White blood cells contribute to patient-specific warfarin dose for Han Chinese / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Warfarin is the most commonly prescribed anticoagulant worldwide. Factors which influence warfarin's inter-individual requirements including age, weight, and genetic factors explained about 50% of dose variance, and unidentified factors still remain. The aim of this study was to explore whether white blood cell count affects warfarin dose requirements.</p><p><b>METHODS</b>Three hundred and twenty-two patients suffering from venous thromboembolism (VTE) and taking warfarin were recruited in this study. Genotyping of selected genes was conducted and other information was collected using the Epidata software. Dosing algorithms were constructed by multivariate linear regression analyses.</p><p><b>RESULTS</b>In addition to well-known factors such as age, body weight, CYP2C9*3, and VKORC1 c.1173C > T, white blood cell counts negatively related to warfarin dose requirements and contributed to warfarin variability in Han Chinese by about 0.6%.</p><p><b>CONCLUSION</b>White blood cell count has a small but significant contribution to warfarin dose requirements in Han Chinese.</p>

Progress of anti-tumor study based on BRAF / 药学学报

BRAF is one of the most important pro-oncogenes, which is mutated in approximately 8% of human tumors. The most common BRAF mutation is a valine-to-glutamate transition (V600E) that is expressed primarily in melanoma, colorectal cancer and thyroid carcinoma. MEK/ERK is constitutively activated in the cells expressing BRAFV600E, leading to tumor development, invasion, and metastasis. Therefore, BRAFV600E is a therapeutic target for melanoma and some other BRAFV600E tumors. Vemurafenib, a BRAFV600E inhibitor, which was approved by FDA for the treatment of late-stage melanoma in 2011, produces improved rates of overall and progression-free survival in patients with the BRAFV600E mutation, making a dramatic breakthrough in melanoma treatment. Vemurafenib is also an individual target drug based on genetic diagnosis. However, its therapeutic success is limited by the emergence of drug resistance. Therefore, it is important to explore the mechanisms underlying the resistance for developing new inhibitor drugs and for preventing or delaying the resistance evolution to BRAF inhibitor drugs. In this review, we described the role of BRAFV600E as an anti-tumor drug target and the development of BRAF inhibitors. We also discussed the mechanisms leading to resistance of BRAFV600E inhibitors. Furthermore, therapeutic strategies that might be employed to overcome acquired resistance were proposed.

Effects of phytoestrogens on testosterone production of rat Leydig cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of phytoestrogens (daidzein and genistein) on the testosterone production of rat Leydig cells and the possible mechanisms.</p><p><b>METHODS</b>Primary Leydig cells were obtained from 3-month old male SD rats using discontinuous Percoll density gradient centrifugation. The effects of phytoestrogens at various concentrations were evaluated by ELISA, with hCG as the positive control. The mRNA expression of P450 side-chain cleavage enzyme (P450scc) was analyzed by semi-quantitative RT-PCR.</p><p><b>RESULTS</b>Genistein at 0.1 micromol/L obviously promoted the secretion of testosterone and upregulated the mRNA level of P450scc. At a higher concentration of 5 micromol/L, however, both daidzein and genistein significantly inhibited the testosterone production of Leydig cells (P > 0.05).</p><p><b>CONCLUSION</b>Genistein can promote the testosterone production of Leydig cells at a low concentration (0.1 micromol/L), but both daidzein and genistein can inhibit it at a higher concentration ( >5 micromol/L).</p>