BLADDER CANCER--SUPPESSOR GENES AND RADIATION RESPONSE

兆伏射线的全剂量放射治疗效果不佳 浸润性膀胱癌（只有30-50%治愈）。 这需要 临床医生推荐cyclohexane，其相关的重大损失， 泌尿生殖系统功能，肌肉浸润肿瘤患者，即使 治愈率仍然不到50%。 最近的创新使用组合 方式治疗（经尿道手术、放疗和化疗） 初步表明，改善的结果（60%的患者具有完整的 无肿瘤的膀胱）。 然而，没有已知的客观肿瘤 在诊断时仍存在临床特征， 通过这种膀胱保留治疗的成功的令人满意的预测。 的 个别病人的护理将大大改善，如果这样的话， 确定的预后因素。 MGH泌尿肿瘤组已经治疗了115名患者， 膀胱癌的前瞻性临床试验，使用这些组合 方式。 这代表了一个庞大的患者群体， 肿瘤起始队列，完成或正在进行随访，70% 膀胱保存，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在肿瘤的发生发展中起着重要作用。 在许多形式的癌症的发病机制中起重要作用， 与某些恶性特征有关 主要研究目标 MGH泌尿肿瘤分子生物学研究小组的研究 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， 整合了这个临床基础科学团队来评估p53基因 （外显子5-8）冷冻和固定石蜡包埋档案的改变 膀胱肿瘤标本。 我们的研究目的是 确定两个最佳表征的肿瘤的改变是否 抑制基因RB和p53将与辐射反应相关，和/或 治疗结果的其他方面。 我们设想这是一个 膀胱癌发病机制的系统遗传学分析 癌 我们判断我们的实验室技术，可用的档案初始 我们强大的临床和统计分析系统 所有这些都表明，这项短期研究项目， 肿瘤抑制基因改变与放射治疗相关， 化疗反应将完成，并将提供坚实的新的 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.