Cancer Stem Cell News Volume 5.27 | Jul 13 2016

TOP STORY

Where Did It All Go Wrong? Scientists Identify ‘Cell of Origin’ in Skin Cancers

Scientists have identified for the first time the ‘cell of origin’ – in other words, the first cell from which the cancer grows – in basal cell carcinoma, the most common form of skin cancer, and followed the chain of events that lead to the growth of these invasive tumors. [Press release from the University of Cambridge discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells

Since acute myeloid leukemia (AML) is characterized by the blockade of hematopoietic differentiation and cell death, the authors interrogated RIPK3 signaling in AML development. Genetic loss of Ripk3 converted murine FLT3-ITD-driven myeloproliferation into an overt AML by enhancing the accumulation of leukemia-initiating cells. [Cancer Cell] Abstract | Graphical Abstract

Single-Cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-Renewal of Human Bladder Cancer Stem Cells

Scientists conducted single-cell sequencing on 59 cells including bladder cancer stem cells (BCSCs), bladder cancer non-stem cells (BCNSCs), bladder epithelial stem cells (BESCs) and bladder epithelial non-stem cells (BENSCs) from three bladder cancer (BC) specimens. Specifically, BCSCs demonstrate clonal homogeneity and suggest their origin from BESCs or BCNSCs through phylogenetic analysis. [Eur Urol] Abstract

The Loss of Ezh2 Drives the Pathogenesis of Myelofibrosis and Sensitizes Tumor-Initiating Cells to Bromodomain Inhibition

Loss-of-function mutations in EZH2 are associated with poorer outcomes in patients with myeloproliferative neoplasms, particularly those with primary myelofibrosis (PMF). To determine how EZH2 insufficiency is involved in the pathogenesis of PMF, researchers generated mice compound for an Ezh2 conditional deletion and activating mutation in JAK2 present in patients with PMF. [J Exp Med] Abstract

Endogenous GABA_A Receptor Activity Suppresses Glioma Growth

Scientists demonstrated functional GABA_A receptor-activated currents in human glioblastoma cells and showed the existence of a continuous GABA signaling within the tumor cell mass that significantly affects tumor growth and survival expectancy in mouse models. [Oncogene] Abstract

Serine-Arginine Protein Kinase 1 Promotes a Cancer Stem Cell-Like Phenotype through Activation of Wnt/β-Catenin Signaling in NSCLC

Investigators showed that Serine-arginine protein kinase 1 (SRPK1) is highly expressed at both the mRNA and protein levels in human non-small-cell lung carcinoma (NSCLC). SRPK1 associated with the clinical features of human NSCLC, including clinical stage and T, N and M classifications. [J Pathol] Abstract

MLN0128, a Novel mTOR Kinase Inhibitor, Disrupts Survival Signaling and Triggers Apoptosis in AML and AML Stem/ Progenitor Cells

MLN0128 is an orally-administered, second-generation active-site mTOR inhibitors, currently in clinical development. Investigators examined the anti-leukemic effects and the mechanisms of action of MLN0128 in acute myeloid leukemia (AML) cell lines and primary samples, with a particular focus on its effect in AML stem/progenitor cells. [Oncotarget] Full Article

Notch Pathway Activation Is Essential for Maintenance of Stem-Like Cells in Early Tongue Cancer

Researchers analyzed the Notch signaling pathway in 68 early stage tongue squamous cell carcinoma primary tumor samples by whole exome and transcriptome sequencing, real-time PCR based copy number, expression, immuno-histochemical, followed by cell based biochemical and functional assays. [Oncotarget] Full Article

Single Cell Dual Adherent-Suspension Co-Culture Micro-Environment for Studying Tumor-Stromal Interactions with Functionally Selected Cancer Stem-Like Cells

To enable single cell derived tumorsphere formation within a stromal microenvironment, the authors present a dual adherent/suspension co-culture device, which combines a suspension environment for single-cell tumorsphere assays and an adherent environment for co-culturing stromal cells in close proximity by selectively patterning polyHEMA in indented microwells. [Lab Chip] Abstract

The Eicosanoids Leukotriene D₄ and Prostaglandin E₂ Promote the Tumorigenicity of Colon Cancer-Initiating Cells in a Xenograft Mouse Model

The authors advanced understanding of the role of the eicosanoids leukotriene D₄ and prostaglandin E₂ in the tumorigenic ability of cancer-initiating cells and investigates the consequential changes occurring in the tumor environment that might support tumor growth. [BMC Cancer] Full Article

miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and Glioblastoma SNB19 Cells

A therapeutic strategy to inhibit autophagy and promote apoptosis could greatly help control growth of glioblastoma. Scientists created hypoxia using sodium sulfite for induction of substantiated autophagy in human glioblastoma stem cells and glioblastoma SNB19 cells. Induction of autophagy was confirmed by acridine orange staining and significant increase in Beclin-1 in autophagic cells. [PLoS One] Full Article

The Combination of Bleomycin with Suicide or Interferon-β Gene Transfer Is Able to Efficiently Eliminate Human Melanoma Tumor Initiating Cells

Researchers explored the potential of a chemogene therapy combination to eradicate melanoma tumor initiating cells, key producers of recurrence and metastatic spread. Three new human melanoma cell lines, two obtained from lymph nodes and one from spleen metastasis were established and characterized. [Biomed Pharmacother] Abstract

Targeting Cancer Stem-Like Cells in Glioblastoma and Colorectal Cancer through Metabolic Pathways

The reviewers discuss the association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks. [Int J Cancer] Abstract

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

Vigilant Biosciences Announces Oral Presentation on CD44 and Associated Markers in Oral Rinses and Tissues from Oral Cancer Patients

Vigilant Biosciences, Inc. announced a presentation of data related to proof-of-concept studies by Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, titled CD44 and Associated Markers in Oral Rinses and Tissues from Oral Cancer Patients. [Press release from American Head and Neck Society discussing research presented at 9^th International Conference on Head and Neck Cancer, Seattle] Press Release

Trovagene and USC Norris Comprehensive Cancer Center Collaborate to Standardize the Use of Trovera™ ctDNA Liquid Biopsy Tests in Patient Care

Trovagene, Inc. announced that it has entered into a broad collaboration agreement with the University of Southern California (USC) Norris Comprehensive Cancer Center. This collaboration will seek to establish a standardized framework for the use of Trovera™ urine liquid biopsy testing at USC as well as to define practical considerations and best practices for liquid biopsy testing from urine. [Oncternal Therapeutics, Inc.] Press Release

Lilly and Boehringer Ingelheim Announce Clinical Trial Collaboration in Metastatic Breast Cancer

Eli Lilly and Company and Boehringer Ingelheim announced a new collaboration on a Phase Ib study that will evaluate the safety and tolerability of abemaciclib, Lilly’s cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor, in combination with BI 836845, Boehringer Ingelheim’s insulin-like growth factor (IGF)-1/IGF-2 ligand neutralizing antibody, in patients diagnosed with HR⁺, HER^2- metastatic breast cancer. [Eli Lilly and Company] Press Release

TK216 Receives Orphan Drug Designation for the Treatment of Ewing Sarcoma, a Rare Pediatric Cancer

Oncternal Therapeutics, Inc. announced that TK216 has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of Ewing sarcoma. TK216 is a first-in-class small molecule inhibiting ets-family transcription factor oncoproteins, which are the main disease drivers in Ewing tumors. [Oncternal Therapeutics, Inc.] Press Release

CytRx Announces Initial Results of Phase III Trial of Aldoxorubicin in Patients with Second-Line Soft Tissue Sarcoma; Subsequent Analysis to Be Announced Fourth Quarter 2016

CytRx Corporation announced the results of an analysis of its global, randomized, Phase III clinical trial of aldoxorubicin compared to investigator’s choice therapy in patients with relapsed or refractory soft tissue sarcomas. [CytRx Corporation] Press Release

Policy Implications of Aging in the NIH-Funded Workforce

Because of national interest in the “graying” of the biomedical workforce, the authors examine aging and funding within the pool of NIH-funded investigators and applicants, particularly in the growing field of stem cell research. They provide evidence of a maturing and more competitive stem cell workforce and discuss policy implications. [Cell Stem Cell] Editorial

FDA Should Stand Firm on Stem-Cell Treatments

You may have heard that regulators in the United States are too strict when it comes to stem-cell treatments. The assumption in these accusations — that these treatments work — is at the heart of the problem. The FDA is right to insist that only proper clinical trials can make that case. [Nature News] Editorial

House Panel Would Give NIH a 4% Raise to $33 Billion

The National Institutes of Health (NIH) is slated to receive a $1.25 billion increase, to $33.3 billion, in a proposed spending measure released by a House of Representatives spending panel. That 4% boost is good news for an agency that has been flat funded for a decade, although it falls short of a 6% raise approved by a Senate panel. [ScienceInsider] Editorial | Press Release

Canada’s Health Funder Agrees to Meet with Researchers Outraged by Peer-Review Changes

Canadian Institute of Health Research (CIHR) President Alain Beaudet said the agency will heed Jane Philpott’s request to “convene a working meeting in the very near future with key representatives of the research community, including those who have raised this issue publicly, to find common ground and move forward with solutions that address the issues raised with regard to the quality and integrity of CIHR’s peer review system.” [ScienceInsider] Editorial

U.K. Research Charity Will Self-Publish Results from Its Grantees

Starting sometime this fall, the Wellcome Trust will launch its own open-access online journal. Publication will be limited to the thousands of scientists worldwide working on research funded by a Wellcome grant, and it will be free not only for readers, but authors—the charity is covering the costs charged by the company that will provide the journal’s software and online platform. [ScienceInsider] Editorial

Beat It, Impact Factor! Publishing Elite Turns against Controversial Metric

A paper posted to the preprint server bioRxiv, authored by senior employees at several leading science publishers (including Nature’s owner, SpringerNature), calls on journals to downplay the figure in favor of a metric that captures the range of citations that a journal’s articles attract. [Nature News] Editorial | Article

Brexit Watch: Scientists Grapple with the Fallout

Two weeks after the United Kingdom voted to leave the European Union, the future remains opaque. Concerns within the research community are particularly intense for those who rely on the EU for funding, or who have the right to work in the United Kingdom only because they are citizens of other EU countries. [Nature News] Editorial

The Past, Present and Future of the PhD Thesis

According to one of those often-quoted statistics that should be true but probably isn’t, the average number of people who read a PhD thesis all the way through is 1.6. And that includes the author. More interesting might be the average number of PhD theses that the typical scientist — and reader of Nature — has read from start to finish. [Nature News] Editorial

Major Funders Launch International Repository of Cutting-Edge Cancer Models

U.S. and European funding agencies are launching the Human Cancer Models Initiative, which aims to give the research community tumor cells that behave more like actual human tumors. [ScienceInsider] Editorial

Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry

Direct-to-consumer marketing of unapproved stem cell interventions is a well-known phenomenon in countries with lax medical regulations. However, an examination of Internet-based marketing claims revealed widespread promotion of such interventions by businesses based in the United States. Such commercial activity suggests that regulatory agencies must better oversee this marketplace. [Cell Stem Cell] Editorial

NEW 4^th International Oncology Conference
September 29-30, 2016
Abu Dhabi, United Arab Emirates

NEW Cancer Stem Cell Conference 2016
September 20-23, 2016
Cleveland, United States

Visit our events page to see a complete list of events in the cancer stem cell community.

NEW Postdoctoral Research Assistant – Epigenetics and Immune-Oncology (University of Oxford)

NEW PhD Studentship – Self-Renewal, Differentiation and Metastasis of Tumor Initiating Cells (German Cancer Research Center)

Postdoctoral Fellow – Synthetic Cancer Biology (Beth Israel Deaconess Medical Center and Harvard Medical School)

Postdoctoral Fellow – Tumor Biology in Multiple Myeloma (Lerner Research Institute, Cleveland Clinic)

Institute Associate Scientist III – Target Biology (MD Anderson Cancer Center)

Postdoctoral Fellowship – Wnt Pathway in Sarcoma Pathogenesis (University of Miami Health System)

Postdoctoral Scientist – Leukemic Stem Cells (University of Oxford)

Senior Cancer Analyst – 100,000 Genomes Project (Queen Mary University of London)

Postdoctoral Researcher – DNA Damage Signaling (University of Oxford)

Postdoctoral Fellow – Cancer Stem Cell Biology (Cleveland Clinic Lerner Research Institute)

Postdoctoral Fellow – Biology of Tumor Initiating Cells (German Cancer Research Center)

Assistant Professor – Molecular Pharmacology, Systems Biology, Cancer Therapeutics (German Cancer Research Center)

Team Leader – Immune-Oncology (Fondation Toulouse Cancer Sante)

Postdoctoral Fellow – Adaptive T-Cell Therapy for Cancer (Memorial Sloan Kettering Cancer Center)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Cancer Stem Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.