Metformin extended-release versus immediate-release:An international, randomized, double-blind, head-to-head trial in pharmacotherapy-naïve patients with type 2 diabetes

This international, randomized, double-blind trial (NCT01864174) compared the efficacy and safety of metformin extended-release (XR) and immediate-release (IR) in patients with type 2 diabetes. After a 4-week placebo lead-in, pharmacotherapy-naïve adults with glycated haemoglobin (HbA1c) at 7.0% to 9.2% were randomized (1:1) to receive once-daily metformin XR 2000mg or twice-daily metformin IR 1000mg for 24weeks. The primary endpoint was change in HbA1c after 24weeks. Secondary endpoints were change in fasting plasma glucose (FPG), mean daily glucose (MDG) and patients (%) with HbA1c <7.0% after 24weeks. Overall, 539 patients were randomized (metformin XR, N=268; metformin IR, N=271). Adjusted mean changes in HbA1c, FPG, MDG and patients (%) with HbA1c <7.0% after 24weeks were similar for XR and IR: -0.93% vs -0.96%; -21.1 vs -20.6mg/dL (-1.2 vs -1.1mmol/L); -24.7 vs -27.1mg/dL (-1.4 vs -1.5mmol/L); and 70.9% vs 72.0%, respectively. Adverse events were similar between groups and consistent with previous studies. Overall, metformin XR demonstrated efficacy and safety similar to that of metformin IR over 24weeks, with the advantage of once-daily dosing

Epistasis between MicroRNAs 155 and 146a during T Cell-Mediated Antitumor Immunity

An increased understanding of antitumor immunity is necessary for improving cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs), miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits interferon γ (IFNγ) responses by T cells and reduces solid tumor growth in vivo. Using a double-knockout (DKO) mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155^(−/−) mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4^+ and CD8^+ T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses

RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype.

Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the&nbsp;cholesterol-biosynthesis program and an attractive target for TNBC

The effects of Bleomycin A5 on infantile maxillofacial haemangioma

<p>Abstract</p> <p>Objective</p> <p>To examine the effects of bleomycin A5 on infantile maxillofacial haemangiomas.</p> <p>Methods</p> <p>Bleomycin A5 was given by multiple intralesinoal injections and the dosage was given according to the age of the patient and size of the lesion. Parts of patients were accompanied by prednisone treatment(2-5 mg/kg, po, QOD.</p> <p>Results</p> <p>All the haemangiomas involuted completely after treated with bloemycin A5 with better recovery of skin color and less scar forming in small haemangiomas.</p> <p>Conclusion</p> <p>Infantile haemangioma could be effectively treated with bleomycin A5 without serious side effects.</p