Gene therapy for oral cancer by cell cycle regulators and tumor vaccine genetically mokified to secrete cytokines.

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1)The effect of p53, p33 or p27 gene transfer by adenoviral vector were investigated in oral squamous cell carcinoma cell lines, HSC3,4. Overexpression of p53 induced apoptosis in both of cell lines, and overexpression of p27 suppressed cell growth in both cell lines. But, overexpression of p33 did not affect cell growth Furthermore, direct injection of p53 into established s.c. xenogiaft of HSC3 in nude mice inhibited tumor growth.2)The V-ATPase inhibitors concanamycin A induced apoptosis in human oral squamous cell carcinoma cell lines, HSC2,3,4. Furthermore, direct injection of concanamycin A into established s.c. xenograft of HSC3 in nude mice inhibited tumor growth. These-results showed the potential of concanamycin A as anticancer drug on oral squamous cell carcinoma3)Vaccination with irradiated tumor cells genetically modified to secrete cytokines were studied using murine oral squamous cell line, sq1979. The murine cDNA of II2, IL4, IL10, GM-CSF, TNF-α, IFN-γ were tmafered into … More sq1970 by retrovairal vector. We found that irradiated tumor cells expressing GM-CSF or IFN-γ suppressed the growth of parental sg1979 cells in vivo.4)We examined the expression profile of cyclin E1 and E2 in human oral squamous cell carcinoma cell lines, and found that the expression of cyclin E1 protein were hardly detected in HSC2. Although cyclin E2 was abundantly expressed, histone H1 kinase activities of both type of cyclin were undetectable in HSC2. Inhibition of cyclin E1 nor E2 suppressed the growth of HSC2. In contrast, HSC2 expressed cyclin D1 and hyperphosphorelated form of Rb protein family, and were arrested in G1 by overexpression of p16. These results indicate hat HSC2 lost proper growth control specifically mediated by cyclin E and suggest that deregulation of its downstream pathway contribute to tumorigenesis of SCC.5)We investigated the characterization of a high-metastatic cell line LMF4 and a low-metastatic cell line HSC3 in comparison with non-metatic cell line HSC2 and HSC4. Morphological and motility analyses revealed LMF4 to have the highest motility, but LMF4 shared the similar features with HSC3, high level secretion Autocrone Motility Factor (AMF), enhancement of gp78 expression, co-expression of vimentin and cytokeratin. AMF-transfected HSC3 augmented the AMF-R and vimentin expression, but abrogated cytokeratin expression.6)The correlation between expression of pRb2/p130 and clinicopathologic factors in oral squamous cell carcinoma was studied. Expression of pRb2/p130 may be a good prognostic indicator in patients with oral squamous cell carcinoma and also may be utilized for the subclassification of tumors with Grade 3 mode of invasion.7)The clinicopathological studies on sarcomas of oral and maxillofacial region and late metastasis in patients with Stage I〜II tongue squamous cell carcinoma was performed Adequate excision with safety surgical margin as the initial therapy is important for better survival in treatment of sarcoma. The pattern of invasion at the invasive font and invasive front grading score had predictive values for late nodal metastasis. Less