Filtered By:
Drug: Herceptin
This page shows you your search results in order of date. This is page number 3.
Order by Relevance | Date
Total 51 results found since Jan 2013.
Abstract C26: Development of selective MELK kinase inhibitors for breast cancer treatment
In this study, we are reporting development of a series of selective MELK kinase inhibitors. Synthesized compounds exert excellent selectivity and potency in MELK inhibition in a low nanomolar range. Therapeutic effect of the compounds was investigated in the panel of breast cancer cell lines with different genetic background as well as with different MELK kinase levels; it was shown that for some cell lines compounds induced cell death with nanomolar ED50 values. The compound's effect on the proliferation and in the colony formation assay was also investigated. Taken altogether, the presented data supports our rationale o...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kowalczyk, P., Węgrzyn, P., Prokopowicz, M., Knop, M., Mazur, K., Dziedzic, K., Gluza, K., Knop, M., Dziedzic, K., Mazur, K., Radzimierski, A., Commandeur, C., Zawadzka, M., Bloudoff, K., Vaillancourt, F., Larsen, N., Wang, J., Reynolds, D., Ito, D Tags: Cancer Stem Cells: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A62: PARP-1 regulates NF-{kappa}B-mediated IL-8 expression in HER2 positive breast cancer
Conclusions:Trastuzumab resistant HER2+ breast cancer cells remain sensitive to PARP inhibition. Further, PARP-1 regulates the expression of IL-8, an NF-B regulated gene. These results suggest that inhibition of the interaction between PARP-1 and the NF-B signaling pathway may be a potential mechanism behind the sensitivity to PARPi in HER2+ trastuzumab resistant breast cancer cells.Citation Format: Monicka E. Wielgos, Rajani Rajbhandari, Susan Nozell, C. Kent Osborne, Rachel Schiff, Eddy S. Yang. PARP-1 regulates NF-B-mediated IL-8 expression in HER2 positive breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORT...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Wielgos, M. E., Rajbhandari, R., Nozell, S., Osborne, C. K., Schiff, R., Yang, E. S. Tags: EGFR / Her2: Poster Presentations - Proffered Abstracts Source Type: research
Abstract 737: Clonal evolution of the HER2 L755S mutation as a mechanism of acquired HER-targeted therapy resistance
Conclusion: Acquired L/LT resistance in the two BT474 R lines is due to selection of HER2 L755S subclones present in parental cells. The higher HER2 L755S levels in BT474 parentals compared with other parentals, and detection of its subclonal presence in a pre-treatment HER2+ BC patient, suggest that sensitive mutation detection methods will be needed to identify patients with potentially actionable HER family mutations in primary tumor. Treating this patient group with an irreversible TKI like Afa may prevent resistance and improve clinical outcome of this subset of HER2+ BC.Citation Format: Xiaowei Xu, Agostina Nardone, ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Xu, X., Nardone, A., Hu, H., Qin, L., Nanda, S., Heiser, L., Wang, N., Covington, K., Chen, E., Renwick, A., Mitchell, T., Shea, M., Wang, T., De Angelis, C., Contreras, A., Gutierrez, C., Fuqua, S., Chamness, G., Shaw, C., Li, M., Wheeler, D., Hilsenbeck Tags: Experimental and Molecular Therapeutics Source Type: research
Caveolin-1 Dependent Endocytosis Enhances the Chemosensitivity of HER-2 Positive Breast Cancer Cells to Trastuzumab Emtansine (T-DM1)
In this study, the relationship between caveolin-1 expression and the chemosensitivity of HER-2-positive breast cancer cells to T-DM1 was investigated. Samples from 32 human breast cancer biopsy and normal tissue specimens were evaluated immunohistochemically for caveolin-1 expression. Caveolin-1 was shown to be expressed in 68% (22/32) of the breast cancer specimens. In addition, eight (72.7%, 8/11) HER-2 positive breast cancer specimens had a higher caveolin-1 expression than normal tissues. HER-2-positive BT-474 and SKBR-3 breast cancer cells that express low and moderate levels of caveolin-1, respectively, were treated...
Source: PLoS One - July 14, 2015 Category: Biomedical Science Authors: Yuan-Chiang Chung et al. 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
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 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
Targeting of EGFR and HER2 with therapeutic antibodies and siRNA
Conclusion
The epidermal growth factor receptor HER2 is a promising anti-tumor target for the therapy of glioblastoma. HER2 targeting may represent a promising strategy to induce cell physiological and radiobiological anti-tumor effects in glioblastoma.
Source: Strahlentherapie und Onkologie - January 29, 2015 Category: Cancer & Oncology Source Type: research
Examining the Protective Role of ErbB2 Modulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from...
Source: Toxicological Sciences - October 6, 2014 Category: Toxicology Authors: Eldridge, S., Guo, L., Mussio, J., Furniss, M., Hamre, J., Davis, M. Tags: Cardiovascular Toxicology Source Type: research
Abstract 218: MEOX-1 as a novel cancer stem cell target for treatment of trastuzumab-resistant Her2+ breast cancers
Introduction: Previous studies showed that 60-80% of Her2+ breast cancers develop Trastuzumab-resistance after one year treatment and more than 50% of Her2+ Trastuzumab-resistant breast cancers have PTEN deletion and increased populations of cancer stem cells (CSCs). The purpose of this study is to explore novel targets to regulate cancer stem cells and to test treatment option for Her2+ Trastuzumab-resistant breast cancer.
Method: Trastuzumab resistance of Her2+ breast cancer cells (BT474) was induced by shRNA knockdown of PTEN and long term treatment of Trastuzumab (LTT) in comparison with Trastuzumab-sensitive BT474. Th...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Sun, L., Burnett, J. P., Gasparyan, M., Korkaya, H., Jiang, H., Liu, Y., Connarn, J., Wicha, M., Sun, D. Tags: Tumor Biology Source Type: research
Abstract 4381: MiR-205 and Trastuzumab: Potential as adjuvant therapeutic tool and predictive biomarker
Despite the improvement in the management of HER2+ breast cancer patients with the approval of Trastuzumab in the clinical practise, and the success rate of this treatment, a still considerable percentage of patients do not respond or eventually develop a secondary resistance, leading to relapse and poor outcome. A crucial issue is represented by the urgent need of biomarkers able to predict the response to treatment, and certainly of new therapeutic tools to counteract the resistance mechanisms. It is known that resistance to anti-HER2 therapies can be due to escape mechanisms triggered by alternative receptors: here we s...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: D'Ippolito, E., Piovan, C., Plantamura, I., Giussani, M., Casalini, P., Campiglio, M., Tagliabue, E., Iorio, M. V. Tags: Molecular and Cellular Biology Source Type: research
Abstract 5416: Development of a nanoparticle platform for the targeted delivery of siRNA to HER2-positive breast cancers
Successful siRNA based therapy has the potential to revolutionize cancer therapy by mediating the silencing of any gene deemed important for disease progression. However, unprotected siRNA has a short half-life in blood and lacks the ability to selectively identify target cells. Our group is developing an effective siRNA based nanoparticle platform that overcomes these shortcomings by utilizing a mesoporous silica nanoparticle electrostatically loaded with siRNA and conjugated with an antibody for target homing. The human epidermal growth receptor type 2 (HER2) is a highly validated therapeutic target in breast cancer due ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Goodyear, S. M. Tags: Cancer Chemistry Source Type: research
Abstract 1165: Focal adhesion kinase (FAK) mediates fibroblast-induced HER2+ breast cancer cell migration and invasion through a mechanism involving Stat3
In this study, we have investigated the metastatic responses of HER2+ breast cancer cells to fibroblasts and whether FAK is involved in these events.
Conditioned medium derived from human lung fibroblast MRC-5 cells was used to stimulate Her2+ SKBr3 breast cancer cells in the presence or absence of FAK inhibitor, PF271, or after FAK gene knockdown, prior to determining changes in migration (Boyden Chamber assay), 3d matrix invasion, growth and FAK-mediated signalling. To compare the role of FAK with HER2 in these cells, the HER2 targeted agent, trastuzumab was additionally employed.
Whilst fibroblast-conditioned medium (FC...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lazaro, G., Smith, C., Hiscox, S. Tags: Tumor Biology Source Type: research
Abstract 3783: Adipocytes inhibit trastuzumab-mediated ADCC via induction of GDF15
Conclusion: Adipocytes inhibit antitumor activity of trastuzumab in HER2-expressing breast cancer cells via secretion of factors that reduce cancer cell sensitivity to ADCC. Our findings underline the importance of adipose tissue in the resistance to trastuzumab, and suggest that development of approaches targeting GDF15 may sensitize cancer cells to trastuzumab-based therapy.
Citation Format: Minh Ngoc Duong, Aurore Cleret, Eva-Laure Matera, Kamel Chettab, Doriane Poloni, Sandrine Valsesia-Wittmann, Béatrice Clémenceau, Charles Dumontet. Adipocytes inhibit trastuzumab-mediated ADCC via induction of GDF15. [abstract]. In...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Duong, M. N., Cleret, A., Matera, E.–L., Chettab, K., Poloni, D., Valsesia–Wittmann, S., Clemenceau, B., Dumontet, C. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 1821: HER3 activation by MET contributes to trastuzumab resistance in HER2-positive breast cancer
Conclusion: MET may play a key role in maintaining HER3 phosphorylation during trastuzumab treatment and resistance in HER2 positive breast cancer.
Citation Format: Kenji Hashimoto, Valentine Macaulay, Anthony Kong. HER3 activation by MET contributes to trastuzumab resistance in HER2-positive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1821. doi:10.1158/1538-7445.AM2014-1821
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Hashimoto, K., Macaulay, V., Kong, A. Tags: Experimental and Molecular Therapeutics Source Type: research
