Mammary Cell News Volume 5.08 | Feb 28 2013

LABORATORY RESEARCH
 
GLI1 Regulates a Novel Neuropilin-2/α6β1 Integrin Based Autocrine Pathway that Contributes to Breast Cancer Initiation
The authors investigated the hypothesis that VEGF receptors expressed on triple-negative breast cancer (TNBC) cells mediate autocrine signaling that contributes to tumor initiation. They discovered the VEGF receptor neuropilin-2 is expressed preferentially on tumor-initiating cells, involved in the genesis of TNBCs and necessary for tumor initiation. [EMBO Mol Med] Full Article

Epithelial-to-Mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T Cell-Mediated Lysis
Researchers investigated the functional consequences of this mode of epithelial cell plasticity on targeted cell lysis by cytotoxic T lymphocytes. Acquisition of the epithelial-to-mesenchymal transition (EMT) phenotype in various derivatives of MCF-7 human breast cancer cells was associated with dramatic morphological changes and actin cytoskeleton remodeling, with CD24-/CD44+/ALDH+ stem cell populations present exhibiting a higher degree of EMT relative to parental cells. [Cancer Res] Abstract

HDAC Inhibitors Induce Transcriptional Repression of High Copy Number Genes in Breast Cancer through Elongation Blockade
Using global run-on sequencing to measure nascent transcription, the authors found that histone deacetylase inhibitors (HDACI) cause transcriptional repression by blocking RNA polymerase II elongation. Their data show that HDACI preferentially repress the transcription of highly expressed genes as well as high copy number genes in HER2+ breast cancer genomes. [Oncogene] Abstract

Anandamide Inhibits the Wnt/β-Catenin Signaling Pathway in Human Breast Cancer MDA MB 231 Cells
As accumulating evidences indicate that the constitutive activation of the canonical Wnt pathway in human breast cancer may highlight a key role for aberrant activation of the β-catenin-T Cell Factor cascade and tumor progression, scientists studied the anandamide effect on the key elements of Wnt pathway in breast cancer cells. [Eur J Cancer] Abstract

The Overexpression of Hypomethylated miR-663 Induces Chemotherapy Resistance in Human Breast Cancer Cells by Targeting Heparin Sulphate Proteoglycan 2 (HSPG2)
The authors found that microRNA (miR)-663 was up-regulated in their induced multidrug-resistant MDA-MB-231/ADM cell line and that this up-regulation was closely related to chemosensitivity. They aimed to clarify the role of miR-663 in regulating the chemoresistance of breast cancer. [J Biol Chem] Abstract | Full Article

CDCP1 Regulates the Function of Membrane-Type 1 Matrix Metalloproteinase and Invadopodia-Mediated Invasion of Cancer Cells
Researchers demonstrated that CUB-domain-containing protein 1 (CDCP1) is required for extracellular matrix degradation by invadopodia in human breast cancer and melanoma cells. CDCP1 localized to caveolin-1-containing vesicular structures and lipid rafts and was detected in close proximity to invadopodia. [Mol Cancer Res] Abstract

Aurora-A Identifies Early Recurrence and Poor Prognosis and Promises a Potential Therapeutic Target in Triple Negative Breast Cancer
122 triple negative breast cancer (TNBC) patients were subjected to analysis of Aurora-A (Aur-A) expression and survival prognosis. The authors found that Aur-A high expression was positively associated with initial clinical stage, the proliferation marker Ki-67, and the recurrence rate of TNBC patients. [PLoS One]
Full Article

CLINICAL RESEARCH

Comparison of Subcutaneous and Intravenous Administration of Trastuzumab: A Phase I/Ib Trial in Healthy Male Volunteers and Patients with HER2-Positive Breast Cancer
This open-label, two-part, Phase I/Ib study was undertaken in healthy male volunteers and female patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer to identify the dose of subcutaneous trastuzumab that resulted in exposure comparable with the approved intravenous trastuzumab dose. [J Clin Pharmacol] Abstract

Severe and Prolonged Lymphopenia Observed in Patients Treated with Bendamustine and Erlotinib for Metastatic Triple Negative Breast Cancer
Researchers performed a Phase I trial of bendamustine and erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with metastatic triple negative breast cancers, ECOG performance status ≤2, and ≤1 prior chemotherapy for metastatic disease. [Cancer Chemother Pharmacol] Abstract

FDA Approves Roche’s Kadcyla (Trastuzumab Emtansine), the First Antibody-Drug Conjugate for Treating HER2-Positive Metastatic Breast Cancer
Roche announced that the U.S. Food and Drug Administration (FDA) has approved Kadcyla for the treatment of people with HER2-positive metastatic breast cancer who have received prior treatment with Herceptin and a taxane chemotherapy. Kadcyla is the fourth medicine from Roche to receive FDA approval for people with advanced cancers within the past two years. [F. Hoffmann-La Roche Ltd.] Press Release

First Patient Treated for Phase II Trial with AEZS-108 in Triple-Negative Breast Cancer
Aeterna Zentaris Inc. announced that a first patient has been treated for the randomized Phase II trial in chemotherapy refractory triple-negative luteinizing hormone-releasing hormone receptor-positive metastatic breast cancer, with the company’s targeted doxorubicin peptide conjugate, AEZS 108. [Aeterna Zentaris Inc.] Press Release

Expanding Public Access to the Results of Federally Funded Research
In a policy memorandum, Office of Science and Technology Policy Director John Holdren has directed Federal agencies with more than $100 million in R&D expenditures to develop plans to make the published results of federally funded research freely available to the public within one year of publication and requiring researchers to better account for and manage the digital data resulting from federally funded scientific research. [Office of Science and Technology Policy, The White House, United States] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

Postdoctoral Position – Impact of Ubiquitin-Proteasome Pathway in Genome Stability and Breast Cancer (University of Pittsburgh)

Postdoctoral Position – Cancer Biology and Functional Genomics (North Carolina Central University)

Research Fellow – Breast Cancer Research (Monash University)

Research Associate – Lung and Breast Cancer Bioinformatics (University College London)

Vice President – Sales and Marketing for Breast and Colon Cancer (Genomic Health)

PhD Studentship – Signal Transduction and Cancer Research (McGill University)

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