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

1)研究了腺病毒载体在口腔鳞状细胞癌细胞株HSC3、4中转染p53、p33、p27基因的效果。在两种细胞系中，p53过表达诱导细胞凋亡，p27过表达抑制细胞生长。然而，p33的过表达并不影响细胞的生长。此外，将p53直接注射到裸鼠HSC3异种造血干细胞中，可以抑制肿瘤的生长。2) v - atp酶抑制剂康那霉素A诱导人口腔鳞状细胞癌细胞株（HSC2、3、4）凋亡。此外，直接注射康纳霉素A到裸鼠造血干细胞移植瘤中可以抑制肿瘤的生长。这些结果表明康那霉素A作为口腔鳞状细胞癌的抗癌药物的潜力。(3)用小鼠口腔鳞状细胞株系，1979年研究了经基因修饰的放射肿瘤细胞的免疫接种。通过逆转录病毒载体将小鼠i2、IL4、IL10、GM-CSF、TNF-α、IFN-γ的cDNA重组为…More sq1970。我们发现，在体内，表达GM-CSF或IFN-γ的辐照肿瘤细胞抑制亲本sg1979细胞的生长。4)我们检测了cyclin E1和E2在人口腔鳞癌细胞系中的表达谱，发现在HSC2中几乎检测不到cyclin E1蛋白的表达。尽管细胞周期蛋白E2大量表达，但两种类型的细胞周期蛋白的组蛋白H1激酶活性在HSC2中均未检测到。抑制细胞周期蛋白E1和E2可抑制HSC2的生长。相比之下，HSC2表达cyclin D1和Rb蛋白家族的高磷酸化相关形式，并在G1期通过p16的过表达而被抑制。这些结果表明，HSC2失去了细胞周期蛋白E特异性介导的正常生长控制，并表明其下游通路的解除有助于scc的肿瘤发生。5)我们研究了高转移细胞系lf4和低转移细胞系HSC3与非转移细胞系HSC2和HSC4的特性。形态学和运动性分析显示LMF4的运动性最高，但与HSC3具有相似的特征，高水平分泌自激运动因子（AMF）， gp78表达增强，波形蛋白和细胞角蛋白共表达。转染amf的HSC3增强了AMF-R和vimentin的表达，但抑制了细胞角蛋白的表达。6)研究pRb2/p130在口腔鳞状细胞癌中的表达与临床病理因素的相关性。pRb2/p130的表达可能是口腔鳞状细胞癌患者良好的预后指标，也可用于3级侵袭模式肿瘤的亚分类。7)对I ~ II期舌鳞癌患者口腔颌面部肉瘤及晚期转移的临床病理研究认为，充分的手术切除和安全的手术切缘是提高肉瘤治疗生存率的重要起始治疗方法。浸润前浸润模式及浸润前分级评分对晚期淋巴结转移有预测价值。少

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