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寻找治疗脑胶质瘤的新型小分子抗侵袭化合物。

Identifying new small molecule anti-invasive compounds for glioma treatment.

机构信息

Wallace H. Coulter Department of Biomedical Engineering; Georgia Institute of Technology; Atlanta, GA, USA.

出版信息

Cell Cycle. 2013 Jul 15;12(14):2200-9. doi: 10.4161/cc.25334.

Abstract

Glioblastoma is a disease with poor survival rates after diagnosis. Treatment of the disease involves debulking of the tumor, which is limited by the degree of invasiveness of the disease. Therefore, a treatment to halt the invasion of glioma is desirable for clinical implementation. There have been several candidate compounds targeting specific aspects of invasion, including cell adhesions, matrix degradation, and cytoskeletal rearrangement, but they have failed clinically for a variety of reasons. New targets against glioma invasion include upstream mediators of these classical targets in an effort to better inhibit invasion with more specificity for cancer. Included in these treatments is a new class of compounds inhibiting the generation of reactive oxygen species by targeting the NADPH oxidases. These compounds stand to inhibit multiple pathways, including nuclear factor kappa B and Akt. By conducting a screen of compounds thought to inhibit these pathways, a new compound to halt invasion was found that may have a beneficial effect against glioma, based on recent publications. Further, there are still limitations to the treatment of glioblastoma regardless of the discovery of new targets and compounds that should be addressed to better the therapies against this deadly cancer.

摘要

胶质母细胞瘤是一种诊断后生存率较低的疾病。该疾病的治疗包括肿瘤的减瘤,这受到疾病侵袭程度的限制。因此,对于临床实施来说,一种能够阻止神经胶质瘤侵袭的治疗方法是理想的。已经有几种针对侵袭特定方面的候选化合物,包括细胞黏附、基质降解和细胞骨架重排,但由于各种原因,它们在临床上都失败了。针对神经胶质瘤侵袭的新靶点包括这些经典靶点的上游介质,以更特异性地抑制侵袭,具有更高的特异性。这些治疗方法包括一类新的化合物,通过靶向 NADPH 氧化酶来抑制活性氧的产生。这些化合物有望抑制多种途径,包括核因子 kappa B 和 Akt。通过对被认为能抑制这些途径的化合物进行筛选,发现了一种新的能阻止侵袭的化合物,根据最近的出版物,它可能对神经胶质瘤有有益的作用。此外,无论发现新的靶点和化合物如何,胶质母细胞瘤的治疗仍然存在限制,这些限制应该得到解决,以改善针对这种致命癌症的治疗方法。

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