BLADDER CANCER--SUPPESSOR GENES AND RADIATION RESPONSE

用巨量射束进行全剂量放射治疗效果不佳。 对于浸润性膀胱癌(只有30%-50%治愈)。这需要 临床医生建议膀胱切除术，并与其相关的主要损失 对肌肉侵袭性肿瘤患者的泌尿生殖功能 治愈率仍不到50%。使用组合的最新创新 综合治疗(经尿路手术、放疗和化疗) 初步表明结果有所改善(60%的患者完好无损 无肿瘤的膀胱)。然而，目前尚无已知的目的肿瘤 在诊断时仍然存在的特征是临床上 通过这种保留膀胱的治疗成功的令人满意的预测。这个 如果这样的话，对个别病人的护理将大大改善 确定了预后因素。 MGH泌尿外科肿瘤科小组已经治疗了115名侵入性 使用这些组合进行前瞻性临床试验的膀胱癌 医疗模式。这代表着一大群穿着制服的病人 肿瘤初始队列，有完整或持续的随访，占70% 保留膀胱，并提供完整的初始肿瘤标本 组织病理学亚型和DNA细胞术。 肿瘤抑制基因的改变被认为是一种 在多种癌症的发病机制中起重要作用，并可能 与某些恶性特征相关。主要研究目标是 MGH泌尿外科肿瘤-分子生物学课题组正在调查 肿瘤抑制基因在泌尿系肿瘤中的作用。我们有 在过去的8个月里建立了所需的实验室技术和 已经整合了这个临床基础科学团队来评估P53基因 (ExOne 5-8)冷冻和固定石蜡包埋档案的更改 膀胱癌标本。我们建议进行研究的目的是 确定两个最具特征性的肿瘤的改变 抑制基因Rb和P53将与辐射反应和/或 治疗结果的其他方面。我们设想这是 膀胱病发病机制的系统遗传学分析 癌症。我们判断我们的实验室技术，可用的档案初始 肿瘤标本和我们强大的临床和统计分析系统 都表明这一短期研究项目将 抑癌基因改变与放射治疗及预后的关系 化疗反应将完成，并将提供坚实的新 信息，无论结果如何。

Full-dose radiation therapy by megavoltage beams has yielded poor results for invasive bladder cancer (only 30-50% cured). This has required clinicians to recommend cystectomy, with its associated major losses of genitourinary function, to patients with muscle-invading tumors even though the cure rate is still less than 50%. Recent innovations using combined modality therapy (transurethral surgery, radiation and chemotherapy) indicate, preliminarily, improved results (60% of patients have intact bladders that are tumor-free). However, no known objective tumor characteristic yet exists at the time of diagnosis that is a clinically satisfactory predictor for success by such bladder-sparing treatments. The care of individual patients would be sharply improved were such a prognostic factor identified. The MGH Urologic Oncology Group has treated 115 patients with invasive bladder cancer on prospective clinical trials using these combined modalities. This represents a large patient population with a uniform tumor inception cohort, with complete or ongoing follow up, with 70% bladder preservation, and with initial tumor specimens available with full histopathologic subtyping and DNA cytometry. Alterations of tumor suppressor genes have been implicated to play a significant role in the pathogenesis of many forms of cancer and may correlate with certain malignant characteristics. The main research goal of MGH Urologic Oncology-Molecular Biology Research Group is to investigate the role of tumor suppressor genes in urologic cancers. We have established over the past 8 months the needed laboratory techniques and have integrated this clinical-basic science team to evaluate p53 gene (exone 5-8) alterations on frozen and fixed paraffin-embedded archival bladder tumor specimens. Our objective of the proposed research is to determine whether alterations of the two best characterized tumor suppressor genes, RB and p53, will correlate with radiation response and/or other aspects of treatment outcome. We envision this as a first step in a systemic approach to the genetic analysis of the pathogenesis of bladder cancer. We judge our laboratory technology, the available archival initial tumor specimens and our strong system of clinical and statistical analysis of patient outcome all indicate that this short-term research project to correlate tumor suppressor gene alterations with radiotherapy and chemotherapy response will be completed and will provide solid new information, whatever the outcome.