Establishment of telomerase-based novel gene therapy and diagnosis for gynecologic tumors

为了研究新的肿瘤标志物的可能性，我们用TRAP法检测了各种妇科肿瘤患者的血液样本中端粒酶的活性。为了纯化血液样品中的上皮成分，使用基于珠粒的方法，其中将血细胞与缀合有特异性抗上皮抗原的珠粒孵育。结果显示，在40例正常健康志愿者中，无一例端粒酶活性阴性，约20%的晚期妇科肿瘤（宫颈癌、卵巢癌）患者端粒酶活性阳性。有趣的是，在这些患者中观察到的端粒酶活性在初始治疗后下降，如化疗和放疗，这表明它可能反映疾病的进展。我们还研究了使用脱落的子宫内膜刮削样本进行子宫内膜癌的端粒酶为基础的筛查方法的可能性。用TRAP法检测子宫内膜癌的敏感性可达80%以上。联合经典细胞学涂片检查可提高筛查子宫内膜癌的敏感性和特异性。

To examine the possibility of novel tumor markers, telomerase activity was measured by the TRAP assay using blood samples from patients with various gynecologic tumors. To purify the epithelial components in blood samples, beads-based method was used, in which blood cells were incubated with beads that were conjugated with specific anti-epithelial antigen. Approximately, 20% of patients exhibited telomerase activity in this method, all of them had advanced gynecologic tumors, such as cervical and ovarian cancers, while none of 40 normal healthy volunteers showed no telomerase activity. Interestingly, telomerase activity observed in these patients decreased after initial treatment, such as chemotherapy and radiotherapy, suggesting that it might reflect disease progression.We also examined the possibility of telomerase-based screening method for endometrial cancers using exfoliated endometrial scarping samples. We could achieved more than 80% of sensitivity to detect endometrial cancers using TRAP assay with endometrial scarping samples. Combination of this method with classical cytologic smear test may improve sensitivity and specificity to screen endometrial cancers.