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Drug: Tamoxifen

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Total 112 results found since Jan 2013.

Abstract PD6-1: The long noncoding RNA M41 promotes aggressiveness and tamoxifen resistance in ER-positive breast cancers
In this study, we identify M41 as the top outlier lncRNA in ER-positive vs ER-negative breast cancer and investigate its role in preclinical cancer phenotypes and clinical outcomes. Methods and Materials: RNA sequencing was performed on 89 breast cancer samples and cell lines, including 42 ER+ cases, and a modified cancer outlier analysis was used to identify lncRNAs enriched in ER-positive disease. To assess ER regulation of the top enriched lncRNA (M41), ChIP-Seq and ChIP-PCR was used to detect binding of ER to M41 promoter and qPCR was used to determine changes in M41 expression following 10 nM estradiol treatment in MC...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Feng, F. Y., Ma, T., Speers, C., Iyer, M. K., Zhao, S., Prensner, J. R., Rae, J. M., Pierce, L. J., Chinnaiyan, A. M. Tags: Poster Discussion Abstracts Source Type: research

Abstract P3-05-11: Glutamine metabolism promotes survival through the unfolded protein response in endocrine resistant breast cancer
About 70% of all breast cancers are estrogen receptor alpha positive (ER+). Anti-hormone therapy such as antiestrogens (e.g.,Tamoxifen; TAM) are often used to treat ER+ breast cancer but breast cancer cells can develop resistance to these drugs (endocrine resistance). Unfortunately, ∼50% percent of all antiestrogen treated tumors eventually develop endocrine resistance, and therefore, there is an urgent need to find ways to treat this incurable disease. Endocrine resistant cells survive antiestrogen treatment by initiating a pro-survival pathway mediated by an evolutionary conserved process call the unfolded protein resp...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Shajahan-Haq, A. N., Demo, S., Clarke, R. Tags: Poster Session Abstracts Source Type: research

Triptolide inhibits human breast cancer MCF-7 cell growth via downregulation of the ERα-mediated signaling pathway.
CONCLUSION: The anticancer activity of triptolide against ERα-positive human breast cancer is partially mediated by downregulation of the ERα-mediated signaling pathway. PMID: 25864647 [PubMed - as supplied by publisher]
Source: Acta Pharmacologica Sinica - April 13, 2015 Category: Drugs & Pharmacology Authors: Li H, Pan GF, Jiang ZZ, Yang J, Sun LX, Zhang LY Tags: Acta Pharmacol Sin Source Type: research

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

A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors.
Abstract Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity ...
Source: Toxicology and Applied Pharmacology - February 2, 2015 Category: Toxicology Authors: Kumar R, Verma V, Sharma V, Jain A, Singh V, Sarswat A, Maikhuri JP, Sharma VL, Gupta G Tags: Toxicol Appl Pharmacol Source Type: research

Secretory prostate apoptosis response (Par)-4 sensitizes multicellular spheroids (MCS) of glioblastoma multiforme cells to tamoxifen-induced cell death
Publication date: Available online 21 November 2014 Source:FEBS Open Bio Author(s): Jayashree C. Jagtap , Parveen D , Reecha D. Shah , Aarti Desai , Dipali Bhosale , Ashish Chugh , Deepak Ranade , Swapnil Karnik , Bhushan Khedkar , Aaishwarya Mathur , Kumar Natesh , Goparaju Chandrika , Padma Shastry Glioblastoma multiforme (GBM) is the most malignant form of brain tumor and is associated with resistance to conventional therapy and poor patient survival. Prostate apoptosis response (Par)-4, a tumor suppressor, is expressed as both an intracellular and secretory/extracellular protein. Though secretory Par-4 induces apopto...
Source: FEBS Open Bio - November 22, 2014 Category: Molecular Biology Source Type: research

O2-15-2 * y-box binding protein-1 activation may modify the responses to endocrine and her2-targeted therapeutics in breast cancer
Conclusion and Discussion: Based on our basic and clinical study, YB-1 activation plays an essential role in expression of HER2/ErbB2, depending upon the absence or presence of ERα in breast cancer. The cross-talk of ERα and HER2 through activated YB-1 may thus specify biological characteristics in breast cancers luminal A, luminal B (HER2+), luminal B (HER2-), HER2 disease and triple negative. This study may propose an idea how endocrine and HER2-targeted therapeutics are mutually optimized against breast cancer.
Source: Annals of Oncology - October 19, 2014 Category: Cancer & Oncology Authors: Kuwano, M., Shibata, T., Kawahara, A., Hattori, S., Takahashi, R., Watari, K., Murakami, Y., Izumi, H., Kage, M., Ono, M. Tags: Oral Session (Oral presentations categorized by each organ) Source Type: research

Abstract 3943: siRNA-mediated HuR silencing sensitizes triple-negative breast cancer cells to radiation therapy
HuR is a ubiquitously expressed member of the Elav/Hu family of RNA-binding proteins which can associate with mRNAs containing AU-rich elements in their 3′-untranslated regions. It is predominantly a nuclear protein that translocates to the cytoplasm in response to stress signals and stabilizes mRNAs encoding proteins implicated in cell proliferation, angiogenesis, apoptosis, and stress response. Studies examining HuR expression in human cancers indicated that elevated cytoplasmic HuR expression is associated with a high histologic grade, large tumor size, and poor survival of patients with cancer, leading to the hypothe...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Basalingappa, K. M., Mehta, M., Griffith, J. N., Muralidharan, R., Gorospe, M., Ramesh, R., Munshi, A. Tags: Tumor Biology Source Type: research

Abstract 620: Evidence for combination tamoxifen and betulinic acid to treat hormone responsive- and unresponsive breast cancer by attenuation of Pygopus expression
The presence of the estrogen and progesterone hormone receptors (ER and PR) in advanced breast cancer tumour nuclei is predictive for response to hormone disruptive therapy. However, the accuracy of ER and PR testing can be variable and although patients receive significant benefit from hormone therapy, they ultimately become refractory to treatment. The chromatin remodeling protein: human Pygopus2 (hPygo2), is important for oncogenic growth and cell cycle progression and may serve as a diagnostic or targetable biomarker for breast cancer. Here we demonstrate that ER-alpha (Erα)−Sp1 transcription factor (Sp1) complexes ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Tzenov, Y., Andrews, P., Popadiuk, C., Kao, K. R. Tags: Endocrinology Source Type: research

Abstract 4227: The ribonucleotide reductase inhibitor Didox reverses tamoxifen resistance in breast cancer cells
In this study, we report that the inhibition of RRM2 by the small molecule inhibitor of ribonucleotide reductase activity Didox (3, 4-dihydroxybenzohydroxamic acid), significantly reduced tamoxifen induced cell proliferation in AKT overexpressing cells and tamoxifen resistant tumors generated by these cells. As well, Didox in combination with tamoxifen also inhibited cell proliferation in acquired tamoxifen resistant breast cancer cell lines. Employing comprehensive cell culture and in vivo models, we demonstrate that combining tamoxifen with Didox may reverse tamoxifen resistance in AKT expressing breast cancer cells. Cit...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Shah, K. N., Elford, H. L., Faridi, J. S. Tags: Molecular and Cellular Biology Source Type: research

Abstract 1969: Overexpression of specific CD44 variants mediate endocrine insensitivity and invasion in breast cancer cells
The majority of breast cancers express the oestrogen receptor and are potentially amenable to antihormone therapy; however the clinical effectiveness of these agents is limited by the phenomenon of acquired resistance which is associated with disease relapse and poor prognosis. In vitro evidence suggests that acquired resistance to tamoxifen and fulvestrant results in a significant gain to the migratory and invasive nature of breast cancer cells which may augment their metastatic potential in vivo. We have previously demonstrated that the CD44 receptor is overexpressed in acquired endocrine resistance and contributes to a ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Bellerby, R. L., Smith, C., Gee, J., Martin, T., Barrett-Lee, P., Hiscox, S. Tags: Tumor Biology Source Type: research

Abstract 4048: GFR{alpha}1 is required for GDNF-induced viability, migration, and signaling through RET in breast cancer cells
In this study we tested the functional consequences of silencing GFRα1 in ERα + MCF7 cells on tumor cell migration, invasion, and RET signaling. We showed that targeted reduction of GFRα1 significantly inhibited GDNF-induced migration in both a transwell (p=
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Ferrante, C. A., DeAngelis, N., Verona, R. Tags: Tumor Biology Source Type: research

Abstract 4755: Estrogen receptor mediates novel mechanisms of estrogen-induced growth and tamoxifen resistance in invasive lobular carcinoma
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer representing ∼10% of newly diagnosed breast tumors. Over 90% of ILC cases are ER-positive, however, endocrine response and estrogen signaling are not well described in ILC. Retrospective analyses suggest that ILC patients treated with endocrine therapy have poorer outcomes than invasive ductal carcinoma (IDC) patients with similar biomarkers, and that ILC patients may not benefit from adjuvant tamoxifen. Additionally, we have recently identified ILC-specific ER-target genes and de novo tamoxifen resistance driven by ER in ILC model systems. Based...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Sikora, M. J., Bahreini, A., Oesterreich, S. Tags: Endocrinology Source Type: research

151pd * arid1a role in cell cycle regulation and proliferation in mouse and human gynaecological tissues reveals potential therapeutic targets
Conclusions: A core ARID1A-driven transcriptional programme, conserved accross normal tissues and species appears to exist, centred around regulation of genes involved in the G2/M checkpoint. ARID1A loss promotes proliferation in normal tissues, providing important clues as to the mechanisms of ARID1A-driven carcinogenesis. Mitotic kinases emerge as potential therapeutic targets in ARID1A mutant tumours, an observation that is not evident from studies in cancer cell lines.Disclosure: All authors have declared no conflicts of interest.
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Gounaris, I., Brenton, J. Tags: basic science Source Type: research

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