Molecular mechanisms of tumor response to cytotoxic chemotherapy

描述(申请人提供)：本项目的长期目标是了解肿瘤对细胞毒性化疗的反应机制。我们将检验低氧诱导因子基因在决定肿瘤对细胞毒性癌症治疗的反应中起关键作用的假设。我们将使用新的分子成像方法，在小鼠肿瘤模型中进行实验，以表征细胞毒性化疗诱导的HIF-1和HIF-2基因激活。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(特定目标1)中的作用。我们还将努力确定一氧化氮在细胞毒化疗中介导治疗诱导的HIF-1和2激活的分子机制(特定目标2)。此外，我们还将评估HIF基因在肿瘤化疗反应中的作用(具体目标3)。公共卫生相关性：本项目研究HIF基因参与实体瘤化疗治疗的机制。它可能提供新的见解，允许开发新的疗法，以加强目前的癌症治疗。

DESCRIPTION (provided by applicant): 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). PUBLIC HEALTH RELEVANCE: This project studies the mechanism of the involvement of the HIF genes in chemotherapy treatment of solid tumors. It may provide new insights that allow for the development of new therapeutics that can enhance current treatments for cancer.