系合併症が8例(34.7%)で最多であった。開腹と腹腔鏡での手術成績の比較において、手術時間の中央値に差はなく、腹腔鏡で出血量が少なく入院期間が短い傾向にあったが有意差はなかった。観察期間(7.7ヵ月〜105.2ヵ月)における全患者23例の5年生存率は64.2%であった。全生存期間中央値は34.5ヵ月で、無増悪期間中央値は26.7ヵ月であった。予後因子を検討したところ、切除断端陽性では全生存率、無増悪生存率ともに、切除断端陰性より有意に予後不良となった。今回の検討において、骨盤内臓全摘術は、周囲臓器に浸潤した進行・再発婦人科悪性腫瘍に対して、比較的安全に施行できる術式と考えられた。また、腹腔鏡下手術は開腹と比較して低侵襲な可能性があり、合併症や早期回復の点で、腹腔鏡下手術を選択することも可能と考える。(著者抄録) 子宮内膜異型増殖症の診断で子宮全摘出術を施行した48症例における術前・術後病理診断の比較 藤田 和寿, 池田 芳紀, 秋田 寛佳, 茂木 一将, 服部 諭美, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 東海産科婦人科学会雑誌   Vol. 58   page: 313 - 313   2022.3  More details Language:Japanese   Publisher:東海産科婦人科学会   子宮体癌に対する免疫療法における新たな標的の検索 マルチカラーフローサイトメトリーによる腫瘍浸潤リンパ球の解析 服部 諭美, 鈴木 史朗, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 330   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   若年境界悪性卵巣腫瘍患者に対する腫瘍核出術の妊孕性温存治療としての可能性 池田 芳紀, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 498   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   絨毛癌の免疫微小環境の解明 NK細胞抑制型受容体に着目して 柴田 真由, 新美 薫, 服部 諭美, 西子 裕規, 小田 結加里, 渡邉 絵里, 横井 暁, 西野 公博, 山本 英子, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 338   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   絨毛癌MTX耐性株の作成と解析 西子 裕規, 新美 薫, 横井 暁, 吉田 康将, 柴田 真由, 小田 結加里, 渡邉 絵里, 西野 公博, 山本 英子, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 512   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   新たな診断・治療開発に向けた婦人科がん分子機構の解明 卵巣がん細胞由来核酸搭載エクソソームの機能解析と臨床応用 横井 暁 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 24   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   広汎子宮頸部摘出術の卵巣予備能に対する影響 中川 敦史, 玉内 学志, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 465   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   子宮平滑筋肉腫に対する新規治療薬開発を目指した化合物探索 長尾 有佳里, 横井 暁, 吉田 康将, 渡邉 絵里, 北川 雅美, 杉山 麻衣, 吉原 雅人, 玉内 学志, 池田 芳紀, 芳川 修久, 加藤 友康, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 485   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   若年境界悪性卵巣腫瘍患者に対する腫瘍核出術の妊孕性温存治療としての可能性 池田 芳紀, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 498   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   子宮体癌に対する免疫療法における新たな標的の検索 マルチカラーフローサイトメトリーによる腫瘍浸潤リンパ球の解析 服部 諭美, 鈴木 史朗, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 330   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   子宮平滑筋肉腫に対する新規治療薬開発を目指した化合物探索 長尾 有佳里, 横井 暁, 吉田 康将, 渡邉 絵里, 北川 雅美, 杉山 麻衣, 吉原 雅人, 玉内 学志, 池田 芳紀, 芳川 修久, 加藤 友康, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 485   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   広汎子宮頸部摘出術の卵巣予備能に対する影響 中川 敦史, 玉内 学志, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 465   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   新たな診断・治療開発に向けた婦人科がん分子機構の解明 卵巣がん細胞由来核酸搭載エクソソームの機能解析と臨床応用 横井 暁 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 24   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   絨毛癌MTX耐性株の作成と解析 西子 裕規, 新美 薫, 横井 暁, 吉田 康将, 柴田 真由, 小田 結加里, 渡邉 絵里, 西野 公博, 山本 英子, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 512   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   絨毛癌の免疫微小環境の解明 NK細胞抑制型受容体に着目して 柴田 真由, 新美 薫, 服部 諭美, 西子 裕規, 小田 結加里, 渡邉 絵里, 横井 暁, 西野 公博, 山本 英子, 梶山 広明 日本産科婦人科学会雑誌   Vol. 74 ( 臨増 ) page: S - 338   2022.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   I期卵巣癌症例に対する妊孕性温存術後補助化学療法の検討 茂木 一将, 吉原 雅人, 池田 芳紀, 藤本 裕基, 北見 和久, 横井 暁, 芳川 修久, 玉内 学志, 西野 公博, 新美 薫, 梶山 広明 日本がん・生殖医療学会誌   Vol. 5 ( 1 ) page: 153 - 153   2022.1  More details Language:Japanese   Publisher:(一社)日本がん・生殖医療学会   バルトリン腺癌との鑑別に難渋したクローン病合併痔瘻癌の1例 松井 真実, 新美 薫, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 梶山 広明 日本婦人科腫瘍学会雑誌   Vol. 40 ( 1 ) page: 10 - 16   2022.1  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   外陰部腺癌は稀であり、腟前庭後部の病変はバルトリン腺原発と考えやすい。今回クローン病罹患中の外陰部腺癌が、術後に痔瘻癌と判明した症例を経験したので報告する。症例は48歳の女性で、クローン病で内科的治療を継続していた。前医を受診する6ヵ月前に左腟前庭部に腫瘤が出現し前医を受診した。生検でadenocarcinomaと診断された。腸管由来の可能性も示唆されたため、上下部消化管内視鏡精査を行ったが悪性腫瘍を認めず、バルトリン腺癌疑いで当院を紹介受診した。初診時、左バルトリン腺領域に4cm大、その腹側の陰核左側に1.5cm大の腫瘤を認めた。CT検査で両側鼠径リンパ節の軽度腫大を認めた。2週間後に単純外陰切除術、両側鼠径リンパ節生検を施行した。病理診断は中分化腺癌であり、大腸粘膜上皮と腺癌との連続性が確認できたため痔瘻癌と診断した。切除断端は左腟壁深部剥離面が陽性であり、両側鼠径リンパ節にも転移を認めた。前手術から3ヵ月後に外科にてロボット支援腹腔鏡下腹会陰式直腸切除術、腟会陰切除術、大腸ストーマ造設術、鼠径リンパ節郭清術を施行され、現在化学療法(CAPOX療法)を行っている。外陰部は痔瘻が発生する場所として矛盾しないため、クローン病既往の外陰部腺癌は痔瘻由来の可能性を積極的に考慮し、術前に痔瘻の精査を十分に行う必要がある。(著者抄録) 境界悪性卵巣腫瘍に対する妊孕性温存術式・腫瘍核出術の安全性に関する多施設協同研究 北見 和久, 池田 芳紀, 吉原 雅人, 芳川 修久, 玉内 学志, 横井 暁, 西野 公博, 新美 薫, 梶山 広明 日本がん・生殖医療学会誌   Vol. 5 ( 1 ) page: 125 - 125   2022.1  More details Language:Japanese   Publisher:(一社)日本がん・生殖医療学会   高用量medroxyprogesterone acetateの再投与は有効か;子宮体癌および子宮内膜異型増殖症に対する妊孕性温存治療 呉 尚郁, 玉内 学志, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 梶山 広明 日本がん・生殖医療学会誌   Vol. 5 ( 1 ) page: 133 - 133   2022.1  More details Language:Japanese   Publisher:(一社)日本がん・生殖医療学会   悪性卵巣腫瘍の再発疑い例において妊孕性温存療法を施行した3症例 関 友望, 大須賀 智子, 三宅 菜月, 玉内 学志, 横井 暁, 池田 芳紀, 後藤 真紀, 梶山 広明 日本がん・生殖医療学会誌   Vol. 5 ( 1 ) page: 150 - 150   2022.1  More details Language:Japanese   Publisher:(一社)日本がん・生殖医療学会   悪性卵巣腫瘍の再発疑い例において妊孕性温存療法を施行した3症例 関 友望, 大須賀 智子, 三宅 菜月, 玉内 学志, 横井 暁, 池田 芳紀, 後藤 真紀, 梶山 広明 日本がん・生殖医療学会誌   Vol. 5 ( 1 ) page: 150 - 150   2022.1  More details Language:Japanese   Publisher:(一社)日本がん・生殖医療学会   境界悪性卵巣腫瘍に対する妊孕性温存術式・腫瘍核出術の安全性に関する多施設協同研究 北見 和久, 池田 芳紀, 吉原 雅人, 芳川 修久, 玉内 学志, 横井 暁, 西野 公博, 新美 薫, 梶山 広明 日本がん・生殖医療学会誌   Vol. 5 ( 1 ) page: 125 - 125   2022.1  More details Language:Japanese   Publisher:(一社)日本がん・生殖医療学会   バルトリン腺癌との鑑別に難渋したクローン病合併痔瘻癌の1例 松井 真実, 新美 薫, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 梶山 広明 日本婦人科腫瘍学会雑誌   Vol. 40 ( 1 ) page: 10 - 16   2022.1  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   外陰部腺癌は稀であり、腟前庭後部の病変はバルトリン腺原発と考えやすい。今回クローン病罹患中の外陰部腺癌が、術後に痔瘻癌と判明した症例を経験したので報告する。症例は48歳の女性で、クローン病で内科的治療を継続していた。前医を受診する6ヵ月前に左腟前庭部に腫瘤が出現し前医を受診した。生検でadenocarcinomaと診断された。腸管由来の可能性も示唆されたため、上下部消化管内視鏡精査を行ったが悪性腫瘍を認めず、バルトリン腺癌疑いで当院を紹介受診した。初診時、左バルトリン腺領域に4cm大、その腹側の陰核左側に1.5cm大の腫瘤を認めた。CT検査で両側鼠径リンパ節の軽度腫大を認めた。2週間後に単純外陰切除術、両側鼠径リンパ節生検を施行した。病理診断は中分化腺癌であり、大腸粘膜上皮と腺癌との連続性が確認できたため痔瘻癌と診断した。切除断端は左腟壁深部剥離面が陽性であり、両側鼠径リンパ節にも転移を認めた。前手術から3ヵ月後に外科にてロボット支援腹腔鏡下腹会陰式直腸切除術、腟会陰切除術、大腸ストーマ造設術、鼠径リンパ節郭清術を施行され、現在化学療法(CAPOX療法)を行っている。外陰部は痔瘻が発生する場所として矛盾しないため、クローン病既往の外陰部腺癌は痔瘻由来の可能性を積極的に考慮し、術前に痔瘻の精査を十分に行う必要がある。(著者抄録) Other Link: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J03271&link_issn=&doc_id=20220224040002&doc_link_id=10.57291%2Fjsgo.40.1_10&url=https%3A%2F%2Fdoi.org%2F10.57291%2Fjsgo.40.1_10&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif I期卵巣癌症例に対する妊孕性温存術後補助化学療法の検討 茂木 一将, 吉原 雅人, 池田 芳紀, 藤本 裕基, 北見 和久, 横井 暁, 芳川 修久, 玉内 学志, 西野 公博, 新美 薫, 梶山 広明 日本がん・生殖医療学会誌   Vol. 5 ( 1 ) page: 153 - 153   2022.1  More details Language:Japanese   Publisher:(一社)日本がん・生殖医療学会   初期粘液性卵巣癌における系統的リンパ節郭清の意義 プロペンシティスコア解析 茂木 一将, 吉原 雅人, 玉内 学志, 伊吉 祥平, 横井 暁, 河井 通泰, 長坂 徹郎, 高橋 邦彦, 松井 茂之, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 59回   page: O9 - 5   2021.10  More details Language:English   Publisher:(一社)日本癌治療学会   腹腔鏡下子宮全摘術に対する手技の工夫(腹腔内操作、腟式操作)や合併症への注意点 合併症を起こさないために意識すべき三角形と脂肪 池田 芳紀, 植草 良輔, 甲木 聡, 長尾 有佳里, 大野 真由, 北見 和久, 村上 真由子, 鈴木 徹平, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 中村 智子, 大須賀 智子, 梶山 広明 東海産婦人科内視鏡手術研究会雑誌   Vol. 9   page: 24 - 24   2021.10  More details Language:Japanese   Publisher:東海産婦人科内視鏡手術研究会   卵巣境界悪性腫瘍における腫瘍核出術の安全性に関する多施設共同研究 北見 和久, 池田 芳紀, 吉原 雅人, 宇野 枢, 茂木 一将, 玉内 学志, 芳川 修久, 横井 暁, 西野 公博, 新美 薫, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 59回   page: O9 - 4   2021.10  More details Language:English   Publisher:(一社)日本癌治療学会   卵巣境界悪性腫瘍における腫瘍核出術の安全性に関する多施設共同研究 北見 和久, 池田 芳紀, 吉原 雅人, 宇野 枢, 茂木 一将, 玉内 学志, 芳川 修久, 横井 暁, 西野 公博, 新美 薫, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 59回   page: O9 - 4   2021.10  More details Language:English   Publisher:(一社)日本癌治療学会   初期粘液性卵巣癌における系統的リンパ節郭清の意義 プロペンシティスコア解析 茂木 一将, 吉原 雅人, 玉内 学志, 伊吉 祥平, 横井 暁, 河井 通泰, 長坂 徹郎, 高橋 邦彦, 松井 茂之, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 59回   page: O9 - 5   2021.10  More details Language:English   Publisher:(一社)日本癌治療学会   Chemical libraryによる絨毛癌の新規治療薬の探索 渡邉 絵里, 横井 暁, 吉田 康将, 山本 雄介, 西野 公博, 新美 薫, 梶山 広明 日本癌学会総会記事   Vol. 80回   page: [J14 - 6]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   ドラッグリポジショニングを用いた卵巣がん細胞のエクソソーム分泌抑制剤のスクリーニング 吉岡 祐亮, 横井 暁, 落谷 孝広 日本癌学会総会記事   Vol. 80回   page: [E11 - 6]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   HBOC乳癌患者において、乳房切除及び乳房再建術とRRSOを同一症例に施行する際に注意すべきこと 西野 公博, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 新美 薫, 梶山 広明 日本産科婦人科内視鏡学会雑誌   Vol. 37 ( Suppl.I ) page: 340 - 340   2021.9  More details Language:Japanese   Publisher:(一社)日本産科婦人科内視鏡学会   卵巣がんにおける脂肪系幹細胞由来small extracellular vesiclesの抗腫瘍効果 横井 暁, 吉田 康将, 宇野 枢, 梶山 広明 日本癌学会総会記事   Vol. 80回   page: [E11 - 4]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   子宮平滑筋肉腫における新規治療薬剤探索 長尾 有佳里, 横井 暁, 吉田 康将, 渡邉 絵里, 吉原 雅人, 玉内 学志, 芳川 修久, 山本 雄介, 加藤 友康, 梶山 広明 日本癌学会総会記事   Vol. 80回   page: [P14 - 6]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   卵巣漿液性がん患者に対する血清中マイクロRNAの予後予測バイオマーカーとしての意義 吉田 康将, 横井 暁, 松崎 潤太郎, 加藤 友康, 落谷 孝広, 梶山 広明, 山本 雄介 日本癌学会総会記事   Vol. 80回   page: [P21 - 5]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   卵巣がんにおける脂肪系幹細胞由来small extracellular vesiclesの抗腫瘍効果 横井 暁, 吉田 康将, 宇野 枢, 梶山 広明 日本癌学会総会記事   Vol. 80回   page: [E11 - 4]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   卵巣漿液性がん患者に対する血清中マイクロRNAの予後予測バイオマーカーとしての意義 吉田 康将, 横井 暁, 松崎 潤太郎, 加藤 友康, 落谷 孝広, 梶山 広明, 山本 雄介 日本癌学会総会記事   Vol. 80回   page: [P21 - 5]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   子宮平滑筋肉腫における新規治療薬剤探索 長尾 有佳里, 横井 暁, 吉田 康将, 渡邉 絵里, 吉原 雅人, 玉内 学志, 芳川 修久, 山本 雄介, 加藤 友康, 梶山 広明 日本癌学会総会記事   Vol. 80回   page: [P14 - 6]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   Chemical libraryによる絨毛癌の新規治療薬の探索 渡邉 絵里, 横井 暁, 吉田 康将, 山本 雄介, 西野 公博, 新美 薫, 梶山 広明 日本癌学会総会記事   Vol. 80回   page: [J14 - 6]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   ドラッグリポジショニングを用いた卵巣がん細胞のエクソソーム分泌抑制剤のスクリーニング 吉岡 祐亮, 横井 暁, 落谷 孝広 日本癌学会総会記事   Vol. 80回   page: [E11 - 6]   2021.9  More details Language:English   Publisher:(一社)日本癌学会   DDIT4は上皮間葉転換の活性化を介して子宮頸癌リンパ節転移のドライバーとして作用する(DDIT4 Acts as a Driver of Lymph Node Metastasis of Cervical Cancer Through Activation of Epithelial-mesenchymal-transition) 林 欣欣, 芳川 修久, 吉原 雅人, 横井 暁, 玉内 学志, 池田 芳紀, 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: 202 - 202   2021.7  More details Language:English   Publisher:(公社)日本婦人科腫瘍学会   フラボノイドを用いた卵巣癌の新規治療戦略 玉内 学志, 吉原 雅人, 横井 暁, 芳川 修久, 池田 芳紀, 西野 公博, 新美 薫, 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: 198 - 198   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   バルトリン腺癌との鑑別に難渋したクローン病合併痔瘻癌の1例 松井 真実, 新美 薫, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 西野 公博, 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: 341 - 341   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   プラズマ活性化溶液を用いた難治性腹膜播種に対する新規治療戦略 芳川 修久, 吉原 雅人, 玉内 学志, 池田 芳紀, 横井 暁, 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: 128 - 128   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   高異型度漿液性進行卵巣癌に対する後腹膜リンパ節郭清の予後への寄与 池田 芳紀, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 教久, 西野 公博, 新美 薫, 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: 264 - 264   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   進行・再発卵巣明細胞癌におけるX染色体長腕27.3領域のマイクロRNAクラスターの発現意義 吉田 康将, 横井 暁, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 鈴木 史朗, 吉川 史隆, 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: 197 - 197   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   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  More details Language:English   Publisher:(公社)日本婦人科腫瘍学会   早期子宮体癌に対する当院の低侵襲手術手順の変遷と再発例の検討 池田 芳紀, 秋田 寛佳, 茂木 一将, 服部 諭美, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 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: 306 - 306   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   既存薬ライブラリスクリーニングによる絨毛癌新規治療薬探索 渡邉 絵里, 横井 暁, 吉田 康将, 西野 公博, 新美 薫, 山本 雄介, 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: 345 - 345   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   子宮頸癌における断端陽性円錐切除術の骨盤リンパ節転移への影響に関する検討 長尾 有佳里, 横井 暁, 角 真徳, 吉原 雅人, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 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: 217 - 217   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   婦人科がんにおけるliquid biopsyの有用性 卵巣がん細胞外小胞の機能解析と臨床応用へ向けた基盤研究 横井 暁 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: 149 - 149   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   妊孕性温存手術を実施した早期卵巣癌患者の再発予後因子の検討 茂木 一将, 宇野 枢, 伊吉 祥平, 北見 和久, 吉原 雅人, 玉内 学志, 池田 芳紀, 横井 暁, 芳川 修久, 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: 209 - 209   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   卵巣類内膜癌における妊孕性温存手術の腫瘍学的予後 北見 和久, 茂木 一将, 宇野 枢, 吉原 雅人, 玉内 学志, 池田 芳紀, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 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: 274 - 274   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   卵巣癌におけるプラチナ分布に基づいたプラチナ抵抗性の可視化と新規治療戦略 宇野 枢, 芳川 修久, 吉原 雅人, 北見 和久, 伊吉 祥平, 大沼 章子, 田崎 啓, 玉内 学志, 横井 暁, 加藤 昌志, 吉川 史隆, 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: 194 - 194   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   卵巣明細胞癌におけるGlypican-3由来ペプチドワクチン療法の治療反応性を予測するバイオマーカーとしての血清中miRNA(Serum miRNAs as Predictive Responsive Biomarkers of Glypican-3-derived Peptide Vaccine Therapy in Ovarian Clear Cell Carcinoma) 大野 真由, 横井 暁, 吉田 康将, 鈴木 史朗, 柴田 清澄, 吉川 史隆, 中面 哲也, 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: 203 - 203   2021.7  More details Language:English   Publisher:(公社)日本婦人科腫瘍学会   卵巣性索間質性腫瘍I期における子宮温存手術の予後解析 茂木 一将, 吉原 雅人, 伊吉 祥平, 宇野 枢, 北見 和久, 玉内 学志, 池田 芳紀, 横井 暁, 芳川 修久, 河井 通泰, 長坂 徹郎, 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: 274 - 274   2021.7  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   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  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   難治性卵巣癌の微小環境が誘導する抗癌剤ホルミシスとその克服へ向けての新展開 玉内 学志, 茂木 一将, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 270   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   進行卵巣類内膜癌の後腹膜リンパ節郭清に関する検討 大野 真由, 吉原 雅人, 横井 暁, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 322   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   当院における早期子宮体癌に対する腹腔鏡下手術と開腹手術の後方視的比較検討 秋田 寛佳, 池田 芳紀, 茂木 一将, 服部 諭美, 大野 真由, 北見 和久, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 404   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   当院で手術した80歳以上の子宮体癌患者の臨床的検討 池田 芳紀, 秋田 寛佳, 茂木 一将, 服部 諭美, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 481   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   子宮頸癌における断端陽性円錐切除術が骨盤リンパ節転移に与える影響についての検討 長尾 有佳里, 横井 暁, 角 真徳, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 559   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   子宮頸癌IB1期において脈管侵襲は術後再発リスク因子となるか 服部 諭美, 芳川 修久, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 308   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   難治性卵巣癌の微小環境が誘導する抗癌剤ホルミシスとその克服へ向けての新展開 玉内 学志, 茂木 一将, 吉原 雅人, 横井 暁, 池田 芳紀, 芳川 修久, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 270   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   進行卵巣類内膜癌の後腹膜リンパ節郭清に関する検討 大野 真由, 吉原 雅人, 横井 暁, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 322   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   当院における早期子宮体癌に対する腹腔鏡下手術と開腹手術の後方視的比較検討 秋田 寛佳, 池田 芳紀, 茂木 一将, 服部 諭美, 大野 真由, 北見 和久, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 404   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   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  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   子宮頸癌IB1期において脈管侵襲は術後再発リスク因子となるか 服部 諭美, 芳川 修久, 吉原 雅人, 玉内 学志, 横井 暁, 池田 芳紀, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 308   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   子宮頸癌における断端陽性円錐切除術が骨盤リンパ節転移に与える影響についての検討 長尾 有佳里, 横井 暁, 角 真徳, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 559   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   当院で手術した80歳以上の子宮体癌患者の臨床的検討 池田 芳紀, 秋田 寛佳, 茂木 一将, 服部 諭美, 吉原 雅人, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 日本産科婦人科学会雑誌   Vol. 73 ( 臨増 ) page: S - 481   2021.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   血液マイクロRNAによる子宮肉腫と変性筋腫の術前鑑別診断 加藤 友康, 横井 暁, 松崎 潤太郎, 山本 雄介, 舘 慶生, 米岡 完, 清水 華子, 植原 貴史, 石川 光也, 滝澤 聡子, 青木 良晃, 加藤 健, 落谷 孝広, 東レ株式会社新事業開発部門DNAチップG 日本婦人科腫瘍学会雑誌   Vol. 39 ( 1 ) page: 297 - 297   2021.1  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   血液マイクロRNAによる子宮肉腫と変性筋腫の術前鑑別診断 加藤 友康, 横井 暁, 松崎 潤太郎, 山本 雄介, 舘 慶生, 米岡 完, 清水 華子, 植原 貴史, 石川 光也, 滝澤 聡子, 青木 良晃, 加藤 健, 落谷 孝広, 東レ株式会社新事業開発部門DNAチップG 日本婦人科腫瘍学会雑誌   Vol. 39 ( 1 ) page: 297 - 297   2021.1  More details Language:Japanese   Publisher:(公社)日本婦人科腫瘍学会   当院での早期子宮体癌に対する腹腔鏡下子宮悪性腫瘍手術の後方視的検討 茂木 一将, 池田 芳紀, 秋田 寛佳, 伊吉 祥平, 宇野 枢, 小田 結加里, 甲木 聡, 服部 諭美, 大野 真由, 北見 和久, 村上 真由子, 渡邉 絵里, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 中村 智子, 大須賀 智子, 梶山 広明 日本産科婦人科内視鏡学会雑誌   Vol. 36 ( Suppl.I ) page: [O - 465]   2020.11  More details Language:Japanese   Publisher:(一社)日本産科婦人科内視鏡学会   当院での早期子宮体癌に対する腹腔鏡下子宮悪性腫瘍手術の後方視的検討 茂木 一将, 池田 芳紀, 秋田 寛佳, 伊吉 祥平, 宇野 枢, 小田 結加里, 甲木 聡, 服部 諭美, 大野 真由, 北見 和久, 村上 真由子, 渡邉 絵里, 玉内 学志, 横井 暁, 芳川 修久, 西野 公博, 新美 薫, 中村 智子, 大須賀 智子, 梶山 広明 日本産科婦人科内視鏡学会雑誌   Vol. 36 ( Suppl.I ) page: [O - 465]   2020.11  More details Language:Japanese   Publisher:(一社)日本産科婦人科内視鏡学会   核由来DNA搭載エクソソームを用いた新規リキッドバイオプシー戦略 International journal 横井 暁 日本癌学会総会記事   Vol. 79回   page: IS5 - 6   2020.10  More details Language:English   Publisher:(一社)日本癌学会   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 International journal 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  More details Language:English   Publisher:(一社)日本癌学会   卵巣癌の腹膜播種における腹膜中皮と脂肪組織の影響 International journal 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  More details Language:English   Publisher:(一社)日本癌学会   卵巣明細胞癌におけるchrXq27.3 miRNAクラスターの転移・再発への役割 International journal 吉田 康将, 横井 暁, 吉原 雅人, 玉内 学志, 芳川 修久, 西野 公博, 新美 薫, 吉川 史隆, 梶山 広明 日本癌学会総会記事   Vol. 79回   page: OE5 - 2   2020.10  More details Language:English   Publisher:(一社)日本癌学会   卵巣性索間質性腫瘍I期における妊孕性温存手術の後方視的解析 International journal 茂木 一将, 吉原 雅人, 伊吉 祥平, 宇野 枢, 北見 和久, 玉内 学志, 横井 暁, 芳川 修久, 池田 芳紀, 河井 通泰, 長坂 徹郎, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 58回   page: O64 - 3   2020.10  More details Language:English   Publisher:(一社)日本癌治療学会   卵巣がんにおける核酸搭載細胞外小胞の機能解析と臨床応用 International journal 横井 暁 日本癌学会総会記事   Vol. 79回   page: YIA - 2   2020.10  More details Language:English   Publisher:(一社)日本癌学会   卵巣がんにおける核酸搭載細胞外小胞の包括的解析 International journal 横井 暁, 落谷 孝広 日本癌学会総会記事   Vol. 79回   page: ISEV - 5   2020.10  More details Language:English   Publisher:(一社)日本癌学会   LuteolinはVRK1の発現を低下させることにより卵巣癌の進行抑制 International journal 常 続博雅, 梶山 広明, 芳川 修久, 横井 暁, 玉内 学志, 吉原 雅人 日本癌学会総会記事   Vol. 79回   page: PE14 - 3   2020.10  More details Language:English   Publisher:(一社)日本癌学会   I期卵巣癌における術中被膜破綻と縮小手術及び術後化学療法の予後に与える影響 International journal 吉原 雅人, 宇野 枢, 北見 和久, 伊吉 祥平, 田野 翔, 茂木 一将, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 58回   page: O18 - 6   2020.10  More details Language:English   Publisher:(一社)日本癌治療学会   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 International journal 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  More details Language:English   Publisher:(一社)日本癌学会   I期卵巣癌における術中被膜破綻と縮小手術及び術後化学療法の予後に与える影響 吉原 雅人, 宇野 枢, 北見 和久, 伊吉 祥平, 田野 翔, 茂木 一将, 玉内 学志, 横井 暁, 池田 芳紀, 芳川 修久, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 58回   page: O18 - 6   2020.10  More details Language:English   Publisher:(一社)日本癌治療学会   卵巣性索間質性腫瘍I期における妊孕性温存手術の後方視的解析 茂木 一将, 吉原 雅人, 伊吉 祥平, 宇野 枢, 北見 和久, 玉内 学志, 横井 暁, 芳川 修久, 池田 芳紀, 河井 通泰, 長坂 徹郎, 梶山 広明 日本癌治療学会学術集会抄録集   Vol. 58回   page: O64 - 3   2020.10  More details Language:English   Publisher:(一社)日本癌治療学会   卵巣がんにおける核酸搭載細胞外小胞の包括的解析 横井 暁, 落谷 孝広 日本癌学会総会記事   Vol. 79回   page: ISEV - 5   2020.10  More details Language:English   Publisher:(一社)日本癌学会   核由来DNA搭載エクソソームを用いた新規リキッドバイオプシー戦略 横井 暁 日本癌学会総会記事   Vol. 79回   page: IS5 - 6   2020.10  More details Language:English   Publisher:(一社)日本癌学会   子宮頸癌断端陽性円錐切除術による骨盤リンパ節転移への影響についての検討 角 真徳, 横井 暁, 玉内 学志, 池田 芳紀, 芳川 修久, 西野 公博, 新美 薫, 梶山 広明 愛知産科婦人科学会学術講演会プログラム   Vol. 112回   page: 7 - 7   2020.10  More details Language:Japanese   Publisher:愛知産科婦人科学会   卵巣がんにおける核酸搭載細胞外小胞の機能解析と臨床応用 横井 暁 日本癌学会総会記事   Vol. 79回   page: YIA - 2   2020.10  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   卵巣明細胞癌におけるchrXq27.3 miRNAクラスターの転移・再発への役割 吉田 康将, 横井 暁, 吉原 雅人, 玉内 学志, 芳川 修久, 西野 公博, 新美 薫, 吉川 史隆, 梶山 広明 日本癌学会総会記事   Vol. 79回   page: OE5 - 2   2020.10  More details Language:English   Publisher:(一社)日本癌学会   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  More details Language:English   Publisher:(一社)日本癌学会   LuteolinはVRK1の発現を低下させることにより卵巣癌の進行抑制 常 続博雅, 梶山 広明, 芳川 修久, 横井 暁, 玉内 学志, 吉原 雅人 日本癌学会総会記事   Vol. 79回   page: PE14 - 3   2020.10  More details Language:English   Publisher:(一社)日本癌学会   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 International journal 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   Vol. 72 ( 臨増 ) page: S - 401   2020.3  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   【産婦人科領域で話題の新技術-時代の潮流に乗り遅れないための羅針盤】(Part2)注目の最新技術 腫瘍 マイクロRNA測定技術を用いた卵巣がんの早期診断 International journal 横井 暁, 落谷 孝広 臨床婦人科産科   Vol. 73 ( 12 ) page: 1222 - 1226   2019.12  More details Language:Japanese   Publisher:(株)医学書院   <文献概要>●血液中を循環するマイクロRNAをバイオマーカーとして臨床応用することを目的とした取り組み.●卵巣がん患者群において有意に変化する複数のマイクロRNAを同定し,それらの組み合わせにより,早期から高精度でがんの存在を検出できる診断モデルを作成.●卵巣がん診断血液スクリーニングの実現に大きな前進をもたらす成果である. Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01564&link_issn=&doc_id=20191202060012&doc_link_id=10.11477%2Fmf.1409209874&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1409209874&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif 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) International journal 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   Vol. 78回   page: SST7 - 4   2019.9  More details Language:English   Publisher:日本癌学会   卵巣成熟奇形腫の悪性転化における特徴的なmiRNA発現プロファイルの同定(Identification of unique miRNA profiling in squamous cell carcinoma arising from mature teratoma of ovary) International journal 吉田 康将, 横井 暁, 玉内 学志, 吉原 雅人, 芳川 修久, 西野 公博, 新美 薫, 鈴木 史朗, 梶山 広明, 吉川 史隆 日本癌学会総会記事   Vol. 78回   page: P - 1350   2019.9  More details Language:English   Publisher:日本癌学会   卵巣成熟奇形腫の悪性転化における特徴的なmiRNA発現プロファイルの同定(Identification of unique miRNA profiling in squamous cell carcinoma arising from mature teratoma of ovary) International journal 吉田 康将, 横井 暁, 玉内 学志, 吉原 雅人, 芳川 修久, 西野 公博, 新美 薫, 鈴木 史朗, 梶山 広明, 吉川 史隆 日本癌学会総会記事   Vol. 78回   page: P - 1350   2019.9  More details Language:English   Publisher:日本癌学会   エクソソーム分泌を阻害する低分子化合物のスクリーニング(Discovery of an inhibitor for EV secretion in cancer cells using a small-molecule library approach) International journal 吉岡 祐亮, 横井 暁, 落谷 孝広 日本癌学会総会記事   Vol. 78回   page: E - 3047   2019.9  More details Language:English   Publisher:日本癌学会   エクソソーム分泌を阻害する低分子化合物のスクリーニング(Discovery of an inhibitor for EV secretion in cancer cells using a small-molecule library approach) International journal 吉岡 祐亮, 横井 暁, 落谷 孝広 日本癌学会総会記事   Vol. 78回   page: E - 3047   2019.9  More details Language:English   Publisher:日本癌学会   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) International journal 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  More details Language:English   Publisher:日本癌学会   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) International journal 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  More details Language:English   Publisher:日本癌学会   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) International journal 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   Vol. 78回   page: SST7 - 4   2019.9  More details Language:English   Publisher:日本癌学会   卵巣がん腹膜播種形成時における腹膜の変化と役割 International journal 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   Vol. 71 ( 臨増 ) page: S - 293   2019.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   院内助産で分娩管理を行った生殖補助医療(ART)妊婦の産後過多出血の検討 International journal 大島 和美, 横井 暁, 柴田 幸子, 真野 真紀子 日本助産学会誌   Vol. 32 ( 2 ) page: 169 - 177   2018.12  More details Language:Japanese   Publisher:(一社)日本助産学会   目的 バースセンター(以下BC)は、総合周産期母子医療センターに併設する院内助産施設である。BCでは妊娠分娩経過は正常であっても、出産後に予期せぬ多量出血を経験することがある。生殖補助医療(以下ART)妊娠は癒着胎盤のリスク因子と言われており、且つ癒着胎盤は産科危機的出血の原因となり得る。当施設ではART妊娠であっても院内助産分娩希望があれば、産科医許可のもとBCで分娩を取扱っている。本研究ではART妊娠(新鮮胚移植妊娠、融解胚移植妊娠)の産後過多出血(以下PPH)を検証し、院内助産におけるリスク評価、及び対応を検討した。対象と方法 研究デザインは症例対照研究である。対象は2013年4月から2016年3月の調査期間中にBCで取り扱った分娩604例で、うち非ART妊娠は567例、ART妊娠は37例(新鮮胚移植9例、融解胚移植28例)であった。非ART妊娠と新鮮胚移植妊娠、融解胚移植妊娠で分娩後出血量、産褥24時間出血量、及びPPH(分娩後出血500ml以上、産褥24時間出血800ml以上)頻度の統計解析を行った。分娩後出血量、産褥24時間出血量を重回帰分析で、PPH頻度を多変量ロジスティック分析により検証した。結果 融解胚移植妊娠は分娩後出血量、産褥24時間出血量が非ART妊娠より有意に多く、PPHの頻度は非ART妊娠より有意に高かった。PPHのうち4例が産科危機的出血であったが、うち3例は融解胚移植のART妊婦であった。結論 ART妊婦の中でも融解胚移植妊娠はPPHのリスク因子になることが示唆された。融解胚移植妊娠については医師と速やかな医療連携がとれる体制の確立、及び将来的に院内助産分娩の対象から除外すべきか検討するための調査が必要と考える。(著者抄録) Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02875&link_issn=&doc_id=20190107430008&doc_link_id=130007549960&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007549960&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif Notch signaling enhances the mutual association with epithelial ovarian cancer and mesothelial cells Mai Sugiyama, Masato Yoshihara, Yoshihiro Koya, Akira Yokoi, Buntei Ryu, Fumitaka Kikkawa, Hiroaki Kajiyama CANCER SCIENCE   Vol. 109   page: 864 - 864   2018.12  More details Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY   Web of Science Cancer-associated mesothelial cells as a potential therapeutic target in epithelial ovarian cancer 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  More details Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY   Web of Science RNA生物学の発展ががん研究にもたらしたもの 卵巣がんにおける細胞外RNAの関与(Progress in cancer research through RNA biology The role of extracellular RNAs in ovarian cancer) International journal 横井 暁, 吉岡 祐亮, 山本 雄介, 松崎 潤太郎, 加藤 友康, 加藤 健, 梶山 広明, 吉川 史隆, 落谷 孝広 日本癌学会総会記事   Vol. 77回   page: 231 - 231   2018.9  More details Language:English   Publisher:日本癌学会   表層上皮性卵巣癌におけるNotch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(Notch signaling enhances the mutual association with epithelial ovarian cancer and mesothelial cells) International journal 杉山 麻衣, 吉原 雅人, 小屋 美博, 横井 暁, 劉 文亭, 吉川 史隆, 梶山 広明 日本癌学会総会記事   Vol. 77回   page: 1351 - 1351   2018.9  More details Language:English   Publisher:日本癌学会   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) International journal 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  More details Language:English   Publisher:日本癌学会   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 International journal 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   Vol. 70 ( 2 ) page: 857 - 857   2018.2  More details Language:Japanese   Publisher:(公社)日本産科婦人科学会   Carcinoma-associated mesothelial cells promote dissemination and platinum resistance in epithelial ovarian cancer. 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  More details Language:English   Publishing type:Research paper, summary (international conference)   Publisher:WILEY   Web of Science 【最新免疫学×周産期医学】基礎医学 免疫学の最初の一歩 細胞が放出する"エクソソーム"を対象とした新たな研究展開 International journal 横井 暁, 落合 孝広 周産期医学   Vol. 47 ( 12 ) page: 1539 - 1546   2017.12  More details Language:Japanese   Publisher:(株)東京医学社   卵巣癌細胞由来悪性エクソソームによる腹膜播種性転移促進メカニズム International journal 横井 暁, 吉岡 祐亮, 山本 雄介, 石川 光也, 加藤 友康, 清野 透, 梶山 広明, 吉川 史隆, 落谷 孝広 日本癌学会総会記事   Vol. 76回   page: IS1 - 6   2017.9  More details Language:English   Publisher:日本癌学会   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 International journal 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   Vol. 76回   page: E - 1054   2017.9  More details Language:English   Publisher:日本癌学会   血清中miRNAプロファイルによる早期卵巣がん診断バイオマーカーの開発 International journal 横井 暁, 吉岡 祐亮, 加藤 友康, 梶山 広明, 吉川 史隆, 落谷 孝広 日本分子腫瘍マーカー研究会誌   Vol. 32   page: 27 - 28   2017.3  More details Language:Japanese   Publisher:日本分子腫瘍マーカー研究会   【Liquid biopsy】乳癌におけるエクソソーム研究 International journal 横井 暁, 吉岡 祐亮, 落谷 孝広 乳癌の臨床   Vol. 32 ( 1 ) page: 21 - 29   2017.2  More details Language:Japanese   Publisher:(株)篠原出版新社   ▼display all To the head of MISC.▲ Presentations Presentations 18 細胞外循環型マイクロRNAによる新しいバイオマーカー戦略 Invited 横井 暁 日本婦人科がん検診学会総会・学術講演会  2021.9.11   More details Event date: 2021.9 卵巣がん新規診断バイオマーカーとしての血中miRNAの可能性 Invited 横井 暁 「体液中マイクロRNA測定技術基盤開発」第7回ユーザーフォーラム報告会  2017.10   More details Language:Japanese   Presentation type:Oral presentation (invited, special)   Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer Invited Akira Yokoi, Yusuke Yoshioka, Yusuke Yamamoto, Mitsuya Ishikawa, Tomoyasu Kato, Tohru Kiyono, Hiroaki Kajiyama, Fumitaka Kikkawa, Takahiro Ochiya The 76th Annual Meeting of the Japanese Cancer Association  2017.9   More details Language:Japanese   Presentation type:Oral presentation (invited, special)   Indispensable Roles of Extracellular RNA in Ovarian Cancer Invited Akira Yokoi, Yusuke Yoshioka, Takahiro Ochiya The 9th JARI/ The 4th JSEV Annual Meeting  2017.9   More details Language:Japanese   Presentation type:Oral presentation (invited, special)   Comprehensive analyses of ovarian cancer exosomes for clinical applications Invited Akira Yokoi ASGO 2022 7th International Workshop on Gynecologic Oncology  2022.8.27   More details Language:English   Presentation type:Symposium, workshop panel (nominated)   卵巣がん細胞由来核酸搭載エクソソームの機能解析と臨床応用 Invited 横井 暁 第74回日本産科婦人科学会学術講演会  2022.8.5   More details Presentation type:Symposium, workshop panel (nominated)   卵巣がん細胞外小胞の機能解析と臨床応用へ向けた基盤研究 Invited 横井 暁 第63回日本婦人科腫瘍学会学術講演会  2021.7.17   More details Language:Japanese   Presentation type:Oral presentation (invited, special)   EVシートによる生体内微量腹水中エクソソーム解析 Invited 横井 暁 第7回 Liquid Biopsy 研究会  2023.1.28  DNA損傷応答/分裂期のチェックポイント 子宮平滑筋肉腫に対するPLK1/CHEK1阻害剤 Invited 横井 暁 第7回日本肉腫学会年次学術集会  2022.11.19  Physician/Surgeon Scientistとしてのトランスレーショナルエクソソーム研究の展開 Invited 横井暁 SGR講演会 第37回 Surgical Grand Round  2024.3.11  Malignant Mechanisms of Intercellular Communication in Gynecologic Cancers Invited Akira Yokoi 8th Biennial Meeting of Asian Society of Gynecologic Oncology (ASGO 2023)  2023.12.3   More details Language:English   Presentation type:Oral presentation (invited, special)   Translational Research for Extracellular Vesicles in Ovarian Carcinoma Invited Akira Yokoi 2023.7.15   More details Language:English   「紙で ペタッ とエクソソーム回収」EVシートによる生体内微量腹水中エクソソーム解析 Invited 横井暁 The 166th Scienc-ome  2023.11.8  卵巣がんにおける細胞外小胞エクソソームの包括的機能解析 Invited 横井 暁 第75回 日本産科婦人科学会学術講演会  2023.5.13  新しいエクソソーム捕捉ツール「EVシート」を開発 ― 生体内におけるエクソソームの空間解析とがん医療応用に期待 ― Invited 横井暁 AMED iD3 第15回 Top Runners in TRS  2023.12.28  産婦人科領域におけるエクソソーム研究の可能性 Invited 横井暁 慶應薬学 先端実学セミナー  2023.10.12  空間的腹水中エクソソーム解析による新しい卵巣がん進展メカニズム解析 Invited 横井 暁 第65回日本婦人科腫瘍学会  2023.7.16  Application of novel exosome isolation technologies for realizing liquid biopsy strategies Invited Akira Yokoi 2024.2.2  ▼display all To the head of Presentations.▲ KAKENHI (Grants-in-Aid for Scientific Research) KAKENHI (Grants-in-Aid for Scientific Research) 9 Novel heterogeneity analyses for extracellular vesicles in micro volume bio-fluids Grant number:22K18394  2022.6 - 2025.3 Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Pioneering)   More details Authorship:Principal investigator  Grant amount:\26000000 ( Direct Cost: \20000000 、 Indirect Cost:\6000000 ) 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 日本学術振興会  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   More details 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。本課題では、腹腔内全体を一つの生態的環境(エコシステム)と見なし、「卵巣癌-腹膜間の細胞コミュニケーション」をつなぐ主要な媒体である悪性腹水中のペプチドバランスに着目した新規卵巣癌腹膜進展の機序解明を目的とする。そして、フライブルグ大学分子医学研究所及び病理部に所属するOliver Schilling博士との国際共同研究の上、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明らかとするために、TMT-TAILS法を用いて、N-ターミノームを網羅的探索することで、癌性腹膜炎化に対する寄与の大きい基質を見出すデグラドミクス解析を行う。さらに、腹腔内エコシステムにおける卵巣癌細胞と宿主細胞としての腹膜中皮細胞や脂肪細胞とが織りなす相互作用を標的として、進行卵巣癌の癌性腹膜炎化に至る新規メカニズムを解明する。最終的に、卵巣癌における腹膜環境の正常化に焦点にあてたジペプチジルペプチダーゼ阻害剤を治療応用につなげるべく、臨床上の活用を目指す。本年度は、ジョイントディグリープログラムの一環として留学していた大学院生1名が留学を終えて帰国し、学位取得に至った。また前年度に行った卵巣癌悪性腹水の大規模プロテオミクス解析の結果得られた新たに3つの腹水分子型サブタイプと新規予後マーカーの同定という成果を踏まえ、得られたマーカー分子の機能解析実験を行った。これらの結果は今後の卵巣癌個別化医療の発展に寄与するものと考えられ、現在論文として報告準備中である。本年度の研究により、以下の内容に関する成果を挙げることができたと考える。前年度までに高悪性度漿液性卵巣癌(HGSOC)91例から採取した悪性腹水を用いて、データ非依存解析(DIA)法による大規模プロテオミクス解析を行い、3つの異なる分子型サブグループを同定するとともに、Cox proportional hazards model by componentwise likelihood based boosting (CoxBoost法)を用いて、予後に関連するバイオマーカーを同定した。本年度は、この結果を発展させ、予後と最も相関するタンパク質Aの機能解析に着手した。大網手術検体から得られるヒト腹膜中皮細胞に、悪性腹水中で高濃度存在するTGF-bを添加すると、中皮細胞の中皮-間葉転換(Mesothelial-Mesenchymal Transition)が誘導され、卵巣癌細胞の接着・増殖が亢進することが知られている。リコンビナント・タンパク質Aで処理した後に、蛍光タンパク質を導入した卵巣癌細胞株(Ov-90-GFP)を用いて同様の検討を行うと、中皮細胞への卵巣癌細胞の接着が抑制されることを見出した。リコンビナント・タンパク質Aによる中皮細胞への影響については、現在オミクス解析により分析中である。これらの結果はプロテオームリソースとしての腹水の有用性を示唆するのみにとどまらず、腹膜播種を伴う進行卵巣癌に対する新規治療法の開発に示唆を与えるものである。今後、卵巣癌実験モデル動物を使用した検証実験を行い、これらを統合した内容の論文の作成準備をしている。COVID-19感染症の動向を考慮し、2023年度下旬に渡欧を予定している。これまでに得られている基礎的データをもとに、研究代表者がアミノペプチダーゼを用いた酵素反応実験を含むデータ解析やデグラドミクス解析を、Oliver Schilling博士とともに行う予定である。それまでは、フライブルク大学側の研究協力者とともにwebミーティングによる打ち合わせを行い、各施設での研究を進める。また当初からの標的である腹水中に存在する免疫細胞に対して、腹水が抑制的あるいは促進的に作用するかを、原因となる特異的物質とともに同定することで、腹腔内エコシステムにおける卵巣癌細胞の悪性化プロセスの解明と腹膜環境の正常化を目指した研究基盤の確立を目指す。 腹腔内細胞コミュニケーションが誘導するオカルト播種の休眠維持環境構築のメカニズム Grant number:21K19562  2021.7 - 2024.3 日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽) 梶山 広明, 吉原 雅人, 横井 暁, 芳川 修久   More details Authorship:Coinvestigator(s)  本課題は腹腔内微小環境における癌関連腹膜中皮細胞に注目して、腹腔内オカルト播種の休眠の機能および維持メカニズムを追究する研究である。休眠の維持に関する解析項目に「腫瘍-CAMのNotchシグナル」や免疫回避の第一歩として「SDF-1α制御-腫瘍関連マクロファージ」との関連を取り入れた斬新かつ挑戦的な研究である。本課題で得られた知見によって腹膜全体をターゲットとした包括的治療戦略の策定や新規バイオマーカーの同定を目指す。特に腹膜は面積的に広範囲であるため、標的にしえた場合の治療及びQOL改善の効果も大きいと考えられる。さらに本研究は卵巣癌に限らず癌性腹膜炎を形成しうる他癌にも応用可能となりうる。現在、腹膜播種に対する有効な治療法は確立されているとはいえず、比較的、腹膜播種の発生が多いとされる卵巣癌、大腸癌、および胃癌の腹膜進展に関する分子生物学的機序については未だ不明な点が多い。よい植物が育つにはよい“種”とよい“土壌”が必要であり、腹膜播種の克服には、癌(種)だけではなく腹膜微小環境(土壌)も一体化して考える必要がある。本研究では、「土壌」となる“腫瘍の手先”にさせられた本来生体防御的であった腹膜中皮{癌関連腹膜中皮細胞: Cancer-associated peritoneal mesothelial cell:(CAM)}により、よい「種」としての腹腔内微小環境ストレスに抵抗性を有する生存能力の高い卵巣癌細胞の成立過程を検証し、CAMがどのようなメカニズムで腫瘍細胞の休眠や進化を助け、既存の抗腫瘍薬からの攻撃回避に機能しているかを解明することを最大の研究目的とした。
これまでの研究成果により、CAMに発現するNotchリガンドの一つであるDLL3を介して、一部の卵巣癌細胞にNotchシグナルが誘導されることが判明した。Notch陽性となった卵巣癌細胞は、幹細胞形質を獲得し、細胞周期の遅延や低栄養耐性などの休眠様の状態を呈することを解明した。さらにNotch陽性卵巣癌細胞はNotch陰性細胞から出現し、一方でNotch陰性卵巣癌細胞はNotch陽性細胞からも出現することが明らかとなった。またNotch陽性細胞は代謝変容を引き起こし、プラチナ製剤などへのストレス抵抗性を獲得している機序を明らかにした。さらに本メカニズムを標的とした薬剤を同定し、その効果を各種実験モデルで実証し、これら一連の成果の論文投稿を予定している。これまでに卵巣癌腹膜播種実験モデルを樹立し、腹膜中皮細胞との共培養で生じる癌細胞の変化を解析し、Notchシグナルの関与を同定した。昨年の成果のより、卵巣癌腹膜播種巣において、癌細胞間の極性により生じたNotchシグナルが亢進した細胞では、休眠や幹細胞様の性質を獲得し、治療抵抗性を誘導していると考えられた。またNotchシグナルを阻害するγセクレターゼ阻害剤により卵巣癌腹膜播種マウスモデルに使用したところ、双方で有意な癌細胞増殖や腫瘍形成の低下が見られた。一方でγセクレターゼ阻害剤は副作用の観点から直接的な臨床応用は困難であり、別の薬剤による臨床応用が期待される。本年度は、卵巣癌腹膜播種巣において、Notchシグナルを介した癌細胞の極性が腫瘍内不均一性を標的とした薬剤の探索を行い、既存薬Xを同定した。本薬剤は前述のNotchシグナルが誘導する幹細胞様の性質を間接的に阻害することで、卵巣癌細胞の治療抵抗性を解除する性質があることを明らかにした。実験動物モデルでも同様の効果の検証を行い、治療効果の確認を現在行っている。本年度に得られた結果を元に、論文化に向けた研究をさらに推し進める。卵巣癌において腹膜誘導性のNotch依存性腫瘍内不均一性が、主に代謝変容に基づく細胞運命のダイナミクスを生み出し、卵巣癌腹膜播種の進展を促進することが示されたことから、治療抵抗性の腹膜転移のこれらのメカニズムを標的とした既存薬Xは卵巣癌の治療効果を向上させる可能性が考えられる。次年度は主に動物実験を主体とした薬剤効果の検証を行い、論文化を進めていく予定である。 難治性卵巣がんにおける細胞外小胞機能解析と臨床応用基盤創生 Grant number:21H03075  2021.4 - 2024.3 日本学術振興会  科学研究費助成事業  基盤研究(B) 横井 暁, 梶山 広明, 山本 雄介, 吉田 康将   More details Authorship:Principal investigator  Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 ) 本研究は、卵巣がんにおけるエクソソームを始めとした細胞外小胞(Extracellular Vesicle: EV)を対象とし、EVが有する未だ明らかにされていない腫瘍生物学的意義を明らかにし、臨床応用へ向けた基盤となる知見を得ることを目的とします。未だ臨床的問題点が多く残る難治性卵巣がんにおけるEVの機能解明は極めて重要と考えられます。本研究では、①卵巣がん悪性化に関わるEVの機能解析 ②個別化医療を実現するEVバイオマーカーの創出 ③EVによる難治進行性卵巣がんの新規治療開発の、3点を軸に研究を展開し、卵巣がん患者予後の改善に繋が成果を得ることを目指します。本研究は、卵巣がんにおけるエクソソームを始めとした細胞外小胞(Extracellular Vesicle: EV)を対象とし、EVが有する未だ明らかにされていない腫瘍生物学的意義を明らかにし、臨床応用へ向けた基盤となる知見を得ることを目的とする。あらゆる生細胞が恒常的に放出するEVは、細胞間情報伝達手段として注目されている。今後臨床応用へ向けたトランスレーショナル研究がさらに加速することが予想される一方で、EV研究はその定義や取扱いが未だ議論の的になるほど発展途上である。未だ臨床的問題点が多く残る難治性卵巣がんに於けるEVの機能解明は極めて重要と考えられる。本研究では、①卵巣がん悪性化に関わるEVの機能解析 ②個別化医療を実現するEVバイオマーカーの創出 ③EVによる難治進行性卵巣がんの新規治療開発 の、3点を軸に研究を展開し、卵巣がん患者予後の改善に繋がる成果を得ることを目的として展開する。現在も複数のプロジェクトが進行中であり、特許出願3件、投稿中論文も複数ある。複数学会で招待講演も行った。②に関連して、下記報告をした。Kazuhiro Suzuki, Akira Yokoi(責任著者), Hiroaki Kajiyama, et al., Preoperative serum microRNAs as potential prognostic biomarkers in ovarian clear cell carcinoma. Journal of gynecologic oncology 2022年12月23日
また、難治性婦人科腫瘍の新規戦略創出治療として4報の論文報告を行った。3つの研究項目を提案し、現時点で特許出願3件、投稿中論文も複数あり、順調に進展している。次年度が最終年度となるがおおむね問題なく進行しており、引き続き期間内の目的達成を目指す。 Elucidating functional intratumoral heterogeneity by patient-derived cell culture system Grant number:21H02721  2021.4 - 2024.3 Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)   More details Authorship:Coinvestigator(s)  がん細胞外小胞の臨床応用へ向けた基盤技術開発研究 2021 - 2027 科学技術振興機構  戦略的な研究開発の推進 創発的研究支援事業  横井 暁   More details Authorship:Principal investigator  本研究で挑戦する課題は、ナノテクノロジーを最大限活用した細胞外小胞(Extracellular Vesicle: EV)抽出の技術革新と、新しいEVリキッドバイオプシー戦略の創生です。EVの利用価値への大きな期待から、昨今世界的に急速に市場が拡大しているEVを対象に、血液や腹水、尿といったヒト体液からEVを効率的かつ簡便に、純度の高い抽出プラットフォームを創り出し、がんを始めとした様々な疾患で苦しむ患者さんの助けとなるような技術革新を実現します。 Investigation of cancer extracellular vesicles for their revealing heterogeneity Grant number:20K22806  2020.9 - 2022.3 Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up Yokoi Akira   More details Authorship:Principal investigator  Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 ) Extracellular vesicles (EVs) were extracted from bio-fluids of ovarian cancer patient and fresh tumor tissue and profiled for both protein and nucleic acids (DNA, miRNA). Ovarian cancer-specific proteins have been identified and are in the process of being published and patent pending. We have also identified DNA profiles associated with response rates to therapeutic drugs in ovarian cancer patients, and we will submit a patent application and prepare the manuscript. The data from sequencing and LC-MS/MS indicated that EVs of different sizes have different characteristics, and that it is appropriate to analyze small EVs as targets for body fluid diagnostics, and that they have different biological functions. Elucidation of malignancy, peritoneal dissemination and spread mechanism of ovarian cancer by interaction with peritoneal mesothelium. Grant number:19H03797  2019.4 - 2022.3 Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B) Kikkawa Fumitaka   More details Authorship:Coinvestigator(s)  The aim of this study was to elucidate new disease mechanisms by focusing on cell-cell interactions in the ovarian cancer tumor-microenvironment (TME), and to discover novel therapeutic targets for ovarian cancer patients. Throughout the three-year research period, we have elucidated the malignant mechanisms of refractory ovarian cancer from extremely multiple aspects. The research included metabolomic analysis, small RNA sequencing, therapeutic effects of vitamins, and the relationship with adipose tissue. All of the results are the whole new findings, which have been reported for the first time. The function of mesothelial cells in TME is still under investigation. Although this research grant is in its final year, we will continue to elucidate the functions of various cells in the ovarian cancer TME and leading to develop them for clinical applications such as diagnosis and treatment. Elucidation of peritoneal dissemination mechanism by exosome from ovarian cancer and development of new treatment Grant number:16K15704  2016.4 - 2018.3 Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research Kikkawa Fumitaka   More details Authorship:Coinvestigator(s)  We demonstrated that the exosome from ovarian cancer stimulated the peritoneal dissemination. By mouse model the exosome also prompted abdominal metastasis and causes morphological change in mesothelial cells. This phenomenon was caused by induction of apoptosis. We observed that the exosome increased MMP1 expression in mesothelial cells.Using clinical data base, we observed that MMP1 is an important prognostic marker and there are ovarian cancer patients with ascites including MMP1 mRNA.In conclusion, the exosome including MMP1 mRNA may be a prognostic biomarker and a treatment target for preventing abdominal metastasis. ▼display all To the head of KAKENHI (Grants-in-Aid for Scientific Research).▲   Copyright © Nagoya University

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