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Total 16 results found since Jan 2013.

An Ensemble Strategy to Predict Prognosis in Ovarian Cancer Based on Gene Modules
Conclusion Considering the heterogeneity and complexity of ovarian cancer, we demonstrated a new method to predict the prognosis of ovarian cancer based on the clustering information and gene co-expression network in each subtype of cancer patients. We divided the ovarian cancer data into three subtypes by clustering analysis and we found that the survival risks in these three subtypes were significantly different. We mined the important communities based on the co-expression networks in each subtype. There are 50, 73, and 92 communities in the first, second and third subtype, respectively. Next, we constructed a new ense...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells 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 B45: A genome-scale screen identifies the microcephaly gene, ZNF335, as a regulator of DNA end resection
We examined the recruitment of known resection factors to DSB sites and determined that the localization of CtIP and BLM were impaired in cells depleted of ZNF335. Our data suggests that ZNF335 plays an important role in promoting resection and ATR activation in response to DSBs.Citation Format: Jordan Young, Mikhail Bashkurov, Andrea McEwan, Thomas Sun, Alessandro Datti, Daniel Durocher. A genome-scale screen identifies the microcephaly gene, ZNF335, as a regulator of DNA end resection [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montre...
Source: Molecular Cancer Research - April 2, 2017 Category: Cancer & Oncology Authors: Young, J., Bashkurov, M., McEwan, A., Sun, T., Datti, A., Durocher, D. Tags: Exploiting Repair Defects in the Tumor Microenvironment: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B16: Activation of NRF2 and adaptive resistance to chemotherapy
Nuclear factor-erythroid-2-related factor 2 (NRF2), a member of the cap ‘n’ collar family of bZIP transcription factors, confers protection against oxidative and electrophilic stress. NRF2 is of great interest in cancer research, due to its role in response to chemotherapy, including the class of drugs targeting thymidylate synthase (TYMS). It has long been known that inhibition of TYMS leads to depletion of thymidine levels and the onset of programmed cell death, deriving from the enzyme's function as the sole de novo source of thymidine for DNA replication and repair. Exposing cells to TYMS inhibitors such as fluorop...
Source: Cancer Research - January 30, 2017 Category: Cancer & Oncology Authors: Sarah A. Clinton, Karen W. Barbour, Franklin G. Berger Tags: New Therapeutic Approaches to Colorectal Cancer 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

LSC Abstract - Activation of FGF9 and 18 in idiopathic pulmonary fibrosis promote survival and migration and inhibit myofibroblast differentiation of human lung fibroblasts
Key developmental lung signaling pathways are reactivated in IPF. FGF9 and FGF18 are involved in epithelial–mesenchymal interactions and are critical for lung development.We evaluated the expression of FGF9, FGF18 and FGFR in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration and differentiation of control and IPF human lung fibroblasts (HLF).HLF were cultured with FGF9 and FGF18. FAS-ligand induced apoptosis was assayed by measuring cleaved-PARP expression. Expression of FGFR mRNA, α-smooth muscle actin, collagen I and MMPs was analyzed with qPCR, western...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Joannes, A., Jaillet, M., Mailleux, A., Crestani, B. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research

Regulating gene expression towards solving ocular surface diseases
SummaryTreatment of genetic eye disease poses significant medical and surgical challenges. We used a bioluminescent corneal reporter gene mouse model to assess efficacy and potency of a number of gene therapy approaches for corneal dystrophy. Various modalities were assessed for delivery of short interfering RNA (siRNA) targeting one of five mutant alleles present in the corneal bioluminescent mouse model enabling assessment of topical, subconjunctival and intrastromal delivery. Potent and sustained in vivo gene silencing >50% for up to 7 days was observed. This siRNA therapy only provides a transient silencing of the ...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: T. Moore, S. Atkinson, E. Maurizi, D. Schiroli, L. Mairs, K. Christie, I. McLean, E. Allen, D.L. Pedrioli, J. Moore, A. Nesbit Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research

Abstract IA06: Spatial systems biology of cancer
International efforts have now defined the genomic landscapes of most major human cancer types. The genomic landscape of breast cancer is particularly well described in several recent publications. The high level view of this disease suggests a remarkable level of inter- and intra-tumor heterogeneity, the presence of a few recurrent and many rare genomic aberrations and substantial genomic and epigenomic heterogeneity. The challenge now is to understand how these aberrations and tumor extrinsic influences from the microenvironment collaborate to deregulate aspects of cell differentiation, proliferation, apoptosis, DNA repa...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Gray, J. Tags: Genomics - Sporadic and Hereditary: Oral Presentations - Invited Abstracts 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

Abstract B37: The histone deacetylase inhibitor panobinostat sensitizes cyclin E-amplified ovarian cancer cells to poly ADP ribose polymerase inhibitors via E2F1 downregulation.
Conclusions: The development of a new PARPi combination therapy with panobinostat has immediate prospects for rapid translation to the clinic and great potential for improving clinical outcomes for non-BRCAness, chemoresistant ovarian cancer.Citation Format: Andrew J. Wilson, Jeanette Saskowski, Dineo Khabele. The histone deacetylase inhibitor panobinostat sensitizes cyclin E-amplified ovarian cancer cells to poly ADP ribose polymerase inhibitors via E2F1 downregulation.. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR;...
Source: Cancer Research - January 14, 2016 Category: Cancer & Oncology Authors: Wilson, A. J., Saskowski, J., Khabele, D. Tags: Epigenetic Cancer Therapies Source Type: research

Abstract C59: Role of MTH1 (NUTD1) in cancer cell survival
Human mutT homolog MTH1 (also known as NUDT1) is a purine nucleoside triphosphatase which hydrolyses oxidised nucleotides (8-oxo-dGTP and 2-OH-dATP) into mono-phosphate forms to prevent these damaged bases from being incorporated into DNA. Recent studies have suggested a key role of MTH1 in the survival of cancer cells. It was hypothesized that in cancer cells with high levels of reactive oxygen species (ROS), small molecule inhibition or loss of MTH1 would lead to accumulation of oxidised nucleotides in DNA, increased genome instability and loss of cell viability. In order to validate MTH1 as a potential cancer therapeuti...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Alwan, H., Eckersley, K., Goodwin, L., Lau, A., Jones, D., Kettle, J., Nissink, W. M., Read, J., Scott, J. S., Taylor, B. J. M., Walker, G. E., Foote, K. M. Tags: DNA Repair and Modulation: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A62: PARP-1 regulates NF-{kappa}B-mediated IL-8 expression in HER2 positive breast cancer
Conclusions:Trastuzumab resistant HER2+ breast cancer cells remain sensitive to PARP inhibition. Further, PARP-1 regulates the expression of IL-8, an NF-B regulated gene. These results suggest that inhibition of the interaction between PARP-1 and the NF-B signaling pathway may be a potential mechanism behind the sensitivity to PARPi in HER2+ trastuzumab resistant breast cancer cells.Citation Format: Monicka E. Wielgos, Rajani Rajbhandari, Susan Nozell, C. Kent Osborne, Rachel Schiff, Eddy S. Yang. PARP-1 regulates NF-B-mediated IL-8 expression in HER2 positive breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORT...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Wielgos, M. E., Rajbhandari, R., Nozell, S., Osborne, C. K., Schiff, R., Yang, E. S. Tags: EGFR / Her2: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A155: Small molecule metabolic inhibitors, compound A and the derivatives specifically inhibit the cell growth of Ewing's sarcoma cells harbor EWS-FLI1 in vitro and in vivo
Conclusions: Compound A and its derivatives may be a therapeutic agent with potent antitumor activity for Ewing's sarcoma patients.Citation Format: Hiromichi Kosaka, Yasuo Watanabe, Michihiro Maemoto, Masamori Sugawara, Miwa Watanabe, Yoko Ono, Yoshisuke Nakasato, Masahiro Matsubara, Ryuichiro Nakai. Small molecule metabolic inhibitors, compound A and the derivatives specifically inhibit the cell growth of Ewing's sarcoma cells harbor EWS-FLI1 in vitro and in vivo. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (P...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kosaka, H., Watanabe, Y., Maemoto, M., Sugawara, M., Watanabe, M., Ono, Y., Nakasato, Y., Matsubara, M., Nakai, R. Tags: Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A164: The small molecule UAE inhibitor TAK-243 (MLN7243) prevents DNA damage repair and reduces cell viability/tumor growth when combined with radiation, carboplatin and docetaxel
Clinical results of VELCADE® (bortezomib) For Injection have prompted evaluation of other enzymes within the ubiquitin proteasome system (UPS) as druggable targets for human cancer. We have identified a first in class investigational drug, TAK-243 (MLN7243), which targets the ubiquitin activating enzyme, UAE (UBA1), an essential cellular enzyme responsible for activating > 99% of all cellular ubiquitin. Ubiquitin is involved in multiple cellular processes including ubiquitin-dependent protein turnover, cell cycle progression, regulation of apoptosis, protein localization and response to DNA damage. Experiments combi...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Milhollen, M. A., Shi, J., Traore, T., Huck, J., Sappal, D., Duffy, J., Lightcap, E., Ishii, Y., Ciavarri, J., Fleming, P., Bence, N., Hyer, M. L. Tags: Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts Source Type: research

Abstract PR09: MYCN and is a therapeutic target in neuroblastoma
Neuroblastoma is a childhood cancer of the sympathetic nervous system. Approximately 20% of patients present with an aggressive metastatic disease characterized by amplification of the MYCN locus. However, an additional 30% of patients suffer from an equally aggressive disease, yet there are no unified genetic markers available.To identify potential biomarkers of poor prognosis in neuroblastoma, we conducted unsupervised hierarchical clustering on 649 primary neuroblastoma tumors based on a 51 gene MYC core target signature. This demonstrated strong activation within the MYCN amplified cohort as expected, but surprisingly ...
Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Carter, D. R., Murray, J., Cheung, B. B., Kalla, H., Gamble, L., Tsang, J., Sutton, S., Koach, J., Syed, S., Gifford, A., Issaeva, N., Biktasova, A., Atmadibrata, B., Sun, Y., Sokolowski, N., Ling, D., Kim, P. Y., Webber, H., Clark, A., Ruhle, M., Liu, B. Tags: Targeting Myc-Driven Cancers: Oral Presentations - Proffered Abstracts Source Type: research