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Gene therapy for augmentation chemosentivities to anticancer drugs with improvement of therapeutic index

Research Project

Project/Area Number 10470265
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOsaka Medical College

Principal Investigator

TANIGAWA Nobuhiko  Faculty of Medicine, Osaka Medical College professor, 医学部, 教授 (00111956)

Co-Investigator(Kenkyū-buntansha) NIKI Masami  Faculty of Medicine, Osaka Medical College lecturer, 医学部, 講師 (90271402)
MORITA Shinsyo  Faculty of Medicine, Osaka Medical College assistant professor, 医学部, 助教授 (90200419)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Keywordsgene therapy / augmentation of chemosensitivity to anticancer drugs / Fluoro-pyrimidine / Thymidine phosphorylase / PD-ECGF / retroviral vector / digestive cancer / angiogenesis / PD-GCGF / retroviral vcctor
Research Abstract

Novel approaches are being investigated for improvement of therapies of human cancers. We have identified a strong association between sensitivity to 5-FU and levels of thymidine phosphorylase (TP) and thymidine kinase (TK) in either human gastric or colon cancer. In addition, after TP/PD-ECGF cDNA was successfully transfected into PC9 cells with use of a plasmid vector, the in vitro mechanism of augmentation of sensitivities to Doxifluridine and 5-FU was partly clarified, by use of the transfected cells, with obtaining confirmatory data of a bystander effect of a type of cell attachment included in the augmentation. A part of our research works, collaborating with the Department of Bacteriology I in Tokyo Jikeikai Medical College, firstly succeeded in yielding a retroviral vector involving TP/PD-ECGF cDNA and we are now conducting the investigation for further clarification of augmentation mechanism of chemosensitivities to Fluoro-pyrimidines. In the mean time, the level of TP enzyme, one of angiogenic peptides, is drastically decreased in both peritoneal seeding cells and in vitro cancer cells. Taken together, it can be considered that this newly developed retroviral vector involving TP/PD-ECGF cDNA may be substantially useful for study of tumor angiogenesis. Thus, the study of a virally directed enzyme prodrug therapy like this would have potential to propose invaluable methods for improvement of cancer chemotherapies.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] T.Nohara: "Expression of cell-cycle regulator p27 is correlated to the prognosis and ER expression in breast carcinoma patients"Oncology. 60. 94-100 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nishiguchi: "Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma."Dis Colon Rectum. 44(2). 223-230 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Tanaka: "Expression of survivn and its relationship to loss of apoptosis in breast carcinomas."Clinical Cancer Research. 6. 127-134 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Tenjyo: "Prognostic significance of p27^<kip1> protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas"Oncology. 58. 45-51 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shinohara: "Intensfied regression of colon cancer liver metastasis in mice treated with irinotecan and the immunomodulaor JBT 3002"J.Immunother. 23. 321-331 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ohtani: "Impact of the expression of cyclin-dependent kinase inhibitor p27^<kip1> and apoptosis in tumor cells on the over all survival of patients with non-early stage gastric carcinoma"Cancer. 85. 1711-1718 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] C-D.Lu: "Loss of p27^<kip1> expression independently predicts poor prognosis for resectable pancreatic adenocarcinomas"Cancer. 85. 1250-1260 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Kawasaki: "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer"Cancer Research. 58. 5071-5074 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Nohara: "Expression of cell-cycle regulator p27 is correlated to the prognosis and ER expression in breast carcinoma patients."Oncology. 60. 94-100 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nishiguchi: "Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma"Dis Colon Rectum. 44(2). 223-230 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Tanaka: "Expression of survivn and its relationship to loss of apoptosis in breast carcinomas."Clinical Cancer Research. 6. 127-134 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Tenjyo: "Prognostic significance of p27^<kip1> protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas."Oncology. 58. 45-51 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shinohara: "Intensified regression of colon cancer liver metastases in mice treated with irinotecan and the immunomodulaor JBT 3002."J.Immunotherapy. 23. 321-331 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Ohtani: "Impact of the expression of cylindependent kinase inhibitor p27^<kip1> and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma."Cancer. 85(8). 1711-1718 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] C-D.Lu: "Loss of p27^<kip1> expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma."Cancer. 85(6). 1250-1260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Kawasaki: "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer."Cancer Research. 58. 5071-5074 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Nohara: "Expression of cell-cycle regulator p27 is correlated to the prognosis and ER expression in breast carcinoma patients"Oncology. 60. 94-100 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Nishiguchi: "Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma."Dis Colon Rectum. 44(2). 223-230 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Tanaka: "Expression of survivn and its relationship to loss of apoptosis in breast carcinomas."Clinical Cancer Research. 6. 127-134 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Tenjyo: "Prognostic significance of p27^<kip1> protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas"Oncology. 58. 45-51 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Shinohara: "Intensified regression of colon cancer liver metastases in mice treated with irinotecan and the immunomodulaor JBT 3002"J.Immunotherapy. 23. 321-331 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Ohtani: "Impact of the expression of cyclin-dependent kinase inhibitor p27^<kip1> and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma"Cancer. 85(8). 1711-1718 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] C-D.Lu: "Loss of p27^<kip1> expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma"Cancer. 85(6). 1250-1260 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Kawasaki: "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer"Cancer Research. 58. 5071-5074 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] 谷川允彦: "シンチレーション・アッセイ"組織培養工学. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 谷川允彦、野村栄治、等: "化学療法と手術 II.胃癌 1.進行度別術後遠隔成績と補助療法の現状"外科. 62(2). 145-149 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Tenjyo.,N.Tanigawa.et al: "Prognostic Significance of p27^<kipl> Protein Expression and Spontaneous Apoptosis in Patients with Colorectal Adenocarcinomas"Oncology. 58. 45-51 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Tanaka.,N.Tanigawa.et al: "Expression of survivin and Its Relationship to Loss of Apoptosis Breast Carcinomas"Clinical Cancer Research. 6. 127-134 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Ohtani.,N.tanigawa.et al: "Impact of Expression of Cyclin-Dependent Kinase Inhibition p27^<kipl> and Apoptosis in Tumor Cells on Overall survival of patients with Non-Early Gastric Carcinoma"Cancer. 85(8). 1711-1718 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] C-D.Lu.,N.Tanigawa.et al: "Loss of p27^<kipl> expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma"Cancer. 85(6). 1250-1260 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 谷村弘、谷川允彦、等: "抗癌剤感受性試験の現況"医薬ジャーナル社. 132 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Ohtani: "Impact of expression of cyclin-dependent kinase inhibitor p27k^<klrl> and apoptosis in tumor cells on overall survival of patients with non-early gastric carcimoma" Cancer. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] C-D.Lu: "Loss p27k^<klkl> expression independently predicts poor prognosis for resectable pancreatic adenocarcinomas" Cancer. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Aotake: "Changes of angiogenesis and tumor cell apoptosis during colorectal carcinogenesis" Clinical Cancer Research. 5. 135-142 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Kawasaki: "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer" Cancer Research. 58. 5071-5074 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] C-D.Lu: "Expression of a novel antiapoptosis gene,survivin,correlated with tumor cell apoptosis and p53 accumulation in gastric carcinoma" Cancer Research. 58. 1808-1812 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Matsumura: "Platelet-derived endo the lial cell growth factor/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophage infiltration in colorectal cancer" Cancer Letters. 128. 55-63 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Aotake: "Efficacious diagnosis of primary and metastatic human carcinomas with a combination of p53 mutation analysis and clonality analysis of androgen receptor gene" International J Oncology. 13. 773-779 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Kato: "Enhancement of drug sensivity and a bystander effect in PC9-cells transfacted with a pletekt-derived endothelial cell growth factor thymidine phosphorylase cDNA" British Journal of Cancer. 75. 506-511 (1997)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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