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[哺乳动物雷帕霉素靶蛋白复合物活性及代谢变化作为实体瘤的潜在靶点]

[mTOR complex activity and metabolic changes as potential targets in solid tumors].

作者信息

Petővári Gábor

机构信息

Patológiai Tudományok Doktori Iskola, Semmelweis Egyetem, Budapest, Hungary.

出版信息

Magy Onkol. 2022 Oct 5;66(3):239-241. Epub 2022 Aug 16.

Abstract

We investigated the activity and inhibition of mTOR and other metabolic pathways with their clinical significance in human breast tumors (using ten cell lines and nearly a hundred biopsy samples).Based on our results, the metabolic and mTOR inhibitor treatments showed a moderate tumor growth inhibitory effect in the cell lines subtype independently, which indicates tumor cell and tissue adaptation. Providing human tissue samples, we found a subtype independent correlation between high mTOR activity and protein expression characterizing alternative metabolic pathways with increased expression and the poor prognosis of breast tumors. Breast tumors are characterized by metabolic heterogeneity and significant metabolic plasticity, which can be targeted by combining anti-metabolic treatments and new therapies. Concerning these, an immunohistochemical evaluation (IHC panel) can be recommended, which is suitable for both metabolic plasticity evaluation and recognition of cases that may require stricter follow-up or metabolic targeted therapy due to the expected poor prognosis.

摘要

我们研究了mTOR及其他代谢途径的活性和抑制作用及其在人乳腺肿瘤中的临床意义(使用了10种细胞系和近100份活检样本)。基于我们的结果,代谢和mTOR抑制剂治疗在细胞系亚型中分别显示出适度的肿瘤生长抑制作用,这表明肿瘤细胞和组织具有适应性。通过提供人体组织样本,我们发现mTOR高活性与表征替代代谢途径的蛋白表达之间存在亚型独立相关性,这些替代代谢途径的表达增加且乳腺肿瘤预后不良。乳腺肿瘤具有代谢异质性和显著的代谢可塑性,可通过联合抗代谢治疗和新疗法来靶向治疗。关于这些,可推荐进行免疫组织化学评估(免疫组化panel),其既适用于评估代谢可塑性,也适用于识别因预期预后不良可能需要更严格随访或代谢靶向治疗的病例。

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