Renal cell carcinoma (RCC), the third most prevalent urological cancer, claims more than 100,000 lives/year worldwide. The clear cell variant (ccRCC) is the most common and aggressive subtype of this disease. While commonly asymptomatic, more than 30% of ccRCC are diagnosed when already metastatic, resulting in a 95% mortality rate. Notably, nearly one-third of organ-confined cancers treated by nephrectomy develop metastasis during follow-up care. At present, diagnostic and prognostic biomarkers to screen, diagnose, and monitor renal cancers are clearly needed. The gene encoding the cell surface molecule HAVCR1/KIM-1 is a suggested susceptibility gene for ccRCC and ectodomain shedding of this molecule may be a predictive biomarker of tumor progression. Microarray analysis of 769-P ccRCC-derived cells where HAVCR/KIM-1 levels have been upregulated or silenced revealed relevant HAVCR/KIM-1–related targets, some of which were further analyzed in a cohort of 98 ccRCC patients with 100 month follow-up. We found that HAVCR/KIM-1 activates the IL-6/STAT-3/HIF-1A axis in ccRCC-derived cell lines, which depends on HAVCR/KIM-1 shedding. Moreover, we found that pSTAT-3 S727 levels represented an independent prognostic factor for ccRCC patients. Our results suggest that HAVCR/KIM-1 upregulation in tumors might represent a novel mechanism to activate tumor growth and angiogenesis and that pSTAT-3 S727 is an independent prognostic factor for ccRCC. Cancer Res; 74(5); 1416–28. ©2014 AACR.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A‐I, named ApoA‐Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS‐unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA‐Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS‐unrelated proteinuria tested positive for ApoA‐Ib, and was not detected in familial patients. Urinary ApoA‐Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.

Successful eradication of Helicobacter pylori infection clearly modifies the natural history of peptic ulcer disease and prevents further recurrences of duodenal and gastric ulcers. However, there are few prospective studies about actual rates of rebleeding after H. pylori eradication, a highly relevant aspect of management as re-infection, relapse of ulcer disease for other reasons (i.e. antiinflammatory agents) or idiopathic ulcers unrelated to H. pylori may develop and cause further bleeding episodes. To determine the incidence of bleeding episodes after eradication of H. pylori infection in patients who had bled from an H. pylori -positive peptic ulcer. H. pylori -positive patients who bled from a gastric or duodenal ulcer were treated with appropriate triple and/or quadruple therapy. H. pylori eradication was confirmed by urea breath test 4 weeks after treatment. Patients received no further treatment but were followed clinically and additional urea breath tests were performed every 6 months. Endoscopy with antral and corpus biopsies and urea breath test were repeated as soon as patients manifested any dyspeptic symptoms that might signal recurrence. A total of 103 patients with bleeding duodenal ulcer were included in the study; H. pylori was successfully eradicated in 93 of these patients, who were followed for a median interval of 27 months. The yearly re-infection rate was calculated to be 0.6%. There were no instances of rebleeding in any patients during the follow-up period. Even after prolonged follow-up, successful H. pylori eradication prevents rebleeding. Eur J Gastroenterol Hepatol 12:733-737

Background. The use of cyclosporine A (CsA) as a potent immunosuppressant has been limited by its severe nephrotoxic effects. The mechanisms involved are haemodynamic but also related to direct toxic effects of CsA on proximal tubule epithelial cells. We focused on defining a proteomic profile in CsA-treated proximal tubule cells to distinguish the direct impact of CsA on these cells from overlapping haemodynamically mediated phenomena that occur in an in vivo system.