多西他赛联合重组人血管内皮抑素治疗非小细胞肺癌的临床效果

目的：探讨多西他赛联合重组人血管内皮抑素治疗非小细胞肺癌（NSCLC）的临床效果。方法选择2010年1月~2013年3月收治的76例一线化疗初治后进展或不能耐受毒性反应的NSCLC患者,观察组38例给予多西他赛联合重组人血管内皮抑素治疗,对照组38例采用单药多西他赛治疗,比较两组的疾病进展时间（TTP）、客观缓解率（ORR）、临床受益率（CBR）及不良反应情况。结果观察组及对照组的ORR均为0,CBR分别为63.2%（24/38）和52.6%（20/38）（P=0.712）。观察组及对照组的TTP分别为（2.6±0.4）、（2.0±0.8）个月（P=0.083）。观察组及对照组初治后进展的TTP分别为（1.3±0.4）、（1.6±0.8）个月（P=0.907）;不能耐受毒性的TTP分别为（4.7±0.1）、（3.1±0.8）个月（P=0.092）。观察组及对照组经治疗后获疾病稳定患者的TTP分别为（6.2±0.4）、（3.2±0.8）个月,观察组较对照组长（P=0.038）。观察组及对照组的不良反应比较差异无统计学意义（P>0.05）。结论对于初治后进展或不能耐受毒性反应的NSCLC患者,重组人血管内皮抑素在不增加毒副作用的情况下可延长多西他赛化疗获益患者的TTP。     

重组人血管内皮抑素与薄芝糖肽联合化疗治疗晚期非小细胞肺癌的临床研究

目的：探讨重组人血管内皮抑素与薄芝糖肽联合化疗治疗晚期非小细胞肺癌的近期临床效果和安全性。方法选取2012年1月~2014年4月来本院就诊的102例经病理证实的晚期非小细胞肺癌患者,根据治疗方法,将患者分为两组。对照组48例单纯给予奥沙利铂(L-OHP)+培美曲塞(PEM)化疗方案;实验组54例在对照组基础上给予重组人血管内皮抑素和薄芝糖肽治疗。比较两组患者的临床疗效、生活质量KPS评分、药物毒性反应发生率以及外周血免疫功能变化情况。结果治疗后,实验组患者的近期临床疗效、生活质量KPS评分优于对照组(P<0.05)。两组患者治疗后的CD4+、CD8+均较治疗前降低,对照组降低更明显,两组治疗后的CD4+、CD8+差异有统计学意义(P<0.05)。结论重组人血管内皮抑素与薄芝糖肽联合化疗治疗晚期非小细胞肺癌具有较好的近期效果,能提高患者在化疗过程中的生活质量,改善其免疫功能。     

重组人血管内皮抑制素对小鼠胃癌c-Myc,bFGF表达的影响

目的 通过构建荷胃癌小鼠模型研究重组人血管内皮抑制素对癌基因c-Myc和成纤维细胞生长因子(bFGF)表达的影响及可能机制.方法 20只小鼠皮下注射MFC小鼠前胃癌细胞从而构建小鼠胃癌移植瘤模型,后随机分成两组,每组10只,观察组腹腔注射0.8mg/kg重组人血管内皮抑素,对照组腹腔注射等量生理盐水.每天观察小鼠的一般情况,每3天测量肿瘤体积,绘制肿瘤体积生长曲线并对两实验组肿瘤体积进行比较;应用RT-PCR、Western bolt及免疫组织化学法检测两组小鼠肿瘤组织中c-Myc和bFGF的表达,免疫组织化学染色法检测肿瘤组织微血管密度(MVD)的表达,并通过Spearman分析c-Myc和bFGF两者的相关性.结果 在用药的过程中,对照组小鼠随着移植瘤结节的增大而发生行为明显改变,但观察组小鼠精神、反应、活动及进食饮水均如初,未见明显不良反应.治疗后第9d开始,观察组小鼠移植瘤体积明显小于对照组(P＜0.05),在第21 d最明显(P＜0.01).RT-PCR检测显示e-Myc,bFGF mRNA相对表达量明显低于对照组(P＜0.05);Western blot检测显也显示观察组c-Myc,bFGF蛋白的表达量明显低于对照组(P＜0.05);免疫组织化学检测显示c-Myc,bFGF阳性细胞数均明显低于对照组(P＜0.05),c-Myc,bFGF平均灰度值明显高于对照组(P＜0.05);对照组平均MVD为9.2±1.3,观察组为2.9±1.0,两组之间差异亦具有统计学差异(P＜0.05).且Spearman分析得出小鼠胃移植瘤中e-Myc和bFGF mRNA存在正相关(r=0.853,P=0.000).结论 重组人血管内皮抑制素通过抑制胃癌组织c-Myc,bFGF基因表达和血管生成.     

超声微泡介导内皮抑素基因转染人脐静脉内皮细胞的实验研究

目的：探讨超声微泡介导内皮抑素（endostatin,ES）基因对人脐静脉内皮细胞（human umbilical vein endothelial cells ,HUVECs）转染的效率及可行性。方法 HUVECs种于24孔板内,培养24 h后加入5μg pIRES2-EGFP-ES质粒及超声造影剂SonoVue微泡,启动超声照射进行转染,设定MI分别为0.7、1.0、1.5,辐照时间分别为10 s、30 s、60 s、120 s,微泡浓度分别为10％、20％、50％。转染24 h后观察绿色荧光蛋白表达,计数活细胞数,MTT检测细胞增殖抑制率。结果超声爆破微泡介导了内皮抑素基因转染HUVECs,并具有强度、时间及微泡浓度依赖关系,但随着强度、微泡浓度增加及辐照时间延长,细胞凋亡率增加、细胞活力下降,转染率随之下降,当超声强度MI1.5、辐照时间60 s、微泡浓度20％转染率相对最高。结论超声微泡可介导内皮抑素基因转染脐静脉内皮细胞,但转染受多因素影响,在相对最佳转染条件下可实现内皮抑素的高表达。     

重组人血管内皮抑素介入栓塞治疗对肝癌恶性生物学行为的影响

目的:研究重组人血管内皮抑素介入栓塞治疗对肝癌恶性生物学行为的影响.方法:选取本院收治的80例原发性肝癌患者纳入研究,随机分为两组,观察组接受重组人血管内皮抑素+吉西他滨+奥沙利铂介入栓塞化疗,对照组接受吉西他滨+奥沙利铂介入栓塞化疗,比较两组血清肿瘤标志物含量、增殖和黏附分子含量以及外周血中免疫分子含量.结果:(1)肿瘤标志物:观察组血清高尔基体蛋白73(GP73)、缺氧诱导因子-1α(HIF-1α)、DDK1含量低于对照组,差异有统计学意义(P＜0.05);(2)增殖和黏附分子:观察组血清Polo样激酶1(Plk1)、可溶性细胞间黏附分子-1(sICAM-1)、CD44v含量低于对照组,差异有统计学意义(P＜0.05);(3)免疫分子:观察组外周血中Th1/Th2比例高于对照组、Treg/Th17比例低于对照组,差异有统计学意义(P＜0.05).结论:重组人血管内皮抑素介入栓塞治疗有助于杀灭肝癌细胞、抑制细胞增殖和黏附、增强细胞免疫功能,是治疗原发性肝癌的理想方法.     

Reversal effect of recombinant human Endostatin on cisplatin resistance in A549/DDP human lung adenocarcinoma cells in vitro

Objective： Recombinant human Endostatin （rh-Endostatin, YH-16） can reverse cisplatin resistance in A549/DDP cells. However, the possible effect of rh-Endostatin in reversing DDP-resistance in A549/DDP cells and the mechanism are needed to be investigated. Methods： Lung adenocarcinoma cell line A549 and its DDP-resistant cell line A549/DDP were treated with DDP and/or recombinant human Endostatin. Difference in drug resistance was analyzed between different regi- mens and between different cell lines after a 72 h-treatment in vitro. And below the non-cytotoxic concentration of rh-End- ostatin, the possibility of rh-Endostatin in reversing DDP-resistance in A549/DDP was evaluated. The resistance protein which was detected in the study included P glycoprotein （P-gp） and topoisomerase II （Topo-II）. Results： Rh-Endostatin below 400 IJg/mL showed no cytotoxicity in either A549 or A549/DDP after 72 h-treatment with it. The inhibited concentration of 50% （IC50） observed for DDP was （0.79 _＋ 0.05） IJg/mL in A549 and （13.2 ＋ 1.1） in A549/DDP respectively. IC50 was reduced to 2.57 ＋ 0.05 #g/mL in A549/DDP treated by rh-Endostatin below the non-cytotoxic concentrations in combination with DDP, with a reversal fold （RF） of 5.14 and a relative reversal rate of 85.6%. Apoptotic rates were 2.01%, 13.47% and 29.26% re- spectively for cells treated with rh-Endostain, DDP, and the combination. The rate of the A549/DDP control group was 0.99%. The expression level of P-gp or Topo-II was higher in A549/DDP cells than in A549 cells. Rh-Endostatin may partially reverse DDP-resistance in A549/DDP cells in vitro, with a probable mechanism related to lowering expression of P-gp and Topo-II. Conclusien： Rh-Endostatin of non-cytotoxic dose partially reversed cisptatin resistance in cisplatin-resistant human lung adenocarcinoma cell line A549/DDP. Rh-Endostatin reversed the resistance of A549/DDP cells to DDP, which may be related to decreased protein expression of P-gp and Topo-II in A549/DDP cells.     

Biomarker for early renal microvascular and diabetic kidney diseases

Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1?mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60?mL/min/1.73?m², is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.     

芍甘附子汤加味对胶原诱导性关节炎大鼠滑膜血管生成抑制因子干预作用的机制研究

目的研究芍甘附子汤（SGFZ）加味对胶原诱导性关节炎（CIA）大鼠滑膜内皮抑素（Es）、血管生成抑素（AS）蛋白表达水平的影响。方法健康雌性Wistar大鼠60只，分为正常组10只和造模组50只，采用牛Ⅱ型胶原与完全弗氏佐剂建立大鼠CIA模型。造模成功后分组，正常组、模型组给予等量蒸馏水灌胃，雷公藤多甙组按8．75ms／（kg·d）灌胃，SGFZ加味小、中、大剂量组依次按每毫升药液含0．708、1．42、2．83g生药灌胃，均为每日1次，连续给药28天。造模后第0、14、28、42、56天观察大鼠关节炎指数（AI），灌胃治疗结束后Westernblot法检测ES、AS表达水平。结果与正常组比较，造模组AI评分显著升高（P〈0．01）；经药物治疗后，与模型组比较，雷公藤多甙组与SGFZ加味大、中剂量组AI评分降低（P〈0．01）。与正常组比较，模型组ES、AS蛋白表达水平均下调（P〈0．01）；与模型组比较，雷公藤多甙组和SGFZ加味各剂量组Es蛋白表达水平均上调（P〈0．01），SGFZ加味大、中剂量组AS蛋白表达水平上调（P〈0．01）。结论SGFZ加味可有效改善CIA大鼠关节肿胀程度，其作用机制可能与调节ES、AS蛋白表达水平有关。     

Matricryptins and matrikines: biologically active fragments of the extracellular matrix

Numerous extracellular proteins and glycosaminoglycans (GAGs) undergo limited enzymatic cleavage resulting in the release of fragments exerting biological activities, which are usually different from those of the full‐length molecules. In this review, we define matrikines and matricryptins, which are bioactive fragments released from the extracellular matrix proteins, proteoglycans and GAGs and report their major biological activities. These fragments regulate a number of physiopathological processes including angiogenesis, cancer, fibrosis, inflammation, neurodegenerative diseases and wound healing. The challenges to translate these fragments from molecules biologically active in vitro and in experimental models to potential drugs are discussed in the last part of the review.