Cancer Stem Cell News Volume 5.44 | Nov 9 2016

TOP STORY

p53^-/- Synergizes with Enhanced Nras^G12D Signaling to Transform Megakaryocyte-Erythroid Progenitors in Acute Myeloid Leukemia

Investigators found that p53^-/- cooperates with Nras^G12D/+ to promote increased quiescence in megakaryocyte-erythroid progenitors (MEPs). Nras^G12D/+; p53^-/- MEPs are transformed to self-renewing acute myeloid leukemia (AML) initiating cells and are capable of inducing AML in serially transplanted recipients. [Blood] Abstract

(Ranked by impact factor of the journal)

Cytokine Induced Killer Cells Kill Chemo-Surviving Melanoma Cancer Stem Cells

The MHC-unrestricted activity of cytokine-induced killer cells against chemo-surviving melanoma cancer stem cells (mCSCs) was explored, as CSCs are considered responsible for chemo-resistance and relapses. [Clin Cancer Res] Abstract

Protease-Activated Receptor-1 Inhibits Proliferation but Enhances Leukemia Stem Cell Activity in Acute Myeloid Leukemia

Scientists found upregulation of several hemostasis-related genes, including the thrombin-activatable receptor PAR-1 (protease-activated receptor-1), in Runx1/Cbfb-deleted MLL-AF9 cells. Similar to the effect of Runx1/Cbfb deletion, PAR-1 overexpression induced CDKN1A/p21 expression and attenuated proliferation in MLL-AF9 cells. [Oncogene] Abstract

Induction of Endoplasmic Reticulum Stress by Deletion of Grp78 Depletes Apc Mutant Intestinal Epithelial Stem Cells

The most frequent initiating mutation occurs in Apc, which results in hyperactivated Wnt signaling. This causes hyperproliferation and reduced sensitivity to chemotherapy, but whether these mutated stem cells are sensitive to endoplasmic reticulum (ER) stress induced differentiation remains unknown. The authors examined this by generating mice in which both Apc and ER stress repressor chaperone Grp78 can be conditionally deleted from the intestinal epithelium. [Oncogene] Full Article

An Active IGF-1R-AKT Signaling Imparts Functional Heterogeneity in Ovarian CSC Population

Researchers investigated the effect of this oscillatory IGF-1R-AKT signaling upon cancer stem cells (CSC) functionality during generation of chemoresistance. While gradual increase in CSC properties from early to late resistant stages was observed in three different cellular models created in two ovarian cancer cell lines, the stemness gene expressions reached a plateau at early resistant stages. [Sci Rep] Full Article

Sulforaphane Improves Chemotherapy Efficacy by Targeting Cancer Stem Cell-Like Properties via the miR-124/IL-6R/STAT3 Axis

The authors aimed to identify whether sulforaphane (SFN) could enhance the anti-cancer effects of low-dose cisplatin (CDDP) and to determine the underlying mechanisms. Co-exposure of SFN and CDDP significantly inhibited the viabilities of gastric cancer cells. [Sci Rep] Full Article

Identification of MicroRNA Profile Specific to Cancer Stem-Like Cells Directly Isolated from Human Larynx Cancer Specimens

Emerging evidences proposed that microRNAs are associated with regulation of distinct physio-pathological processes including development of normal stem cells and carcinogenesis. Researchers aimed to investigate microRNA profile of cancer stem-like cells isolated form freshly resected larynx cancer tissue samples. [BMC Cancer] Full Article

Requirement of ABC Transporter Inhibition and Hoechst 33342 Dye Deprivation for the Assessment of Side Population-Defined C6 Glioma Stem Cell Metabolism Using Fluorescent Probes

The metabolic status of C6 side population and main population cells are evaluated by CellROX, MitoTracker Green and JC-1 for cellular oxidative stress, mitochondrial amount, and mitochondrial membrane potential, respectively. [BMC Cancer] Full Article

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

Investigators verified the presence of stem cell-like cancer cells in renal cell cancer cell lines. They aimed to characterize phenotype and cell biology of CD105⁺ cells, defined previously as renal cell carcinoma tumor-initiating cells. [PLoS One] Full Article

Serine Synthesis Helps Hypoxic Cancer Stem Cells Regulate Redox

Recent studies have revealed a critical role for phosphoglycerate dehydrogenase (PHGDH) and downstream enzymes of the serine synthesis pathway and one carbon metabolism in NADPH production and the maintenance of redox homeostasis, which are required for enrichment of breast cancer stem cells in response to hypoxia or chemotherapy. [Cancer Res] Abstract

ROS Homeostasis and Metabolism: A Critical Liaison for Cancer Therapy

The authors explore the molecular mechanisms responsible for the metabolic reprogramming of tumor microenvironments, the functional modulation of which may disrupt the effects of or may be disrupted by redox homeostasis modulating cancer therapy. [Mol Med] Full Article

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.

Ascend Biopharmaceuticals Announces Encouraging Phase I/IIa Interim Results of ASN-002 Treatment of Nodular Basal Cell Carcinoma (nBCC)

Ascend Biopharmaceuticals Ltd. announced interim results from the first nine patients of its Phase I/IIa clinical trial evaluating the safety and clinical activity of its lead candidate, ASN-002. The study is evaluating three escalating doses in nBCC patients, a common type of skin cancer. [Ascend Biopharmaceuticals Ltd.] Press Release

CryoVax^®: Next Generation Immunotherapy for Metastatic Colorectal Cancer Begins USA Phase IIb Clinical Trial

Immunovative Therapies, Ltd. announced the start of a Phase IIb study of CryoVax^®, a next generation immunotherapy cancer vaccine product, for patients with chemotherapy-refractory metastatic colorectal cancer. [Immunovative Therapies, Ltd.] Press Release

Regorafenib from Bayer Submitted to Health Authorities Seeking Approval in Second-Line Treatment of Liver Cancer

Bayer announced the submission of applications to extend the marketing authorization for its oral multi-kinase inhibitor regorafenib in the U.S., Japan and Europe, for the second line treatment of patients with unresectable hepatocellular carcinoma. Regorafenib is already approved under the brand name Stivarga^® in many countries to treat metastatic colorectal cancer and metastatic gastrointestinal stromal tumors. [Bayer] Press Release

Bristol-Myers Squibb and Infinity Pharmaceuticals Announce Clinical Collaboration to Evaluate Opdivo (Nivolumab) in Combination with IPI-549 in Advanced Solid Tumors

Bristol-Myers Squibb Company and Infinity Pharmaceuticals, Inc. announced a clinical trial collaboration to evaluate Bristol-Myers Squibb’s Opdivo in combination with Infinity’s IPI-549 in patients with advanced solid tumors. The dose-escalation portion exploring IPI-549 as a monotherapy in Infinity’s Phase I study is continuing, and the first dose-escalation cohort studying IPI-549 in combination with Opdivo, a PD-1 immune checkpoint inhibitor, is expected to begin this fall. [Infinity Pharmaceuticals, Inc.] Press Release

Donald Trump’s US Election Win Stuns Scientists

Republican businessman and reality-television star Donald Trump will be the United States’ next president. Although science played only a bit part in this year’s dramatic, hard-fought campaign, many researchers expressed fear and disbelief as Trump defeated former secretary of state Hillary Clinton. [Nature News] Press Release

Big Brain Projects Urged to Aid Public Health

Major brain-mapping projects have multiplied in recent years, as neuroscientists develop new technologies to decipher how the brain works. These initiatives focus on understanding the brain, but the World Health Organization wants to ensure that they work to translate their early discoveries and technological advances into tests and treatments for brain disorders. [Nature News] Editorial

Hard Work, Little Reward: Nature Readers Reveal Working Hours and Research Challenges

A poll answered by thousands of Nature readers suggests that nearly two-thirds have considered quitting research, and that almost 40% work more than 60 hours in a week. The fight for funding is the greatest challenge facing early-career scientists, readers said. [Nature] Editorial

Twitterstorm Shows Why Scientific Evidence Matters

Grammar and Twitter rarely sit happily, so it would be churlish to point out that when the Welsh MP Glyn Davies tweeted at the weekend: “Nothing more irritating than academics ­rubbishing the efforts of those operating at the sharp end, without facing up to the hard decisions”, he was inadvertently complaining that people at the sharp end (himself included presumably) do not confront hard decisions. [Nature] Editorial

NEW Gordon Research Conference: Stem Cells & Cancer
February 12-17, 2017
Barga, Italy

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

NEW Tier 2 Canada Research Chair – Pharmacology (University of Ottawa)

NEW Assistant Professor – Cancer Biology, Cancer Genomics and Precision Medicine (Wake Forest Baptist Comprehensive Cancer Center)

Postdoctoral Position – Physical Oncology (Houston Methodist Research Institute)

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

Research Scientist – Epigenetic Mechanisms Involving Histone Deacetylases, Methyltransferases and Demethylases (The University of Texas MD Anderson Cancer Center)

Lecturer – Cancer Biology (NUI Galway)

Associate Professor – Experimental Radiation Oncology (The University of Texas MD Anderson Cancer Center)

Assistant Professor (Tenure Track) – Mechanisms Related to Aging, Cancer and Stem Cell Biology)

Scientific Developer – Computational Systems Biology of Cancer (Institut Curie)

Post-Doctoral Researcher – Influential Nodes and Links in Multi-Level Cancer-Related Networks (Luxembourg Institute of Health)

Two Assistant Professor Positions – Molecular Medicine (University of Georgia)

Postdoctoral Associate – Glioma Stem Cell Biology and Cerebral Organoid (Weill Cornell Medicine)

Postdoctoral Positions – Stem Cell Research, Hematopoiesis, Cancer, Genome Editing (Icahn School of Medicine at Mount Sinai)

Postdoctoral Position – Tumor Immunology (Memorial Sloan Kettering Cancer Center)

Postdoctoral Position – Metastatic Breast Cancer (Purdue Center for Cancer Research)

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