TELOMERASE AS A PROGNOSTIC INDICATOR FOR WILMS TUMOR

端粒酶作为肾母细胞瘤的预后指标

• 批准号: 6191092
• 负责人: JEFFREY S DOME
• 金额: $ 19.98万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6191092
• 关键词: Wilms' tumor; child (0-11); enzyme activity; human tissue; neoplasm /cancer relapse /recurrence; prognosis; telomerase

The goal of this project is to determine whether measurements of telomerase expression and activity provide an independent prognostic indicator for children with Wilms' tumor. Advances in the treatment of Wilms' tumor have produced cure rates in excess of 85 percent. If the risk of recurrence could be more accurately predicted, risk-appropriate therapies could be used to further improve cure rates while minimizing treatment-related toxicity. The enzyme telomerase has recently shown promise as a prognostic indicator. Telomerase is a specialized reverse transcriptase that maintains telomeres, compensating for the loss of DNA that occurs during replication. The enzyme, which plays a key role in the cellular immortalization process, is expressed in 85 percent to 90 percent of human cancers. High telomerase levels are correlated with adverse clinical outcomes in various adult and childhood malignancies. A pilot study of Wilms' tumor demonstrated a strong positive correlation between expression of TERT, the gene that encodes the catalytic portion of the enzyme, and tumor recurrence. This finding suggests that measurement of telomerase in Wilms' tumor may provide a useful indicator of the risk of recurrence, allowing the assignment of risk-directed therapy. The applicant's propose to perform a prospective case-control study in collaboration with the National Wilms' Tumor Study Group to confirm the pilot study's findings and to test the hypothesis that telomerase level is an independent prognostic indicator for children with Wilms' tumor. Telomerase levels will be quantified by assaying enzyme activity, expression of TERT, and expression of hTR, the RNA template component of the enzyme.

该项目的目标是确定是否测量 端粒酶表达和活性是一个独立的预后指标 为患有肾母细胞瘤的儿童准备的。肾母细胞瘤的治疗进展 治愈率超过85%。如果复发的风险可能是 更准确地预测，风险适当的治疗方法可以用来进一步 提高治愈率，同时最大限度地减少与治疗相关的毒性。这种酶 端粒酶最近显示出作为预后指标的前景。端粒酶是 一种特殊的逆转录酶，维持端粒，补偿 复制过程中发生的DNA丢失。这种酶起着关键作用 在细胞永生化过程中的作用，用85%到90%来表示 人类癌症的百分比。高端粒酶水平与不良反应相关 各种成人和儿童恶性肿瘤的临床转归。一项初步研究 Wilms‘s瘤的表达与其基因表达呈显著正相关 编码酶催化部分的TERT基因与肿瘤 复发。这一发现表明，Wilms的端粒酶的测量 肿瘤可能提供一个有用的复发风险指标，使 风险导向治疗的分配。申请人提议履行一项 与国立肾母细胞瘤联合进行的前瞻性病例对照研究 研究小组确认初步研究的结果并检验假设 端粒酶水平是儿童慢性支气管炎独立的预后指标 威姆斯肿瘤。端粒酶水平将通过分析酶活性来量化， TERT的表达和hTR的表达，hTR是TERT的RNA模板成分 酵素。