Filtered By:
Source: Molecular Cancer Research
This page shows you your search results in order of date. This is page number 4.
Order by Relevance | Date
Total 53 results found since Jan 2013.
Abstract B50: MEK inhibitors mount a two-pronged attack to kill estrogen receptor positive (ER+) breast cancer cells undergoing hormonal therapy: Attenuated autophagy and induction of apoptosis
In this study, we hypothesized that the requirement of MEK1/MAPK1/2 for pro-survival autophagy is due, in part, to its role in blocking the intracellular accumulation of dephosphorylated BimEL. To test this hypothesis, we modulated the expression of dephosphorylated BimEL with either a BimEL cDNA expression vector, siRNA targeting of BimEL, or MEK1 blockade with the small molecule inhibitor U0126 and determined the levels of the autophagic flux in ER+ breast cancer cells undergoing antiestrogen treatment. The determination of autophagic flux was made by comparing the levels of two proteins involved in autophagy -the LC3 /A...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Takhar, S., Manning, M., Eason, A., Dix, M., Periyasamy-Thandavan, S., Padi, R., Bieberich, E., Hill, W., Browning, D., Ganapathy, V., Thangaraju, M., Schoenlein, P. V. Tags: RAS Targeting: Poster Presentations - Proffered Abstracts Source Type: research
Abstract B52: Therapeutic targeting of human KRAS in pancreatic cancer using a novel method of gene-silencing: U1 adaptors
Conclusion: We have demonstrated that the U1 Adaptor method of gene silencing can be successfully applied to target human KRAS both in vitro and in vivo. These results support the continued investigation of U1 Adaptor technology as a strategy for therapeutic targeting of RAS oncogenes.Citation Format: Ashley T. Tsang, Xin Yu, Rafal Goraczniak, Mark Brenneman, Samuel Gunderson, Darren R. Carpizo. Therapeutic targeting of human KRAS in pancreatic cancer using a novel method of gene-silencing: U1 adaptors. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; La...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Tsang, A. T., Yu, X., Goraczniak, R., Brenneman, M., Gunderson, S., Carpizo, D. R. Tags: RAS Targeting: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A55: KRAS gene amplification is a distinct molecular subgroup of gastroesophageal adenocarcinoma that may benefit from combined RAS/RAF/MEK/ERK and PI3K/PTEN/AKT/mTOR pathway inhibition
Conclusions: In this series, we observed KRAS wild type gene amp+ to be present in a subset (16%) of GEC patients at diagnosis, correlating with very high protein expression. KRAS amp+ was present after treatment with trastuzumab in HER2+ patients, and also after anti-MET therapy. These data suggest that KRAS amp+ represents a molecular subset with advanced disease at diagnosis. The observation of acquired KRAS amp+ after targeted therapies may be a resistance mechanism to anti-HER and anti-MET inhibitors. Inhibition using combined MEK/AKT pathway inhibitors, and proof-of-principle siRNA, warrants further investigation for...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Henderson, L., Xu, P., Rambo, B., Liao, W.-L., Hembrough, T., Catenacci, D. Tags: Role of WT RAS and RAS Isoforms: Poster Presentations - Proffered Abstracts Source Type: research
ATR and ATM Loss-of-Function
Mechanisms to maintain genomic integrity are essential for cells to remain viable. Not surprisingly, disruption of key DNA damage response pathway factors, such as ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia and RAD3-related (ATR) results in loss of genomic integrity. Here, a synthetic lethal siRNA-screening approach not only confirmed ATM but identified additional replication checkpoint proteins, when ablated, enhanced ATR inhibitor (ATRi) response in a high-content -H2AX assay. Cancers with inactivating ATM mutations exhibit impaired DNA double-stranded break (DSB) repair and rely on compensatory repair pat...
Source: Molecular Cancer Research - January 15, 2015 Category: Cancer & Oncology Authors: Menezes, D. L., Holt, J., Tang, Y., Feng, J., Barsanti, P., Pan, Y., Ghoddusi, M., Zhang, W., Thomas, G., Holash, J., Lees, E., Taricani, L. Tags: DNA Damage and Repair Source Type: research
Role of ATX and LPA Receptors in the Tumor Microenvironment
Autotaxin (ENPP2/ATX) and lysophosphatidic acid (LPA) receptors represent two key players in regulating cancer progression. The present study sought to understand the mechanistic role of LPA G protein–coupled receptors (GPCR), not only in the tumor cells but also in stromal cells of the tumor microenvironment. B16F10 melanoma cells predominantly express LPA5 and LPA2 receptors but lack LPA1. LPA dose dependently inhibited invasion of cells across a Matrigel layer. RNAi-mediated knockdown of LPA5 relieved the inhibitory effect of LPA on invasion without affecting basal invasion. This suggests that LPA5 exerts an anti-...
Source: Molecular Cancer Research - January 15, 2015 Category: Cancer & Oncology Authors: Lee, S.-C., Fujiwara, Y., Liu, J., Yue, J., Shimizu, Y., Norman, D. D., Wang, Y., Tsukahara, R., Szabo, E., Patil, R., Banerjee, S., Miller, D. D., Balazs, L., Ghosh, M. C., Waters, C. M., Oravecz, T., Tigyi, G. J. Tags: Signal Transduction Source Type: research
LOXL2 Regulates Integrin {alpha}5/{beta}1 in ccRCC Cells
In conclusion, LOXL2 is a potent regulator of integrin α5 and integrin β1 protein levels and functions in a tumor-promoting capacity in ccRCC.
Implications: This is the first report demonstrating that LOXL2 is highly expressed and involved in ccRCC progression by regulating the levels of integrins α5 and β1. Mol Cancer Res; 12(12); 1807–17. ©2014 AACR.
Source: Molecular Cancer Research - December 17, 2014 Category: Cancer & Oncology Authors: Hase, H., Jingushi, K., Ueda, Y., Kitae, K., Egawa, H., Ohshio, I., Kawakami, R., Kashiwagi, Y., Tsukada, Y., Kobayashi, T., Nakata, W., Fujita, K., Uemura, M., Nonomura, N., Tsujikawa, K. Tags: Oncogenes and Tumor Suppressors Source Type: research
Abstract A36: Knockdown of integrin-linked kinase reduces invasive and metastatic potential of renal cell carcinoma
Conclusions: ILK is highly expressed in advanced RCC and its high expression is related to EMT-related protein in RCC. Knockdown of ILK inhibited molecular EMT markers and suppressed cell migration and invasion in vitro and metastasis in orthotopic tumor model. These results suggest the therapeutic potential of ILK inhibition on invasion and metastasis in advanced RCC.Citation Format: Han Kyung Seok, Raven Peter, Awrey Shannon, Li Estelle, Fazli Ladan, Gleave Martin, So Alan. Knockdown of integrin-linked kinase reduces invasive and metastatic potential of renal cell carcinoma. [abstract]. In: Proceedings of the AACR Specia...
Source: Molecular Cancer Research - November 13, 2014 Category: Cancer & Oncology Authors: Seok, H. K., Peter, R., Shannon, A., Estelle, L., Ladan, F., Martin, G., Alan, S. Tags: Target Discovery and Validation: Poster Presentations - Proffered Abstracts Source Type: research
STAT3 Activates GM-CSFR{alpha} in CLL
Here, it was determined that chronic lymphocytic leukemia (CLL) cells express the α subunit, but not the β subunit, of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR/CSF2R). GM-CSFRα was detected on the surface, in the cytosol, and in the nucleus of CLL cells via confocal microscopy, cell fractionation, and GM-CSFRα antibody epitope mapping. Because STAT3 is frequently activated in CLL and the GM-CSFRα promoter harbors putative STAT3 consensus binding sites, MM1 cells were transfected with truncated forms of the GM-CSFRα promoter, then stimulated with IL6 to activa...
Source: Molecular Cancer Research - September 11, 2014 Category: Cancer & Oncology Authors: Li, P., Harris, D., Liu, Z., Rozovski, U., Ferrajoli, A., Wang, Y., Bueso-Ramos, C., Hazan-Halevy, I., Grgurevic, S., Wierda, W., Burger, J., O'Brien, S., Faderl, S., Keating, M., Estrov, Z. Tags: Genomics Source Type: research
