Volume 5.05 | Feb 7

Mammary Cell News 5.05 February 7, 2013
Mammary Cell News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
APOBEC3B Is an Enzymatic Source of Mutation in Breast Cancer
Several mutations are required for cancer development, and genome sequencing has revealed that many cancers, including breast cancer, have somatic mutation spectra dominated by C-to-T transitions. Most of these mutations occur at hydrolytically disfavored non-methylated cytosines throughout the genome, and are sometimes clustered. Scientists showed that the DNA cytosine deaminase APOBEC3B is a probable source of these mutations. [Nature] Abstract | Press Release

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PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition
Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, scientists characterized EMT in circulating tumor cells from breast cancer patients. [Science] Abstract | Press Release

Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus
Investigators retargeted herpes simplex virus tropism to HER-2 oncoprotein p185, overexpressed in ovary and breast cancers. The HER-2-retargeted R-LM249 exclusively infects and kills tumor cells expressing high levels of human HER-2. [PLoS Pathol] Full Article

MicroRNA-7 Suppresses Brain Metastasis of Breast Cancer Stem-Like Cells by Modulating KLF4
Cancer stem-like cells (CSCs) are considered to play a role in metastatic progression of breast cancer; however, the exact pathologic role of CSCs is yet to be elucidated. Researchers found that CSCs (CD24/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ-specific manner. [Cancer Res] Abstract | Press Release

FOXC2 Expression Links Epithelial-Mesenchymal Transition and Stem Cell Properties in Breast Cancer
Scientists report that the transcription factor FOXC2 induced in response to multiple epithelial-mesenchymal transition (EMT) signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT and cancer stem cell-enriched breast cancer cell lines. [Cancer Res] Abstract

Ink4a/Arf−/− and HRAS(G12V) Transform Mouse Mammary Cells into Triple-Negative Breast Cancer Containing Tumorigenic CD49f Quiescent Cells
Investigators proposed to engineer a mouse mammary tumor model with intratumoral heterogeneity by using defined genetic perturbations. To achieve this, they used mice with knockout (-/-) of Ink4a/Arf, a tumor suppressor locus; these mice are known to be susceptible to non-mammary tumors such as fibrosarcoma. [Oncogene] Abstract

Microfabricated Collagen Tracks Facilitate Single Cell Metastatic Invasion in 3D
Studies have shown that some cancer cells can use proteolysis to mechanically rearrange their extracellular matrix to form tube-like “microtracks” which other cells can follow without using matrix metalloproteinases themselves. The authors speculate that this mode of migration in the secondary cells may be one example of migration which can occur without endogenous protease activity in the secondary cells. They present a technique to study this migration in a 3D, collagen-based environment which mimics the size and topography of the tracks produced by proteolytically active cancer cells. [Integrative Biol] Abstract

The HER2- and Heregulin β1 (HRG)-Inducible TNFR Superfamily Member Fn14 Promotes HRG-Driven Cell Migration, Invasion and Matrix Metalloproteinase-9 Expression
In a previous study, the authors found that fibroblast growth factor-inducible 14 (Fn14), a member of the TNF receptor (TNFR) superfamily, was frequently overexpressed in human epidermal growth factor receptor-2 (HER2)+ breast tumors. They report here that HER2 and Fn14 are also co-expressed in mammary tumors that develop in two different transgenic mouse models of breast cancer. [Mol Cancer Res] Abstract

Peroxisome Proliferator Activated Receptor-α/Hypoxia Inducible Factor-1α Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells
The authors report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. [PLoS One] Full Article

CLINICAL RESEARCH

Phase II Randomized Study of Trastuzumab Emtansine versus Trastuzumab Plus Docetaxel in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer
Patients with human epidermal growth factor receptor 2-positive metastatic breast cancer or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel or trastuzumab emtansine as first-line treatment until disease progression or unacceptable toxicity. [J Clin Oncol] Abstract

Multicenter Phase II Trial of Bevacizumab Combined with Docetaxel-Carboplatin for the Neoadjuvant Treatment of Triple-Negative Breast Cancer (KCSG BR-0905)
Women with hormone receptor- and human epidermal growth factor receptor 2-negative, stage II/III breast cancer received six cycles of docetaxel, carboplatin and bevacizumab every 21 days. [Ann Oncol] Abstract

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REVIEWS
CCL5 as a Potential Immunotherapeutic Target in Triple-Negative Breast Cancer
The authors review the clinical and laboratory work that has led to their own hypothesis that targeting CCL5 in triple-negative breast cancer will have favorable therapeutic outcomes with minimal adverse impact on the general physiology. [Cell Mol Immunol] Abstract
INDUSTRY NEWS

Aduro Announces Acquisition of GVAX Assets from BioSante
Aduro BioTech, Inc. announced the acquisition of all GVAX assets from BioSante Pharmaceuticals, Inc., including intellectual property and cell lines. Aduro previously licensed two GVAX vaccines, GVAX Pancreas and GVAX Prostate, for use in combination with its Listeria-based vaccines. This new acquisition covers all uses and includes additional vaccines for multiple myeloma and breast and colon cancer and assumes rights to the existing license agreement for GVAX Melanoma. [Business Wire] Press Release

Oasmia Signs Marketing and Distribution Agreement for Product Candidate Paclical® in Russia and CIS Countries
Oasmia Pharmaceutical and Pharmasyntez have entered into an exclusive marketing and distribution agreement concerning Oasmia’s product candidate Paclical, for the treatment of ovarian cancer, lung cancer and second line breast cancer. [Oasmia Pharmaceutical AB] Press Release

POLICY NEWS

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)

EVENTS
NEW Keystone Symposium: The Hippo Tumor Suppressor Network: From Organ Size Control to Stem Cells and Cancer
May 19-23, 2013
Monterey, United States

Visit
our events page to see a complete list of events in the mammary cell community.
JOB OPPORTUNITIES

Postdoctoral Position – Gene Regulation in Breast Cancer/Stem Cell Biology (UC College of Medicine)

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

Postdoctoral Position – Bioinformatics Position in Cancer Research (San Raffaele Scientific Institute)

Postdoctoral Position – Regulation of Gene Expression in Breast Cancer (University of Cincinnati)

Postdoctoral Research Assistant – Breast Cancer Campaign (University of Oxford)

PhD Student – Breast Cancer Biology (IDIBELL, Catalan Institute of Oncology)

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

Postdoctoral Position – Stem Cell Biology (Ludwig Institute for Cancer Research)


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