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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Basic Mechanisms of Cancer Therapeutics Study Section (BMCT)
Program Officer
Bernhard, Eric J
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Duke University
Schools of Medicine
United States
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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
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
Ma, Jingjing; Tian, Ling; Cheng, Jin et al. (2013) Sonic hedgehog signaling pathway supports cancer cell growth during cancer radiotherapy. PLoS One 8:e65032
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
Brogan, John; Li, Fang; Li, Wenrong et al. (2012) Imaging molecular pathways: reporter genes. Radiat Res 177:508-13
Liu, Xinjian; Li, Fang; Stubblefield, Elizabeth A et al. (2012) Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res 22:321-32
Li, Wenrong; Li, Fang; Huang, Qian et al. (2011) Quantitative, noninvasive imaging of radiation-induced DNA double-strand breaks in vivo. Cancer Res 71:4130-7
Huang, Qian; Li, Fang; Liu, Xinjian et al. (2011) Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med 17:860-6
Wolf, Frank; Li, Wenrong; Li, Fang et al. (2011) Novel luciferase-based reporter system to monitor activation of ErbB2/Her2/neu pathway noninvasively during radiotherapy. Int J Radiat Oncol Biol Phys 79:233-8
Li, Fang; Huang, Qian; Chen, Jiang et al. (2010) Apoptotic cells activate the "phoenix rising" pathway to promote wound healing and tissue regeneration. Sci Signal 3:ra13

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