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Full-Text Articles in Medicine and Health Sciences
Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden
Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden
Wayne State University Dissertations
Triple negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive cancer that lacks an effective targeted therapeutic. Although many TNBCs, both in vitro and in vivo, have increased expression of epidermal growth factor receptor (EGFR), EGFR targeted inhibitors, such as gefitinib (GEF), have yet to demonstrate efficacy. Using mass spectrometry to identify pathways that remain activated in the presence of GEF, we found that components of the mTOR signaling pathway remain phosphorylated. While inhibiting mTOR with temsirolimus (TEM) decreased mTOR signaling, EGFR signaling pathways remained activated and the TNBC cell lines continued to proliferate. However, dual treatment …
Pathway Profiling Of Replicative And Induced Senescence, Maggie Purcell
Pathway Profiling Of Replicative And Induced Senescence, Maggie Purcell
Wayne State University Dissertations
Senescence is a permanent withdrawal from cell cycle that occurs naturally in cells in response to the shortening of telomeres. This natural "clock" serves to limit the number of cell divisions and therefore protects the cell from potentially carcinogenic mutations. However, senescence also occurs in response to external stresses to the cell, which is known as induced senescence. This study compares the mechanisms of natural senescence, a response to the shortening of telomeres during replication, with induced senescence by using various drugs to induce senescence: 5-aza-2-deoxycytidine (a demethylating agent), Adriamycin (a chemotherapeutic drug), and H2O2 (an agent causing oxidative stress). …
Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt
Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt
Wayne State University Dissertations
The ubiquitin-proteasome pathway is crucial to normal cellular function, and as such, has been extensively investigated as a potential target for cancer therapeutics. Many compounds have been tested for their proteasome inhibitory ability, including various small peptide aldehydes, and, following the success of cisplatin, several metal-containing complexes. The efficacy of these compounds in preclinical studies ultimately resulted in the development and approval of the first-in-class proteasome inhibitor bortezomib, the use of which, unfortunately, has been hindered by toxicity and resistance. These limitations have led to a massive push toward designing and developing new, less toxic proteasome inhibitors for clinical use. …
Tmprss2-Erg Regulation Of Androgen Biosynthetic Enzyme Expression, Dht Synthesis, And Androgen Receptor Activation In Prostate Cancer, Katelyn Ann Powell
Tmprss2-Erg Regulation Of Androgen Biosynthetic Enzyme Expression, Dht Synthesis, And Androgen Receptor Activation In Prostate Cancer, Katelyn Ann Powell
Wayne State University Dissertations
Intratumoral androgen synthesis in prostate cancer (PCa) contributes to the development of castration-resistant prostate cancer (CRPC). Several enzymes responsible for androgen biosynthesis have been shown to be overexpressed in CRPC, thus, contributing to CRPC in a castrated environment. Although intratumoral androgen synthesis is thought to contribute to the development and progression of CRPC, currently little is known regarding the regulation of androgen biosynthetic enzyme gene expression in PCa. The TMPRSS2-ERG transcription factor has been shown to be present in primary PCa tumors as well as CRPC tumors. The hypothesis was investigated that TMPRSS2-ERG fusions regulate androgen biosynthetic enzyme (ABE) gene …