| Cancer Stem Cell News 8.39 October 9, 2019 | |
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TOP STORYLoss of Xanthine Oxidoreductase Potentiates Propagation of Hepatocellular Carcinoma Stem Cells Investigators identified that xanthine oxidoreductase, which was expressed at low levels in human hepatocellular carcinoma (HCC) samples and liver CSC, restrained HCC formation and chemoresistance by attenuating liver CSCs propagation. Mechanistically, xanthine oxidoreductase physically interacted with USP15, thereby promoting deubiquitination of Kelch Like ECH Associated Protein 1 to stabilize its expression, which led to degradation of Nrf2 via ubiquitination and subsequently reactive oxygen species accumulation in liver CSCs. [Hepatology] Abstract |
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PUBLICATIONS(Ranked by impact factor of the journal)Modeling Breast Cancer Using CRISPR/Cas9-Mediated Engineering of Human Breast Organoids Researchers demonstrated that breast epithelial organoids could be generated from human reduction mammoplasties, thus creating a tool to study the clonal evolution of breast cancer. To recapitulate de novo oncogenesis, they exploited CRISPR/Cas9 for targeted knock-out of four breast cancer-associated tumor suppressor genes in mammary progenitor cells from six donors. [J Natl Cancer Inst] Abstract SOD2 Acetylation on Lysine 68 Promotes Stem Cell Reprogramming in Breast Cancer Acetylated superoxide dismutase (SOD2) promoted hypoxic signaling via increased mitochondrial reactive oxygen species (mtROS). mtROS, in turn, stabilized hypoxia-induced factor 2α, a transcription factor upstream of “stemness” genes such as Oct4, Sox2, and Nanog. [Proc Natl Acad Sci USA] Abstract Carbenoxolone, a glycyrrhetinic acid derivative, was identified as a potential FOXO3-inhibitory compound that bound to the FOXO3-FOXO3-DNA-binding-domain (DBD) with a binding affinity of 19 µM. Specific interaction of carbenoxolone with the FOXO3-DBD was validated by fluorescence-based electrophoretic mobility shift assay. [Oncogene] Full Article Epithelial cell adhesion molecule (EpCAM) overexpression increased the expression of stemness markers and epithelial-to-mesenchymal transition (EMT) markers under the condition of hypoxia in breast cancer. Knockdown of EpCAM and mutation of N-glycosylation of EpCAM maintained in severe hypoxia led to a significant reduction of stemness/EMT markers. [J Cell Physiol] Abstract Primary Colonospheres Maintain Stem Cell-Like Key Features after Cryopreservation Tumor biopsy-derived colonospheres were frozen in standard freezing media and stored in liquid nitrogen for ten months. Then, cryopreservation effect on preservation of CSC-related features was verified using real-time polymerase chain reaction for evaluation of stemness genes and flow cytometry for the putative colorectal CSC surface biomarkers. [J Cell Physiol] Abstract CD133+CD24+ liver (L) CSCs were sorted and identified. A series of experiments were carried out to determine the proliferation, colony formation rate, migration, invasion, and apoptosis of LCSCs after interfering with FOXM1. [IUBMB Life] Abstract Lung cancer stem cells were determined in lung cancer cells using fluorescence-activated cell sorting. qRT-PCR and western blot were performed to examine the expressions of (maternally expressed gene 3) MEG3, miR-650, solute carrier family 34 member 2 (SLC34A2), octamer-binding transcription factor 4, and CD133. [Biomed Pharmacother] Full Article Investigators report that the ms2 conversion mediated by Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) in mt-tRNAs was required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. [iScience] Abstract | Full Article | Graphical Abstract Subscribe to one of our other 19 science newsletters such as Neural Cell News & Hematopoiesis News. |
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REVIEWSThe authors review literature about the suggested methods of CSC escape from immune responses and the effect of cancer niche characteristics on the ability of CSCs to develop resistant strains of cancers. Moreover, they discuss immune-mediated tumor targeting methods and bring in trials focused on CSC targeted therapies. [Int Rev Immunol] Abstract Visit our reviews page to see a complete list of reviews in the cancer stem cell research field. |
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INDUSTRY NEWSCity of Hope Is Enrolling Patients in First of Its Kind Clinical Trial for Brain Tumor Patients City of Hope has opened a first-in-human clinical trial for patients with recurrent glioblastoma – the trial is the first to combine City of Hope’s chimeric antigen receptor T cells that target the IL13Rα2 antigen common on brain tumor cells in combination with nivolumab, an anti-PD1 antibody, and ipilimumab, also a checkpoint inhibitor that blocks the CTLA-4 protein. [City of Hope] Press Release Eagle Pharmaceuticals, Inc. announced that its marketing partner SymBio Pharmaceuticals Limited has submitted a New Drug Application (NDA) for TREAKISYM ready-to-dilute liquid formulation in Japan. The NDA covers all indications for which TREAKISYM is currently approved (low-grade non-Hodgkin’s lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia). [Eagle Pharmaceuticals, Inc.] Press Release | |
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POLICY NEWSNIH Marquee Awards for ‘High Risk, High Reward’ Projects Skew Male—Again For three of the four types of “high risk, high reward” awards, women won in numbers that met or exceeded their representation in the applicant pool. However, that representation was meager: 18% percent to 38% of the applicants for these four awards were women, although women have earned more than 50% of US PhDs in biological sciences in every year since 2008. [ScienceMagazine] Editorial Biologists Who Decoded How Cells Sense Oxygen Win Medicine Nobel A trio of researchers has won the 2019 Nobel Prize in Physiology or Medicine for describing how cells sense and respond to changing oxygen levels by switching genes on and off – a discovery that has been key in understanding human diseases such as cancer and anemia. [Nature News] Editorial
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EVENTSNEW Tumor Immunology and Immunotherapy Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Scientist – Pancreatic Cancer (The Francis Crick Institute) Chief Editor – Nature Ageing (Nature Research) Assistant, Associate or Professor – Oncological Sciences (University of Utah) Postdoctoral Researcher – Cancer (Max Planck Institute for Molecular Genetics) Associate Professor – T-Cell Therapy (Dana-Farber Cancer Institute) Postdoctoral Researcher – Stem Cells and Cancer (IRB Barcelona) Postdoctoral Fellow – Cancer Progression (NIH/NCI – Center for Cancer Research) Associate Professor – Immunology (Icahn School of Medicine at Mount Sinai) Postdoctoral Researcher – Cancer Stem Cells in Glioblastoma (The Institut Curie Research Center) Postdoctoral Associate – Hematopoietic Stem Cells and Leukemia (The Jackson Laboratory)
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