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Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
The Regulation And Mechanisms Of Egfr-Mediated Apoptosis In Mda-Mb-468 Cells., Nicole Marion Jackson
The Regulation And Mechanisms Of Egfr-Mediated Apoptosis In Mda-Mb-468 Cells., Nicole Marion Jackson
Electronic Theses and Dissertations
Background: The Epidermal Growth Factor Receptor (EGFR) is a 170- kilodalton transmembrane protein that belongs to the ErbB family of receptor tyrosine kinases. Upon ligand-mediated activation, the EGFR responsible for cell growth, proliferation, and tissue homeostasis in epithelial cells; however, the EGFR is overexpressed in many human malignancies including MDA-MB-468 cells, a metastatic breast epithelial cell line. Previous studies have indicated that within the MDA-MB-468 cell line, receptors at the cell surface promote cell growth when activated with Epidermal Growth Factor (EGF) ligand. Activated receptors that are internalized to the endosomes however induce apoptosis. This contrasting response at different cellular …
Suramin Protects From Cisplatin-Induced Acute Kidney Injury., Tess Dupre
Suramin Protects From Cisplatin-Induced Acute Kidney Injury., Tess Dupre
Electronic Theses and Dissertations
In rodent models, suramin improves recovery following acute kidney injury (AKI). We hypothesized that suramin would be useful in protection against cisplatin-induced AKI. This hypothesis was tested by pre-treating C57BL/6j mice with suramin prior to cisplatin. Our data indicates that suramin protects the kidney from injury by decreasing cisplatininduced decreases in kidney function. Renal histology indicated that suramin significantly protected from cisplatin-induced AKI. Data indicate that suramin pretreatment attenuated mRNA expression of pro-inflammatory cytokines and chemokines following cisplatin treatment, while also decreasing markers of cell stress and cell death. We utilized the same experimental design with 10-month old FVB mice …
Identifying Hepatocellular Carcinoma (Hcc) Cells With Cancer Stem Cell-Like Properties., Harshulkumar M. Pandit
Identifying Hepatocellular Carcinoma (Hcc) Cells With Cancer Stem Cell-Like Properties., Harshulkumar M. Pandit
Electronic Theses and Dissertations
Hepatocellular Carcinoma (HCC) is a challenging condition to treat in the clinic due to its distinct tumor phenotype, aggressive growth, and chemotherapy resistance. Cancer Stem Cells (CSCs) are a poorly differentiated subpopulation of cells within the tumor microenvironment, and role of CSCs in tumor initiation and chemotherapy resistance is not well understood in HCC. In this study, we have successfully identified HCC cells with CSC-like properties that showed resistance to Doxorubicin. Using the established serum free culture techniques, we have enriched CSC-like cells among hepatocellular cancer cells. These enriched cells exhibit all CSC-like properties i.e. self-renewal capability, anchorage independent growth …
Searching For Novel Ligands For The Cannabinoid And Related Receptors., Pritesh Prakash Kumar
Searching For Novel Ligands For The Cannabinoid And Related Receptors., Pritesh Prakash Kumar
Electronic Theses and Dissertations
The first purpose of the present dissertation was to apply a high throughput assay to systematically screen a library of food and drug administration (FDA)-approved drugs as potential ligands for the cannabinoid receptor 2 (CB2). A cell-based, homogenous time resolved fluorescence (HTRF) method for measuring changes in intracellular cAMP levels was validated and found to be suitable for testing ligands that may act on CB2. Among the 640 FDA-approved drugs screened, raloxifene, a drug used to treat/prevent post-menopausal osteoporosis, was identified for the first time to be a novel CB2 inverse agonist. The dissertation reporting these results demonstrated that by …
Improved Oncolytic Virotherapy By Increasing Virus Spread Within Tumors., Stephen Wechman
Improved Oncolytic Virotherapy By Increasing Virus Spread Within Tumors., Stephen Wechman
Electronic Theses and Dissertations
Oncolytic adenoviruses (Ads) have great therapeutic potential for lung cancer. Cancer selective E1b-deleted Ads are safe, however their efficacy remains limited clinically. To improve E1b-deleted Ads, Adhz60 was selected for greater anti-cancer efficacy by a process called bioselection, producing AdUV. AdUV preferentially lysed A549 and H1299 lung cancer cells more effectively than both the cancer selective Adhz60 and non-selective Ad5. AdUV induced greater LC3-II expression, relative to LC3-I, indicating that AdUV (30.9-fold) induced autophagy more effectively than Ad5 (12.2-fold) and Adhz60 (7.8-fold) in A549 cells. Mice treated with AdUV had significantly smaller tumors (p-value < 0.001) and prolonged survival (p-value = 0.0005) than mice treated with the negative control AdGFP. These results suggest that AdUV efficiently lyses lung cancer cells in vitro and in vivo.
Chronic Ethanol Exposure Sensitizes The Lung In A Mouse Model Of Endotoxemia-Induced Acute Lung Injury : Potential Role Of Plasminogen Activator Inhibitor-1., Lauren G. Poole
Electronic Theses and Dissertations
The goal of this project is to characterize a new mouse model of alcohol-enhanced acute lung injury (ALI) and to determine the role of plasminogen activator inhibitor-1 (PAI-1) in this model. Male mice (WT and PAI-1-/-) were exposed to ethanol-containing Lieber-DeCarli diet or pair-fed control diet for 6 weeks; some animals were administered intraperitoneal lipopolysaccharide (LPS) prior to sacrifice. Chronic alcohol feeding enhanced induction of the chemokines MIP-2 and KC (murine IL-8 homologues) after LPS injection in wild type animals. This enhanced chemokine expression did not correlate with enhanced pulmonary neutrophil infiltration, however animals exposed to chronic ethanol showed sustained …
Regulation Of Receptor Tyrosine Kinases By Ubiquilin1., Zimple Kurlawala
Regulation Of Receptor Tyrosine Kinases By Ubiquilin1., Zimple Kurlawala
Electronic Theses and Dissertations
Receptor Tyrosine Kinases (RTK’s) like EGFR, Insulin Receptor, IGF1R and others mediate growth, proliferation and balance between apoptosis and survival. Dysregulation of RTK activity has been identified in a wide range of cancers and contributes to initiation, progression and metastasis of tumors. Ubiquilins (UBQLN) are fairly novel proteins and are studied mostly in the field of neurodegenerative disorders. Our laboratory recently discovered a link between UBQLN1 function and tumorigenesis. UBQLN1 is lost in about 50% of non-small cell lung cancer (NSCLC) cases. We have identified an interaction between UBQLN1 and IGF1R. Furthermore, UBQLN1 regulates activity of IGF1R and EGFR. Following …
Metabolomics Of Transformed Mda-Mb-231 Cell Lines Expressing Different Levels Of Human Arylamine N-Acetyltransferase 1 (Nat1)., Samantha Marie Carlisle
Metabolomics Of Transformed Mda-Mb-231 Cell Lines Expressing Different Levels Of Human Arylamine N-Acetyltransferase 1 (Nat1)., Samantha Marie Carlisle
Electronic Theses and Dissertations
Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme that is found in almost all tissues of the body. Expression of NAT1 is commonly elevated in several cancers including breast cancer. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Three MDA-MB-231 breast adenocarcinoma cell lines that stably express wild-type, increased, and decreased levels of human NAT1 have been constructed and characterized for NAT1 mRNA, NAT1 acetylation activity, cell doubling rates, and endogenous acetyl-CoA levels. Differences in polar metabolic profile between these three cell lines were investigated using a comprehensive GC×GC−TOF …
Promoting Differentiation And Survival Of Human C-Kit+ Cardiac Progenitor Cells Ex Vivo., Tareq Al-Maqtari
Promoting Differentiation And Survival Of Human C-Kit+ Cardiac Progenitor Cells Ex Vivo., Tareq Al-Maqtari
Electronic Theses and Dissertations
c-kit+ cardiac progenitor cells (CPCs) have recently gained much attention due to the therapeutic effects they exert on cardiac function following their administration into the infarcted heart as evidenced by animal studies and by a recent clinical trial (SCIPIO). However, injecting these cells in the heart is associated with poor differentiation into specialized cardiac cell types and with rapid death of the engrafted cells. With the ultimate goal of advancing cardiac stem cell therapy, we sought to facilitate the differentiation of human CPCs into cardiac cell types (e.g. cardiomyocytes, smooth muscle cells, endothelial cells and cardiac fibroblasts) by overexpressing selected …
Exploring The Roles Of Host And Tumor Cell Α4 And Α7 Nicotinic Acetylcholine Receptors In Lung Cancer., John Caleb Greenwell
Exploring The Roles Of Host And Tumor Cell Α4 And Α7 Nicotinic Acetylcholine Receptors In Lung Cancer., John Caleb Greenwell
Electronic Theses and Dissertations
Lung cancer is the leading cause of cancer death in men and women worldwide. Tobacco exposure represents the major risk factor. Nicotine, an addictive plant alkaloid found in tobacco, has been demonstrated to stimulate lung carcinoma cells directly via nicotinic acetylcholine receptors (nAChRs) that trigger downstream signals capable of promoting lung cancer growth and progression. Attention has been given to α7 nAChRs, while less is known about α4 nAChRs. However, most studies evaluating these receptors relied on chemical inhibitors notorious for their off-target effects. Consequently, the true role of α4 and α7 nAChRs in lung cancer remains unclear. To address …