REGULATION OF APOPTOSIS IN NEUROBLASTOMA

这是一项申请，建议确定是否未通过 程序性细胞死亡在人类疾病发病机制中的作用 神经母细胞瘤。具体地说，调查员建议确定 调控细胞程序性死亡(PCD)的癌基因产物 影响调控细胞程序性死亡的癌基因产物 (PCD)影响神经母细胞瘤的恶性表型。调查员 先前确定抑制PCD的Bcl-2存在于 神经母细胞瘤的预活检，当放松管制时， 抑制神经母细胞瘤肿瘤活检，当放松管制时，抑制 神经母细胞瘤化疗引起的PCD。基于这些先前的发现， 调查人员试图将这些观察扩展到一个系统中，在该系统中 有人认为，神经母细胞瘤是一种由失败引起的疾病 细胞凋亡。第一个目标将解决癌基因协同性的问题。 在神经母细胞瘤的恶性表型中，尤其是Bcl2、 在其抑制细胞凋亡的能力方面，与N-myc合作转化 细胞。第二个目的是确定Bcl-Xs的表达 会导致神经母细胞瘤细胞死亡和对化疗的反应增强 (通过盗版现有的牢房机器)。第三个具体目标提出 检测正常人死亡基因和生存基因的表达 神经母细胞瘤发生的组织。调查员 我觉得这些实验将解决良性的 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.