Cancer Stem Cell News Volume 6.46 | Nov 22 2017

TOP STORY

Changes in Chromatin State Reveal ARNT2 at a Node of a Tumorigenic Transcription Factor Signature Driving Glioblastoma Cell Aggressiveness

Researchers mapped the changes in active and repressive histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. They found that ARNT2 knockdown decreased the expression of SOX9, POU3F2 and OLIG2, transcription factors implicated in glioblastoma cell tumorigenicity, and repressed glioblastoma stem-like cell tumorigenic properties in vivo. [Acta Neuropathol] Abstract

(Ranked by impact factor of the journal)

Role of Epithelial to Mesenchymal Transition Associated Genes in Mammary Gland Regeneration and Breast Tumorigenesis

Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts, scientists demonstrated that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of epithelial to mesenchymal transition-associated genes. [Nat Commun] Full Article

A Copper(II)-Phenanthroline Metallopeptide that Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells

The mitochondrial-targeting metallopeptide, 1 exploited the higher mitochondrial load in breast CSCs over corresponding non-CSCs, and the vulnerability of breast CSCs to mitochondrial damage, to potently and selectivity kill breast CSCs. [Angew Chem Int Ed Engl] Abstract

C/EBPα-Dependent Pre-Neoplastic Tumor Foci Are the Origin of Hepatocellular Carcinoma and Aggressive Pediatric Liver Cancer

Researchers found that de-ph-C/EBPα creates pre-neoplastic foci with CSCs that give rise to hepatocellular carcinoma and aggressive hepatoblastoma. [Hepatology] Abstract

EMT Programs Promote Basal Mammary Stem Cell and Tumor-Initiating Cell Stemness by Inducing Primary Ciliogenesis and Hedgehog Signaling

Scientists showed that mammary stem cell (MaSC) and mammary tumor-initiating cell (MaTIC) epithelial–mesenchymal transition programs induce primary cilia formation and Hedgehog (Hh) signaling, which has previously been implicated in both MaSC and MaTIC function. Ablation of these primary cilia was sufficient to repress Hh signaling, the stemness of MaSCs, and the tumor-forming potential of MaTICs. [Proc Natl Acad Sci USA] Abstract

GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma

Investigators report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibited glioblastoma (GBM) mesenchymal differentiation and radioresistance. GPR56 loss of function promoted mesenchymal differentiation and radioresistance of glioma initiating cells both in vitro and in vivo. [Cell Rep] Full Article | Graphical Abstract

Secretion-Mediated STAT3 Activation Promotes Self-Renewal of Glioma Stem-Like Cells During Hypoxia

The authors identified a hypoxia-induced pathway that utilizes the hypoxia inducible factor 1α transcription factor and the janus kinase 1/2-signal transducer and activator of transcription 3 (STAT3) axis to enhance the self-renewal of glioma stem-like cells. [Oncogene] Full Article

Blocking Stemness and Metastatic Properties of Ovarian Cancer Cells by Targeting p70S6K with Dendrimer Nanovector-Based siRNA Delivery

Scientists demonstrated that the generation 6 poly(amidoamine) dendrimer can be used as a nanovector to effectively deliver p70^S6K siRNA by forming uniform dendriplex nanoparticles which protect the siRNA from degradation. These nanoparticles were able to significantly knockdown p70^S6K in ovarian CSCs, leading to a marked reduction in CSC proliferation and expansion without obvious toxicity towards normal ovarian surface epithelial cells. [Mol Ther] Abstract | Graphical Abstract

miR-5100 Increases the Cisplatin Resistance of the Lung Cancer Stem Cells by Inhibiting the Rab6

The authors demonstrated that miR-5100 was significantly up-regulated in CD44⁺ CD133⁺ lung CSCs compared with non-CSCs. [Mol Carcinog] Abstract

Yeast Display Biopanning Identifies Human Antibodies Targeting Glioblastoma Stem-Like Cells

A single domain antibody VH-9.7 showed selectivity for five distinct patient-derived glioblastoma (GBM) stem-like cell lines and visualized orthotopic GBM xenografts in vivo after conjugation with a near-infrared dye. [Sci Rep] Full Article

NEAT1 Acts as an Inducer of Cancer Stem Cell-Like Phenotypes in NSCLC by Inhibiting EGCG-Upregulated CTR1

Investigators observed that nuclear enriched abundant transcript 1 (NEAT1) was up-regulated while copper transporter 1 (CTR1) was down-regulated in the enriched non-small-cell lung carcinoma (NSCLC) CSCs. [J Cell Physiol] Abstract

Cancer Stem Cells as Targets for Immunotherapy

Scientists discuss potential off-target effects of inhibiting cancer stem-cell self-renewal pathways on immune cells, and summarize some recent immunological studies specifically targeting cancer stem cells based on their unique antigen expression. [Immunology] Abstract

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.

Medicenna Presents Updates on Phase IIb Clinical Trial of MDNA55

Medicenna Therapeutics Corp. announced that early results and additional clinical data from the on-going Phase IIb clinical trial of MDNA55 were presented. [Press release from Medicenna Therapeutics Corp. discussing research presented at the 22^nd Annual Meeting and Education Day of the Society for Neuro-Oncology (SNO), San Francisco] Press Release

DelMar Presents Positive Interim Results from VAL-083 Study in MGMT-Unmethylated Recurrent GBM

DelMar Pharmaceuticals, Inc. provided an overview of three scientific posters. DelMar reported that 93% of glioblastoma (GBM) patients enrolled were alive at the time of the analysis and 40% of patients enrolled were reported to have achieved stable disease as assessed by MRI following treatment with VAL-083 as a single agent. [Press release from DelMar Pharmaceuticals discussing research presented at the 22^nd Annual Meeting and Education Day of the Society for Neuro-Oncology (SNO), San Francisco] Press Release

LLS Funds $46 Million in New Research to Find Cures

The Leukemia & Lymphoma Society^® (LLS) committed an additional $46 million to fund the most innovative science at leading medical institutions around the world, including Memorial Sloan Kettering Cancer Center in New York, Dana-Farber Cancer Institute in Boston, City of Hope in Duarte, California, and the Walter & Eliza Hall Institute of Medical Research in Australia. [The Leukemia & Lymphoma Society^®] Press Release

CHLA Is Awarded More than $1 Million from St. Baldrick’s Foundation to Fund Cancer Research

Three physician-researchers with the Children’s Center for Cancer and Blood Diseases at Children’s Hospital Los Angeles (CHLA) have been awarded more than $1 million in grants from the St. Baldrick’s Foundation, the largest private funder of childhood cancer research. The funding will be used to support research efforts spanning both neuroblastoma and acute lymphoblastic leukemia – two of the most aggressive childhood cancers. [Children’s Hospital Los Angeles] Press Release

Seattle Children’s Opens First CAR T-Cell Immunotherapy Trial in the U.S. for Children and Young Adults with Leukemia that Targets CD22 and CD19 Proteins Simultaneously

Seattle Children’s has opened the first chimeric antigen receptor (CAR) T-cell immunotherapy trial in the U.S. for children and young adults with relapsed or refractory CD19- and CD22-positive acute lymphoblastic leukemia that will simultaneously attack two targets on cancer cells. [Seattle Children’s Hospital] Press Release

Still No Science Advisor at the White House

Ten months into his presidency, Donald Trump has yet to name a science advisor. It’s the longest amount of time a modern president has taken to nominate someone to the position since at least 1976, when Congress established the White House’s Office of Science and Technology Policy. [MIT Technology Review] Editorial

Director of HHS Scientific Fraud Office Is out after Stormy 2-Year Tenure

The controversial director of the office that polices research fraud in U.S.-funded biomedical labs is temporarily moving to another agency. Kathy Partin has been removed after nearly two years as director of the U.S. Office of Research Integrity in Rockville, Maryland, according to Retraction Watch. [ScienceInsider] Editorial

European Medicines Agency Will Move to Amsterdam

The European Medicines Agency, charged with evaluating human and animal medicinal products for the European Union, will relocate to Amsterdam after it was selected in a draw of lots between it and Milan. [ScienceInsider] Editorial

Hungary Rewards Highly Cited Scientists with Bonus Grants

Some top researchers prosper in Hungary as country tries to improve its international standing in science. [Nature News] Editorial

NEW World Vaccine Congress Washington 2018
April 3-5, 2018
Washington, D.C., United States

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