Citations

AbstractThe accuracy of theFramingham risk score (FRS) in identifying patients with nonalcoholic fatty liver disease (NAFLD) at higher 10‐year coronary heart disease (CHD) risk remains unknown. We aimed at evaluating both the baseline probability ofCHDas predicted by theFRSand the actual long‐term occurrence ofCHDinNAFLDpatients. This was a longitudinal study of a community‐based cohort. A total of 309NAFLDpatients were followed up for 11.5 ± 4.1 years (total 3554 person‐years). The overall calculated 10‐yearCHDrisk was significantly higher in theNAFLDcohort than the absoluteCHDrisk predicted by theFRSfor persons of the same age and gender (10.9 ± 9.3% vs. 9.9 ± 5.9%, respectively,P < 0.0001), and higher in men than women (12.6 ± 10.3% vs. 9.6 ± 8.1%, respectively,P = 0.006). New onsetCHDoccurred in 34 patients (11% vs. 10.9% predicted at baseline,P = NS), whereas 279 (89%) patients did not developCHD. Using multivariable analysis, theFRSwas the only variable significantly associated with new onsetCHD(OR = 1.13, 95%CI = 1.05–1.21;P = 0.001). AFRScut‐point of 11 in women, and 6 in men had a sensitivity of 80% and 74%, respectively, and a negative predictive value of 97% and 93% respectively.NAFLDpatients have a higher 10‐yearCHDrisk than the general population of the same age and gender. TheFRSaccurately predicts the higher 10‐yearCHDrisk inNAFLDpatients, and helps identify those patients expected to derive the most benefit from early intervention to preventCHDevents.

Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function. The lead compound, termed MJC13, inhibits AR function by preventing hormone-dependent dissociation of the Hsp90-FKBP52-AR complex, which results in less hormone-bound receptor in the nucleus. Assays in early and late stage human prostate cancer cells demonstrated that MJC13 inhibits AR-dependent gene expression and androgen-stimulated prostate cancer cell proliferation.

The fourth Leon Thal Symposium (LTS2010) was convened in Toulouse, France, on November 3, 2010. This symposium reviewed design parameters that are necessary to develop comprehensive national databases on healthy aging. Such datasets offer the potential to serve as the foundation for a systems‐approach to solve the dual public health problems of: (1) early detection of people who are at elevated risk for Alzheimer's disease, and (2) the development of interventions to delay onset of, or prevent, late‐life dementia. The symposium considered three interrelated components of a National Database for Longitudinal Studies on Healthy Aging as follows: (a) a registry of healthy aging adults; (b) refined computer‐based assessments for data gathering, including assessments of behavioral/memory changes associated with aging that are appropriate for broad use in nonexpert settings; and (c) high performance computing/supercomputer‐based approaches for health data modeling and mining.

Abstract Purpose: To describe the demographic and clinical features and outcomes for children and adolescents with primary CNS lymphoma (PCNSL). Experimental Design: A retrospective series of children and adolescents with PCNSL was assembled from 10 cancer centers in 3 countries. Results: Twenty-nine patients with a median age of 14 years were identified. Sixteen (55%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or greater. Frontline therapy consisted of chemotherapy only in 20 patients (69%), while 9 (31%) had chemotherapy plus cranial radiotherapy. Most patients received methotrexate (MTX)-based regimens. Overall response rate was 86% (complete remission 69%, partial remission 17%). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 61% and 86%, respectively; the 3-year OS was 82%. Univariate analyses were conducted for age (≤14 vs. &gt;14 years), PS (0 or 1 vs. &gt;1), deep brain lesions, MTX dose, primary treatment with chemotherapy alone, intrathecal chemotherapy, and high-dose therapy. Primary treatment with chemotherapy alone was associated with better overall response rates with an odds ratio (OR) of 0.125 (P = 0.02). There was a marginally significant relationship between higher doses of MTX and response (OR = 1.5, P = 0.06). ECOG-PS of 0 to 1 was the only factor associated with better outcome with hazard ratios of 0.136 (P = 0.017) and 0.073 (P = 0.033) for PFS and OS, respectively. Conclusion: This is the largest series collected of pediatric PCNSL. The outcome of children and adolescents seems to be better than in adults. PS of 0 to 1 is associated with better survival. Clin Cancer Res; 17(2); 346–52. ©2011 AACR.