These responses are modulated by signaling mediators and microRNAs that amplify or inhibit TGF-beta and Wnt signaling. Gain-of-function and loss-of-function abnormalities of these mediators may account for the characteristic activated phenotype of SSc fibroblasts. The nuclear orphan receptor PPAR-gamma plays a particularly

important role in limiting the duration and intensity of fibroblast activation and differentiation, and impaired PPAR-gamma expression or function in SSc may underlie the uncontrolled progression of fibrosis.\n\nIdentifying the perturbations in signaling pathways, mediators and differentiation programs that are responsible for SSc tissue damage allows their selective targeting. This in turn FRAX597 inhibitor Bucladesine opens the door for therapies utilizing novel compounds, or drug repurposing by innovative uses of already-approved drugs. In view of the heterogeneous clinical presentation and unpredictable course of SSc, as well as its

complex pathogenesis. only robust clinical trials incorporating the judicious application of biomarkers will be able to clarify the clinical utility of these innovative approaches. (C) 2010 Elsevier B.V. All rights reserved.”
“It is well known that early-onset breast cancer may be due to an inherited predisposition. When evaluating women diagnosed with breast cancer under age 30, two important syndromes are typically considered: Hereditary

Breast and Ovarian Cancer Syndrome and Li-Fraumeni syndrome. Many women are offered genetic testing for mutations in the BRCA1 and BRCA2 genes; however, few are offered genetic testing for mutations in the TP53 gene. There is a concern that overly restrictive testing of TP53 may fail to recognize families with Li-Fraumeni syndrome. We reviewed the genetic test results and family histories of all women with early-onset see more breast cancer who had genetic testing of the TP53 gene at the Toronto Hospital for Sick Children. Of the 28 women tested, six (33.3 %) had a mutation in the TP53 gene; a mutation was found in 7.7 % of women who did not meet current criteria for Li-Fraumeni syndrome. By reviewing similar data published between 2000 and 2011, we estimate that 5-8 % of women diagnosed with early-onset breast cancer, and who have a negative family history, may have a mutation in the TP53 gene. Given the potential benefits versus harms of this testing, we discuss the option of simultaneous testing of all three genes (BRCA1, BRCA2, and TP53) for women diagnosed with breast cancer before age 30.”
“Objectives: Geographic information systems (GIS) tools can help expand our understanding of disparities in health outcomes within a community.