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通过使用目前市售的高亲和力抗精神病药物抑制强效血清素受体-7,辅助胶质母细胞瘤的化学疗法。

Glioblastoma chemotherapy adjunct via potent serotonin receptor-7 inhibition using currently marketed high-affinity antipsychotic medicines.

机构信息

Department of Psychiatry, University of Vermont, Burlington, VT, USA.

出版信息

Br J Pharmacol. 2010 Oct;161(3):481-7. doi: 10.1111/j.1476-5381.2010.00923.x.

Abstract

Glioblastoma treatment as now constituted offers increased survival measured in months over untreated patients. Because glioblastomas are active in synthesizing a bewildering variety of growth factors, a systematic approach to inhibiting these is being undertaken as treatment adjunct. The serotonin 7 receptor is commonly overexpressed in glioblastoma. Research documentation showing agonists at serotonin receptor 7 cause increased extracellular regulated kinase 1/2 activation, increased interleukin-6 synthesis, increased signal transducer and activator of transcription-3 activation, increased resistance to apoptosis and other growth enhancing changes in glioblastoma is reviewed in this paper. Because three drugs in wide use to treat thought disorders - paliperidone, pimozide and risperidone - are also potent and well-tolerated inhibitors at serotonin receptor 7, these drugs should be studied for growth factor deprivation in an adjunctive role in glioblastoma treatment.

摘要

胶质母细胞瘤的治疗方法现在已经可以提高患者的生存率,与未接受治疗的患者相比,患者的生存时间可以延长几个月。由于胶质母细胞瘤在合成各种令人困惑的生长因子方面非常活跃,因此正在作为治疗辅助手段对这些因子进行系统抑制。5-羟色胺 7 受体在胶质母细胞瘤中普遍过表达。本文综述了研究文献,证明 5-羟色胺受体 7 的激动剂会导致细胞外调节激酶 1/2 的激活增加、白细胞介素-6 合成增加、信号转导和转录激活因子 3 的激活增加、抗凋亡能力增加以及胶质母细胞瘤的其他生长增强变化。由于三种广泛用于治疗精神障碍的药物——帕利哌酮、匹莫齐特和利培酮——也是 5-羟色胺受体 7 的有效且耐受性良好的抑制剂,因此应该研究这些药物在胶质母细胞瘤治疗中的辅助作用,以剥夺生长因子。

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