Cancer Stem Cell News Volume 8.30 | Aug 7 2019

TOP STORY

Interconversion between Tumorigenic and Differentiated States in Acute Myeloid Leukemia

Investigators showed in murine and human models of acute myeloid leukemia that, upon perturbation of endogenous expression of the lineage-determining transcription factor PU.1 or withdrawal of established differentiation therapies, some mature leukemia cells could de-differentiate and reacquire clonogenic and leukemogenic properties. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

CD97 Is a Critical Regulator of Acute Myeloid Leukemia Stem Cell Function

Researchers identified CD97, a member of the adhesion class of G protein-coupled receptors, as a frequently up-regulated antigen on acute myeloid leukemia blasts that was a critical regulator of blast function. High levels of CD97 correlated with poor prognosis, and silencing of CD97 reduced disease aggressiveness in vivo. [J Exp Med] Abstract

SFRPs Are Biphasic Modulators of Wnt-Signaling-Elicited Cancer Stem Cell Properties beyond Extracellular Control

Using the established system, the authors found that nuclear secreted frizzled-related proteins (SFRPs) interacted with β-catenin and either promoted or suppressed TCF4 recruitment. SFRPs bound with β-catenin on both their N and C termini, with the repressive effects caused by SFRP-β-catenin-N-terminus binding overpowering the promoting effects of their binding at the C terminus. [Cell Rep] Full Article | Graphical Abstract

HDAC7 Regulates Histone 3 Lysine 27 Acetylation and Transcriptional Activity at Super-Enhancer-Associated Genes in Breast Cancer Stem Cells

Scientists investigated the CSC-specific function of HDAC1 and HDAC7 mechanistically by using a stem-like breast cancer (BrCa) cell model BPLER and matched non-stem tumor cell-like HMLER, along with conventional BrCa cell lines with different CSC enrichment levels. [Oncogene] Full Article

Disulfiram’s Anti-Cancer Activity Reflects Targeting NPL4, Not Inhibition of Aldehyde Dehydrogenase

Researchers found that the anti-cancer activity of disulfiram (DSF) did not involve aldehyde dehydrogenase inhibition, and rather reflected the impact of DSF’s copper-containing metabolite, that formed spontaneously in vivo and in cell culture media, and killed cells through aggregation of NPL4, a subunit of the p97/VCP segregase. [Oncogene] Abstract

Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia

In Meis1a/Hoxa9-driven acute myeloid leukemia (AML), deletion of Gata2 impeded maintenance and self-renewal of leukemia stem cells (LSCs). Ablation of Gata2 enforced an LSC-specific program of enhanced apoptosis, exemplified by attenuation of anti-apoptotic factor BCL2, and re-instigation of myeloid differentiation- which is characteristically blocked in AML. [Stem Cell Reports] Full Article | Graphical Abstract

Antrodia cinnamomea Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

In vitro assays including cell viability, colony formation, Antrodia cinnamomea (AC) + 5-Fluorouracil (F-FU) drug combination index and tumor sphere generation were applied to determine the inhibitory effect of AC. Mouse xenograft models also incorporated to evaluate in vivo effect of AC. [Biomolecules] Full Article | Graphical Abstract

Pancreatic (Pro)enzymes Treatment Suppresses BXPC-3 Pancreatic Cancer Stem Cell Subpopulation and Impairs Tumor Engrafting

Scientists investigated in vitro and in vivo the effects of a pancreatic (pro)enzyme mixture composed of chymotrypsinogen and trypsinogen (PRP) on CSCs derived from a human pancreatic cell line, BxPC3. Exposure of pancreatic CSCs spheres to PRP resulted in a significant decrease of ALDEFLUOR and specific pancreatic CSC markers signal tested by flow cytometry. Further CSCs marker expression was also analyzed by western and immunofluorescence assays. [Sci Rep] Full Article

Subscribe to one of our other 19 science newsletters such as Neural Cell News & Hematopoiesis News.

Insights into New Mechanisms and Models of Cancer Stem Cell Multidrug Resistance

The authors provide an integrated picture of the multi-drug resistance mechanisms that operate in CSCs’ behavior and propose a novel model of tumor evolution during chemotherapy. Targeting the pathways mentioned might hold promise and reveal new strategies for future clinical therapeutic approaches. [Semin Cancer Biol] Abstract

Hyaluronan-CD44 Axis Orchestrates Cancer Stem Cell Functions

Investigators overview recent advances in the importance of hyaluronan-CD44 interactions in the acquisition and maintenance of a CSC phenotype. The hyaluronan-CD44 axis has a substantial impact on stemness properties of CSCs and drug resistance through induction of epithelial-to-mesenchymal transition program, oxidative stress resistance, secretion of extracellular vesicles/exosomes and epigenetic control. [Cell Signal] Abstract

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

Rafael Pharmaceuticals Announces Expansion into Austria, South Korea and Spain of Pivotal Phase III Trial (ARMADA 2000) of CPI-613^® (Devimistat) in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)

Rafael Pharmaceuticals, Inc. announced the expansion of its Phase III clinical trial of CPI-613^® in patients with relapsed or refractory acute myeloid leukemia (AML) into Austria, South Korea and Spain. The multicenter, open-label, randomized pivotal trial is evaluating the efficacy and safety of its lead compound devimistat in combination with high dose cytarabine and mitoxantrone in older patients with relapsed or refractory AML. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

Oncternal Therapeutics Announces Opening of Randomized Phase II Study of Cirmtuzumab in Combination with Ibrutinib

Oncternal Therapeutics, Inc. announced that it has opened for enrollment its randomized Phase II study of cirmtuzumab, a ROR1-targeted monoclonal antibody, combined with ibrutinib in patients with chronic lymphocytic leukemia. [Oncternal Therapeutics, Inc.] Press Release

Forty Seven, Inc. Announces $6 Million in Funding from the Leukemia & Lymphoma Society TAP to Accelerate the Development of 5F9 in Myelodysplastic Syndrome

Forty Seven, Inc. announced additional funding commitments from The Leukemia & Lymphoma Society, aimed at accelerating the development of 5F9 for the treatment of myelodysplastic syndromes. [Forty Seven, Inc.] Press Release

USDA Labs’ Move to Kansas City Might Be Illegal

The US Department of Agriculture should have obtained approval from Congress before deciding to relocate two research facilities from Washington, DC, to Kansas City, a report by the agency’s inspector general finds. The USDA may have violated federal law because the Omnibus Act requires congressional approval before creating, canceling, or moving a project, according to The Kansas City Star. [The Scientist] Editorial

Novartis CEO: ‘We Tried to Do the Right Things’ in FDA Data Scandal

Novartis CEO Vas Narasimhan on Wednesday defended his company’s decision to wait three months to tell authorities about falsified data submitted to the FDA, saying the company “tried to do the right things” in the process. He also said Novartiswas now “in the process of exiting” a small number of scientists at AveXis, Novartis’s gene therapy business, who were “involved in these data inaccuracies.” [STAT News] Editorial

With Its CRISPR Revolution, China Becomes a World Leader in Genome Editing

In 2012, the year researchers transformed a bacterial immune system into the fast and versatile tool for genome engineering, scientific publications mentioning CRISPR totaled 127. Since then there have been more than 14,000. Although the United States has had the most CRISPR publications—and continues to have the most cited papers—China is now a close second and is pouring money into CRISPR’s uses. [ScienceInsider] Editorial

First Human-Monkey Chimeras Developed in China

Juan Carlos Izpisúa Belmonte of the Salk Institute in San Diego is spearheading the project with scientists from his own lab and those from the Murcia Catholic University in Murcia, Spain. The team wants to develop chimeras—organisms composed of cells from two or more species—capable of growing human organs. [The Scientist] Editorial

NEW Indonesia International Institute for Life Sciences (i3L) Conference 2019
November 5-7, 2019
East Jakarta, Indonesia

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

NEW Postdoctral Fellow – Leukemic Stem Cell Biology (McGill University Health Centre)

Postdoctoral Researcher – Cancer Stem Cells in Glioblastoma (The Institut Curie Research Center)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Associate – Hematopoietic Stem Cells and Leukemia (The Jackson Laboratory)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Postdoctoral Research Position – B-Cell Acute Lymphoblastic Leukemia Research (University of California San Francisco)

Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

Postdoctoral Scientist – Cancer Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Tier I Canada Research Chair – Precision & Molecular Oncology (University of Calgary)

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.