Volume 5.25 | Jun 27

Mammary Cell News 5.25 June 27, 2013
Mammary Cell News
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First FDA Approval of Dual Anti-HER2 Regimen: Pertuzumab in Combination with Trastuzumab and Docetaxel for HER2-Positive Metastatic Breast Cancer
The U.S. Food and Drug Administration (FDA) approved pertuzumab for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 808 patients with HER2-positive MBC. Patients were randomized to receive pertuzumab or placebo in combination with trastuzumab and docetaxel. The primary endpoint was progression-free survival, and a key secondary endpoint was overall survival. [Clin Cancer Res] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

mTOR Signaling Feedback Modulates Mammary Epithelial Differentiation and Restrains Invasion Downstream of PTEN Loss
Investigators used isogenic benign mammary organotypic cultures to interrogate the role of mTOR-mediated negative feedback in the specific setting of PTEN inactivation. They found that mTOR signaling promoted basal-like differentiation and repressed nuclear hormone receptor expression after short-term PTEN loss in murine cell cultures analyzed ex vivo. [Cancer Res] Abstract

A Leukotriene B4 Receptor-2 Is Associated with Paclitaxel Resistance in MCF-7/DOX Breast Cancer Cells
The levels of leukotriene B4 receptor-2 (BLT2) in multidrug-resistant MCF-7/DOX cells were determined using quantitative PCR and FACS analysis. The potential role of BLT2 in the paclitaxel resistance of MCF-7/DOX cells was assessed using a pharmacological inhibitor and small interfering RNA knockdown, and the BLT2-associated resistance mechanism was assessed. [Br J Cancer] Abstract

Growth Hormone Potentiates 17β-Estradiol-Dependent Breast Cancer Cell Proliferation Independently of IGF-I Receptor Signaling
Researchers examined growth hormone (GH) action in a panel of estrogen receptor positive breast cancer cell lines and found that T47D cells express significant levels of GH receptor and that GH significantly enhances E2-stimulated proliferation in these cells. GH action in T47D cells was independent of changes in insulin-like growth factor-I (IGF-I) and IGF-IR expression and IGF-IR signaling, suggesting that GH can exert direct effects on breast cancer cells. [Endocrinology] Abstract

Recombinant GnRH-p53 Protein Sensitizes Breast Cancer Cells to 5-Fluorouracil-Induced Apoptosis In Vitro and In Vivo
Researchers constructed a fusion protein consisting of gonadotropin-releasing hormone (GnRH-p53) and p53 moieties. The recombinant protein was directly used to treat human breast cancer cells and athymic nude mice bearing breast cancer xenografts, with or without DNA synthesis-arresting agent 5-fluorouracil. [Apoptosis] Abstract

Co-Inhibition of Epidermal Growth Factor Receptor and Insulin-Like Growth Factor Receptor 1 Enhances Radiosensitivity in Human Breast Cancer Cells
Scientists investigated the impact of co-inhibition of epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 (IGF-1R) receptor on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression. [BMC Cancer] Abstract | Full Article

Hypoxia Stimulates 18F-Fluorodeoxyglucose Uptake in Breast Cancer Cells via Hypoxia Inducible Factor-1 and AMP-Activated Protein Kinase
The effect of hypoxia on 18F-fluorodeoxyglucose uptake, and key proteins involved in glucose transport and glycolysis, was studied in MCF7 and MDA231 breast cancer cell lines. [Nucl Med Biol] Abstract

Isolation and Characterization of Human Breast Cancer Cells with SOX2 Promoter Activity
Researchers developed a reporter system using fluorescent protein driven by the promoter for sex-determining region Y-box 2 (SOX2) gene to detect and isolate living SOX2-positive cells. Results suggested that the cell population with SOX2 promoter activity contains cancer stem cell (CSC)-like cells which show expression profiles different from those of CSC-marker genes previously recognized in human breast cancers. [Biochem Biophys Res Commun] Abstract

PLK1 Signaling in Breast Cancer Cells Cooperates with Estrogen Receptor-Dependent Gene Transcription
The authors report that PLK1 mediates estrogen receptor (ER)-regulated gene transcription in human breast cancer cells. PLK1 interacts with ER and is recruited to ER cis-elements on chromatin. PLK1-coactivated genes included classical ER target genes such as Ps2, Wisp2, and Serpina3 and were enriched in developmental and tumor-suppressive functions. [Cell Rep]
Abstract | Graphical Abstract | Full Article | Press Release


Clinical Relevance of Cancer Stem Cells in Bone Marrow of Early Breast Cancer Patients
Investigators hypothesized that if cancer stem cells (CSCs) are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients. BM aspirates were collected at the time of surgery from 108 patients with EBC. BM was analyzed for CSCs and aldehyde dehydrogenase activity by flow cytometry. [Ann Oncol] Abstract

Cediranib in Combination with Fulvestrant in Hormone-Sensitive Metastatic Breast Cancer: A Randomized Phase II Study
Vascular endothelial growth factor (VEGF) may mediate resistance to estrogen receptor (ER) antagonists. Cediranib is a highly potent VEGF signaling inhibitor with activity against all three VEGF receptors. This randomized Phase II study evaluated cediranib plus fulvestrant. The primary endpoint was progression-free survival. [Invest New Drugs] Abstract

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The Immune System and Inflammation in Breast Cancer
The authors review recent findings showing how the immune system plays dual host-protective and tumor-promoting roles in breast cancer initiation and progression. They then discuss estrogen receptor α (ERα)-dependent and ERα-independent mechanisms that shield breast cancers from immunosurveillance and enable breast cancer cells to evade immune cell induced apoptosis and produce an immunosuppressive tumor microenvironment. Finally, they discuss protumorigenic inflammation that is induced during tumor progression and therapy, and how inflammation promotes more aggressive phenotypes in ERα positive breast cancers. [Mol Cell Endocrinol] Full Article

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Nuclea Biotechnologies and Berkshire Medical Center Announce Research Agreement
Nuclea Biotechnologies, Inc. announced that it has signed a new research and collaboration agreement with Berkshire Medical Center which could lead to more effective treatment for prostate and breast cancer. This partnership will advance research and development of biomarkers, which are a vital component in the growing field of personalized medicine. [Nuclea Biotechnologies, Inc.] Press Release

Breast Cancer Clinical Trial Looks at Targeting Cancer Stem Cells
A phase Ib study will test reparixin, which is taken orally, along with the chemotherapy drug paclitaxel in women with HER2-negative metastatic breast cancer. The study is primarily intended to test how patients tolerate this drug combination, but researchers will also look at how reparixin appears to be impacting markers for cancer stem cells and signs of inflammation. [University of Michigan] Press Release

Johns Hopkins Students’ Device Aims to Avert Repeated Breast Cancer Surgeries
Four Johns Hopkins graduate students have designed a device to allow pathologists to quickly inspect excised breast tissue within 20 minutes, while the patient is still in the operating room. If this inspection indicates that the tumor was not fully removed, additional tissue can then be removed during the same operation. Eliminating the need for a second operation could also curb some of the additional anxiety these patients face. [Johns Hopkins University] Press Release

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NEW BioConference Live – Cancer: Research, Discovery and Therapeutics
October 16-17, 2013
Online Conference

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NEW Postdoctoral Fellow – Breast Cancer Research (Albert Einstein College of Medicine)

Postdoctoral Fellow – Breast and Renal Cell Carcinoma Research (University of North Carolina – Chapel Hill)

Postdoctoral Position – lncRNA and RNA Binding Protein Interaction in Mammary Cancer Stem Cell (CIBIO, University of Trento)

PhD Studentship – Breast Cancer Biology (Royal College of Surgeons in Ireland)

Postdoctoral Position – Breast and Ovarian Cancer Biology (University of Pennsylvania School of Medicine)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

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

Postdoctoral Position – Breast Cancer Metastasis (Weizmann Institute of Science)

Postdoctoral Fellow – Cancer Genes in Breast Cancer (MD Anderson Cancer Center)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

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