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Full-Text Articles in Medicine and Health Sciences
Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson
Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson
Wayne State University Dissertations
Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …
Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish
Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish
Wayne State University Dissertations
Breast cancer is the most common cancer and the second leading
cause of cancer death in women. While ER-positive breast cancer subtypes are initially
well-managed by targeted therapies targeting estrogen signaling, many women are
suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients
who were previously successfully treated with anti-estrogen therapies worsens
overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of
a tumor may allow for the possibility …
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. …
Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah
Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah
Wayne State University Dissertations
The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.
Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …