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Source: Cancer Research
Cancer: Brain Cancers
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Total 39 results found since Jan 2013.
Abstract 5093: Pre-clinical assessment of a novel anti-invasion nanoparticle therapeutic in combination with bevacizumab for the treatment of glioblastoma
We report a novel strategy by which GBM tumours invade and proliferate via overexpression of the GEF beta-PIX which was shown to be increased at the invasive edge in 74% of GBM tumours assessed (n = 19) compared with tumour core (5). We have further shown that siRNA-mediated knockdown of beta-PIX in GBM patient-derived xenograft cell cultures and cell lines resulted in decreased cell invasion in 3D, cell proliferation and survival assays in vitro. Furthermore, we have uncovered a role for beta-PIX expression in endothelial cell function, as knockdown of beta-PIX inhibits HUVEC cell migration in vitro. To interrogate in viv...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Murray, D. W., O'Halloran, P., Jarzabek, M., MacCarthy, B., Sarkaria, J. N., Schiffelers, R. M., Symons, M., Byrne, A. T. Tags: Tumor Biology 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 2312: Identifying novel cancer stem cell target for triple-negative breast cancer
The objective of this study was to investigate the role of HN1L in regulating BCSC and metastasis in TNBC, and to determine the mechanism of action of HN1L in BCSC. Knocking down HN1L by shRNA in SUM159 and MDAMB231 cell lines significantly decreased mammosphere forming efficiency (MSFE) and CD44+/CD24low/- population. To assess the contribution of HN1L to BCSC and tumor growth, a patient derived human-cancer-in-mouse xenograft model and two cancer cell line xenograft models were employed. To ensure targeted delivery, siRNA was packaged into DOPC liposomes and delivered into mice via intraperitoneal injection. Results show...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Liu, Y., Choi, D. S., Grandos-Principal, S., Qian, W., Burey, L., Wong, H., Rodriguez-Aguayo, C., Sood, A., Li, Z., Wong, S., Weiss, H., Dave, B., Landis, M., Chang, J. C. Tags: Tumor Biology Source Type: research
Abstract LB-207: mTORC2/Akt signaling is modulated by noncanonical mitochondrial Notch1/PINK1 interaction in myc-amplified medulloblastoma tumorigenesis
Medulloblastoma is known to be the most malignant pediatric brain tumor. The armamentarium of targeted therapies to currently treat medulloblastoma and similar pediatric central nervous system malignancies is extremely limited, often necessitating the need to combat such tumors with modified regimens of therapeutic options designed originally to target adult neoplasms. Given such limited therapies, a budding focus on the role of mitochondrial dysregulation in the tumorigenesis of such pathologies merits consideration. Mitochondria are known to play fundamental roles in multiple processes conserved across eukaryotic species...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Feroze, A. H., Lee, K.-S., Gholamin, S., Wu, Z., Weissman, I., Lu, B., Mitra, S. S., Cheshier, S. Tags: Tumor Biology Source Type: research
Abstract 511: EGFR-initated NADPH oxidase activity regulates Fyn expression in glioblastoma multiforme
Glioblastoma multiforme (GBM) constitute the most aggressive and common form of primary brain tumors, conferring the worst clinical prognosis. Epidermal growth factor receptor (EGFR) amplification, mutation and re-arrangement are commonly observed genetic lesions in GBM. The most frequently occurring EGFR variant in GBM, EGFRvIII, is characterized by a truncated extracellular domain, leading to a receptor which is unable to bind ligand yet rendered constitutively active. In addition to increasing proliferation and survival signaling, EGFRvIII increases the production of reactive oxygen species (ROS); redox signaling in GBM...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Johnson, B., Chandra, J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3443: Wnt-beta-catenin-Rac1 signaling axis regulates metastasis-associated phenotypes in TNBC
Conclusion: Results of our experiments show that upregulation of WP regulates metastasis-associated phenotypes in TNBC via activation of RAC1 GTP-ase. The functional link between WP, metastasis and the activation of RAC1 is being currently worked out using RAC1SiRNA and pharmacological inhibitor of RAC1 in brain metastasizing MDA-MB231BR cells to specifically address the role of Wnt-beta-catenin-RAC1 signaling axis in the context of distant metastasis, the results of which will be presented at the meeting.
Citation Format: Nandini Dey, Jennifer Carlson, Pradip De, Brian Leyland-Jones. Wnt-beta-catenin-Rac1 signaling axis r...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Dey, N., Carlson, J., De, P., Leyland-Jones, B. Tags: Molecular and Cellular Biology Source Type: research
Abstract 5449A: PI3K and MEK inhibition in intracranial triple negative breast cancer: Efficacy of BKM120 and AZD6244 in preclinical mouse models
Conclusions: BKM120 and AZD6244 both improved survival in an IC TNBC SUM149 mouse model, with single agent AZD6244 being most efficacious. The siRNA screens indicate that combined treatment with BKM120 and AZD6244 should be synthetically lethal, suggesting that combination therapy may have underperformed due to toxicity. Ongoing in vitro and in vivo studies (including dosing schedules) will further characterize the effects of these drugs in intracranial TNBC.
Citation Format: Amanda E.D. Van Swearingen, Marni B. Siegel, Ryan Bash, Brian Golitz, Charlene Santos, David Darr, Joel Parker, Gary L. Johnson, C. Ryan Miller, Care...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Swearingen, A. E. D. V., Siegel, M. B., Bash, R., Golitz, B., Santos, C., Darr, D., Parker, J., Johnson, G. L., Miller, C. R., Anders, C. K. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4170: The role of VEGF-C for cell viability, tumor growth and bevacizumab resistance in glioblastoma multiforme
In conclusion, our current results show that VEGF-C is of importance for GBM cell viability and tumor growth presumable due to its ability to stimulate autocrine activation of VEGFR2. VEGF-C expression therefore could respresent a possible mechanism behind Bevacizumab resistance. An update on this will be presented.Citation Format: Signe R. Michaelsen, Mette K. Nedergaard, Thomas Urup, Mette Villingshoej, Andreas Kjaer, Lara Perryman, Janine T. Erler, Ulrik Lassen, Hans S. Poulsen. The role of VEGF-C for cell viability, tumor growth and bevacizumab resistance in glioblastoma multiforme. [abstract]. In: Proceedings of the 1...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Michaelsen, S. R., Nedergaard, M. K., Urup, T., Villingshoej, M., Kjaer, A., Perryman, L., Erler, J. T., Lassen, U., Poulsen, H. S. Tags: Tumor Biology Source Type: research
Abstract 4360: Validation of phosphodiesterase 10A as a cancer target
Phosphodiesterase 10A (PDE10) is a cAMP and cGMP degrading PDE isozyme that is highly expressed in the brain striatum where it plays an important role in cognition and psychomotor activity. PDE10 inhibitors are being developed for the treatment of schizophrenia and Huntington's disease and are generally well tolerated, likely because of low expression levels in peripheral tissues. We recently reported high levels of PDE10 in tumors and that genetic silencing by siRNA inhibits tumor cell growth with a high degree of selectivity over normal cells (Li et al., Oncogene 2014). These observations suggest that PDE10 may have an u...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Lee, K., Li, N., Chen, X., Zhu, B., Yet, L., Madeira da Silva, L., Russo, S., Keeton, A. B., Boyd, M. R., Piazza, G. A. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4944: Identification of B-cell lymphoma 6 as a novel therapeutic target in glioblastoma
ConclusionOur data suggest that BCL6 is involved in glioma tumorigenesis through regulating both the TP53 and MEK-ERK pathways, and that BCL6 is a potential therapeutic target for glioma treatment.Citation Format: Ye Chen, Liang Xu, Masaharu Hazawa, Anand M. Thippeswamy, Henry Yang, Markus Müschen, De-Chen Lin, Phillip Koeffler. Identification of B-cell lymphoma 6 as a novel therapeutic target in glioblastoma. [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 Res 2015;75(15 Suppl):Abstract nr 4944. doi:...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chen, Y., Xu, L., Hazawa, M., Thippeswamy, A. M., Yang, H., Muschen, M., Lin, D.–C., Koeffler, P. Tags: Molecular and Cellular Biology Source Type: research
iNOS Drives mTOR Pathway Activation by Nitrosylation of TSC2
Melanoma is one of the cancers of fastest-rising incidence in the world. Inducible nitric oxide synthase (iNOS) is overexpressed in melanoma and other cancers, and previous data suggest that iNOS and nitric oxide (NO) drive survival and proliferation of human melanoma cells. However, specific mechanisms through which this occurs are poorly defined. One candidate is the PI3K–AKT–mTOR pathway, which plays a major role in proliferation, angiogenesis, and metastasis of melanoma and other cancers. We used the chick embryo chorioallantoic membrane (CAM) assay to test the hypothesis that melanoma growth is regulated by iNOS-d...
Source: Cancer Research - February 16, 2014 Category: Cancer & Oncology Authors: Lopez-Rivera, E., Jayaraman, P., Parikh, F., Davies, M. A., Ekmekcioglu, S., Izadmehr, S., Milton, D. R., Chipuk, J. E., Grimm, E. A., Estrada, Y., Aguirre-Ghiso, J., Sikora, A. G. Tags: Molecular and Cellular Pathobiology Source Type: research
Abstract 1762: Phosphodiesterase 10, a novel target for colorectal cancer therapeutics
Phosphodiesterase 10 (PDE10) is a newly characterized PDE isozyme that is expressed in regions of the brain affecting cognition and psychomotor activity. Inhibitors are currently being developed for the treatment of schizophrenia and Huntington's disease, one of which, Pf-2545920 (MP-10), is in clinical trials. Although PDE10 is not expressed in most peripheral tissues, we recently found high levels in colon tumor cells compared with normal colonocytes and that genetic silencing by siRNA selectively suppressed colon tumor cell growth. These observations suggest that PDE10 may represent a novel anticancer target. Pf-2545920...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lee, K. J., Li, N., Chen, X., Zhu, B., Yet, L., Piazza, G. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 1774: Polysialyltransferase ST8SiaII: a new target for the treatment of metastatic tumors
Polysialic acid (polySia) is a carbohydrate polymer expressed on the surface of NCAM (neuronal cell adhesion molecule) in many cancer cells where it modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis. PolySia-NCAM expression is strongly associated with poor clinical prognosis and correlates with aggressive/invasive disease in small cell lung cancer, pancreatic cancer, neuroblastoma and many other tumors principally of neuroendocrine origin [1]. SiRNA knockdown of polysialyltransferase ST8SiaII (STX), the enzyme primarily responsible for polySia synthesis in tumors, has been shown to abolish tu...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Viprey, V., Springett, B. R., Al-Saraireh, Y., Northrop, M., Sutherland, M., Saeed, R., Loadman, P. M., Patterson, L. H., Shnyder, S. D., Falconer, R. A. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 3107: The role of LIN28 in atypical teratoid rhabdoid tumor (ATRT) pathogenesis
Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant brain tumor developing almost exclusively in children. It belongs to the embryonal brain tumor group which consists of primitive tumors recapitulating early embryogenesis of nervous system. It is known that loss of INI protein expression is the hallmark of ATRT pathogenesis. LIN28 is a key gene in embryonic development and maintenance of pluripotency in stem cells. Considering the primitive nature and young age onset of ATRT, LIN28 may be an important co-player in ATRT pathogenesis.
We explored the expression and functional role of LIN28 in ATRT. In tumor tissue...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Phi, J. H., Choi, S. A., Kim, Y. H., Kim, Y.-H., Park, C.-K., Wang, K.-C., Kim, S.-K. Tags: Tumor Biology Source Type: research
Abstract 3143: Sodium butyrate induced cellular senescence, inhibited invasion and modulated cellular metabolism in glioblastoma cells
Sodium butyrate (SB) -C-4 saturated fatty acid (short-chain fatty acids) present in the human bowel membrane in the quite high concentration (2 mM) as food metabolites. It was previously reported that SB showed anti-tumor effect as HDAC inhibitor, however, the precise mechanism has not been elucidated yet. Here, we focused on the role of SB on cancer cell growth, motility and invasion. Physiological concentration of SB (0.25-4 mM) induced inhibition of cell growth, colony formation in soft agar, in vitro motility and invasiveness with Boyden chamber and wound healing assay in a dose-dependent fashion using human glioblasto...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Nakagawa, H., Shindou, M., Sasagawa, S., Itoh, K. Tags: Tumor Biology Source Type: research
