FN1在胃癌组织和细胞中的表达及意义

目的:研究纤维连接蛋白1（fibronectin-1,FN1）在胃癌组织和细胞中的表达,探讨其与预后的关系。方法:利用Oncomine数据库挖掘FN1在胃癌组织中的表达;实时荧光定量聚合酶链反应检测FN1在人胃癌细胞系中的表达;利用Kaplan-Meier Plotter分析FN1表达水平与胃癌预后的关系。结果:Oncomine 数据库分析FN1在多种肿瘤组织中表达增加,与胃正常组织相比,FN1在胃癌组织中表达增加,并具有统计学差异（P=1.41E-5)。FN1 mRNA在人胃癌细胞系SGC7901中表达水平增高,在胃癌组织中FN1蛋白表达增加。KM Plotter数据库分析结果显示FN1表达量与胃癌患者总体生存率存在相关性,即高表达FN1的患者总体生存率较差。结论:FN1在胃癌组织和细胞中的表达高于正常组织和细胞,是胃癌的危险因素,其表达水平越高预后越差。     

Increasing Antimicrobial Resistance Monitored in Surveillance Analysis of Blood Stream Infections in Febrile Neutropenic Pediatric Oncology Patients

Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia(FN)especially with the recent escalating trend in the management of pediatric cancer patients towards intensifiedregimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics.Aim: To monitor change in pattern of blood stream infections (BSI) in FN pediatric cancer patients. Materialsand Methods: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to aprevious surveillance in the same pediatric oncology unit. Results: A total of 232 BSI positive episodes weredocumented in 192 patients during a 6 months period. The results of recent surveillance analysis showed anincrease in intensified regimens of chemotherapy, antimicrobial resistance, fungal infections, and prolongedduration of episodes when compared to previous surveillance, with p value sof <0.001, 0.005, 0.021, and <0.001,respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, to6% in 2011 from 10 % in 2006. Conclusions: The pattern of BSI at our institution is still inclining towards grampositive organisms but is showing a shift towards more antibiotic resistance and fungal infections.     

肾病患者血清IL-8,FN和尿IL-8水平检测的临床意义

目的 :了解肾病患者血清IL - 8、FN和尿IL - 8水平、变化及意义。方法 :采用ELISA夹心法在疾病活动期和激素冲击治疗后 8周测定 5 1例肾病患者血清IL - 8、FN和晨尿IL - 8水平 ,并以 36例随机健康者作比较。结果 :肾病患者血清及尿IL - 8含量显著高于正常人组 (P <0 0 1)但与Scr无显著相关性 (r =0 .12 5 ,P >0 .0 5和r =0 .0 75 ,P >0 .0 5 )而血清FN水平则低于正常人组 (P <0 0 5 )。激素治疗 8周后 ,血、尿IL - 8水平均降低 (P <0 0 5 ) ,血清FN水平有所升高 ,但与治疗前比较无显著差异 (P >0 0 5 )。结论 :IL - 8、FN与肾病的发病机制有关 ,测定血清IL - 8、FN和尿IL - 8有助于判断肾病患者的炎症活动状况 ,有一定的临床价值。     

Gambogic acid inhibits tumor cell adhesion by suppressing integrin β1 and membrane lipid rafts-associated integrin signaling pathway

Cell adhesion plays an important role in the steps of cancer metastasis. Regulation of cell–cell (intercellular) and cell–matrix adhesion is a promising strategy for cancer progression. Gambogic acid is a xanthone derived from the resin of the Chinese plant Garciania hanburyi, with potent anti-metastasis activity on highly metastatic cells. The aim of this study was to investigate the function and mechanism of gambogic acid on tumor adhesion. We found that gambogic acid strongly inhibited the adhesion of human cancer cells to fibronectin. This inhibition was associated with the deformation of focal adhesion complex, which was mediated by suppressing the expression of integrin β1 and integrin signaling pathway. In vitro, cell lipid rafts clustering was inhibited following treatment of gambogic acid, which induced the suppression of integrin β1 and focal adhesion complex proteins colocalization within rafts. Moreover, gambogic acid significantly decreased cellular cholesterol content, whereas cholesterol replenishment lessened the inhibitory effect of gambogic acid on cell adhesion. Real-time PCR analysis showed that gambogic acid reduced mRNA levels of hydroxymethylglutaryl-CoA reductase and sterol regulatory element binding protein-2, while increased acetyl-CoA acetyltransferase-1/2. Taken together, these results demonstrate that gambogic acid inhibits cell adhesion via suppressing integrin β1 abundance and cholesterol content as well as the membrane lipid raft-associated integrin function, which provide new evidence for the anti-cancer activity of gambogic acid.     

Inhibition of arsenic-induced rat liver injury by grape seed exact through suppression of NADPH oxidase and TGF-β/Smad activation

Chronic arsenic exposure induces oxidative damage to liver leading to liver fibrosis. We aimed to define the effect of grape seed extract (GSE), an antioxidant dietary supplement, on arsenic-induced liver injury. First, Male Sprague-Dawley rats were exposed to a low level of arsenic in drinking water (30 ppm) with or without GSE (100 mg/kg, every other day by oral gavage) for 12 months and the effect of GSE on arsenic-induced hepatotoxicity was examined. The results from this study revealed that GSE co-treatment significantly attenuated arsenic-induced low antioxidant defense, oxidative damage, proinflammatory cytokines and fibrogenic genes. Moreover, GSE reduced arsenic-stimulated Smad2/3 phosphorylation and protein levels of NADPH oxidase subunits (Nox2, Nox4 and p47phox). Next, we explored the molecular mechanisms underlying GSE inhibition of arsenic toxicity using cultured rat hepatic stellate cells (HSCs). From the in vitro study, we found that GSE dose-dependently reduced arsenic-stimulated ROS production and NADPH oxidase activities. Both NADPH oxidases flavoprotein inhibitor DPI and Nox4 siRNA blocked arsenic-induced ROS production, whereas Nox4 overexpression suppressed the inhibitory effects of GSE on arsenic-induced ROS production and NADPH oxidase activities, as well as expression of TGF-β1, type I procollagen (Coll-I) and α-smooth muscle actin (α-SMA) mRNA. We also observed that GSE dose-dependently inhibited TGF-β1-induced transactivation of the TGF-β-induced smad response element p3TP-Lux, and that forced expression of Smad3 attenuated the inhibitory effects of GSE on TGF-β1-induced mRNA expression of Coll-I and α-SMA. Collectively, GSE could be a potential dietary therapeutic agent for arsenic-induced liver injury through suppression of NADPH oxidase and TGF-β/Smad activation.     

Sensory axon targeting is increased by NGF gene therapy within the lesioned adult femoral nerve

Even though peripheral nerves regenerate well, axons are often misrouted and reinnervate inappropriate distal pathways post-injury. Misrouting most likely occurs at branch points where regenerating axons make choices. Here, we show that the accuracy of sensory axon reinnervation is enhanced by overexpression of the guidance molecule nerve growth factor (NGF) distal to the bifurcation. We used the femoral nerve as a model, which contains both sensory and motor axons that intermingle in the parent trunk and distally segregate into the saphenous (SB) and motor branches (MB). Transection of the parent trunk resulted in misrouting of axon reinnervation to SB and MB. To enhance sensory axon targeting, recombinant adenovirus encoding NGF was injected along the SB close to the bifurcation 1 week post-injury. The accuracy of axon reinnervation was assessed by retrograde tracing at 3 or 8 weeks after nerve injury. NGF overexpression significantly increased the accuracy of SB axon reinnervation to the appropriate nerve branch, in a manner independent of enhancing axon regeneration. This novel finding provides in vivo evidence that gradient expression of neurotrophin can be used to enhance targeting of distal peripheral pathways to increase axon regeneration into the appropriate nerve branch.     

氧化苦参碱降低盆腔放疗患者血清TGF-β1、FN的含量及其意义

目的:对放疗患者应用氧化苦参碱观察其是否具有阻断正常组织放射性损伤的生物活性.方法:78例确诊的妇科肿瘤患者随机分为治疗组和对照组,两组均进行单纯盆腔野根治性放疗,治疗组用岩舒注射液静滴.采用酶联免疫吸附法(ELISA)动态检测所有患者放疗过程中及放疗后血清转化生长因子-β1(TGF-β1)、纤维连接蛋白(FN)的含量.结果:氧化苦参碱能降低血清TGF-β1的含量,但反应较迟缓,对于晚期的放射性损伤可能更具有临床意义.放疗过程中氧化苦参碱能明显降低血清FN含量,预防急性放射性损伤的发生.结论:氧化苦参碱可以干预盆腔组织放射性损伤的发生.     

Dynamic MR-Mammography as the best method for diagnosis of invasive lobular breast carcinoma: A retrospective study

Aim of the study

It is a retrospective study aiming to provide diagnostic characterization of ILC in Dynamic MR-Mammography and to compare its diagnostic performance to mammography and ultrasonography.

Material and Method

A total of 56 cases of ILC were selected in retrospective review of mammography, ultrasonography and Dynamic MRM of 420 patients with invasive breast cancer.

Results

Asymmetric density was the commonest mammography finding and the measured sensitivity of mammography in detecting ILC was 87.5% (9/56 FN).The most common US manifestation of ILC was focal shadowing without a discrete mass and its sensitivity in detecting ILC was 84.9% (10/56 FN). At MR imaging, the most common manifestation of ILC was a solitary irregular or angular mass with speculated or ill-defined margins (33.9%of cases [n = 19]).The measured sensitivity is 96.5% (2/56 FN). Additional data such as those affected the patient management including the presence of multifocal or multicentric disease, chest wall involvement and contralateral breast cancer were encountered in 48.2% of cases [n = 27]. ILC has a tendency to demonstrate delayed maximum enhancement with washout exhibited by only a minority of lesions (21.4% [n = 12]).

Conclusion

MR imaging has proved to be superior to mammography and US in the detection and management of ILC. It provides useful information for further management and pre-surgical planning.