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

宫颈原位癌（CIS）是否经过宫颈发育不良，或这两种上皮内肿瘤病变是否属于不同的疾病实体，目前尚不清楚。本研究利用PXGR基因限制性内切片段长度多态性（RFLP）对CIS和发育不良的序列进行了研究。RFLP分析显示CIS病变的肿瘤细胞与侵袭性子宫癌的单克隆性一致。然而，对发育不良细胞的分析表达了不同的克隆结果。它们在某些情况下是单克隆的，而其他情况是多克隆的。通过比较mol-1和mol-2基因的表达谱，研究了CIS和异型增生细胞的不朽性。由于针对mol蛋白的特异性抗体结合活性不稳定，本实验未发现与肿瘤细胞不朽相关的mol-1蛋白向mol-2蛋白的表达转化。端粒酶活性的增加是CIS病变肿瘤细胞中另一个与细胞不朽相关的指标。由于宫颈发育不良病变周围的正常组织受到污染，因此对取自发育不良细胞的实验结果存在争议。不典型增生通常被认为是非常小的病变，层状结构总是向正常组织转移，这使得正常上皮细胞在细胞取样过程中受到污染。目前，我们正在探索一种在显微镜下获得发育不良细胞纯材料的方法。人类恶性肿瘤的发生通常涉及宿主基因组印迹和免疫监视的异常。在这项研究中，我们发现H-19和SNRPN基因的印迹在子宫恶性混合穆勒氏瘤中丢失。我们也报道了异体输血引起的免疫抑制与肿瘤复发密切相关的临床研究。这些结果表明，人子宫癌的发病机制与基因组印迹畸变和免疫抑制密切相关。此外，我们还证实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治疗效果（双标准杀伤效果）。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