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2000 Fiscal Year Final Research Report Summary

Establishment of combined gene therapy with immunogene and suicide gene for gastrointestinal cancer

Research Project

Project/Area Number 10470263
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionWakayama Medical University, School of Medicine

Principal Investigator

YAMAUE Hiroki  Wakayama Medical University, School of Medicine, Assistant Prof., 医学部, 助教授 (20191190)

Co-Investigator(Kenkyū-buntansha) NAKAMORI Mikihito  Wakayama Medical University, School of Medicine, Assistant, 医学部, 助手 (10322372)
IWAHASHI Makoto  Wakayama Medical University, School of Medicine, Assistant, 医学部, 助手 (70244738)
TANIMURA Hiroshi  Wakayama Medical University, School of Medicine, Prof., 医学部, 教授 (10026990)
Project Period (FY) 1998 – 2000
Keywordsgastrointestinal cancer / gene therapy / adenoviral vector / immunogene / suicide gene
Research Abstract

Using a syngeneic murine model, we investigated the therapeutic efficacy of combined gene therapy using adenoviral vectors expressing murine interleukin-2(AdmIL-2)and Escherichia coli cytosine deaminase(AdCD). In a subcutaneous tumor model, tumor-bearing mice were treated with an intratumoral injection of adenoviral vectors and received an intraperitoneal administration of 5-fluorocytosine(5-FC). Only the mice treated with AdCD(2x10^8 pfu)and an intermediate dose of AdmIL-2(1x10^6 pfu)survived significantly longer than mice treated with AdCD alone(p<0.01). Moreover, 40% of these treated mice obtained complete remission from tumor-bearing status. The cytotoxicity of splenocytes obtained from the treated mice was related to the survival period. A cold target competition assay showed that the cell-mediated cytotoxic response was specific for parental tumor cells. In a hepatic metastasis model, mice treated with an intravenous administration of both AdCD(2x10^8 pfu)and an intermediate dose of AdmIL-2(1x10^6 pfu)demonstrated the most significant reduction of metastatic foci and the longest survival following a 5-FC administration. These results suggest that gene therapy combined with AdmIL-2 and AdCD may be a promising strategy for a clinical application and in addition that translation of combined gene therapy from murine models into the clinical setting will require careful attention to the variables of cytokine expression levels in the design of clinical trials and in the evaluation of treatment efficacy.

  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Yamaue H: "Multidisciplinary treatment for gastric cancer patients by chemoimmunotherapy."Hepato-Gastroenterology. 46. 620-625 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terasawa H: "Antitumor effects of interleukin-2 gene-modified fibroblasts in an orthotopic colon cancer model."Jpn J Cancer Res. 90. 1000-1006 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hotta T: "P-glycoprotein expression and chemosensitivity in highly purified fresh human gastrointenstinal cancer cells."Hepato-Gastroenterology. 46. 316-321 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tani M: "Establishment and analysis of biological characteristics of a human duodenal carcinoma cells line, WDC-1."Jpn J Clin Oncol. 29. 596-599 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwahashi M: "Clinical evaluation of hepatic arterial infusion of low dose-CDDP and 5-FU with hyperthermotherapy : A preliminary study for liver metastases from esophageal and gastric cancer."Hepato-Gastroenterology. 46. 2504-2510 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsunoda T: "In vitro antitumore effect of topoisomerase-I inhibitor, CPT-11, on freshly isolated human gastric and colorectal cancer."Anticancer Res. 19. 5451-5455 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hotta T: "P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer."Surg Today. 29. 591-596 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsunoda T: "In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer."J Surg Oncol. 73. 6-11 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arii K: "Neutrophil functions and cytokine production in patients with gastric cancer."Hepato-Gastroenterology. 47. 291-297 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kondo T: "Cumulative results of chemosensitivity tests for antitumor agents in Japan. Japan Research Society for Appropriate Cancer Chemotherapy."Anticancer Res. 20. 2389-2392 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueda K: "Enhanced selective gene expression by adenovirus vector using Cre/lox pregulation system for human carcinoembryonic antigen-producing carcinoma."Oncology. 59. 255-265 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka H: "Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER 2/neu. -Possible immunotherapy for colorectal carcinomas"Br J Cancer. 78 (in press) . (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaue H, Tanimura H, Mizobata S, Noguchi K, Tani M, Tsunoda T, Iwahashi M, Nakamori M: "Multidisciplinary treatment for gastric cancer patients by chemoimmunotherapy."Hepato-Gastroenterology. 46. 620-625 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terasawa H, Tanimura H, Nakamori M, Tsunoda T, Iwahashi M, Tani M, Yamaue H: "Antitumor effects of interleukin-2 gene-modified fibroblasts in an orthotopic colon cancer model."Jpn J Cancer Res. 90. 1000-1006 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hotta T, Tanimura H, Tsunoda T, Iwahashi M, Tani M, Noguchi K, Mizobata S, Arii K, Terasawa H, Nakamori M, Yamaue H: "P-glycoprotein expression and chemosensitivity in highly purified fresh human gastrointestinal cancer cells."Hepato-Gastroenterology. 46. 316-321 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tani M, Tanimura H, Terasawa H, Yamade N, Shono Y, Yamaue H: "Establishment and analysis of biological characteristics of a human duodenal carcinoma cell line, WDC-1."Jpn J Clin Oncol. 29. 596-599 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwahashi M, Tanimura H, Nakamori M, Nagai Y, Hirabayashi N, Ueda K, Tsunoda T, Yamaue H: "Clinical evaluation of hepatic arterial infusion of low dose-CDDP and 5-FU with hyperthermotherapy : A preliminary study for liver metastases from esophageal and gastric cancer."Hepato-Gastroenterology. 46. 2504-2510 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsunoda T, Tanimura H, Hotta T, Tani M, Iwahashi M.Tanaka H, Matsuda K, Yamaue H: "In vitro antitumor effect of topoisomerase-I inhibitor, CPT-11, on freshly isolated human gastric and colorectal cancer."Anticancer Res. 19. 5451-5455 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hotta T, Tanimura H, Iwahashi M, Tani M, Tsunoda T, Noguchi K, Mizobata S, Arii K, Terasawa H, Nakamori M, Yamaue H: "P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer."Surg Today. 29. 591-596 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsunoda T, Tanimura H, Hotta T, Tani M, Iwahashi M, Ishimoto K, Tanaka H, Matsuda K, Yamaue H: "In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer."J Surg Oncol. 73. 6-11 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arii K, Tanimura H, Iwahashi M, Tsunoda T, Tani M, Noguchi K, Mizobata S, Hotta T, Nakamori M, Yamaue H: "Neutrophil functions and cytokine production in patients with gastric cancer."Hepato-Gastroenterology. 47. 291-297 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kondo T, Kubota T, Tanimura H, Yamaue H, Akiyama S, Maehara Y, Tanigawa N, Kitajima M, Takagi H: "Cumulative results of chemosensitivity tests for antitumor agents in Japan. Japan Research Society for Appropriate Cancer Chemotherapy."Anticancer Res. 20. 2389-2392 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueda K, Iwahashi M, Nakamori M, Nakamura M, Yamaue H, Tanimura H: "Enhanced selective gene expression by adenovirus vector using Cre/lox P regulation system for human carcinoembryonic antigen-producing carcinoma."Oncology. 59. 255-265 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka H, Tsunoda T, Nukaya I, Sette A, Matsuda K, Umano Y, Yamaue H, Takesako K, Tanimura H: "Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER 2/neu. -Possible immunotherapy for colorectal carcinomas"Br J Cancer. (in press)78. (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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