Cancer Stem Cell News Volume 8.27 | Jul 17 2019

TOP STORY

GPD1 Specifically Marks Dormant Glioma Stem Cells with a Distinct Metabolic Profile

Through a ribosome-profiling analysis of mouse neural stem cells (NSCs) and brain tumor stem cells (BTSCs), researchers found glycerol-3-phosphate dehydrogenase 1 expression specifically in BTSCs and not in NSCs. GPD1 expression was present in the dormant BTSC population, which was enriched at tumor borders and drove tumor relapse after chemotherapy. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

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Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation

In both human chronic myeloid leukemia K562 cells and murine Ba/F3 cells expressing BCR-ABL1, lead compound GMB-475 induced rapid proteasomal degradation and inhibition of downstream biomarkers, such as STAT5, and showed increased sensitivity compared to diastereomeric controls lacking degradation activity. [Cancer Res] Abstract

Downregulation of FOXO3a by DNMT1 Promotes Breast Cancer Stem Cell Properties and Tumorigenesis

Researchers report that DNMT1-mediated FOXO3a promoter hypermethylation led to downregulation of FOXO3a expression in breast cancer. FOXO3a was functionally related to the inhibition of FOXM1/SOX2 signaling and to the consequent suppression of breast cancer stem cells’ properties and tumorigenicity. [Cell Death Differ] Full Article

Brexpiprazole, a Serotonin-Dopamine Activity Modulator, Can Sensitize Glioma Stem Cells to Osimertinib, a Third-Generation EGFR-TKI, via Survivin Reduction

Brexpiprazole treatment sensitized glioma stem cells to osimertinib and reduced the expression of survivin, an antiapoptotic factor, and the pharmacological and genetic inhibition of survivin mimicked the effects of brexpiprazole. Moreover, co-treatment of brexpiprazole and osimertinib suppressed tumor growth more efficiently than either drug alone without notable toxicity in vivo. [Cancers] Full Article | Graphical Abstract

Identification of GSK3β Inhibitor Kenpaullone as a Temozolomide Enhancer against Glioblastoma

Investigators screened drug libraries composed of 1,301 existing drugs using cell viability assays to evaluate effects on glioma stem cells (GSCs), which led to selection of kenpaullone, a kinase inhibitor, as a emozolomide enhancer targeting GSCs. Kenpaullone efficiently suppressed activity of glycogen synthase kinase 3β. [Sci Rep] Full Article

A Role for ABCB1 in Prognosis, Invasion and Drug Resistance in Ependymoma

ABCB1 gene expression was observed in four out of five pediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly potentiated the response to three chemotherapeutic drugs. [Sci Rep] Full Article | Press Release

Inhibition of M2-Like Macrophages by All-Trans Retinoic Acid Prevents Cancer Initiation and Stemness in Osteosarcoma Cells

Scientists report that M2 macrophages were enriched in osteosarcoma tissues from patients, and M2-polarized tumor-associated macrophages (TAMs) enhanced cancer initiation and stemness of osteosarcoma cells, thereby establishing M2-polarized TAMs as a therapeutic target for blocking osteosarcoma formation. [Acta Pharmacol Sin] Abstract

LW-213, a Newly Synthesized Flavonoid, Induces G2/M Phase Arrest and Apoptosis in Chronic Myeloid Leukemia

Researchers investigated whether LW-213 exerted anti-chronic myeloid leukemia (CML) effects and the underlying mechanisms. They showed that LW-213 inhibited the growth of human CML cell lines K562 and imatinid-resistant K562 in dose- and time-dependent manners with IC50 values at the low μmol/L levels. [Acta Pharmacol Sin] Abstract

Notch Pathway in Ependymoma RELA-Fused Subgroup: Upregulation and Association with Cancer Stem Cells Markers Expression

The authors evaluated the effects of two Notch inhibitors on cell proliferation, apoptosis, colony formation, and CSC markers gene expression on ependymoma cell line of the RELA-fused subgroup. In addition, in silico signatures of the Notch genes and CSC markers were analyzed on a large clinical dataset from GSE64415 study. [Cancer Gene Ther] Abstract

Surface Expression Marker Profile in Colon Cancer Cell Lines and Sphere-Derived Cells Suggests Complexity in CD26⁺cancer Stem Cells Subsets

Investigators showed the presence of a subset of E-cadherin⁺ expressing CD26⁺ (or CD26^high) together with the well-known CSC markers LGR5 and EpCAM^high, sometimes in the absence of CD44 or CD133. The CD26⁺/E-cadherin^low or negative and CD26⁺/EpCAM⁻/CD133⁻ subsets were also present. [Biol Open] Abstract

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The Connection between the Th17 Cell Related Cytokines and Cancer Stem Cells in Cancer: Novel Therapeutic Targets

The authors summarize current findings of the characteristics and functions of the T helper 17 (Th17) cell and its signature cytokines in different cancers and their interconnections with cancer stem cells and with their markers. They also discuss the functional properties of CSCs and how the CSC markers can be distinguished from normal stem cells markers. [Immunol Lett] Abstract

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Forty Seven, Inc. and Ono Pharmaceutical Co., Ltd. Sign Regional License Agreement to Develop, Manufacture and Commercialize 5F9 in Japan, South Korea, Taiwan and Select Countries in Southeast Asia

Forty Seven, Inc. announced an exclusive license agreement for the development, manufacture and commercialization of 5F9, Forty Seven’s monoclonal antibody against CD47. The agreement includes all therapeutic uses of 5F9 as a monotherapy or combination agent in Japan, South Korea, Taiwan and the ASEAN countries. [Forty Seven, Inc.] Press Release

Ivy Brain Tumor Center and Karyopharm Therapeutics Collaborate to Develop Tissue-Based Clinical Trial for Brain Cancer

The Ivy Brain Tumor Center at the Barrow Neurological Institute has announced a partnership with Karyopharm Therapeutics to accelerate the treatment of brain cancer. The Ivy Brain Tumor Center will employ Karyopharm’s first-in-class oral selective inhibitor of nuclear export compound, selinexor, in combination with other new-in-class drugs, as a dual-drug experimental therapy for adult glioblastoma. [The Ivy Brain Tumor Center] Press Release

Genmab and BliNK Biomedical Enter into Commercial License Agreement

Genmab A/S announced that it has entered into an agreement with BliNK Biomedical for an exclusive commercial license to certain antibodies targeting CD47, for potential development and commercialization into novel bispecific therapeutics created via Genmab’s proprietary DuoBody Platform technology. [Genmab A/S] Press Release

AIVITA Biomedical Announces New Clinical Data in Ongoing Phase II Brain Cancer Trial

AIVITA Biomedical, Inc. announced new clinical data from its ongoing glioblastoma Phase II clinical trial investigating AIVITA’s platform immunotherapy targeting cancer stem cells. Blood plasma biomarker analyses have identified predictive markers of efficacy in seven of eight treated subjects, a sample that represents 15% of the total clinical trial size. [AIVITA Biomedical, Inc.] Press Release

Avalon GloboCare Provides Updates on Its Lead Clinical Programs in CAR-T Therapy and Exosome-Based Regenerative Therapeutics

Avalon GloboCare Corp. announced an update on its four clinical programs in cellular therapy, including AVA-001 and AVA-101, that leverage individualized chimeric antigen receptor T-cell therapy for immuno-oncology, as well as AVA-201 and AVA-202 exploring novel development with stem cell derived exosomes. [Avalon GloboCare Corp.] Press Release

Propanc Biopharma Provides Update on Preparation of PRP for Clinical Trial Application Submission and Recently Completed Reverse Stock Split

Propanc Biopharma, Inc. announced an update on their preparation of PRP, its anti-cancer lead product candidate, for clinical trial application submission and its recently completed reverse stock split. [Propanc Biopharma, Inc.] Press Release

Aptose Doses First CLL Patient in Phase I Study of CG-806 and Doses Third Cohort in Phase I Study of APTO-253

Aptose Biosciences Inc. announced that dosing of CG-806, the company’s highly potent, first-in-class pan-FLT3/pan-BTK inhibitor, has commenced its Phase Ia/b dose-escalation study in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma or non-Hodgkin lymphomas who have failed or are intolerant to standard therapies. [Aptose Biosciences Inc.] Press Release

The Plan to Mine the World’s Research Papers

Carl Malamud is on a crusade to liberate information locked up behind paywalls — and his campaigns have scored many victories. Now, the 60-year-old American technologist is turning his sights on a new objective: freeing paywalled scientific literature. And he thinks he has a legal way to do it. [Nature News] Editorial

Virologists Escorted Out of Lab in Canada

Canada’s national police force is investigating “possible policy breaches” after researchers were escorted from a lab at Canada’s National Microbiology Laboratory in Winnipeg, CBC News reported. Prominent virologist Xiangguo Qiu, her colleague and husband Keding Cheng, and an unknown number of her students from China were removed from the lab. [The Scientist] Editorial

US Senators Call for International Guidelines for Germline Editing

Senators Dianne Feinstein, Marco Rubio, and Jack Reed introduced a resolution calling for global collaboration in developing guidelines for the use of gene editing technologies in the context of reproduction. [The Scientist] Editorial

A Brief Guide to the Current CRISPR Landscape

Hundreds of CRISPR patents have been granted around the world, and the number of applications continues to grow at a rapid pace. [The Scientist] Editorial

NEW Wnt Signaling Networks in Development, Disease and Regeneration
August 11-16, 2019
West Dover, Vermont, United States

NEW Cancer Stem Cells: Advances in Biology and Clinical Translation
October 13-17, 2019
Hong Kong, China

NEW San Antonio Breast Cancer Symposium
December 10-14, 2019
San Antonio, Texas, United States

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

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

NEW Professor – Cancer and Stem Cell Immunology (University of Sherbrooke)

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)

Postdoctoral Fellow – Jak-Stat Signaling in Prostate & Pancreatic Cancer (Medical College of Wisconsin)

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

Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University)

Faculty Positions – Cancer Research (The University of Texas MD Anderson Cancer Center)

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