Comparison of pathogenesis between human uterine cervical dysplasia and carcinoma in situ

子宫颈原位癌（CIS）是否经过宫颈不典型增生，或者这两种上皮内肿瘤病变是否属于不同的疾病实体，还有待阐明。采用限制性片段长度多态性（RFLP）分析CIS和异型增生基因序列RFLP分析表明，CIS病变的肿瘤细胞与浸润性子宫癌的肿瘤细胞是一致的单克隆的，但是，通过比较mol-1和mol-2基因的表达谱，研究了CIS和异型增生细胞的永生性，并观察了mol-1蛋白表达向mol-2蛋白表达的转化，发现它们的表达与细胞的分化程度有关。由于特异性抗体结合活性不稳定，本实验未能鉴定出与肿瘤细胞永生化相关的端粒酶2蛋白，端粒酶活性的增加与肿瘤细胞的增殖有关， ...更多信息 在CIS病变的肿瘤细胞中检测到活性，这是与细胞永生相关的另一个指标。由于子宫颈异型增生病变周围正常组织的污染，在异型增生细胞中的实验结果存在争议。通常，异型增生被认为是非常小的病变，层状结构总是向正常组织转移，我们正在建立一种在显微镜下获得异型增生细胞纯品的方法，人类恶性肿瘤的发生往往涉及到基因组的异常印记和宿主的免疫监视。在这项研究中，我们证明了H的印记-19和SNRPN基因在子宫恶性苗勒管混合瘤中丢失，并报道了肿瘤复发与异基因输血诱导的免疫抑制密切相关的临床研究，这些结果表明人类子宫癌的发病与基因组印迹异常密切相关此外，我们还证明了自杀基因联合单纯疱疹病毒和胸苷激酶的基因治疗对人子宫癌有明显的疗效（双标准杀伤效应）。少

It has yet to be elucidated whether carcinoma in situ (CIS) of uterine cervix passes through cervical dysplasia or whether these two lesions of intraepithelial neoplasm belong to distinctive disease entity.In this study, the sequence of CIS and dysplasia was investigated by using restriction fragment length polymorphism (RFLP) of PXGR gene.The RFLP analysis showed that tumor cells from CIS lesion are consistently monoclonal same as the invasive uterine cancer.However, the analysis of dysplastic cells expressed diverse results of clonality.They were to be monoclonal in some cases and the others were to be polyclonal.The immortality of cells from CIS and dysplasia was studied by comparing expression profiles of mol-1 and mol-2 genes.The conversion of expression from mol-1 protein to mol-2 protein, which is related to immortality in tumor cells, was not identified in this experiments due to unstable binding activity of the specific antibody against mol protein.The increasing of telomerase … More activity that is another index related to cell immortality was detected in tumor cells from CIS lesion.The result of the experiments in cells from dysplasia were controversial because of contamination of normal tissue surrounding dysplastic lesion of the cervix.Generally, dysplasia is recognized as very small lesion and the stratiform structure are always shifting to normal tissue, which facilities contamination of normal epithelial cells in the process of cell sampling.We are now on the road of establishing a method for obtaining pure materials of the dysplastic cells under a microscope.Carcinogenesis of human malignancy often involves the abnormality of genome imprinting and immuno-surveillance of the host.In this study, we showed that imprinting of H-19 and SNRPN genes were lost in a malignant mixed muellerian tumor of the uterus.We also reported the clinical study in which tumor recurrence are strongly related to immunosuppression induced by allogeneic blood transfusion.These results indicate that pathogenesis of human uterine cancer is deeply related to aberration of genome imprinting and immunosuppression.Furthermore, we demonstrated that the gene therapy of suicide gene combined with herpes simplex virus and thymidine kinase was clearly effective in human uterine cancer (bistandard killing effect). Less