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Cancers, Vol. 12, Pages 3260: Improving Radiation Response in Glioblastoma Using ECO/siRNA Nanoparticles Targeting DNA Damage Repair
Camphausen Radiation therapy is a mainstay in the standard of care for glioblastoma (GBM), thus inhibiting the DNA damage response (DDR) is a major strategy to improve radiation response and therapeutic outcomes. Small interfering RNA (siRNA) therapy holds immeasurable potential for the treatment of GBM, however delivery of the siRNA payload remains the largest obstacle for clinical implementation. Here we demonstrate the effectiveness of the novel nanomaterial, ECO (1-aminoethylimino[bis(N-oleoylcysteinylaminoethyl) propionamide]), to deliver siRNA targeting DDR proteins ataxia telangiectasia mutated and DNA-dependen...
Source: Cancers - November 4, 2020 Category: Cancer & Oncology Authors: Jennifer A. Lee Nadia Ayat Zhanhu Sun Philip J. Tofilon Zheng-Rong Lu Kevin Camphausen Tags: Article Source Type: research

Silencing of ATM expression by siRNA technique contributes to glioma stem cell radiosensitivity in vitro and in vivo.
In conclusion, silencing of ATM via the siRNA technique improved radiosensitivity of GSCs both in vitro and in vivo. PMID: 28560406 [PubMed - as supplied by publisher]
Source: Oncology Reports - June 2, 2017 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Abstract B42: Silencing of DNA repair proteins with ECO/siRNA nanoparticles for the enhancement of radiation response in glioblastoma
In this study we investigate the use of these nanoparticles to deliver siRNA to inhibit ATM and DNApk activity and enhance radiation response in both glioma and glioma stem cell lines.Established glioma (U251) and glioma stem cell (NSC11) lines were used to evaluate the effectiveness of ECO nanoparticle delivery of siRNA in vitro . Cellular uptake of ECO nanoparticles loaded with fluorescent siRNA was assessed using flow cytometry and fluorescent microscopy, demonstrating the rapid uptake of ECO/siRNA nanoparticles in comparison to commercially available transfection agents. Protein and mRNA analyses revealed the kinetics ...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Jennifer A. Lee, Nadia Ayat, Anita Tandle, Zheng-Rong Lu, Kevin Camphausen Tags: Drug Delivery and Nanomedicine Source Type: research

Silencing of ataxia-telangiectasia mutated by siRNA enhances the in vitro and in vivo radiosensitivity of glioma.
In conclusion, silencing of ATM via the siRNA technique could improve the in vitro and in vivo radiosensitivity of glioma cells. PMID: 27108486 [PubMed - as supplied by publisher]
Source: Oncology Reports - April 27, 2016 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

MutL homolog 1 contributes to temozolomide-induced autophagy via ataxia-telangiectasia mutated in glioma.
Abstract In the present study, mutL homolog 1 (MLH1) small interfering (si)RNA, KU‑55933, an ataxia‑telangiectasia mutated (ATM) inhibitor, and compound C, an adenosine monophosphate‑activated protein kinase (AMPK) inhibitor, were used to investigate the mechanisms underlying temozolomide (TMZ)‑induced autophagy and to determine the role of MLH1 and ATM in autophagy. MLH1 siRNA and KU‑55933 inhibited the phosphorylation of AMPK and ULK1 and reduced the levels of autophagy. MLH1 siRNA inhibited the phosphorylation of ATM and attenuated TMZ cytotoxicity, whereas the inhibition of ATM‑AMPK augmented TM...
Source: Molecular Medicine - February 3, 2015 Category: Molecular Biology Authors: Zou Y, Wang Q, Wang W Tags: Mol Med Rep Source Type: research