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Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh
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 …
Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez
Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez
Theses and Dissertations
Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …
The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin
The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin
Theses and Dissertations
Breast cancer is the second leading cause of death amongst women ages 20 to 59. Despite advancements in cancer therapies, more research is necessary to improve the diagnoses and treatment of several types of breast cancer. Paclitaxel (Taxol) is a commonly utilized anti-cancer drug for various types of solid tumors. However, the molecular mechanism utilized by paclitaxel to induce cell death is still elusive. Previous studies in our laboratory have shown that the pro-apoptotic BCL-2 family protein, BAK (BCL-2 homologous antagonist/killer) plays an important role in paclitaxel-induced cell death. In untreated breast cancer cells, BAK is associated with the anti-apoptotic …
The Effect Of Cobalt Protoporphyrin And Cobalt Chloride On Heme Oxygenase Expression And Protection From Deoxycholate-Induced Apoptosis, Tina Lawson
Theses and Dissertations
The inner surface of the stomach is lined by a mucous membrane known as the gastric mucosa. The integrity of the gastric mucosa is critical for protecting the stomach from the low pH and proteolytic environment within the lumen. Both clinically and experimentally, exposure of gastric mucosal cells to bile salts is known to cause injury. Bile salts present in duodenogastric reflux are thought to play a significant role in gastric ulcer formation and alkaline gastritis. In vitro, studies using physiologic concentrations of the secondary bile salt, deoxycholic acid, indicate that bile salts can induce apoptosis in cultured human gastric …
Generation Of Macrophage Chemotactic Factors By Spla2, Andria Chambers
Generation Of Macrophage Chemotactic Factors By Spla2, Andria Chambers
Theses and Dissertations
Removal of apoptotic cells by macrophages is required in order to prevent autoimmune responses. Previous studies have reported that group IIA secretory phospholipase A2 (sPLA2) preferentially binds to apoptotic cells and induces a chemotactic factor which promotes the migration of macrophages to apoptotic cells. Based on these observations, we hypothesized that the pool of sPLA2 trapped on apoptotic cells produces chemoattractant lipids that recruit macrophages to phagocytose the apoptotic cells. To test this hypothesis, Jurkat cells were cultured under normal conditions and induced to undergo early apoptosis through treatment with D,L-threo-dihydrosphingosine. Live and early apoptotic cells were incubated with catalytically …
Phospholipase A2 Induced Monocyte Chemotaxis To Apoptotic Cells, Kwasi Karikari
Phospholipase A2 Induced Monocyte Chemotaxis To Apoptotic Cells, Kwasi Karikari
Theses and Dissertations
Apoptosis is a form of programmed cell death that is essential in such processes as organ and tissue remodeling and maturation of hematopoietic cells. The clearance of apoptotic cells is essential to prevent autoimmune responses to sequestered antigens. This process is mediated by phagocytes of the monocyte lineage. Before phagocytosis can occur, macrophages must be recruited to the apoptotic cells through chemotaxis. Products of the reaction catalyzed by the phospholipases A2 (PLA2) have been shown to induce monocyte chemotaxis either directly or indirectly. Some investigators have implicated a cytosolic calcium-independent PLA2 (iPLA2) in the production of these products during apoptosis. …
Novel Cancer Therapeutics, The Generation Of Ros, And Cell Survival, Clint Mitchell
Novel Cancer Therapeutics, The Generation Of Ros, And Cell Survival, Clint Mitchell
Theses and Dissertations
The impact of Ad.mda-7 on the survival of renal cell carcinoma lines (RCC), primary renal epithelial cells, glioblastoma multiforme lines (GBM), and primary rodent astrocytes is unknown. The present studies examine whether the GST fusion protein, GST-MDA-7, and the adenovirus, Ad.mda-7, altered the growth and survival of the A498 and UOK121N RCC lines or radiosensitized GBM, respectively. Due to previous findings that the RCC lines, but not primary renal epithelial cells, were resistant to type 5 adenoviral infection, we used purified GST-MDA-7 protein to show that GST-MDA-7, but not GST, caused a dose-dependent reduction in A498 and UOK121N proliferation but …
Identification Of The Rna Cis-Elements That Interact With Srp30a To Regulate The Alternative Splicing Of Caspase 9 Pre-Mrna, Prabhat Mukerjee
Identification Of The Rna Cis-Elements That Interact With Srp30a To Regulate The Alternative Splicing Of Caspase 9 Pre-Mrna, Prabhat Mukerjee
Theses and Dissertations
Studies have shown that the alternative splicing of caspase 9 and the phospho-status of SR proteins, a conserved family of splicing factors, are regulated by chemotherapy and de novo ceramide via the action of protein phosphatase-1 (PP1). Two RNA splice variants are derived from the caspase 9 gene, pro-apoptotic caspase 9a and anti-apoptotic caspase 9b, via alternative splicing by either the inclusion or exclusion of an exon 3, 4, 5, and 6 cassette. In this study, the link between SR proteins and the alternative splicing of caspase 9 was established. Sequence analysis of the exon 3, 4, 5, and 6 …
Type-5 Phosphodiesterase Inhibition In The Prevention Of Doxorubicin Cardiomyopathy, Patrick William Fisher
Type-5 Phosphodiesterase Inhibition In The Prevention Of Doxorubicin Cardiomyopathy, Patrick William Fisher
Theses and Dissertations
Prior studies have demonstrated the effect of diazoxide in protecting against apoptosis via mitochondrial KATP channel opening in vitro. The current investigations are designed to determine if sildenafil, a phosphodiesterase-5 inhibitor and known mitochondrial KATP channel opener, would protect against chronic doxorubicin cardiomyopathy both in vivo and in vitro.Male ICR mice were randomized to 1 of 4 treatments: saline, sildenafil (0.7 mg/kg IP), doxorubicin (5 mg/kg IP), and sildenafil (0.7 mg/kg IP)+doxorubicin. Apoptosis was determined using the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling and in situ oligo ligation methods. Desmin distribution was determined via immunofluorescence. Bcl-2 was analyzed by …