PERK信号通路介导结肠癌细胞对5-氟尿嘧啶耐药机制的研究

目的:观察PERK蛋白对结肠癌细胞药物敏感性的影响，并进一步探讨其相关作用机制。方法:结肠癌细胞系HCT116分为三组:空白对照（Control）组、下调PERK表达（si-PERK）组、阴性对照（si-NC）组；采用免疫荧光及RT-PCR验证转染效率；利用CCK-8实验检测下调PERK表达后结肠癌细胞对化疗药物5-FU的敏感性变化；Annexin V-FITC凋亡实验检测下调PERK表达对结肠癌细胞凋亡的影响；利用RT-PCR及Western Blot实验检测PERK信号通路中关键分子eIF2α、ATF4、CHOP、XIAP的mRNA及蛋白表达变化。结果:RT-PCR实验表明:与正常对照组相比，si-PERK 组mRNA的表达显著下降（P＜0.05）,免疫荧光提示转染效率达80%以上；CCK-8实验发现与si-NC组相比，5-FU对 si-PERK组细胞的半数抑制浓度（IC50）明显降低（P＜0.01）；Annexin V-FITC凋亡实验发现与si-NC组相比，si-PERK组细胞的凋亡发生率显著升高（P＜0.05）；RT-PCR及Western Blot实验发现与si-NC组相比，si-PERK组细胞中PERK信号通路下游关键分子eIF2α、ATF4、CHOP的mRNA及蛋白表达均明显降低（P＜0.05）。结论:在结肠癌细胞中，抑制PERK表达后，其可能通过下调eIF2α、ATF4、CHOP的表达促进细胞发生凋亡，从而促进细胞对化疗药物5-FU的敏感性。     

Disulfiram (DSF) acts as a copper ionophore to induce copper‐dependent oxidative stress and mediate anti‐tumor efficacy in inflammatory breast cancer

Cancer cells often have increased levels of reactive oxygen species (ROS); however, acquisition of redox adaptive mechanisms allows for evasion of ROS‐mediated death. Inflammatory breast cancer (IBC) is a distinct, advanced BC subtype characterized by high rates of residual disease and recurrence despite advances in multimodality treatment. Using a cellular model of IBC, we identified an oxidative stress response (OSR) signature in surviving IBC cells after administration of an acute dose of an ROS inducer. Metagene analysis of patient samples revealed significantly higher OSR scores in IBC tumor samples compared to normal or non‐IBC tissues, which may contribute to the poor response of IBC tumors to common treatment strategies, which often rely heavily on ROS induction. To combat this adaptation, we utilized a potent redox modulator, the FDA‐approved small molecule Disulfiram (DSF), alone and in combination with copper. DSF forms a complex with copper (DSF‐Cu) increasing intracellular copper concentration both in vitro and in vivo, bypassing the need for membrane transporters. DSF‐Cu antagonized NFκB signaling, aldehyde dehydrogenase activity and antioxidant levels, inducing oxidative stress‐mediated apoptosis in multiple IBC cellular models. In vivo, DSF‐Cu significantly inhibited tumor growth without significant toxicity, causing apoptosis only in tumor cells. These results indicate that IBC tumors are highly redox adapted, which may render them resistant to ROS‐inducing therapies. DSF, through redox modulation, may be a useful approach to enhance chemo‐ and/or radio‐sensitivity for advanced BC subtypes where therapeutic resistance is an impediment to durable responses to current standard of care.     

肝细胞生长因子及受体、XIAP在卵巢癌组织中的表达及相关关系的探讨

目的探讨肝细胞生长因子及受体（HGF、c=Met）、XIAP基因在卵巢癌中的表达及相关关系。方法采用EnVision免疫组织化学法检测在30例卵巢癌组织中HGF、c-Met及XIAP的表达情况。结果HGF、c-Met、XIAP的表达与临床分期有关（P=0．000、P=0．001、P=0．008），HGF、C—Met、XIAP的表达与年龄、病理分型、淋巴转移均无明显相关性；HGF与XIAP呈正相关（r=0．853，P=0．000）。结论HGF、c—Met与XIAP在卵巢癌组织中呈高表达，HGF与XIAP呈正相关，可作为卵巢癌早期临床诊断的参考指标。     

Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

Cancer remains the topmost disorder of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.     

特发性胎儿生长受限患者胎盘组织中XIAP和Bax的意义

目的:探讨特发性胎儿生长受限(IFGR)胎盘组织中XIAP、Bax的表达及意义。方法:选取我院2010年7月～2011年4月剖宫产分娩的IFGR孕妇30例作为实验组,同期因社会因素剖宫产分娩的正常足月孕妇30例作为对照组。用免疫组化法检测胎盘组织XIAP、Bax的表达水平。结果:①XIAP在胎盘合体滋养细胞中的表达,实验组(114.562±5.167)低于对照组(144.430±7.311),差异有统计学意义(P<0.05)。②Bax在胎盘合体滋养细胞中的表达,实验组(146.513±10.611)高于对照组(113.673±9.631),差异有统计学意义(P<0.05);③实验组胎盘组织中XIAP与Bax的表达呈负相关(r=-0.761,P<0.05);对照组胎盘组织中XIAP与Bax的表达无相关性(r=0.034,P>0.05)。结论:胎盘组织中XIAP表达降低、Bax表达增加促使了胎盘滋养细胞的过度凋亡,可能是IFGR发病机制中的重要环节之一。     

XIAP在鼻咽癌细胞株CNE1、CNE2和5-8F中的表达与研究

目的比较CNE1、CNE2及5-8F鼻咽癌细胞株中X链锁调亡抑制蛋白(XIAP)的表达差异。方法体外培养鼻咽癌细胞株CNE1、CNE2及5-8F,采用RT-PCR法检测CNE1、CNE2及5-8F细胞株中XIAP基因表达情况。结果 XIAP基因在CNE1低表达,而在CNE2和5-8F高表达。结论 XIAP与NPC的恶性程度和转移潜能有关。     

NF-κB、XIAP、bcl-2在胃肠道间质瘤中的表达及其与临床病理行为的关系

目的 探讨胃肠道间质瘤(GIST)中NF-κB、XIAP、bcl-2的表达及其与临床病理行为的关系。方法应用RT-PCR方法检测93例GIST标本及癌旁正常组织对照组中NF-κB、XIAP、bcl-2mRNA水平。结果 NF-κB、XIAP、bcl-2mRNA在GIST组织与对照组相比呈现高表达,三者之间正相关。NF-κB、XIAPmRNA表达的变化与NIH分级、肿瘤侵袭转移、粘膜受侵密切相关(P<0.05),但bcl-2mRNA表达无关(P>0.05)。结论 NF-κB、XIAP、bcl-2mRNA在GIST高表达。     

Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled immune activation and is traditionally associated with inherited gene defects or acquired causes. In addition to abnormalities in cytotoxic granules and lysosomes, various primary immune deficiency disorders (PID) have been identified among patients suffering from HLH. Our purpose was twofold: to better characterize and detail the association between PID and HLH.     

紫杉醇联合奥沙利铂对非小细胞肺癌模型小鼠的治疗作用

目的观察紫杉醇联合奥沙利铂对荷瘤裸鼠非小细胞肺癌治疗效果以及对PDCD5和XIAP表达的影响。方法制备裸鼠肺癌荷瘤模型,将荷瘤小鼠随机分为空白组、0.9%氯化钠溶液组、奥沙利铂组、紫杉醇组和紫杉醇联合奥沙利铂组;q-PCR检测各组PDCD5和XIAP基因表达水平;Western bolt分析各组PDCD5和XIAP蛋白表达情况;对比分析各组肿瘤组织重量。结果紫杉醇联合奥沙利铂组PDCD5 mRNA表达水平最高(P0.01),XIAP mRNA表达水平最低(P0.01);紫杉醇联合奥沙利铂组PDCD5蛋白表达最高(P0.01),XIAP蛋白表达最低(P0.01);对比各分组肿瘤组织重量,紫杉醇联合奥沙利铂组肿瘤质量最小(P0.01)。结论紫杉醇联合奥沙利铂化疗能显著增加PDCD5表达和降低XIAP表达,能使已发生的非小细胞肺癌组织质量显著减少。