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TELOMERASE AS A PROGNOSTIC INDICATOR FOR WILMS TUMOR

端粒酶作为肾母细胞瘤的预后指标

基本信息

批准号：
6522820
负责人：
JEFFREY S DOME
金额：
$ 17.82万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-08-01 至 2005-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6522820
关键词：
Wilms' tumor child (0-11) enzyme activity human tissue neoplasm /cancer relapse /recurrence prognosis telomerase

项目摘要

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提供了独立的预后指标为患有肾母细胞瘤的孩子们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，风险适当的治疗可以用来进一步提高治愈率，同时使治疗相关毒性最小化。酶端粒酶最近显示出作为预后指标前景。端粒酶是一种专门的逆转录酶，维持端粒，在复制过程中DNA的丢失。这种酶，在细胞永生化过程中的作用，在85%到90%的人中表达， %的人类癌症。高端粒酶水平与不良反应有关。各种成人和儿童恶性肿瘤的临床结果。的初步研究肾母细胞瘤的表达与肿瘤细胞凋亡之间存在强的正相关性。编码该酶催化部分的基因TERT与肿瘤复发这一发现表明，在肾母细胞瘤中，肿瘤可以提供复发风险的有用指标，风险导向治疗的分配。申请人拟进行的与国家肾母细胞瘤合作的前瞻性病例对照研究研究小组确认试点研究的结果并检验假设端粒酶水平是一个独立的预后指标，肾母细胞瘤端粒酶水平将通过测定酶活性来定量，表达，以及hTR的表达，所述hTR是所述细胞的RNA模板组分。酵素