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Specialty: Cancer & Oncology
Cancer: HER2
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Total 124 results found since Jan 2013.
Abstract 2804: The thiazolidinedione pioglitazone enhances the cancer preventive activity of the rexinoid LG100268 in Her2/neu induced breast cancer
Two major unresolved issues for breast cancer prevention are the lack of effective preventive agents for estrogen receptor (ER)-negative disease and the potential toxicity of long-term pharmacologic treatment. The ability of retinoid X receptor (RXR)-selective retinoids (rexinoids) to inhibit breast cancer formation independently of ER-status was previously demonstrated in various preclinical models. The goal of our study was to identify ideal druggable targets for the synergistic amplification of the cancer preventive effect of synthetic rexinoids and test the efficacy of a low-dose combination treatment in vivo. We ident...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Uray, I. P., Rodenberg, J. M., Zhang, Y., Hill, J. L., Brown, P. H. Tags: Prevention Research Source Type: research
Abstract 3573: Novel G protein-coupled receptor targets in HER2+ breast cancer
Conclusion: In summary, functional knockdown screening and differential gene expression of GPCRs is a powerful tool for identifying GPCRs as candidate targets in BC. Using the combination of these two approaches, we have discovered that melatonin MT1 receptor as a potential drug target in HER2+ BC cells. The place in therapy for MT1 receptor antagonists, however, still remains to be determined.Citation Format: Raksha Bhat, Puja Yadav, Pavel Christiny, Rachel Schiff, Meghana V. Trivedi. Novel G protein-coupled receptor targets in HER2+ breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American As...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Bhat, R., Yadav, P., Christiny, P., Schiff, R., Trivedi, M. V. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 5109: The CARMA3-Bcl10-MALT1 signalosome mediates NF-{kappa}B activation and cellular invasion in AGTR1-positive breast cancer
Angiotensin II (Ang II) is a potent vasoconstrictor and vascular pro-inflammatory mediator, known classically for its role in promoting arterial dysfunction. Many of these pathogenic effects result from activation of NF-κB in response to stimulation of the type-1 Ang II receptor (AGTR1), a G protein-coupled receptor. We previously discovered that a complex composed of three proteins, CARMA3, Bcl10 and MALT1 (CBM signalosome) mediates AGTR1-dependent activation of NF-κB in vascular cells. Despite its principal role in vascular pathobiology, we recently found that AGTR1 is aberrantly overexpressed in 10-20% of breast cance...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ekambaram, P., Hubel, N., Lee, J.-Y., Klei, L., Concel, V., Delekta, P., Tomlins, S., McAllister-Lucas, L., Lucas, P. Tags: Tumor Biology Source Type: research
SERPINA1 is a direct estrogen receptor target gene and a predictor of survival in breast cancer patients.
Authors: Chan HJ, Li H, Liu Z, Yuan YC, Mortimer J, Chen S
Abstract
Of all breast cancer patients, about 70% are ER+ and 10% are ER+/HER2+. The ER+/HER2+ patients have a worse outcome compared to ER+/HER2- patients. Currently there is a lack of effective prognosis biomarkers for the prediction of outcome in ER+/HER2+ patients. Genome-wide differences in ER binding between the endocrine-responsive and endocrine-resistant cells were discovered using ChIP-seq, and combined with gene expression microarray data to identify direct ER target genes. These genes were correlated to survival outcome using publicly available b...
Source: Oncotarget - July 13, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Abstract PR01: Inhibitory role of phosphatidylinositol-3,4-bisphosphate in triple-negative breast cancers
Triple-negative breast cancer (lacking expression of estrogen receptor, progesterone receptor and amplification of HER2/Neu) remains one of the most aggressive subtypes, affects the youngest patients and yet still lacks an effective targeted therapy. Novel insights into the molecular mechanisms that drive these cancers are imperative to guide development and application of such targeted therapies. Data from The Cancer Genome Atlas and other sources have suggested that phospho-Akt (pAkt) levels are significantly higher in triple-negative tumors compared to either hormone receptor positive tumors (express estrogen and/or pro...
Source: Molecular Cancer Therapeutics - July 6, 2015 Category: Cancer & Oncology Authors: Reed, D. E., Shokat, K. M. Tags: Molecular Regulation of the PI3K-mTOR Network: Oral Presentations - Proffered Abstracts Source Type: research
Clinical significance of glycoprotein nonmetastatic B and its association with HER2 in breast cancer
Abstract
Glycoprotein nonmetastatic B (GPNMB) is a potential oncogene that is particularly expressed in melanoma and breast cancer (BC). To clarify its clinical significance in BC, we measured serum GPNMB in vivo and investigated its cross talk with human epidermal growth factor 2 (HER2). GPNMB was expressed in four of six breast cell lines (SK‐BR‐3, BT‐474, MDA‐MD‐231, and MDA‐MD‐157), two of six colorectal cell lines, and two of four gastric cancer (GC) cell lines. We established a GPNMB quantification system using enzyme‐linked immunosorbent assay (ELISA) for these cell lines. We measured serum GPNMB in...
Source: Cancer Medicine - June 16, 2015 Category: Cancer & Oncology Authors: Masako Kanematsu, Manabu Futamura, Masafumi Takata, Siqin Gaowa, Atsuko Yamada, Kasumi Morimitsu, Akemi Morikawa, Ryutaro Mori, Hideaki Hara, Kazuhiro Yoshida Tags: Original Research Source Type: research
Novel HER3/MUC4 oncogenic signaling aggravates the tumorigenic phenotypes of pancreatic cancer cells.
Authors: Lakshmanan I, Seshacharyulu P, Haridas D, Rachagani S, Gupta S, Joshi S, Guda C, Yan Y, Jain M, Ganti AK, Ponnusamy MP, Batra SK
Abstract
Several studies have demonstrated that MUC4 is involved in progression and metastasis of pancreatic cancer (PC). Here, we report that HER3/MUC4 interaction in HER2 low cells is critical in driving pancreatic tumorigenesis. Upon HER2 knockdown, we observed elevated expression of HER3 and MUC4 and their interactions, which was confirmed by immunoprecipitation and bioinformatics analyses. In paired human PC tissues, higher percentage of HER3 positivity (10/33, 30.3%; p = 0....
Source: Oncotarget - June 5, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Abstract P5-05-11: Growth hormone receptor silencing sensitizes triple negative breast cancer cells to chemotherapy
In this study we investigated the impact of GHR silencing in TNBC cells and further analyzed the possible mechanisms associated with GHR silencing induced sensitization. GHR was silenced using small interfering RNAs in metastatic breast cancer cells MDA MB 231 and MDA MB 468. Molecular analyses were performed to determine apoptosis, cytotoxicity, colony formation, invasion and migration in GHR knockdown cells. Silencing of GHR induced cytotoxicity and apoptosis in TNBC cells. Migratory and invasive potentials were drastically reduced in GHR silenced cells. Moreover, epithelial to mesenchymal transition markers were signifi...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Arumugam, A., Subramani, R., Nandy, S., Lopez-Valdez, R., Lakshmanaswamy, R. Tags: Poster Session Abstracts Source Type: research
Abstract P2-07-04: Treatment of metastatic breast cancer using two nanoparticles combined with siRNA targeting Twist1 to inhibit EMT
Breast cancer is the 2nd leading cause of cancer related deaths among women in the US with over 240,000 diagnoses and 40,000 deaths expected in 2014. Among the more serious and deadly forms of breast cancer are the Triple Negative Breast Cancers (TNBC) (ER-, PR-, HER2-). Mortality rates among patients rise dramatically when these cancers spread beyond the primary tumor site. Therefore reduction of tumor cell dispersion is a key component to minimizing mortality rates. Epithelial-Mesenchymal Transition (EMT) is the process by which cancer cells downregulate proteins associated with cell to cell adhesion (e.g. E-cadherin) re...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Finlay, J. B., Roberts, C. M., Lowe, G., Peng, L., Zink, J. I., Tamanoi, F., Glackin, C. A. Tags: Poster Session Abstracts Source Type: research
Abstract P5-07-06: Exploring the involvement of TTK kinase in centrosome amplification and Her2+ breast cancer
The centrosome is the cellular organelle responsible for accurate chromosome segregation. In normal cellular function, regulation of the centrosome duplication cycle in concert with the cell cycle is necessary for accurate passage of genetic information. However, when modulators of the cell and/or centrosome duplication cycles are deregulated, this process can result in centrosome amplification (CA, the acquisition of more than two centrosomes), leading to improper segregation of chromosomes and genomic instability. CA generates low-level aneuploidy (which is tolerated) and polyploidy (selected against when checkpoints are...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: King, J. L., Saavedra, H. I. Tags: Poster Session Abstracts Source Type: research
Abstract P4-05-15: Examining the role of Nm23-H1 in the metastatic profile of triple negative breast cancer (TNBC)
Conclusion: These results suggest a paradoxical role of the metastasis suppressor protein Nm23-H1 as an oncogene in TNBC cells. Nm23-H1 plays a vital role in the promotion of TNBC cellular migration, invasion, and the expression of proteins associated with motility and invasion. These data strongly suggest an oncogenic potential of Nm23-H1 in a subset of TNBCs and warrants further investigation of this protein a potential molecular marker for metastatic TNBCs.
Citation Format: Tanisha Z McGlothen, Rachel Tobin, Tiffanie Alcaide, LaTonia Taliaferro-Smith, Liu Tongrui, O'Regan Ruth. Examining the role of Nm23-H1 in the metas...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: McGlothen, T. Z., Tobin, R., Alcaide, T., Taliaferro-Smith, L., Tongrui, L., Ruth, O. Tags: Poster Session Abstracts Source Type: research
Abstract P3-05-13: Overexpression of insulin receptor substrate 4 can mediate acquired resistance to lapatinib-containing regimens in HER2+ breast cancer cells
Conclusion: IRS4 overexpression is a critical factor in causing resistance to lapatinib-containing regimens in BT474 cells. Investigation of IRS4 and its signaling partners in HER2+ human tumors resistant to lapatinib will be important to determine if this mechanism is also operative in patients.
Citation Format: Lanfang Qin, Maria B Hahn, Xiaoyong Fu, Martin J Shea, Mario Giuliano, Sarmistha Nanda, Xiaowei Xu, Huizhong Hu, Sung Yun Jung, Laura M Heiser, Nicholas Wang, Joe W Gray, Susan G Hilsenbeck, Chad Creighton, Chad A Shaw, Gary C Chamness, Dean P Edwards, Sabrina Herrera, Carolina Gutierrez, C Kent Osborne, Rachel Sc...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Qin, L., Hahn, M. B., Fu, X., Shea, M. J., Giuliano, M., Nanda, S., Xu, X., Hu, H., Jung, S. Y., Heiser, L. M., Wang, N., Gray, J. W., Hilsenbeck, S. G., Creighton, C., Shaw, C. A., Chamness, G. C., Edwards, D. P., Herrera, S., Gutierrez, C., Osborne, C. Tags: Poster Session Abstracts Source Type: research
Abstract P6-03-11: Erk5 as a therapeutic target in triple negative breast cancer (TNBC)
TNBC is a subtype of breast cancer known for its aggressive behavior and poor prognosis. TNBC accounts for 17-24% of all invasive breast cancers and is a subtype that lacks the expression of hormone receptors; oestrogen [ER], progesterone [PR]) and epidermal growth factor receptor 2 (HER2) receptors. Currently there has been a shift from using empirically derived agents that inhibit tumor cell growth and/or survival, to molecular therapies that target specific molecules that regulate these and other important biological processes. Despite the success of some new-targeted therapies to treat breast cancer, the outlook for th...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Miranda, M. S., Ejeh, F. A., Shi, W., Simpson, P., Lakhani, S., Khanna, K. K. Tags: Poster Session Abstracts Source Type: research
Abstract P2-06-04: Proteosome inhibitor bortezomib inhibits NF{kappa}B and effectively overcomes cancer stem cell escape triggered by Wnt inhibitor therapy in FOXC1+ basal-Like/claudin-low breast cancer
In this study, we sought to investigate the link between Wnt signaling and FOXC1 and its potential in regulating CSC biology in basal-Like/claudin-low breast cancer. We observed that exposure of the MDA-MB-231 basal-like/claudin-low cell line (low constitutive FOXC1 expressor) to Wnt3a (a canonical Wnt signaling ligand), resulted in increased expression of FOXC1. Reciprocally, overexpression of FOXC1 in MCF10A human mammary epithelial cells led to a pronounced increase in Wnt signaling activity, strongly suggestive of a direct or indirect positive feedback loop between Wnt signaling and FOXC1. More importantly, BT549 and H...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Ray, P. S., Tsai, C. Y., Ray, T., Kim, B., Jensen, T. W. Tags: Poster Session 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
