• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular cancer therapy based on the pathological analysis of the pancreatic cancer

Research Project

Project/Area Number 10470258
Research Category

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

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

Principal Investigator

HOSOTANI Ryo  Graduate School of Medicine, KYOTO UNIVERSITY Associate Professor, 医学研究科, 助教授 (00139908)

Co-Investigator(Kenkyū-buntansha) SASAI Keishi  Graduate School of Medicine, KYOTO UNIVERSITY Associate Professor, 医学研究科, 助教授 (20225858)
FUJII Nobutaka  Graduate School of Pharmaceutical Science, KYOTO UNIVERSITY Professor, 薬学研究科, 教授 (60109014)
IMAMURA Masayuki  Graduate School of Medicine, KYOTO UNIVERSITY, Professor, 医学研究科, 教授 (00108995)
KOGIRE Masafumi  Graduate School of Medicine, KYOTO UNIVERSITY Assistant Professor, 医学研究科, 助手 (60283595)
DOI Ryuichiro  Graduate School of Medicine, KYOTO UNIVERSITY Instructor, 医学研究科, 講師 (20301236)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsApoptosis / Bcl-X gene / p16 / Signal transduction / integrin αV β3 / Pancreatic cancer / DcR3 / 膵癌治療 / 遺伝子 / 受容体
Research Abstract

1.Signal transduction of apoptosis and pancreatic cancer therapy
Expression analysis of the pancreatic cancer tissue demonstrated over-expression of Bcl2-related proteins, particularly Bcl-X.In pancreatic cancer cells, i) cellular susceptibility to radiation-induced apoptosis was correlated with Bax/Bcl-2 ratio, ii) exogenous CDK inhibitor induced apoptosis with the rise in Bax/Bcl-2 ratio, and iii) Bcl-X expression was induced in radiation-resistant cells. Bcl-X antisense treatment in cancer cells caused sequence-specific transcriptional inhibition and subsequent augmentation of radiation-induced apoptosis.
2.Development of new anti-cancer agents based on gene abnormalities
A new synthetic retinoid, TAC-101, showed a potent growth inhibition of pancreatic cancer cells. Induction of endogenous CDK inhibitor, p21 and p27, was involved in the mechanism. We have synthesized p16-peptide with antennapedia carrier peptide. The peptide penetrated into the cells and showed significant growth inhi … More bition, which was associated with G1 arrest of the cell cycle. p16 treatment in mice demonstrated a marked inhibition of tumor growth in subcutaneous tumor model and significant survival benefit in peritoneal dissemination model. The results suggest the possible strategy for the development of new anti-cancer agents based on the gene abnormalities.
3.Pancreatic cancer therapy for tumor dormancy
Expression analysis of the cancer tissue showed strong expression of VEGF and PD-ECGF in cancer cells and significant correlation of the expression of these angiogenic factors with tumor angiogenesis. When chemotaxis of the angiogenic endothelial cells were concerned, SDF-1 gene was expressed in the cancer stromal cells and its receptor CXCR-4 was expressed in cancer cells and endothelial cells. This SDF/CXCR-4 system was involved in the mechanism of migration of pancreatic cancer cells and endothelial cells. We have newly synthesized cyclic RGD peptide with E-alkane bond which is specific for integrin αV β3. This RGD peptide showed potent inhibitory effect on both attachment and growth of endothelial cells. In subcutaneous tumor model, RGD peptide treatment induced tumor dormancy, when the treatment started before tumor growth depends on angiogenesis. Less

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Fujimoto K: "Expression of two angiogenic factors vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relation to angiogenesis."Eur.J.Cancer. 34. 1439-1447 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wada M: "An exogenous CDK inhibitor.Butyrolactone-1, induces apoptosis with increased Bax/Bcl-2 ratio in p53-mutated pancraetic cancer cells."Anticancer Res.. 18. 2559-2566 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto Y: "Immunohistochmical analysis of Bcl-2,Bax, Bcl-X and Mel-1 expression in pancreatic cancers."Oncology. 56. 73-82 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimoto K: "Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative,TAC-101,in human pancreatic cancer cells."Int J Cancer. 81. 637-644 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koshiba K: "Role of stromal derived factor-1(SDF-1) and CXCR4 ligand receptor system in pancreatic cancer."Clin Cancer Res.. 6. 3530-3535 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimoto K: "Inhibition of pRB phosphorylation and cell cycle progression by an antennapedia-p16(INK4A) fusion peptide in pancreati cacncer cells."Cancer Lett.. 159. 151-158 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimoto K: "Expression of two angiogenic factors vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relation to angiogenesis."Eur.J.Cancer. 34. 1439-1447 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wada M: "An exogenous CDK inhibitor, Butyrolactone-I, induces apoptosis with increased Bax/Bcl-2 ratio in p53-mutated pancraetic cancer cells."Anticancer Res.. 18. 2559-2566 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyamoto Y: "Immunohistochemical analysis of Bcl-2, Bax, Bcl-X and Mcl-1 expression in pancreatic cancers."Oncology. 56. 73-82 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimoto K: "Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative, TAC-101, in human pancreatic cancer cells."Int J Cancer. 81. 637-644 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koshiba K: "Role of stromal derived factor-1 (SDF-1) and CXCR4 ligand receptor system in pancreatic cancer."Clin Cancer Res.. 6. 3530-3535 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimoto K: "Inhibition of pRB phosphorylation and cell cycle progression by an antennapedia-p16 (INK4A) fusion peptide in pancreati cacncer cells."Cancer Lett.. 159. 151-158 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawaguchi M. et al.: "Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells."Int J Oncol.. 16. 37-41 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuno S. et al.: "Pancreatic cancer : current status of treatment and surviral of 16071 patients diagnosed from 1981-1996, using the Japanese National Pancreatic cancer Database."Int J Clin Oncol. 5. 153-157 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujimoto K, et al.: "Inhibition of pRB phosphorylation and cell cycle progression by an antennapedia-plb (INK 4A) fusion peptide in pacreati cancer cells."Cancer Lett.. 159. 151-158 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koshiba T, et al.: "Role of stromal dericed factor-1 (SDF-1) and CXCR4 ligand receptor system in pancreatic cancer."Clin Cancer Res.. 6. 3530-3535 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamoto Y, et al.: "Delayed (18) F-fluoro-2-deoxy-D-glucose positron emission tomography scan for differentiation between malignant and benign lesions in the pancreas."Cancer. 89. 2547-2554 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto Y, et al.: "Ineterleukin-6 inhibits radiation-induced apoptosis in pancreatic cancer cells."Ancticancer Research. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyamoto Y.: "Immunohistochemical analysis of Bcl-2, Bax, Bcl-x and Mcl-1 expression in pancreatic cancers"Oncology. 56. 73-82 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kato M.: "Characterization of six cell lines established from human pancreatic adenocarcinemors"Cancer. 85. 832-840 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujimoto K.: "Inductron of cell-oycie arrest and apoptosis by a novel retinobenzoic acid, TAC101, in pancreatic cancer"Int. J. Cancer. 81. 637-644 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koshiba T.: "Immunohistochemical analysis of oyeloxigenase-2 expression in pancreatic tumors"Int. J. Pancreatol. 26. 69-76 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lee J.V.: "Role of Bcl-2 family proteins (Bax, Bcl_2 and Bcl-x) on cellular susceptability treadiation in pomuectic cancer"Eur. J. Cancer. 35. 1374-1380 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawaguchi M.: "Auto-induction and growth stimulating effect of hetacellulein human pancreatic cancer cells"Int. J. Oncol.. 16. 37-41 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koshiba T: "Involvement of matrix metalloproteinase-2 acfivity in invasion and metastasis of pancreatic carcinoma." Cancer. 82. 642-650 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujimoto K: "Expression of two angiogenic factors VEGF and PD-ECGF in human pancrealic cancer and its relation to angiogenesis" Eur.J.Cancer. 34. 1439-1447 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wada M.: "An exogenous CDK inhibitor, Budyrolaction-I, induces apoptosis with inacasod Bry/Bcl-2 ratio in porncreatic cancer cells." Anticanur Res.18. 2559-2566 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyamoto Y.: "Immunohistochemical analysis of Bcl-2, Bax, Bcl-X and Mcl-1 expression in pancreatic cancer" Oncology. 56. 73-82 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suwa H: "Detection of multiple hepatic methstasis in pancreatic adonocarcinoma with a solitorey liver metastasis." Surgery. 125. 113-116 (1999)

    • Related Report
      1998 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi