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Pulmonary Cell News| Cancer Stem Cell News 5.46 November 23, 2016 | |
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TOP STORYEpigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth Scientists developed a de novo glioblastoma multiforme model derived from immortalized human neural stem/progenitor cells (NSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. [Cell] Abstract | Press Release | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Investigators found that IL6-mediated inflammation programs constitutive activation of the TAK1-NFκB signaling cascade in CD133+ liver stem cells (LSCs) and this program interacts with deficient TGFβ signaling, thereby accelerating the transformation of normal LSCs to metastatic cancer stem cells (CSCs). [Hepatology] Abstract Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia. However, the resistance of leukemia stem cells (LSCs) to BET inhibitors remains a major challenge. Scientists evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. [Clin Cancer Res] Abstract Researchers discovered that AXL tyrosine kinase was selectively overexpressed in primary chronic myelogenous leukemia (CML) CD34+ cells. Their findings improve the understanding of leukemia stem cell (LSC) regulation and validate Gas6/AXL as a pair of therapeutic targets to eliminate CML LSCs. [Clin Cancer Res] Abstract Resetting Cancer Stem Cell Regulatory Nodes upon MYC Inhibition The authors addressed MYC function in cancer stem cells through the inducible expression of Omomyc – a MYC-derived polypeptide interfering with MYC activity – as to model the most lethal brain tumor, glioblastoma. [EMBO Rep] Abstract CD274 Promotes Cell Cycle Entry of Leukemia-Initiating Cells through JNK/Cyclin D2 Signaling Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. Investigators established an MLL-AF9-induced acute myeloid leukemia model with wild-type and CD274-null mice to elucidate the role of CD274 in the cell fates of leukemia-initiating cells, including self-renewal, differentiation, cell cycle, and apoptosis. [J Hematol Oncol] Full Article Proteome and Secretome Characterization of Glioblastoma-Derived Neural Stem Cells Researchers performed quantitative proteomics to globally characterize and compare total proteome plus the secreted proteome (secretome) between glioblastoma multiforme (GBM)-derived neural stem (GNS) cells and neural stem (NS) cells. GBM consists of heterogeneous cell types including a subset of stem cell-like cells thought to sustain tumor growth. These tumor-initiating GNS cells as well as their genetically normal NS counterparts can be propagated in culture as relatively pure populations. [Stem Cells] Abstract Patient-Derived Glioblastoma Stem Cells Respond Differentially to Targeted Therapies Scientists demonstrated that patient-derived glioblastoma stem cells (GSCs) exhibit different growth rates in culture, possess differential capabilities to form a tumor, and have varied responses to targeted therapies. To address this, they isolated and characterized ten GSC lines from established cell lines, xenografts, or patient specimens. [Oncotarget] Full Article Researchers confirmed that the high invasive epithelial ovarian cancer cells forming the spheroids expressed a high level of a cancer stem cell marker, aldehyde dehydrogenase 1 family member A1, which was significantly down-regulated by curcumin treatment. [Oncotarget] Full Article The Efflux Transporter ABCG2 Maintains Prostate Stem Cells Using the HPr-1-AR and CWR-R1 prostate cell lines, investigators demonstrated that inhibiting the ATP binding cassette sub-family G Member 2 (ABCG2)-mediated androgen efflux, with Ko143, increased the nuclear androgen receptor (AR) expression due to elevated intracellular androgen levels. Increased nuclear translocation of AR was followed by increased expression of AR regulated genes, a delayed cell growth response, and increased luminal differentiation. [Mol Cancer Res] Abstract The expression of candidate cancer stem cell (CSC) markers is associated with a poor prognosis in a number of cancer types, but their clinical significance remains unclear and there have been no clinical studies in melanoma. Investigators aimed to determine the clinical significance of four molecules identifying putative CSCs, namely CD133, ABCG2, ALDH1A1 and CD44v7/8. [Br J Dermatol] Abstract The authors found that the inverse correlation between Wnt signaling and repression of estrogen receptor 1 (ESR1) and progesterone receptor expression was magnified in cancer stem cell (CSC) subpopulations in triple-negative breast cancer (TNBC) cell lines. Co-suppression of Wnt, histone deacetylase (HDAC), and ESR1 using clinically relevant low-dose inhibitors effectively repressed both bulk and CSC subpopulations and converted CSCs to non-CSCs in TNBC cells without affecting MCF-10A mammary epithelial cells. [FEBS Lett] Abstract Researchers used two murine colorectal cancer (CRC) cell lines MC38 and CT26 to analyze the impact of Salinomycin (Sal) on tumor cell proliferation, viability, migration, cell cycle progression and cell death in vitro. CRC growth in vivo was likewise inhibited upon Sal treatment. [BMC Cancer] Full Article Scientists determined the effects of mesenchymal stromal cells (MSCs) on osteosarcoma (OS) stemness and migration, two major features associated with recurrence and chemoresistance. The presence of stromal cells enhanced the number of floating spheres enriched in cancer stem cells of the OS cell population. Furthermore, the co-culturing with MSC stimulated the migratory capacity of OS via TGFβ1 and IL-6 secretion, and the neutralizing antibody anti-IL-6 impaired this effect. [PLoS One] Full Article Defective Autophagy Leads to the Suppression of Stem-Like Features of CD271+ Osteosarcoma Cells As an important stress-response mechanism, autophagy plays crucial role in the tumor formation and drug resistance of cancer cells including osteosarcoma (OS). OS cancer stem cells (CSCs) also are considered a key factor of tumorigenesis, drug resistance and tumor recurrence. Researchers demonstrated that autophagy contributes to the stem-like features of CD271+ OS CSCs. [J Biomed Sci] Full Article Suberoylanilide Hydroxamic Acid Represses Glioma Stem-Like Cells In order to find new strategies aimed at reducing glioma stem-like cell (CSC) stemness and improving glioblastoma multiforme patient survival, the authors investigated the effects and mechanism of a histone deacetylases inhibitor (HDAC), suberoylanilide hydroxamic acid, since HDAC activity has been linked to CSC abundance and properties. [J Biomed Sci] Full Article | |
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REVIEWSCancer Stem Cell-Targeted Therapeutics and Delivery Strategies Cancer stem cells (CSCs) usually reside within the tumor and are responsible for reoccurrence of cancer. The imprecise, inaccessible nature and increased efflux of conventional therapeutic drugs make these cells resistant to drugs. The authors discuss the specific markers for identification of these cells, role of CSCs in chemotherapy resistance and use of different therapeutic means to target them, including elucidation of specific cell markers, exploitation of different signaling pathways and use of nanotechnology. [Expert Opin Drug Deliv] Abstract Visit our reviews page to see a complete list of reviews in the cancer stem cell research field. | |
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SCIENCE NEWSImmunoCellular Therapeutics, Ltd. announced the presentation of updated immune monitoring data from the Phase II trial of ICT-107 in patients with newly diagnosed glioblastoma. Also presented were updated long-term survival data from the Phase I trial of ICT-107. ICT-107 is a dendritic cell-based immunotherapy targeting multiple tumor-associated antigens on glioblastoma stem cells. [Press release from ImmunoCellular Therapeutics, Ltd. discussing research presented at the 21st Annual Scientific Meeting and Education Day of the Society for NeuroOncology, Scottsdale] Press Release DelMar Pharmaceuticals, Inc. delivered an oral address about research and recent clinical trial results and how these data position VAL-083 as a potential solution for newly diagnosed GBM patients whose cancer exhibits features, such as a high expression of MGMT, implicated in resistance to currently approved chemotherapy. [Press release from DelMar Pharmaceuticals, Inc. (PR Newswire Association LLC.) discussing research presented at the 2nd Annual CNS Anticancer Drug Discovery and Development Conference and Society for NeuroOncology, Scottsdale] Press Release | Poster | |
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INDUSTRY NEWSOnxeo Announces 9th Positive DSMB Recommendation to Continue Livatag® ReLive Phase III Trial in HCC Onxeo S.A. announced that the company has received the 9th unanimous recommendation from the Data Safety Monitoring Board, an independent European board of experts that monitors the safety of the Livatag® Phase III trial, “ReLive”, to continue the study without modification. The ReLive study is designed to evaluate the efficacy of intravenous administration of Livatag® in patients with advanced hepatocellular carcinoma (HCC) after failure or intolerance to sorafenib. [Onxeo S.A.] Press Release AbilityPharma announced the initiation of the first Phase II Trial with its targeted drug candidate ABTL0812 as first-line therapy to evaluate its efficacy and safety combined with paclitaxel and carboplatin in 80 patients with advanced or recurrent endometrial cancer or squamous lung cancer. [AbilityPharma (PR Newswire Association LLC.)] Press Release Bristol-Myers Squibb Company announced the European Commission approved Opdivo for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin. Opdivo is now the first and only PD-1 inhibitor approved for a hematologic malignancy in the European Union. [Bristol-Myers Squibb Company] Press Release Janssen Biotech, Inc. announced the U.S. Food and Drug Administration (FDA) has approved DARZALEX® in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. [Janssen Biotech, Inc.] Press Release Teva Pharmaceutical Industries Ltd., announced it has obtained approval from the European Commission for an indication extension of Trisenox® (arsenic trioxide). This marks an important advancement in treatment for Acute Promyelocytic Leukemia patients in Europe, as it is the first time that a form of acute leukemia can be effectively treated with a regimen that is entirely chemotherapy-free. [Teva Pharmaceutical Industries Ltd.] Press Release QuintilesIMS announced that it will lead a collaborative initiative involving founding partners Bristol-Myers Squibb, Eli Lilly and Company, Merck KGaA, Darmstadt, Germany and Pfizer, which aims to provide clearer and more proactive insight into how anti-cancer treatments are used in a real-world setting across key European markets. [QuintilesIMS (Business Wire, Inc.)] Press Release MD Anderson Receives $22 Million in CPRIT Funding for Research, Recruitment and Training The University of Texas MD Anderson Cancer Center was awarded $22 million from the Cancer Prevention and Reasearch Insitute of Texas, receiving 24 percent of the total $93 million awarded. The MD Anderson awards included $990,905 for early translational research, $8.9 million for individual investigator research, $6 million for research training and $6 million for recruitment of an established investigator. [The University of Texas MD Anderson Cancer Center] Press Release Van Andel Research Institute, in collaboration with Cedars-Sinai, has received a $2.5 million, five-year grant from the National Cancer Institute, part of the National Institutes of Health, that will fuel efforts by investigators to uncover the underpinnings of cancer, ultimately helping scientists develop better diagnostic and treatment strategies for a class of diseases that claim more than eight million lives each year worldwide. [Van Andel Institute] Press Release | |
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POLICY NEWSImmigrant and Minority Scientists Shaken by Trump Win Scientists are reconsidering whether to work or study in the United States. Worries include job prospects, discrimination — and safety. [Nature News] Editorial Peer-Review ‘Heroes’ Do Lion’s Share of the Work In 2015, the number of scientists in the life sciences far exceeded the demand on them for peer review, according to Michail Kovanis, a computational physicist at the French National Institute of Health and Medical Research in Paris, and his colleagues. Yet their study also suggests – based on data obtained from a rapidly-growing website of peer-review activity – that 20% of the scientists undertook between 69% and 94% of reviews last year, lending credence to some researchers’ complaints that they are overburdened. [Nature News] Editorial NgAgo Gene-Editing Controversy Escalates in Peer-Reviewed Papers A heated dispute over gene-editing that began online is now playing out in the scientific literature. Six months ago, Chinese researchers reported that an enzyme called NgAgo could be used to edit mammalian genes – and that it might be more accurate and more versatile than the popular CRISPR-Cas9 gene-editing technique. [Nature News] Editorial
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EVENTSNEW Challenges, Solutions and Progress in Stem Cell Medicine Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) NEW Postdoctoral Fellow – Computational Cancer Genomics (European Molecular Biology Laboratory) NEW Assistant Professor – Cancer Research (National University of Singapore) NEW Postdoctoral Fellow – Cancer Research (National University of Singapore) NEW Postdoctoral Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Fellow – Viruses & Cancer (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Fellow – RNA Biology and Cancer (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Fellow – Pancreas Cancer (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Fellow – Cancer Epidemiology (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Fellow – Ubiquitin System and Cancer (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Position – Tumor Immunology (Moffitt Cancer Center) NEW Postdoctoral Position – Computational Cancer Biologist (University of Oxford) Tier 2 Canada Research Chair – Pharmacology (University of Ottawa) Postdoctoral Position – Physical Oncology (Houston Methodist Research Institute) Assistant, Associate or Full Professor – Cancer Biology (University of Pennsylvania) Assistant Professor (Tenure Track) – Mechanisms Related to Aging, Cancer and Stem Cell Biology) Scientific Developer – Computational Systems Biology of Cancer (Institut Curie) Two Assistant Professor Positions – Molecular Medicine (University of Georgia) Postdoctoral Position – Metastatic Breast Cancer (Purdue Center for Cancer Research) 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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