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NF-кB inhibition by DHMEQ: in vitro antiproliferative effects on pilocytic astrocytoma and concise review of the current literature.
Child's Nervous System ( IF 1.3 ) Pub Date : 2020-05-08 , DOI: 10.1007/s00381-020-04625-3
M F Candido 1 , G C Baldissera 2 , M Medeiros 1 , K Umezawa 3 , María Sol Brassesco 4
Affiliation  

INTRODUCTION Pilocytic astrocytoma (PA) is the most common brain tumor that affects the pediatric population. Even though PA is benign and treatment only involves surgery, recurrent or unresectable tumors require chemo- and radiotherapy. Besides BRAF, CDKN2A, or IDH mutations, the hyperactivation of the nuclear factor NF-κB contributes to tumor growth and survival. METHODS In the present study, we used publicly available data for the in silico analysis of NF-κB subunits (RELA, RELB, REL, NF-κB1, and NF-κB2) expression in PA samples. Besides, in vitro assays were performed to evaluate proliferation, migration, cell death, on the PA cell line Res286 comparing to human primary astrocytes. Sensitization to radiation therapy and temozolomide (TMZ) was also assayed. RESULTS Our results showed that all the members of the NF-kB family are upregulated in PA datasets compared to normal brain tissues. Moreover, DHMEQ treatment significantly reduced cell growth and motility, while sensitized cells to ionizing radiation and TMZ, as previously seen in high-grade gliomas. CONCLUSIONS This drug presents a potential application in clinical practice for the treatment of recurrent or inoperable PA. Moreover, its use might assist adjuvant chemotherapy and reduce irradiation doses to avoid toxicity to the surrounding tissues.

中文翻译:

DHMEQ对NF-кB的抑制作用:对毛细胞星形细胞瘤的体外抗增殖作用,并简要综述当前文献。

简介星形细胞瘤(PA)是影响儿童人群的最常见的脑肿瘤。即使PA是良性的,并且治疗仅涉及手术,但复发或不可切除的肿瘤仍需要化学疗法和放射疗法。除了BRAF,CDKN2A或IDH突变外,核因子NF-κB的过度活化也有助于肿瘤的生长和存活。方法在本研究中,我们使用公开可用的数据对PA样品中NF-κB亚基(RELA,RELB,REL,NF-κB1和NF-κB2)的表达进行了计算机分析。此外,与人原代星形胶质细胞相比,在PA细胞系Res286上进行了体外测定以评估增殖,迁移,细胞死亡。还测定了对放射疗法和替莫唑胺(TMZ)的敏感性。结果我们的结果表明,与正常脑组织相比,PA数据集中的NF-kB家族的所有成员均被上调。而且,DHMEQ治疗可显着降低细胞生长和运动能力,同时使细胞对电离辐射和TMZ敏感,如先前在高级神经胶质瘤中所见。结论该药物在临床实践中可能用于治疗复发性或无法手术的PA。此外,它的使用可能有助于辅助化疗并减少辐射剂量,以避免对周围组织的毒性。结论该药物在临床实践中可能用于治疗复发或无法手术的PA。此外,它的使用可能有助于辅助化疗并减少辐射剂量,以避免对周围组织的毒性。结论该药物在临床实践中可能用于治疗复发或无法手术的PA。此外,它的使用可能有助于辅助化疗并减少辐射剂量,以避免对周围组织的毒性。
更新日期:2020-05-08
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