LABORATORY RESEARCH Synergy of Topical Toll-Like Receptor 7 Agonist with Radiation and Low Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer Researchers tested the hypothesis that topical Toll-Like Receptor (TLR) 7 agonist imiquimod promotes anti-tumor immunity and synergizes with other treatments in a model of skin-involving breast cancer. [Clin Cancer Res] Abstract E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation To identify novel oncogenic E3 ubiquitin ligases as anti-cancer targets, scientists screened an E3 ubiquitin ligase siRNA library containing siRNA pools against 555 individual E3s using the SRB assay in the MDA-MB-231 breast cancer cell line and the PC3 prostate cancer cell line. RNF126 was identified and validated as a candidate from this screening. [Cancer Res] Abstract Breast Tumor-Associated Osteoblast-Derived CXCL5 Increases Cancer Progression by ERK/MSK1/Elk-1/Snail Signaling Pathway Researchers analyzed the soluble factors secreted by breast tumor-associated osteoblasts (TAOBs), which are responsible for promoting cancer progression. The addition of CXCL5 (chemokine (C-X-C motif) ligand 5), present in large amounts in TAOB-condition medium (TAOB-CM), mimicked the inductive effect of TAOB-CM on breast cancer epithelial-mesenchymal transition, migration and invasion. [Oncogene] Abstract Downregulation of Stromal BRCA1 Drives Breast Cancer Tumor Growth via Upregulation of HIF-1a, Autophagy and Ketone Body Production Researchers stably knocked-down BRCA1 expression in human hTERT-immortalized fibroblasts (shBRCA1) using an shRNA lentiviral approach. As expected, shBRCA1 fibroblasts displayed an elevated growth rate. [Cell Cycle] Abstract Specific Inhibition of Notch1 Signaling Enhances the Antitumor Efficacy of Chemotherapy in Triple Negative Breast Cancer through Reduction of Cancer Stem Cells Researchers generated Notch1 monoclonal antibodies that specifically bind to the negative regulatory region of human Notch1. Notch1 inhibition in triple negative breast cancer Sum149 and patient derived xenograft 144580 models led to significant TGI particularly in combination with docetaxel. [Cancer Lett] Abstract Negative Regulation of NF-κB by the ING4 Tumor Suppressor in Breast Cancer Investigators present evidence that the Inhibitor of Growth 4 (ING4) tumor suppressor negatively regulates Nuclear Factor kappa B (NF-κB) in breast cancer. They surveyed primary breast tumor samples for ING4 protein expression using tissue microarrays and a newly generated antibody. [PLoS One] Full Article Zinc Inhibits Magnesium-Dependent Migration of Human Breast Cancer MDA-MB-231 Cells on Fibronectin Researchers hypothesized that zinc, a divalent cation, can modulate breast cancer metastasis through interfering with divalent cation-dependent integrin-mediated cancer cell adhesion and migration. MDA-MB-231 cells were cultured in a zinc-depleted medium supplemented with 0 (control), 2.5, 5, 10, 25 and 50 µM of zinc to mimic severe zinc-deficiency, moderate zinc-deficiency, adequate zinc and three levels of zinc-supplementation: low-, moderate- and high-levels of zinc-supplementation, respectively. [J Nutr Biochem] Abstract Decidua Mesenchymal Stem Cells Migrated toward Mammary Tumors In Vitro and In Vivo Affecting Tumor Growth and Tumor Development Researchers aimed to investigate the migration capacity of decidua-derived mesenchymal stem cells (DMSCs) in vitro, and in vivo in a preclinical model of mammary tumors induced by N-nitroso-N-methylurea. Additionally, they assessed the safety of DMSC administration in vivo and their effect on tumor growth. [Cancer Gene Ther] Abstract Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis Variability in signaling pathway activation between neighboring epithelial cells can arise from local differences in the microenvironment, noisy gene expression, or acquired genetic changes. To investigate the consequences of this cell-to-cell variability in signaling pathway activation on coordinated multicellular processes such as morphogenesis, researchers used DNA-programmed assembly to construct three-dimensional MCF10A microtissues that are mosaic for low-level expression of activated H-Ras. [Cell Reports] Abstract CLINICAL RESEARCH Zoledronic Acid (Zoledronate) for Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole (ZO-FAST study): Final 60-Month Results Postmenopausal women receiving adjuvant letrozole were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every six months for five years, or delayed zoledronate. The primary end point was the change in lumbar spine bone mineral density (BMD) at 12 months. Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival, and overall survival were assessed as secondary end points. [Ann Oncol] Abstract Brain-Only Metastatic Breast Cancer Is a Distinct Clinical Entity Characterized by Favorable Median Overall Survival Time and a High Rate of Long-Term Survivors All breast cancer patients with brain metastases treated at the authors’ institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed. [Br J Cancer] Abstract |