Cancer Stem Cell News Volume 3.41 | Oct 22 2014

DNMT-Dependent Suppression of MicroRNA Regulates the Induction of GBM Tumor-Propagating Phenotype by Oct4 and Sox2
Researchers show that the reprogramming transcription factors Oct4 and Sox2 induce glioblastoma (GBM) cells to become stem-like and tumor-propagating via a mechanism involving direct DNA methyl transferase (DNMT) promoter transactivation, resulting in global DNA methylation- and DNMT-dependent downregulation of multiple microRNAs. [Oncogene] Abstract

A Phase I Dose Escalation and Expansion Study of the Anti-Cancer Stem Cell Agent Demcizumab (Anti-DLL4) in Patients with Previously Treated Solid Tumors
This Phase I trial evaluated the safety, pharmacokinetics, pharmacodynamics and of demcizumab, a humanized IgG2 monoclonal antibody targeting the Notch ligand DLL4 in adult patients with advanced malignancies. [Clin Cancer Res] Abstract | Full Article

Dual mTORC1/2 Blockade Inhibits Glioblastoma Brain Tumor Initiating Cells In Vitro and In Vivo and Synergizes with Temozolomide to Increase Orthotopic Xenograft Survival
Human brain tumor-initiating cell lines with different combinations of endogenous EGFR wild-type, EGFRvIII, and PTEN mutations were used to investigate response to the EGFR inhibitor gefitinib, mTORC1 inhibitor rapamycin, and dual mTORC1/2 inhibitor AZD8055 alone and in combination with temozolomide. [Clin Cancer Res] Abstract

SPARC Mediates Metastatic Cooperation between CSC and Non-CSC Prostate Cancer Cell Subpopulations
Cancer stem cell (CSC)-enriched subpopulation (M) and non-CSC subpopulation (S) secretomes were compared by stable isotope labeling by amino acids in cell culture. Comparative secretome analysis yielded 213 proteins differentially secreted between M and S cells. [Mol Cancer] Abstract | Full Article

CXCL12/CXCR4 Blockade by Oncolytic Virotherapy Inhibits Ovarian Cancer Growth by Decreasing Immunosuppression and Targeting Cancer-Initiating Cells
Scientists investigated the antitumor efficacy of a CXCR4 antagonist expressed by oncolytic vaccinia virus against an invasive variant of the murine epithelial ovarian cancer cell line ID8-T. This variant harbors a high frequency of cancer-initiating cells that form multilayered spheroid cells and express the hyaluronan receptor CD44, as well as stem cell factor receptor CD117. [J Immunol] Abstract

SOX2 Regulates Self-Renewal and Tumorigenicity of Stem-Like Cells of Head and Neck Squamous Cell Carcinoma
Researchers created cells ectopically expressing sex-determining region Y-box (SOX2) from previously established head and neck squamous cell carcinomas (HNSCC) cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, they knocked down SOX2 in primary spheres obtained from HNSCC tumor tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. [Br J Cancer] Abstract

Fibroblasts Induce Expression of FGF4 in Ovarian Cancer Stem-Like Cells/Cancer-Initiating Cells and Upregulate Their Tumor Initiation Capacity
Researchers investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian cancer stem-like cells (CSCs)/cancer-initiating cells (CICs). CSCs/CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high population by the ALDEFLUOR assay. [Lab Invest] Abstract

Impairment of Lysosomal Activity as a Therapeutic Modality Targeting Cancer Stem Cells of Embryonal Rhabdomyosarcoma Cell Line RD
Scientists isolated rhabdomyosarcoma cancer stem cells (CSC) with stem-like features. Rhabdomyosarcoma CSC showed higher invasive ability and a reduced cytotoxicity to doxorubicin in comparison to native cells, through a mechanism unrelated to the classical multidrug resistance process. [PLoS One] Full Article

Chaetocin Antileukemia Activity against Chronic Myelogenous Leukemia Cells Is Potentiated by Bone Marrow Stromal Factors and Overcomes Innate Imatinib Resistance
Bone marrow stromal cytokines and growth factors did not inhibit imatinib activities when TonB210 cells expressing Bcr-Abl were cotreated with chaetocin. Chaetocin showed similar activities against leukemic stem cells-enriched chronic myelogenous leukemia (CML) cell populations isolated from a murine transplant model of CML blast crisis that were phenotypically negative for lineage markers and positive for Sca-1 and c-Kit. [Oncogenesis] Full Article

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The Leukemia & Lymphoma Society Awards Six New Research Grants Focused on Innovative New Ideas
Six academic investigators will receive grants from The Leukemia & Lymphoma Society to support innovative ideas that that have the potential to take research in a new direction and fundamentally impact the future of blood cancer diagnosis and treatment. [The Leukemia & Lymphoma Society] Press Release

MabVax Therapeutics Nominates the Fully Human Antibody HuMab 5B1 as the Company’s Lead Clinical Development Candidate
MabVax Therapeutics Holdings, Inc. announced that it has formally nominated its HuMab 5B1 antibody as a clinical candidate for the diagnosis and treatment of pancreatic and colon cancer. [MabVax Therapeutics Holdings, Inc. (PR Newswire Association LLC)] Press Release

Boehringer Ingelheim Initiates Global Phase III Study Investigating Nintedanib in Patients with Colorectal Cancer
Boehringer Ingelheim announced enrollment of the first patient in a new global Phase III study in patients with metastatic colorectal cancer. [Boehringer Ingelheim GmbH] Press Release

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Postdoctoral Position – Stem Cells and Cancer (Brigham & Women’s Hospital – Harvard Medical School)

Postdoctoral Fellow – Gene Regulation in Breast Cancer/Stem Cell Biology (UC College of Medicine)

Postdoctoral Position – Leukemic Stem Cells (BC Cancer Agency)

Assistant or Associate Professor – Cancer Biology (University of Pennsylvania)

Senior Research Scientist – DNA Damage Response and Genome Instability (International Clinical Research Center)

Faculty Positions – Stem Cells and Regenerative Medicine (Baylor College of Medicine)

Research Assistant or Research Associate – Stem Cell & Cancer Biology (University of North Texas Health Science Center)

Postdoctoral Fellow – Stem Cells and Breast Cancer (Albert Einstein College of Medicine in New York)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

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