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Total 146 results found since Jan 2013.
Abstract 2679: Overexpression of Mcl-1 confers resistance to BRAFV600E inhibitors alone and in combination with MEK1/2 inhibitors in melanoma
Melanoma harboring BRAF mutations frequently develop resistance to BRAF inhibitors, limiting the impact of treatment. The most prevalent mechanisms of acquired resistance appear to reactivate MAPK pathway. Furthermore, relatively little is known about the determinants of de novo resistance. Here, we establish such a mechanism of resistance and subsequently identified a suitable drug combination to overcome the resistance. Single treatment of BRAF mutant melanoma cell lines with vemurafenib or dabrafenib (BRAF inhibitors) alone or in combination with trametinib (MEK1/2 inhibitor) resulted in overexpression of Mcl-1. Overexp...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Fofaria, N. M., Frederick, D. T., Sullivan, R. J., Flaherty, K. T., Srivastava, S. K. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 5504: Penfluridol suppresses triple negative breast cancer metastasis to brain by inhibiting {alpha}6{beta}4 integrins
Breast cancer is the second leading cause of cancer related deaths in the United States. Breast tumor metastasis to brain is primary cause of deaths. Brain metastasis of triple negative breast cancer cells (TNBC) is highly resistant to current therapies and is a cause of reduced survival rates in patients. In the current study, we evaluated the anti-cancer effects of penfluridol, a first generation antipsychotic drug against three different highly aggressive TNBC cell line. The IC50 of penfluridol was around 6 μM in 4T1, MDA-MB-231 and HCC-1806, breast cancer cells respectively. Our result showed that the expression of in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ranjan, A., Gupta, P., Srivastava, S. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4043: A novel CXCR4 pathway is required for migration of metastatic breast cancer cells
The research presented here supports a model whereby a novel CXCR4-Arf6-ERK pathway is critical for CXCR4 functionality in metastatic breast cancer cells. CXCR4 is a chemokine G protein-coupled receptor essential for migration of select neuronal and hematopoietic cells towards SDF (CXCL12), and is now recognized to promote cancer metastasis. Aberrant expression of CXCR4 in nonmotile primary tumor cells unmasks a migratory capacity and promotes metastatic homing of tumor cells to distal SDF-expressing organs. Metastasis is a major cause of mortality in cancer patients, leading to vigorous attempts to identify molecular path...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Freed, J., Shaffer, C. V., Moore, C. C. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3838: Functional crosstalk between histone deacetylase 5 (HDAC5) and lysine-specific demethylase 1 (LSD1) as a novel therapeutic target in triple-negative breast cancer cells
In this study, we demonstrated that HDAC5 physically interacts with LSD1 in MDA-MB-231 cells. Overexpression of HDAC5 increased LSD1 protein level through a reduction of LSD1 polyubiquitination. siRNA-mediated knockdown of HDAC5 mRNA, but not other class II HDACs or LSD1-containing complex members (HDAC1, HDAC2 and CoREST), significantly decreased LSD1 protein expression and half-life. HDAC5 overexpression reduced levels of H3K4me1/2, suggesting that HDAC5 acts as a positive regulator of LSD1-mediated H3K4 demethylation activity. Enhanced proliferation mediated by HDAC5 overexpression in MDA-MB-231 cells was diminished by ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Cao, C., Vasilatos, S., Oesterreich, S., Davidson, N. E., Huang, Y. Tags: Molecular and Cellular 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 4372: Phosphodiesterase 10A inhibition suppresses lung tumor cell growth by activating PKG to inhibit ras and Wnt signaling
We recently reported that phosphodiesterase 10A (PDE10) is overexpressed in colon tumors and essential for colon tumor cell growth (Li et al., Oncogene 2014), but a role in lung cancer has not been well studied. Human non-small cell lung cancer (NSCLC) cell lines were found to express appreciably higher PDE10 levels compared with normal airway epithelial cells, while silencing of PDE10 expression with siRNA or inhibition of PDE10 activity with small molecule inhibitors selectively inhibits NSCLC cell growth. Here we study the mechanism by which PDE10 inhibitors suppress NSCLC cell growth. At concentrations effective for in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Zhu, B., Lee, K., Canzoneri, J., Ramirez-Alcantara, V., Sigler, S., Gary, B., Butler, E., Keeton, A., Chen, X., Boyd, M., Piazza, G. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4405: Tumor-targeted nanotherapeutics
Directing anticancer agents specifically to tumors and/or cancer cells by targeting specific extracellular receptors fulfills the following three most important tasks: (1) preventing or at least substantially limiting adverse side effects on healthy tissues, (2) enhancing drug internalization by cancer cells, and (3) overcoming (at least in part) resistance mechanisms that are based on the active efflux of exogenous drugs from cancer cells.We developed several tumor-targeted nanoscale-based formulations: various nanocarriers (liposomes, lipid nanoparticles, dendrimers, polymers, quantum dots, mesoporous silica and supermag...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Garbuzenko, O. B., Kuzmov, A., Sapiezynski, J. E., Taratula, O., Shah, V., Zhang, M., Savla, R., John, S., Rodriguez-Rodriguez, L., Minko, T. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 3164: Inflammasomes: fanning the flames of malignant mesothelioma initiation
Malignant mesothelioma (MM) is an aggressive and devastating cancer of the pleural/peritoneal mesothelium related to asbestos exposure. MM has a low survival rate (average: less than 12 months). Despite the causal relationship between asbestos and MM development, the exact mechanism by which asbestos causes MM is still poorly understood. There is an urgent need for the identification of mechanism(s) that may help in early detection and finding new treatment targets for prevention and treatment of MM.We have recently shown that asbestos exposure of human mesothelial cells (HMCs) leads to the activation of the NLRP3 inflamma...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Thompson, J. K., MacPherson, M. B., Beuschel, S. L., Shukla, A. Tags: Immunology Source Type: research
Inhibition of DDAH1, but not DDAH2, results in apoptosis of a human trophoblast cell line in response to TRAIL
This study used the human extravillous trophoblast-derived cell line SGHPL-4 cells. All experiments were performed at least three times.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The effect of DDAH on trophoblast apoptosis was examined using siRNA and time-lapse microscopy. Changes in the expression of DDAH were followed by PCR and western blot analysis. Receptor expression was followed by flow cytometry.
MAIN RESULTS AND THE ROLE OF CHANCE
Inhibiting the expression of DDAH1, but not DDAH2, resulted in a significant increase in the sensitivity of the EVT cell line SGHPL-4 to tumour necrosis factor related apoptosis induci...
Source: Human Reproduction - July 19, 2015 Category: Reproduction Medicine Authors: Lumicisi, B. A., Cartwright, J. E., Leslie, K., Wallace, A. E., Whitley, G. S. Tags: Early pregnancy Source Type: research
Abstract P5-06-07: A novel role for breast cancer associated protein 2 (BCA2) in regulation replication-stress mediated DNA damage responses
Breast cancer associated gene 2 (BCA2) has been originally identified from invasive breast cancer cells and shown to be overexpressed in over 50% of invasive breast cancers. Its expression is known to be highly associated with estrogen receptor-alpha (ER-α) status and promote cell proliferation and invasive properties. Importantly, expression of BCA2 is minimal or undetectable in most normal cells and tissues, which makes it as a valuable biomarker for ER-α positive breast cancers and a potential therapeutic target. BCA2 protein is a RING and ZINC-finger domain containing E3 ubiquitin ligase that has been shown to auto-u...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Lee, Y.-H., Tripathi, K., Clark, D., Palle, K. Tags: Poster Session Abstracts Source Type: research
Abstract 1060: Integrated target discovery in the EMPathy Breast Cancer Network - Multidimensional analysis of epithelial mesenchymal plasticity (EMP) in experimental systems
The ability of breast cancer cells to switch between epithelial and mesenchymal phenotypes may be key to their survival in new environments, resistance to therapies and ability to form metastases. Epithelial mesenchymal plasticity (EMP) is instrumental in embryological development and has been implicated in stemness, therapy resistance and metastasis of breast cancer. EMP markers are enriched in basal-like, triple negative breast cancer, which is a type of breast cancer associated with early recurrence and poor prognosis, and established as a common phenotype in women with BRCA1 mutations. The EMPathy Breast Cancer Network...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Blick, T., Phillip, G., Tomaskovic-Crook, E., Hammacher, A., Wong, N., Haviv, I., The EMPathy Breast Cancer Network, Goodall, G., Davis, M., Thompson, E. W. Tags: Tumor Biology Source Type: research
Abstract 861: Survivin-mediated adaptive response: a risk factor for IGRT
Exposure of cells to very low doses of ionizing radiation can induce an enhanced resistance or adaptive response to a subsequent larger radiation dose as demonstrated by an increase in cell survival. Expression of a radio-adaptive response has been attributed to pro-survival signaling processes induced by very low radiation doses in the range of 5 to 100 mGy. The radiation-induced adaptive response is gaining considerable attention due in part to the expanding use of imaging technologies such as computerized axial tomography and portal imaging to monitor tumor response and positioning during multi-dose standard radiation t...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Grdina, D. J., Murley, J. S., Miller, R. C., Woloschak, G. E., Li, J. J., Weichselbaum, R. R. Tags: Clinical Research (Excluding Clinical Trials) Source Type: research
Abstract 1121: Extracellular matrix-integrin B1 signaling is a major mediator of epithelial-to-mesenchymal transition and contributes to prostate cancer invasion and metastasis
Within North America, prostate cancer is the most commonly diagnosed cancer in men with devastating implications deriving from metastasis, particularly those established in the bone. We have elucidated mechanisms by which prostate cancer undergoes metastasis with particular focus on the relationship between extracellular-matrix binding proteins, Integrin B1 (ITGB1) and epithelial-to-mesenchymal transition (EMT). Previous results in the laboratory suggested that prostate tumor cells depleted of ITGB1 were unable to form colonies in soft agarose and were impaired in their invasive abilities in vitro. In order to determine th...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Bugiel, S. R., McKittrick, E., Zhao, H., Howe, G. A., Addison, C. L. Tags: Tumor Biology Source Type: research
Abstract 2330: Transcription factor MAZ promotes cell growth and aggressive behavior of human pancreatic cancer cells
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cancer in the United States and the eighth worldwide. PDAC is most aggressive type of cancer that spreads rapidly and is seldom detected in its early stages as signs and symptoms may not appear until pancreatic cancer is quite advanced. MAZ (Myc-associated zinc-finger protein) or SAF1 (Serum amyloid A activating factor 1) gene is a member of multiple Cys2-His2-type zinc finger proteins that are activated in response to various inflammatory signals and may act as a transcription factor with dual roles in transcription initiation and termination. Deregulation ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Maity, G., Sarkar, S., Dhar, K., Dhar, G., Haque, I., Banerjee, S. K., Banerjee, S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2332: Oncogenic mutant KRAS modulates EZH2 expression through MEK-ERK signaling by remodeling gene expression in NSCLC
In this study, we investigated whether pharmacological disruption of signaling MEK-ERK pathway would affect EZH2 expression in a panel of NSCLC cell lines with and without KRAS mutation. Moreover, we analyzed the transcriptome expression following knockdown of EZH2 expression in NSCLC cell lines with different types of KRAS mutations.
Methods. NSCLC cell lines were treated with different doses of MEK inhibitor AZD6244 (0, 0.5 and 1μM) and the expressions of EZH2, MEK and MAPK were determined by Western-blots. Cell lines were transfected with gene-specific EZH2 siRNA and control siRNA. Gene expression profiling was perform...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Riquelme, E. M., Shen, L., Wang, J., Behrens, C., Minna, J. D., Wistuba, I. I. Tags: Molecular and Cellular Biology Source Type: research
