c‐Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme

Genomic amplification of c‐Jun and its upstream kinases have been implicated as a mechanism of progression from well‐differentiated to dedifferentiated liposarcoma. To further define the role of c‐Jun in liposarcoma progression, we performed immunohistochemistry for c‐Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c‐Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c‐Jun amplification. c‐Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well‐differentiated components (59%), but only in the minority of pure well‐differentiated liposarcomas (27%). When c‐Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c‐Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c‐Jun in c‐Jun‐amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c‐Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

《东医宝鉴》与《万病回春》方剂内容的初步比较分析

通过比较《东医宝鉴·内景篇一》19首方剂引用《万病回春》内容与《万病回春》原文,可知许浚引用中国古代医籍并非照搬原文,而是具有自己的编撰思路。尤其是其对《万病回春》原文的删改调整,既参考了许浚自身的临床体会,也考虑到了朝鲜本土的具体情况,从而迈出了中医学在朝鲜本土化的步伐。     

杨廉方教授治疗神经根型颈椎病的用药特点及学术思想探析

目的:运用数据挖掘方法分析杨廉方教授治疗神经根型颈椎病的用药规律及思路,为临床治疗神经根型颈椎病提供参考.方法:收集2020年2月至2021年2月就诊于重庆市垫江县中医院全国名老中医药专家杨廉方传承工作室的门诊患者病历,对其进行规范化处理.采用Excel 2019、SPSS Modeler 18.0、SPSS 22.0...     

A feedback loop between BEX2 and ErbB2 mediated by c-Jun signaling in breast cancer

BEX2 is a member of brain expressed X-linked gene family that is differentially expressed in primary breast tumors. We have previously demonstrated that BEX2 expression protects breast cancer cells against mitochondrial apoptosis and G1 cell cycle arrest. In addition, we have shown that BEX2 is a c-Jun target gene and, in turn, regulates the phosphorylation of c-Jun in breast cancer cells. In our study, we investigated BEX2 protein expression in a tissue microarray cohort of 225 breast tissue samples with known clinical, pathological and biomarker information. We observed that BEX2 protein was overexpressed in ～50% of malignant breast tumors compared to only 7% of benign breast samples. Notably, BEX2 positive tumors identified a subset of breast cancers with the overexpression of ErbB2 and phosphorylated c-Jun proteins. Furthermore, using in vitro models, we demonstrated that the mechanism of this association is a functional feedback loop involving ErbB2, c-Jun and BEX2 in breast cancer cells. In this feedback loop, ErbB2 overexpression results in an induction of c-Jun and BEX2 expression. Importantly, ErbB2 induction of BEX2 expression was abrogated by a dominant-negative mutant of c-Jun, suggesting that this effect was mediated through the regulation of c-Jun signaling. In turn, the overexpression of BEX2 led to an increase in both c-Jun-mediated induction of ErbB2 and c-Jun binding to the ErbB2 promoter in MCF-7 cells. Our study suggests that BEX2 protein is overexpressed in approximately half of breast cancers and has a positive feedback loop with ErbB2 mediated by c-Jun signaling in breast cancer cells.     

杨宗孟教授临床用药探析

杨宗孟教授是国家名医,全国500名师承指导老师。从事中医妇科临床50余年,尤其擅长治疗女性不孕不育症,在多年的临床诊疗过程中,形成了自己的用药规律及特点。总结了杨老临床诊疗用药的经验,为后世妇科医者提供了临诊的宝贵经验。     

Inhibitory effect of fucoidan on nitric oxide production in lipopolysaccharide‐activated primary microglia

1. Microglial activation plays an important role in the pathogenesis of neurodegenerative diseases by producing various pro‐inflammatory cytokines. Microglia‐derived nitric oxide (NO) is critical for the lipopolysaccharide (LPS)‐induced selective loss of dopaminergic neurons. 2. Fucoidan is a sulphated polysaccharide extracted from brown seaweeds. It has a variety of biological actions, including anticoagulant, antiviral and anti‐inflammatory effects. The aim of the present study was to investigate the effects of fucoidan on LPS‐induced cellular activation in microglia and to evaluate the inhibitory mechanisms involved. 3. To investigate the effects of fucoidan on LPS‐induced cellular activation in microglia, primary microglial cells were preincubated with fucoidan (31.25, 62.5 and 125 μg/mL) for 10 min, followed by stimulation with LPS (0.01 μg/mL). Then, cell shape and NO production were determined 24 h after LPS stimulation, whereas inducible nitric oxide synthase (iNOS) mRNA and protein expression were determined at 6 and 18 h after LPS stimulation, respectively. To evaluate the inhibitory mechanisms involved, mitogen‐activated protein kinase (MAPK) activation was also evaluated. 4. Lipopolysaccharide transformed cells into an amoeboid shape, whereas 62.5 μg/mL fucoidan inhibited this activation. Moreover, 125 μg/mL fucoidan significantly inhibited microglial NO production to 75% of that in LPS‐treated group and also significantly diminished the expression of iNOS mRNA and protein by nearly 50%. Fucoidan (125 μg/mL) also suppressed phosphorylation of p38 and extracellular signal‐regulated kinase (ERK) by approximately 50%, but not that of c‐Jun N‐terminal kinase. 5. The results provide the first evidence that fucoidan has a potent inhibitory effect against LPS‐induced NO production by microglia. The results also suggest that this inhibitory action of fucoidan involves suppression of p38 and ERK phosphorylation.