Mammary Cell News Volume 7.16 | Apr 30 2015

Blockade of a Key Region in the Extracellular Domain Inhibits HER2 Dimerization and Signaling
To test the hypothesis that HER2 activation requires a protein sequence in the human epidermal growth factor receptor 2 (HER2)-extracellular domain (ECD) that mediates HER2 homo- and heterodimerization, researchers introduced a series of deletion mutations in the third subdomain of HER2-ECD. These deletion mutants were retrovirally expressed in breast cancer cells that naturally overexpress HER2 and in noncancerous, HER2-negative breast epithelial cells. [J Natl Cancer Inst] Abstract | Press Release | Video

Adipose Cells Promote Resistance of Breast Cancer Cells to Trastuzumab-Mediated Antibody-Dependent Cellular Cytotoxicity
Investigators set up a co-culture system to study the effect of adipocytes on antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. They found that adipocytes, as well as preadipocytes, inhibited trastuzumab-mediated ADCC in human epidermal growth factor receptor 2-expressing breast cancer cells via the secretion of soluble factors. [Breast Cancer Res] Abstract | Full Article

Small Molecule Inhibition of Group I p21-Activated Kinases in Breast Cancer Induces Apoptosis and Potentiates the Activity of Microtubule Stabilizing Agents
PAK1 dysregulation was evaluated in two cohorts of breast cancer tissues. A novel small molecule inhibitor, FRAX1036, and RNA interference were used to examine PAK1 loss of function and combination with docetaxel in vitro. [Breast Cancer Res] Abstract | Full Article

MicroRNA-33b Inhibits Breast Cancer Metastasis by Targeting HMGA2, SALL4 and Twist1
Investigators report the identification of miR-33b as a negative regulator of cell stemness and metastasis in breast cancer. Compared with paired normal breast tissues, miR-33b expression is downregulated in breast tumor samples and inversely correlated with lymph node metastatic status. [Sci Rep] Full Article

Epithelial-Mesenchymal Transition Induces Similar Metabolic Alterations in Two Independent Breast Cancer Cell Lines
Two epithelial breast cancer cell lines were compared to their respective epithelial-mesenchymal transition-derived mesenchymal progeny for changes in metabolic pathways including glycolysis, glycogen metabolism, anabolic pathways and gluconeogenesis. [Cancer Lett] Abstract

Down-Regulating HIF-1α by Lentivirus-Mediated shRNA for Therapy of Triple Negative Breast Cancer
Investigators designed a recombinant lentivirus containing hypoxia inducible factor 1 (HIF-1) siRNA, developed stably transfected cell lines, and tested the anticancer effects of the siRNA on cancer cells in vitro and in vivo. [Cancer Biol Ther] Abstract

A Combination of the Telomerase Inhibitor, BIBR1532, and Paclitaxel Synergistically Inhibit Cell Proliferation in Breast Cancer Cell Lines
Scientists studied the combination of BIBR1532 and paclitaxel in breast cancer cell lines. Cell viability assays revealed that 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532) or paclitaxel alone inhibited proliferation in a dose-dependent manner, and combining the drugs synergistically induced growth inhibition in all breast cell lines tested independent of their p53, ER, and HER2 status. [Target Oncol] Abstract

CLINICAL RESEARCH

Moderate Level of HER2 Expression and Its Prognostic Significance in Breast Cancer with Intermediate Grade
Investigators analyzed the prognostic significance of moderate expression of human epidermal growth factor receptor 2 (HER2) in breast cancer with intermediate differentiation grade. They performed a multicenter retrospective register study of 8494 patients with primary non-metastatic breast cancer admitted between 2000 and 2011 to eight clinics in Germany. [Breast Cancer Res Treat] Abstract

Adjuvant Dose-Dense Chemotherapy in Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Trials
Researchers performed an updated systematic review and meta-analysis of the existing data from randomized Phase III trials regarding the efficacy and toxicity of this adjuvant dose-dense-chemotherapy strategy in early breast cancer. [Breast Cancer Res Treat] Abstract

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Dual mTOR Inhibitor-Fulvestrant Combo Feasible, with Clinical Benefit for Advanced Breast Cancer Patients
The dual mTOR inhibitor AZD2014, when combined with the hormonal therapy fulvestrant, was found to be safe in patients with advanced estrogen receptor-positive breast cancer, and some of them experienced clinical benefit from the drug combination. [Press release from American Association for Cancer Research (AACR) discussing research presented at the 2015 AACR, Philadelphia] Press Release | Clinical Trial

Adding the PI3K Inhibitor BYL719 to Letrozole Was Safe, with Early Signs of Activity against Metastatic ER-Positive Breast Cancer
Postmenopausal women with metastatic breast cancer positive for the estrogen receptor (ER) found that combination therapy with the phosphatidylinositol-3-kinase (PI3K) inhibitor BYL719 (alpelisib) and the antiestrogen letrozole was safe and tolerable, and a subset of the women gained clinical benefit from the combination. [Press release from American Association for Cancer Research (AACR) discussing research presented at the 2015 AACR, Philadelphia] Press Release | Clinical Trial

New Antibody-Drug Conjugate Shows Early Promise for Patients with Metastatic HER2-Positive Breast Cancer
An investigational antibody-drug conjugate called MM-302 was safe, tolerable, and showed signs of clinical activity in heavily pretreated patients with metastatic, HER2-positive breast cancer. [Press release from American Association for Cancer Research (AACR) discussing research presented at the 2015 AACR, Philadelphia] Press Release

Investigational ER Degrader Safe, with Early Signs of Antitumor Activity Against Advanced ER-Positive Breast Cancer
The new investigational estrogen receptor (ER) degrader GDC-0810 was safe and tolerable in postmenopausal women with advanced ER-positive breast cancer, and a subset of the women, all of whom were previously treated with standard endocrine therapy, gained clinical benefit from the drug, according to data from a first-in-human Phase I/IIa clinical trial. [Press release from American Association for Cancer Research (AACR) discussing research presented at the 2015 AACR, Philadelphia] Press Release

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Quest Diagnostics and Inserm Launch Multinational BRCA Gene Datashare Initiative, with LabCorp as First Participant, to Improve the Detection of Inherited Risk of Breast and Ovarian Cancers
Quest Diagnostics and Inserm launched BRCA Share^™, a novel datashare initiative they co-founded to provide scientists and laboratory organizations around the world with open access to BRCA1 and BRCA2 genetic data. [Quest Diagnostics] Press Release

Cleveland BioLabs and Roswell Park Cancer Institute Announce Award of Department of Defense Breast Cancer Research Program Breakthrough Grant for Entolimod
Cleveland BioLabs, Inc. and Roswell Park Cancer Institute announced the award of a three-year, $1.2 million Breast Cancer Research Program Breakthrough Award to Roswell Park from the Department of Defense Congressionally Directed Medical Research Program for research into the immunotherapy of metastatic breast cancer with entolimod, a toll-like receptor 5 agonist. [Roswell Park Cancer Institute] Press Release

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Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Extracellular Matrix Alterations Associated with Breast Cancer (Institute of Cancer Research)

Senior Cancer Bioinformatics Officer – Breast Cancer (Institute of Cancer Research)

Biostatistician – Molecular and Genetic Breast Cancer Epidemiology (Netherlands Cancer Institute)

Postdoctoral Research Fellow – Prostate Cancer and Breast Cancer (Baylor College of Medicine)

Postdoctoral Fellow – Breast Cancer & Stem Cell Biology (University of Cincinnati)

Postdoctoral Fellow – Gene Regulation in Breast Cancer/Stem Cell Biology (University of Cincinnati College of Medicine)

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