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癌症治疗期间顺铂肾毒性中的自噬

Autophagy in Cisplatin Nephrotoxicity during Cancer Therapy.

作者信息

Hu Xiaoru, Ma Zhengwei, Wen Lu, Li Siyao, Dong Zheng

机构信息

Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha 410011, China.

Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.

出版信息

Cancers (Basel). 2021 Nov 10;13(22):5618. doi: 10.3390/cancers13225618.

Abstract

Cisplatin is a widely used chemotherapeutic agent but its clinical use is often limited by nephrotoxicity. Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged or dysfunctional cellular organelles for maintaining cell homeostasis. Upon cisplatin exposure, autophagy is rapidly activated in renal tubule cells to protect against acute cisplatin nephrotoxicity. Mechanistically, the protective effect is mainly related to the clearance of damaged mitochondria via mitophagy. The role and regulation of autophagy in chronic kidney problems after cisplatin treatment are currently unclear, despite the significance of research in this area. In cancers, autophagy may prevent tumorigenesis, but autophagy may reduce the efficacy of chemotherapy by protecting cancer cells. Future research should focus on developing drugs that enhance the anti-tumor effects of cisplatin while protecting kidneys during cisplatin chemotherapy.

摘要

顺铂是一种广泛使用的化疗药物,但其临床应用常常受到肾毒性的限制。自噬是一种溶酶体降解途径,可清除蛋白质聚集体以及受损或功能失调的细胞器,以维持细胞内稳态。顺铂暴露后,肾小管细胞中的自噬会迅速激活,以抵御急性顺铂肾毒性。从机制上讲,这种保护作用主要与通过线粒体自噬清除受损线粒体有关。尽管该领域的研究具有重要意义,但目前尚不清楚自噬在顺铂治疗后的慢性肾脏问题中的作用和调控机制。在癌症中,自噬可能会预防肿瘤发生,但自噬也可能通过保护癌细胞而降低化疗效果。未来的研究应集中于开发在顺铂化疗期间既能增强顺铂的抗肿瘤作用又能保护肾脏的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3d/8616020/1bfb76d712d3/cancers-13-05618-g001.jpg

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