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Condition: Ataxia
Cancer: Cancer
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Total 26 results found since Jan 2013.
ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage
In this study, we investigated the expression, function, and potential of ATR as a therapeutic target in liposarcoma. Activation and expression of ATR in liposarcoma was analyzed by immunohistochemistry, which was further explored for correlation with patient clinical characteristics. ATR-specific siRNA and the ATR inhibitor VE-822 were applied to determine the effect of ATR inhibition on liposarcoma cell proliferation and anti-apoptotic activity. Migration activity and clonogenicity were examined using wound healing and clonogenic assays. ATR (p-ATR) was overexpressed in 88.1% of the liposarcoma specimens and correlated w...
Source: Cell Research - May 9, 2022 Category: Cytology Authors: Juncheng Cui Dylan Dean Francis J Hornicek Raphael E Pollock Robert M Hoffman Zhenfeng Duan Source Type: research
Olaparib-induced Apoptosis Through EBNA1-ATR-p38 MAPK Signaling Pathway in Epstein-Barr Virus-positive Gastric Cancer Cells
CONCLUSION: Olaparib treatment led to different cellular responses depending on EBV infection in gastric cancer cell lines. These results provide new insights into the mechanism of olaparib-induced apoptosis in gastric cancer cells and suggest that EBV infection should be considered when developing new potential therapeutic agents for gastric cancer.PMID:34969765 | DOI:10.21873/anticanres.15513
Source: Cell Research - December 31, 2021 Category: Cytology Authors: Sung Ho Moon Nam-Sook Park Min Hye Noh Yeong Seok Kim Soon Ho Cheong Dae Young Hur Source Type: research
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
Co-inhibition of Pol η and ATR sensitizes cisplatin-resistant non-small cell lung cancer cells to cisplatin by impeding DNA damage repair.
In this study, we showed that there was no difference in intracellular uptake of cisplatin or the removal of platinum-DNA adducts between a cisplatin-resistant NSCLC cell line (A549/DR) and a cisplatin-sensitive NSCLC cell line (A549). However, the capacity to repair DNA interstrand crosslinks (ICLs) and double-strand breaks (DSBs) was significantly enhanced in the A549/DR cell line compared to 3 cisplatin-sensitive cell lines. We found that the protein and mRNA expression levels of Pol η, a Y-family translesion synthesis (TLS) polymerase, were markedly increased upon cisplatin exposure in A549/DR cells compared with A549...
Source: Acta Pharmacologica Sinica - May 31, 2018 Category: Drugs & Pharmacology Authors: Li XQ, Ren J, Chen P, Chen YJ, Wu M, Wu Y, Chen K, Li J Tags: Acta Pharmacol Sin Source Type: research
Inhibition of DNA ‑PK activity sensitizes A549 cells to X‑ray irradiation by inducing the ATM‑dependent DNA damage response.
In conclusion, inhibition of DNA‑PK activity increased the radiosensitivity of A549 cells to X‑ray irradiation. NU7026 treatment activated the ATM‑dependent DNA damage response and induced p73 apoptosis pathway. DNA‑PK inhibitor may be an effective constituent of radiosensitization products. DNA damage repair pathway could be a potential target for radiosensitization.
PMID: 29620203 [PubMed - as supplied by publisher]
Source: Molecular Medicine Reports - April 6, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research
53BP1 loss suppresses the radiosensitizing effect of icotinib hydrochloride in colorectal cancer cells.
CONCLUSIONS: Our studies confirmed that the loss of 53BP1 serves as a negative regulator of the radiosensitizing effect of icotinib in part by suppressing the ATM-CHK2-P53 apoptotic pathway.
PMID: 29388453 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - February 3, 2018 Category: Radiology Tags: Int J Radiat Biol Source Type: research
ATM Signaling Pathway Is Implicated in the SMYD3-mediated Proliferation and Migration of Gastric Cancer Cells.
Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.
PMID: 29302370 [PubMed]
Source: Journal of Gastric Cancer - January 7, 2018 Category: Gastroenterology Tags: J Gastric Cancer 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
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
Low-dose irradiation promotes proliferation of the human breast cancer MDA-MB-231 cells through accumulation of mutant P53.
Abstract
Low-dose irradiation (LDIR) has been proven to have differential biological effects on normal mammalian somatic cells and cancer cells. Our previous study showed that p53 gene status is a critical factor regulating the effect of LDIR on cancer cells. We investigated the effect of LDIR on the breast cancer cell line MDA-MB-231 that harbors a mutant p53 gene, and the normal breast fibroblast cell line Hs 578Bst. In the present study, we showed that 150 mGy LDIR pormoted growth of MDA-MB-231 cells but not Hs 578Bst cells. Through cell cycle analyses, we found that LDIR accelerated cell cycle into S phase i...
Source: International Journal of Oncology - December 5, 2016 Category: Cancer & Oncology Authors: Li SJ, Liang XY, Li HJ, Li W, Zhou L, Chen HQ, Ye SG, Yu DH, Cui JW Tags: Int J Oncol Source Type: research
IGF-1R inhibition sensitizes breast cancer cells to ATM-Related Kinase (ATR) inhibitor and cisplatin.
Authors: O'Flanagan CH, O'Shea S, Lyons A, Fogarty FM, McCabe N, Kennedy RD, O'Connor R
Abstract
The complexity of the IGF-1 signalling axis is clearly a roadblock in targeting this receptor in cancer therapy. Here, we sought to identify mediators of resistance, and potential co-targets for IGF-1R inhibition. By using an siRNA functional screen with the IGF-1R tyrosine kinase inhibitor (TKI) BMS-754807 in MCF-7 cells we identified several genes encoding components of the DNA damage response (DDR) pathways as mediators of resistance to IGF-1R kinase inhibition. These included ATM and Ataxia Telangiectasia and RAD3-r...
Source: Oncotarget - July 30, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
The ATM inhibitor KU55933 sensitizes radioresistant bladder cancer cells with DAB2IP gene defect.
CONCLUSIONS: Loss of DAB2IP expression in BCa cells signifies their radioresistance. KU55933, which suppresses ATM phosphorylation upon irradiation, could be applied in the radiotherapy of BCa patients with a DAB2IP gene defect.
PMID: 25585815 [PubMed - indexed for MEDLINE]
Source: International Journal of Radiation Biology - February 18, 2016 Category: Radiology Tags: Int J Radiat Biol Source Type: research
Abstract B29: LRP16 is an essential mediator for DNA double-strand breaks induced NF-kappaB activation
In this study, we demonstrate that LRP16 constitutively interacts with PARP1 and IKKgamma. This interaction is essential for efficient interactions among PARP1, IKKgamma, and PIASy, the modifications of IKKgamma, and the activation of NF-kappaB following DSB induction. The regulation of LRP16 in NF-kappaB activation is dependent on its poly (ADP-ribose) binding capability through the unique macro domain. The depletion of the DSB-specific sensor Ku80 resulted in a significant reduction in the physical interactions among LRP16, PARP1 and IKKgamma. Additionally, the knockdown of either endogenous Ku80 or Ku70 by siRNA markedl...
Source: Molecular Cancer Research - January 15, 2016 Category: Cancer & Oncology Authors: Wu, Z., Wang, C., Bai, M., Li, X., Mei, Q., Li, X., Wang, Y., Fu, X., Luo, G., Han, W. Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research
Androgen Receptor in Telomeres DNA and Chromosomes
Androgen receptor (AR) plays a role in maintaining telomere stability in prostate cancer cells, as AR inactivation induces telomere dysfunction within 3 h. Since telomere dysfunction in other systems is known to activate ATM (ataxia telangiectasia mutated)-mediated DNA damage response (DDR) signaling pathways, we investigated the role of ATM-mediated DDR signaling in AR-inactivated prostate cancer cells. Indeed, the induction of telomere dysfunction in cells treated with AR-antagonists (Casodex or MDV3100) or AR-siRNA was associated with a dramatic increase in phosphorylation (activation) of ATM and its downstream effector...
Source: Journal of Biological Chemistry - October 16, 2015 Category: Chemistry Authors: Reddy, V., Wu, M., Ciavattone, N., McKenty, N., Menon, M., Barrack, E. R., Reddy, G. P.-V., Kim, S.-H. Tags: Cell Biology Source Type: research
