BIOCHEMICAL AND CYTOGENETIC MARKERS IN RETINOBLASTOMA

描述：实验室与其他实验室的最新结果表明， 改变RB或p53状态，特别是两者一起， 成为进展和总生存期的预后标志物的候选者 在浅表性和晚期膀胱癌（以及可能的其他肿瘤类型， well）。 这些初步结果的确认可能导致这些 用于开发不同治疗策略的标记物， 在某些情况下提高生存率和更保守的方法， 膀胱癌治疗在其他方面（即，膀胱保存）。 个人 核RB染色异常强的人也被发现具有 与RB蛋白表达缺失者预后相似， 尽管其分子基础目前尚不清楚。 此外 初步数据表明，肺小细胞癌（SCLC）和 非典型癌可以通过其RB状态来区分， 具有重要的诊断和治疗意义， 不同的疗法。 因此，我们的具体目标包括：1。 进行 对浅表性和晚期膀胱癌的大型前瞻性研究， 确定给定肿瘤中RB或p53状态，尤其是两者一起 可用作肿瘤进展的真正预后标志物， 总体生存率。 RB和/或p53状态可能与 还将评估对化疗反应的影响，以及其他 RB和p53通路中的基因，包括p16、p21、细胞周期蛋白D1和细胞周期蛋白E。 2. 为了确定机制或分子基础（？ 过度磷酸化） 某些膀胱肿瘤的恶性百分比异常 细胞核RB染色强。 3. 要确定单元格中的 如果RB功能丧失的膀胱肿瘤细胞系更多， 对辐射敏感，这是从最初的临床建议 结果 4. 为了在大型前瞻性研究中验证RB状态可以 区分SCLC和非典型癌。 5. 研究其他 RB通路中的基因包括p16、细胞周期蛋白D1、细胞周期蛋白E， 其他特定肿瘤类型的发病机制，其中直接损失 RB功能罕见。 免疫组织化学分析将主要用于预后 以及基于先前发现的诊断研究。 然而，南方， 还将对某些基因进行北方和西方分析， 特定的肿瘤类型 此外，DNA测序和其他分子 在适当情况下，也将使用生物技术。 常规 技术来测量细胞毒性和辐射引起的细胞凋亡， 在培养中和体内也将被利用。

DESCRIPTION: Recent results from the laboratory with others indicate that altered RB or p53 status and particularly both together are strong candidates to become prognostic markers for progression and overall survival in superficial and advanced bladder cancer (and likely other tumor types as well). The confirmation of these initial results could lead to these markers being used to develop different therapeutics strategies leading to improved survival in certain cases and a more conservative approach to bladder cancer therapy in others (i.e., bladder preservation). Individuals with abnormally strong nuclear RB staining have also been found to have a similarly poor prognosis as those with absent RB protein expression, although the molecular basis for this is presently unknown. In addition preliminary data suggest that small cell carcinomas of the lung (SCLCs) and atypical carcinomas can be distinguished by their RB status, which in turn has important diagnostic and therapeutic implications, since they receive different therapies. Our Specific Aims therefore include: 1. To undertake large prospective studies on both superficial and advanced bladder cancer to determine if RB or p53 status in a given tumor and especially both together can be used as bona fide prognostic markers for tumor progression and overall survival. The possibility that RB and/or p53 status can be related to chemotherapeutic response will also be evaluated as well as whether other genes in the RB and p53 pathway including p16, p21, cyclin D1 and cyclin E. 2. To determine the mechanisms or molecular basis (? hyperphosphorylation) by which certain bladder tumors show an abnormal percentage of malignant cells with strong RB nuclear staining. 3. To determine both in cell culture and in vivo if bladder tumor lines with loss of RB function are more sensitive to radiation, which is suggested from the initial clinical results. 4. To verify in a large prospective that RB status can distinguish between SCLCs and atypical carcinomas. 5. To examine other genes in the RB pathway including p16, Cyclin D1, Cyclin E, are important in the pathogenesis of other specific tumor types in which the direct loss of RB function is rare. Immunohistochemical analysis will primarily be utilized for the prognostic and diagnostic studies based on the previous findings. However, Southern, Northern and Western analysis will also be done for certain genes and specific tumor types. In addition DNA sequencing and other molecular biology techniques will be used when appropriate as well. Routine techniques to measure cytotoxicity, and apoptosis produced by radiation both in culture and in vivo will also be utilized.