■精氨酸剥夺疗法(ADT)通过减少外周血精氨酸来阻碍神经胶质瘤细胞获得营养,在各种研究中表现出巨大的功效,这表明它是一种潜在的有希望的治疗神经胶质瘤的方法。本系统综述旨在探讨ADT对胶质瘤的作用机制。基于现有研究的治疗效果,和可能的联合疗法。
■我们对PubMed,根据PRISMA指南,ScienceDirect和WebofScience数据库,寻找ADT在胶质瘤中的疗效的文章。
■我们在786个搜索结果中确定了17个研究,其中ADT治疗主要基于无精氨酸条件,精氨酸脱亚胺酶和精氨酸酶,包括三项已完成的临床试验。ADT治疗已在体内和体外显示出有希望的结果,其安全性在临床试验中得到证实。在治疗的早期阶段,胶质母细胞瘤(GBM)细胞发展应激和自噬的保护机制,最终演变成胱天蛋白酶依赖性细胞凋亡或衰老,分别。精氨酸耗竭也改变了免疫抑制微环境,例如小胶质细胞转化为促炎表型和T细胞的活化。因此,ADT疗法在存在多种机制的情况下证明了神经胶质瘤的杀伤作用。结合各种常规疗法和研究药物,如放疗,替莫唑胺(TMZ),细胞周期蛋白依赖性激酶抑制剂(CDK)抑制剂和自噬诱导剂,ADT疗法已被证明更有效。然而,由于ASS1而不是干细胞的再表达而导致的耐药现象仍有待研究。
■尽管文献研究很少,现有数据证明了精氨酸剥夺疗法对神经胶质瘤的治疗潜力,并鼓励进一步研究,特别是对其联合疗法的探索,以及我们对ADT从其他肿瘤到神经胶质瘤的作用和机制的了解。
UNASSIGNED: Arginine deprivation therapy (ADT) hinders glioma cells\' access to nutrients by reducing peripheral blood arginine, showing great efficacy in various studies, which suggests it as a potentially promising treatment for glioma. The aim of this systematic
review was to explore the mechanism of ADT for gliomas, the therapeutic effect based on existing research, and possible combination therapies.
UNASSIGNED: We performed a systematic literature
review of PubMed, ScienceDirect and Web of Science databases according to PRISMA guidelines, searching for articles on the efficacy of ADT in glioma.
UNASSIGNED: We identified 17 studies among 786 search results, among which ADT therapy mainly based on Arginine free condition, Arginine Deiminase and Arginase, including three completed clinical trials. ADT therapy has shown promising results in vivo and in vitro, with its safety confirmed in clinical trials. In the early phase of treatment, glioblastoma (GBM) cells develop protective mechanisms of stress and autophagy, which eventually evolve into caspase dependent apoptosis or senescence, respectively. The immunosuppressive microenvironment is also altered by arginine depletion, such as the transformation of microglia into a pro-inflammatory phenotype and the activation of T-cells. Thus, ADT therapy demonstrates glioma-killing effect in the presence of a combination of mechanisms. In combination with various conventional therapies and investigational drugs such as radiotherapy, temozolomide (TMZ), cyclin-dependent kinase inhibitors (CDK) inhibitors and autophagy inducers, ADT therapy has been shown to be more effective. However, the phenomenon of drug resistance due to re-expression of ASS1 rather than stem cell remains to be investigated.
UNASSIGNED: Despite the paucity of studies in the literature, the available data demonstrate the therapeutic potential of arginine deprivation therapy for glioma and encourage further research, especially the exploration of its combination therapies and the extrapolation of what we know about the effects and mechanisms of ADT from other tumors to glioma.