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胰腺炎疼痛的基因治疗。

Gene therapy for pancreatitis pain.

机构信息

Department of Physiology, Chandler Medical Center, University of Kentucky, Lexington, KY 40536-0298, USA.

出版信息

Gene Ther. 2009 Apr;16(4):483-92. doi: 10.1038/gt.2009.27. Epub 2009 Mar 5.

Abstract

Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replication defective Herpes (HSV-1, DPE) viral vector construct encoding the human preproenkephalin gene (HSV-Enk), used as a molecular therapy for alleviation of pancreatitis pain, is reviewed here. The characteristics of the gene therapy treatment for inflammation and pain-related behavior in two alcoholic pancreatitis animal models is described. Significant analgesia and protection of pancreatic tissue was provided for the duration of the transgene expression (approximately 4-6 weeks). These studies establish a basis for use of HSV-based gene therapy for chronic visceral pain. Targeted enkephalin gene therapy approaches are providing clear promise for pain control. As innovative means of significantly reducing pancreatic inflammation and preserving tissue architecture, they may extend their clinical usefulness for pancreatitis and pancreatic cancer pain patients.

摘要

胰腺癌和慢性胰腺炎是与难以控制的严重疼痛相关的临床综合征。因此,有必要寻求额外的疼痛缓解疗法。长期大量饮酒是胰腺炎的主要致病因素。本文综述了一种复制缺陷型单纯疱疹病毒(HSV-1,DPE)病毒载体构建体,该构建体编码人类前脑啡肽原基因(HSV-Enk),用作减轻胰腺炎疼痛的分子治疗方法。描述了该基因治疗方法在两种酒精性胰腺炎动物模型中的炎症和疼痛相关行为的特征。在转基因表达的持续时间内(约 4-6 周),提供了显著的镇痛和胰腺组织保护。这些研究为慢性内脏疼痛的 HSV 为基础的基因治疗奠定了基础。针对内啡肽的基因治疗方法为疼痛控制提供了明确的希望。作为显著减少胰腺炎症和保持组织结构的创新手段,它们可能会扩展其在胰腺炎和胰腺癌疼痛患者中的临床应用。

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