贝伐单抗辅助的23G玻璃体切割术治疗严重增生性糖尿病视网膜病变的疗效观察

目的：2011年,我国糖尿病患者人数高达9240万。糖尿病视网膜病变（diabeticretinopathy,DR）作为糖尿病患者的常见并发症,在糖尿病人群中的患病率为37％,是导致成人获得性盲的最主要原因之一。严重增生性糖尿病视网膜病变以牵拉性视网膜脱离、玻璃体出血为特征,具有致盲率大,手术难度高等特点。针对与此,本文主要探讨术前注射贝伐单抗对23G玻璃体切割手术治疗严重增生性糖尿病视网膜病变患者效果的影响。方法：回顾性病例对照研究。共收集严重增生性糖尿病视网膜病变患者70例,药物辅助手术组（A组）21例,术前3—7天行玻璃体腔注射贝伐单抗（1．25mg／O．05mL）;单纯手术组（B组）49例,行23G玻璃体切割术。分析两组术前及术后视力、手术时间、医源性裂孔、电凝、术后出血的不同。结果：在术后3月,两组视力提高有统计学意义（P〈O．05）。A组平均手术时间为74分钟,而B组平均手术时间为85分钟（P〉0．05）。医源性裂孔在A组中有1例,而B组中有16例（P〈0．05）,在A组中有3例使用电凝,B组中有25例使用电凝（P〈0．05）。A组有1例出现术中及术后出血,B组为20例（P〈O．05）。结论：在这个回顾性研究中,我们发现对于严重增生性糖尿病视网膜病变的病人,术前玻璃体腔注射1．25mg／O．05ml贝伐单抗可以显著减少医源性裂孔的发生,减少术中电凝使用及术中术后出血的发生。     

转移性结直肠癌抗血管生成靶向治疗的研究进展

近年来,由于各种新的化疗药物及分子靶向药物的使用,转移性结直肠癌(metastatic colorectal cancer,m CRC)的个体化治疗逐步取得了重要的成果。研究表明,抗血管生成靶向药物与化疗药物的联合使用作为转移性结直肠癌的一线治疗方案,可明显改善治疗效果,延长患者的生存时间。血管内皮生长因子(vascularendothelial growth factor,VEGF)是肿瘤血管生成过程中最主要的因子。贝伐单抗是通过基因工程技术得到的针对血管内皮生长因子-A(VEGF-A)的单克隆抗体,作为抗血管生成靶向药物用于转移性结直肠癌的临床治疗。本文对近年来转移性结直肠癌的抗血管生成靶向治疗,尤其是贝伐单抗治疗的相关研究进展进行综述并展望未来抗血管生成靶向治疗的发展前景。     

贝伐珠单抗联合化疗治疗晚期非鳞非小细胞肺癌的临床观察

目的:观察贝伐珠单抗联合化疗对晚期非小细胞肺癌患者的疗效、安全性及影像学改变。方法:对2007年至2014年于我院治疗的晚期NSNSCLC(非鳞非小细胞肺癌non-squamous non-small cell lung cancer)患者,给予贝伐珠单抗(15 mg/kg或7.5mg/kg)联合化疗(紫杉醇175 mg/m~2,d1,卡铂AUC=5或6,d1,q3 w)6周期及贝伐珠单抗维持治疗(15 mg/kg或7.5 mg/kg,d1,q3w)。观察疗效、不良反应、肺部病灶空洞改变的情况、恶性胸腔积液的治疗效果及部分患者EGFR、KRAS基因突变状况。结果:共观察26例患者,均接受贝伐珠单抗联合化疗,17例行贝伐珠单抗维持治疗。部分缓解(partial response,PR)、疾病稳定(stable disease,SD)、疾病进展(disease progression,PD)率分别为53.8%、42.3%、3.8%。中位无进展生存期(progression free survival,PFS)为11.0个月,中位总生存期(overall survival,OS)达25.8个月。26例患者中15.4%治疗后病变发生空洞改变,空洞组的2年、3年生存率略高于无空洞组,但无统计学差异(P值分别为0.586、0.509)。13例患者伴有恶性胸腔积液,胸腔积液的疾病控制率为100%。11例患者标本可进行EGFR基因检测,敏感突变占36.4%,未突变占63.6%。对10例患者标本行KRAS基因检测,均为突变阴性。不良反应包括骨髓抑制、消化道反应、鼻衄、咯血、高血压、蛋白尿等。大多数不良反应程度较轻,可控制。结论:贝伐珠单抗联合化疗治疗晚期NSNSCLC患者疗效确切,副反应可耐受,控制恶性胸腔积液效果较好。肺部病灶空洞改变的临床意义有待进一步研究。     

贝伐单抗对ALA—PDT诱导的新生血管形成和胶质瘤生长的影响

探讨贝伐单抗对低剂量5-氨基乙酰丙酸（5-Aminolevulinicacid,ALA）介导的光动力学疗法（photodynamic therapy,PDT）诱导的脑组织新生血管形成和U87脑胶质瘤生长的影响。通过将裸小鼠随机分为对照组、ALA．PDT预处置组（ALA：2．3×10-3mol／kg,能量密度：10J／cm2）、贝伐单抗预处置组（1．6×10-5mol／kg）和联合预处置组（ALA—PDT＋贝伐单抗）,并接受相应处置。第10d,检测PDT照射及相应区域内新生血管形成和VEGF表达并种植U87脑胶质瘤细胞,21d后观察肿瘤体积。与对照组比较,低剂量ALA-PDT预处置后新生血管增多、VEGF表达增高,肿瘤体积增大,这些变化在联合预处置组被抑制;贝伐单抗预处置组的血管形态和VEGF表达虽无明显变化,但肿瘤体积减小。研究结果表明低剂量ALA-PDT可通过刺激VEGF表达诱导照射区新生血管形成,这种微环境的改变有利于U87胶质瘤细胞生长,但这些作用可被贝伐单抗所抑制。     

抗血管生成药物联合化疗治疗进展期非小细胞肺癌研究现状

大部分非小细胞肺癌患者需要进行系统化疗。研究表明以铂类药物为基础的标准一线系统化疗联合贝伐单抗能一定程度改善晚期非小细胞肺癌患者的预后。另有一些研究对多靶点抗血管生成的酪氨酸激酶抑制剂(如:索拉非尼,舒尼替尼,西地尼布,凡德他尼等)联合标准化疗的疗效进行了评估,为非小细胞肺癌患者提供了更多的治疗策略。本文主要对抗血管生成药物联合细胞毒性化疗药物治疗非小细胞肺癌的临床研究进行系统回顾。     

Actualización en el manejo de la degeneración macular asociada a la edad

Age-related macular degeneration is the leading cause of legal blindness in people over 50 in developed countries. It is a multifactorial disease resulting from the interaction of genetic and environmental factors, and the age is the only worldwide admitted risk factor. The socioeconomic impact of the disease reaches enormous proportions, if we take into account the high cost of the available antiangiogenic therapy, the strict schedule of medical visits that it requires, and the impairment that it gives rise to. The response to treatment and the visual outcomes improve with early management of the retinal lesions, thus the early diagnosis of the disease in its initial phases, based on self-control with an Amsler grid and with regular ophthalmologic assessments, is essential.     

Resolving the micro-heterogeneity and structural integrity of monoclonal antibodies by hybrid mass spectrometric approaches

For therapeutic monoclonal antibodies (mAbs), detailed analysis of the structural integrity and heterogeneity, which results from multiple types of post-translational modifications (PTMs), is relevant to various processes, including product characterization, storage stability and quality control. Despite the recent rapid development of new bioanalytical techniques, it is still challenging to completely characterize the proteoform profile of a mAb. As a nearly indispensable tool in mAb analysis, mass spectrometry (MS) provides unique structural information at multiple levels. Here, we tested a hybrid strategy for the comprehensive characterization of micro-heterogeneity by integrating 2 state-of-the-art MS-based approaches, high-resolution native MS and targeted glycan profiling, to perform complementary analysis at the intact protein level and released glycan level, respectively. We compared the performance of these methods using samples of engineered half-body IgG4s and a panel of mAbs approved for human use. The glycosylation characterization data derived from these approaches were found to be mutually consistent in composition profiling, and complementary in identification and relative-quantitation of low-abundant uncommon glycoforms. In addition, multiple other sources of micro-heterogeneity, such as glycation, lack of glycosylation, and loss of light chains, could be detected by this approach, and the contribution of multiple types of modifications to the overall micro-heterogeneity could be assessed using our superposition algorithm. Our data demonstrate that the hybrid strategy allows reliable and thorough characterization of mAbs, revealing product characteristics that would easily be missed if only a single approach were used.     

Intracameral bevacizumab and mitomycin C Trabeculectomy for eyes with neovascular glaucoma: a case series

The purpose of this study was to describe the surgical outcomes and safety of intracameral bevacizumab during trabeculectomy in eyes with neovascular glaucoma. Pilot study included four eyes (four patients) with refractory neovascular glaucoma submitted to fornix-based trabeculectomy with adjunctive use of bevacizumab in the anterior chamber during the procedure. Patients were previously treated with panretinal photocoagulation as standard therapy. Variables evaluated were intraocular pressure, bleb appearance, iris neovascularization, intraoperative/postoperative complications, and visual outcomes. No intraoperative complication was observed. The mean follow-up period was 12.75 (range, 12–15 months). All eyes showed significant intraocular pressure control postoperatively. Iris neovascularization reduced significantly within 1 month after surgery. Mild anterior chamber inflammation was observed during follow-up in all eyes. No significant postoperative complication was observed, and no patient presented visual acuity deterioration. Intracameral bevacizumab may be used as an adjunctive therapy during trabeculectomy in eyes with neovascular glaucoma.     

CFH, VEGF, and PEDF genotypes and the response to intravitreous injection of bevacizumab for the treatment of age-related macular degeneration

We determined whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and the response to treatment with a single intravitreous injection of bevacizumab for age-related macular degeneration (AMD). Eighty-three patients with exudative AMD treated by bevacizumab injection were genotyped for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, three SNPs (rs699947, rs1570360, rs2010963) in the VEGF gene, and four SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay. The CT genotype (heterozygous) of CFH-rs1061170 was more frequently represented in nonresponders in vision than TT genotypes (nonrisk allele homozygous) at the time points of 1 and 3 months, while there was no CC genotype (risk allele homozygous) in our study cohort (p = 7.66 × 10⁻³, 7.83 × 10⁻³, respectively). VEGF-rs699947 was also associated with vision changes at 1 month and PEDF-rs1136287 at 3 months (p = 5.11 × 10⁻³, 2.05 × 10⁻², respectively). These variants may be utilized for genetic biomarkers to estimate visual outcomes in the response to intravitreal bevacizumab treatment for AMD.     

Vascular endothelial growth factors and receptors: anti-angiogenic therapy in the treatment of cancer

Vascular endothelial growth factors (VEGFs) are critical regulators of vascular and lymphatic function during development, in health and in disease. There are five mammalian VEGF ligands and three VEGF receptor tyrosine kinases. In addition, several VEGF co-receptors that lack intrinsic catalytic activity, but that indirectly modulate the responsiveness to VEGF contribute to the final biological effect. This review describes the molecular features of VEGFs, VEGFRs and co-receptors with focus on their role in the treatment of cancer.