Background: The excision repair cross complementing (ERCC1) gene product plays a vital role in the nucleotide excision repair (NER) and DNA interstrand crosslink repair pathways, which protect the genome from mutations and chromosomal aberrations, respectively. Genetic deletion of Ercc1 in the mouse causes dramatically accelerated aging. We examined the effect of Ercc1 deletion in the development of prostate cancer in a prostate recapitulation model as Ercc1 deficient mice die within four weeks of birth.
View Article and Find Full Text PDFFibrin glue (FG) is used in a variety of clinical applications and in the laboratory for localized and sustained release of factors potentially important for tissue engineering. However, the effect of different fibrinogen concentrations on FG scaffold delivery of bioactive adeno-associated viruses (AAVs) has not been established. This study was performed to test the hypothesis that FG concentration alters AAV release profiles, which affect AAV bioavailability.
View Article and Find Full Text PDFBackground: Prostate specific membrane antigen (PSMA) is a unique folate hydrolase that is significantly upregulated in prostate cancer. In a mouse model, PSMA is able to facilitate prostate carcinogenesis, however, little is known about the mechanism by which this occurs. As PSMA is able to hydrolyze polyglutamated folates, and cancer cells proliferate directly in response to available folate, we examined if expression of human PSMA in PC-3 cells confers a proliferative advantage in a microenvironment with physiologically relevant folate levels.
View Article and Find Full Text PDFIncreased expression of PSMA, a differentiation antigen with folate hydrolase activity, is an independent marker of prostate cancer progression. Mice expressing moderate levels of human PSMA in their prostate develop PIN-like lesions by 9 months. The aim of this study was to determine whether PSMA is involved in prostate carcinogenesis and progression and, if so, the possible mechanism by which PSMA may exert its effects.
View Article and Find Full Text PDFBackground: Prostate specific membrane antigen (PSMA) expression is correlated with stage and grade of prostate cancer suggesting that it confers a growth advantage. We studied if PSMA folate hydrolase activity provides cells a growth advantage in a low folate (LF) micro-environment by hydrolyzing extracellular poly-gamma-glutamated folate to a form that cells can import.
Methods: Proliferation of LNCaP and DU-145 cells was assessed in media containing low (LF), physiological (PF), or high (HF) folate with or without penta-gamma-glutamated folate and a PSMA specific folate hydrolase inhibitor, 2-(phosphonomethyl)-pentanedioic acid (2-PMPA).
Purpose: There is a lack of clinical evidence supporting the use of lavage in patients with peritonitis. It is known that fluids such as normal saline cause temporary damage to the peritoneum and that increased production of proinflammatory mediators is associated with a poor outcome. This study used an experimental model to evaluate the effect of lavage on the peritoneal mesothelium and the ability of peritoneal mesothelial cells to produce a battery of proinflammatory mediators (TNFalpha, IL-1beta, GROalpha, and ICAM-I.
View Article and Find Full Text PDFSurg Infect (Larchmt)
March 2005
Background: Many of the effector mechanisms that characterize peritonitis are generated by neutrophils and macrophages. However, it is now appreciated that peritoneal mesothelial cells can also produce mediators of inflammation when grown in culture. This study tested the hypothesis that peritoneal mesothelial cells produce inflammation-related cytokines in a murine model of peritonitis.
View Article and Find Full Text PDFBackground: Peritonitis involves cascading interactions between cytokines that initiate robust signalling processes via the interferon-g and nuclear factor kappa B pathways. The present study evaluates the interplay between various putative inducers of peritonitis and a battery of inflammation-related cytokines.
Methods: Cultures of peritoneal mesothelial cells were isolated from omenta harvested from male Wistar rats.
Introduction: The production of nitric oxide is an important peritoneal defense mechanism. We have evaluated the effect of various putative stimulants on nitric oxide production by peritoneal mesothelial cells.
Methods: Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneally).
Introduction: Patients with peritonitis often exhibit systemic manifestations of sepsis, especially in the lungs. The aim of the present study was to evaluate the local and systemic effects of the neutrophil response to peritonitis in a rat model.
Methods: Fifty Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneal).
Obtaining normal cells has become increasingly important for use in comparative genetic analytical techniques to examine alterations in gene expression during transformation and progression into malignancy. Normal mesothelial cells are not currently available in cell banks and are essential for comparison of genetic expression analysis in current mouse mesothelioma models. The purpose of this investigation was to extract normal mouse peritoneal mesothelial cells using minimal culture techniques to obtain sufficient cells for gene expression analysis.
View Article and Find Full Text PDFDendritic cells (DC) are the most effective or 'professional' of the antigen-presenting cells (APC) that initiate primary immune responses. They are located at surveillance sites where they capture and process antigens. They then initiate and regulate T- and B-cell responses by expressing lymphocyte costimulatory molecules, migrating to lymphoid organs and secreting biologically active molecules.
View Article and Find Full Text PDFPurpose: Peritonitis continues to be a major source of mortality and morbidity in patients undergoing abdominal surgery. The aim of this study was to develop a nonfatal model of bacterial peritonitis in mice so that we could study aspects of the pathobiology and treatment of peritonitis in an in vivo model.
Methods: Mice were inoculated via a midline laparotomy with 0.