Cancer Stem Cell News Volume 8.38 | Oct 2 2019

TOP STORY

The Acetyltransferase GCN5 Maintains ATRA-Resistance in Non-APL AML

Non-acute promyelocytic leukemia (APL) acute myeloid luekemias (AMLs) were resistant to all-trans retinoic acid (ATRA). Researchers demonstrated that the acetyltransferase GCN5 contributed to ATRA resistance in non-APL AML via aberrant acetylation of histone 3 lysine 9 residues maintaining the expression of stemness and leukemia associated genes. [Leukemia] Abstract

(Ranked by impact factor of the journal)

Dedifferentiation Process Driven by Radiotherapy-Induced HMGB1/TLR2/YAP/HIF-1α Signaling Enhances Pancreatic Cancer Stemness

The authors confirmed that X-ray irradiation induced differentiation of CD133^– pancreatic cancer cells, either sorted from patient samples or established cell lines, into cancer stem-like cells. Using an in vitro co-culture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133^– pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. [Cell Death Dis] Full Article

A Novel Multi-Target Small Molecule, LCC-09, Inhibits Stemness and Therapy-Resistant Phenotypes of Glioblastoma Cells by Increasing miR-34a and Deregulating the DRD4/Akt/mTOR Signaling Axis

Investigators predicted that a novel 5-(2′,4′-difluorophenyl)-salicylanilide derivative could target dopamine receptors and oncogenic markers implicated in glioblastomas (GBMs). Bioinformatics data indicated that dopamine receptor 2, DRD4, CD133 and Nestin were elevated in GBM clinical samples and correlated to temozolomide resistance and increased aldehyde dehydrogenase activity as well as enhanced neurosphere formation efficiency in U87MG and D54MG GBM cell lines. [Cancers] Full Article

c-Myc Acts as a Competing Endogenous RNA to Sponge miR-34a, in the Upregulation of CD44, in Urothelial Carcinoma

Bioinformatics and experimental analysis confirmed that miR-34a targeted CD44 (a CSC surface marker) and c-Myc in urothelial carcinoma (UC). Scientists found that, surprisingly, most UC cell lines and patient samples did express miR-34a, although epigenetic silencing by promoter hypermethylation of miR-34a expression was observed only in UMUC3 cells, and a subset of patient samples. [Cancers] Full Article

The Notch Pathway Promotes Osteosarcoma Progression through Activation of Ephrin Reverse Signaling

Based on in vitro analysis, Notch signaling promoted osteosarcoma proliferation, enhanced chemoresistance, facilitated both migration and invasion, and up-regulated stem-cell like characteristics. Xenograft models demonstrated that Notch signaling promoted primary tumor growth and pulmonary metastasis, and Notch inhibition was effective in reducing tumor size and preventing metastasis. [Mol Cancer Res] Abstract

Prognostic Impact of Glioblastoma Stem Cell Markers OLIG2 and CCND2

Immunohistochemical expression analysis of oligodendrocyte lineage transcription factor 2 (Olig2) and cyclin D2 (Ccnd2) was carried out on a cohort of human paired glioblastoma samples comparing initial resections with local recurrent tumors after radiation therapy alone or radio-chemotherapy with temozolomide. [Cancer Med] Full Article

Metastatic Renal Cell Carcinoma Cells Growing in 3D on Poly-D-Lysine or Laminin Present a Stem-Like Phenotype and Drug Resistance

In optimal 3D culture conditions, ACHN cells formed small spheroids with remaining adherent cells of an epithelial phenotype, while Caki-1 cells formed large dark spheroids with significantly reduced cell viability in the center. In the 3D structures, expression levels of genes encoding stem transcription factors and renal cell carcinoma stem cell markers were deregulated in comparison to these expression levels in traditional 2D culture. [Oncol Rep] Abstract | Download Full Article

Extract from Aloysia polystachya Induces the Cell Death of Colorectal Cancer Stem Cells

Investigators determined the flavonoid composition and biological action of Aloysia polystachya extracts in colorectal cancer. The chemical characterization of extracts was performed by HPLC. Assays of cytotoxicity, apoptosis, migration and invasion, metalloproteases activity, clonogenic growth, tumorspheres formation, Hoechts efflux, pluripotency marker expression and sensitization to chemotherapeutic drugs were performed in vitro in human HCT116 and murine CT26 colorectal cancer cells. [Nutr Cancer] Abstract

Similarities between Stem Cell Niches in Glioblastoma and Bone Marrow: Rays of Hope for Novel Treatment Strategies

Recently, researchers showed similarities between glioblastoma stem cell (GSC) niches and hematopoietic stem cell (HSC) niches in bone marrow. Here, they elaborated further on these similarities by immunohistochemical analyses of 17 biomarkers in paraffin sections of human glioblastoma and human bone marrow. They found all 17 biomarkers to be expressed both in hypoxic peri-arteriolar HSC niches in bone marrow and hypoxic peri-arteriolar GSC niches in glioblastoma. [J Histochem Cytochem] Abstract

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Cancer Stem Cells and Epithelial-to-Mesenchymal Transition in Cancer Metastasis

Cellular plasticity, including the epithelial-to-mesenchymal transition, enables the generation of CSCs at different steps of the metastatic process including metastatic colonization. The authors update the concept of CSCs and provide evidence of the existence of metastatic stem cells. [Cold Spring Harb Perspect Med] Abstract

LIN28: A Cancer Stem Cell Promoter for Immunotherapy in Head and Neck Squamous Cell Carcinoma

Multiple studies demonstrate that Lin28 critically contributes to anti-tumor immunity and production of cancer stem cells in head and neck squamous cell carcinoma (HNSCC). Thus, Lin28 has potential application in HNSCC treatment. [Oral Oncol] Abstract

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Tmunity Announces Exclusive License and Research Collaboration with Children’s Hospital of Philadelphia to Advance GPC2 CAR-T Cell Therapy for Neuroblastoma

Tmunity Therapeutics, Inc. announced it has entered into an exclusive license and research collaboration agreement with Children’s Hospital of Philadelphia to advance a glypican 2 (GPC2) chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of neuroblastoma, a rare cancer that affects the developing nervous system. [Tmunity Therapeutics, Inc.] Press Release

Ziopharm Oncology Announces FDA Clearance of IND for Rapid Personalized Manufacture of CD19-Specific CAR-T

Ziopharm Oncology, Inc. announced that the FDA has cleared an investigational new drug application (IND) for a Phase I clinical trial to evaluate CD19-specific CAR-T, produced using a process termed rapid personalized manufacture, as an investigational treatment for patients with relapsed CD19⁺ leukemias and lymphomas. [Ziopharm Oncology, Inc.] Press Release

Genmab Announces US FDA Approval of DARZALEX^® (Daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone for Frontline Multiple Myeloma

Genmab A/S announced that the FDA has approved the use of daratumumab in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant. [Genmab A/S] Press Release

‘There’s No Taboo, No Bad Ideas’: Anyone Can Help Shape European Union’s New €94 Billion Research Program

These encouraging words were spoken here last week at the European Research and Innovation Days, where policy bigwigs working with the European Commission invited the audience to help shape Europe’s next seven-year research funding program, Horizon Europe, set to begin in 2021. Their message: Anyone can help “cocreate” the program’s outlines. [ScienceMagazine] Editorial

Trump Set to Nominate Stephen Hahn as FDA Commissioner, Pending Vetting Process

President Trump is set to nominate Dr. Stephen Hahn to lead the FDA, pending completion of the vetting process, according to two people familiar with the selection process. Hahn, an oncologist, is the chief medical executive at MD Anderson Cancer Center in Houston. [STAT News] Editorial

Human Reference Genome Doesn’t Capture Full Genetic Diversity

It’s hard to study genetic sequences if they’re absent from the human reference genome, the product of the $2.7 billion Human Genome Project, which is typically used as a guide for genomic studies. A new study has identified more than 61,000 novel genetic sequences across 1,000 Swedish genomes that are absent from the human reference genome. [The Scientist] Editorial

NEW AACR-KCA Joint Workshop on Precision Medicine
November 14-15, 2019
Seoul, Korea

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

NEW 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)

Associate Professor – Immunology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Scientist – Cancer and Leukemia (St. Jude Children’s Research Hospital)

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

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

Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

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