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Medical Sciences

Virginia Commonwealth University

Theses and Dissertations

Apoptosis

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Full-Text Articles in Medicine and Health Sciences

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee Jan 2020

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee

Theses and Dissertations

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Although standard treatments such as androgen deprivation therapies (ADT) and antiandrogens have increased survival for many patients, most men placed on these therapies will develop castration-resistant disease (CRPC). Previous studies have shown that these treatments have limited cytotoxicity and instead promote cell growth arrest. Our current work demonstrates that prostate tumor cells grown in the absence of androgens by using charcoal-stripped serum undergo senescence-mediated or senescent-like growth arrest, based on the cellular expression of senescence-associated-beta-galactosidase (SA-β-Gal). Our studies further suggest that this senescence is transient and …


Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav Jan 2018

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …


Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh Jan 2018

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …


Cytotoxic Properties Of Novel Platinum Compounds, Bbr3610-Dach And Trans-4-Nbd In Tumor Cells: Cellular Effects Of 1, 2-Dach And Nbd Ligands, Vijay Menon May 2013

Cytotoxic Properties Of Novel Platinum Compounds, Bbr3610-Dach And Trans-4-Nbd In Tumor Cells: Cellular Effects Of 1, 2-Dach And Nbd Ligands, Vijay Menon

Theses and Dissertations

Platinum-based chemotherapeutics are used for the treatment of a wide range of cancers and a number of attempts have been made toward developing compounds with better cellular stability and similar or enhanced cytotoxicity as compared to their predecessors. The first part of the work reported here focuses on the cellular effects of the metabolically stable dinuclear platinum compound, BBR3610-DACH. Comet assay showed this compound to form interstrand crosslinks, a highly toxic DNA lesion in HCT116 cells, at equimolar concentrations to its parental compound, BBR3610. Cell cycle studies showed that BBR3610-DACH causes G1/S and G2/M cell cycle arrest with S phase …


Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen May 2012

Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen

Theses and Dissertations

Title of Dissertation: FUNCTION OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7(IGFBP7) IN HEPATOCELLULAR CARCINOMA By Dong Chen. Purpose: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring the development of innovative and effective targeted therapies. The oncogene Astrocyte Elevated Gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates Insulin-like Growth Factor Binding Protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function. Experimental Design: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarrays by real-time PCR …


The Substituted Pyrrole Jb-03-14 Induces Autophagic Cell Death And Growth Arrest In Breast Tumor Cells, Christopher Ryan Arthur Jan 2007

The Substituted Pyrrole Jb-03-14 Induces Autophagic Cell Death And Growth Arrest In Breast Tumor Cells, Christopher Ryan Arthur

Theses and Dissertations

The use of chemotherapy in the treatment of cancer has stimulated the demand for better chemotherapeutic agents that are more potent at destroying tumor cell populations and more selective for the specific tumor versus normal host tissues. This project is directed at discovering new anti-tumor agents that are effective against breast cancer based on structures derived from marine organisms, specifically brominated pyrroles. We utilized an in vitro breast cancer model to study the effects of pyrroles on tumor proliferation and survival, as well as growth arrest and cell death. Our findings indicate that the substituted pyrrole JG-03-14 induces time dependent …


Characterization Of The Tcof1 Gene Using A Neuroblastoma Cell Line And A Mouse Model, Lin Li Jan 2006

Characterization Of The Tcof1 Gene Using A Neuroblastoma Cell Line And A Mouse Model, Lin Li

Theses and Dissertations

Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial development disorder and is caused by mutations in the TCOF1 gene. The TCOFl protein treacle is a nucleolar protein and may function in ribosome biogenesis.Previously, we identified downstream candidate genes using microarray analysis after manipulating Tcofl levels in a murine neuroblastoma (NB) cell line. The list of genes includes cell cycle genes as well as the transcription factors Cnbp and Tbx2, which are known to affect the cell cycle through the c-myc and p19-Mdm2-p53-p21 pathways respectively. To further characterize the cellular effects of Tcofl, stably transfected NB cell lines with overexpression …