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

  • Germline BRCA2 variant with low variant allele frequency detected in tumor-only comprehensive genomic profiling.

    Hideyuki Hayashi, Kei Kunimasa, Shigeki Tanishima, Kohei Nakamura, Marin Ishikawa, Yasutaka Kato, Eriko Aimono, Ryutaro Kawano, Hiroshi Nishihara

    Cancer science  2023.12

    Accepted

     View Summary

    Germline BRCA1/2 variants in comprehensive genomic profiling (CGP) often exhibit variant allele frequency (VAF) exceeding 50%. However, when genomic loss occurs at the ipsilateral allele, including the germline variant in tumor cells, the VAF is low. This case report presents a patient with uterine sarcoma with a pathogenic BRCA2 mutation and low VAF in tumor-only CGP, which was later identified as a germline variant. When genomic alterations in BRCA1/2 are identified in tumor-only CGP, the possible germline origin of the variants should be considered, even if their VAF is very low.

  • Eribulin inhibits growth of cutaneous squamous cell carcinoma cell lines and a novel patient-derived xenograft

    Che Yuan Hsu, Teruki Yanagi, Takuya Maeda, Hiroshi Nishihara, Kodai Miyamoto, Shinya Kitamura, Keiko Tokuchi, Hideyuki Ujiie

    Scientific Reports 13 ( 1 )  2023.12

    Accepted

     View Summary

    Advanced cutaneous squamous cell carcinoma (cSCC) is treated with chemotherapy and/or radiotherapy, but these typically fail to achieve satisfactory clinical outcomes. There have been no preclinical studies to evaluate the effectiveness of eribulin against cSCC. Here, we examine the effects of eribulin using cSCC cell lines and a novel cSCC patient-derived xenograft (PDX) model. In the cSCC cell lines (A431 and DJM-1 cells), eribulin was found to inhibit tumor cell proliferation in vitro as assessed by cell ATP levels. DNA content analysis by fluorescence-activated cell sorting (FACS) showed that eribulin induced G2/M cell cycle arrest and apoptosis. In xenograft models of cSCC cell lines, the administration of eribulin suppressed tumor growth in vivo. We also developed a cSCC patient-derived xenograft (PDX) which reproduces the histological and genetic characteristics of a primary tumor. Pathogenic mutations in TP53 and ARID2 were detected in the patient’s metastatic tumor and in the PDX tumor. The cSCC-PDX responded well to the administration of eribulin and cisplatin. In conclusion, the present study shows the promising antineoplastic effects of eribulin in cSCC. Also, we established a novel cSCC-PDX model that preserves the patient’s tumor. This PDX could assist researchers who are exploring innovative therapies for cSCC.

  • Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer.

    Shoko Kitazawa, Tatsuyuki Chiyoda, Kohei Nakamura, Kensuke Sakai, Tomoko Yoshihama, Hiroshi Nishio, Yusuke Kobayashi, Takashi Iwata, Kouji Banno, Wataru Yamagami, Hiroshi Nishihara, Daisuke Aoki

    International journal of clinical oncology  2023.08

    Accepted

     View Summary

    BACKGROUND: Japan's health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. METHODS: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. RESULTS: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. CONCLUSION: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients' prognosis and performance status should be considered before performing the test.

  • Cancer gene analysis of liquid-based cytology specimens using next-generation sequencing: A technical report of bimodal DNA- and RNA-based panel application.

    Toshiaki Akahane, Tomomi Isochi-Yamaguchi, Natumi Hashiba-Ohnuki, Nobuyuki Bandoh, Eriko Aimono, Yasutaka Kato, Hiroshi Nishihara, Hajime Kamada, Akihide Tanimoto

    Diagnostic cytopathology 51 ( 8 ) 493 - 500 2023.05

    Accepted

     View Summary

    BACKGROUND: As liquid-based cytology (LBC) specimens harbor high-quality DNA, genomic analysis using LBC specimens is beneficial for integrative diagnosis. This study aimed to clarify the feasibility of LBC specimens for a bimodal application of DNA- and RNA-based next-generation sequencing (NGS) panels. METHODS: LBC specimens were prepared from cultured human cancer HEC59 cells using commercially available fixatives (Cellprep, CytoRich Red, and SurePath solutions), and were subjected to NGS for a feasibility study. Clinical LBC specimens of thyroid and salivary gland tumors were prepared using CytoRich Red solution. After DNA and RNA extraction, NGS analyses were performed in a single run using combined DNA- and RNA-based custom-made cancer panels for the detection of gene mutations and fusions. RESULTS: High-quality DNA and RNA were obtained, and the expected gene mutations and fusions were detected in HEC59 cells using all types of LBC fixatives. Most available clinical cases (18 out of 20) exhibited pathogenic gene mutations (15 cases) and fusion genes (3 cases) using the bimodal DNA- and RNA-based panels. Overall, 18 cases (90%) showed oncogenic mutations or fusion genes of diagnostic values. CONCLUSION: Simultaneous application of bimodal DNA- and RNA-based gene panels was useful in NGS analysis using residual LBC specimens for integrative diagnosis. Residual LBC specimens for genomic analysis, including fusion gene analysis, are particularly useful for obtaining genomic information before surgical resection.

  • Diffuse-Type Tenosynovial Giant Cell Tumor Arising in the Temporomandibular Joint Extending to the External Auditory Canal: A Case Report and Literature Review.

    Suzuki S, Tsuda H, Bandoh N, Goto T, Uemura A, Aoyama T, Nishio A, Makino S, Yamaguchi T, Aimono E, Nishihara H, Harabuchi Y

    Ear, nose, & throat journal 102 ( 5 ) 291 - 296 2023.05

    Accepted,  ISSN  0145-5613

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

Reviews, Commentaries, etc. 【 Display / hide

  • 【新しいバイオマーカーと分子標的治療の展開】核酸医薬

    谷口 博昭, 名取 幸和, 西原 広史, 今井 浩三

    腫瘍内科 ((有)科学評論社)  32 ( 4 ) 383 - 390 2023.10

    ISSN  1881-6568

  • 食道癌治療における血中circulating tumor DNAを用いた腫瘍モニタリングの有用性

    小林 亮太, 松田 諭, 川久保 博文, 中村 康平, 竹内 優志, 福田 和正, 中村 理恵子, 西原 広史, 北川 雄光

    日本癌治療学会学術集会抄録集 ((一社)日本癌治療学会)  61回   YOA O5 - 1 2023.10

  • 遺伝子検査を用いた、大腸癌に対する術後補助化学療法の再発予防効果の層別化

    清島 亮, 鈴木 佳透, 中村 康平, 茂田 浩平, 岡林 剛史, 西原 広史, 北川 雄光

    日本癌治療学会学術集会抄録集 ((一社)日本癌治療学会)  61回   P19 - 2 2023.10

  • 脳腫瘍こそ個別化治療が必要! 髄膜腫に対するプレシジョンメディシンの可能性

    西原 広史

    日本癌治療学会学術集会抄録集 ((一社)日本癌治療学会)  61回   OWS16 - 2 2023.10

  • 泌尿器科癌における悪性度の配分と遺伝子変化の関連について

    水谷 晃輔, 杉山 誠治, 亀山 紘司, 亀井 信吾, 横井 繁明, 平出 耕石, 松永 研吾, 山田 鉄也, 坂本 一平, 加藤 容崇, 西原 広史, 石原 哲, 佐治 重豊, 出口 隆

    日本癌治療学会学術集会抄録集 ((一社)日本癌治療学会)  61回   P47 - 4 2023.10

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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

    2023

  • ADVANCED MEDICAL TECHNOLOGIES

    2022