The role of Aflibercept in the management of age-related macular degeneration

ABSTRACT

Introduction: During the past decade, significant advances have occurred in the management of neovascular age-related macular degeneration (NV-AMD). The advent of anti-vascular endothelial growth factor (anti-VEGF) therapy has shifted the treatment goal of NV-AMD from merely salvaging vision to improving visual acuity and maintaining a good quality of life. Aflibercept (AFL) is a significant addition to the arsenal of anti-VEGF therapies against the NV-AMD. In the index review, pharmacology and efficacy of AFL has been reviewed.

Areas Covered: An extensive literature search was performed to identify preclinical and clinical studies performed to illustrate the role of AFL in NV-AMD. Randomized clinical trials evaluating other anti-VEGF agents were also included for comparison. Additionally, studies where AFL was employed to treat anti-VEGF-resistant cases agents have been reviewed.

Expert Opinion: AFL is an effective agent in the management of NV-AMD and its efficacy has been found to be comparable to ranibizumab (RBZ). Additionally, AFL is a good alternative agent in patients with NV-AMD resistant to RBZ and bevacizumab (BVZ), and can potentially lessen the treatment burden. As more research is conducted, the role of AFL in varying dosing regimens, as monotherapy and in combination with other agents, will become further defined.     

成年斑马鱼脊髓修复中脑内uegf基因的表达变化

目的斑马鱼具有很强的脊髓损伤后修复的能力,但是目前机制尚不明确。为研究斑马鱼脊髓修复过程中大脑对脊髓的可能作用与影响,本文采用成年斑马鱼脊髓损伤模型,检测了其脑组织中血管内皮生长因子（vas—cular endothelial frowth factor,vegf）基因的表达情况。方法建立成年斑马鱼脊髓损伤模型,应用实时定量PCR方法以及原位杂交技术,在成年斑马鱼脊髓损伤后4h、12h、6d、11d检测脑组织中血管内皮生长因子（vascular endo-thelial frowth factor,vegf）基因的表达情况。结果成年斑马鱼脊髓损伤以后,血管内皮生长因子基因损伤急性期（4h、12h）在脑内呈现显著性升高（P〈0．05）,而在神经修复期（6d）脑内的血管内皮生长因子（vegf）基因则呈现恢复趋势,在损伤后1ld此基因出现显著性下降的趋势（P〈0．05）。结论成年斑马鱼脊髓损伤后,短期内高表达vegf基因可能为修复中血管的再生提供有利的刺激与内环境,随着修复时间的延长和修复的逐渐完成,此基因则呈现恢复直至下降的趋势。     

vegf shRNA 对耐药白血病细胞化疗敏感性的增强作用

本研究采用RNA干扰技术探讨血管内皮生长因子(VEGF)对耐药白血病细胞K562/A02药物敏感性的影响及其机制。针对人vegf基因合成3个特异性shRNA干扰片段,采用脂质体介导的方法将其导入K562/A02细胞,用RT-PCR检测vegf及mrp1的mRNA表达水平,用Western blot检测VEGF、MRP1、AKT及P-AKT的蛋白表达情况,用MTT法检测阿霉素对各组细胞的半数抑制浓度(IC50),用流式细胞术检测细胞凋亡、胞内罗丹明123(Rho123)积聚情况。结果表明:转染vegf shRNA后,K562/A02细胞vegf的mRNA表达下调,其中vegf shRNA2组和vegf shRNA3组与HK组比较有显著差异(p<0.05),以vegf shRNA3组最显著,VEGF蛋白表达也出现下调,与mRNA的表达基本一致;MTT检测结果显示阳性转染组对阿霉素的敏感性增加,其中vegf shRNA2组和vegfshRNA3组的半数抑制浓度(IC50)与HK组比较具有显著的统计学差异(p<0.05);阳性转染组胞内Rho123积聚增多,与HK组比较均有统计学差异(p<0.05);阳性转染组细胞凋...     

Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma

Objective

We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc).

Methods

The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test.

Results

Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan–Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non–clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001).

Conclusions

Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.     

Use of anti‐vascular endothelial growth factor in the management of pterygium

The rising success of anti‐vascular endothelial growth factor (VEGF) therapies in ocular disease has stimulated the use of such treatments in the surgical management of pterygium. We reviewed the literature to better understand the safety and efficacy of the adjunctive role of anti‐VEGF treatments for pterygium excision. Without surgery, anti‐VEGF alone may favourably alter symptoms and vascularity, but does not cause pterygium regression. Some evidence supports the use of anti‐VEGF as an adjuvant therapy to surgery, especially when using a higher dose and a more frequent dosing regimen. Overall, anti‐VEGF is generally safe and well tolerated in patients with pterygium. Currently, the evidence does not conclusively support the use of anti‐VEGF in pterygium surgery. However, further research may guide unanswered questions regarding the interaction between VEGF and other factors responsible for pterygium growth. In addition, the optimal route and dosage of anti‐VEGF administration is not yet known.     

A bio-mathematical model of time prediction in corneal angiogenesis after alkali burn

BACKGROUND: The determination of angiogenesis time is the key prerequisite to obtaining a balance between valid repair and excessive angiogenesis in wound healing. The aim of the investigation was to establish a bio-mathematical model predicting corneal angiogenesis time after alkali burn by back propagation neural network (BP neural network). METHODS: The corneas of mice in 24 groups were burned by 0.01 mol/l NaOH. Five mice in each group were sacrificed at 6h after alkali burn. The expression levels of vegf and tsp2, determined by real-time quantitive PCR, were used as input vectors in BP neural network. Meanwhile, the corneal angiogenesis of other mice, inspected every 3h in 24 groups till the angiogenesis time were determined, served as output vectors. The data of 18 groups were randomly chosen for network adaptation while that of other 6 groups for simulation forecasting with functions of minmax (), postreg, prepca, trapca, respectively. RESULTS: A bio-mathematical model of two-level BP neural network was established, for its purpose to predict the angiogenesis time through the expression values of vegf and tsp2. The performance index (0.00999996) was smaller than the target value (0.01) after adapting 36,557 times and the accuracy rate of this predict system was 83.33%. Furthermore, the ideal regression line and the optimization regression line were almost coincident (R=0.988 in network adaptation and R=0.793 in simulation forecasting). CONCLUSIONS: The investigation indicated that the bio-mathematical model had available performance of simulation and forecasting. It might provide a novel method to solve clinical problems.     

上颌窦鳞癌Bcl-2、Vegf、E-cad蛋白表达的临床意义

目的 探讨基因Bcl-2、血管内皮生长因子（vascular endothelial growth factor,VEGF）、上皮钙粘附素（epithelial-cadherin,E-cad）蛋白产物在上颌窦癌中的表达情况及其临床意义。方法 采用免疫组织化学方法,对55例上颌窦癌及20例正常鼻粘膜组织中基因Bcl-2、Vegf、E-cad蛋白产物进行检测。结果 1-Bcl-2在正常鼻腔粘膜组织中表达率为（10％）。上颌窦癌中有较高表达（58．1％）。Vegf在正常鼻腔粘膜组织中表达率（56．3％）明显高于上颌窦癌（30％）中表达;E-cad在正常鼻腔粘膜组织中表达率（80％）明显高于上颌窦癌（60％）;Bcl-2、Vegf、E-cad阳性表达在鼻腔粘膜组织与上颌窦癌组织之间相比,均具有显著性差异。2．Vegf蛋白阳性率随临床分期的增加而升高,其中Ⅲ～Ⅳ期阳性率（70．9％）明显高于Ⅰ～Ⅱ期（37．5％）Bcl-2和E-cad阳性率在Ⅰ～Ⅱ期（79．1％、75％）高于Ⅲ～Ⅳ期（41．9％、48．3％）两者差异有显著性,P〈0．05。结论 Bcl-2、E-cad、Vegf基因参与了上颌窦的癌变及发展过程,其表达水平是判断病情及制订合理的治疗方案的敏感基因学指标,具有重要的临床意义。     

Minds That Matter: 2007 Gairdner International Awards Lectures

On October 25 and 26, 2007, at the University of Toronto, the Gairdner Foundation in partnership with Canadian Institutes of Health Research presented a two-day international symposium titled Minds That Matter. The symposium featured academic lectures by Gairdner Award winners past and present and by other leading biomedical scientists. These distinguished researchers share many characteristics in common: creativity, vision, tenacity, and driving curiosity to illuminate discovery with high degree of relevance. The present article summarizes the 2007 Gairdner Award lectures.