Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 9 via Balzaretti, 20133, Milan, Italy.
Adv Exp Med Biol. 2013;986:13-30. doi: 10.1007/978-94-007-4719-7_2.
Purines and pyrimidines are fundamental signaling molecules in controlling the survival and proliferation of astrocytes, as well as in mediating cell-to-cell communication between glial cells and neurons in the healthy brain. The malignant transformation of astrocytes towards progressively more aggressive brain tumors (from astrocytoma to anaplastic glioblastoma) leads to modifications in both the survival and cell death pathways which overall confer a growth advantage to malignant cells and resistance to many cytotoxic stimuli. It has been demonstrated, however, that, in astrocytomas, several purinergic (in particular adenosinergic) pathways controlling cell survival and death are still effective and, in some cases, even enhanced, providing invaluable targets for purine-based chemotherapy, that still represents an appropriate pharmacological approach to brain tumors. In this chapter, the current knowledge on both receptor-mediated and receptor-independent adenosine pathways in astrocytomas will be reviewed, with a particular emphasis on the most promising targets which could be translated from in vitro studies to in vivo pharmacology.
嘌呤和嘧啶是控制星形胶质细胞存活和增殖的基本信号分子，也是在健康大脑中神经胶质细胞和神经元之间进行细胞间通讯的介质。星形胶质细胞向越来越具有侵袭性的脑肿瘤（从星形细胞瘤到间变性神经胶质瘤）的恶性转化导致存活和细胞死亡途径的改变，这些改变总体上赋予恶性细胞生长优势和对许多细胞毒性刺激的抗性。然而，已经证明，在星形细胞瘤中，控制细胞存活和死亡的几种嘌呤能（特别是腺苷能）途径仍然有效，在某些情况下甚至增强，为基于嘌呤的化疗提供了宝贵的靶点，这仍然是一种针对脑肿瘤的合适的药理学方法。在这一章中，将回顾星形细胞瘤中受体介导和受体非依赖的腺苷途径的最新知识，特别强调最有前途的靶点，这些靶点可以从体外研究转化为体内药理学。
