Nishihara, Hiroshi

写真a

Affiliation

School of Medicine, Clinical and Translational Research Center Genomics Unit, Keio Cancer Center, Keio University Graduate School of Medicine (Shinanomachi)

Position

Professor

Related Websites

Contact Address

35 Shinanomachi, Shinjukuku, Tokyo, Japan

Telephone No.

0353154375

Fax No.

+81353154495

Profile 【 Display / hide

  • 学 歴
    1995年(平成7年)3月 北海道大学医学部卒業(医学士)
    1999年(平成11年)3月 北海道大学大学院医学研究科 病理系専攻医学博士課程修了、学位取得(博士(医学))
    2002年(平成14年)3月 ~ 2004年(平成16年)7月
    Molecular pharmacology at University of California, San Diego, Department of Pharmacology (Dr. Paul A. Insel; as a research fellow)

    職 歴
    1999年(平成11年)4月 北海道大学医学部附属病院 病理部 (医員)
    2000年(平成12年)4月 北海道大学大学院医学研究科 分子細胞病理学 (助手)
    2008年(平成20年)10月 北海道大学大学院医学研究科 探索病理学講座 (特任准教授)
    2012年(平成24年)11月 北海道大学病院臨床研究開発センター 生体試料管理室 (室長(兼任))
    2015年(平成27年)1月 北海道大学大学院医学研究科探索病理学講座 (特任教授)
    2016年(平成28年)4月 北海道大学病院がん遺伝子診断部 (統括マネージャー(兼任))
    2017年(平成29年)4月 国立病院機構 北海道がんセンター がんゲノム医療センター(センター長)
    北海道大学病院 がん遺伝子診断部 客員教授(兼任;2018年3月まで)
    札幌医科大学医学部 客員教授(兼任;2019年3月まで)
         長崎大学医学部 客員教授(兼任)
    2017年(平成29年)7月 慶應義塾大学医学部 客員教授(兼任) 腫瘍センターゲノム医療ユニット  
    2017年(平成29年)11月 慶應義塾大学医学部 特任教授 腫瘍センターゲノム医療ユニット長
    社会医療法人北斗 北斗病院 病理・遺伝子診断科長(兼任)
    2018年(平成30年)10月 鹿児島大学医学部 客員教授(兼任)
    2019年(平成31年)4月  慶應義塾大学医学部 教授 臨床研究推進センター・腫瘍センターゲノム医療ユニット
    筑波大学医学部 客員教授(兼任)

Academic Background 【 Display / hide

  • 1989.04
    -
    1995.03

    Hokkaido University, 医学部, 医学科

    University, Graduated, Master's course

  • 1995.04
    -
    1999.03

    Hokkaido University, 大学院, 医学研究科

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Hokkaido University, Coursework, 1999.03

Licenses and Qualifications 【 Display / hide

  • 医師, 医師, 1995.04

 

Books 【 Display / hide

  • がんゲノム医療時代の分子腫瘍学

    西原, 広史, 文光堂, 2022.04,  Page: vii, 412p

  • がんゲノム病理学

    田中, 伸哉, 西原, 広史, 文光堂, 2021.11,  Page: vii, 225p

  • がんゲノム医療の最前線

    矢冨, 裕, 深川, 雅史, 滝川, 一, 武藤, 学, 宮地, 勇人, 西尾, 和人, 小川, 誠司, 西原, 広史, 秋田, 弘俊, 織田, 克利, 栗原, 友, H.U.グループホールディングス,ニッセイエブロ), 2021.07,  Page: 233p

Papers 【 Display / hide

  • Recommendations related to the analytical equivalence assessment of gene panel testing.

    Sumimasa Nagai, Hiroshi Nishihara, Takayoshi Suzuki, Kazuto Nishio, Hiroya Taniguchi, Katsuya Tsuchihara, Kohei Nakamura, Reika Takamatsu, Toshihide Ueno, Hiroyuki Aburatani, Takashi Kohno, Shinji Kohsaka

    Cancer science  2022.07

     View Summary

    Advances in cancer genome care over the past few years have included the development of gene panel testing for various biomarkers. This article summarizes issues and provides recommendations related to analytical performance evaluations for new oncology gene panels. The scope of these recommendations includes comprehensive genomic profiling assays related to gene panel testing that uses histological or serum specimens to detect gene mutations. As a research project of the Japan Agency for Medical Research and Development Research on Regulatory Science of Pharmaceuticals and Medical Devices, we convened the working group committee that consisted of more than 30 experts from academia, industry, and government. We have discussed the points that should be considered to allow maximal simplification of assessments using clinical specimens in evaluating accuracy and limit of detection in equivalence and analytical performance for three years. We provide recommendations specific to each type of gene mutation as well as to reference standards or specimens used for evaluations. In addition, in order to facilitate the discussion on the analytical performance of gene panel tests by multidisciplinary tumor boards of hospitals, the present recommendations also describe the items that companies are expected to provide information on in their packaging inserts and reports, and the items that are expected to be discussed by multidisciplinary tumor boards. Our working group document will be important for participants in multidisciplinary tumor boards including medical oncologists and genome scientists, and developers of gene panels not only in Japan but also in other countries.

  • Real-world application of next-generation sequencing-based test for surgically resectable colorectal cancer in clinical practice.

    Masayo Ogiri, Ryo Seishima, Kohei Nakamura, Eriko Aimono, Shimpei Matsui, Kohei Shigeta, Tatsuyuki Chiyoda, Shigeki Tanishima, Koji Okabayashi, Hiroshi Nishihara, Yuko Kitagawa

    Future oncology (London, England)  2022.07

     View Summary

    Aim: To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. Materials & methods: A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. Results: More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors. The copy number alteration count was significantly lower in right-sided colon tumors and early-stage tumors. Homologous recombination deficiency was more often identified in advanced-stage tumors, and high homologous recombination deficiency status was useful for identifying high-risk stage II tumors. Conclusion: Homologous recombination deficiency was identified as a useful result of gene panel testing with novel utility in clinical practice.

  • Hybridisation chain reaction-based visualisation and screening for lncRNA profiles in clear-cell renal-cell carcinoma.

    Ryohei Kufukihara, Nobuyuki Tanaka, Kimiharu Takamatsu, Naoya Niwa, Keishiro Fukumoto, Yota Yasumizu, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Takeo Kosaka, Eriko Aimono, Hiroshi Nishihara, Ryuichi Mizuno, Mototsugu Oya

    British journal of cancer  2022.06

     View Summary

    BACKGROUND: Analysis of long noncoding RNA (lncRNA) localisation at both the tissue and subcellular levels can provide important insights into the cell types that are important for their function. METHODS: By applying new fluorescent in situ hybridisation technique called hybridisation chain reaction (HCR), we achieved a high-throughput lncRNA visualisation and evaluation of clinical samples. RESULTS: Assessing 1728 pairs of 16 lncRNAs and clear-cell renal-cell carcinoma (ccRCC) specimens, three lncRNAs (TUG1, HOTAIR and CDKN2B-AS1) were associated with ccRCC prognosis. Furthermore, we derived a new lncRNA risk group of ccRCC prognosis by combining the expression levels of these three lncRNAs. Examining genomic alterations underlying this classification revealed prominent features of tumours that could serve as potential biomarkers for targeting lncRNAs. We then derived combination of HCR with expansion microscopy and visualised nanoscale-resolution HCR signals in cell nuclei, uncovering intracellular colocalization of three lncRNA (TUG1, HOTAIR and CDKN2B-AS1) signals such as those located intra- or out of the nucleus or nucleolus in cancer cells. CONCLUSION: LncRNAs are expected to be desirable noncoding targets for cancer diagnosis or treatments. HCR involves plural probes consisting of small DNA oligonucleotides, clinically enabling us to detect cancerous lncRNA signals simply and rapidly at a lower cost.

  • Influence of response to prior docetaxel on sensitivity to cabazitaxel in prostate cancer patients with PTEN alterations.

    Ken Kamisawa, Takeo Kosaka, Kohei Nakamura, Yota Yasumizu, Hiroshi Hongo, Toshikazu Takeda, Kazuhiro Matsumoto, Hiroshi Nishihara, Mototsugu Oya

    Cancer science  2022.06

     View Summary

    The purpose of this study was to investigate factors predicting the sensitivity to cabazitaxel therapy in metastatic castration-resistant prostate cancer (mCRPC) patients with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) alterations. This single-institution, retrospective study included 12 mCRPC patients with PTEN alterations who had received cabazitaxel therapy. Five patients (41%) responded to cabazitaxel therapy with a prostate-specific antigen (PSA) level decline of ≥30% from baseline, and all of them had responded to prior docetaxel therapy with a PSA decline of ≥30%. None of the patients with a poor response to prior docetaxel therapy responded well to cabazitaxel therapy. Of the seven patients who did not respond to cabazitaxel and whose PSA declined from baseline was <30%, five (71%) were also refractory to prior docetaxel therapy. The PSA responses to docetaxel and cabazitaxel were significantly correlated (p = 0.027). Kaplan-Meier analysis revealed that progression-free survival (PFS) for cabazitaxel was significantly shorter for prior docetaxel nonresponders (3.3 versus 9.1 months, p = 0.028). Multivariate analysis revealed that a poor response to prior docetaxel (PSA decline < 30%) (hazard ratio [HR] = 6.382, 95% confidence interval [CI] 1.172-34.750, p = 0.032) and baseline PSA of ≥20 ng/ml (HR = 33.584, 95% CI 2.332-483.671, p = 0.010) were independent prognostic factors for PFS with cabazitaxel therapy. These results demonstrate cross-resistance between docetaxel and cabazitaxel. The response to prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy in mCRPC patients with PTEN alterations.

  • A Japanese case of castration-resistant prostate cancer with BRCA2 and RB1 co-loss and TP53 mutation: a case report.

    Tomohiro Iwasawa, Takeo Kosaka, Shinya Morita, Shuji Mikami, Kohei Nakamura, Hiroshi Hongo, Hiroshi Nishihara, Mototsugu Oya

    BMC medical genomics 15 ( 1 ) 138 - 138 2022.06

     View Summary

    BACKGROUND: Abnormalities in homologous recombination contribute to the aggressive nature of castration-resistant prostate cancer. Retinoblastoma transcriptional corepressor 1 (RB1) and breast cancer 2 (BRCA2) exist close to each other in the same chromosome, and the significance of their concurrent loss has become a hot topic in the field of cancer research. CASE PRESENTATION: A 61-year-old man presented with a chief complaint of a mass on his head and was diagnosed as multiple bone metastases from prostate cancer. He was treated with standard medication, but he died 2 years 6 months after being diagnosed with prostate cancer. Simultaneous biallelic loss of RB1 and BRCA2 as well as a truncating mutation of tumor protein p53 (TP53) were revealed by genomic analysis. CONCLUSION: To our knowledge, this is the first report of castration-resistant prostate cancer (CRPC) with BRCA2 and RB1 co-loss and TP53 mutation. To establish a treatment strategy for highly malignant cases with such multiple genetic features is important.

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

Reviews, Commentaries, etc. 【 Display / hide

  • cutting-edge medicine IT/AIの医療への実装 医療現場のデジタルトランスフォーメーションを目指して ビッグデータを活用したがんゲノム医療の現状

    西原 広史

    Precision Medicine ((株)北隆館)  5 ( 9 ) 777 - 780 2022.08

    ISSN  2434-3625

  • ゲノム医療 がんゲノム医療の光と陰 何がわかり、何ができるのか?

    西原 広史

    癌の臨床 ((株)篠原出版新社)  66 ( 3 ) 147 - 156 2022.07

    ISSN  0021-4949

  • 【臨床実装が進む次世代がんバイオマーカー 新規の検出技術、AIが加速するリキッドバイオプシーとその先の診断モダリティ】(第4章)臨床実装の実際 PleSSisionシステムによるがんゲノム検査の実践

    西原 広史

    実験医学 ((株)羊土社)  40 ( 10 ) 1625 - 1632 2022.06

    ISSN  0288-5514

     View Summary

    慶應グループでは、三菱スペース・ソフトウエア社と共同開発してきたPleSSision検査という独自のクリニカルシークエンスプラットフォームを臨床実装させ、ヒトのほぼ全遺伝子に相当する約2万遺伝子を調べるがんゲノム検査や、保険診療のがんゲノム検査の解析においても活用され、研究用シークエンスを含めると4,000症例以上の解析を行ってきた。3段階のカンファレンスシステムやタンパク質機能ダメージ予測ツール、PleSSisionスコアなど、独自のシステムを搭載した可変的なゲノム解析システムである。(著者抄録)

  • がんゲノム医療 ゲノム検査の今後の展望

    西原 広史

    西日本皮膚科 (日本皮膚科学会-西部支部)  84 ( 3 ) 249 - 249 2022.06

    ISSN  0386-9784

  • PleSSision-Rapidを用いた骨・軟部腫瘍のがん遺伝子パネル検査

    中山 ロバート, 中村 康平, 弘實 透, 山口 さやか, 森 智章, 浅野 尚文, 四十物 絵理子, 西原 広史, 松本 守雄, 中村 雅也

    日本整形外科学会雑誌 ((公社)日本整形外科学会)  96 ( 6 ) S1284 - S1284 2022.06

    ISSN  0021-5325

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

  • Gene profiling for pressure ulcer

    2017.07
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • Clinical Sequence Platform for Brain Tumor

    2017.04
    -
    2020.03

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

 

Courses Taught 【 Display / hide

  • ADVANCED MEDICAL TECHNOLOGIES

    2022