The growth and vascularization of many tumours has been reported to be associated with the overexpression of the potent mitogenic and angiogenic polypeptide basic fibroblast growth factor (beta-FGF). Consequently, it has been proposed that inhibition of beta-FGF action would prevent the growth of beta-FGF-dependent tumours. In this study, cell culture assays were established to assess the ability of mouse monoclonal DG-2 anti-beta-FGF antibodies to inhibit the mitogenic action of beta-FGF in vitro. Following in vitro characterisation, the monoclonal DG-2 antibodies were used to evaluate the role of beta-FGF in promoting the vascularization and growth of rat chondrosarcoma tumours. The effect the monoclonal anti-B-FGF antibodies had on tumour vascularization and growth in vivo were monitored using a 99m Technetium (99mTc)-labelled red blood cell procedure. The characterization studies confirmed that the DG-2 monoclonal antibody recognised beta-FGF and inhibited its mitogenic action on mouse Balb/c cells and bovine endothelial cells in vitro. When examined in vivo, intralesional administration of mouse monoclonal DG-2 antibody significantly inhibited rat chondrosarcoma growth and vascularization. However when the monoclonal DG-2 antibody was administered intraperitoneally or intravenously no attenuation of rat chondrosarcoma tumour vascularization or growth was observed. This report has confirmed the potential effectiveness of anti-beta-FGF antibodies in the regulation of tumour growth. It has also demonstrated that further studies on the pharmacokinetics of administered antibodies and their mode of delivery are required so that the effectiveness of such anti-growth factor immunotherapy can be assured.

译文

据报道,许多肿瘤的生长和血管化与有效的有丝分裂和血管生成多肽碱性成纤维细胞生长因子 (β-FGF) 的过表达有关。因此,已经提出抑制 β-FGF作用将阻止 β-FGF依赖性肿瘤的生长。在这项研究中,建立了细胞培养试验以评估小鼠单克隆DG-2抗 β-FGF抗体在体外抑制 β-FGF的促有丝分裂作用的能力。在体外表征之后,使用单克隆DG-2抗体来评估 β-FGF在促进大鼠软骨肉瘤肿瘤的血管化和生长中的作用。使用99m tech (99mTc) 标记的红细胞程序监测单克隆抗B-FGF抗体对体内肿瘤血管化和生长的影响。表征研究证实,DG-2单克隆抗体在体外识别 β-FGF并抑制其对小鼠Balb/c细胞和牛内皮细胞的促有丝分裂作用。当在体内检查时,小鼠单克隆DG-2抗体的病灶内给药可显着抑制大鼠软骨肉瘤的生长和血管形成。然而,当腹膜内或静脉内施用单克隆DG-2抗体时,未观察到大鼠软骨肉瘤肿瘤血管化或生长的减弱。该报告证实了抗 β-FGF抗体在调节肿瘤生长中的潜在有效性。还表明,需要对所给药抗体的药代动力学及其传递方式进行进一步研究,以便可以确保这种抗生长因子免疫疗法的有效性。

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