Molecular mechanisms of tumor response to cytotoxic chemotherapy

该项目的长期目标是了解肿瘤对 细胞毒性化疗。 我们将检验低氧诱导因子基因在以下方面发挥关键作用的假设 确定肿瘤对细胞毒性癌症治疗的反应。 我们将进行实验，以确定细胞毒化疗诱导的HIF-1和 新型分子成像技术在小鼠肿瘤模型HIF-2基因激活中的应用 接近了。我们将研究特定的一氧化氮合酶基因在 化疗(环磷酰胺和依托泊苷)诱导的HIF-1和2激活(特异性 目标1)。我们还将努力定义分子机制，通过它 一氧化氮在细胞毒化疗中介导治疗诱导的HIF-1和2的激活 治疗(特定目标2)。此外，我们还将评估HIF基因在癌症中的作用 对化疗的反应遗传方法(具体目标3)。

The long-term objective of this project is to understand mechanisms of tumor response to cytotoxic chemotherapy. We will examine the hypothesis that hypoxia inducible factor genes play key roles in determining tumor responses to cytotoxic cancer therapy. We will conduct experiments to characterize cytotoxic chemotherapy-induced HIF-1 and HIF-2 gene activation in murine tumor models using novel molecular imaging approaches. We will examine the roles of specific nitric oxide synthase genes in chemotherapy (cyclophosphamide and etoposide)- induced HIF-1&2 activation (Specific aim 1). We will also make efforts to define the molecular mechanism through which nitric oxide mediates therapy-induced HIF-1&2 activation in cytotoxic chemotherapy therapy (Specific aim 2). In addition, we will evaluate the roles of HIF genes in cancer response to chemotherapy the genetic approaches (Specific Aim 3).