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Gene Diagnosis/Therapy of Oral Cancer Targetted for Autocrine Growth Factor and Angiogenic Factor Genes

Research Project

Project/Area Number 11470437
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionHiroshima University

Principal Investigator

OKAMOTO Tetsuji  Hiroshima Univ., Faculty of Dentistry, Prof., 歯学部, 教授 (00169153)

Co-Investigator(Kenkyū-buntansha) HAYASHIDO Yasutaka  Hiroshima Univ., Dental Hospital, Assistant Prof., 歯学部・附属病院, 講師 (70243251)
TORATANI Shigeaki  Hiroshima Univ., Dental Hospital, Assistant Prof., 歯学部・附属病院, 講師 (90172220)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2000: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1999: ¥9,600,000 (Direct Cost: ¥9,600,000)
KeywordsOral Cancer / tumor angiogenesis / FGFs / VEGF / HBp17 / FGFBP / FGFR3 / Gene Diagnosis / Oral Leukoplakia / 偏平上皮癌 / 唾液腺腫瘍 / FGF / 自己増殖促進因子 / 遺伝子診断 / 遺伝子治療
Research Abstract

Angiogenesis is an essential pre-requisit for tumorigenesis.
Tumor angiogenesis is regulated by many angiogenic factors. Among the several angiogenic factors identified to date, heparin binding growth factor FGF-2 has been regarded as the most likely candidate for the induction of tumor angiogenesis. Heparin binding protein 17 (HBp17/FGF-BP) is a 17 KDa novel binding fox FGF family. This binding protein binds with HBGFs in a non-covalent and reversible manner. Binding of HBp17 with FGF-2 mediates the release of immobilized FGF-2 from the extracellular matrix. Thus HBp17 participates in angiogenesis in paracrine manner. In this study by using immunohistochemical technique co-localization of FGF-2 and HBp17 was observed in oral tissues including normal mucosa, dysplasia of different degrees and squamous cell carcinoma (SCC). The expression score for FGF-2 and HBp17 became higher with the severity of epithelial dysplasia and highest in severe dysplasia and had high correlation between (P=0 … More .045) at all stages of oral tumorigenesis. The expression of FGF-2 and HBp17 also showed significant association with MVD (P=0.045). But it did not correlate with TNM stages or recurrence interval (P>0.05). Our results demonstrated that angiogenic factors FGF-2 and HBp17 might provide the equal essential regulatory signals needed for the induction of tumor angiogenesis. The highest expression score of heparin binding angiogeric factors (FGF-2 and HBp17) and MVD in the severe dysplasia stage indicated the potential point of target for novel anti-angiogenic therapeutic strategies.
We have studied transcript levels of the two FGFR3 variants, FGFR3-IIIb and FGFR3-IIIc by RT-PCR in oral squamous cell carcinomas and normal oral epithelial cells. As expected, the FGFR3-IIIb variant, characteristic of the epithelial lineage, was the only form expressed in both malignant and non-malignant epithelial tissues. We performed PCR-SSCP analysis of the coding region of FGFR3 of 71 OSCC samples. The sequences of abnormally migrating bands revealed single nucleotide substitution in 44 of 71 OSCC (62%). G697C mutation create cysteine residue in the 2nd kinase domain of the receptor.
FGFR3 currently appears to be the most frequently mutated oncogene in oral squamous cell carcinomas : it is mutated in more than 60% of cases. FGFR3 seems to mediate opposite signals, acting as a negative regulator of growth in bone and as an oncogene in several tumor types. Less

Report

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

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Zhang Yang,Tetsuji Okamoto et.al: "Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis"Proc.Natl.Acad.Sci.USA.2001. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue.M.,Zhang.Y.,Okamoto.Hata.R-1.,and Asashima.M.: "Activin A induces expression of rat Sel-11 mRNA. a negative regulator of Notch signaling. in rat salivary gland-derived epithelial cells."Biochemical and Biophysical Research Communications.. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Michimukai.E.,Zhang.Y.,Toratani.S.,and Okamoto.T.,: "Mutation of human homologue of Drosophia patched in oral squamous cell caremoma cell lines and its unresponsiveness to sonic hedgchog."In Vitro Cell.Dev.Biol.. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayashido.Y.,Urabe.Okamoto.T.and Matsuya.T.: "Fibroblasts enhance theability of oral squamous cell carcinoma cells to activate matrix metalloproteinase-2 by inducing the expression of membrane type-1 MMP."Cancer Letter. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata.K.,Michimukai.E.,Sakamoto.A.,Ozaki.T.,Okamoto.T.: "Nevoid basal cell carcinoma syndrome with a palmer epidermoid eyst and jaw eyst."British J.Dermatology. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nii.M.,Kayada.Y.,Yoshiga.K.Okamoto.T.: "Suppression of metastasis by tissueinhibitor of metalloproteinase-1 in a newly established human oral squamous cellcarcinoma cell line."Int.J.Oncology. 16. 119-124 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang,H.,Zhang,Y.,Okamoto,T.: "Gene diagnosis of venous malformations,"J.Biomedicine & Therapeutics. 34. 95-99 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamanaka.T.,Zhang.Y.,Toratani.S.and Okamoto.T.,: "Isolation and serum-free culture of epithelial cells derivedfrom epithelial rests of malassez in human periodontal ligament."In.Vitro Cell.Dev.Biol.. 36. 548-553 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue,M.,Okamoto,T.Asajima,M.,: "Isoleucine prevents rat salivary glandepithelial cells from apoptosis in serum-free culture."In Vitro Cell.Dev.Biol.. 36. 187-189 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue,M.,Okamoto,T. et al.: "Effects of HGF and activin A on the three dimensional growth and morphogenesis of rat SHG epithelial cells in callagengels"In Vitro Cell.Dev.Biol.. 35. 131-135 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toratani,S.,Kimoto,N Shinki,T.Okamoto,T.: "Effect of photodynamic action with pheophorbide-a on human oral carcinoma cells in serum-free culture"Tissue Culture Research Communications. 18. 345-352 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue,M,Okamoto,T.,Asashima,M.: "Effect of TGF-β on morphogenesis in rat salivary gland-derived RSMG-1 cells"Tissue Culture Research Communications. 18. 339-343 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] SATO,J.D,OKAMOTO,T.: "Specific cell types and their requirements : In : Basic Animal Cell Culture : A practical approach (J.M.Davised.).pp.181-222.2nd Edition"Oxford Univ. Press. Oxford.England.. 301 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhang, Y., Wang, H., Toratani, S., Sato, J.D., Kan, M., McKeehan, W.L., and Okamoto, T.: "Wild-type keratinocyte growth factor receptor (KGFR) inhibits the growth and induces differentiation and apoptosis of human salivary adenocarcinoma cells in vitro and in vivo."Proc.Natl.Acad.Sci.USA.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue, M., Zhang, Y., Okamoto, T., Hata, R-L.and Asashima, M.: "Activin A induces expression of rat Scl-11 mRNA.a negative regulator of Notch signaling. in rat salivary gland-derived epithelial cells."Biochemical and Biophysical Research Communications.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Michimukai, E., Kitamura, N., Zhang, Y., Wang, H., Hiraishi, Y., Hayashido, Y., Toratani, S., and Okamoto, T.: "Mutation of human homologue of Drosophia patched in oral squamous cell carcinoma cell lines and its unresponsiveness to sonic hedgehog."In Vitro Cell.Dev.Biol.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Liu, X., Kan, M., Okamoto, T., Sato, G.H.and Sato, J.D.: "Fibroblast growth factor binding protein HBp17 confers a tumorigenic phenotype to anepidermoid carcinoma variant."Proc.Natl.Acad.Sci.USA.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasashido, Y., Urabe, Yoshioka, Okamoto, T.and Matsuya, T.: "Fibroblasts enhance theability of oral squamous cell carcinoma cells to activate matrix metalloproteinase-2 hyinducing the expression of membrane type-1 MMP."Cancer Letter.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata, K., Michimukai, E., Tanaka, Y., Sakamoto, A., Yamamoto, Ozaki, T., Okamoto, T.: "Nevoid basal cell carcinoma syndrome with a palmer epidermoid cyst and jaw cyst."British J.Dermatology. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang, H., Zhang, Y.and Okamoto, T.: "Gene diagnosis of venous malformations."J.Biomedicine and Therapentics. 34. 95-99 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamaka, T., Sakamoto, A., Tanaka, Y., Zhang, Y., Hayashido, Y., Toratani, S., Akagawa, Y.and Okamoto, T.: "Isolation and serum-free culture of epithelial cells derivedfrom epithelial rests of malasse/ in human periodontal ligament."In Vitro Cell.Dev.Biol.. 36. 548-553 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nii, M., Kayada, Y., Yoshiga, K.and Okamoto, T.: "Suppression of metastasis by tissueinhibitor of metalloproteinase-1 in a newly established human oral squamous cellcarcinoma cell line."Int.J.Oncology.. 16. 119-124 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue, M., Okamoto, T.and Asajima, M.: "Isoleucine prevents rat salivary glandepithelial cells from apoptosis in serum-free culture."In Vitro Cell.Dev.Biol.. 36. 187-189 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue, M., Okamoto, T., Asajima, M.and Sato, J.D.: "Effects of hepatocyte growth factorand activin A on the three dimensional growth and morphogenesis of rat submandibulargland epithelial cells embedded in collagen gels."In Vitro Cell.Dev.Biol.. 35. 131-135 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toratani, S., Kimoto, N., Shinki, T.and Okamoto, T.: "Effect of photodynamic action withpheophorbide-a on human oral carcinoma cells in serum-free culture."Tissue Culture Research Communications.. 18. 345-352 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Furue, M., Okamoto, T.and Asajima, M.: "Effectt of transforming growth factor-β (TGF-β) on morphogenesis in rat salivary gland-derived RSMG-1 cells."Tissue Culture Research Communications.. 18. 339-343 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhang Yang,Tetsuji Okamoto et al.: "Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis"Proc.Natl.Acad.Sci.USA.2001. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Furue,M.,Zhang,Y.,Okamoto,T.,Hata,R-I.,and Asashima,M.: "Activin A induces expression of rat Sel-II mRNA, a negative regulator of Notch signaling, in rat salivary gland-derived epithelial cells."Biochemical and Biophysical Research Communications.. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Michimukai,E,.Zhang,Y.,Hayashido,Y.Toratani,S.,and Okamoto,T.,: "Mutation of human homologue of Drosophia patched in oral squamous cell carcinoma cell lines and its unresponsiveness to sonic hedgchog,"In Vitro Cell.Dev.Biol., . (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashido.Y.,Urabe,Yoshioka.Okamoto,T.and Matsuya,T.:: "Fibroblasts enhance theability of-oral, squamous cell carcinoma cells to activate matrix metalloproteinase-2 by inducing the expression of membrane type-I MMP."Cancer Letter. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogata,K.,Michimukai,E.,Tanaka,Y.,Sakamoto,A.,Ozaki.T.,Okamoto,T. : "Nevoid basal cell carcinoma syndrome with a palmer epidermoid cyst and jaw cyst."British J.Dermatology, . (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nii,M.,Kayada,Y.,Yoshiga,K.and Okamoto,T.: "Suppression of metastasis by tissueinhibitor of metalloproteinase-I in a newly established human oral squamous cellcarcinoma cell line."Int.J.Oncology.. 16. 119-124 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang,H.,Zhang,Y.Okamoto,T.,: "Gene diagnosis of venous malformations,"J.Biomedicine and Therapeutics,. 34. 95-99 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamanaka.T...Zhang.Y..Hayashido.Y..Toratani.S.and Okamoto.T.: "Isolation and serum-free culture of epithelial cells derivedfrom epithelial rests of malassez in human periodontal ligament."In Vitro Cell.Dev.Biol.,. 36. 548-553 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furue,M.,Okamoto,T.and Asajima,M.,: "Isoleucine prevents rat salivary glandepithelial cells from apoptosis in serum-free culture."In Vitro Cell.Dev.Biol.. 36. 187-189 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furue,M.,Okamoto,T.,Asajima,M.and Sato,J.D.: "Effects of hepatocyte growth fatorand activin A on the three dimensional growth and morphogenesis of rat submandibulargland epithelial cells embedded in collagen gels."In Vitro Cell.Dev.Biol.. 35. 131-135 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toratani,S.,Kimoto,N.,Shinki,T.and Okamoto,T.: "Effect of photodynamic action withpheophorbide-a on human oral carcinoma cells in serum-free culture."Tissue Culture Resesrch Communications,18:345-352,1999. 18. 345-352 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Furue,M.,Okamoto,T.and Asajima,M.: "Effect of transforming growth factor-b (TGF-b) on morphogenesis in rat salivary gland-derived RSMG-I cells."Tissue Culture Research Communications,18:339-343,1999.. 18. 339-343 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sato,J.D.,Hayashi,I.,Hayashi,J.,Hoshi,H.,Mckeehan,W.L.,Okamoto.: "Specific cell types and their requirements : In : Basic Animal Cell Culture : A practical approach (J.M.Davis ed.).pp.181 -222. 2nd Edition"Oxford Univ.Press,Oxford,England.. 301 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] FURUE, M., et al.: "Effects of Hepatocyte Growth Factor (HGF)and Activin A on the Morphogenesis or Rat Submandibular Gland-derived Epithelial Cells in Serum-free collagen Gel Culture."In Vitro Cellular & Developmental Biology. 35. 131-135 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nii, M., et al.: "Suppression or metastasis by tissue inhibitor of metalloproteinase-l in a newly established human oral squamous cell carcinoma cell line."Int. J. Oncol.. 16. 119-124 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] FURUE, M., et al: "Effect of transforming growth factor-β (TGF-β) on morphogenesis in rat salivary gland-derived RSMG-1 cells."Tissue Culture Research Communications. 18. 339-343 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] TORATANI, S., et al.: "Effect of photodynamic action with pheophorbide-a on human oral carcinoma cells in serum-free culture."Tissue Culture Research Communications. 18. 345-352 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] HAYASHIDOU, Y., et al.: "Fibroblasts enhance the ability of oral aquamous cell carcinoma cells to activate matrix metalloproteinase-2 by inducing the expression of membrane type I matrix metalloproteinase."Cancer Letter. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] OGATA, K., et al.: "Nevoid Basal Cell Carcinoma Syndrome with a Palmar Epidermoid Cyst and Jaw Cyst."British J. Cancer. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] SATO J. D.: "BASIC ANIDAL CELLCULTURE (J. M. DAUISieditor)"OXFORD UNIV. PRESS, OXFORD, ENGLAND. 301 (1999)

    • Related Report
      1999 Annual Research Report

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

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