REGULATION OF APOPTOSIS IN NEUROBLASTOMA

这是一份申请，旨在确定是否未能接受 程序性细胞死亡有助于人类的发病机制 神经母细胞瘤 具体而言，研究人员建议确定 调节程序性细胞死亡（PCD）的癌基因产物是否 影响调节程序性细胞死亡癌基因产物 (PCD)影响神经母细胞瘤的恶性表型。 研究者 先前确定抑制PCD的Bcl-2存在于 预处理神经母细胞瘤肿瘤活检，并且，当解除管制时， 抑制神经母细胞瘤肿瘤活组织检查，并且当解除管制时， 神经母细胞瘤中化疗诱导的PCD。 基于这些先前的发现， 研究人员试图在一个系统中扩展这些观察结果， 认为神经母细胞瘤是一种由于 凋亡 第一个目标是解决致癌基因协同性的问题 在神经母细胞瘤的恶性表型中，特别是Bcl-2， 在其抑制细胞凋亡的能力中，与N-myc合作转化 细胞 第二个目的是确定Bcl-xs表达是否 会导致神经母细胞瘤细胞死亡和增强对化疗的反应 (by盗版现有的细胞机器）。 第三个具体目标建议， 测定正常人中死亡基因和存活基因的表达， 被认为是神经母细胞瘤产生的组织。 研究者 我认为这些实验将解决良性肿瘤和恶性肿瘤之间的分子联系 病变和恶性神经母细胞瘤。

This is application proposing to determine whether failure to undergo programmed cell death contributes to the pathogenesis of human neuroblastoma. Specifically, the investigator proposes to determine whether oncogene products which modulate programmed cell death (PCD) influence whether oncogene products which modulate programmed cell death (PCD) influence the malignant phenotype of neuroblastoma. The investigator previously determined that Bcl-2, which suppresses PCD, is present in pretreatment neuroblastoma tumore biopsies, and that, when deregulated, inhibits neuroblastoma tumor biopsies, and that, when deregulated, inhibits chemotherapy-induced PCD in neuroblastoma. Based on these prior findings, the investigator seeks to extend these observations in a system in which it is proposed that neuroblastoma is a disease resulting from failed apoptosis. The first aim will address the issue of oncogene cooperativity in the malignant phenotype of neuroblastoma,, specifically whether Bcl-2, in its capacity to inhibit apoptosis, cooperates with N-myc to transform cells. The second aim is proposed to determine whether Bcl-xs expression will lead to neuroblastoma cell death and enhanced response to chemotherapy (by pirating existing cell machinery). The third specific aim proposes to determine the expression of the death gene and survival gene in normal tissue from which neuroblastoma is thought to arise. The investigator feels these experiments will address the molecular link between the benign lesions and malignant neuroblastoma.