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Targeted gene therapy for brain tumor

Research Project

Project/Area Number 12470294
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionSapporo Medical University

Principal Investigator

HAMADA Hirofumi  Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (00189614)

Co-Investigator(Kenkyū-buntansha) 振津 琢磨  札幌医科大学, 医学部, 助手 (20315526)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2000: ¥7,100,000 (Direct Cost: ¥7,100,000)
KeywordsAdeno viral vector / Gene therapy / malignant glioma / malignant melanama / receptor / peptide ligand / tumor / adenoviral fiber / 悪性黒色腫
Research Abstract

In order to introduce tumor-specific tropism for the proteoglycan NG2, which is exclusively expressed in the vasculature of glioma and melanoma cells, we genetically incorporated an NG2-binding peptide, TAASGVRSMH (TAA), in the C-terminal end of the fiber of Adv F/40S. The specificity for the NG2 proteoglycan was tested by flow cytometric analysis using various kinds of tumor and normal cells. The expression of NG2 was high in human melanoma A375 and human glioma A172 cells, but NG2 was not expressed in human colon carcinoma DLD-1 cells and primary cultures of normal human melanocytes and hepatocytes. The Adv F/40S-TAA showed a remarkably enhanced efficiency in genetic transduction of NG2-positive cells. In A375 and A172 cells expressing NG2, Adv F/40S-TAA increased transduction threefold to fivefold compared with Adv F/40S or Adv F/wt. In contrast, in the several different NG2-negative cells, the gene transduction of Adv F/40S or Adv F/40S/TAA was very low, while that of Adv F/wt was high. Furthermore, the gene transduction of Adv F/40S-TAA was dose-dependently blocked by the TAA peptide, but the recombinant Ad5 fiber or Ad40S fiber did not inhibit the transduction. These results suggested that Adv F/40S-TAA specifically infected A375 melanoma and A172 glioma cells through its target NG2 receptor. In order to target tumor cells in vivo, we examined the in vivo distribution of the Adv F/40S-TAA after intravenous admini stration to mice carrying NG2-positive A375 cells. The bgal of Adv F/40S-TAA was selectively expressed in the tumor vasculature rather than tumor cells, sparing the lung, heart, liver, spleen, kidney, and blood. In contrast, the Adv F/40S-TAA was incapable of targeting the tumor in receptor-negative DLD-1-bearing mice. Thus the fiber-mutant Adv F/40S-TAA achieved a CAR-independent, NG2-targeted gene delivery capacity into melanoma cells in vitro and in vivo.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Nakamura T, Sato K., Hamada, H.: "Effective gene transfer for human melanomas by integrin-targeted adenoviral vectors.Hum.Gene Ther.13(5): in press, 2002"Human Gene Ther.. 13(5)(In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto S., et al., Hamada, H.: "Reduced transduction efficiency of adenoviral vectors expressing human p53 gene by repeated transduction into glioma cells in vitro"Clinical Cancer Res.. (In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Uchida H, Shinoura N, Kitayama J, Watanabe T, Nagawa H, Hamada, H.: "Caspase-8 gene transduction augments radiation-induced apoptosis in DLD-1 cells.Biochem.Biophys.Res.Commun.in press, 2002"Biochem. Biophys. Res. Commun. (In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura N, Furitsu T, Asai A, Kirino T, Hamada, H.: "Co-transduction of p27Kip1 strongly augments Fas ligand-and caspase-8-mediated apoptosis in U-373MG glioma cells"Anticancer Res.. 21(5). 3261-3268 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura N, Sakurai S, Asai A, Kirino T., Hamada H.: "Caspase-9 transduction overrides the resistance mechanism against p53-mediated apoptosis in U-87MG glioma cells"Neurosurgery. 49(1). 177-186 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura N, Sakurai S, Asai A, Kirino T, Hamada H.: "Over-expression of APAF-1 and caspase-9 augments radiation-induced apotosis in U-373MG glioma cells"Int J Cancer. 93(2). 252-261 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawamura, K., Bahar, R., Namba, H., Seimiya, M., Takenaga, K., Hamada, H., Sakiyama, S. and Tagawa, M.: "Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication."Int. J. Oncology. (jn press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Lin Hui Wang, Dian Wen Ju, Yinghao Sun, Qun Tao, Songxi Qian, Jing Mi, Hirofumi Hamada. Xuetao Cao: "The potent antitumor effects of combined p16 gene.and GM-CSF gene therapy through efficient induction of antitumor immunity"Cancer Res Clin Oncol. 127. 101-108 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang LH, Ju DW, Sun Y, Tao Q, Qian S, Mi J, Hamada H. Cao X: "The potent antitumor effects of combined p16 gene and GM-CSF gene therapy through efficient induction of antitumor immunity"J Cancer Res Clin Oncol. 127(2). 101-108 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinohara T, Miki, T, Nishimura N, Nokihara H, Hamada H, and Ohno T. /Nuclear factor-kappaB-dependent expressing of metastasis suppressor KAI 1: "CD82 gene in lung cancer cell lines expressing mutant p53"Cancer Res. 61(2). 673-678 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ding, L-H, Iimura, E., Saijo, K, Hamada. H. and Ohno, T.: "A speedy method to detect inserted DNA fragment in cell lines transfected with retrovirus vectors"Cytotechnology. 34. 243-252 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugibayashi, R., Shimizu, T., Suzuki, T., Yamamoto, N., Hamada, H., and Takada, K.: "Upregulation of p21(WAF1/CIP1) leads to morphologic changes and esterase activity in TPA-mediated differentiation of human prostate cancer cell line TSU-Pr1"Oncogene. 20(10). 1220-1228 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimizu, T., Shimada, H., Ochiai, T., and Hamada. H.: "Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion ggne transfer (uracl phosphoribosyl-transferase and herpes simplex virus thymidine kinase)"Cancer Gene Therapy. 8(7). 512-521 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura, N.,Sakurai, S. Asai, A. Kirino, T., and Hamada, H.: "Co-transduction of apaf-1 and caspase-9 augments etposide-induced apoptosis in U-373MG glioma cells"Jpn J Cancer Res. 92(4). 467-474 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohashi, M., Kanai, F., Tateishi, K., Taniguchi, H., Marignani, PA., Yoshida, Y., Shiratori, Y., Hamada, H., and Omata, M.: "Target gene therapy for a-fetoprotein-producing hepatocellular carcinoma by E1B55K-attenuated adenovirus"Biochem. Biophys. Res. Commun.. 282. 529-535 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura, N.,Sakurai, S. Asai, A. Kirino, T., and Hamada, H.: "Over-expression of APAF-1 and caspase-9 augments radiation-induced apoptosis in U-373MG glioma cells"Int J Cancer. 93(2). 252-261 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura, N.,Sakurai, S. Asai, A. Kirino, T., and Hamada, H.: "Caspase-9 transduction overrides the resistance mechanism against p53-mediated apaptosis in U-87MG glioma cells"Neutosurgery. 49(1). 177-86-186-7 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Desakunai, Sz., Lumniczky, K., Hidvegi, EJ., Hamada, H., and Safrany, G.: "Brain tumor treatment with IL-2 and IL-12 producing autologous cancer cell vaccines"Adv. Exp. Med. Biol.. 495. 369-372 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishimura S, Adachi M, Ishida T, Matsunaga T, Uchida H, Hamada H, Imai K.: "Adenovirus-mediated transfection of caspase-8 augments, anoikis and inhibits peritoneal dissemination of human gastric carcinoma cells"Cancer Res.. 61(19). 7009-7014 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinohara T, Nishimura N, Hanibuchi M, Nokihara H, Miki T, Hamada H, and Sone S: "Transduction of KAI1/CD82 cDNA promotas hematogenous spread ot human lung-cancer cells in natural killer cell-depleted SCID mice"Int J Cancer. 94(1). 16-23 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura H, Sekiguchi H, Akiyama S, Hamada H, Fujiwara M, Kasai Y, Ito K, Nakao A: "Adenovirus-mediated transfection of Escherichia coli-uracil phosphoribosyltransferase gene increases the sensitivity of esophageal cancer cells to 5-fluorouracil"Surg Today. 31(9). 785-790 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujita N, Kagamu H, Yoshizawa H, Itoh K, Kuriyama H, Matsumoto N, Ishiguro T, Tanaka J, Suzuki E, Hamada H, Gejyo F: "CD40 Ligand Promotes Priming of Fully Potent Antitumor GD4(+) T Cells in Draining Lymph Nodes in the Presence of Appptotic Tumor Cells"J Immunol. 167(10). 5678-5688 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueno M, Koyama F, Yamada Y, Fujimoto H, Takayama T, Kamada K, Naito A, Hirao S, Mukogawa T, Hamada H, and Nakajima Y: "Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene"Anticancer Res.. 21(4A). 2601-2608 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura N, Furitsu T, Asai A, Kirino T, and Hamada H: "Co-transduction of p27Kip1 strongly augments Fas ligand-and caspase-8-mediated apoptosis in U-373MG glioma cells"Anticancer Res.. 21(5). 3261-3268 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimada H, Liu TL, Ochiai T, Shimizu T, Haupt Y, Hamada H, Abe T, Oka M, Takiguchi M, and Hiwasa T: "Facilitation of adenoviral wild-type p53-induced apoptotic cell-deaty by overexpression of p33(INGI) in T.Tn human esophageal carcinoma cells"Oncogene. 21(8). 1208-1216 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Uchida H. Shinoura N. Kitayama J. Watanabe T. Nagawa H. and Hamada H.: "Caspase-8 gene transduction augments radiation-induced apoptosis in DLD-1 cells"Biochem. Biophys. Res. Commun.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto S., et al. and Hamada H.: "Reduced transduction efficiency of adenoviral vectors expressing human p53 gene by repeated transduction into glioma cells in vitro"Clinical Cancer Res.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura T, Sato K, and Hamada H: "Ellective Gene therapy for human melanomas by integrin-targeted adenoviral vectors"Hum.Gene Ther.. 13(5):(in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Damniczky, K., Desaknai, Sz., Mangel, L., Szende, B., Hamada. H. Hidvegi, E.J. and Safrany G.: "Local tumor irradiation augments the.antitumor effect of cytokine-producing autologous cancer cell vaccines in a murine glioma model"Cancer Gene Ther.. 9. 44-52 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Xia DJ, Zhang WP, et al., Hamada H, and Cao X.: "Lymphotactia co transfecfion enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100"Gene Ther.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinoura N., Sakurai S., Shibasaki F., Asai A., Kurino T., and Hamada H.: "Co-transduction of Apaf-1 and caspase-9 highly enhanced p53-mediated apaptosis in gliomas"Br J Cancer.. 88(4). 587-595 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura T, Sato K., Hamada H.: "Effective gene transfer for human melanomas by integrin-targeted adenoviral vectors"Human Gene Ther.. 13(5)(In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto S, Hamada H et al.: "Reduced transduction efficiency of adenoviral vectors expressing humant p53 gene by repeated transduction into glioma cells in vitro"Clinical Cancer Res.. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uchida H, Shinoura N, Kitayama J, Watanabe T, Nagawa H, Hamada. H.: "Caspase-8 gene transduction augments radiation-induced apoptosis in DLD-1 cells"Biochom. Biophys. Res. Commun. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinoura N, Furitsu T, Asai A, Kirino T, Harnada, H.: "Co-transduction of p27Kip1 strongly augments Fas ligand-and caspase-8-mediated apoptosis in U-373MG glioma cells"Anticancer Res.. 21(5). 3261-3268 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinoura N, Sakurai S, Asai A, Kirino T, Hamada, H.: "Caspase-9 transduction overrides the resistance mechanism against p53-mediated apoptosis in U-87MG glioma cells"Neurosurgery. 49(1). 177-186 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinoura N, Sakurai S, Asai A, Kirino T, Hamada, H.: "Over-expression of APAF-1 and caspase-9 augments radiation-induced apoptosis in U-373MG glioma cells"Int J Cancer. 93(2). 252-261 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Motoi,F., et al.and Hamada,H.: "Effective gene therapy for pancreatic cancer by cytokines mediated by restricted replication-competent adenovirus."Human Gene Ther.. 11. 223-235 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinoura,N., et al.and Hamada,H.: "Adenovirus-mediated transfer of Bcl-xl protects neuronal cells from Bax-induced apoptosis."Exp.Cell Res.. 254. 221-231 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinoura,N., et al.and Hamada,H.: "Adenovirus-mediated transfer of caspase-3 with Fas ligand Induces drastic apoptosis In U373MG glioma cells."Exp.Cell Res.. 256. 423-433 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinoura,N., et al.and Hamada,H.: "Adenovirus-mediated transfer of caspase-8 augments cell death in gliomas : Implication for gene therapy."Human Gene Ther.. 11. 1123-1137 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinoura,N., et al.and Hamada,H.: "Adenovirus-mediated transfer of caspase-8 in combination with super-repressor of NF-kB drastically induced apoptosis in gliomas."Biochem.Biophys.Res.Commun.. 271. 544-552 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinoura,N., et al.and Hamada,H.: "Transduction of Apaf-1 or caspase-9 induces apoptosis in A172 cells, which are resistant to p53-mediated apoptosis."Biochem.Biophys.Res.Commun.. 272. 667-673 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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