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质子泵抑制剂在神经胶质瘤中显示出抗肿瘤潜力。

Proton pump inhibitors display anti-tumour potential in glioma.

机构信息

Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin 130021, China.

NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, Jilin 130021, China.

出版信息

Cell Prolif. 2023 Jul;56(7):e13321. doi: 10.1111/cpr.13321. Epub 2022 Aug 12.

Abstract

OBJECTIVES

Glioma is one of the most aggressive brain tumours with poor overall survival despite advanced technology in surgical resection, chemotherapy and radiation. Progression and recurrence are the hinge causes of low survival. Our aim is to explain the concrete mechanism in the proliferation and progression of tumours based on tumour microenvironment (TME). The main purpose is to illustrate the mechanism of proton pump inhibitors (PPIs) in affecting acidity, hypoxia, oxidative stress, inflammatory response and autophagy based on the TME to induce apoptosis and enhance the sensitivity of chemoradiotherapy.

FINDINGS

TME is the main medium for tumour growth and progression. Acidity, hypoxia, inflammatory response, autophagy, angiogenesis and so on are the main causes of tumour progress. PPIs, as a common clinical drug to inhibit gastric acid secretion, have the advantages of fast onset, long action time and small adverse reactions. Nowadays, several kinds of literature highlight the potential of PPIs in inhibiting tumour progression. However, long-term use of PPIs alone also has obvious side effects. Therefore, till now, how to apply PPIs to promote the effect of radio-chemotherapy and find the concrete dose and concentration of combined use are novel challenges.

CONCLUSIONS

PPIs display the potential in enhancing the sensitivity of chemoradiotherapy to defend against glioma based on TME. In the clinic, it is also necessary to explore specific concentrations and dosages in synthetic applications.

摘要

目的

尽管在手术切除、化疗和放疗方面拥有先进技术,神经胶质瘤仍是一种侵袭性最强的脑肿瘤,整体存活率仍较差。进展和复发是低存活率的关键原因。我们旨在基于肿瘤微环境(TME)解释肿瘤增殖和进展的具体机制。主要目的是说明质子泵抑制剂(PPIs)通过影响酸度、缺氧、氧化应激、炎症反应和自噬,基于 TME 诱导细胞凋亡和增强放化疗敏感性的作用机制。

发现

TME 是肿瘤生长和进展的主要介质。酸度、缺氧、炎症反应、自噬、血管生成等是肿瘤进展的主要原因。PPIs 作为一种抑制胃酸分泌的常用临床药物,具有起效快、作用时间长、不良反应小等优点。目前,有多种文献强调了 PPI 抑制肿瘤进展的潜力。然而,长期单独使用 PPI 也有明显的副作用。因此,到目前为止,如何应用 PPI 来提高放化疗的效果,寻找具体的联合使用剂量和浓度,仍是新的挑战。

结论

PPIs 显示了基于 TME 增强放化疗敏感性以抵抗神经胶质瘤的潜力。在临床上,也需要探索特定的浓度和剂量在综合应用中的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d96/10334276/582d74f020db/CPR-56-e13321-g004.jpg

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