Cancer Stem Cell News Volume 8.40 | Oct 16 2019

TOP STORY

Aggregable Nanoparticles-Enabled Chemotherapy and Autophagy Inhibition Combined with Anti-PD-L1 Antibody for Improved Glioma Treatment

The legumain-responsive gold nanoparticles could be passively delivered to glioma site and form in situ aggregated in response to legumain, leading to enhanced accumulation of doxorubicin (DOX) and hydroxychloroquine (HCQ) at glioma site. HCQ could inhibit the DOX-induced cytoprotective autophagy and thus re-sensitize glioma cells to DOX. [Nano Lett] Abstract

(Ranked by impact factor of the journal)

A Mutant KRAS-Induced Factor REG4 Promotes Cancer Stem Cell Properties via Wnt/β-Catenin Signaling

The authors identified the factors mediating the promotion of CSC properties induced by KRAS mutation through microarray analyses of genes specifically induced in colorectal cancer spheroids harboring both KRAS and APC mutations. Among them, REG4 was identified as a key factor since CRISPR/Cas9‐mediated knockout of REG4 most significantly affected the stem cell characteristics in which CSC markers were effectively suppressed. [Int J Cancer] Abstract

Targeting Chemoresistant Colorectal Cancer via Systemic Administration of a BMP7 Variant

35 primary human cultures enriched in colorectal (CR) cancer-CSC, including four from chemoresistant metastatic lesions, were used for in vitro studies and to generate CR-CSC-based mouse avatars to evaluate tumor growth and progression upon treatment with variant of BMP7 alone or in combination with standard therapy or PI3K inhibitors. [Oncogene] Abstract

Insights into Fibroblast Plasticity: CCN2 Is Required for Activation of Cancer-Associated Fibroblasts in a Murine Model of Melanoma

Fibroblasts were labeled postnatally with green fluorescent protein using mice expressing a tamoxifen-dependent Cre recombinase under the control of a fibroblast-specific promoter/enhancer. Conversely, fibroblast activation was impaired in mice with a fibroblast-specific deletion of Ccn2, associated with reduced expression of alpha-smooth muscle actin and Sox2. [Am J Pathol] Abstract

CD44/CD133-Positive Colorectal Cancer Stem Cells Are Sensitive to Trifluridine Exposure

CD44⁺CD133⁺ high-expressing and other populations of human DLD-1 colon cancer cells were separately isolated through fluorescence-activated cell sorting. The sphere-forming activity of each population and the anti-sphere-forming effects of trifluridine and fluorouracil on CD44⁺CD133⁺ cells were then measured. [Sci Rep] Full Article

A Novel 3D Nanofibre Scaffold Conserves the Plasticity of Glioblastoma Stem Cell Invasion by Regulating Galectin-3 and Integrin-β1 Expression

Functionalization with laminin increased the spatial anisotropy of migration and modulates its mode from collective to single cell migration. Mechanistically, equally similar to what has been observed for mesenchymal migration of glioblastoma multiforme in vivo, was the upregulation of galectin-3 and integrin-β1 in Gli4 cells migrating on a nanofiber scaffold. [Sci Rep] Full Article

Gomisin M2 from Baizuan Suppresses Breast Cancer Stem Cell Proliferation in a Zebrafish Xenograft Model

Researchers enriched breast cancer stem cells with CD44⁺/CD24^– from MDA-MB-231 and HCC1806 cells through magnetic-activated cell sorting and cultured these in serum-free medium. The ability of gomisin M2 to kill breast cancer stem cells was evaluated in vitro and in vivo. [Aging (Albany NY)] Abstract

SNP rs710886 A>G in Long Noncoding RNA PCAT1 Is Associated with the Risk of Endometriosis by Modulating Expression of Multiple Stemness-Related Genes via MicroRNA-145 Signaling Pathway

Real-time PCR was performed to observe the expression of miR-145 in transfected cells, while Matrigel invasion chamber assays and MTT assay were conducted to examine the invasiveness/proliferation among different cell groups. Moreover, bioinformatics tools, luciferase assays, real-time PCR, and Western blot analysis were used to measure the expression of these target genes in the presence of miR-145. [J Cell Biochem] Abstract

Matrine Suppression of Self-Renewal Was Dependent on Regulation of LIN28A/Let-7 Pathway in Breast Cancer Stem Cells

Investigators showed that the compounds of kushen injection derived matrine could suppress the breast CSCs differentiation and self-renewal through downregulating the expression of Lin28A, resulting in the inactivation of Wnt pathway through a Let-7b-dependent way. [J Cell Biochem] Abstract

The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell

Cancer stem cells were obtained from the PANC-1 cells by the MiniMACS system. CD133⁺ and CD133⁻ PANC-1 cells were treated with different concentrations of resveratrol and quercetin. Cell growth and cytotoxicity were evaluated by MTT assay. [Nutr Cancer] Abstract

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The Great Escape: Tumor Cell Plasticity in Resistance to Targeted Therapy

In the past few years, cell plasticity has emerged as a mode of targeted therapy evasion in various cancers, ranging from prostate and lung adenocarcinoma to melanoma and basal cell carcinoma. Science’s understanding of the mechanisms that control this phenotypic switch has also expanded, revealing the crucial role of reprogramming factors and chromatin remodeling. [Nat Rev Drug Discov] Abstract

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Nektar Therapeutics Announces Initiation of First-in-Human Phase I Clinical Study of NKTR-255, an IL-15 Agonist, in Adults with Relapsed or Refractory Non-hodgkin Lymphoma or Multiple Myeloma

Nektar Therapeutics announced the initiation of a first-in-human, Phase I clinical study evaluating NKTR-255, an interleukin-15 (IL-15) receptor agonist, as monotherapy for patients with relapsed or refractory non-Hodgkin lymphoma or multiple myeloma. The study will also combine NKTR-255 with multiple targeted antibodies, that function through an antibody-dependent cell-mediated cytotoxicity mechanism, to evaluate the safety and efficacy in adults with relapsed or refractory MM. [Nektar Therapeutics] Press Release

Mustang Bio Announces City of Hope Receives $4.1 Million in Grant Awards for Recently Opened First-of-Its-Kind Clinical Trial for Patients with Recurrent Malignant Glioma

Mustang Bio, Inc. congratulated City of Hope, a world-renowned independent cancer research and treatment center, on its receipt of $4.1 million in grant awards for a clinical trial of MB-101 in combination with nivolumab and ipilimumab in patients with recurrent malignant glioma. [Mustang Bio, Inc.] Press Release

German Lab Faces Criminal Charges after Undercover Investigation

Charges have been lodged with a state prosecutor after the release of undercover video brought attention to the conditions under which animals are kept at the Laboratory of Pharmacology and Toxicology near Hamburg, The Guardian reported on October 15. [The Scientist] Editorial

Sanger Institute Accused of Misusing African DNA Samples

The Wellcome Sanger Institute in the UK had planned to commercialize a genetics array based on African DNA samples, whistleblowers allege, which would have violated the terms of agreements for using the materials, The Times reports. Two universities in Africa have condemned any commercial endeavors using the samples, some of which came from indigenous tribes. [The Scientist] Editorial

An ‘Unprecedented’ Analysis Underlines Profound Failure to Study African Genomes

In the case of modern studies of DNA, researchers called to task for studying mainly European populations often defend themselves by pointing out that they included some Yoruba (or Khoisan or Bantu or other African) DNA in their analysis, too. Research presented at the annual meeting of the American Society of Human Genetics on Tuesday and Wednesday shows how “woefully inadequate” such tokenism is, said Dr. Neil Hanchard of Baylor College of Medicine, who led one of the studies. [STAT News] Editorial

NEW Translational Cancer Research for Basic Scientists Workshop
November 17-22, 2019
Boston, Massachusetts, United States

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NEW Postdoctoral Position – Cancer Biology (Weill Cornell Medicine)

NEW Assistant, Associate, or Professor – Hematology (Stanford University)

Chief Editor – Nature Ageing (Nature Research)

Assistant, Associate or Professor – Oncological Sciences (University of Utah)

Postdoctoral Researcher – Cancer (Max Planck Institute for Molecular Genetics)

Associate Professor – T-Cell Therapy (Dana-Farber Cancer Institute)

Postdoctoral Researcher – Stem Cells and Cancer (IRB Barcelona)

Postdoctoral Fellow – Cancer Progression (NIH/NCI – Center for Cancer Research)

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

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

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