JNJ-26481585对人肺腺癌培美曲塞耐药裸鼠移植瘤的抑制作用及其机制探讨

目的:探讨JNJ-26481585对人肺腺癌培美曲塞耐药裸鼠移植瘤的抑制作用及其抗癌机制。方法:构建人肺腺癌A549/培美曲塞耐药细胞(A549/PEM)的移植瘤裸鼠模型,随机分为模型组、培美曲塞组、JNJ组、联合组(培美曲塞+JNJ),第28天治疗观察结束时处死裸鼠,剥离肿瘤组织标本待测。测定4组裸鼠肿瘤体积与体质量,计算抑瘤率,观察各治疗组药物对荷瘤裸鼠的毒副反应,TUNEL方法检测4组移植瘤细胞凋亡情况的差异,qRT-PCR检测4组移植瘤细胞FAM96A、Bax、Bcl-2基因mRNA表达水平差异,Western blot检测4组移植瘤细胞FAM96A、Bax、Bcl-2蛋白表达的差异。结果:联合组的肿瘤体积、体质量低于JNJ组,JNJ组的肿瘤体积、体质量低于培美曲塞组,联合组的抑瘤率高于JNJ组,JNJ组抑瘤率高于培美曲塞组(均P<0.05)。联合组的细胞凋亡率高于JNJ组,JNJ组细胞凋亡率高于培美曲塞组(均P<0.05)。联合组肿瘤细胞的FAM96A、Bax表达水平高于JNJ组,JNJ组FAM96A、Bax表达水平高于培美曲塞组,联合组Bcl-2表达水平低于JN...     

康莱特联合奥沙利铂胸腔灌注治疗恶性胸腔积液及对RCAS1、VEGF表 达的影响

目的:探讨康莱特联合奥沙利铂胸腔灌注治疗恶性胸腔积液的临床价值以及灌注治疗对恶性胸腔积液中SiSo细胞上的受体结合肿瘤抗原(RCAS1)、血管内皮生长因子(VEGF)表达的影响。方法:选取110例非小细胞肺癌并胸腔积液患者,分为康莱特组35例,奥沙利铂组35例及联合用药组40例,分别收集胸腔注药前及每次注药48h后的胸水标本,采用酶联免疫吸附测定（ELISA）方法检测胸水标本中的RCAS1、VEGF水平。结果:三组疗效比较,联合组优于康莱特组（P<0.01）。生活质量改善方面,联合组优于康莱特组与奥沙利铂组（P<0.05）。三组治疗后的毒副反应比较,康莱特组低于联合组及奥沙利铂组（P<0.05）。三组治疗前、第1周期治疗后、第2周期治疗后胸水RCAS1及VEGF表达水平均有逐渐下降趋势（P<0.05）,联合用药组较其它两组下降更明显（P<0.001）。结论:康莱特联合奥沙利铂胸腔灌注对控制恶性胸腔积液具有一定的临床价值,检测胸水RCAS1、VEGF表达水平可评估康莱特联合奥沙利铂灌注治疗效果。     

体外膜肺氧合对重症患者的治疗效果评价

摘要:目的　评估体外膜肺氧合对重症患者的治疗效果,为今后临床救治重症ARDS患者提供依据。方法　选择2008年1月-2013年3月至我院ICU救治的患者中,由于呼吸窘迫综合症机械通气效果不佳进行ECMO支持治疗的重症患者21例作为研究对象。所有患者均采用静脉-静脉（V-V）体外膜肺流转模式,同时采用保护性肺通气策略,监测中心静脉压。评估治疗前后患者血气指标、APACHEⅡ评分、SOFA评分及患者的转归。结果　治疗前患者平均SaO2为0.81±0.03、PaCO2为47.3±6.9,pH值为7.10±0.14,经ECMO治疗后的三项指标分别为0.98±0.02、33.5±4.6及7.42±0.08,与治疗前相比差异均具有统计学意义（P＜0.001）;治疗前患者APACHEⅡ评分为17.1±7.3,SOFA评分为7.5±2.2,经过ECMO治疗后APACHEⅡ评分为6.8±3.0、SOFA评分为6.0±1.8,治疗前后相比差异具有统计学意义（P＜0.05）。在21例接受治疗的患者中,2例死亡,其余19例均顺利出院,死亡率为9.52%。结论　ECMO能减轻重症患者心肺负荷,改善患者缺氧症状,促进心肺的恢复,减少有关并发症的发生。     

Cardiovascular Side Effect Remotely Related to NSAIDs: A Comparative Experimental Study on Albino Rats

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit enzyme cyclo-oxygenase (COX)-1&2, required for antiinflammatory effect, which comes along with side effect of gastric ulceration related to inhibition of COX-1. Whereas recent NSAIDs act selectively on COX-2 isoform. Thus referred as selective NSAIDs. Therefore selective NSAIDs are more beneficial than earlier non-selective NSAIDs in regard of incidence of gastric ulceration. Metabolism of these drugs is associated with liver and kidney. Therefore, we observed the comparative adverse effects of diclofenac sodium (diclo) a non-selective NSAIDs and valdecoxib (valde), a selective NSAIDs on renal function. The experiment was carried on 50 albino rats of duckrey (DR) strain, in equal sex ratio. Animals were divided into five groups (n=10). Group A, B1, B2, C1 & C2. Group A served as control, B1 & B2 were given diclo 5 & 10 mg/kg/day per orally, C1 & C2 were given valde 1 & 2 mg/kg/day per orally respectively, for 30 days. Renal histological examination and biochemical parameters were estimated. We estimated serum creatine, blood urea nitrogen (BUN), uric acid (UA), Na+ & K+ for renal function. Kidney sections of all the groups showed thickening of glomerular basement membrane, increase in glomerular cellularity, and degeneration of proximal and distal convoluted tubule. Tubule in medulla showed degeneration with intraluminal protein exudates. Histopathological changes were more significant with valdecoxib. In biochemical estimation lower dose of diclo showed increase in serum K+ only, on other hand lower dose of valde showed more significant change and there was increase in serum creatine, BUN & K+. Whereas higher doses of diclo and valde showed highly significant increase in serum creatine, BUN & K+. Increased UA was observed only with higher dose of valde. Thus these result show renal insufficiency, fluid overload and accumulation of urea & K+. These can lead to congestive heart failure, pericarditis, hypertension, arrhythmias. Thus, chronic renal failure patient suffers from accelerated atherosclerosis and high incidence of cardiovascular disease can be explained. Valdecoxib though banned due to cardiovascular effects and atherosclerosis which can also linked indirectly from renal insufficiency.