Combination therapy with vidaza and entinostat suppresses tumor growth and reprograms the epigenome in an orthotopic lung cancer model.

Epigenetic therapy for solid tumors could benefit from an in vivo model that defines tumor characteristics of responsiveness and resistance to facilitate patient selection. Here we report that combining the histone deacetylase inhibitor entinostat with the demethylating agent vidaza profoundly affected growth of K-ras/p53 mutant lung adenocarcinomas engrafted orthotopically in immunocompromised nude rats by targeting and ablating pleomorphic cells that occupied up to 75% of the tumor masses. A similar reduction in tumor burden was seen with epigenetic therapy in K-ras or EGFR mutant tumors growing orthotopically.

MMP12, lung function, and COPD in high-risk populations.

Background: Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups.

Methods: We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV(1)]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD.

Sin Nombre viral RNA load in patients with hantavirus cardiopulmonary syndrome.

To address the role that viral load plays in pathogenesis in patients with hantavirus cardiopulmonary syndrome (HCPS), we quantified Sin Nombre virus S segment viral RNA in plasma samples from 27 acutely ill patients. For 6 patients, we examined viral load in matched plasma, urine, and/or tracheal aspirate throughout the time when the patients were in intensive care. Peak titers in plasma reached 1.