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Oncolytic virus therapy for biliary and pancreas cancer using a replication-competent herpes simplex virus mutant and proapoptotic reagent

Research Project

Project/Area Number 13671310
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

NAKANO Kenji  Kyushu University Hospital, Assistant Professor, 医学部附属病院, 助手 (00315061)

Co-Investigator(Kenkyū-buntansha) UEDA Junji  Kyushu University Hospital, Presearch Associate, 医学部附属病院, 医員
CHIJIIWA Kazuo  Miyazaki Medical University, Professor, 第1外科, 教授 (90179945)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsherpes simplex virus / oncolytic virus therapy / systemic antitumor immunity / gallbladder cancer / pancreas cancer / colo-rectal cancer / gastric cancer / 変異型ヘルペス1型ウイルス / 膵癌
Research Abstract

1) Antitumor efficacy of oncolytic virus therapy for gallbladder cancer
Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbaladder carcinoma cell lines (4 human and 1 hamster) showed nearly total cell killing within 72 hours of G207 infection at a MOI of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 107 pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (3 times with 4-day intervals) were significantly more effications than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one … More tumor alone with G207 caused regression or growth reduction of noninoculated tumors as well as inoculated tumors. In athymic mice, however, the antitumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T cell-mediated immune responses to both local and systemic antitumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.
2) Combination effect of oncolytic virus and proapoptotic factor for pancreas cancer
A proapoptotic reagent, Tetrocarcin A, did not enhance the oncolytic effect of G207 for pancreas cancer cells in vitro. Combination of irradiation and chemotherapeutic reagents did not increase the oncolytic viral activity. These results suggest that pancreas cancer has a resistance to the proapoptotic reagent or the cytopathic effect of oncolytic virus does not depend on the apoptosis.
3) Therapeutic efficacy of oncolytic virus for peritoneal dissemination
We also elucidated the therapeutic efficacy of oncolytic virus on peritoneal dissemination of gallbladder, colonic and gastric cancer, G207 prolonged the survival of animals bearing a microscopic peritoneal dissemination as compared with the controls, and some of the animals were cured. On the other hand, the animals harboring macroscopic dissemination were not cured although their survivals were also elongated than the control group.
These data above have been summarized and published in Molechular Therapy 3(4), 2001 and Surgical Therapy 87 (3), 2002. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Nakano K, Todo T, Chijiiwa K, Tanaka M: "Therapeutic efficacy of G207, a conditionally-replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters"Molecular Therapy. 3(4). 431-437 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 中野賢二, 千々岩一男, 田中雅夫: "胆嚢癌に対する腫瘍溶解性ウイルス療法"外科治療. 87(3). 273-279 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakano K, Todo T, Chijiiwa K, and Tanaka M: "Therapeutic efficacy of G207, a conditionally-replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters"Molecular Therapy. 3(4). 431-437 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakano K, Chijiiwa K, and Tanaka M: "Oncolytic therapy for gallbladder cancer"Surgical Therapy. 87(3). 273-279 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakano K, Todo T, Chijiiwa K, Tanaka M: "Therapeutic efficacy of G207, a conditionally-replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters"Molecular Therapy. 3(4). 431-437 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中野賢二, 千々岩一男, 田中雅夫: "胆嚢癌に対する腫瘍溶解性ウイルス療法"外科治療. 87(3). 273-279 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakano K, Todo T, Chijiiwa K, Tanaka M: "Therapeutic efficacy of G207, a conditionally-replicating herpes simplex virus type 1 mutant, for Gallbladder carcinoma in immunocompetent hamsters"Molecular Therapy. 3(4). 431-437 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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