内皮抑素与眼部新生血管

眼部新生血管导致眼结构和功能的破坏,造成严重的视功能损害,是当前最难解决的眼科难题之一。内皮抑制素(endostatin,ES)是目前公认的最强的血管生成抑制因子之一,已经用于抑制眼部新生血管的实验研究,表明内皮抑制素具有强大的抗眼部新生血管作用。本文就内皮抑素的结构、功能及与眼部新生血管的相关研究进行综述。     

重组人血管内皮抑素静脉泵入联合窗口期化疗治疗晚期非小细胞肺癌的临床观察

目的 探讨重组人血管内皮抑素（恩度）静脉泵入联合窗口期化疗在晚期非小细胞肺癌（NSCLC）治疗中的疗效及安全性。方法 2012年2月至2013年12月34例ⅢB～Ⅳ期NSCLC患者采用恩度持续静脉泵入联合窗口期化疗。具体方案：恩度15mg／m2每天持续24h静脉泵入,连续7d;在第4天窗口期接受含铂两药方案化疗;21天为1周期。治疗2～6个周期,每2个周期评价疗效,每周期记录不良反应。结果 34例患者均完成至少2个周期的治疗,获完全缓解 1例,部分缓解 14例,稳定 8例,进展 11例,有效率（RR）为44.1％;其中非鳞癌患者的RR为38.9％,鳞癌患者的RR为50.0％;一线治疗患者的RR为53.9％。治疗过程中与恩度相关的主要毒副反应为：2级窦性心动过速1例,2级高血压1例;无1例出现出血等严重毒副反应。结论 恩度（15mg／m2）静脉泵入联合窗口期化疗治疗晚期NSCLC的近期疗效较好,不良反应无明显增加,值得临床进一步扩大样本量进行研究。     

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

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.     

Pancreatic tumor growth is regulated by the balance between positive and negative modulators of angiogenesis

There is increasing evidence for the implication of tumor-derived angiogenic and anti-angiogenic factors in controlling tumor growth in vivo. In this study, we documented the production of inhibitors of angiogenesis by pancreatic cancer cells and examined how changes in the balance between pro- and anti-angiogenic factors regulate tumor growth in vivo. The human pancreatic cancer cell line Hs-776T (HS-W) produces slow-growing tumors in SCID mice. Cells of a variant form (HS-R) of Hs-776T produced faster-growing tumors compared to HS-W. Characterization of HS-W and HS-R cells in vitro showed similar proliferation rates and production of the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Analyzes of anti-angiogenic factors showed comparable levels of angiostatin and thrombospondin 1 and 2, but endostatin was only detected in conditioned media of HS-W cells and was absent in HS-R. Cell proliferation was similar in both tumor types in vivo, whereas HS-W tumors demonstrated increased apoptosis with a high percentage of apoptotic endothelial cells (EC). Subsequently, VEGF was over-expressed in Hs-776T cells (HS-VF), resulting in rapidly growing tumors and lowering tumor and EC apoptosis. Collectively, our study confirms that tumor growth is dependent on its ability to increase the angiogenic stimulus or to reduce the amounts of endogenous anti-angiogenic factors.     

光热疗同步血管内皮抑制素联合化疗在局部晚期食管癌中的效果研究

研究光热疗同步血管内皮抑制素联合化疗对局部晚期食管癌患者的治疗效果及安全性。将局部晚期食管鳞癌(T2-4N0-1M0-1a)患者70例作为观察对象,其中,30例予以光热疗同步血管内皮抑制素联合化疗治疗(观察组),40例予以化疗(对照组)。比较两组疗效、不良反应、复发和转移率。结果显示,观察组的部分缓解(PR)和客观效率(ORR)均显著高于对照组;两组的1年复发率和转移率、Ⅰ-Ⅱ和Ⅲ-Ⅳ级不良反应无显著差异;2年后,观察组复发率及转移率显著低于对照组。结果提示,光热疗同步血管内皮抑制素联合化疗比单纯给予化疗对局部晚期食管癌患者的治疗效果好,且复发率和转移率低。     

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.     

血管抑制素和内皮抑制素的协同作用

血管抑制素和内皮抑制素是内源性的血管生成抑制剂,对肿瘤有明显的抑制作用,具有良好的应用前景,近年来,对于它们之间协同作用的研究已经成为新的热点。本文除对两者做了结构、性质、功能等方面的一般性介绍外,重点介绍了它们之间的协同作用。与血管抑制素和内皮抑制素单体的作用相比,它们之间的联合使用具有更强的抑制血管生成和肿瘤生长的作用。     

人内皮抑素基因改造、表达、纯化及活性检测

目的克隆诱变的人内皮抑素(human endostatin,hES)氨基端基因,并检测其活性。方法双酶切已诱变的人内皮抑素基因,电泳回收氨基端片段,与质粒pTYB-2重组,转化E．coli BL-21(DE3)。通过鸡胚绒毛尿囊膜(CAM)实验,MTT实验,HE染色及流式细胞术检测重组小分子人内皮抑素对新生血管生成、细胞增殖和细胞凋亡的影响。结果基因重组小分子内皮抑素对鸡胚尿囊膜新生血管生成具有明显的抑制作用;对脐静脉内皮细胞和肝癌细胞增殖的抑制存在量效关系;作用24h后,观察到细胞凋亡现象;与对照组相比,细胞凋亡数增加。结论成功构建了人内皮抑素氨基端基因工程菌,得到了具有生物活性的氨基端小分子内皮抑素,为便利临床应用奠定了基础。