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

基于端粒酶的妇科肿瘤新型基因治疗与诊断的建立

• 批准号: 13671702
• 负责人: KYO Satoru
• 金额: $ 2.37万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671702/
• 关键词: Telomerase; Gene therapy; Diagnosis; hTR; hTERT; Gynecologic tumors; 遺伝子診断hTERT

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.

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。

项目成果

Kyo S, Jnoue M: "Complex regulatory mechanisms of telomerase activity in normal and cancer cell : How can we apply them for cancer therapy?"Oncogene. 21. 688-697 (2002)

Kyo S、Jnoue M：“正常细胞和癌细胞中端粒酶活性的复杂调节机制：我们如何将它们应用于癌症治疗？”Oncogene。

Kyo S, Masutomi K, Maida M, et al.: "Significance of immunological detection of hTERT : re-evaluation of expression and localization of hTERT"Am.J.Pathol.. (印刷中).

Kyo S、Masutomi K、Maida M 等人：“hTERT 免疫学检测的意义：重新评估 hTERT 的表达和定位”Am.J.（正在出版）。

Kyo S, Inone M: "How to inhibit telomerase activity for cancer therapy"Curr. Med. Chem Anti-Cancer Agents. 2. 613-626 (2002)

Kyo S、Inone M：“如何抑制端粒酶活性以进行癌症治疗”Curr。

Oh ST. Kyo S, et al.: "Telomerase Activation by Human Papillomavirus Type 16 E6 Protein: Induction of Human Telomerase Reverse Transcriptase Expression through Myc and GC-Rich Sp1 Binding Sites"Jounal of Virology. 75. 5559-5566 (2001)

哦，ST。

Tanaka M, Kyo S, Kanaya T, et al.: "Evidence of monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium"Am.J.Pathol.. (印刷中).

Tanaka M、Kyo S、Kanaya T 等人：“人类子宫内膜上皮腺体的单克隆组成和管腔上皮中克隆分布的马赛克模式的证据”Am.J.（出版中）。