|Cancer Stem Cell News 6.40 October 11, 2017|
Using both genetic and pharmacologic inhibition, scientists found that proneural glioma stem cells (GSCs) were preferentially sensitive to EZH2 disruption, whereas mesenchymal GSCs were more sensitive to BMI1 inhibition. Given that glioblastomas contained both proneural and mesenchymal GSCs, combined EZH2 and BMI1 targeting proved more effective than either agent alone both in culture and in vivo. [Nat Med]
Researchers found that BE-43547A2 can significantly reduce the percentage of pancreatic cancer stem cells in Panc-1 cells, and dramatically ablate the tumorsphere forming capability of Panc-1 cells. The tumor-initiating assay in vivo confirmed that BE-43547A2 could abolish the tumorigenesis of Panc-1 cells. [Angew Chem Int Ed Engl]
An integrated genomic and functional analysis to elucidate DNA damage signaling factors promoting self-renewal of glioma stem cells (GSCs) identified proliferating cell nuclear antigen-associated factor (PAF) up-regulation in glioblastoma. [Proc Natl Acad Sci USA]
While β‐catenin has been demonstrated as an essential molecule and therapeutic target for various CSCs including those driven by MLL fusions, researchers show that transcriptional memory from cells of origin predicts acute myeloid leukemia patient survival and allows β‐catenin‐independent transformation in MLL‐CSCs derived from hematopoietic stem cell‐enriched Lin–Sca-1+c-kit+ population but not myeloid–granulocyte progenitors. [EMBO J]
Scientists showed that brachyury was a crucial regulator of stemness in chordoma and in more common aggressive cancers. Furthermore, this effect of brachyury was mediated by control of synthesis and stability of Yes-associated protein (YAP), a key regulator of tissue growth and homeostasis, providing an unexpected mechanism of control of YAP expression. [Cell Rep]
Investigators report the crucial role of methyltransferase-like 3 (METTL3)-mediated m6A modification in glioma stem-like cells (GSC) maintenance and dedifferentiation of glioma cells. METTL3 expression was elevated in GSC and attenuated during differentiation. [Oncogene]
Resistin was found to promote epithelial–mesenchymal transition and stemness in breast cancer cells—mechanisms critical to tumorigenesis and metastasis—through a toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells/signal transducer and activator of transcription 3 signaling pathway and negated by TLR4-specific antibody and antagonist. [Oncogene]
The authors identified the role of FAT1 in regulating epithelial-mesenchymal transition (EMT) and stemness characteristics in glioblastoma (GBM). The expression of FAT1, EMT (Snail/LOX/Vimentin/N-cad), stemness (SOX2/OCT4/Nestin/REST) and hypoxia markers (HIF-1α/VEGF/PGK1/CA9) was upregulated in ≥39% of GBM tumors with significant positive correlation of the expression of FAT1 with LOX/Vimentin/SOX2/HIF-1α/PGK1/VEGF/CA9. [Int J Cancer]
Researchers investigated the role of Wnt/β-catenin pathway in chronic tobacco smoke (TS) exposure induced urocystic epithelial–mesenchymal transition (EMT), stemness acquisition and the preventive effect of curcumin. Long time TS exposure induced EMT changes and the levels of CSCs’ markers were significant upregulated. [Cell Death Dis]
Investigators profiled extracellular vesicles harvested from therapeutic induced senescent (TIS) triple negative breast cancer (TNBC) cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy. [Oncogenesis]
Scientists discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging. [Nat Med]
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Medicenna Therapeutics Corp. announced that new clinical data demonstrated successful delivery in brain cancer patients and a reassuring safety profile for MDNA55, the company’s lead immunotherapeutic agent targeting the interleukin-4 receptor. [Press release from Medicenna Therapeutics Corp. discussing research presented at the 2017 Congress of Neurological Surgeons, Boston]
The FDA announced that it has awarded 15 new clinical trial research grants totaling more than $22 million over the next four years to boost the development of products for patients with rare diseases. [U.S. Food and Drug Administration]
Astellas Pharma Inc. announced that the FDA has granted Fast Track designation for the development of gilteritinib for adult patients with FLT3 mutation-positive relapsed or refractory acute myeloid leukemia. [Astellas Pharma Inc.]
Trovagene, Inc. announced that the FDA granted an orphan drug designation to PCM-075 for the treatment of patients with AML. PCM-075 is an oral, highly-selective adenosine triphosphate competitive inhibitor of the serine/threonine Polo-like Kinase 1 (PLK1) enzyme, which appears to be over expressed in several different hematologic malignancies and solid tumor cancers. [Trovagene, Inc.]
Millions of articles might soon disappear from ResearchGate, the world’s largest scholarly social network. Five publishers said they had formed a coalition that would start ordering ResearchGate to remove research articles from its site because they breach publishers’ copyright. [Nature News]
When the Navajo Nation opens its first oncology center next year in Tuba City, Arizona, clinicians there may be able to offer a service that has been banned on tribal lands for 15 years: analyzing the DNA of Navajo tribe members to guide treatments and study the genetic roots of disease. [Nature News]
The only physicist in Congress has introduced a bill that could rekindle a debate over how to deal with geographic disparities in the allocation of federal research funding [ScienceInsider]
Anxiety is growing in Brazil over the country’s collapsing research budgets. President Michel Temer had slashed funding for science by 44% and has proposed additional decreases for 2018 — even as some science institutes run out of money for basic needs, such as paying electricity bills. The 2017 science budget, at 3.2 billion reais (US$1 billion), is the lowest the country has seen in at least 12 years. [Nature News]
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