|Cancer Stem Cell News 8.30 August 7, 2019|
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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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.)]
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.]
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.]
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]
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]
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]
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]
NEW Indonesia International Institute for Life Sciences (i3L) Conference 2019
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