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THE EFFECTS OF ACIDIC TUMOR MICROENVIRONMENT ON LYMPHOMA CELL RESPONSES TO CHEMOTHERAPEUTICS
(East Carolina University, 2014)
Acidic tumor microenvironment exists in many types of cancer. Altered glycolytic metabolism of tumor cells and deficient blood supply in tissues are major causes for this phenomenon. Lymphoma cells may have different ...
Expression of microRNA in Alveolar Macrophages Deficient in PPARy
(East Carolina University, 2014)
The nuclear transcription factor Peroxisome proliferator-activated receptor gamma (PPARgamma) is a negative regulator of macrophage activation and inflammatory mediators. Alveolar macrophages of healthy individuals constitutively express PPARgamma Decreased activity and expression of PPARgamma are observed in the alveolar macrophages from patients suffering from inflammatory conditions such as pulmonary alveolar proteinosis (PAP) and sarcoidosis. These finding suggest that PPARf× activity may have an integral role in maintaining lung homeostasis. This study tested the hypothesis that microRNA expression would be dysregulated in murine alveolar macrophages deficient in PPARgamma. microRNA (miR) are small non-coding RNA molecules that post-transcriptionally regulate the expression of messenger RNA. Evaluation of microRNA in the murine model of PAP, the GM-CSF-KO mouse, demonstrates the elevation of miR-27a and miR-27b which target PPARgamma. The deficiency of PPARgamma and the lipid transporters ABCA1 and ABCG1 have been shown to contribute to the pathology of PAP. The microRNA miR-33-3p and miR-33-5p, which target these lipid transporters, were also elevated in GM-CSF-KO mice. Pulmonary granulomas comparable to those observed in pulmonary sarcoidosis are induced by instillation of multiwall carbon nanotubes (MWCNT) in C57Bl/6 mice. These animals have decreased PPARgamma activity and show elevated expression of miR-27a and miR-27b. It was also observed that the expression of the transporters ABCA1 and ABCG1 were decreased in MWCNT instilled mice. Expression of miR-33-3p and miR-33-5p was elevated in MWCNT instilled animals. The expression of microRNA that affects the activity of NF-£eB is also elevated in both murine models. We next investigated the use of PPARgamma agonist rosiglitazone on the expression of microRNA and messenger RNA. The use of rosiglitazone altered the expression of microRNA in both GM-CSF-KO and C57Bl/6+MWCNT mice. Rosiglitazone treatment altered the expression of the lipid transporter ABCA1and ABCG1 in C57Bl/6+MWCNT mice. The elevation of proinflammatory cytokines was also observed. Taken together, these observations support the hypothesis that PPARgamma activity effects the microRNA and gene expression in alveolar macrophages which is critical to overall lung homeostasis. Understanding the relationship between PPARgamma and microRNA in alveolar macrophage biology will provide insight into the regulation of the lung environment and possible therapeutic targets. ...
Developmental lead exposure and the exacerbation of Alzheimer's pathology: an immunological analysis
(East Carolina University, 2014)
Early neuroimmune dysfunction may play a driving role in the etiopathology of Alzheimer's disease (AD), stemming from the hypothesis that many late-stage adult diseases have an early-life basis. Here we explore whether ...
Interrelated role of Notch signaling and mTORC pathways in prostate cancer cell survival and growth
(East Carolina University, 2014)
Prostate cancer is currently the second highest leading cause of
cancer death in men. Notch is a transmembrane receptor protein that
is part of a signaling pathway necessary in the normal development of
the prostate. ...
Intratracheal instillation of silver nanoparticles exacerbates cardiac ischemia/reperfusion injury in male sprague-dawley rats
(East Carolina University, 2014)
The uses of engineered nanomaterials have expanded in biomedical technology and consumer manufacturing. Exposure to particulate matter has been demonstrated to negatively influence cardiovascular health and expand myocardial ...
Fesselin, an intrinsically disordered smooth muscle protein, organizes and stabilizes actin-myosin and myosin
(East Carolina University, 2014)
Fesselin is an intrinsically disordered protein that is known to bind a large variety of cytoskeletal proteins. The proteins fesselin is known to bind include: actin (Leinweber et al. 1999), [alpha]-actinin (Pham et al. ...
TMEFF2 is an epigenetic modulator that promotes androgen independent growth in castration-resistant prostate cancer cells
(East Carolina University, 2014)
While the ability to detect PCa has improved significantly due to PSA screenings, the survival rate for men diagnosed with PCa has remained stagnant, and the disease remains the second leading cause of cancer related deaths ...
Use of monoamine oxidase and redox enzymes in atrial tissue as novel predictors of postoperative atrial fibrillation
(East Carolina University, 2014)
Postoperative atrial fibrillation (POAF) occurs in approximately 30% of cardiac surgery patients. The complication occurs despite advances in surgical procedures. It is associated with increased mortality, morbidity, and ...