BIOCHEMICAL AND CYTOGENETIC MARKERS IN RETINOBLASTOMA

描述：该实验室与其他机构的最新结果表明 改变的Rb或P53状态，特别是两者结合在一起，是很强的 成为疾病进展和总体生存的预后标志物的候选人 在浅表性和晚期膀胱癌(以及可能的其他肿瘤类型，如 好的)。对这些初步结果的确认可能导致以下结果 标记物被用来开发不同的治疗策略，导致 在某些情况下提高存活率，并采取更保守的方法 其他方面的膀胱癌治疗(即保留膀胱术)。个人 具有异常强烈的核Rb染色的人也被发现有 预后与Rb蛋白表达缺失者相似， 尽管目前尚不清楚这一现象的分子基础。此外 初步数据显示，肺小细胞癌(SCLC)和 非典型癌可以通过其Rb状态来区分，而Rb状态又反过来 具有重要的诊断和治疗意义，因为它们收到了 不同的疗法。因此，我们的具体目标包括：1.承担 浅表性和晚期膀胱癌的大型前瞻性研究 确定Rb或P53在特定肿瘤中的状态，特别是两者同时存在 可作为肿瘤进展和预后的真正标志物 总体存活率。Rb和/或P53状态可能相关 也将评估对化疗的反应以及其他 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.确定致病机理或分子基础(？过度磷酸化) 某些膀胱肿瘤显示出异常的恶性百分比 Rb核染色较强的细胞。3.在单元格中确定两者 培养和体内培养的Rb功能丧失的膀胱癌细胞系更多 对辐射敏感，这是从最初的临床上建议的 结果。4.在很大程度上验证RB状态是否可以 区分小细胞肺癌和不典型癌。5.检查其他 Rb途径中的基因包括p16、Cyclin D1、Cyclin E，在 在其他特定肿瘤类型的发病机制中， Rb功能少见。 免疫组织化学分析将主要用于预测预后 以及基于先前发现的诊断研究。然而，南方人， 北方和西方的分析也将对某些基因和 特定的肿瘤类型。此外，DNA测序和其他分子 生物学技术也将在适当的时候使用。例程 测量辐射产生的细胞毒性和细胞凋亡的技术 在培养和体内也将被利用。

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.