内源性VEGF对TMP促进大鼠脊髓损伤修复的影响

目的观察VEGF对TMP治疗大鼠脊髓损伤的影响。方法实验大鼠随机分为假手术组、生理盐水组、 TMP组和TMP+Avastin组,观察术后8周脊髓损伤处VEGF、 vWF和IL-8表达,以及神经纤维再生、后肢运动功能。结果 TMP+Avastin组内源性VEGF表达减少,限制血管新生及炎性反应(P <0.05)。对于神经纤维再生及其后肢运动,TMP组优于生理盐水组(P <0.05), TMP+Avastin组的效果更优(P <0.05)。结论内源性VEGF阻碍了TMP对大鼠脊髓损伤的修复,Avastin通过降低炎性反应提高TMP治疗大鼠脊髓损伤的疗效,促进神经纤维再生及后肢运动功能恢复。     

The developing trend of monoclonal antibodies in the treatment of colorectal cancer

Monoclonal antibodies (mAbs) against growth factors, receptors and tumor-specific/tumor-selective antigens represent a rapidly growing class of pharmaceutical agents which are poised to make a major impact on the treatment of colorectal cancer. mAbs targeting the epidermal growth factor receptor and the vascular endothelial growth factor have already been approved for the treatment of metastatic colorectal cancer. Other antibodies to the same and other molecular targets implicated in tumor growth and metastasis are undergoing intense preclinical and clinical evaluation. In both the neoadjuvant and adjuvant clinical settings, although mAbs are typically administered in combination with established cytotoxic chemotherapy regimens given their synergistic effect, several agents have demonstrated efficacy when given as monotherapy. At the same time, combination therapies with multiple targeted biological agents are actively being investigated. Existing clinical data and recent progress in preclinical and clinical studies of mAbs are reviewed.     

Targeting the Vascular Endothelial Growth Factor Pathway in the Treatment of Human Malignancy

Over 30 years ago, it was proposed that blocking new blood vessel formation would significantly inhibit solid tumor growth and hence, limit cancer progression. Efforts guided by this philosophy have resulted in a better understanding of the molecular basis of tumor angiogenesis. The first successful therapeutic to emerge from this work, an antibody (bevacizumab) targeting the vascular endothelial growth factor (VEGF), was recently approved for the treatment of colorectal cancer. Additional positive clinical data with bevacizumab in the treatment of breast and lung carcinoma have also been reported. These clinical achievements have validated the approach of anti-angiogenesis therapy for cancer and provided further confirmation for antibodies as a therapeutic class in this disease. Nevertheless, important unanswered questions with regard to preclinical and clinical results of VEGF pathway inhibitors remain. For example, preclinical models with a number of VEGF pathway inhibitors suggest that these agents would have significant clinical activity on their own; yet, clinical activity in patients with bevacizumab or other VEGF pathway inhibitors as monotherapy have been disappointing. Moreover, while bevacizumab is approved for the treatment of colorectal cancer in combination with cytotoxics, the mechanism for the benefits of this combination are still poorly understood, with a number of viable mechanisms under active experimental evaluation. The 3–8-month survival benefit in colorectal cancer patients treated with bevacizumab is a positive step forward. However, improving our understanding of the mechanism for these effects, as well as the mechanism underlying the inability as yet to achieve greater effects, is needed in order to follow up on the positive clinical results with improved strategies. This review discusses the experimental results surrounding the current status of our understanding of the mechanism of action of VEGF signaling inhibitors, and the potential for utilizing these agents in the future so that clinical benefits will be measured in years rather than months.     

Avastin在眼科应用的研究进展

Avastin是第一个被美国FDA批准的通过抑制血管生成发挥抗癌作用的新药,是现行几种抗血管生成制剂之一,可抑制血管内皮生长因子(VEGF)的生成,近年研究表明,该药在治疗眼部新生血管性以及渗出性病变中疗效显著,而且价格便宜,应用前景十分广阔。     

RPE-rip after intravitreal bevacizumab (Avastin) treatment for vascularised PED secondary to AMD

Background Retinal pigment epithelial (RPE)-rips in age-related macular degeneration (AMD)-associated pigment epithelial detachment (PED) occur in the natural course of the disease but also after therapy (e.g. laser photocoagulation, photodynamic therapy), possibly triggered by the specific therapy. We report here on four patients that received intravitreal bevacizumab (Avastin) for AMD-associated vascularised PED and developed RPE-rips during the follow-up. Methods The case reports of four consecutive patients that developed RPE-rips after intravitreal injection of bevacizumab at 1 mg/0.1 ml were reviewed. Results The RPE-rips occurred in all patients between 1 week and 1 month following intravitreal injection. Two of the four patients improved in vision despite the rip, but 3 months after the initial intervention, three patients suffered deterioration in visual acuity and had to be re-injected. Conclusion Improvement in visual acuity may occur following intravitreal bevacizumab despite RPE-rips, but the patients need close follow-up and eventual re-treatment in the case of deterioration. None of the authors has a propietary interest in the presented cases.     

噬菌体随机12肽库中VEGF模拟表位的筛选及初步鉴定

目的:从噬菌体随机12肽库中筛选能与抗血管内皮生长因子(VEGF)mAb阿瓦斯汀(Avastin)特异性结合的多肽.方法:用Avastin为靶分子,对噬菌体12肽库进行3轮生物淘洗,随机挑取80个克隆,ELISA法鉴定其亲和性,将亲和性高的阳性克隆进行DNA序列测定,推导与噬菌体外壳融合的12肽氨基酸序列.Fmoe固相法合成12肽,戊二醛交联12肽与血蓝蛋白(KLH),打点印迹(Dot blot)检测偶联物能否与Avastin结合.结果:ELISA显示,42个噬菌体克隆与Avastin有较强的亲和性,测序发现41个阳性克隆表达的融合12肽的序列一致,1个不同;化学合成的12肽能与Avastin特异性结合,12肽-KLH偶联物也能与Avastin特异性结合.结论:初步证明12肽模拟了VEGF部分表位.     

前房注射Bevacizumab治疗虹膜红变的疗效观察

目的:观察眼前房注射Bevacizumab(avastin)对虹膜红变的疗效及安全性。方法:5例(5眼)虹膜红变者分别继发于糖尿病视网膜病变,静脉周围炎,静脉阻塞。其中2例为玻璃体切割术后硅油填充眼,给予前房注射0.03ml(0.75mg)Bevacizumb(avastin)。其中1例联合小梁切除手术,1例联合睫状体冷凝术。结果:所有手术眼虹膜新生血管迅速消退,眼内压在联合使用抗青光眼手术或药物后降低,随访2~5mo没有虹膜红变复发,眼内压控制良好。结论:前房注射Bevacizumab(avastin)有效地减轻了虹膜红变,特别是在一些不适合玻璃体腔注射的病例,短期的研究随访证实前房注射迅速消退虹膜新生血管且无明显副作用。     

Intraocular inflammation following intravitreal injection of bevacizumab

Background Injection of drugs into the vitreous can lead to intraocular inflammation through infectious and non-infectious processes. Failure to recognize an eye with anterior chamber and vitreous cell as sterile inflammation can lead to unnecessary treatment for endophthalmitis. Methods Four cases of uveitis following intravitreal bevacizumab (Avastin) for exudative age-related macular degeneration are described followed by review of the literature. Results Four patients presented with uveitis. Two patients presented with pain and red eye associated with iritis and two patients with vitritis, several days following intravitreal injection of bevacizumab. No paracentesis was performed and no corneal epithelial defect was created. Both patients with iritis were presumed to have sterile intraocular inflammation since the anterior chamber cell was much greater than the vitreous cell and resolved with cycloplegic and topical corticosteroid therapy. The third patient presented only with vitreous cell which resolved without therapy. The fourth patient had anterior chamber cell and vitreous cell with clumps, which resolved with topical prednisolone acetate. The inflammation resolved in all cases within 1 to 2 weeks. Conclusion There are few published cases of uveitis following bevacizumab. With its rising use, it is important to be aware of its potential to be associated with intraocular inflammation. The authors have no financial interests in this study. All primary data is within the author’s full control and Graefes Archive for Clinical and Experimental Opthalmology may review it upon request.     

Platelet‐activated serum might have a therapeutic effect on damaged articular cartilage

Platelet‐activated serum (PAS) was collected from rabbits. This contains high concentrations of growth factors, including vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF)‐BB, and transforming growth factor‐beta (TGF‐β). PAS was injected into the knee joints of Japanese White rabbits subjected to anterior cruciate ligament transection (ACL‐T) to investigate its therapeutic effects on articular cartilage. The effect of Avastin (an anti‐VEGF monoclonal antibody) on VEGF expression was also investigated. The levels of VEGF, PDGF‐BB, and TGF‐β in PAS, platelet‐rich plasma (PRP) and autologous serum from untreated rabbits were analysed by enzyme‐linked immunosorbent assays. The samples (n = 24 rabbits) were divided into control (C), PAS (S), Avastin (A) and PAS + Avastin (S + A) treatment groups. Intra‐articular injections were administered weekly for 7 weeks after ACL‐T, during which the weight distribution ratios of the damaged limbs were evaluated. Histological evaluation was performed 12 weeks after ACL‐T using Mankin score. The VEGF, PDGF‐BB and TGF‐β expression levels were significantly higher (P < 0.05) in the PAS than in the PRP or autologous serum samples. The weight distribution ratios of damaged limbs improved significantly after ACL‐T in all treatment groups (P < 0.05). The proximal medial, distal medial and lateral aspects of joints in the treatment groups showed significant differences in Mankin scores compared with controls (P < 0.05). The damaged limb weight distribution ratios, Mankin scores and articular cartilage structure did not differ significantly among the three treatment groups, which all showed significant improvements in structure compared with controls. Copyright © 2017 John Wiley & Sons, Ltd.