@article {1625, title = {Anti-leukemic activity of dasatinib in both p53(wild-type) and p53(mutated) B malignant cells.}, journal = {Invest New Drugs}, volume = {30}, year = {2012}, month = {2012 Feb}, pages = {417-22}, abstract = {

The multi-kinase inhibitor dasatinib induced a variable but significant decrease of viability in both p53(wild-type) (EHEB, JVM-2, JVM-3) and p53(mutated) (MEC-1, MEC-2, BJAB) prolymphocytic B leukemic cells, due to a combination of cell cycle block in G1 and apoptosis. Antibody phospho-kinase array analysis revealed that dasatinib inhibited the phosphorylation of various kinases, including ERK1/2 and p38/MAPK as well as of STAT3 transcription factors, in both p53(wild-type) and p53(mutated) cells. Therefore, dasatinib might offer a novel therapeutic strategy not only for p53(wild-type), but also for p53(mutated) B malignancies that have the worst prognosis and urgently need innovative therapeutic approaches.

}, keywords = {Antineoplastic Agents, Apoptosis, B-Lymphocytes, Cell Line, Tumor, Cell Survival, G1 Phase Cell Cycle Checkpoints, Granulocyte Precursor Cells, Humans, Leukemia, Prolymphocytic, B-Cell, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mutation, p38 Mitogen-Activated Protein Kinases, Phosphorylation, Protein Kinase Inhibitors, Pyrimidines, STAT3 Transcription Factor, Thiazoles, Time Factors, Tumor Suppressor Protein p53}, issn = {1573-0646}, doi = {10.1007/s10637-010-9564-6}, author = {Bosco, Raffaella and Rabusin, Marco and Voltan, Rebecca and Celeghini, Claudio and Corallini, Federica and Capitani, Silvano and Secchiero, Paola} } @article {1612, title = {Association of tumor necrosis factor-related apoptosis-inducing ligand with total and cardiovascular mortality in older adults.}, journal = {Atherosclerosis}, volume = {215}, year = {2011}, month = {2011 Apr}, pages = {452-8}, abstract = {

OBJECTIVE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits biological activity on vascular cells in vitro. Rapid variation of circulating TRAIL levels occurs during acute coronary ischemia, suggesting that biological pathways involving TRAIL may be activated during ischemic heart disease. However, whether differential levels of soluble TRAIL in normal individuals are associated with adverse health outcomes has not been investigated. We tested the hypothesis that TRAIL levels predict mortality in a population based sample of community dwelling men and women.

METHODS: Plasma TRAIL level was measured by ELISA at baseline in 1282 adults (mean age 68 years) enrolled in the InCHIANTI study. Vital status was ascertained over the six-year follow-up.

RESULTS: In multivariable Cox regression analysis adjusted for potential confounders including prevalent cardiovascular diseases (CVD), ankle-brachial index, electrocardiogram abnormalities, and inflammatory markers, baseline TRAIL levels were inversely related to all-cause mortality (p=0.008). In stratified analyses, the prognostic effect of TRAIL level was strong and highly significant in participants with prevalent CVD (N=321), (lowest versus highest quartile: HR 3.1; 95\% CI 1.5-6.5) while it was negligible in those free of CVD (p value for the interaction term between CVD status and TRAIL levels=0.038). Similar findings were obtained when CVD mortality was considered as the outcome of interest.

CONCLUSIONS: In older patients with CVD, low levels of TRAIL were associated with increased risk of death over a period of 6 years. Lower concentration of circulating TRAIL may be related to the clinical evolution of older adults with CVD.

}, keywords = {Adult, Aged, Ankle Brachial Index, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Italy, Male, Middle Aged, TNF-Related Apoptosis-Inducing Ligand}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2010.11.004}, author = {Volpato, Stefano and Ferrucci, Luigi and Secchiero, Paola and Corallini, Federica and Zuliani, Giovanni and Fellin, Renato and Guralnik, Jack M and Bandinelli, Stefania and Zauli, Giorgio} }