Cancer Stem Cell News Volume 6.39 | Oct 4 2017

TOP STORY

Genetic Targets to Chemo-Resistant Breast Cancer Identified

Scientists identified potential targets for treatment of triple negative breast cancer. Increased activity of two genes, MCL1 and MYC, was associated with the development of chemotherapy resistance. [Press release from UT Southwestern Medical Center discussing online prepublication in Cell Metabolism] Press Release | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Downregulation of DNMT3A by miR-708-5p Inhibits Lung Cancer Stem Cell-Like Phenotypes through Repressing Wnt/β-Catenin Signaling

The authors revealed a novel role for miR-708-5p in inhibiting lung cancer stem cell-like features. Phenotypic effects of miR-708-5p on the lung CSC-like properties were examined by in vitro sphere formation assay and in xenografted animal models. [Clin Cancer Res] Abstract

MYC Inhibition Depletes Cancer Stem-Like Cells in Triple-Negative Breast Cancer

Researchers reported that triptolide (C1572), a small molecule natural product selectively depleted CSCs in a dose-dependent fashion in human triple-negative breast cancer cell lines. Nanomolar concentrations of C1572 markedly reduced c-MYC (MYC) protein levels via a proteasome-dependent mechanism. [Cancer Res] Abstract

JAM-C Identifies Src Family Kinase-Activated Leukemia-Initiating Cells and Predicts Poor Prognosis in Acute Myeloid Leukemia

Investigators showed that JAM-C expression defined a subset of leukemic cells endowed with leukemia-initiating cell activity. Stratification of de novo acute myeloid leukemia patients at diagnosis based on JAM-C-expressing cells frequencies in the blood served as an independent prognostic marker for disease outcome. [Cancer Res] Abstract

Using a Novel Computational Drug-Repositioning Approach (DrugPredict) to Rapidly Identify Potent Drug Candidates for Cancer Treatment

The authors assessed whether non-steroidal anti-inflammatories (NSAIDs) could have chemoadjuvant applications in epithelial ovarian cancer. They found that NSAID Indomethacin induced robust cell death in primary patient-derived platinum-sensitive and platinum-resistant ovarian cancer cells and ovarian cancer stem cells and downregulation of β-catenin was partially driving effects of Indomethacin in cisplatin-resistant cells. [Oncogene] Full Article

NF-kB–Mediated Invasiveness in CD133⁺ Pancreatic TICs Is Regulated by Autocrine and Paracrine Activation of IL-1 Signaling

The authors found that overexpression of CD133 increased expression and secretion of IL-1β, which activated an autocrine signaling loop that upregulated NF-κB signaling, epithelial-mesenchymal transition, and cellular invasion. This signaling pathway also induced CXCR4 expression, which in turn was instrumental in imparting an invasive phenotype to these cells. [Mol Cancer Res] Abstract

CD24, CD44 and EpCAM Enrich for Tumor-Initiating Cells in a Newly Established Patient-Derived Xenograft of Nasopharyngeal Carcinoma

Researchers evaluated the tumorigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in nasopharyngeal carcinoma. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumorigenic cells leading to tumors with larger volume and higher mitotic figures. [Sci Rep] Full Article

Meis2 as a Critical Player in MN1-Induced Leukemia

To identify key genes and pathways underlying leukemic activity, scientists functionally assessed meningioma 1 (MN1) cell phenotypic heterogeneity, revealing leukemic and non-leukemic subsets. Using gene expression profiling of these subsets combined with previously published comparisons of full-length MN1 and mutants with varying leukemogenic activity, they identified candidate genes critical to leukemia. [BMC Cancer] Full Article

Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer

The authors revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acted as a downstream mediator of podocalyxin-like protein 1 (PODXL) in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. [Int J Mol Sci] Full Article

Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using CYFRA 21-1

The authors examined whether K19⁺ hepatocellular carcinoma-CSCs can be tracked using cytokeratin 19 fragment CYFRA 21-1. In 147 hepatocellular carcinoma patients who underwent curative resection and evaluated K19 expression by immunohistochemistry, preoperative serum CYFRA 21-1 levels were significantly higher in K19⁺ patients than in K19⁻ patients. [Cancer Med] Full Article

Targeting Cellular Pathways in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) has a very complex pathogenesis that involves mutations and alterations of several key cellular pathways that are involved in cell proliferation, survival, migration and angiogenesis. Scientists outline the alterations commonly associated with GBM pathogenesis and summarize therapeutic strategies that are aimed at targeting aberrant cellular pathways in GBM. [Signal Transduct Target Ther] Full Article

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Medicenna Updates On-Going Phase IIb Clinical Trial Protocol for Recurrent Glioblastoma

Medicenna Therapeutics Corp. announced that based on encouraging drug distribution and safety data observed in the on-going Phase IIb clinical trial of MDNA55 for the treatment of patients with recurrent glioblastoma, the company has commenced implementation of an updated protocol following its submission to the FDA and approval by the respective Institutional Review Boards. [Medicenna Therapeutics Corp.] Press Release

National Cancer Institute Awards Grant to NuvOx Pharma for Phase II Clinical Trial in Brain Cancer

The National Cancer Institute has awarded a grant for up to $3 million to NuvOx Pharma to initiate a Phase II clinical trial for the investigational drug, NVX-108, in the brain cancer, glioblastoma multiforme. [NuvOx Pharma (Business Wire, Inc.)] Press Release

Mylan Launches Generic Gleevec^® Tablets

Mylan N.V. announced the U.S. launch of Imatinib Mesylate Tablets, a generic version of Novartis’s Gleevec^® Tablets. Mylan received final approval from the FDA for its Abbreviated New Drug Application for this product, which has multiple indications, including for several blood cancers. [Mylan N.V.] Press Release

MD Anderson and BridgeBio Pharma Launch Navire Pharma to Develop Targeted Therapy for Patients with Difficult-to-Treat Cancer

The University of Texas MD Anderson Cancer Center and BridgeBio Pharma announced the launch of Navire Pharma, a biopharmaceutical company aimed at developing novel small-molecule inhibitors of a tyrosine-protein phosphatase called SHP2 for genetically-driven and treatment-resistant cancer. [MD Anderson Cancer Center (Business Wire, Inc.)] Press Release

Judge Recommends Ruling to Block Internet Access to Sci-Hub

The American Chemical Society (ACS) brought a case against Sci-Hub, a pirate site providing access to scientific articles, for copyright and trademark infringement. Following a hearing at a court in Virginia, Magistrate Judge John Anderson filed a report that recommended ruling in favor of ACS on all counts. [The Scientist] Editorial

After Upheaval, Russian Academy of Sciences Gets New Leader

After months of uncertainty, the Russian Academy of Sciences here finally has a new leader. Russian President Vladimir Putin approved physicist Alexander Sergeyev as the academy’s president for the next 5 years. Sergeyev has vowed to secure more money for Russian science and create a fund, through a new tax on fossil fuel company profits, for upgrading the country’s antiquated research infrastructure. [ScienceInsider] Editorial

French Government Proposes Big Science-Spending Boost

French research funding is set for a heartening increase in the country’s first budget under President Emmanuel Macron, if draft 2018 plans are voted into law. [Nature News] Editorial

NEW 7^th International Symposium on Hereditary Breast and Ovarian Cancer
May 8-11, 2018
Montreal, Canada

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NEW Postdoctoral Fellow – Leukemia Stem Cells (Memorial Sloan Kettering Cancer Center)

NEW Assistant Professor – Cancer Biology (Perelman School of Medicine)

NEW Assistant Professor – Cancer Research (University of Minnesota)

Postdoctoral Fellow – Cancer Stem Cell Research (MD Anderson Cancer Center)

Postdoctoral Positions – Stem Cell and Cancer Biology (Johns Hopkins University)

Director – Stanford Cancer Institute (Stanford University)

Faculty Position – Stem Cell Biology (University of Texas Southwestern Medical Center)

Faculty Positions – Cancer and Stem Cell Biology (Sun Yat-Sen University)

Postdoctoral Fellows – Cancer Stem Cell Biology (Genome Institute of Singapore)

Research Officers – Cancer Stem Cell Biology (Genome Institute of Singapore)

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