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Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph
Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph
Electronic Theses and Dissertations
The aberrant fibrous, extracellular, and intracellular proteinaceous deposits in cells, organs and tissues are referred to as amyloids. These deposits are dominated by β-sheet structures that have been implicated in several neurodegenerative diseases and cancer. In this work, the types of amyloidosis studied include Parkinson’s disease (PD) using UA196 and NL5901 strains of Caenorhabditis elegans (C. elegans), Alzheimer’s disease (AD) using GMC101 strain of C. elegans, and cancer-associated mutant p53 aggregation in MIA PaCa-2 mutant cells. Several molecules including SK-129, NS132, NS163, bexarotene, a polyphenol (-)-epi-gallocatechine gallate (EGCG), ADH40, RD148, and RD242 were screened in vitro and in …
Exploration Of Ataxia Telangiectasia And Rad3-Related’S (Atr’S) Role In Cell Death Regulation: Implications In Development, Cancer, And Stroke, Brian Cartwright
Exploration Of Ataxia Telangiectasia And Rad3-Related’S (Atr’S) Role In Cell Death Regulation: Implications In Development, Cancer, And Stroke, Brian Cartwright
Electronic Theses and Dissertations
From gametogenesis until death an organism’s genome is under constant bombardment from endogenous and exogenous sources of DNA damage. To maintain genomic integrity amid this damage, cells have evolved responses which allow them to either preserve viability for recovery or initiate self-destructive pathways depending on the severity of DNA damage. One protein involved in initiating and carrying out these responses is the protein kinase ataxia telangiectasia and Rad3-related (ATR). ATR is known primarily for its regulatory role in initiating the checkpoint-signaling cascade following DNA damage and replicative stress. These signaling events lead to cell cycle arrest, DNA repair, or apoptosis …
Investigation Of Phosphoserine Aminotransferase 1(Psat1) In Breast Cancer Progression., Stephanie Metcalf
Investigation Of Phosphoserine Aminotransferase 1(Psat1) In Breast Cancer Progression., Stephanie Metcalf
Electronic Theses and Dissertations
This dissertation describes my research into the involvement of phosphoserine aminotransferase 1 (PSAT1) in breast cancer progression; specifically, in triple negative breast cancer (TNBC) metastasis and endocrine resistance in estrogen receptor positive breast cancer (ER+BC). Breast cancer is the most common tumor diagnosis among women. While the overall 5-year survival for breast cancer is reaching 90%, the 5-year survival for metastatic disease is only 22%. Metastasis and endocrine resistance combined can affect over 50% of patients. One of the proteins and pathways implicated in both metastasis and endocrine resistance in breast cancer is phosphoserine aminotransferase 1 (PSAT1) and the serine …
Small Molecule Disruption Of Ros-Regulating Pathways In Human Carcinoma, Rebecca E. Mccall
Small Molecule Disruption Of Ros-Regulating Pathways In Human Carcinoma, Rebecca E. Mccall
Electronic Theses and Dissertations
Gold (I) coordinated N-heterocyclic carbenes containing appended redox cycling moieties were designed and analyzed for their ability to target the antioxidant network via multiple mechanisms in various human cancer cell models. Complexes containing either ferrocene or naphthoquinone redox cycling moieties were screened for inhibition of cell growth, inhibition of thioredoxin reductase (TrxR), and accentuation of exogenous ROS. The cell death pathway employed was determined by flow cytometry via detection of Annexin-V FITC. Furthermore, differential gene expression between treated cells and untreated cells revealed the induction of endoplasmic reticulum stress and unfolded protein response pathways.
Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker
Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker
Electronic Theses and Dissertations
Cancer is a multistep disease that begins with malignant cell transformation and frequently culminates in metastasis and death. MicroRNAs (miRNAs) are small regulatory 21-25-nt RNA molecules and are frequently deregulated in cancer. The majority of miRNAs are estimated to be co-expressed with neighboring miRNAs as clusters. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. miR-200a is a member of the miR-200 family, which are known to be strong inhibitors of the epithelial to mesenchymal transition. As such, the tumor suppressive role of miR-200a in oncogenesis has been well studied; however, recent studies have …
Autoimmunity, Immune Deficiency And Cancer: Multiple Roles Of The Protein Tyrosine Phosphate Shp-1, Melissa J. Joliat
Autoimmunity, Immune Deficiency And Cancer: Multiple Roles Of The Protein Tyrosine Phosphate Shp-1, Melissa J. Joliat
Electronic Theses and Dissertations
One of a large number of mutant mice used in immunological research, the "motheaten" mouse was the first model of a specific protein tyrosine phosphatase deficiency. Mice carrying one of two allelic mutations at the "motheaten" locus have severe systemic autoimmunity and immune dysfunction as a result of mutations in the hematopoietic-cell phosphatase (Hcph) gene, which encodes the protein tyrosine phosphatase SHP-1. Studies using "motheaten" (me/me) and "viable motheaten" (mev/mev) mice have increased the understanding of numerous signaling pathways in immune and hematopoietic cells. A number of studies on SHP-1 function …