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首页> 外文期刊>Biochimica et biophysica acta. Reviews on cancer >Latest perspectives on glucocorticoid-induced apoptosis and resistance in lymphoid malignancies
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Latest perspectives on glucocorticoid-induced apoptosis and resistance in lymphoid malignancies

机译：关于糖皮质激素诱导的凋亡和淋巴恶性肿瘤抗性的最新视角

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摘要

Glucocorticoids are essential drugs in the treatment protocols of lymphoid malignancies. These steroidal hormones trigger apoptosis of the malignant cells by binding to the glucocorticoid receptor (GR), which is a member of the nuclear receptor superfamily. Long term glucocorticoid treatment is limited by two major problems: the development of glucocorticoid-related side effects, which hampers patient quality of life, and the emergence of glucocorticoid resistance, which is a gradual process that is inevitable in many patients. This emphasizes the need to reevaluate and optimize the widespread use of glucocorticoids in lymphoid malignancies. To achieve this goal, a deep understanding of the mechanisms governing glucocorticoid responsiveness is required, yet, a recent comprehensive overview is currently lacking. In this review, we examine how glucocorticoids mediate apoptosis by detailing GR's genomic and non-genomic action mechanisms in lymphoid malignancies. We continue with a discussion of the glucocorticoid-related problems and how these are intertwined with one another. We further zoom in on glucocorticoid resistance by critically analyzing the plethora of proposed mechanisms and highlighting therapeutic opportunities that emerge from these studies. In conclusion, early detection of glucocorticoid resistance in patients remains an important challenge as this would result in a timelier treatment reorientation and reduced glucocorticoid-instigated side effects.
机译：糖皮质激素是淋巴恶性肿瘤治疗方案中的必需药物。这些甾体激素通过与糖皮质激素受体（GR）结合而引发恶性细胞的凋亡，这是核受体超家族的成员。长期糖皮质激素治疗受到两个主要问题的限制：糖皮质激素相关副作用的发展，妨碍了患者的生命质量，以及糖皮质激素抵抗的出现，这是许多患者在不可避免的过程中。这强调需要重新评估和优化糖皮质激素在淋巴恶性肿瘤中的广泛使用。为了实现这一目标，需要深入了解控制糖皮质激素响应能力的机制，但目前缺乏最近的全面概述。在本综述中，我们研究糖皮质激素如何通过详细说明GR的基因组和非基因组作用机制来介导细胞凋亡。我们继续讨论与糖皮质激素相关的问题以及这些问题的互相交织在一起。我们进一步通过批判性拟议机制分析了含有促进机制的血糖皮质激素抵抗力，并突出了从这些研究中出现的治疗机会。总之，患者糖皮质激素抗性的早期检测仍然是一个重要的挑战，因为这会导致速度治疗重新定位和降低糖皮质激素的副作用。

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