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Ribozyme approach to study functions of vascular endothelial growth factor isoforms on the progression of non-small cell lung cancer

Research Project

Project/Area Number 11670227
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionTokai University

Principal Investigator

NAKAMURA Masato  Tokai University School of Medicine Associate Professorr, 医学部, 助教授 (00164335)

Co-Investigator(Kenkyū-buntansha) UEYAMA Yoshtio  Tokai University School of Medicine Associate Professor, 医学部, 助教授 (30072408)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsribozyme / vascular endothelial growth factor / non-small cell lung cancer / isoform / angiogenesis / cancer gene therapy / 肺癌 / 遺伝子導入
Research Abstract

The specific role of the cell-associated isoform of vascular endothelial growth factor (VEGF189) has not been clarified, while five isoforms of VEGF which have different biological activities (VEGF121, VEGF145, VEGF165, VEGF189, VEGF206) are generated by alternative splicing. We used a hammerhead-type ribozyme (V189Rz) to suppress VEGF189 mRNA.The V189Rz specifically cleaved exon 6 of VEGF189 mRNA, but showed no activity against VEGF121 or VEGF165 isoforms. The V189Rz was introduced into the human non-small cell lung cancer cell line (OZ-6/VR). The expression level of VEGF189 mRNA was decreased in the OZ-6/VR, while VEGF121 and 165 expression were preserved. The OZ-6/VR xenotransplanted into nude mice showed markedly reduced vascularisation and growth, whereas the cell line did not show any decreased growth under tissue culture conditions. The OZ-6/VR cells (1×10^5/mouse) formed no tumours, whereas the parental OZ-6 cells formed huge tumours within 8 weeks. The specific suppression of VEGF189 by the ribozyme decreased vascularity and xenotranplantability of the lung cancer cell line. The cell-associated isoform of VEGF (VEGF189) might have key roles on stromal vascularisation and growth of non-small cell lung cancer xenografts in vivo.

Report

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

    (36 results)

All Other

All Publications (36 results)

  • [Publications] H.Osada,M.Nakamura, et.al.: "Gene expression of angiogenesis related factors in glioma"International Journal of Oncology. 18. 305-306 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Oshika,M.Nakamura, et al.: "Ribozyme approach to downregulate vacular endoethelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC)"European Journal of Cancer. 36(18). 2390-2396 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Tokunaga,M.Nakamura, et.al.: "Ribozyme mediated inactivation of mutant K-ras oncogene in a colon cancer cell line"British Journal of Cancer. 83(6). 833-839 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Hatanaka,M.Nakamura, et.al.: "Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer"Annals of Oncology. 11. 815-819 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Nakamura,Y.Abe, et.al.: "A case of Pulmonary Adenocarcinoma with Overexpression of Multidrug Resistance-Associated Protein and p53 Aberration"Anticancer Research. 20. 1921-1926 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Tsuchida,M.Nakamura, et.al.: "Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma"Cancer Gene Therapy. 7(3). 373-383 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto K,Nakamura M et al.,: "Xenografts of human solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189."Oncology Reports. 6. 1201-1204 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lee Y H,Nakamura M. et al.,: "Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma."European Journal of Cancer.. 35(7). 1089-1093 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto K,Nakamura M. et al.: "Inhibition of liver metastasis of colon cancer by in vivo administration of anti-vascular endothelial growth factor antibody."Oncology Reports.. 6. 553-556 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tomisawa M,Nakamura M. et al.: "Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularization in renal cell carcinoma."European Journal of Cancer.. 35(1). 133-137 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokunaga T,Nakamura M. et al.: "Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer."British Journal of Cancer.. 79(2). 354-359 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuchida T,Nakamura M. et al.: "Hammerhead ribozyme specifically inhibits mutant K-ras mRNA of human pancreatic cancer cells."Biochemical and Biophysical Research Communications. 253. 368-373 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Osada H., Tokunaga T., hatanaka H., Kawakami T., Tsuchida T., Abe Y., Tsugu A., Kijima H., Yamazaki H., Shima K., osamura Y., Ueyama Y., Nakamura M.: "Gene expression of angiogenesis related factors in glioma"International Jounral of Oncology. 18. 305-306 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oshika Y., Nakamura M., Tokunaga T., Ohnishi Y., Abe Y., Tsuchida T., Tomii Y., Kijima H., Yamazaki H., Ozeki Y., Tamaoki N., Ueyama Y.: "Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC)."Euroepan Journal of Cancer. 36(13). 2390-2396 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokunaga Y., Tsuchida T., Kijima H., Okamoto K., Oshika Y., Sawa N., Ohnishi Y., Yamazaki H., Miura S., Ueyama Y., Nakamura M.: "Ribozyme mediated inactivation of mutant K-ras oncogene in a colon cancer cell line."British Journal of Cancer. 83(6). 833-839 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hatanaka H., Abe Y., Kamiya T., Morino F., Nagata J., Tokunaga T., Oshika Y., Suemizu H., Kijima H., Tsuchida T., Yamazaki H., Inoue H., Nakamura M.and Ueyama Y.: "Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer."Annals of Oncology. 11. 815-819 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakamura M., Abe Y., Katoh Y., Oshika Y., Hatanaka H., Tsuchida T., yamazaki H., Inoue H., Ueyama Y.: "A case of Pulmonary Adenocarcinoma with Overexpression of Multidrug Resistance-Associated Protein and p53 Aberration.a"Anticancer Research. 20. 1921-1926 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuchida T., Kijima H., Hori S., Oshika Y., Tokunaga T., Kawai K., Yamazaki H., Ueyama Y., Scanlon K.J., Tamaoki N., Nakamura M.: "Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma."Cancer Gene Therapy. 7(3). 373-383 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto K, Oshika Y, Fukushima Y, Ohnishi Y, Tokunaga T, Tomii Y, Kijima H, Yamazaki H, Ueyama Y, Nakamura M.: "Xenografts of human solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189."Oncology Reports. 6. 1201-1204 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lee Y H, Tokunaga T, Oshika Y, Suto R, Yanagisawa K, Tomisawa M, Fukuda H, Nakano H, Abe S, Tateishi A, Kijima H, Yamazaki H, Tamaoki N, Ueyama Y, Nakamura M.: "Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma."European Journal of Cancer.. 35(7). 1089-1093 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto K, Oshika Y, Fukushima Y, Yoshimura M, Ohnishi Y, Tokunaga T, Hashimoto T, Hatanaka H, Tomii, Y, Yoshida Y, Miura S, Tsuchida T, Kijima H, Yamazaki H, Nakamura M, Ueyama Y.: "Inhibition of liver metastasis of colon cancer by in vivo administration of anti-vascular endothelial growth factor antibody."Oncology Reports.. 6. 553-556 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tomisawa M, Tokunaga T, Oshika Y, Tsuchida T, Fukushima H, Sato H,Kijima H, Yamazaki H, Ueyama Y, Tamaoki N, Nakamura M.: "Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularization in renal cell carcinoma."European Journal of Cancer. 35(1). 133-137 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokunaga T, Nakamura M, Oshika Y, Abe Y, Ozeki Y, Fukushima Y, Hatanaka H, Sadahiro S, Kijima H, Tsuchida T, Yamazaki H, Tamaoki N, Ueyama Y.: "Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer."British Journal of Cancer.. 79(2). 354-359 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuchida T, Kijima H, Oshika Y, Tokunaga T, Abe Y, Yamazaki H, Tamaoki N, Ueyama Y, Scanlon K J, Nakamura M: "Hammerhead ribozyme specifically inhibits mutant K-ras mRNA of human pancreatic cancer cells."Biochemical and Biophysical Research Communications. 253. 368-373 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Osada,M.Nakamura, et.al.: "Gene expression of angiogenesis related factors in glioma"International Journal of Oncology. 18. 305-306 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Oshika,M.Nakamura, et al.: "Ribozyme approach to downregulate vacular endoethelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC)"European Journal of Cancer. 36(18). 2390-2396 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Tokunaga,M.Nakamura, et.al.: "Ribozyme mediated inactivation of mutant K-ras oncogene in a colon cancer cell line"British Journal of Cancer. 83(6). 833-839 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Hatanaka,M.Nakamura, et.al.: "Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer"Annals of Oncology. 11. 815-819 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Nakamura,Y.Abe, et.al.: "A case of Pulmonary Adenocarcinoma with Overexpression of Multidrug Resistance-Associated Protein and p53 Aberration"Anticancer Research. 20. 1921-1926 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Tsuchida,M.Nakamura, et al.: "Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma"Cancer Gene Therapy. 7(3). 373-383 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okamoto K, et al.: "Xenografts of human solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189"Oncology Reports. 6. 1201-1204 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lee Y H, et al.: "Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma"European Journal of Cancer.. 35(7). 1089-1093 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto K, et al.: "Inhibition of liver metastasis of colon cancer by in vivo administration of anti vascular endothelial growth factor antibody"Oncology Reports.. 6. 553-556 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomisawa M, et al.: "Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularization in renal cell carcinoma"European Journal of Cancer.. 35(1). 133-137 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokunaga T, et al.: "Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer"British Journal of Cancer.. 79(2). 354-359 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuchida T, et al.: "Hammerhead ribozyme specifically inhibits mutant K-ras mRNA of human pancreatic cancer cells"Biochemical and Biophysical Research Communications. 253. 368-373 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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