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Gene therapy for ulcerations of the gastrointestinal tract.

机译:胃肠道溃疡的基因治疗。

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摘要

Ulcer healing requires cell proliferation, migration (re-epithelialization) and angiogenesis - all ultimately leading to scar formation. All these processes are controlled by growth factors. Gene therapy has shown only limited promise for effective treatment of congenital diseases. This is due to time-limited gene expression, adverse immune responses and/or complications related to viral vectors. However, short- term expression of genes encoding angiogenic growth factors appears to be ideal for treatment of chronic ulcers and wounds, which require only limited temporal gene overexpression. Since angiogenesis is essential for wound and ulcer healing, the genes encoding proangiogenic growth factors have been utilized for treatment of experimental esophageal, gastric and duodenal ulcers. These studies demonstrated that a single local injection of plasmids expressing vascular endothelial growth factor and angiopoietin-1 dramatically accelerates the healing of duodenal, gastric and esophageal gastric ulcers. Preliminary data indicate that such treatment can also be effective for the healing of experimental colitis.
机译:溃疡愈合需要细胞增殖,迁移(重新上皮化)和血管生成-所有这些最终都会导致疤痕形成。所有这些过程均受生长因子控制。基因疗法显示出有效治疗先天性疾病的前景有限。这是由于时间有限的基因表达,不良的免疫反应和/或与病毒载体有关的并发症。然而,编码血管生成生长因子的基因的短期表达似乎是治疗慢性溃疡和伤口的理想选择,这些溃疡和伤口仅需要有限的暂时性基因过表达。由于血管生成对于伤口和溃疡的愈合必不可少,因此编码促血管生成生长因子的基因已被用于治疗实验性食道,胃和十二指肠溃疡。这些研究表明,单次局部注射表达血管内皮生长因子和血管生成素-1的质粒可显着加速十二指肠,胃和食道胃溃疡的愈合。初步数据表明,这种治疗也可以有效治愈实验性结肠炎。

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