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Silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation using gold nanoparticles
We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor...
Source: Environmental Toxicology and Pharmacology - May 11, 2017 Category: Environmental Health Source Type: research

Silencing of DNA repair sensitizes pediatric brain tumor cells to ɣ-irradiation using gold nanoparticles
We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor...
Source: Environmental Toxicology and Pharmacology - April 28, 2017 Category: Environmental Health Source Type: research

Abstract 3338: Pharmacological inhibition of MRK/ZAK kinase for the treatment of medulloblastoma
In conclusion, we have developed a new small molecule inhibitor of MRK/ZAK that radio-sensitizes medulloblastoma cells. We hypothesize that combining radio-therapy with M443 will allow us to lower the radiation dose while maintaining therapeutic efficacy, thereby minimizing radiation-induced side effects.Citation Format: Rosamaria Ruggieri, Daniel Markowitz, Caitlin Powell, Nhan Tran, Magimairajanissai Vanan, Mingzu He, Yousef Al-Abed, Marc Symons. Pharmacological inhibition of MRK/ZAK kinase for the treatment of medulloblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ruggieri, R., Markowitz, D., Powell, C., Tran, N., Vanan, M., He, M., Al-Abed, Y., Symons, M. Tags: Tumor Biology Source Type: research

NT-16 * NANOPARTICLE-MEDIATED DELIVERY OF ANTI-Ape1 siRNA SENSITIZES PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY BY INHIBITING DNA REPAIR
Pediatric brain tumors are the leading cause of death in children, and survival is frequently accompanied by one or more radiation-induced adverse developmental and psychosocial sequelae. Radiotherapy (RT) is an integral component of the treatment for medulloblastoma (MB) and the only effective adjuvant therapy for ependymoma (EP). Therefore, there is an urgent need to develop strategies to enhance the tumoricidal action of RT while sparing adjacent normal tissue. The multifunctional DNA repair protein Ape1/Ref-1 has been implicated in conferring radiation resistance in pediatric brain tumors. However, inhibiting Ape1 acti...
Source: Neuro-Oncology - November 3, 2014 Category: Cancer & Oncology Authors: Kievit, F., Stephen, Z., Wang, K., Dayringer, C., Ellenbogen, R., Silber, J., Zhang, M. Tags: NOVEL THERAPEUTICS (CLINICAL AND/OR LABORATORY RESEARCH) Source Type: research