The Association between EGFR and cMET Expression and Phosphorylation and Its Prognostic Implication in Patients with Breast Cancer

EGFR and cMET cross-talk is involved in breast cancer (BC) progression and resistance to different targeted therapies, however little is known about the co-expression patterns of EGFR and cMET or its prognostic significance in BC. Protein levels of EGFR, cMET and their phosphorylated proteins were measured in 825 BC samples using reverse phase protein array (RPPA). Given unimodal distribution of proteins, the median was selected as a cut-off after sensitivity analyses. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall survival (OS). Cox-proportional hazards models were utilized to determine associations between EGFR and cMET with outcomes. Mean age was 58 years with 457 (55%) hormone receptor (HR) positive, 211 (26%) triple-negative (TN) and 148 (18%) HER2 positive tumors (HER2+). HER2+ was associated with higher EGFR expression and phosphorylation, compared to HR and TN (p<0.05). High EGFR expression was associated with higher phosphorylated-cMET (p-cMET) but not cMET (ANOVA p-cMET p < 0.001; cMET p = 0.34). The same association was found with high phosphorylated-EGFR (p-EGFR) group at Tyr992 and Tyr1068 (both p < 0.001). High expressions in either of two p-EGFRs were linked with higher cMET as well (all p<0.001). For the TN subtype, high expression in EGFR and p-EGFR at Tyr992 but not at Tyr1068 was associated with higher p-cMET (p<0.00, p = 0.012, p = 0.4 respectively). Only high expression in p-EGFR at Tyr992 was linked with higher expression of cMET (p = 0.02). In contrast, among HER2 subtype, high expression in p-EGFR at Tyr1068 but not at Tyr992 was associated with higher cMET and p-cMET (cMET p = 0.023;p-cMET p<0.001). Four subgroups of patients defined by dichotomized EGFR/p-EGFR and cMET/p-cMET level demonstrated no significant differences in survival. In multivariate analyses, neither cMET nor EGFR expression/activation was found to be an independent prognostic factor in survival outcome.     

Lipophosphoglycans from Leishmania amazonensis Strains Display Immunomodulatory Properties via TLR4 and Do Not Affect Sand Fly Infection

The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in sugars that branch off the conserved Gal(β1,4)Man(α1)-PO₄ backbone of repeat units. Here, the immunomodulatory activity of LPGs from Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis, was evaluated in two strains from Brazil. One strain (PH8) was originally isolated from the sand fly and the other (Josefa) was isolated from a human case. The ability of purified LPGs from both strains was investigated during in vitro interaction with peritoneal murine macrophages and CHO cells and in vivo infection with Lutzomyia migonei. In peritoneal murine macrophages, the LPGs from both strains activated TLR4. Both LPGs equally activate MAPKs and the NF-κB inhibitor p-IκBα, but were not able to translocate NF-κB. In vivo experiments with sand flies showed that both stains were able to sustain infection in L. migonei. A preliminary biochemical analysis indicates intraspecies variation in the LPG sugar moieties. However, they did not result in different activation profiles of the innate immune system. Also those polymorphisms did not affect infectivity to the sand fly.     

淹水胁迫下江南牡丹生长及光合特性研究

以3年生江南牡丹品种‘凤丹白’为材料,利用盆栽淹水法,设置正常管理、轻度胁迫和重度胁迫3个水平,研究不同淹水胁迫水平对牡丹生长和光合特性的影响。结果表明：经过30 d胁迫后,正常管理、轻度胁迫和重度胁迫下的江南牡丹苗高生长量分别为3.6、1.1和0.73 cm,地径生长量分别为0.21、0.11和0.06 cm,植株总生物量增加量分别为7.0、3.0和2.75 g,淹水胁迫和正常生长差异显著,淹水胁迫严重影响了江南牡丹的生长。同时,在正常管理时,牡丹总叶绿素含量升高,而在淹水胁迫下呈下降趋势。淹水胁迫不同时间根系活力均呈下降趋势且随着胁迫程度的增加下降越大。正常管理下光合速率逐渐增加而胁迫条件下光合速率逐渐降低。同时胁迫条件下,牡丹蒸腾速率、气孔导度均明显下降;轻度淹水胁迫下胞间CO2浓度先升高后降低;而重度胁迫下胞间CO2浓度呈现逐渐升高的变化趋势。淹水胁迫对牡丹根系活力、茎段生长和叶片光合特性影响较大。该研究结果为江南牡丹耐涝胁迫机理研究奠定了理论基础。     

2018年感染病领域十大进展

2018年已缤纷落幕,2019年带着对未来的期许纷至沓来。回顾过去,展望未来,本文整理了2018年世界乃至中国感染病界的几项重大事件与进展,并进一步梳理了该领域的发展趋势。     

子痫前期患者血清APN、TNF-α、Apelin水平的表达及相关性研究

目的:探讨子痫前期患者血清脂联素(APN)、肿瘤坏死因子-α(TNF-α)、Apelin水平的表达及相关性。方法:选取2015年10月到2017年8月在辽河油田总医院妇产科就诊的子痫前期患者86例,根据患者的病情严重程度将其分为轻度子痫前期组(46例)和重度子痫前期组(40例),另选取同期在我院进行产检的健康孕妇40例作为对照组,比较三组受试者血清中APN、TNF-α、Apelin、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和总胆固醇(TC)水平,并分析子痫前期患者血清中APN、TNF-α、Apelin、LDL-C、TG、HDL-C、TC的相关性。结果:重度子痫前期组血清中APN水平低于轻度子痫前期组和对照组,TNF-α、Apelin水平高于轻度子痫前期组和对照组(P0.05);轻度子痫前期组血清中APN水平低于对照组,TNF-α、Apelin水平高于对照组(P0.05)。重度子痫前期组血清中LDL-C、TG、TC水平高于轻度子痫前期组和对照组,HDL-C水平低于轻度子痫前期组和对照组(P0.05);轻度子痫前期组LDL-C、TC水平高于对照组,HDL-C水平低于对照组(P0.05)。Pearson相关性分析结果显示,子痫前期患者血清中APN与TNF-α、Apelin、LDL-C、TG呈负相关,与HDL-C呈正相关(P0.05);TNF-α与Apelin、LDL-C、TG、TC呈正相关,与HDL-C呈负相关(P0.05);Apelin与LDL-C、TG、TC呈正相关,与HDL-C呈负相关(P0.05)。结论:子痫前期患者血清中APN水平明显下降,TNF-α、Apelin明显升高,三种指标可相互影响,且均可影响机体的脂质代谢水平,共同调节子痫前期患者的疾病进展。