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Full-Text Articles in Molecular Biology
Novel Insights Into The Use Of Ercc1 As A Biomarker For Response To Platinum-Based Chemotherapy In Lung Cancer, Joshua Ryan Heyza
Novel Insights Into The Use Of Ercc1 As A Biomarker For Response To Platinum-Based Chemotherapy In Lung Cancer, Joshua Ryan Heyza
Wayne State University Dissertations
ERCC1/XPF is a DNA endonuclease with variable expression in primary tumor specimens, and has been investigated as a predictive biomarker for efficacy of platinum-based chemotherapy in non-small cell lung cancers where up to 30-60% of tumors harbor low to undetectable ERCC1 expression. The failure of an international, randomized Phase III clinical trial utilizing ERCC1 expression to predict response to platinum-based chemotherapy suggests additional mechanisms underlying the basic biology of ERCC1 in the response to platinum-DNA damage remain unknown. In this work, we aimed to characterize a panel of ERCC1 knockout cell lines generated via CRISPR-Cas9 where we identified a synthetic …
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Wayne State University Dissertations
Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …