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Total 78 results found since Jan 2013.

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

TROY signals through JAK1-STAT3 to promote glioblastoma cell migration and resistance.
Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and carries a discouraging prognosis. Its aggressive and highly infiltrative nature renders the current standard treatment of maximal surgical resection, radiation, and chemotherapy relatively ineffective. Identifying the signaling pathways that regulate GBM migration/invasion and resistance is required to develop more effective therapeutic regimens to treat GBM. Expression of TROY, an orphan receptor of the TNF receptor superfamily, increases with glial tumor grade, inversely correlates with patient overall survival, stimulates...
Source: Neoplasia - July 2, 2020 Category: Cancer & Oncology Authors: Ding Z, Kloss JM, Tuncali S, Tran NL, Loftus JC Tags: Neoplasia Source Type: research

Arachidonate 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid contribute to stromal aging-induced progression of pancreatic cancer Molecular Bases of Disease
In this study, we investigated whether the chronological aging of normal human fibroblasts (NHFs), a previously underappreciated area in pancreatic cancer research, influences the progression and therapeutic outcomes of PDAC. Results from experiments with murine xenografts and 2D and 3D co-cultures of NHFs and PDAC cells revealed that older NHFs stimulate proliferation of and confer resistance to radiation therapy of PDAC. MS-based metabolite analysis indicated that older NHFs have significantly increased arachidonic acid 12-lipoxygenase (ALOX12) expression and elevated levels of its mitogenic metabolite, 12-(S)-hydroxy-5,...
Source: Journal of Biological Chemistry - May 14, 2020 Category: Chemistry Authors: Ehab H. Sarsour, Jyung Mean Son, Amanda L. Kalen, Wusheng Xiao, Juan Du, Matthew S. Alexander, Brianne R. O'Leary, Joseph J. Cullen, Prabhat C. Goswami Tags: Cell Biology Source Type: research

Cancers, Vol. 12, Pages 1122: The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer
Muders Sommer Baretton Wirth Horn In search of new biomarkers suitable for the diagnosis and treatment of prostate cancer, genome-wide transcriptome sequencing was carried out with tissue specimens from 40 prostate cancer (PCa) and 8 benign prostate hyperplasia patients. We identified two intergenic long non-coding transcripts, located in close genomic proximity, which are highly expressed in PCa. Microarray studies on a larger cohort comprising 155 patients showed a profound diagnostic potential of these transcripts (AUC~0.94), which we designated as tumor associated prostate cancer increased lncRNA (TAP...
Source: Cancers - April 29, 2020 Category: Cancer & Oncology Authors: Friedrich Wiedemann Reiche Puppel Pfeifer Zipfel Binder K öhl M üller Engeland Aigner F üssel Fr öhner Peitzsch Dubrovska Rade Christ Schreiber Hackerm üller Lehmann Toma Muders Sommer Baretton Wirth Horn Tags: Article Source Type: research

The COX-2 inhibitor NS398 selectively sensitizes hypoxic HeLa cells to ionising radiation by mechanisms both dependent and independent of COX-2
Publication date: Available online 28 January 2020Source: Prostaglandins & Other Lipid MediatorsAuthor(s): Shailendra Anoopkumar-Dukie, Tom Conere, Aileen Houston, Liam King, David Christie, Catherine McDermott, Ashley AllshireAbstractIt is widely accepted that the hypoxic nature of solid tumors contribute to their resistance to radiation therapy. There is increasing evidence that cyclooxygenase-2 (COX-2) contributes to increased resistance of tumors to radiation therapy. Several studies demonstrate that combination of COX-2 selective inhibitors with radiation therapy selectively enhances radioresponsiveness of tumor cells...
Source: Prostaglandins and Other Lipid Mediators - January 28, 2020 Category: Lipidology Source Type: research

BMP Antagonists Secreted by Mesenchymal Stromal Cells Improve Colonic Organoid Formation: Application for the Treatment of Radiation-induced Injury.
This study provides evidence of the potential of ECO to limit late radiation effects on the colon and opens perspectives on combined strategies to improve their amplification abilities and therapeutic effects. PMID: 33108903 [PubMed - in process]
Source: Cell Transplantation - January 1, 2020 Category: Cytology Authors: Moussa L, Lapière A, Squiban C, Demarquay C, Milliat F, Mathieu N Tags: Cell Transplant Source Type: research

Network-based analysis of prostate cancer cell lines reveals novel marker gene candidates associated with radioresistance and patient relapse
by Michael Seifert, Claudia Peitzsch, Ielizaveta Gorodetska, Caroline B örner, Barbara Klink, Anna Dubrovska Radiation therapy is an important and effective treatment option for prostate cancer, but high-risk patients are prone to relapse due to radioresistance of cancer cells. Molecular mechanisms that contribute to radioresistance are not fully understood. Novel computational strategies are needed to i dentify radioresistance driver genes from hundreds of gene copy number alterations. We developed a network-based approach based on lasso regression in combination with network propagation for the analysis of prostate can...
Source: PLoS Computational Biology - November 3, 2019 Category: Biology Authors: Michael Seifert 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

Role of the NRP-1-mediated VEGFR2-independent pathway on radiation sensitivity of non-small cell lung cancer cells.
CONCLUSIONS: We demonstrated that when VEGFR2 was inhibited, NRP-1 appeared to regulate RAD51 expression through the VEGFR2-independent ABL-1 pathway, consequently regulating radiation sensitivity. In addition, the combined inhibition of VEGFR2 and NRP-1 appears to sensitize cancer cells to radiation. PMID: 29777301 [PubMed - indexed for MEDLINE]
Source: Clinical Lung Cancer - June 30, 2018 Category: Cancer & Oncology Authors: Hu C, Zhu P, Xia Y, Hui K, Wang M, Jiang X Tags: J Cancer Res Clin Oncol Source Type: research

Role of the NRP-1-mediated VEGFR2-independent pathway on radiation sensitivity of non-small cell lung cancer cells
ConclusionsWe demonstrated that when VEGFR2 was inhibited, NRP-1 appeared to regulate RAD51 expression through the VEGFR2-independent ABL-1 pathway, consequently regulating radiation sensitivity. In addition, the combined inhibition of VEGFR2 and NRP-1 appears to sensitize cancer cells to radiation.
Source: Journal of Cancer Research and Clinical Oncology - June 14, 2018 Category: Cancer & Oncology Source Type: research

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 B21: The selective ATR inhibitor VX-970 enhances the therapeutic effects of standards of care in glioblastoma
Glioblastoma (GBM) represents one of the most aggressive cancer types with the vast majority of patients succumbing to disease within the first five years. This dire prognosis reflects the limited efficacy of our frontline therapies which include radiation therapy and temozolomide (TMZ) chemotherapy. The cellular response to these therapies is critically mediated by DNA damage response signaling networks that are regulated by Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia And Rad3-Related Protein (ATR). Preliminary studies from our laboratory suggest the ATR inhibitor VX-970 has single agent efficacy in both...
Source: Molecular Cancer Research - April 2, 2017 Category: Cancer & Oncology Authors: Burgenske, D., Mladek, A., Sarkaria, J. Tags: Therapies Targeting Checkpoints and Mismatch Repair: Poster Presentations - Proffered Abstracts Source Type: research

Silencing BMI1 radiosensitizes human breast cancer cells by inducing DNA damage and autophagy.
Authors: Griffith J, Andrade D, Mehta M, Berry W, Benbrook DM, Aravindan N, Herman TS, Ramesh R, Munshi A Abstract Overexpression of BMI1 in human cancer cells, a member of the polycomb group of repressive complexes, correlates with advanced stage of disease, aggressive clinico-pathological behavior, poor prognosis, and resistance to radiation and chemotherapy. Studies have shown that experimental reduction of BMI1 protein level in tumor cells results in inhibition of cell proliferation, induction of apoptosis and/or senescence, and increased susceptibility to cytotoxic agents and radiation therapy. Although a role...
Source: Oncology Reports - March 6, 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