DNA STUDIES & P53 GENE ABNORMALITIES IN PROSTATE CANCER

DNA研究

• 批准号: 2100724
• 负责人: Ralph W. deVere White
• 金额: $ 14.76万
• 依托单位: CTRC RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2100724
• 关键词: African American; DNA; aneuploidy; biomarker; biopsy; cancer risk; cell sorting; clinical trials; combination therapy; cooperative study; fluorouracil; gene mutation; human subject; human therapy evaluation; male; molecular oncology; neoplasm /cancer radiation therapy; nucleic acid sequence; prognosis; prostate neoplasms; prostate surgery; racial /ethnic difference; restriction fragment length polymorphism; tumor suppressor genes

The number of patients diagnosed with prostate cancer (CaP) has increased 63% in the last seven years. Over the same time period, the number of deaths has risen from 24,000 to 32,000 cases a year. With the aging of the American male population and the increased use of screening for CaP, these figures can only be expected to rise over the coming years. Although increased numbers of patients are currently being diagnosed with localized CaP, the malignant potential of an individual tumor cannot be accurately determined with present methodology. Without definition or identification of the malignant potential of the tumor, clinical investigators are unable to distinguish the cancers that will remain dormant from those that will progress and compete as a cause of mortality. For patients who require therapy, current knowledge is also lacking to allow clinicians to predict whether their tumor will respond to radiation therapy. If an accurate marker of tumors malignant potential were found, patients could be offered a more rational approach to therapy that, in many cases, would mean observation alone. Presently, two markers show promise in both these areas, namely tumor ploidy and mutation in the p53 gene. These markers have not yet been evaluated in a large, multi-institutional study. This proposal will study ploidy and p53 in patients with CaP who are entered on an ongoing clinical trial (INT-0086/SWOG-8794). Eligible patients will have been found to be margin positive after radical prostatectomy and thus have a high likelihood of disease progression. In this trial, patients are randomized to observation or adjuvant radiation therapy. The usefulness of these markers will then be evaluated utilizing specimens of 558 patients from this large multi-institutional trial. Specific aims of this proposal include the following: 1) to evaluate the clinical usefulness of DNA ploidy of a prostate biopsies; 2) to determine whether the ploidy of the positive margins predicts clinical outcome; 3) to determine whether ploidy is a stronger predictor of outcome than whether the patient receives adjuvant radiation therapy; 4) to determine whether the p53 status of the tumor is an accurate predictor of malignant potential and response to radiation therapy; and 5) to evaluate whether determining the ploidy and p53 status of the tumor gives additive information. Determination of the usefulness of these markers in CaP may be an initial step in the rationalization and individualization of treatment of patients with localized CaP.

诊断患有前列腺癌（CaP）的患者人数 在过去的七年里增长了63%。 在同一时期， 死亡人数从每年的24，000例上升到32，000例。 与 美国男性人口的老龄化和越来越多的使用 筛查CaP，这些数字只能预期在 未来几年。 尽管目前越来越多的患者 被诊断为局部CaP， 单个肿瘤不能被精确地确定 方法论 没有定义或识别恶性肿瘤 由于肿瘤的潜在性，临床研究人员无法 区分那些将保持休眠状态的癌症， 进步和竞争是导致死亡的原因。 对于需要 治疗，目前的知识也缺乏，使临床医生， 预测他们的肿瘤是否会对放射治疗产生反应。 如果 发现肿瘤恶性潜能的准确标记物， 可以提供一种更合理的治疗方法，在许多情况下， 这就意味着观察本身。 目前，有两种标记物在这两个领域显示出希望，即肿瘤标记物。 倍性和p53基因突变。 这些标记尚未被 在一项大型的多机构研究中进行了评估。 这项建议会 研究正在进行的CaP患者的倍体和p53 临床试验（INT-0086/SWOG-8794）。 合格患者将 在根治性乳房切除术后发现边缘阳性，因此 疾病进展的可能性很高。 在这项试验中，患者 随机接受观察或辅助放射治疗。是否有用 然后将使用558份样本对这些标记物进行评价 这一大型多机构试验的患者。 该提案的具体目标包括：（1）评估 前列腺活检DNA倍体的临床应用; 2） 确定阳性边缘的倍性是否预示着临床 结果; 3）确定倍性是否是一个更强的预测因子， 结果比患者是否接受辅助放射治疗; 4)为了确定肿瘤的p53状态是否是一个准确的 预测恶性潜能和对放射治疗的反应;以及 5)为了评估确定细胞的倍性和p53状态是否 肿瘤提供附加信息。 确定的有用性 CaP中的这些标记物可能是合理化的初始步骤， 局部CaP患者的个体化治疗。