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You searched for +publisher:"Texas Medical Center" +contributor:("Victor Krasnykh, Ph.D."). One record found.

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Texas Medical Center

1. Chiang, Yun-Chen. Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging.

Degree: PhD, 2013, Texas Medical Center

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study. Using this screening platform, we identified a promising lead candidate and further chemically derivatized the lead candidate to assess the structure-activity relationship (SAR). The most effective first generation drug inhibitors were selected and their pharmacodynamics and anti-tumor efficacy in vivo were verified by bioluminescence imaging (BLI) of HIF-1α/β heterodimerization in the xenograft tumor model. Furthermore, the first generation drug inhibitors, M-TMCP and D-TMCP, demonstrated efficacy as monotherapies, resulting in tumor growth inhibition via disruption of HIF-1 signaling-mediated tumor stromal neoangiogenesis. Advisors/Committee Members: Juri Gelovani, M.D., Ph.D., Victor Krasnykh, Ph.D., Edward F. Jackson, Ph.D..

Subjects/Keywords: HIF-1α/β heterodimerization; HIF-1α inhibitor; cancer therapy; molecular imaging; high-content screnning; split luciferase complementation assay; Medical Biotechnology; Medical Molecular Biology; Medicine and Health Sciences; Pharmaceutics and Drug Design; Therapeutics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Chiang, Y. (2013). Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging. (Doctoral Dissertation). Texas Medical Center. Retrieved from http://digitalcommons.library.tmc.edu/utgsbs_dissertations/383

Chicago Manual of Style (16th Edition):

Chiang, Yun-Chen. “Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging.” 2013. Doctoral Dissertation, Texas Medical Center. Accessed November 22, 2019. http://digitalcommons.library.tmc.edu/utgsbs_dissertations/383.

MLA Handbook (7th Edition):

Chiang, Yun-Chen. “Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging.” 2013. Web. 22 Nov 2019.

Vancouver:

Chiang Y. Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging. [Internet] [Doctoral dissertation]. Texas Medical Center; 2013. [cited 2019 Nov 22]. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/383.

Council of Science Editors:

Chiang Y. Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging. [Doctoral Dissertation]. Texas Medical Center; 2013. Available from: http://digitalcommons.library.tmc.edu/utgsbs_dissertations/383

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