Cancer Stem Cell News Volume 7.25 | Jun 27 2018

TOP STORY

Bioreducible Polymeric Nanoparticles Containing Multiplexed Cancer Stem Cell-Regulating miRNAs Inhibit Glioblastoma Growth and Prolong Survival

The authors combined nanobiotechnology with newly discovered cancer stem cell inhibiting miRNAs to develop self-assembled miRNA-containing polymeric nanoparticles (nano-miRs) to treat gliomas. They showed that these nano-miRs effectively intracellularly delivered single and combination miRNA mimics that inhibited the stem cell phenotype of human glioblastoma cells in vitro. [Nano Lett] Abstract

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Nuclear Smad6 Promotes Gliomagenesis by Negatively Regulating PIAS3-Mediated STAT3 Inhibition

The molecular mechanism underlying constitutive signal transducer and activator of transcription 3 (STAT3) activation in gliomas is largely unclear. Scientists reported that Smad6 was overexpressed in nuclei of glioma cells, which correlated with poor patient survival and regulated STAT3 activity via negatively regulating the protein inhibitors of activated STAT3 (PIAS3). [Nat Commun] Full Article

Mitotic Polarization of Transcription Factors during Asymmetric Division Establishes Fate of Forming Cancer Cells

In hypoxic, Tgf-β1-rich interiors of adenomas, researchers showed that adenoma cells divide asymmetrically to produce cancer-generating cells highlighted by epithelial mesenchymal transition and a CD44/Zeb1 loop. [Nat Commun] Full Article

Coexpression Profile of Leukemic Stem Cell Markers for Combinatorial Targeted Therapy in AML

To identify target antigen combinations specific for acute myeloid leukemia (AML) and leukemic stem cells, scientists generated a detailed protein expression profile based on flow cytometry of primary AML and normal bone marrow samples, and a recently reported integrated normal tissue proteomic data set. [Leukemia] Full Article

Genome-Wide Methylomic and Transcriptomic Analyses Identify Subtype-Specific Epigenetic Signatures Commonly Dysregulated in Glioma Stem Cells and Glioblastoma

The authors determined the DNA methylation signatures in transcriptomically pre-classified glioma stem cell (GSC) and glioblastoma (GBM) bulk tumors subtypes. They hypothesized that these DNA methylation signatures correlate with gene expression and are uniquely associated either with only GSCs or only GBM bulk tumors. [Epigenetics] Abstract

Prolonged Inhibition of Class I PI3K Promotes Liver Cancer Stem Cell Expansion by Augmenting SGK3/GSK-3β/β-Catenin Signaling

Researchers found that serum and glucocorticoid-regulated kinase 3 (SGK3) is preferentially activated in liver CSCs. Upregulated SGK3 significantly increased the expansion of liver CSCs. Conversely, suppression of SGK3 in human hepatocarcinoma cells had an opposite effect. [J Exp Clin Cancer Res] Full Article

Quiescence Status of Glioblastoma Stem-Like Cells Involves Remodelling of Ca²⁺ Signaling and Mitochondrial Shape

Investigators showed that proliferating glioblastoma stem-like cells (GSLCs) can be induced and maintained in a quiescent state by lowering the extracellular pH. Through RNAseq analysis they identified Ca²⁺ signaling genes differentially expressed between proliferating and quiescent GSLCs. [Sci Rep] Full Article

Zerumbone Inhibits Epithelial‐Mesenchymal Transition and Cancer Stem Cells Properties by Inhibiting the β‐Catenin Pathway through miR‐200c

The authors investigated the inhibitory action of zerumbone on the epithelial‐mesenchymal transition process, CSC markers, and the β‐catenin signaling pathway in the presence or absence of miR‐200c. [J Cell Physiol] Abstract

R-Spondin1/Wnt-Enhanced Ascl2 Autoregulation Controls the Self-Renewal of Colorectal Cancer Progenitor Cells

Scientists showed that Ascl2 autoregulation formed a transcriptional switch that was enhanced by Wnt signaling in the CD133⁺CD44⁺ colorectal cancer population, thus conferring their self-renewal. [Cell Cycle] Abstract

KLF4 Functions as an Oncogene in Promoting Cancer Stem Cell-Like Characteristics in Osteosarcoma Cells

Investigators showed that the expression level of kruppel-like factor 4 (KLF4) was highly associated with human osteosarcoma cancer stemness. [Acta Pharmacol Sin] Abstract

IL‐1β Promotes the Nuclear Translocaiton of S100A4 Protein in Gastric Cancer Cells MGC803 and the Cell’s Stem‐Like Properties through PI3K Pathway

The authors speculated that interleukin‐1β (IL‐1β) might promote the nuclear translocation of S100A4 protein in MGC803 gastric cancer cells and therefore enhance their stem‐like properties. The results from Western‐blot and qRT‐PCR analysis showed that IL‐1β increased the nuclear and total cellular content of S100A4 protein and S100A4 mRNA level in MGC803 cells. [J Cell Biochem] Abstract

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Role of Autotaxin in Cancer Stem Cells

Scientists summarize the evidence linking autotaxin-lysophosphatidic acid signaling to CSCs and its impact on cancer progression and metastasis. They also provide evidence for the efficacy of cancer therapy involving the pharmacological inhibition of this signaling pathway. [Cancer Metastasis Rev] Abstract

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Therapeutic Solutions International Releases “IsoStilbene” Injectable Formulation of Pterostilbene Under Granted Patent for Augmentation of Immunotherapy and Targeting of Cancer Stem Cells

Therapeutics Solutions International, Inc. announced the formulation and initial clinical implementation of an injectable form of pterostilbene called “IsoStilbene” derived from their 047 patent. [Therapeutics Solutions International, Inc.] Press Release

Basilea Starts Clinical Phase IIa Expansion with BAL101553 in Ovarian Cancer and Glioblastoma

Basilea Pharmaceutica Ltd. announced that the first patient has been dosed in the Phase IIa expansion part of Basilea’s ongoing Phase I/IIa clinical study with its novel tumor checkpoint controller BAL101553, administered as weekly 48-hour intravenous infusion. [Basilea Pharmaceutica Ltd. (GlobeNewswire, Inc.)] Press Release

Moleculin Receives Approval for Leukemia Clinical Trial

Moleculin Biotech, Inc. announced it has received Polish National Office approval to begin its second Phase I/II clinical trial to study Annamycin for the treatment of relapsed or refractory acute myeloid leukemia. [Moleculin Biotech, Inc.] Press Release

DelMar Pharmaceuticals Announces Accelerated Patient Enrollment of Phase II Trial in MGMT-Unmethylated Recurrent GBM

DelMar Pharmaceuticals, Inc. updated patient enrollment data for its Phase II open-label clinical trial of VAL-083 in bevacizumab-naïve recurrent glioblastoma multiforme (GBM) patients with MGMT-unmethylated status. [DelMar Pharmaceuticals, Inc.] Press Release

Trovagene Announces Preliminary Clinical Data from First Dosing Cohort Demonstrating Durable Treatment Effect of PCM-075 in Combination with Cytarabine or Decitabine in Patients with Relapsed or Refractory AML

Trovagene, Inc. announced preliminary clinical data from the first dosing cohort showing a treatment effect with PCM-075 in combination with low-dose cytarabine or decitabine, as measured by decreases in leukemic cells in both peripheral blood and bone marrow in patients in its ongoing Phase Ib/II trial in relapsed or refractory AML. [Trovagene, Inc.] Press Release

Macchiarini Guilty of Misconduct, but Whistleblowers Share Blame, New Karolinska Institute Verdict Finds

The Karolinska Institute in Stockholm has finally, officially, found disgraced surgeon Paolo Macchiarini guilty of scientific misconduct. However, the verdict is a bitter pill for the four people who raised the alarm about Macchiarini’s fraud. [ScienceInsider] Editorial

New Drug Approval Should Force the DEA to Rethink Cannabis-Derived Medicines

The Food and Drug Adminstration’s approval of Epidiolex, a medication derived from cannabis, could be life-changing for Americans suffering from certain types of epilepsy. It may also have far-reaching implications for U.S. marijuana policy. [STAT News] Editorial

Worrying Changes in Hungary

The European country’s autocratic government has made a disturbing grab at the nation’s scientific institutions. [Nature News] Editorial

Senate Panel Proposes $2 Billion, 5.4% Increase for NIH

A U.S. Senate appropriations subcommittee approved a spending bill that calls for giving the National Institutes of Health (NIH) a $2 billion, 5.4% increase to $39.1 billion in the 2019 fiscal year that begins 1 October. [ScienceInsider] Editorial

NEW Lorne Cancer Conference 2019
February 14-16, 2019
Lorne, Australia

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NEW Postdoctoral Fellow – Cancer Biology (Children’s Cancer Therapy Development Institute)

Postdoctoral Training Fellow – Breast Cancer Stem Cells (The Francis Crick Institute)

Research Officer – Cancer Research (University of New South Wales)

Tenure-Track Faculty Positions – Various (The Ohio State University)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University Feinberg School of Medicine)

PhD Student – Cell Signaling (German Cancer Research Center)

Postdoctoral Positions – High Mobility Group A Proteins in Cancer, Cancer Stem Cells, and Normal Development (Johns Hopkins University School of Medicine)

Postdoctoral Position – Stem Cell Bioinformatics (University of Copenhagen)

Postdoctoral Research Associate – Stem Cell and Cancer Biology (University of North Texas Health Science Center)

Postdoctoral Position – Cancer Research (Institute for Research in Biomedicine)

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