Mammary Cell News 9.10 March 16, 2017 | |
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TOP STORYClass IIa HDAC Inhibition Reduces Breast Tumors and Metastases through Anti-Tumor Macrophages Researchers utilized a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumor microenvironment and reduces tumor burden and pulmonary metastases by modulating macrophage phenotypes. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)LABORATORY RESEARCHStromal Gli2 Activity Coordinates a Niche Signaling Program for Mammary Epithelial Stem Cells The authors found that Gli2, the major Hedgehog pathway transcriptional effector, acts within mouse mammary stromal cells to direct a hormone-responsive niche signaling program by activating expression of factors that regulate epithelial stem cells as well as receptors for the mammatrophic hormones estrogen and growth hormone. [Science] Abstract Investigators reported that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumor cell progression, impairing tumor onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. [Nat Commun] Full Article Researchers showed that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells. Impaired Y239/Y240-ShcA phosphorylation selectively reduced STAT3 activation in breast tumors, profoundly sensitizing them to immune checkpoint inhibitors and tumor vaccines. [Nat Commun] Full Article The authors individually depleted amino acid nutrients from isogenic cells expressing commonly activated oncogenes to identify correspondences between nutrient supply and viability. In human mammary epithelial cells, deprivation of cystine led to increased cell death in cells expressing an activated epidermal growth factor receptor mutant. [Cell Rep] Abstract | Graphical Abstract A model mimicking the cross-linked hyaluronan (HA) network is required to determine the effect of HA fragments on breast cancer cells. Investigators assessed the differential roles of low versus high molecular weights HA on cancer cell phenotype, a three-dimensional (3D) culture system was set up by covalently cross-linking HA with alginate and investigating the behavior of 4T-1 and SKBR3 breast cancer cells alongside a two-dimensional (2D) control. Their results showed the invasion and migration abilities of 4T-1 and SKBR3 cells are significantly enhanced by the presence of HA35 but inhibited by HA117 in both 2D monolayers and 3D spheroids. [ACS Appl Mater Interfaces] Abstract | Graphical Abstract A CD44v+ Subpopulation of Breast Cancer Stem-Like Cells with Enhanced Lung Metastasis Capacity The authors showed that among the CD24−/CD44+ breast cancer stem-like cells, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform CD44s. [Cell Death Dis] Full Article Treatment with CAT-SKL—a re-engineered protein form of the antioxidant enzyme catalase—inhibited cancer stem-like cells (CSCs), and treatment with the EGFR-specific small molecule kinase inhibitor erlotinib inhibited non-CSCs. Combining the antioxidant CAT-SKL with erlotinib targeted both CSCs and bulk cancer cells in cultures of EGFR-expressing triple-negative breast cancer-derived cells. [Sci Rep] Full Article The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. Scientists modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase downregulation. [Sci Rep] Full Article 3D Hydrogel-Based Microwell Arrays as a Tumor Microenvironment Model to Study Breast Cancer Growth The authors aimed to simulate the breast cancer tumor microenvironment, microwell arrays of defined geometry and dimensions were fabricated using photo-reactive hydrogels for a cancer cell line and primary explant tissue culture. Using these microwell arrays, size-controlled spheroids of human breast cancer cell line HCC1806 were formed and the cell attachment properties, viability, metabolic activity, and migration levels of these spheroids were examined. [Biomed Mater] Abstract CLINICAL RESEARCHTrop-2, expressed in most triple-negative breast cancers (TNBCs), may be a potential target for antibody-drug conjugates. Sacituzumab govitecan, an antibody-drug conjugate, targets Trop-2 for the selective delivery of SN-38, the active metabolite of irinotecan. Scientists evaluated sacituzumab govitecan in a single-arm, multicenter trial in patients with relapsed/refractory metastatic TNBC who received a 10 mg/kg starting dose on days one and eight of 21-day repeated cycles. [J Clin Oncol] Full Article | Press Release | |
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REVIEWSFOXC1: An Emerging Marker and Therapeutic Target for Cancer The authors summarize current knowledge on the function and regulation of Forkhead box C1 (FOXC1) in tumor development and progression with a focus on basal-like breast cancer, as well as the implications of these new findings in cancer diagnosis and treatment. [Oncogene] Abstract Visit our reviews page to see a complete list of reviews in the mammary cell research field. | |
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INDUSTRY NEWSThe US Food and Drug Administration (FDA) has approved Kisqali® in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2) advanced or metastatic breast cancer. [Novartis] Press Release TapImmune, Inc. announced that its collaborators at the Mayo Clinic, recently received a $3.7 million grant from the U.S. Department of Defense to conduct a Phase II clinical study on TapImmune’s HER2/neu-targeted T-cell vaccine that will enroll women diagnosed with an early form of breast cancer called ductal carcinoma in situ. [TapImmune] Press Release Tempus and University of Chicago Collaborate on Groundbreaking Breast Cancer Project Tempus has formed a collaboration with cancer experts at the University of Chicago Medicine to accelerate the pace of discovery and improve and personalize treatment for breast cancer patients. [Tempus] Press Release Agendia, Inc. announced that the company’s MammaPrint® 70-Gene Breast Cancer Risk-of-Recurrence test is now included with the highest medical evidence level 1A in the latest version of AGO guidelines for the care of breast cancer patients in Germany. [Agendia, Inc.] Press Release | |
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POLICY NEWSUS Science Agencies Face Deep Cuts in Trump Budget When it comes to science, there are few winners in US President Donald Trump’s first budget proposal. The plan outlines double-digit cuts for the Environmental Protection Agency and the National Institutes of Health. The Trump budget would cut funding for the entire NIH by 18%, to $25.9 billion, making it one of the hardest-hit research agencies. [Nature News] Editorial ‘Zombie’ Patent Fights over Mutant Mice Return Like a zombie that keeps on kicking, legal battles over mutant mice used for Alzheimer’s research are haunting the field once again — four years after the last round of lawsuits. In the latest case, the University of South Florida in Tampa has sued the US National Institutes of Health for authorizing the distribution of a particular type of mouse used in the field. [Nature News] Editorial U.K. Scientists Prepare for Impending Break with European Union For months after the United Kingdom (U.K.) voted last June to leave the European Union (EU), many British scientists clung to hopes of a “soft Brexit,” which would not cut them off from EU funding and collaborators. But Prime Minister Theresa May, who is expected to trigger the two-year process of exiting the European Union, has signaled the break will be sharp. U.K. researchers are now facing up to the prospect that they won’t be able to apply for EU funding or easily recruit students and colleagues from the rest of Europe. [ScienceInsider] Editorial Canada’s New Genetic Privacy Law Is Causing Huge Headaches for Justin Trudeau A vote in Canada’s Parliament to approve a genetic privacy bill is creating a self-inflicted political headache for Prime Minister Justin Trudeau’s Liberal government—and could result in a relatively rare and unusual court case. [ScienceInsider] Editorial
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EVENTSNEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESPostdoctoral Position – Breast Cancer (Memorial Sloan Kettering Cancer Center) Postdoctoral Research Scholar – Breast Tumor Growth (University of Iowa) Postdoctoral Fellow – Proteoglycans (Thomas Jefferson University) Postdoctoral Fellow – Cancer Research (Houston Methodist Research Institute) Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine) Cancer Bioinformatician – Breast Cancer (Institute of Cancer Research) Assistant or Associate Professor – Breast Cancer (Roswell Park Cancer Institute) Postdoctoral Associate – Mammary Stem Cell and Cancer Biology (University of Miami) Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Mammary Cell News Volume 9.10 | Mar 16 2017