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).
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.
|Feng, Xiao; Tian, Ling; Zhang, Zhengxiang et al. (2015) Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis. Oncotarget 6:32353-67|
|Liu, Xinjian; He, Yujun; Li, Fang et al. (2015) Caspase-3 promotes genetic instability and carcinogenesis. Mol Cell 58:284-96|
|Cheng, Jin; Tian, Ling; Ma, Jingjing et al. (2015) Dying tumor cells stimulate proliferation of living tumor cells via caspase-dependent protein kinase CÎ´ activation in pancreatic ductal adenocarcinoma. Mol Oncol 9:105-14|
|Liu, XinJian; Huang, Qian; Li, Fang et al. (2014) Enhancing the efficiency of direct reprogramming of human primary fibroblasts into dopaminergic neuron-like cells through p53 suppression. Sci China Life Sci 57:867-75|
|Liu, Chad; Li, Chuan-Yuan; Yuan, Fan (2014) Mathematical modeling of the Phoenix Rising pathway. PLoS Comput Biol 10:e1003461|
|Donato, Anne L; Huang, Qian; Liu, Xinjian et al. (2014) Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy. J Invest Dermatol 134:1686-92|
|Ma, Jingjing; Tian, Ling; Cheng, Jin et al. (2013) Sonic hedgehog signaling pathway supports cancer cell growth during cancer radiotherapy. PLoS One 8:e65032|
|Ng, Wooi-Loon; Huang, Qian; Liu, Xinjian et al. (2013) Molecular mechanisms involved in tumor repopulation after radiotherapy. Transl Cancer Res 2:442-448|
|Zimmerman, Mary A; Huang, Qian; Li, Fang et al. (2013) Cell death-stimulated cell proliferation: a tissue regeneration mechanism usurped by tumors during radiotherapy. Semin Radiat Oncol 23:288-95|
|Kon, Takashi; Zhang, Xiuwu; Huang, Qian et al. (2012) Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA. Transl Cancer Res 1:4-14|
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