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The brain tissue response to surgical injury and its possible contribution to glioma recurrence

机译:脑组织对手术损伤的反应及其对神经胶质瘤复发的可能贡献

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Surgery is the first line therapy for glioma. However, glioma recurs in 90 % of the patients in the resection margin. The impact of surgical brain injury (SBI) on glioma recurrence is largely overlooked. Herein, we review some of the mechanisms involved in tissue repair that may impact glioma recurrence at the resection margin. Many processes or molecules involved in tissue repair after brain injury are also critical for glioma growth. They include a wide array of secreted growth factors, cytokines and transcription factors including NFDeB and STAT3 which in turn activate proliferative and anti-apoptotic genes and processes such as angiogenesis and inflammation. Because some residual glioma cells always remain in the tumor resection margin, there are now compelling arguments to suggest that some aspects of the brain tissue response to SBI can also participate to glioma recurrence at the resection margin. Brain tissue response to SBI recruits angiogenesis and inflammation that precede and then follow tumor recurrence at the resection margin. The healing response to SBI is double edged, as inflammation is involved in regeneration and healing, and has both pro- and anti-tumorigenic functions. A promising therapeutic approach is to normalize and re-educate the molecular and cellular responses at the resection margin to promote anti-tumorigenic processes involved in healing while inhibiting pro-tumorigenic activities. Manipulation of the inflammatory response to SBI to prevent local recurrence could also enhance the efficacy of other therapies such as immunotherapy. However, our current knowledge is far from sufficient to achieve this goal. Acknowledging, understanding and manipulating the double-edged role played by SBI in glioma recurrence is surely challenging, but it cannot be longer delayed.
机译:手术是神经胶质瘤的一线疗法。然而,神经胶质瘤在切除边缘复发的患者占90%。手术性脑损伤(SBI)对神经胶质瘤复发的影响在很大程度上被忽略。本文中,我们回顾了一些涉及组织修复的机制,这些机制可能会影响切除边缘的神经胶质瘤复发。脑损伤后参与组织修复的许多过程或分子对于神经胶质瘤的生长也至关重要。它们包括各种分泌的生长因子,细胞因子和转录因子,包括NFDeB和STAT3,它们依次激活增殖和抗凋亡基因以及诸如血管生成和炎症的过程。由于一些残留的神经胶质瘤细胞总是保留在肿瘤切除边缘,因此有令人信服的论点表明,脑组织对SBI反应的某些方面也可以参与切除边缘的神经胶质瘤复发。脑组织对SBI的反应会在切除边缘的肿瘤复发之前引起血管新生和炎症。对SBI的治愈反应是双重的,因为炎症参与再生和治愈,并具有促癌和抗肿瘤作用。一种有前途的治疗方法是使切除边缘的分子和细胞反应正常化并对其进行再教育,以促进参与愈合的抗肿瘤发生过程,同时抑制促肿瘤发生活性。操纵对SBI的炎症反应以防止局部复发也可以增强其他疗法的有效性,例如免疫疗法。但是,我们目前的知识远远不足以实现这一目标。承认,理解和操纵SBI在神经胶质瘤复发中发挥的双重作用无疑是具有挑战性的,但不能再拖延了。

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