2000 Fiscal Year Final Research Report Summary
Gene Diagnosis/Therapy of Oral Cancer Targetted for Autocrine Growth Factor and Angiogenic Factor Genes
| Project/Area Number |
11470437
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
OKAMOTO Tetsuji Hiroshima Univ., Faculty of Dentistry, Prof., 歯学部, 教授 (00169153)
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| 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)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Oral Cancer / tumor angiogenesis / FGFs / VEGF / HBp17 / FGFBP / FGFR3 / Gene Diagnosis / Oral Leukoplakia |
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| 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
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Research Products
(26 results)
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[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)
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[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)
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[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)
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[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)
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