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Source: Cancer Research
Condition: Brain Tumor
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Total 43 results found since Jan 2013.
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 A02: Identification of distinct BUB1B-sensitive and -resistant subtypes of glioblastoma with prognostic value
Glioblastoma multiforme is the most aggressive and common form of brain cancer in adults. The combined analysis of functional genetics with glioblastoma (GBM) network modeling identified BUB1B, a critical mitotic spindle checkpoint player, as a new requirement of glioblastoma tumors to suppress lethal consequences of altered kinetochore (KT) (1). Here, we further collected GBM stem-like cells (GSCs) including both BUB1B-sensitive and -resistant isolates, and performed whole-transcriptome sequencing that capture gene expression levels of each GSC. Based on the expression signature associated with BUB1B-sensitiveness from GS...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Lee, E., Paddison, P. J., Zhu, J. Tags: Computational Genomics and Evolutionary Dynamics Source Type: research
Abstract B12: GABP selectively binds and activates the mutant TERT promoter across multiple cancer types
Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBM), harbor highly recurrent mutations in the TERT promoter specific to two nucleotide positions. The common mutation sites, G228A and G250A, may create de-novo ETS family transcription factor binding sites, but the precise mechanism of how these mutations confer increased TERT expression has been elusive. Here, we demonstrate the de-novo ETS motif to be critical for mutant ...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. F., Nagarajan, R. P., Choi, S., Hong, C., He, D., Pekmezci, M., Wiencke, J. K., Wrensch, M. R., Chang, S. M., Walsh, K. M., Myong, S., Song, J. S., Costello, J. F. Tags: Mutational Landscape in Brain Tumors Source Type: research
Abstract B26: MAPK-interacting kinase inhibition sensitizes glioblastoma and glioma stem cells to arsenic trioxide
In this study, we sought to determine the mechanisms by which MNK signaling regulates arsenic trioxide responses in GBM and glioma stem cells.GBM cell lines were treated with ATO in the presence or absence of MNK inhibitors or siRNA against MNK isoforms. Western blots of treated samples were analyzed with antibodies against phosphorylated eIF4E, the key downstream effector of the MNKs. Following treatment with ATO and MNK inhibitors, proliferation rate and apoptosis were determined by WST-1 assay and Annexin V-FITC/PI staining. GBM cell lines were grown under stem cell conditions and subjected to qPCR and flow cytometry to...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Bell, J. B., Eckerdt, F., Arslan, A. D., Iqbal, A., Alvarez, A. A., Cheng, S.-Y., Nakano, I., Platanias, L. C. Tags: Preclinical Therapeutics/Trials/Models Source Type: research
Abstract 1942: Regulation of GRNMB transcription and cellular effects by chondroitin 4-sulfation
Increased expression of glycoprotein (transmembrane) NMB (GPNMB; osteoactivin) has been identified in triple negative breast cancer, melanoma, glioma, and hepatocellular carcinoma, and followed decline in expression of the enzyme arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase). The expression and regulation of GPNMB was evaluated in HepG2 cells and in ARSB-deficient and control C57BL/6J mouse hepatic tissue. Increased expression of GPNMB was attributable to promoter activation by phospho(Ser)MITF (microphthalmia-associated transcription factor), the phosphorylation of which was activated by phospho(Ser)-p38 MAPK....
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Tobacman, J. K., Feferman, L., Bhattacharyya, S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 680: Identification of GLI1 antagonists for breast cancer therapy
Conclusion: Several agents showed efficacy in in vitro BC cancer models demonstrating that GLI inhibitors may be a valid therapeutic approach for targeting GLI-dependent BC cancers.[1] Z. Thomas, W. Gibson, J. Sexton, K. Aird, S. Ingram, A. Aldrich, H. Lyerly, G. Devi, K. Williams, Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration. British Journal of Cancer 104 (2011) 1575-1586.[2] K.P. Williams, J.L. Allensworth, S.M. Ingram, G.R. Smith, A.J. Aldrich, J. Z Sexton, G. R Devi, Quantitative high-throughput efficacy profiling of approved oncology drugs in inflammat...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Oladapo, H., Fleming, J. M., Addo, K., Tarpley, M., Ehe, B., Ingram, S., Sauer, S., Devi, G., Williams, K. P. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 44: EGFR and Dock180 activate MLK3 to drive invasion of glioblastoma cells
Glioblastoma (GBM) is the most common and deadly form of brain tumor in adults, with an average post-diagnosis survival time of 15 months. While GBMs rarely metastasize to distant organs, they readily invade into surrounding brain tissue, leading to incomplete surgical resection and subsequent tumor recurrence. Epidermal Growth Factor Receptor (EGFR) signaling is aberrantly activated in a majority of GBM tumors, and is clearly implicated in multiple malignant phenotypes, including migration and invasion. However, direct targeting of EGFR has been largely unsuccessful, for multiple reasons, including compensatory upregulati...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Misek, S. A., Chen, J., Gallo, K. A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 487: Whole genome screen to identify genes targeting MYCN-driven embryonal tumors
MYCN is a driver of neuroblastoma (NB) tumorigenesis and is over-expressed in a number of tumors of embryonal origin, including rhabdomyosarcoma, medulloblastoma and diffuse intrinsic pontine gliomas. We sought to identify regulators of MYCN transcription by performing a whole genome screen (WGS) for regulators of MYCN promoter activity using a NB cell model. A plasmid containing the MYCN promoter (1.3kb upstream of MYCN TSS) fused to luciferase and stably integrated into the genome of NGP NB cells was the readout system. NGP-MYCNpluc, was selected based on MYCN luciferase activity inhibition by ATRA and HDAC inhibitors to...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Thiele, C. J., Liu, Z., Veschi, V., Buehler, E., Martin, S. Tags: Tumor Biology 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 2030: FRK regulates glioma cell progression by promoting N-cadherin/{beta}-catenin complex formation
In this study, we found that FRK over-expression increased the protein level of N-cadherin, but not that of E-cadherin. Meanwhile, FRK over-expression promoted β-catenin translocation to the plasma membrane, where it formed complex with N-cadherin, while inhibited β-catenin translocation to the nucleus. In addition, down-regulation of N-cadherin by siRNA promoted the migration/ invasion proliferation and inhibited apoptosis of glioma U251 and U87 cells. Interestingly, N-cadherin down-regulation abolished the effect of FRK on glioma cell migration/invasion, proliferation and apoptosis. In summary, these results indicate t...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Shi, Q., Song, X., Yan, H., Wang, J., Zhang, W., Hu, J., Zhou, X., Yu, R. Tags: Molecular and Cellular 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
Abstract 2081: The CCCTC-binding factor (CTCF) functions to downregulate the transcription of MGMT gene in human glioblastoma cells
The O6-methylguanine-DNA methyltransferase (MGMT) gene located at chromosome 10q26 encodes a DNA repair protein that abrogates the therapeutic effects of alkylating agents by preventing the formation of mutagenic lesions or cytotoxic DNA crosslinks. MGMT is highly expressed in human gliomas and its transcriptional regulation has emerged as a major translational focal point in neuro-oncology, because the epigenetic silencing of the MGMT gene which occurs in a subset of these malignancies confers improved treatment responses to both chemo and radiation therapies. While the promoter methylation and its contribution to glioma ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Srivenugopal, K. S., Al-Obaide, M. I. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2082: Control and function of the PROX1 transcription factor in malignant glioma
We present experimental evidence showing that PROX1 induces p27. By regulating p27, PROX1 may block the activity of Cdk2/Cyclin E complex, and thus inhibit cell cycle progression. The functional consequences of PROX1 expression on the stemness, migration, and invasion phenotypes of glioma cells remain to be further investigated and preliminary results will be presented.Citation Format: Kaveh M. Goudarzi, Tamador Elsir, Monica Nistér, Mikael S. Lindström. Control and function of the PROX1 transcription factor in malignant glioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cance...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Goudarzi, K. M., Elsir, T., Nister, M., Lindstrom, M. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract LB-218: Protein arginine methyltransferase inhibition of malignant gliomas leads to restored chemokine expression and enhanced immune effector function
Patients with Glioblastoma Multiforme (GBM) face a poor prognosis despite multimodal therapy, thus, there is an unmet need for discovery of novel therapeutic targets and approaches. The immune-privileged nature of the central nervous system and down-modulation of cytokines and chemokines in GBM tumors led us to explore epigenetic approaches to restore expression of immune-relevant genes.PRMT5 is a type II arginine methyltransferase that catalyzes symmetric dimethylation of arginine residues on histone proteins leading to transcriptional repression. Our previous work showed PRMT5 overexpression correlates with poor clinical...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yan, F., Banasavadi-Siddegowda, Y., Patton, J. T., Lustberg, M., Wu, X., Kaur, B., Baiocchi, R. A. Tags: Immunology Source Type: research
Abstract 2129: Translational regulation of Id1 expression in glioma cells by the PI-3K pathway involves PPM1G-mediated dephosphorylation of 4E-BP1
In conclusion, our findings provide the first evidence that the PI-3K/AKT signaling pathway translationally regulates Id1 expression through modulation of PPM1G activity, possibly by phosphorylation, altering the balance between hyper- and hypo-phosphorylated 4E-BP1.Citation Format: Kaiming Xu, Lanfang Wang, Hui-Kuo G. Shu. Translational regulation of Id1 expression in glioma cells by the PI-3K pathway involves PPM1G-mediated dephosphorylation of 4E-BP1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Xu, K., Wang, L., Shu, H.-K. G. Tags: Molecular and Cellular Biology Source Type: research
