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Articles 1 - 12 of 12
Full-Text Articles in Life Sciences
Role Of High Molecular Weight Hyaluronan In Ultraviolet B Light-Induced Transformation, Katelyn Cousteils
Role Of High Molecular Weight Hyaluronan In Ultraviolet B Light-Induced Transformation, Katelyn Cousteils
Electronic Thesis and Dissertation Repository
Keratinocyte carcinomas (KCs) are the most common cancers globally. Ultraviolet light is the key risk factor for these cancers but sunscreen has proven ineffective in their prevention, indicating a need for new prophylactic agents. Chronic elevation of high molecular weight (HMW) tissue hyaluronan (HA) in skin is linked to tumor resistance in the naked mole rat. To directly assess the role of this polysaccharide in resistance to keratinocyte tumors, a HMW HA phosphatidylethanolamine (HA-PE) formulation that penetrates skin and accumulates as coats around keratinocytes was prepared. The tumor resistance properties of the HA-PE formulation were tested in a mouse model …
Regulation Of C-Raf Stability By The Ranbpm/Ctlh Complex, Christina J. Mctavish
Regulation Of C-Raf Stability By The Ranbpm/Ctlh Complex, Christina J. Mctavish
Electronic Thesis and Dissertation Repository
RanBPM is an evolutionarily conserved multi-domain protein that has been implicated in the regulation of several cellular process, including protein stability, cell migration, gene transcription, and apoptosis. RanBPM is identified as a key member of the CTLH complex, an orthologous complex to a yeast E3 ubiquitin ligase complex, the exact function of which remains unknown. Previously, our laboratory identified RanBPM as an inhibitor of the ERK1/2 pathway through the modulation of C-RAF protein levels. This study shows that RanBPM-mediated degradation of C-RAF occurs through the proteasome and the entire CRA domain of RanBPM is necessary for direct interaction with C-RAF …
Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma
Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma
Electronic Thesis and Dissertation Repository
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development …
Inhibition Of Pannexin 1 Reduces Tumorigenic Properties Of Human Melanoma, Taylor J. Freeman
Inhibition Of Pannexin 1 Reduces Tumorigenic Properties Of Human Melanoma, Taylor J. Freeman
Electronic Thesis and Dissertation Repository
Pannexin 1 (PANX1) is a channel-forming glycoprotein that allows the passage of important signaling molecules, including ATP. We examined PANX1 levels in a panel of human melanomas and evaluated its potential as an effective target for melanoma therapy. We are the first to report endogenous PANX1 levels in multiple human melanoma cell lines, patient-derived melanoma biopsies, and primary melanoma cells. Treatment with two PANX1 channel blockers, Carbenoxolone (CBX) and Probenecid (PBN), on A375 and A375-MA2 melanoma cells significantly reduced cell growth and migration, and increased the production of melanin, a marker for a melanocytic-like phenotype. Daily treatment with CBX or …
The Role Of P62/Sqstm1 In Tgfβ-Dependent Emt And Autophagy, Evelyn Ng
The Role Of P62/Sqstm1 In Tgfβ-Dependent Emt And Autophagy, Evelyn Ng
Electronic Thesis and Dissertation Repository
Transforming growth factor beta (TGFβ) is a cytokine that regulates cellular adhesion, proliferation and apoptosis. In the context of cancer, TGFβ induces processes such as epithelial-to-mesenchymal transition (EMT). More recently, TGFβ has been discovered to also induce autophagy, and the relationship between TGFβ-induced EMT and autophagy remains unknown. Due to its involvement in autophagy and its established interactions with key TGFβ signaling proteins, this thesis focuses on the sequestosome 1 (p62/SQSTM1) protein. Here, I have shown that p62/SQSTM1 co-localizes with TGFβ receptors at the same time point that the receptors localize to Rab7-positive late endosomes. siRNA-mediated silencing of p62/SQSTM1 was …
The Loss Of Atrx Creates Susceptibility To Kras-Mediated Pancreatic Damage, Claire C. Young
The Loss Of Atrx Creates Susceptibility To Kras-Mediated Pancreatic Damage, Claire C. Young
Electronic Thesis and Dissertation Repository
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a five-year survival rate of 8%. Oncogenic KRAS mutation is found in greater than 95% of PDAC cases, but additional mutations or injury are required for disease initiation and progression. Chromatin remodeling protein ATRX has been previously implicated in DNA repair, replication and maintaining genomic stability. I hypothesized that loss of ATRX could increase the susceptibility of pancreatic tissue to pancreatic injury or KRAS-mediated damage. In this study, combination of inducible ATRX loss in adult mice with recurrent pancreatic injury or oncogenic KRAS activation resulted in increased pancreatic damage, including fibrosis, …
The Role Of Cytoplasmic Polyadenylation Element Binding Protein -2 (Cpeb-2) In Human Breast Cancer, Joshua Tordjman
The Role Of Cytoplasmic Polyadenylation Element Binding Protein -2 (Cpeb-2) In Human Breast Cancer, Joshua Tordjman
Electronic Thesis and Dissertation Repository
Cyclooxygenase-2 (COX-2) is overexpressed in 40-50% of breast cancers, and promotes tumour progression through increased proliferation, migration, invasion, Epithelial-to-Mesenchymal Transition (EMT), and induction of therapy-resistant Stem-Like-Cells (SLCs). COX-2 stimulates expression of two oncogenic and SLC-promoting microRNAs (miR-526b, miR-655), which simultaneously target one gene, Cytoplasmic Polyadenylation Element Binding Protein-2 (CPEB-2). Hypothesis: CPEB-2 is a tumour- and SLC-suppressing gene in breast cancer. Results: CPEB-2 knockout in a non-tumourigenic mammary epithelial cell line MCF10A demonstrated increases in proliferation, migration, invasion, EMT markers, SLC content, and VEGF-D expression. CPEB-2, an mRNA-binding translation-regulating protein, was found to regulate the translation of tumour suppressor p53. When …
Nuak1 Has Tumor Suppressive Activity In Epithelial Ovarian Cancer, Parima Saxena
Nuak1 Has Tumor Suppressive Activity In Epithelial Ovarian Cancer, Parima Saxena
Electronic Thesis and Dissertation Repository
NUAK1, a downstream substrate of the stress metabolism regulator Liver kinase B1 (LKB1), has been implicated as an oncogene and tumor suppressor, with distinct roles in cell cycle, senescence and cell adhesion. Epithelial ovarian cancer (EOC) spheroids remain dormant during intraperitoneal metastasis with reduced proliferation and metabolism to survive metabolically harsh conditions, possibly implicating a role of NUAK1 in EOC spheroid biology. I hypothesize that NUAK1 is regulated by LKB1 to promote dormancy in EOC. I demonstrate that NUAK1 expression and phosphorylation is regulated by LKB1 in EOC cell lines. NUAK1 is largely under-expressed in many established and new ascites-derived …
Regulation Of Smad Anchor Necessary For Receptor Activation (Sara) Protein Levels By The E3 Ubiquitin-Protein Ligase Smurf2 And Smad7, Sanghyun Lee
Electronic Thesis and Dissertation Repository
The TGFβ pathway, which regulates cell proliferation and differentiation, has also been shown to induce non-small cell lung cancer cell (NSCLC) migration and invasion. The TGFβ pathway is initiated through the binding of TGFβ to cell surface Ser/Thr kinase receptors. Activated receptors then phosphorylate intracellular signaling proteins, termed Smads, which translocate into the nucleus to regulate transcriptional responses. The protein Smad anchor for receptor activation (SARA) facilitates the phosphorylation of Smads and allows for efficient signal transduction. On the other hand, the inhibitory Smad, Smad7, recruits the E3 ubiquitin ligase, Smurf2, to catalyze the degradation of TGFβ receptors. Since the …
The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan
The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan
Electronic Thesis and Dissertation Repository
Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration are …
Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, Mario Cepeda
Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, Mario Cepeda
Electronic Thesis and Dissertation Repository
Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease that affects cell function via proteolytic and non-proteolytic mechanisms such as promoting degradation of the extracellular matrix (ECM) or augmentation of cell migration and viability, respectively. MT1-MMP has been implicated in metastatic progression ostensibly due to its ability to degrade ECM components and to allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) that inhibit substrate catalysis as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by …
Discovery Of Novel Diagnostic Biomarkers On Prostate Tumor Microparticles For Discriminating Between Low And High Risk Prostate Cancer And Improving Prostate Cancer Screening, Sabine Brett
Electronic Thesis and Dissertation Repository
There are few protein-based biomarkers to accurately distinguish between patients with low risk prostate cancer from those with high risk disease in a non-invasive manner. Prostate specific antigen (PSA) is used for clinical follow-up of prostate cancer; however, it is not effective as a screening tool. As a result, many men with non-life threatening disease having to undergo unnecessary and painful biopsies. Therefore, there is a dire need for minimally invasive platforms for monitoring patients with clinically significant prostate cancer. Prostate cell microparticles (PCMPs) released by prostate epithelial cells into plasma are a potential source of biomarkers specific for prostate …