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Articles 1 - 15 of 15
Full-Text Articles in Pathology
Mitochondrial Dynamics Regulation Of The Lung Epithelial Response To Complex Allergen, Sierra White
Mitochondrial Dynamics Regulation Of The Lung Epithelial Response To Complex Allergen, Sierra White
Graduate College Dissertations and Theses
Asthma is a chronic inflammatory disease of the lungs that affects roughly 25 million Americans, costing the United States upwards of $80 billion annually in management and economic loss. The airway epithelium, which serves as the first line of defense against insults in the lung, are now appreciated as key contributors to initiation of this disease. A key regulator of the epithelial response to allergens and other inhaled irritants that can induce an allergic asthmatic response is the mitochondria. During an allergic response, the airway epithelial energy requirement changes, and mitochondrial function is altered, enhancing production of reactive oxygen species, …
Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam
Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam
Electronic Thesis and Dissertation Repository
High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …
Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog
Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog
Wayne State University Dissertations
The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …
Redox Regulation Of Src Kinase: Implications For Innate Il-33 Signaling In Allergen Responses, Christopher Michael Dustin
Redox Regulation Of Src Kinase: Implications For Innate Il-33 Signaling In Allergen Responses, Christopher Michael Dustin
Graduate College Dissertations and Theses
The proto-oncogene tyrosine kinase Src is a ubiquitously expressed non-receptor tyrosine kinase involved in critical cellular functions including wound healing, migration, survival, and proliferation. Accordingly, aberrant Src signaling is also significantly involved in many diseases. Src is most well known as an oncogenic protein, however, there are emerging roles for Src signaling in various tissues involved in inflammatory diseases. One such tissue is the respiratory epithelium, which comprises the first line of defense against inhaled microbial, particulate, and chemical insults and is a critical nexus of innate immune signaling. Recent work has detailed the involvement of Src in many innate …
Exosomes And Their Role In Asbestos Exposure And Mesothelioma, Phillip Blake Munson
Exosomes And Their Role In Asbestos Exposure And Mesothelioma, Phillip Blake Munson
Graduate College Dissertations and Theses
Malignant mesothelioma (MM) is a locally invasive and highly aggressive cancer arising on the mesothelial surface of organ cavities (mainly pleural) as a direct result of asbestos exposure. The latency period of MM is long (20-50yrs) after initial asbestos exposure, and the prognostic outcomes are dismal with median life expectancy of 6-12 months post-diagnosis. There are no useful biomarkers for early MM diagnosis, no successful therapeutic interventions. These vast voids of knowledge led to our hypotheses that secreted vesicles, termed exosomes, play an important role in MM development and tumorigenic properties. Exosomes are nano-sized particles secreted from all cell types …
Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall
Electronic Theses and Dissertations
Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …
The Role Of Elevated Hyaluronan-Mediated Motility Receptor (Rhamm/Hmmr) In Ovarian Cancer, Stephanie T. Buttermore
The Role Of Elevated Hyaluronan-Mediated Motility Receptor (Rhamm/Hmmr) In Ovarian Cancer, Stephanie T. Buttermore
USF Tampa Graduate Theses and Dissertations
Ovarian cancer (OC) has the highest mortality among gynecological cancers. The high mortality is associated with the lack of an accurate screening tool to detect disease in early stage. As a result the majority of OCs are diagnosed in late stage. Further, the molecular events responsible for malignant transformation in the ovary remain poorly understood. Consequently, delineating key molecular players driving OC could help elucidate potential diagnostic, prognostic and therapeutic targets.
Receptor for hyaluronan-mediated motility (RHAMM) belongs to a group of hyaladherins, which share a common ability to bind to hyaluronan (HA). Intracellularly, RHAMM is involved in microtubule spindle assembly …
Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr
Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr
Theses & Dissertations
Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …
The Role Of Src Kinase Activation In Lung Epithelial Alterations In Response To The A,B-Unsaturated Aldehyde Acrolein, Robert Bauer
The Role Of Src Kinase Activation In Lung Epithelial Alterations In Response To The A,B-Unsaturated Aldehyde Acrolein, Robert Bauer
Graduate College Dissertations and Theses
Cigarette smoke (CS) exposure is the leading cause of preventable death in the United States contributing to over 480,000 deaths a year with over 300 billion dollars in CS related costs spent per year. While the dangers of CS exposure have been studied and characterized for decades being largely attributed to reactive oxygen species and oxidative stress, increasing evidence suggests that reactive aldehydes in CS, specifically the α,β-unsaturated aldehyde acrolein, are responsible for many of the negative pathologies associated CS exposure. Previous work has shown that acrolein can bind directly to a number of cellular proteins containing redox sensitive cysteine …
Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart
Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart
Theses and Dissertations--Clinical and Translational Science
Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …
Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully
Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully
Graduate College Dissertations and Theses
Nuclear Factor kappaB (NF-êB) is a transcription factor whose activation is increased in settings of allergic asthma. At least two parallel NF-êB pathways exist: the classical pathway, which plays a role in inflammation and cell survival, and the alternative pathway, which regulates lymphoid cell development and organogenesis. The classical NF-êB pathway regulates inflammatory responses derived from lung epithelial cells; however, the role of the alternative pathway in lung epithelial cells remains unclear. We demonstrate that both classical and alternative NF-êB are activated in lung epithelial cells in response to multiple pro-inflammatory agonists, and siRNA-mediated knockdown of alternative NF-êB proteins largely …
Interactions Of Nitric Oxide And Superoxide Pathways In Hyperglycemic Endothelial Cells, Steven Clay Rogers
Interactions Of Nitric Oxide And Superoxide Pathways In Hyperglycemic Endothelial Cells, Steven Clay Rogers
Graduate Theses and Dissertations
Cardiovascular complications arising from diabetic hyperglycemia represents one of the leading causes of death and greatest public health challenges of modern societies. Despite state-of-the-art glucose control, diabetic patients remain at a markedly increased risk of cardiovascular disease. The loss of endothelial function (the development of diabetic endothelial dysfunction) has been implicated in the development of numerous diabetic cardiovascular diseases. The endothelial cell produces many vasoactive substances, hormones and cytoprotective biological factors. Endothelial cells are also involved in and affected by the initiation of inflammatory responses through the release and interaction of cytokines and other immune system molecules. Therefore, regulation of …
Identifying Sm22 As A Key Player In Arterial Diseases, Jianbin Shen
Identifying Sm22 As A Key Player In Arterial Diseases, Jianbin Shen
Wayne State University Dissertations
Background : Expression of vascular smooth muscle cell (VSMC) cytoskeleton markers including SM22 is down-regulated in arterial diseases including atherosclerosis where inflammation and osteochondrogenesis are present. However, the role of this downregulation in arterial pathogenesis is unknown. Hypothesis : Downregulation of SM22 may actively contribute to arterial pathogenesis. Methods : Five Sm22 knockout (Sm22-/-) mice and their wild type littermates were subjected to carotid artery denudation, an artery injury model. Analyses were conducted on carotid arteries 2 weeks after injury. Primary VSMCs were isolated from mouse aortas and investigated individually at passage 2 to 4. Sm22 knockdown was …
Pressure-Induced Intracellular Signaling In Isolated Arteries, Victor A. Miriel
Pressure-Induced Intracellular Signaling In Isolated Arteries, Victor A. Miriel
Theses and Dissertations in Biomedical Sciences
The ability of cells to respond to mechanical stimuli has been studied through a variety of techniques in numerous cell types. The cells of the vascular wall have adapted to specific mechanical stresses through the activation of intracellular signaling pathways which result in cell-specific responses such as hypertrophy, hyperplasia, proliferation, and migration. Vascular smooth muscle of the arteries have been shown to be sensitive to mechanical stimuli such as stretch, and pressure.
This study attempts to add to the current knowledge of mechanotransduction by utilizing the isolated artery preparation. This preparation allows for the study of vascular smooth muscle signal …
Oral Cancer Screening, Damon Omar Watson
Oral Cancer Screening, Damon Omar Watson
Honors Theses
Cancers of the oral cavity and pharynx have increased throughout the decades. Since oral cancer represents a small percentage of the total cancers in the United States, it is often overlooked. Though this is the case, the results of this cancer can be devastating. To address this issue, an Oral Cancer Screening was organized on August 14, 1996 at the West Michigan Cancer Center in Kalamazoo. This was a joint collaboration between the author, the West Michigan Cancer Center, and the Kalamazoo Valley Dental Society. This event allowed research to take place concerning the data obtained. Confidential results and information …