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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

Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology 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

Abstract 3303: Radioresistance in glioma stem cells driven by Rad51 dependent homologous recombination repair
We examined co-expression of stem cell markers with RAD51 protein at whole population level using western blotting, immunocytochemistry and RT-PCR in cultured cells and immunohistochemistry in tumor material. Single cell expression was analysed using the Fluidigm C1 platform. We examined the effect of two specific inhibitors of RAD51 (B02, RI-1) on the same cell pairs in vitro and used the γH2AX assay to assess differences in repair kinetics. We used subcutaneous models of glioma to evaluate the effect of one of these agents (RI-1) on tumour growth delay with and without fractionated radiation doses in vivo.Primary glioma...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: King, H., Payne, H., Brend, T., Patel, A., Wright, A., Englu, T., Stead, L., Wurdak, H., Short, S. C. Tags: Tumor Biology Source Type: research

Abstract 3326: Targeting lysophosphatidic acid receptor 1 (LPAR1) radiosensitizes poor prognosis cancers
Therapies for poor prognosis cancers, such as lung cancer and glioblastoma, are limited due to radio-resistance and tumor recurrence. Development of molecular targeted therapy can serve as a potential method to improve the efficacy of radiation therapy in both glioblastoma and lung cancer. Ionizing radiation (IR) can activate a series of pro-survival pathways which contributes to the pathogenesis of cancer cells. Among these pathways, cytosolic phospholipase A2 (cPLA2) is an integral component which is activated by IR. Following activation, cPLA2 cleaves arachidonic acid to form phosphatidylcholine (PC) and yields lysophos...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Khudanyan, A., Dadey, D., Karvas, R., Kotipatruni, R., Hallahan, D., Thotala, D. Tags: Tumor Biology Source Type: research

Rt-40 * the down-regulation of h-ferritin as an adjuvant therapy in human glioma
This study supports the potential of H-ferritin siRNA as an adjuvant therapy in glioma treatment.
Source: Neuro-Oncology - November 3, 2014 Category: Cancer & Oncology Authors: Pang, M., Liu, X., Madhankumar, A. B., Slagle-Webb, B., Connor, J. Tags: RADIATION THERAPY (CLINICAL AND/OR LABORATORY RESEARCH) Source Type: research

Abstract 3945: Inhibition of MMP2 expression enhances the efficacy of radiation therapy for a murine astrocytoma
This study provides a new treatment option for treating invasive brain tumors. (This study was supported by NHRI-EX103-10132BI and NSC 102-2314-B-007-003-MY3 grants) Citation Format: Ching-Fang Yu, Ying-Chieh Yang, Ji-Hong Hong, Chi-Shiun Chiang. Inhibition of MMP2 expression enhances the efficacy of radiation therapy for a murine astrocytoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3945. doi:10.1158/1538-7445.AM2014-3945
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Yu, C.-F., Yang, Y.-C., Hong, J.-H., Chiang, C.-S. Tags: Tumor Biology Source Type: research

Abstract 1031: Blockade of radiation-induced neuropilin-1 in glioblastoma cells impairs migration of endothelial cells
In this study, we show that the IR-induced NRP-1 role in the VEGFR-2 mediated signaling cascade promotes migration of endothelial cells. We observed that IR (8Gy) significantly elevated levels of VEGF and NRP-1 expression in 4910 and 5310 human GBM xenograft cells. Endothelial cells cultured on tumor- conditioned media from IR induced xenograft cells showed a significant increase in migration of endothelial cells; whereas, conditioned medium (CM) from NRP-1 knockdown xenograft cells inhibited IR-induced migration effects in endothelial cells. Further, CM from NRP-1 inhibited cells downregulated IR-induced expression of VEG...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Maddirela, D. R., Kesanakurti, D., Gogineni, V. R., Chetty, C. Tags: Tumor Biology Source Type: research

Role of moesin in hyaluronan induced cell migration in glioblastoma multiforme
Conclusions: Our results suggest that development of inhibitors which interfere with CD44-moesin interactions may open a new avenue in the future to mitigate cellular migration in gliomas.
Source: Molecular Cancer - July 15, 2013 Category: Cancer & Oncology Authors: Leroi DeSouzaAjay MattaZia KarimJoydeep MukherjeeX WangOlga KrakovskaGelareh ZadehAbhijit GuhaKW Siu Source Type: research