Association between local atherosclerosis and renal cell carcinomas.

OBJECTIVE: Atherosclerosis induce changes in reactive oxygen species and oxidative stress by hypoxia leading to oxidative DNA damage and therefore it could be expected that the cancer risk in patients with atherosclerotic diseases is increased. MATERIALS AND METHODS: The present study therefore aimed to morphometrically compare atherosclerotic changes (e.g., intima-to-media ratio [IMR]) in renal cell cancer (n=514) and tumor-negative renal specimens (n=70). RESULTS: Renal cell cancer specimens, in contrast to tumor-negative renal specimens, had more advanced atherosclerotic lesions, which moreover in immediately peritumorous (near-field) arteries were more strongly developed than in somewhat more distant (far-field) arteries. IMR >1 was significantly associated with renal cell carcinoma and the odds ratio of having renal cell cancer was significantly higher for patients with an IMR >1. CONCLUSION: Local atherosclerosis was more pronounced in tumor-positive than in tumor-negative renal specimens with significant association between IMR > 1 and renal cancer. This finding encourages the hypothesis of atherosclerosis causing oxidative stress as a potential risk factor for the development of renal cell cancer.

Preserved coupling of oxidative phosphorylation but decreased mitochondrial respiratory capacity in IL-1beta-treated human peritoneal mesothelial cells.

The peritoneal mesothelium acts as a regulator of serosal responses to injury, infection, and neoplastic diseases. After inflammation of the serosal surfaces, proinflammatory cytokines induce an "activated" mesothelial cell phenotype, the mitochondrial aspect of which has not previously been studied. After incubation of cultured human peritoneal mesothelial cells with interleukin (IL)-1beta for 48 h, respiratory activity of suspended cells was analyzed by high-resolution respirometry. Citrate synthase (CS) and lactate dehydrogenase (LDH) activities were determined by spectrophotometry. Treatment with IL-1beta resulted in a significant decline of respiratory capacity (p < 0.05). Respiratory control ratios (i.e., uncoupled respiration at optimum carbonyl cyanide p-trifluoromethoxyphenylhydrazone concentration divided by oligomycin inhibited respiration measured in unpermeabilized cells) remained as high as 11, indicating well-coupled mitochondria and functional integrity of the inner mitochondrial membrane. Whereas respiratory capacities of the cells declined in proportion with decreased CS activity (p < 0.05), LDH activity increased (p < 0.05). Taken together, these results indicate that IL-1beta exposure of peritoneal mesothelial cells does not lead to irreversible defects or inhibition of specific components of the respiratory chain, but is associated with a decrease of mitochondrial content of the cells that is correlated with an increase in LDH (and thus glycolytic) capacity.

Perforated Meckel's diverticulum presenting as a gastrointestinal stromal tumor: a case report.

Tumors and perforation of Meckel's diverticulum are rare manifestations. A gastrointestinal stromal tumor in a Meckel's diverticulum causing perforation and subsequent peritonitis in a 75-year-old man is presented. The literature on tumors in Meckel's diverticulum is extensively reviewed and discussed.

Disruption of the integrity of human peritoneal mesothelium by interleukin-1beta and tumor necrosis factor-alpha.

Inflammatory and neoplastic disease processes of the abdominal cavity are frequently associated with disruption of the integrity of the peritoneal mesothelium. In the present study, we analyzed the effects of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) on the morphology and expression of adhesion molecules of human peritoneal mesothelial cells (HPMC). Treatment of HPMC with IL-1beta and TNF-alpha resulted in a time- and dose-dependent alteration of the normal cobblestone morphology of the mesothelium with loss of polarization, cellular retraction and exposure of the submesothelial matrix. The effect was already observable after 6 h of treatment and was most pronounced at a dose of 10 ng/ml of IL-1beta or TNF-alpha. These morphological alterations were associated with a significant rearrangement of the expression of mesothelial adhesion molecules as detected by flow cytometry. IL-1beta and TNF-alpha both led to a loss of the expression of the hemidesmosomal integrin subunits alpha6 ( P<0.01 and P<0.001) and beta4 ( P<0.01) and an increased expression of the integrin subunit alpha5 ( P<0.001 and P<0.01). IL-1beta furthermore upregulated the expression of the integrin subunits alpha1, alpha2 and the adhesion molecule CD44 while the latter was downregulated by TNF-alpha. Our data indicate that IL-1beta and TNF-alpha may significantly affect disease processes of the abdominal cavity by their potential to disrupt the mesothelial basal cell-matrix adhesion and, thus, the integrity of the peritoneal mesothelial cell lining.