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新型抗肿瘤药物 T11TS 治疗脑胶质瘤的研究进展。

Therapeutic intervention of glioma with the novel antineoplastic agent T11TS: the story so far.

机构信息

4D Pharma Research Ltd, Life Sciences Innovation Building, Cornhill Road, Aberdeen, AB25 2ZS, UK, Formerly: Department of Laboratory Medicine, Cellular and Molecular Immunology Lab, School of Tropical Medicine, Kolkata, West Bengal 700073, India.

Department of Zoology, Vidyasagar University, Paschim Medinipur, West Bengal, 721102, India, Formerly: Department of Laboratory Medicine, Cellular and Molecular Immunology Lab, School of Tropical Medicine, Kolkata, West Bengal 700073, India.

出版信息

Immunotherapy. 2022 Oct;14(15):1263-1277. doi: 10.2217/imt-2021-0329. Epub 2022 Aug 25.

DOI:10.2217/imt-2021-0329
PMID:36004447
Abstract

The disease relevance of novel therapeutic agent T11TS, established first by the authors' group, was shown to ameliorate experimental glioma through multimodal mechanistic activities. T11TS reverses immunosuppression in glioma, causing profound effects on immune potentiation via peripheral, intracranial and hematopoietic cells. T-cell signaling in glioma is reversed by T11TS, modulating cytokine levels and favoring apoptotic killing of glioma cells. T11TS arrests the glioma cell cycle at the G1 phase via activation of p21. VEGF downregulation hypophosphorylates the Akt pathway. T11TS hinders endothelial cell progression and metastasis by arresting matrix degradation, inhibiting the Ras-Raf and Akt-PTEN pathways and initiating inflammatory changes, causing apoptosis. T11TS is effective against human glioma. Toxicity studies demonstrate that T11TS is nontoxic. The authors' study promise translational research with T11TS.

摘要

新型治疗剂 T11TS 的疾病相关性,首先由作者团队建立,通过多种机制活动改善实验性脑胶质瘤。T11TS 逆转了脑胶质瘤的免疫抑制,通过外周、颅内和造血细胞对免疫增强产生了深远的影响。T11TS 逆转了脑胶质瘤中的 T 细胞信号,调节细胞因子水平,并有利于凋亡杀伤脑胶质瘤细胞。T11TS 通过激活 p21 将脑胶质瘤细胞周期阻滞在 G1 期。VEGF 下调使 Akt 通路去磷酸化。T11TS 通过阻滞基质降解、抑制 Ras-Raf 和 Akt-PTEN 通路以及引发炎症变化,导致细胞凋亡,从而阻碍内皮细胞的进展和转移。T11TS 对人脑胶质瘤有效。毒性研究表明 T11TS 无毒。作者的研究承诺进行 T11TS 的转化研究。

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Therapeutic intervention of glioma with the novel antineoplastic agent T11TS: the story so far.新型抗肿瘤药物 T11TS 治疗脑胶质瘤的研究进展。
Immunotherapy. 2022 Oct;14(15):1263-1277. doi: 10.2217/imt-2021-0329. Epub 2022 Aug 25.
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T11TS Treatment Augments Apoptosis of Glioma Associated Brain Endothelial Cells, Hint Toward Anti-Angiogenic Action in Glioma.T11TS治疗增强胶质瘤相关脑内皮细胞的凋亡,提示其在胶质瘤中具有抗血管生成作用。
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CD2-SLFA3/T11TS interaction facilitates immune activation and glioma regression by apoptosis.CD2-SLFA3/T11TS相互作用通过凋亡促进免疫激活和胶质瘤消退。
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T11TS inhibits Angiopoietin-1/Tie-2 signaling, EGFR activation and Raf/MEK/ERK pathway in brain endothelial cells restraining angiogenesis in glioma model.T11TS抑制脑内皮细胞中的血管生成素-1/Tie-2信号传导、表皮生长因子受体(EGFR)激活以及Raf/MEK/ERK途径,从而抑制胶质瘤模型中的血管生成。
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