Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients

Metalloproteinase 7 (MMP-7) plays an important role in tumor growth, invasion and dissemination, and is secreted to the media. Because of the close implication of MMP-7 in cancer biology, we sought to define the prognostic significance of serum levels of MMP-7 in metastatic colorectal cancer (CRC) and explore its possible impact in the daily clinical practice. MMP-7 expression was determined by enzyme-linked immunoabsorbent assay. We assessed serum MMP-7 levels in 87 healthy controls, 96 patients with nonmetastatic CRC and 120 patients with advanced CRC. Clinical information was gathered from patient files. Cox proportional hazards model was used to assess survival. MMP-7 and the variables associated with prognosis were entered and a backward elimination method was employed to adjust the model. Inclusion criteria was p /= 0.10. Advanced CRC patients have a significant higher mean serum MMP-7 levels (13.4 ng/ml) than those in nonmetastatic CRC (5.5 ng/ml; p < 0.001) and healthy controls (4.2 ng/ml; p < 0.001). In metastatic patients, after adjusting for other prognostic variables, MMP-7 (entered as a continuous variable) is associated with decreased survival (HR 1.016, IC 95% 1.002-1.031). Serum MMP-7 levels are significantly elevated in patients with advanced CRC. In conclusion, MMP-7 is an independent prognostic factor for survival in advanced CRC. In our sample, the risk of death associated to MMP-7 increase is much higher than the risk of death associated to lactate dehydrogenase elevation.     

Island cartilage tympanoplasty in revision cases: anatomic and functional results

We report our experience with island cartilage tympanoplasty in revision cases and assess the anatomical and functional outcomes. We conducted a retrospective chart review at a tertiary referral center for patients who underwent revision tympanoplasty using cartilage with the island technique without mastoidectomy between January 2002 and December 2008. 60 cases were included in the study and successful closure without reperforation was obtained in 52 of 60 patients (87%). Three failed cases underwent a subsequent procedure endaurally with a positive result (92% accumulated success rate). Average postoperative pure-tone audiometry air-bone gap was 13?±?7?dB compared with 21?±?11?dB preoperatively (p?=?0.004). An overall postoperative air-bone gap of 20?dB or less was achieved in 46 of the 60 patients (76.7%). Tympanoplasty with island cartilage grafting is a reliable procedure for revision cases with excellent anatomic results as well as significant improvement of hearing.     

High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

Background  

Hyperhomocysteinemia (HHcy) causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy) metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD) in rats were investigated.     

Gastric Leak After Sleeve Gastrectomy: Analysis of Its Management

Background  

Bariatric surgery is increasingly being performed and sleeve gastrectomy (SG) has proved to be effective and safe. Among its complications, leaks are the most serious and life threatening.     

Deregulation of FGFR1 and CDK6 oncogenic pathways in acute lymphoblastic leukaemia harbouring epigenetic modifications of the MIR9 family

The role of epigenetic mechanisms in the regulation of microRNAs (miRNAs) with a tumour‐suppressor function in human neoplasms has recently been established. Several miRNAs have been found to be inappropriately regulated by DNA methylation in patients with acute lymphoblastic leukaemia (ALL). We analysed the methylation status of the three members of the MIR9 family (MIR9‐1, MIR9‐2 and MIR9‐3) in a uniformly treated cohort of 200 newly diagnosed ALLs. MIR9 was methylated in 54% of the patients and was associated with downregulation of MIR9 (P < 0·01). Hypermethylation of MIR9 was an independent prognostic factor for disease‐free survival, overall survival and event‐free survival in a multivariate analysis (P < 0·01). Epigenetic downregulation of MIR9 induced upregulation of its targets, FGFR1 and CDK6, while treatment of ALL cells with FGFR1 (PD‐173074) and CDK6 (PD‐0332991) inhibitors induced a decrease in cell proliferation and an increase in apoptosis of ALL cells. Our results indicate that the MIR9 family is involved in the pathogenesis and clinical behaviour of ALL and provide the basis for new therapeutic strategies in the treatment of ALL, targeting the epigenetic regulation of miRNAs and/or the FGFR1 or CDK6‐RB pathway directly.     

Renal effects of exposure to natural and depleted uranium: a review of the epidemiologic and experimental data

Elevated levels of naturally occurring uranium in groundwater have been found in small geographic areas throughout the world. Relevant research was reviewed pertaining to natural and depleted uranium (DU) exposure and nephrotoxicity, including epidemiologic community-based and occupational studies, studies of Gulf War veterans exposed to DU, and experimental studies in animals. Occupational cohort studies do not provide evidence of an increased risk of kidney-related mortality among uranium-exposed workers. However, occupational and community-based studies of populations chronically exposed to elevated drinking-water concentrations of uranium provide some evidence of adverse renal effects, as assessed by biomarkers of proximal tubule damage such as urinary levels of glucose, calcium, and various low-molecular-weight proteins. Indications of proximal tubule effects, as evidenced by increased urinary β(2)-microglobulin and retinol binding protein levels, were also seen in the most recent follow-up surveillance study of Gulf War veterans exposed to DU. The reported β(2)-microglobulin levels in these studies were generally considered to be within normal limits, but the long-term implications of the observed variation in these levels are not established. The kidney was observed to be a target of uranium toxicity following oral and implantation exposure routes in several animal species. The interpretation and importance of the observed changes in biomarkers of proximal tubule function are important questions that indicate the need for additional clinical, epidemiological, and experimental research.