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Biochemistry, Biophysics, and Structural Biology

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Cleveland State University

Theses/Dissertations

2022

Biomedical Research

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Targeting Heat Shock 27 Kda Protein Induces Androgen Receptor Degradation, Yaxin Li May 2022

Targeting Heat Shock 27 Kda Protein Induces Androgen Receptor Degradation, Yaxin Li

ETD Archive

Glioblastoma (GBM) is the most common and aggressive brain tumor, with very poor prognosis. Androgen receptor (AR) plays a significant role in the progression of GBM, and anti-androgen agents have the potential to be used for the treatment of GBM. However, AR mutation commonly happens in GBM, which makes the anti-androgen agents less effective. Heat shock 27 kDa protein (HSP27) is a well-documented chaperone protein to stabilize AR. Inhibition of HSP27 results in AR degradation regardless the mutation status of AR, which makes HSP27 a good target to abolish AR in GBM. Identified compound I ((N-(3-((2,5-dimethoxybenzyl)oxy)-4-(methylsulfonamido) phenyl)-4-methoxybenzamide) inhibits GBM cell …


Development And Analysis Of Next-Generation Polymeric And Bio-Ceramic Based Orthopedic Scaffolds By Advanced Manufacturing Techniques, Sudeep K. Gummadi May 2022

Development And Analysis Of Next-Generation Polymeric And Bio-Ceramic Based Orthopedic Scaffolds By Advanced Manufacturing Techniques, Sudeep K. Gummadi

ETD Archive

Gliomas express mutant isocitrate dehydrogenases producing excessive amounts of D 2-hydroxyglutarate (D2HG) and releasing some of it into the environment. The immune surveillance is reduced as a result, however, the mechanisms behind lymphocyte suppression by the D2HG stereoisomer remain unknown. I incubated Jurkat T cells with D2HG at concentrations present within and surrounding gliomas, or its obverse L2HG stereoisomer, and quantified 2HG isomers within washed cells by TSPC derivatization with stable isotope-labeled D2HG and L2HG internal standards, HPLC separation, and mass spectrometry. D2HG was found in quiescent cells in double the amount of L2HG. External D2HG or L2HG increased the …