Yanokura, Megumi

写真a

Affiliation

School of Medicine, Department of Obstetrics and Gynecology (Gynecology) (Shinanomachi)

Position

Project Assistant Professor (Non-tenured)/Project Research Associate (Non-tenured)/Project Instructor (Non-tenured)

External Links

Academic Background 【 Display / hide

  • 2013.04
    -
    2017.07

    筑波大学, 生命環境科学, 生物科学

    Graduate School, Completed, Doctoral course

  • 2006.03

    Keio University, Graduate School, Division of Medicine, 医科学

    Graduate School, Completed, Master's course

  • 2013.04
    -
    2017.07

    University of Tsukuba, 生命環境科学, 生物科学

Academic Degrees 【 Display / hide

  • 修士(医科学), Keio University, Coursework, 2006.03

  • 博士(理学), 筑波大学大学院, Coursework, 2017.07

 

Research Areas 【 Display / hide

  • Life Science / Obstetrics and gynecology (Obstetrics and Gynecology)

  • Life Science / Obstetrics and gynecology (Obstetrics and Gynecology)

Research Keywords 【 Display / hide

  • DNAメチル化

  • DNAメチル化

  • 子宮体癌

  • 子宮体癌

  • 細胞周期チェックポイント

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Books 【 Display / hide

  • Application of microRNA in the treatment and diagnosis of cervical cancer

    Kouji Banno, Miho Iida, Megumi Yanokura, Iori Kisu, Kanako Nakamura, Masataka Adachi, Takashi Iwata, Kyoko Tanaka, Daisuke Aoki, Springer International Publishing, 2014.02

     View Summary

    MicroRNAs (miRNAs) are small non-coding RNA molecules of 20-23 nucleotides that regulate gene expression by binding to complementary mRNA sequences. Aberrant miRNA expression is implicated in carcinogenesis and malignancy of cancer. miRNAs involved in carcinogenesis are broadly classified into oncogenic and tumor suppressor miRNAs, and overexpression of oncogenic miRNAs and decreased expression of tumor suppressor miRNAs are found in cancer cells. Recent studies using miRNAs with different expression patterns between normal and cancer tissues have proposed use of miRNAs as biomarkers for cancer diagnosis and as treatment targets. In cervical cancer, miRNAs may be useful for onset detection, diagnosis and treatment. Here, we review the potential clinical applications of miRNAs for diagnosis and as a therapeutic strategy in cervical cancer.

  • Aberrant DNA Methylation in Endometrial Cancer

    Kenta Masuda, Kouji Banno, Megumi Yanokura, Kosuke Tsuji, Iori Kisu, Arisa Ueki, Yusuke Kobayashi, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki, Elsevier Inc., 2012.12

Papers 【 Display / hide

  • MicroRNA-34b expression enhances chemosensitivity of endometrial cancer cells to paclitaxel

    Yanokura M., Banno K., Aoki D.

    International Journal of Oncology (International Journal of Oncology)  57 ( 5 ) 1145 - 1156 2020.11

    ISSN  10196439

     View Summary

    Aberrant DNA methylation is widely observed in various types of cancer, and expression of microRNAs (miRNAs/miRs) is suppressed by DNA methylation. The present study explored tumor suppressor miRNAs downregulated by DNA methylation in endometrial cancer cells, as the basis of a novel therapeutic approach for endometrial cancer. Among 821 candidate miRNAs, miR-34b was identified as an upregulated miRNA after demethylation treatment in all four endometrial cancer cell lines (HEC-108, SNG-II, Ishikawa and HHUA) examined. miR-34b expression with or without demethylation treatment in cancer cells was confirmed by TaqMan quantitative PCR. MYC and MET, the predicted target genes of miR-34b, were downregulated at both the RNA and protein levels following miR-34b overexpression. Following miR-34b treatment, inhibition of cell growth and invasion, and cell cycle arrest were observed in HEC-108 cells. Sensitivity to paclitaxel was increased in cancer cells with miR-34b overexpression, compared with untreated cancer cells, but this difference was not identified for cisplatin or doxorubicin. In vivo, combination treatment with miR-34b and paclitaxel markedly reduced tumor growth compared with treatment with negative control miRNA and paclitaxel. These data suggest that miR-34b enhances paclitaxel sensitivity in endometrial cancer cells, and that miR-34b and MET are key targets for treatment of endometrial cancer. The present results may contribute to the development of combination treatment with a demethylation agent, miR-34b mimic or MET inhibitor and an anticancer drug.

  • Erratum: Aurora kinase inhibitors: Potential molecular-targeted drugs for gynecologic malignant tumors (Review).

    Umene K, Banno K, Kisu I, Yanokura M, Nogami Y, Tsuji K, Masuda K, Ueki A, Kobayashi Y, Yamagami W, Nomura H, Tominaga E, Susumu N, Aoki D

    Biomedical reports 11 ( 6 ) 274 2019.12

    Research paper (scientific journal), Accepted,  ISSN  2049-9434

  • Current status of uterine regenerative medicine for absolute uterine factor infertility (Review)

    Matoba Y., Kisu I., Sera A., Yanokura M., Banno K., Aoki D.

    Biomedical Reports (Biomedical Reports)  10 ( 2 ) 79 - 86 2019

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  20499434

     View Summary

    © 2019, Spandidos Publications. All rights reserved. Though assisted reproduction technology has been developed, a treatment for absolute uterine factor infertility (AUFI), such as defects in the uterus, has not yet been established. Regenerative medicine has been developed and applied clinically over recent years; however, whole solid organs still cannot be produced. Though uterine regeneration has the potential to be a treatment for AUFI, there have been only a few studies on uterine regeneration involving the myome-trium in vivo. In the present report, those relevant articles are reviewed. A literature search was conducted in PubMed with a combination of key words, and 10 articles were found, including nine in rat models and one in a mouse model. Of these studies, eight used scaffolds and two were performed without scaffolds. In four of these studies, scaffolds were re-cellularized with various cells. In the remaining four studies, scaffolds were transplanted alone, or other structures were used. Though the methods differed, the injured uterus recovered well, morphologically and functionally, in every study. Only 10 articles were relevant to our investigation, but the results w

  • Mutations of RAS genes in endometrial polyps

    Takeda T, Banno K, Kobayashi Y, Adachi M, Yanokura M, Tominaga E, Kosaki K, Aoki D

    Oncology Reports (Oncology Reports)  42 ( 6 ) 2303 - 2308 2019

    Research paper (scientific journal), Accepted,  ISSN  1021335X

     View Summary

    © 2019 Spandidos Publications. All rights reserved. Endometrial polyps are common, yet the molecular mechanisms underlying their formation and progression remain unclear. We examined gene mutations possibly related to the pathogenesis of endometrial polyps, as well as to their clinical features. Four premenopausal patients with endometrial polyps, who were not under drug treatment, were recruited. Whole exomes of endometrial polyps and peripheral blood lymphocytes were analyzed by next-generation sequencing, and somatic mutations were derived by subtraction. Then, 35 samples of endometrial polyps and 12 samples of atypical polypoid adenomyoma were newly recruited to validate the identified mutations by polymerase chain reaction-reverse sequence specific oligonucleotide method. The mutations were also analyzed in separate stromal and glandular components of the polyps after laser-capture microdissection. Whole exome sequencing revealed that KRASmutations were the only type of mutation detectable in multiple cases (2/4). Targeted mutation analysis revealed that 16 of 35 samples (45.7%) of endometrial polyps harbored RAS mutations. Mutation-positive cases exhibited a significantly hi

  • Synchronous endometrial and ovarian cancer in Lynch syndrome with a MSH2 germline mutation: A case report.

    Takeda T, Banno K, Yanokura M, Anko M, Kobayashi A, Sera A, Takahashi T, Adachi M, Kobayashi Y, Hayashi S, Nomura H, Hirasawa A, Tominaga E, Aoki D

    Molecular and clinical oncology 9 ( 5 ) 479 - 484 2018.11

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2049-9450

     View Summary

    Synchronous endometrial and ovarian cancer (SEOC) is a rare entity among gynecological cancers, which exhibits endometrioid histology in its early stages and generally has a good prognosis. However, diagnosis is difficult and recent reports have demonstrated that most clinically diagnosed cases of SEOC have clonally related cancers, indicating metastatic cancer. The association of SEOC with Lynch syndrome is also not clearly understood. We herein present the case of a 41-year-old SEOC patient with MSH2 mutation. The endometrial cancer was an endometrioid adenocarcinoma and the ovarian cancer was mainly endometrioid, but also included a clear cell carcinoma with a borderline clear cell adenofibromatous component, indicating primary ovarian cancer. Both tumors exhibited microsatellite instability (MSI) and loss of expression of MSH2 and MSH6. The patient had a family history of colorectal and gastric cancers. Genetic analysis revealed a germline mutation in exon 6 of MSH2 (c.1042C>T, p.Gln348*) and the patient was diagnosed with Lynch syndrome. This MSH2 mutation has only been registered in one case in the InSiGHT variant databases and has not been reported in a gynecological tumor or SEOC to date. This case is a rare example of a patient with genetically diagnosed Lynch syndrome who also developed SEOC. This synchronous cancer is not common, but it may be caused by Lynch syndrome. Testing for MSI and immunohistochemistry for mismatch repair deficiency is necessary in cases with suspected SEOC.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • ヒト子宮体癌由来培養細胞を用いたReprogrammed-Cancer cellの作成

    矢野倉 恵, 阪埜 浩司, 的場 優介, 辻 浩介, 小林 佑介, 冨永 英一郎, 田中 守, 青木 大輔

    日本産科婦人科学会雑誌, 

    2019.02

    (公社)日本産科婦人科学会

  • 【婦人科がん(第2版)-最新の研究動向-】 子宮体がん 子宮体癌の発生 子宮内膜癌(類内膜癌)のゲノム解析

    阪埜 浩司, 矢野倉 恵, 青木 大輔

    日本臨床, 

    2018.03

    Other, (株)日本臨床社

  • CIMP-H子宮体癌患者の末梢血を利用したTargeted bisulfite sequencing

    矢野倉 恵, 阪埜 浩司, 安達 将隆, 梅根 紀代子, 小林 佑介, 山上 亘, 冨永 英一郎, 進 伸幸, 青木 大輔

    日本癌学会総会記事, 

    2016.10

    Other, 日本癌学会

  • 子宮体部明細胞癌に対するARID1Aタンパクの発現解析 卵巣明細胞癌との比較

    大川 隆一朗, 阪埜 浩司, 矢野倉 恵, 増田 健太, 安達 将隆, 野上 侑哉, 國富 晴子, 冨永 英一郎, 田中 守, 青木 大輔

    日本産科婦人科学会雑誌, 

    2016.02

    Other, (公社)日本産科婦人科学会

  • メトホルミンとジエノゲストの併用はDNAのメチル化を変化させ子宮体癌細胞の増殖を抑制させる

    矢野倉 恵, 阪埜 浩司, 増田 健太, 梅根 紀代子, 野上 侑哉, 入江 晴子, 飯田 美穂, 中村 加奈子, 安達 将隆, 冨永 英一郎, 田中 守, 青木 大輔

    日本産科婦人科学会雑誌, 

    2015.02

    Other, (公社)日本産科婦人科学会

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Elucidation of implantation inhibition mechanism of endometrial cancer cells using iPS technology

    2022.04
    -
    2025.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

     View Summary

    これまでの臨床学的見知から、子宮体癌担癌状態では着床が成立しないことが知られているが、そのメカニズムは未だ不明である。また近年、子宮体癌患者の増加や妊娠・出産年齢の高齢化に伴い、妊孕性温存療法を求める声が高まっている。そこで、子宮体癌細胞における着床阻害メカニズムを解明し、新たな妊孕性温存療法への応用を目指す。
    1.RC細胞(Reprogrammed-Cancer Cells)におけるin vitro着床能解析
    2.RC細胞および親株細胞のDNAメチル化データ解析
    3.子宮体癌細胞における候補遺伝子の発現解析および発現制御
    4.RC細胞放出microRNAの子宮体癌細胞に対する着床阻害抑制効果の検討

  • Reprogramming study of endometrial cancer cells for restoring fertility

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 矢野倉 恵, Grant-in-Aid for Scientific Research (C), Principal investigator

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    Clinical observations have confirmed that implantation does not occur in patients with endometrial cancer. The mechanism of acquisition of phenotypes characteristic of cancer cells can be examined by identifying epigenomic changes during reprogramming. Therefore, we first produced reprogrammed cancer (RC) cells from human endometrial cancer cell lines. DNA methylation and changes in gene expression and implantation capacity in these cells were then examined to explore the mechanism of inhibition of implantation in endometrial cancer.
    Upregulation of undifferentiated markers and decreased cell proliferation were observed in the RC cells. The in vitro implantation test showed significantly increased implantation capacity in RC cells compared with parent cell lines (p<0.05). DNA methylation array analysis showed significant differences in methylation (31,511/747,192, 4.2%) in parent and RC cells (p<0.05, |β|>0.25). A calcium signaling pathway was identified by KEGG enrichment analysis.

  • Genome-wide DNA methylation analysis in endometrial cancer

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, YANOKURA Megumi, Grant-in-Aid for Scientific Research (C), Principal investigator

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    [Objective] Concurrent DNA methylation of multiple genes occurs in endometrial cancer. However, the features and causes of high-methylation rate endometrial cancer are not well understood. Therefore, the aim of this study was to investigate the DNA methylation status in normal tissue from patients with endometrial cancer.
    [Methods] The study was approved by the Ethics Committee. The subjects were 25 patients with endometrial cancer from whom cancer tissue and peripheral blood cells (PBCs) were obtained. The 25 cancer samples were classified as Methyl-high, and Methyl-negative (Methyl(-)) by methylation-specific PCR (MSP) analysis of three genes. DNA libraries were prepared from peripheral blood DNAs from 2 Methyl-H and 2 Methyl(-) patients, and bisulfite sequencing was performed.
    [Results] PBC DNA in Methyl-H cases had significant hypermethylation in the miR-663a promoter region, compared to Methyl(-) cases.

  • Application to the development and diagnosis of miRNA therapeutic agent in endometrial cancer

    2012.04
    -
    2015.03

    Keio University, Grants-in-Aid for Scientific Research, YANOKURA MEGUMI, Grant-in-Aid for Young Scientists (B), No Setting

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    [Objective] microRNAs have key roles in the onset, development and drug resistance of cancer. We identified miR-34b as a tumor suppressor-type microRNA with expression that is epigenetically suppressed in endometrial cancer. In this study, the antitumor effect of combined miR-34b and antitumor drugs on endometrial cancer was examined.
    [Results] There was no change in cell viability after administration of miR-34b following application of cisplatin or adriamycin to HEC-108, HEC-1B and KLE cells. However, after treatment with paclitaxel, cell viability after administration of miR-34b decreased in all three cell lines. Tumor development occurred 14 days after transplantation of HEC-1B cells in nude mice. Drugs were administered on that day and thereafter. The tumor diameter significantly decreased in mice treated with paclitaxel + miR-34b compared with the results for other treatments (P<0.05). The GFP fluorescence signal also markedly decreased after treatment with paclitaxel + miR-34b.

  • endometrial cancer therapy using epigenetically regulated small RNA

    2010
    -
    2012

    Keio University, Grants-in-Aid for Scientific Research, BANNO Kouji, YANOKURA Megumi, Grant-in-Aid for Scientific Research (C), No Setting

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    It is revealed that CHFR gene is epigenetically regulated in endometrial cancer. CHFR gene methylation is correlated with response to Taxane. Micro RNA is also regulated by DNA methylation in endometrial cancer. miR-34b is important for the oncogenesis of

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