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Oncology Commons

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Full-Text Articles in Oncology

Investigation Of The Role For Methyl-Cpg Binding Protein 2 Variant Mbd2_V2 In Cancer Stem Cells And Obesity-Associated Cancers, Emily A. Teslow Jan 2019

Investigation Of The Role For Methyl-Cpg Binding Protein 2 Variant Mbd2_V2 In Cancer Stem Cells And Obesity-Associated Cancers, Emily A. Teslow

Wayne State University Dissertations

Obesity is a risk factor for both TNBC and PCa, and pro-inflammatory features associated with obesity, including upregulated production of ROS, promote CSCs. Previously published work from the Bollig-Fischer laboratory established that TNBC CSCs could be inhibited by neutralizing ROS in culture with H2O2 targeted antioxidants. In this report, antioxidant treatment resulted in the downregulation of mRNA splicing variant MBD2_v2. MBD2_v2 was highly expressed in CSCs versus bulk TNBC cells and supported self-renewal in vitro. As obesity is coupled with increased ROS, we hypothesized that obesity could drive CSCs via MBD2_v2 expression. The work presented in this thesis addressed this …


Strategies To Enhance The Anti-Leukemic Activity Of Venetoclax (Abt-199) In Aml Through Targeting Of Mcl-1, Daniel Luedtke Jan 2019

Strategies To Enhance The Anti-Leukemic Activity Of Venetoclax (Abt-199) In Aml Through Targeting Of Mcl-1, Daniel Luedtke

Wayne State University Dissertations

Acute Myeloid Leukemia (AML) is a frustratingly difficult to treat disease (67% 5 year survival for children and 24% for adults). The standard of care, similar to outcomes, has seen few improvements over the last several decades. The Bcl-2 family, which controls cell survival and apoptosis, is dysregulated in AML. Bcl-2, which is overexpressed in AML and associated with chemoresistance, is a promising therapeutic target. The now FDA approved venetoclax (ABT-199) is a BH3 mimetic that is able to bind to anti-apoptotic Bcl-2 and prevent it from sequestering pro-apoptotic Bim. While overall response rates are promising, our lab and others …


Novel Insights Into The Use Of Ercc1 As A Biomarker For Response To Platinum-Based Chemotherapy In Lung Cancer, Joshua Ryan Heyza Jan 2019

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 …


Sprouty4 Is A Negative Regulator Of Erk/Mapk Signaling In Breast Cancer And Plays A Role In The Transition From In Situ To Invasive Disease, Ethan Brock Jan 2019

Sprouty4 Is A Negative Regulator Of Erk/Mapk Signaling In Breast Cancer And Plays A Role In The Transition From In Situ To Invasive Disease, Ethan Brock

Wayne State University Dissertations

Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Previous data by our group found that Sprouty4 transcript was differentially expressed between three DCIS cell lines and a non-transformed breast epithelial cell line. Sprouty proteins are important regulators of ERK/MAPK signaling, and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry we …