TP53 缺失通过上调 NF-κB-IFN-β-MHC-Ia 信号促进骨肉瘤对 NK 细胞的抵抗
TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.
TP53失活是骨肉瘤(OS)发生中的关键事件,也是其侵袭性的基础,但其在肿瘤-免疫相互作用中的作用仍知之甚少。
英文原题:Perioperative local anesthetics as modulators of tumor progression and metastasis.
Perioperative local anesthetics as modulators of tumor progression and metastasis.
肿瘤外科手术仍是实体恶性肿瘤治疗的基石;然而,围手术期因素日益成为肿瘤复发和转移的关键调控因素。
癌症手术仍是实体恶性肿瘤治疗的基石,但围手术期因素日益被认为是调节肿瘤复发和转移的重要因素。越来越多证据表明,麻醉技术和镇痛策略可深刻影响肿瘤生物学、免疫功能和长期肿瘤学结局。尤其是阿片类药物,尽管对围手术期镇痛不可或缺,却与肿瘤进展增强有关,可能通过直接刺激致癌信号通路和抑制抗肿瘤免疫发挥作用。相比之下,区域麻醉和局部麻醉药因具有减少阿片用量的作用及潜在抗肿瘤效应而受到关注。局部麻醉药除提供有效镇痛外,还可通过抑制电压门控钠通道、减弱炎症信号、抑制 EGFR 驱动的致癌通路、限制间充质干细胞介导的肿瘤支持,以及维持或增强抗肿瘤免疫应答等多种机制影响肿瘤进展。本综述总结当前临床前和临床证据,阐明局部麻醉药及区域麻醉调节肿瘤生长、转移和免疫监视的机制。理解这些围手术期相互作用,为将麻醉策略纳入综合肿瘤照护提供了有力依据,旨在改善癌症患者的长期结局。
Cancer surgery remains a cornerstone of treatment for solid malignancies; however, perioperative factors increasingly emerge as critical modulators of tumor recurrence and metastasis. Accumulating evidence suggests that anesthesia techniques and analgesic strategies can profoundly influence tumor biology, immune competence, and long-term oncologic outcomes. In particular, opioids-while indispensable for perioperative analgesia-have been associated with enhanced tumor progression through direct stimulation of oncogenic signaling pathways and suppression of antitumor immunity. In contrast, regional anesthesia and local anesthetics have gained attention for their opioid-sparing properties and potential antitumor effects. Beyond effective analgesia, local anesthetics exert multifaceted actions on tumor progression by inhibiting voltage-gated sodium channels, attenuating inflammatory signaling, suppressing EGFR-driven oncogenic pathways, restraining mesenchymal stem cell-mediated tumor support, and preserving or enhancing antitumor immune responses. This review summarizes current preclinical and clinical evidence elucidating the mechanisms by which local anesthetics and regional anesthesia modulate tumor growth, metastasis, and immune surveillance. Understanding these perioperative interactions provides a compelling rationale for integrating anesthetic strategies into comprehensive oncologic care aimed at improving long-term cancer outcomes.
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