Targeted Sensitization of Glioblastoma Multiforme Using AAAPT Technology.
Targeted Sensitization of Glioblastoma Multiforme Using AAAPT Technology.
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DOI：
10.1109/ojemb.2023.3336181
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发表时间：
2023
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
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作者：
多形性胶质母细胞瘤(GBM)是脑肿瘤中恶性程度最高的一种。目前的GBM治疗选择包括手术，然后是放射和化疗。然而，GBM可能会对治疗产生抵抗力，导致肿瘤复发。基底膜细胞通过下调细胞死亡途径(CD95)或上调细胞生存途径(NF-κB(P65))而对治疗产生抵抗力。健康组织可能会受到治疗剂量增加的影响。因此，开发一种只针对GBM肿瘤细胞的方法，从而减少非特异性摄取，从而减少副作用，是很重要的。在这里，我们展示了一种新的先验激活肿瘤凋亡通路技术(AAAPT)的应用，该技术已被用于演示靶向肿瘤增敏剂在乳腺癌、肺癌和前列腺癌中以较低剂量进行化疗的效果。与口服烷化剂替莫唑胺(TMZ)相比，AAAPT在3D PEGDA微孔中处理GBM球体后，细胞死亡增加，细胞死亡途径上调，细胞存活途径下调。替莫唑胺是治疗GBM的常用化疗药物。AAAPT增敏剂的剂量可能为提高治疗效果和减少靶外毒性提供一种有前途的方法，作为现有方法的替代，这些方法会造成显著的靶外损害。
Glioblastoma Multiforme (GBM) is the most malignant type of all brain tumors. Current GBM treatment options include surgery, followed by radiation and chemotherapy. However, GBM can become resistant to therapy, resulting in tumor recurrence. GBM cells develop resistance to treatments by either downregulating cell death pathways (CD95) or upregulating cell survival pathways (NF-κB (p65)). Healthy tissues can be affected by the increased therapeutic dose. Therefore, it is important to develop a method that can only target GBM tumor cells, thereby reducing the non-specific uptake which will reduce the side effects. Here we demonstrate an application of novel priori activation of apoptosis pathways of tumor technology (AAAPT), which has been used to demonstrate the effect of targeted tumor sensitizers to make chemotherapy work at lower doses in breast, lung and prostate cancers. Treatment of GBM spheroids with AAAPT in 3D PEGDA microwells, showed an increase in cell death, an upregulation of cell death pathways, and a downregulation of cell survival pathways, in comparison to Temozolomide (TMZ), an oral alkylating agent, which is a commonly used chemotherapy in the treatment of GBM. The dose of AAAPT sensitizers may provide a promising method to increase treatment efficacy and reduce off-target toxicity, as an alternative to existing methods which cause significant off-target damage.
影响因子：
37.3
作者：
Ametller E;García-Recio S;Costamagna D;Mayordomo C;Fernández-Nogueira P;Carbó N;Pastor-Arroyo EM;Gascón P;Almendro V
通讯作者：
Almendro V