Chiyoda, Tatsuyuki

写真a

Affiliation

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

Position

Assistant Professor/Senior Assistant Professor

Career 【 Display / hide

  • 1998.04
    -
    2004.03

    keio University School of Medicine

  • 2004.04
    -
    2006.03

    慶應義塾大学病院循環プログラム 初期臨床研修医(1年目 静岡赤十字病院 2年目 慶應義塾大学病院)

  • 2006.04
    -
    2008.03

    慶應義塾大学医学部助教(専修医)(産婦人科学)  立川病院出向(2006年4月〜2006年9月) 東京歯科大学市川総合病院出向(2007年4月〜2008年3月)

  • 2008.04
    -
    2011.03

    慶應義塾大学医学部 産婦人科 後期研修医

  • 2009.04
    -
    2013.03

    慶應義塾大学大学院医学研究科 博士課程

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Academic Background 【 Display / hide

  • 1998.04
    -
    2004.03

    慶應義塾大学医学部

    University, Graduated

  • 2009.04
    -
    2013.03

    慶應義塾大学大学院医学研究科博士課程

    Graduated

Academic Degrees 【 Display / hide

  • 博士(医学), 慶應義塾大学, Coursework, 2013

Licenses and Qualifications 【 Display / hide

  • 産婦人科専門医, 2009

  • がん治療認定医, 2012

  • 細胞診専門医, 2013

  • 臨床遺伝専門医, 2013

 

Research Areas 【 Display / hide

  • Obstetrics and gynecology (Gynecologic Oncology)

  • Human genetics

 

Papers 【 Display / hide

  • Estimating copy number using next-generation sequencing to determine ERBB2 amplification status

    Nakamura K., Aimono E., Oba J., Hayashi H., Tanishima S., Hayashida T., Chiyoda T., Kosaka T., Hishida T., Kawakubo H., Kitago M., Okabayashi K., Funakoshi T., Okita H., Ikeda S., Takaishi H., Nishihara H.

    Medical Oncology (Medical Oncology)  38 ( 4 ) 36 2021.04

    ISSN  13570560

     View Summary

    © 2021, The Author(s). Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

  • Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution

    Kobayashi Y., Hirasawa A., Chiyoda T., Ueki A., Masuda K., Misu K., Kawaida M., Hayashi S., Kataoka F., Banno K., Kosaki K., Aoki D.

    Japanese journal of clinical oncology (Japanese journal of clinical oncology)  51 ( 2 ) 213 - 217 2021.02

    ISSN  0368-2811

     View Summary

    © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com. BACKGROUND: Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast-ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast-ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. METHODS: To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. RESULTS: The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38-58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. CONCLUSIONS: Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.

  • Ovarian cancer organoids recapitulate genomic alterations of the parental tumors.

    Nanki Yoshiko, Chiyoda Tatsuyuki, Hirasawa Akira, Ookubo Aki, Itoh Manabu, Yoshimura Takuma, Akahane Tomoko, Yamagami Wataru, Aoki Daisuke

    CANCER SCIENCE 112   450 - 450 2021.02

    ISSN  1347-9032

  • A prospective cohort study on the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer

    Nanki Y., Nomura H., Iwasa N., Saotome K., Dozen A., Yoshihama T., Hirano T., Hashimoto S., Chiyoda T., Yamagami W., Kataoka F., Aoki D.

    Japanese Journal of Clinical Oncology (Japanese Journal of Clinical Oncology)  51 ( 1 ) 54 - 59 2021.01

    ISSN  03682811

     View Summary

    © The Author(s) 2020. Published by Oxford University Press. All rights reserved. Objective: this prospective cohort study aimed to assess the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer. Methods: in this study, 40 Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer selected to receive bevacizumab with chemotherapy were enrolled. Patients in poor general condition were excluded. Each patient was monitored prospectively for adverse events, administration status, disease status and survival. Treatment was continued until intolerable adverse events or disease progression. The primary endpoint was safety. Results: bevacizumab plus platinum-based chemotherapy was performed for 30 patients (median cycle; 16.5), while bevacizumab plus non-platinum chemotherapy was performed for 10 patients (median cycle; 5.5). Among bevacizumab-related adverse events, hypertension occurred in 80% of patients, proteinuria in 83%, mucositis in 25%, bleeding in 20%, thromboembolic events in 5.0% and fistula in 2.5%. Gastrointestinal perforation or other life-threatening lethal adverse events were not observed. Response rate and median progression-free survival were 73% and 19.3 months for patients with bevacizumab plus platinum-based chemotherapy, and 30% and 3.9 months for patients with bevacizumab plus non-platinum chemotherapy, respectively. There was no correlation between response rate and occurrence of adverse events such as hypertension or proteinuria. Conclusion: bevacizumab combined with chemotherapy was tolerable and effective for Japanese patients with relapsed ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Hypertension and proteinuria are frequently occurred and managed properly for continuing treatment.

  • Atypical vessels in hysteroscopy: Usefulness in prediction of malignant diseases in patients treated with tamoxifen

    Oka E., Sakai K., Yamagami W., Hirano T., Makabe T., Yoshihama T., Chiyoda T., Kataoka F., Banno K., Aoki D.

    Journal of Obstetrics and Gynaecology Research (Journal of Obstetrics and Gynaecology Research)   2021

    ISSN  13418076

     View Summary

    © 2021 Japan Society of Obstetrics and Gynecology Aim: Tamoxifen (TAM) is widely used in adjuvant endocrine therapy for invasive breast cancer as a selective estrogen modulator, but this treatment has a risk of developing endometrial malignancy. However, hysteroscopic findings during or after TAM treatment are unclear. The aim of this study is to examine the association between hysteroscopic patterns and malignant histological findings during or after treatment with TAM. Methods: The subjects were patients who received TAM after surgery for breast cancer and underwent hysteroscopy at our institution from January 2016 to December 2019. Clinicopathological factors and hysteroscopic findings were collected from medical records and investigated retrospectively. Histologically, atypical endometrial hyperplasia, endometrial cancer, and carcinosarcoma were classified as malignant diseases. Results: A total of 26 patients were eligible for the study. Hysteroscopic findings included an irregular surface of the endometrium (n = 3, 11.5%), atypical vessels (n = 10, 38.5%), papillary structure (n = 3, 11.5%), and polypoid structure (n = 18, 69.2%). Histological examination revealed malignancy in six patients (23.0%). The percentage of atypical vessels in patients with malignancies was significantly higher than that in patients with a normal endometrium or benign lesion (100% vs. 20%, p = 0.0009). The sensitivity and specificity of atypical vessels in hysteroscopy for diagnosis of malignant diseases were 100% and 80%, respectively. Conclusions: Hysteroscopic findings of atypical vessels may be useful for prediction of malignant diseases in patients treated with TAM.

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

Reviews, Commentaries, etc. 【 Display / hide

  • 体腔液より作成したセルブロックを用いてがん遺伝子パネル検査を行った3症例の検討

    吉浜 智子, 千代田 達幸, 中村 康平, 四十物 絵里子, 同前 愛, 平野 卓朗, 黒田 由香, 吉村 拓馬, 小林 佑介, 西尾 浩, 山上 亘, 青木 大輔

    日本臨床細胞学会雑誌 ((公社)日本臨床細胞学会)  59 ( Suppl.2 ) 560 - 560 2020.11

    ISSN  0387-1193

  • MPA療法の治療効果判定における、子宮内膜細胞診の有用性について

    吉村 拓馬, 山上 亘, 平野 卓朗, 坂井 健良, 真壁 健, 千代田 達幸, 阪埜 浩司, 進 伸幸, 青木 大輔

    日本臨床細胞学会雑誌 ((公社)日本臨床細胞学会)  59 ( Suppl.2 ) 531 - 531 2020.11

    ISSN  0387-1193

  • 卵巣癌オルガノイドは元腫瘍組織の遺伝学的特徴を有する

    南木 佳子, 千代田 達幸, 平沢 晃, 大久保 亜希, 伊藤 学, 吉村 拓馬, 赤羽 智子, 山上 亘, 青木 大輔

    日本癌学会総会記事 ((一社)日本癌学会)  79回   OE14 - 9 2020.10

    ISSN  0546-0476

  • 再発卵巣癌のセカンドライン化学療法におけるリポソーマルドキソルビシン+カルボプラチン療法(PLD-C)の有効性および安全性の検討

    王 洪欣, 千代田 達幸, 黒田 由香, 高橋 美央, 吉村 拓馬, 同前 愛, 平野 卓朗, 山上 亘, 青木 大輔

    関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会)  57 ( 3 ) 331 - 331 2020.10

    ISSN  2186-0610

  • 卵巣高異型度漿液性癌における多段階腫瘍形成の統合マルチオミックス解析

    同前 愛, 小松 正明, 町野 英徳, 中村 康平, 金子 修三, 生水 貫人, 浅田 健, 千代田 達幸, 中山 健太郎, 青木 大輔, 京 哲, 浜本 隆二

    日本癌学会総会記事 ((一社)日本癌学会)  79回   OE14 - 9 2020.10

    ISSN  0546-0476

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Presentations 【 Display / hide

  • Copy number alterationカウントは卵巣悪性腫瘍において進行期分類と相関する

    千代田 達幸

    第58回日本癌治療学会学術集会 ワークショップ1, 2020.10, Symposium, Workshop, Panelist (public offering)

  • 卵巣癌に対するBRCA1/2遺伝学的検査の適用、PARP阻害薬の適応、効果、マネジメント

    千代田 達幸

    第26回日本遺伝性腫瘍学会学術集会 ワークショップ1, 2020.08, Symposium, Workshop, Panelist (public offering)

  • 卵巣癌治療戦略における リムパーザの役割

    千代田 達幸

    Breast & Ovarian Cancer Joint Meeting, 2020.02, Other

  • 当院におけるリムパーザの使用経験

    千代田 達幸

    リムパーザ発売1周年記念講演会in城西, 2019.04, Other

  • Sphingosine kinase 1 is a novel target of metformin in ovarian cancer

    Tatsuyuki Chiyoda

    Sphingosine kinase 1 is a novel target of metformin in ovarian cancer, 2019.04, Other

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

  • 卵巣癌の小分子RNA-mRNAネットワークに基づく核酸医薬の実現

    2019.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 千代田 達幸, Grant-in-Aid for Early-Career Scientists , Principal Investigator

     View Summary

    卵巣癌は約30年間全生存率の大幅な改善を認めていない。核酸化学技術、デリバリー担体の開発により核酸医薬は臨床応用されてきた。本研究では卵巣癌における小分子RNAとメッセンジャーRNAの有機的なネットワークを解明し、核酸医薬を用いて卵巣癌治療を行うことを目指す。卵巣癌マウスモデルおよび卵巣癌組織から樹立した3Dオルガノイドを用いた核酸医薬のin vivo・ex vivo評価システムを確立し、精密医療における核酸医薬の臨床応用にむけた基盤を構築する。
    卵巣漿液性癌における包括的なmRNA-miRNAネットワークを明らかにするため、まず卵巣漿液性癌5検体と正常卵巣2検体を用いて全トランスクリプトーム解析(mRNAseq)および全小分子RNA解析(miRNAseq)を行った。その結果20-23塩基長のmiRNAは卵巣癌と正常卵巣の間で発現パターンが明らかに異なっていた。小分子RNAが作用している可能性のあるmRNAを相補的配列と発現から統合的に解析を行うことにより、卵巣癌に特異的な10個のmiRNA-mRNAネットワーク、5個のpiRNA-mRNAネットワークを同定した。その中でhsa-miR-497-5p-SMARCA4のネットワークに注目した。SMARCA4のノックダウンを行った卵巣癌細胞株(OVSAHO、KURAMOCHI)はコントロールに比較して有意に細胞増殖が抑制された。miR-497 mimic投与では卵巣癌細胞株の増殖は抑制され、miR-497 inhibitor投与では卵巣癌細胞株の増殖は亢進した。このネットワークについて臨床検体を用いた解析およびin vitroでの機能解析を行っている。
    同定したネットワークについて卵巣癌臨床検体および細胞株を用いた解析を進めており、SMARCA4の発現抑制卵巣癌細胞株を用いたトランスクリプトーム解析によりSMARCA4の新たな標的遺伝子を明らかにした。SMARCA4の卵巣癌を使用した免疫組織化学染色も終了し、現在解析中である。
    hsa-miR-497-5p-SMARCA4ネットワークの卵巣癌における機能解析をすすめていく。同定したSMARCA4の標的分子について、SMARCA4による卵巣癌促進にどのように関与するか解析をすすめていく。卵巣癌細胞株を用いたin vivo実験で妥当性を検証する。

  • Elucidating the mechanisms of DNA copy number aberrations in ovarian cancer - role of piRNA in ovarian cancer-

    2017.06
    -
    2019.03

    Keio University, Grant-in-Aid for Scientific Research, Chiyoda Tatsuyuki, SATO Kaoru, Grant-in-Aid for Challenging Research (Exploratory), Research grant, Principal Investigator

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    Piwi-interacting RNA (piRNAs) are animal-specific small RNAs usually restricted to the germline, which act on transposon silencing. We performed whole transcriptome sequencing (mRNA-seq) and whole small RNA sequencing (miRNA-seq) using 5 serous ovarian cancers and 2 normal ovaries. miRNA-seq showed that 20-23 nt miRNA profiles differ greatly among ovarian cancers and normal ovaries. 26-34 nt piRNA profiles differ in some ovarian cancers. Integrative analysis of mRNA-seq and miRNA-seq revealed 26 ovarian cancer specific mRNA-small RNA networks. Among them, high expression of RPS6KL1 was correlated with worse survival in ovarian cancer.

  • 卵巣癌の早期発見と予防を目的とした極初期発癌機構の解明

    2014.04
    -
    Present

    かなえ医薬振興財団 , 海外留学助成金

  • 卵巣癌の極初期発癌機構の解明

    2014.04
    -
    2016.03

    日本学術振興会, 海外特別研究員

  • LATS1を介する分裂制御異常に基づく卵巣癌発生機序の解明と治療戦略の考案

    2012.04
    -
    2014.03

    学術振興会特別研究員奨励費

Awards 【 Display / hide

  • AACR Scholar-in-Training Award, The AACR annual meeting 2013

    2013.04

  • 第64回 日本産科婦人科学会学術講演会 優秀演題賞(婦人科腫瘍学部門)

    2012.04

 

Courses Taught 【 Display / hide

  • LECTURE SERIES, GYNECOLOGY

    2021