Attenuation of soft-tissue sarcomas resistance to the cytotoxic action of TNF-α by restoring p53 function

通过恢复 p53 功能减弱软组织肉瘤对 TNF-α 细胞毒作用的抵抗力

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作者:Jane Muret, Meriem Hasmim, Izabela Stasik, Abdelali Jalil, Aude Mallavialle, Arash Nanbakhsh, Ludovic Lacroix, Katy Billot, Véronique Baud, Jérome Thiery, Philippe Vielh, Philippe Terrier, Joelle Wiels, Lyubomir Vassilev, Axel Lecesne, Sylvie Bonvalot, Salem Chouaib

Background

Isolated limb perfusion with TNF-α and melphalan is used with remarkable efficiency to treat unresectable limb sarcomas. Here we tested the ability of TNF-α to directly induce apoptosis of sarcoma cells. In addition, we investigated the impact of p53 in the regulation of such effect. Methodology/principal findings: We first analysed the ability of TNF-α to induce apoptosis in freshly isolated tumour cells. For this

Significance

More effective therapeutic approaches are critically needed for the treatment of unresectable limb sarcomas. Our results show that restoring p53 activity in sarcoma cells correlated with increased sensitivity to TNF-α, suggesting that this strategy may be an important determinant of TNF-α-based sarcomas treatment.

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