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

为了检测新的肿瘤标志物的可能性，用TRAP法检测了来自不同妇科肿瘤患者的血液样本的端粒酶活性。为了提纯血液样本中的上皮成分，采用了基于珠子的方法，将血细胞与结合了特异性抗上皮抗原的珠子孵育。在这种方法中，大约有20%的患者显示端粒酶活性，所有患者都患有晚期妇科肿瘤，如宫颈癌和卵巢癌，而40名正常健康志愿者中没有一人没有端粒酶活性。有趣的是，在这些患者中观察到的端粒酶活性在最初的治疗后下降，如化疗和放射治疗，这表明它可能反映了疾病的进展。我们还研究了基于端粒酶的子宫内膜癌筛查方法的可能性，使用剥离的子宫内膜刮片样本。用TRAP法检测子宫内膜癌的灵敏度可达80%以上。将该方法与经典细胞学涂片检查相结合，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.