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Research progress in the radioprotective effect of the canonical Wnt pathway

机译:经典Wnt途径的辐射防护作用研究进展

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摘要

Irradiation from diverse sources is ubiquitous and closely associated with human activities. Radiation therapy (RT), an important component of multiple radiation origins, is a common therapeutic modality for cancer. More importantly, RT provides significant contribution to oncotherapy by killing tumor cells. However, during the course of therapy, irradiation of normal tissues can result in a wide range of side effects, including self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Although numerous promising radioprotective agents have emerged, only a few have successfully entered the market because of various limitations. At present, the widely accepted hypothesis for protection against radiation-caused injury involves the Wnt canonical pathway. Activating the Wnt/β-catenin signaling pathway may protect the salivary gland, oral mucosa, and gastrointestinal epithelium from radiation damage. The underlying mechanisms include inhibiting apoptosis and preserving normal tissue functions. However, aberrant Wnt signaling underlies a wide range of pathologies in humans, and its various components contribute to cancer. Moreover, studies have suggested that Wnt/β-catenin signaling may lead to radioresistance of cancer stem cell. These facts markedly complicate any definition of the exact function of the Wnt pathway.
机译:来自各种来源的辐射无处不在,并且与人类活动密切相关。放射治疗(RT)是多种放射起源的重要组成部分,是癌症的常见治疗手段。更重要的是,RT通过杀死肿瘤细胞为肿瘤治疗做出了重大贡献。但是,在治疗过程中,正常组织的照射会导致广泛的副作用,包括自我限制的急性毒性,轻度的慢性症状或严重的器官功能障碍。尽管出现了许多有希望的辐射防护剂,但由于种种限制,只有少数成功地进入了市场。当前,针对辐射致伤害的保护的广为接受的假设涉及Wnt经典途径。激活Wnt /β-catenin信号传导途径可以保护唾液腺,口腔粘膜和胃肠道上皮免受辐射损害。潜在的机制包括抑制细胞凋亡和保持正常的组织功能。但是,异常的Wnt信号传导是人类多种病理的基础,其各种成分也会导致癌症。此外,研究表明Wnt /β-catenin信号传导可能导致癌症干细胞的放射抗性。这些事实使Wnt通路确切功能的任何定义都变得复杂。

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