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Source: Cancer Research
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Total 807 results found since Jan 2013.
Release of the B7-H6 Ectodomain by Tumor Cells
In this study, we report a novel mechanism of immune escape involving tumor cell shedding of B7-H6, a ligand for the activating receptor NKp30 that mediates NK-cell binding and NK-cell–mediated killing. Tumor cells from different cancer entities released B7-H6 by ectodomain shedding mediated by the cell surface proteases “a disintegrin and metalloproteases” (ADAM)-10 and ADAM-17, as demonstrated through the use of pharmacologic inhibitors or siRNA-mediated gene attenuation. Inhibiting this proteolytic shedding process increased the levels of B7-H6 expressed on the surface of tumor cells, enhancing NKp30-mediated acti...
Source: Cancer Research - June 30, 2014 Category: Cancer & Oncology Authors: Schlecker, E., Fiegler, N., Arnold, A., Altevogt, P., Rose-John, S., Moldenhauer, G., Sucker, A., Paschen, A., von Strandmann, E. P., Textor, S., Cerwenka, A. Tags: Microenvironment and Immunology Source Type: research
Functional Screen for Regulators of E-cadherin
In this study, we probed E-cadherin expression at the plasma membrane as a functional assay to identify genes involved in E-cadherin downregulation. The assay was based on the E-cadherin–dependent invasion properties of the intracellular pathogen Listeria monocytogenes. On the basis of a functional readout, automated microscopy and computer-assisted image analysis were used to screen siRNAs targeting 7,000 human genes. The validity of the screen was supported by its definition of several known regulators of E-cadherin expression, including ZEB1, HDAC1, and MMP14. We identified three new regulators (FLASH, CASP7, and PCGF...
Source: Cancer Research - July 14, 2014 Category: Cancer & Oncology Authors: Dragoi, A.-M., Swiss, R., Gao, B., Agaisse, H. Tags: Integrated Systems and Technologies Source Type: research
Role of AMPK in Regulating EMT
In cancer cells, the epithelial–mesenchymal transition (EMT) confers the ability to invade basement membranes and metastasize to distant sites, establishing it as an appealing target for therapeutic intervention. Here, we report a novel function of the master metabolic kinase AMPK in suppressing EMT by modulating the Akt–MDM2–Foxo3 signaling axis. This mechanistic link was supported by the effects of siRNA-mediated knockdown and pharmacologic activation of AMPK on epithelial and mesenchymal markers in established breast and prostate cancer cells. Exposure of cells to OSU-53, a novel allosteric AMPK activator, as well...
Source: Cancer Research - September 1, 2014 Category: Cancer & Oncology Authors: Chou, C.-C., Lee, K.-H., Lai, I.-L., Wang, D., Mo, X., Kulp, S. K., Shapiro, C. L., Chen, C.-S. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Aurora-A Inhibition Is Effective against GB in Mice
Glioblastoma remains a devastating disease for which novel therapies are urgently needed. Here, we report that the Aurora-A kinase inhibitor alisertib exhibits potent efficacy against glioblastoma neurosphere tumor stem–like cells in vitro and in vivo. Many glioblastoma neurosphere cells treated with alisertib for short periods undergo apoptosis, although some regain proliferative activity upon drug removal. Extended treatment, however, results in complete and irreversible loss of tumor cell proliferation. Moreover, alisertib caused glioblastoma neurosphere cells to partially differentiate and enter senescence. These eff...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Van Brocklyn, J. R., Wojton, J., Meisen, W. H., Kellough, D. A., Ecsedy, J. A., Kaur, B., Lehman, N. L. Tags: Priority Reports Source Type: research
Involvement of Polymerase {eta} in Anticancer Drug Resistance
DNA repair processes are a key determinant of the sensitivity of cancer cells to DNA-damaging chemotherapeutics, which may induce certain repair genes as a mechanism to promote resistance. Here, we report the results of a screen for repair genes induced in cancer cells treated with DNA crosslinking agents, which identified the translesion polymerase η (PolH) as a p53-regulated target acting as one defense against interstrand crosslink (ICL)-inducing agents. PolH was induced by fotemustine, mafosfamide, and lomustine in breast cancer, glioma, and melanoma cells in vitro and in vivo, with similar inductions observed in norm...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Tomicic, M. T., Aasland, D., Naumann, S. C., Meise, R., Barckhausen, C., Kaina, B., Christmann, M. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Mechanism of Synergy between GMX1777(8) and Pemetrexed
GMX1778 and its prodrug GMX1777 represent a new class of cancer drugs that targets nicotinamide phosphoribosyltransferase (NAMPT) as a new strategy to interfere with biosynthesis of the key enzymatic cofactor NAD, which is critical for a number of cell functions, including DNA repair. Using a genome-wide synthetic lethal siRNA screen, we identified the folate pathway–related genes, deoxyuridine triphosphatase and dihydrofolate reductase, the silencing of which sensitized non–small cell lung carcinoma (NSCLC) cells to the cytotoxic effects of GMX. Pemetrexed is an inhibitor of dihydrofolate reductase currently used to t...
Source: Cancer Research - October 30, 2014 Category: Cancer & Oncology Authors: Chan, M., Gravel, M., Bramoulle, A., Bridon, G., Avizonis, D., Shore, G. C., Roulston, A. Tags: Priority Report Source Type: research
Abstract PR02: Negative regulation of myogenesis by Mtor: A pathway toward differentiation therapy in rhabdomyosarcoma
Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is composed of skeletal myoblast-like cells that have lost the capacity to terminally differentiate. This suggests that RMS cells may contain a factor that blocks normal muscle differentiation. Because cell cycle arrest is coupled to muscle differentiation, identifying putative negative regulators of differentiation could lead to novel therapeutic approaches aimed at fostering terminal differentiation. To gain insight into the events that normally trigger the initial phase of muscle differentiation, we carried out a high content cell-based screen usin...
Source: Cancer Research - October 9, 2014 Category: Cancer & Oncology Authors: Wilson, R. A., Liu, J., Xu, L., Zheng, Y., Skapek, S. X. Tags: Developmental Biology of Pediatric Malignancies Source Type: research
Abstract A10: Functional characterization of Ewing's sarcoma susceptibility loci
Conclusions: In synopsis, our data indicate that the previously identified ES susceptibility regions and candidate genes may play a prominent role in ES pathobiology.
Citation Format: Thomas Grunewald, Marie-Ming Aynaud, Franck Tirode, Eleni Tomazou, Didier Surdez, Thomas Rio Frio, Virginie Bernard, Virginie Raynal, Carlo Lucchesi, Gaelle Pierron, Pascale Gilardi-Hebenstreit, Patrick Charnay, Heinrich Kovar, Olivier Delattre. Functional characterization of Ewing's sarcoma susceptibility loci. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improve...
Source: Cancer Research - October 9, 2014 Category: Cancer & Oncology Authors: Grunewald, T., Aynaud, M.-M., Tirode, F., Tomazou, E., Surdez, D., Frio, T. R., Bernard, V., Raynal, V., Lucchesi, C., Pierron, G., Gilardi-Hebenstreit, P., Charnay, P., Kovar, H., Delattre, O. Tags: Genetic Predisposition to Pediatric Cancers Source Type: research
Abstract A63: YB-1 is critical for stress granule assembly and protects cells from oxidative stress
Stress granules (SGs) are highly conserved cytoplasmic ribonucleoprotein complexes that modulate gene expression and cellular homeostasis under prototypical stress forms. SG formation protects cells under stress conditions by protecting untranslated mRNAs until stress relief, and cells that are incapable of forming SGs are more vulnerable to diverse stressors compared to cells that are proficient at SG formation. The transcription and translation regulation factor Y-box binding protein 1 (YB-1) is recruited to SG, but its exact contribution to formation of these structures is not clear. Using several stress inducing agents...
Source: Cancer Research - October 9, 2014 Category: Cancer & Oncology Authors: Somasekharan, S. P., Leprivier, G., Evdokimova, V., EI-Naggar, A., Hajee, S., Gleave, M., Sorensen, P. H. Tags: Sarcomas (Bone and Soft Tissue) Source Type: research
Mycoplasma Hyorhinis Infection and Carcinogenesis
In conclusion, our study unveils the effect of M. hyorhinis infection on gastric cancer survival and uncovers the mechanisms by which M. hyorhinis infects mammalian cells and promotes cancer cell migration. Cancer Res; 74(20); 5782–94. ©2014 AACR.
Source: Cancer Research - October 14, 2014 Category: Cancer & Oncology Authors: Duan, H., Chen, L., Qu, L., Yang, H., Song, S. W., Han, Y., Ye, M., Chen, W., He, X., Shou, C. Tags: Oncogenesis, Oncogenesis: In Vitro Molecular and Cellular Pathobiology Source Type: research
Abstract 2: Paxillin enhances angiogenesis through transcriptional regulation of Src in ovarian cancer
Purpose: Paxillin (PXN) expression is increased in various cancer types, but its biological and clinical impact is not well understood. Here, we examined the biological effects of paxillin in ovarian cancer.
Methods: The in vivo (HeyA8 and HeyA8-MDR orthotopic mouse models of ovarian cancer) and in vitro (tube formation assays, reverse phase protein array (RPPA) analysis, RT-PCR chromatin-immunoprecipitation (ChIP) assay) effects of paxillin were examined in ovarian cancer.
Results: Paxillin silencing using siRNA incorporated in DOPC nanoliposomes resulted in 55% reduction in tumor growth in a HeyA8 orthotopic ovarian cancer mouse model (p
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Choi, H. J., Kim, S.-W., Pradeep, S., Dalton, H. J., Rupaimoole, R., Mangala, S., Lopez, G., Anil, S. K. Tags: Tumor Biology Source Type: research
Abstract 20: Adiponectin increases VEGF expression and promotes angiogenesis in human chondrosarcoma
Vascular endothelial growth factor (VEGF) is an angiogenic mediator in tumors and has been implicated in the pathogenesis and progression of cancer. Adiponectin is a protein hormone secreted by adipose tissue. We recently found that adiponectin increased metastasis in human chondrosarcoma. However, the effect of adiponectin on VEGF expression and angiogenesis in human chondrosarcoma cells is mostly unknown. Here we found that adiponectin promoted VEGF expression in human chondrosarcoma and subsequently increased migration and tube formation in endothelial progenitor cells (EPCs). Pretreatment of cells for 30 min with PI3K ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Shih, J.-S., Tang, C.-H. Tags: Tumor Biology Source Type: research
Abstract 26: MUC1 enhances neuropilin-1 signaling in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis of all cancers and is the 4th leading cause of cancer-related deaths in the United States. Mucin1 (MUC1) is a transmembrane glycoprotein over-expressed in more than 60% of PDA and its expression correlates with high metastases and poor prognosis. In PDA, there is a correlation between blood vessel density, tumor levels of VEGF, and disease progression. We have recently discovered a novel association between MUC1 and neuropilin-1 (NRP-1) expression. Neuropilin-1 (NRP-1) is a co-receptor for VEGF165 and blockade of NRP-1-VEGF165 interaction has been shown to inhi...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Zhou, R., Curry, J., Grover, P., Roy, L. D., Leung, T., Mukherjee, P. Tags: Tumor Biology Source Type: research
Abstract 30: Modulating the angiogenic potential of human microvascular endothelial cells by an endogenous zinc finger transcription factor, ZNF24
Angiogenesis, the formation of new blood vessels from preexisting ones, is an indispensible process under normal physiological conditions such as embryonic development, certain stages of the female reproductive cycle and placenta formation during pregnancy as well as under pathological conditions such as wound healing, diabetic retinopathy, and cancer initiation, progression and metastasis. We have previously identified the molecular mechanism by which a zinc finger transcription factor, ZNF24, functions as a new inhibitor of tumor angiogenesis. ZNF24 represses the transcription of vascular endothelial growth factor (VEGF)...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Jia, D., Huang, L., Bischoff, J., Moses, M. Tags: Tumor Biology Source Type: research
Abstract 38: Quantitative proteomic approaches to identify biomarkers for oral cancer & targeting S100A7 by RNA-mediated interference through NF kappa beta-mediated pathway
Oral cancer is a leading cause of cancer death worldwide. The goal of cancer-screening program is to detect tumours at early stage. Moreover the screening tool must be sufficiently non invasive and inexpensive to allow widespread applicability.Protein biomarker discovery for early detection of head and neck squamous cell carcinoma (HNSCC) is a crucial needs to improve patient outcomes. The proteins secreted from cancer tissues are an important molecules which play a vital role, involved in various biological processes related to cancer metastasis and progression which makes a tissue proteome a rich reservoir of potential b...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Dey, K. K., Mandal, M. Tags: Tumor Biology Source Type: research
