NISHIHARA, Hiroshi

写真a

Affiliation

School of Medicine, Center for Cancer Genomics Center for Cancer Genomics, Keio University Graduate School of Medicine (Shinanomachi)

Position

Professor

Related Websites

Contact Address

35 Shinanomachi, Shinjukuku, Tokyo, Japan

Telephone No.

+81353154375

Fax No.

+81353154495
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Profile 【 Display / hide 】

  • <Education>
    * Apr, 1989- Mar, 1995 Hokkaido University School of Medicine, Hokkaido, Japan:
    Bachelor of Medicine in 1995: License of Medical Doctor
    (No.370847) in 1995 * Apr, 1995 – Mar, 1999
    Graduate School of Medicine, Hokkaido University,
    Hokkaido, Japan: Doctor of Philosophy in 1999

    <Special Training>
    * Internal Medicine at Hokkaido University Hospital: Apr-Sep,1995
    * General Pathol at Dept of Pathol, Hokkaido Univ Sch of Med. Oct, 1995- Sep, 1996
    * Molecular Biology at Dept of Pathol, Research Institute, International Medical
    Center of Japan, Toyama, Shinjuku-ku, Tokyo, Japan, Oct, 1996- Apr, 1998
    * General pathology and Molecular biology at Department of Pathology, Hokkaido University School of Medicine. May, 1998-present
    * Molecular pharmacology at University of California, San Diego, Department of Pharmacology (Dr. Paul A. Insel; as a research fellow). Mar, 2002-July, 2004.
    * Clinical research and genomic medicine through clinical biobank at Hokkaido University Hospital. Nov, 2011-present.
    * Genomic diagnosis for cancer patients, Hokkaido University Hospital. Apl. 2016-present

    <Award>
    1. Feb. 2002, 18th Hokkaido Medical Award, Hokkaido Medical Association
    2. Jan. 2005, Frate Research Award, Alumnae of Hokkaido University School of Medicine
    3. May 2008, Neuropathology Award 2008, Japanese Association of Neuropathology
    4. Apr. 2010, Research Award 2010, Japanese Association of Pathology

    <Work>
    1. Department of Translational Pathology, Hokkaido University, Graduate School of Medicine (Professor) ~ March, 2017.
    2. Translational Research Laboratory, Hokkaido University Hospital, Clinical Research and Medical Innovation Center. (Division manager) ~ March. 2017.
    3. Division of Clinical Cancer Genomics, Hokkaido University Hospital. (Division manager) ~ March, 2017.
    4. Division of Clinical Cancer Genomics, Hokkaido Cancer Center. (Division manager)
    April. 2017 ~ Oct. 2017
    5. Genomics Unit, Keio Cancer Center, Keio University School of Medicine, (Unit manager, Professor) Nov. 2017 ~Jul. 2024
    6. Center for Cancer Genomics, Keio University School of Medicine, (Director, Professor) Aug. 2024 ～

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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

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Academic Degrees 【 Display / hide 】

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

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Licenses and Qualifications 【 Display / hide 】

  • 医師, 医師, 1995.04

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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

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Papers 【 Display / hide 】

  • Clinical utility of comprehensive genomic profiling for advanced pancreatic cancer: insights from real-world data analysis

    Eiichiro So, Hideyuki Hayashi, Keitaro Shimozaki, Sara Horie, Shotaro Kishimoto, Akihiko Chida, Yuki Saito, Kai Tsugaru, Kenro Hirata, Shigeki Tanishima, Hiroshi Nishihara, Takanori Kanai, Yasuo Hamamoto

    International Journal of Clinical Oncology (Springer Science and Business Media LLC)   2025.02

    Accepted,  ISSN  1341-9625

  • CXCL9 and CXCL13 shape endometrial cancer immune-activated microenvironment via tertiary lymphoid structure formation.

    Yoshihiro Nagase, Makoto Kodama, Eriko Aimono, Kohei Nakamura, Reika Takamatsu, Keiko Abe, Takuma Yoshimura, Tatsuyuki Chiyoda, Wataru Yamagami, Hiroshi Nishihara

    Cancer science  2025.02

    Accepted

    　View Summary

    Immune checkpoint inhibitor (ICI) therapy has been successfully applied to various cancers; however, not all patients respond to ICI therapy. Tumors with an immune-activated environment are highly responsive to ICIs. To identify the cells and molecules essential to the formation of an immune-activated cancer microenvironment, we focused on the tertiary lymphoid structure (TLS) and performed histological and genomic analyses using endometrial cancer material. In the high immunogenic group, numerous TLSs were observed, and CXCL9 and CXCL13 expression was markedly increased. CXCL9-positive antigen-presenting and CXCL13-positive follicular dendritic cells were distributed in the T- and B-cell zones of TLSs, respectively. A group of molecules whose expression was upregulated along with CXCL9 and CXCL13 expression was strongly associated with cellular immunity. These results suggest that CXCL9-expressing antigen-presenting cells and CXCL13-expressing follicular dendritic cells coordinately shape the immune-activated microenvironment through TLS formation. The current findings will contribute to a better understanding of the mechanisms underlying the activated cancer immune microenvironment, thereby advancing the field of precision cancer medicine.

  • Clinical value of preoperative circulating tumor DNA before surgery in patients with esophageal squamous cell carcinoma.

    Ryota Kobayashi, Satoru Matsuda, Kohei Nakamura, Hirofumi Kawakubo, Keiso Ho, Yosuke Morimoto, Kazuhiko Hisaoka, Yuki Hoshi, Masashi Takeuchi, Kazumasa Fukuda, Jun Okui, Hiroshi Nishihara, Yuko Kitagawa

    European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 51 ( 5 ) 109625 - 109625 2025.01

    Accepted

    　View Summary

    INTRODUCTION: A precise preoperative tumor monitoring method that reflects tumor burden during neoadjuvant treatment is required to guide individualized perioperative treatment strategies for esophageal squamous cell carcinoma (ESCC). This study examined the clinical significance of preoperative circulating tumor DNA (ctDNA) in the plasma of patients undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy. MATERIALS AND METHODS: Plasma samples were collected longitudinally for ctDNA analysis as well as genomic DNA from primary lesions from patients with histologically confirmed ESCC who received neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy. Next-generation sequencing was used to identify mutations in both the plasma and primary tumors. We evaluated the relationship between ctDNA alterations and recurrence in patients with locally advanced ESCC. RESULTS: Pretreatment samples from 25 patients (100 %) showed the same mutations in both ctDNA and primary tumors; therefore, they were classified as ctDNA-positive before treatment. In the cohort of 25 patients analyzed, those who tested positive for ctDNA after NAC had a significantly higher risk of recurrence; the 36-month recurrence-free survival rates were 92 % for ctDNA-negative patients and 8 % for ctDNA-positive patients (p < 0.001). CONCLUSIONS: Preoperative ctDNA status may be a promising prognostic biomarker that can be assessed before surgery in patients with ESCC who received NAC. Expanded cohort validation will allow for more personalized multidisciplinary treatment approaches for ESCC tailored to ctDNA analysis.

  • Clinical characteristics of gastrointestinal stromal tumors with hypoglycemia.

    Akihiko Chida, Kenta Kawasaki, Junko Kuramoto, Hideyuki Hayashi, Toru Kawahara, Satomi Makiuchi, Eiichiro So, Satoko Shimizu, Shotaro Kishimoto, Sara Horie, Yuki Saito, Keitaro Shimozaki, Kai Tsugaru, Kazuhiro Togasaki, Kenro Hirata, Hiroshi Nishihara, Yae Kanai, Takanori Kanai, Yasuo Hamamoto

    Oncology letters 28 ( 6 ) 568 - 568 2024.12

    Accepted

    　View Summary

    The development of tyrosine-kinase inhibitors has improved survival rates for patients with gastrointestinal stromal tumors (GISTs). Despite the progress, not all the patients can universally receive the benefit from treatment due to the individual underlying conditions in a real-world setting. The present study focused on the well-known but understudied condition of GIST with hypoglycemia. Hypoglycemia in GIST is characterized by hypoglycemic symptoms such as dizziness, sweating and confusion. It is caused by several factors such as multiple liver metastases, drug adverse effects, postoperative complications and paraneoplastic syndrome [non-islet cell tumor hypoglycemia (NICTH)]. Comprehensive analysis of this condition has been hindered due to its rarity, and has been mostly limited to case reports. In the present study, a single-institution retrospective analysis of GIST with hypoglycemia was conducted to investigate its prevalence and prognosis, and the cause of this condition. The present study identified that the prevalence of hypoglycemic episodes of GIST was 4.1% in all patients with GIST, and recurrent hypoglycemic cases had a poor prognosis. The present study identified 1 case with recurrent hypoglycemia due to NICTH. Since NICTH is a rare hypoglycemic cause and requires further evaluation, an autopsy and genetic sequencing were performed using the available clinical materials. Through this histological and genetic investigation, the histological diversity of NICTH-GIST was revealed and insulin-like growth factor II (IGF-II) amplification was identified. Furthermore, a chronological analysis was performed using multiple resected archived samples from the same case, and revealed that diffuse IGF-II expression may have occurred in the early phase of tumor development. The present study catalogued the characteristics of GIST with hypoglycemia with a focus on NICTH-GIST.

  • Characterizing multi-PIK3CA mutations across cancer types: Toward precision oncology.

    Kohei Nakamura, Marin Ishikawa, Ryutaro Kawano, Eriko Aimono, Takaaki Mizuno, Sachio Nohara, Shigeki Tanishima, Hideyuki Hayashi, Hiroshi Nishihara

    Cancer medicine 13 ( 14 ) e70052 2024.07

    Accepted

    　View Summary

    BACKGROUND: PIK3CA mutations are implicated in various cancers, but the implications of multiple concurrent mutations and their orientations within the gene have not been fully explored. METHODS: In this study, we analyzed multi-PIK3CA mutations across a diverse pan-cancer cohort comprising 3564 tumors. RESULTS: Multi-PIK3CA mutations were present in 10.3% of all PIK3CA-mutant tumors, predominantly occurring in breast and gynecological cancers. Notably, mutations within the helical domain (E542:E545) exclusively occurred in the trans-orientation, contrasting with mutations in the kinase ABD and C2 domains, which mainly appeared in the cis orientation. CONCLUSIONS: The distinct pattern of mutation orientations in PIK3CA suggests variable oncogenic potential, with helical domain mutations in the trans-orientation potentially being less oncogenic. These findings highlight the importance of mutation orientation in the PIK3CA gene as potential biomarkers for targeted therapy. This understanding is crucial for designing clinical trials that leverage PI3K inhibitors, aiming for more effective and precise cancer treatment.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 内視鏡を用いた診療・研究の現況と展望　膵癌早期診断における3Dオルガノイド樹立の期待と課題

    河瀬 智哉, 吉田 浩司, 馬場 晶吾, 加藤 容崇, 西原 広史

    日本消化器病学会中国支部例会・日本消化器内視鏡学会中国支部例会プログラム・抄録集 (日本消化器病学会-中国支部)  122回・133回   70 - 70 2024.11

  • LDT(RUO)と保険診療(第2弾)　パソロジカルシークエンスの意義と保険収載に向けた取り組みについて

    西原 広史

    日本臨床検査医学会誌 ((一社)日本臨床検査医学会)  72 ( 補冊 ) 073 - 073 2024.10

    ISSN  2436-2727

  • 遺伝子情報に基づいた治療選択と治療の現状

    植村 天受, 西原 広史, 小原 航, 櫻井 晃洋

    Espoir ((株)メディカルレビュー社)  7 ( 2 ) 53 - 60 2024.10

    ISSN  2432-7794

  • 日本人の稀少前立腺導管癌におけるp53及びRB1免疫染色による遺伝子変異予測能の評価

    小林 裕章, 小坂 威雄, 宮居 弘輔, 中村 康平, 木村 徳宏, 楊井 祥典, 馬場 優人, 西原 広史, 大家 基嗣, 伊藤 敬一

    日本癌治療学会学術集会抄録集 ((一社)日本癌治療学会)  62回   O21 - 5 2024.10

  • 子宮体癌の新進行期分類(FIGO2023)を考える　子宮体癌におけるがん遺伝子パネル検査を用いた分子分類の有用性

    中村 康平, 吉村 拓馬, 川野 竜太郎, 高松 玲佳, 千代田 達幸, 山上 亘, 西原 広史

    日本臨床細胞学会雑誌 ((公社)日本臨床細胞学会)  63 ( Suppl.2 ) 475 - 475 2024.10

    ISSN  0387-1193

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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

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Courses Taught 【 Display / hide 】

  • ADVANCED CANCER GENOMICS

    2025

  • INTEGRATION OF BASIC SCIENCE AND CLINICAL MEDICINE

    2025

  • CASE STUDY

    2025

  • CANCER GENOMICS: SEMINAR

    2025

  • CANCER GENOMICS: PRACTICE

    2025

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