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Identification of VEGF-dependent tumor vessels and prediction of effectiveness of bevacizumab-based therapy for colorectal cancer

Research Project

Project/Area Number 16K08690
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKobe University

Principal Investigator

Kamoshida Shingo  神戸大学, 保健学研究科, 教授 (70351020)

Co-Investigator(Kenkyū-buntansha) 新谷 路子 (田中路子)  神戸常盤大学, 保健科学部, 准教授 (40207147)
Research Collaborator ITOH Tomoo  
OHSAKI Hiroyuki  
OKAMURA Shunsuke  
OSAKI Tatsushi  
SHIOGAMA Kazuya  
NISHIMURA Kanae  
MAEDA Kotaro  
MATSUOKA Hiroshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords大腸癌 / 腫瘍新生血管 / チミジンキナーゼ / アポトーシス / 術前化学療法 / 予後予測 / 免疫組織化学 / ネオアジュバント化学療法 / ベバシズマブ / 効果予測 / VEGF / 新生血管
Outline of Final Research Achievements

We investigated the use of TK1/CD31 double immunostaining for identifying activated tumor vessels. TK1-positive vessel rate (PVR) and Ki67-PVR in colorectal cancers (CRCs) was greater than in normal tissues, whereas TK1-PVR in normal tissues was significantly less than Ki67-PVR. We also assessed whether CD31-positive vessel density (PVD), TK1-PVR, and apoptotic marker expression in CRC liver metastasis (CRCLM) after neoadjuvant chemotherapy (NAC) are associated with overall survival (OS). CD31-PVDLow were significantly associated with a longer OS. There were no deaths in patients with TK1-PVRLow tumors. Cleaved caspase-3 (CC3)High and cleaved cytokeratin-18High in tumor cells and CC3-PVRHigh were significantly associated with a shorter OS. Our results suggest that TK1/CD31 double immunostaining can detect activated tumor vessels more accurately than Ki67/CD31 staining, and analyses of tumor vessels and apoptosis in CRCLM after NAC could predict the prognosis of CRCLM patients.

Academic Significance and Societal Importance of the Research Achievements

術前化学療法を施行した大腸癌患者の肝転移巣切除材料を対象として、予後を制御する因子の発現を明らかにすることは、肝転移切除後の治療戦略を構築する上で役立つと期待される。また、予後不良の要因となる因子を標的とした治療薬の開発の構想につながる可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(5 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] Thymidine kinase-1/CD31 double immunostaining for identifying activated tumor vessels2018

    • Author(s)
      Okamura S.、Osaki T.、Nishimura K.、Ohsaki H.、Shintani M.、Matsuoka H.、Maeda K.、Shiogama K.、Itoh T.、Kamoshida S.
    • Journal Title

      Biotechnic & Histochemistry

      Volume: 94 Issue: 1 Pages: 60-64

    • DOI

      10.1080/10520295.2018.1499962

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 大腸癌肝転移巣におけるcleaved caspase-3(CC3)陽性血管:患者予後との関連2019

    • Author(s)
      高畠三景、大﨑 博之、松岡 宏、前田 耕太郎、塩竈 和也、鴨志田 伸吾
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸癌肝転移巣におけるthymidine kinase 1(TK1)陽性血管と予後との関連性2018

    • Author(s)
      岡村 俊佑、西村 奏絵、大﨑 博之、松岡 宏、前田 耕太郎、塩竈 和也、鴨志田 伸吾
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 大腸癌肝転移巣におけるアポトーシス・マーカーの発現:患者予後との関連2018

    • Author(s)
      西村 奏絵、岡村 俊佑、松岡 宏、前田 耕太郎、塩竃 和也、鴨志田 伸吾
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腫瘍新生血管同定のためのthymidine kinase 1/CD31二重免疫染色2017

    • Author(s)
      尾崎達司、大﨑博之、松岡宏、前田耕太郎、塩竈和也、鴨志田伸吾
    • Organizer
      第106回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都・新宿区)
    • Year and Date
      2017-04-27
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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