Characterization of a Human Cell Line Stably Over-Expressing the Candidate Oncogene, Dual Specificity Phosphatase 12

Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12). While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1) which is implicated in metastasis.Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted

Pure seminoma: A review and update

Pure seminoma is a rare pathology of the young adult, often discovered in the early stages. Its prognosis is generally excellent and many therapeutic options are available, especially in stage I tumors. High cure rates can be achieved in several ways: standard treatment with radiotherapy is challenged by surveillance and chemotherapy. Toxicity issues and the patients' preferences should be considered when management decisions are made. This paper describes firstly the management of primary seminoma and its nodal involvement and, secondly, the various therapeutic options according to stage

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

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Not AvailableASSESSMENT OF EROSION RISKS, EEPECIALLY IN THE DEVELOPING COUNTRIES IS A CHALLENGING TASK MAINLY DUE TO NON- AVAILABILITY OF INSUFFICIENCY OF RELEVANT DATA. IN THIS PAPER THE SOIL EROSION RISKS HAVE BEEN ESTIMATED BY INTEGRATING THE SPATIAL DATA ON POTENTIAL EROSION RATES AND SOIL LOSS TOLERANCE LIMITS FOR CONSERVATION PLANNING AT STATE LEVEL IN INDIA. THE EROSION RISK CLASSES HAVE BEEN PRIORITIZED BASED UPON THE DIFFERENT BETWEEN THE PREVAILING EROSION RATES AND THE PERMISSIBLE EROSION LIMITS . THE ANALYSIS REVEALED THAT ABOUT 50% OF THE TOTAL GEOGRAPHICAL AREA (TGA) OF INDIA , FALLING IN THE FIVE PRIORITY EROSION RISK CLASSES, REQUIRES DIFFERENT INTENSITY OF CONSERVATION MEASURES THOUGH ABOUT 91% AREA SUFFERS FROM POTENTIAL EROSION RATES VARYING FROM 40 t ha-1 yr-1. STATEWISE ANALYSIS INDICATED THAT ANDHRA PRADESH, MAHARAHTHRA AND RAJASTHAN SHARE ABOUT 75% OF THE TOTAL AREA UNDER PRIORITY CLASS 1(6.4 M ha) THOUGH THEY ACCOUNT FOR ONLY 19.4% OF THE TOTAL AREA (36.2 m ha) UNDER VERY SEVERE POTENTIAL EROSION RATE CATEGORY (>40 t ha-1 yr-1) . IT WAS OBSERVED THAT ABOUT 75% OF TOTAL GEOGRAPHICAL AREA (TGA) IN THE STATE OF BIHAR , GUJARAT , HARYANA , KERALA AND PUNJAB DOES NOT REQUIRE ANY SPECIFIC SOIL CONSERVATION MEASURE AS THE POTENTIAL EROSION RATES ARE WELL WITHIN THE TOLERANCE LIMITS. THE DEVELOPED METHODOLOGY CAN BE SUCCESSFULLY EMPLOYED FOR PRIORITIZATION OF EROSION RISK AREA AT WATERSHED , REGION OR COUNTRY LEVEL.Not Availabl