Search Our Scientific Publications & Authors

Nat Commun 2020 Jul 10;11(1):3457. Epub 2020 Jul 10.

Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.

Glioblastoma is a deadly cancer, with no effective therapies. Better understanding and identification of selective targets are urgently needed. We found that advillin (AVIL) is overexpressed in all the glioblastomas we tested including glioblastoma stem/initiating cells, but hardly detectable in non-neoplastic astrocytes, neural stem cells or normal brain. Read More

Neurooncol Adv 2019 May-Dec;1(1):vdz004. Epub 2019 May 28.

Department of Neurosurgery, Weill Cornell Medicine, New York, New York.

Background: Midline gliomas like diffuse intrinsic pontine glioma (DIPG) carry poor prognosis and lack effective treatment options. Studies have implicated amplifications in the phosphatidylinositol 3-kinase (PI3K) signaling pathway in tumorigenesis; compensatory activation of parallel pathways (eg, mitogen-activated protein kinase [MEK]) may underlie the resistance to PI3K inhibition observed in the clinic.

Methods: Three patient-derived cell lines (SU-DIPG-IV, SU-DIPG-XIII, and SF8628) and a mouse-derived brainstem glioma cell line were treated with PI3K (ZSTK474) and MEK (trametinib) inhibitors, alone or in combination. Read More

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa067. Epub 2020 Jun 4.

Department of Biomedical Science, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA.

Background: Aberrant MET receptor tyrosine kinase (RTK) activation leads to invasive tumor growth in different types of cancer. Overexpression of MET and its ligand hepatocyte growth factor (HGF) occurs more frequently in glioblastoma (GBM) than in low-grade gliomas. Although we have shown previously that HGF-autocrine activation predicts sensitivity to MET tyrosine kinase inhibitors (TKIs) in GBM, whether it initiates tumorigenesis remains elusive. Read More

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa053. Epub 2020 Apr 28.

Departments of Neurosurgery, New York, New York, USA.

Background: Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown. Read More

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa043. Epub 2020 Mar 28.

Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.

Background: Type I interferons (IFN-α/β) are cytokines that are typically expressed in response to double-stranded RNA associated with viral infections. Glioblastomas are the most common malignant primary brain tumors, characterized by an infiltrative growth pattern and prominent angiogenic activity, and thought to be maintained by a subpopulation of glioma-initiating (stem-like) cells (GICs). The growth of human GIC lines is highly sensitive to IFN-β. Read More

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa033. Epub 2020 Mar 26.

Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Treatment options for patients suffering brainstem gliomas are quite limited as surgery is not an option against intrinsic tumors at brainstem and chemotherapy generally failed to demonstrate its efficacy. Intracerebral convection-enhanced delivery (CED) is a novel approach for administering chemotherapy to patients with brain tumors. We present the results of phase I trial of CED of nimustine hydrochloride (ACNU), designed to determine the maximum tolerable concentration of ACNU, for patients with recurrent brainstem gliomas. Read More

Neurooncol Adv 2019 May-Dec;1(1):vdz040. Epub 2019 Oct 26.

Department of Neurology, Washington University School of Medicine, St. Louis, MO.

As a cancer predisposition syndrome, individuals with neurofibromatosis type 1 (NF1) are at increased risk for the development of both benign and malignant tumors. One of the most common locations for these cancers is the central nervous system, where low-grade gliomas predominate in children. During early childhood, gliomas affecting the optic pathway are most frequently encountered, whereas gliomas of the brainstem and other locations are observed in slightly older children. Read More

Cancer Chemother Pharmacol 2020 Jul 7. Epub 2020 Jul 7.

CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, 500007, Telangana, India.

Glioblastoma multiforme (GBM) is a lethal grade IV glioma (WHO classification) and widely prevalent primary brain tumor in adults. GBM tumors harbor cellular heterogeneity with the presence of a small subpopulation of tumor cells, described as GBM cancer stem cells (CSCs) that pose resistance to standard anticancer regimens and eventually mediate aggressive relapse or intractable progressive GBM. Existing conventional anticancer therapies for GBM do not target GBM stem cells and are mostly palliative; therefore, exploration of new strategies to target stem cells of GBM has to be prioritized for the development of effective GBM therapy. Read More

J Neurooncol 2020 Jul 7. Epub 2020 Jul 7.

Division of Haematology Oncology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Canada.

Background: Diffuse intrinsic pontine gliomas (DIPG) are midline gliomas that arise from the pons and the majority are lethal within a few months after diagnosis. Due to the lack of histological diagnosis the epidemiology of DIPG is not completely understood. The aim of this report is to provide population-based data to characterize the descriptive epidemiology of this condition in Canadian children. Read More

Mol Neurobiol 2020 Jul 6. Epub 2020 Jul 6.

Center for Nanomedicine and Theranostics, Department of Health Technology, Technical University of Denmark, Produktionstorvet, Building 423, 2800, Kongens Lyngby, Denmark.

Glioblastoma (GBM) is the most frequent and devastating primary tumor of the central nervous system with a median survival of 12 to 15 months after diagnosis. GBM is highly difficult to treat due to its delicate location, inter- and intra-tumoral heterogeneity, and high plasticity in response to treatment. In this study, we intracranially implanted primary GBM cells into mice which underwent conventional GBM treatments, including irradiation, temozolomide, and a combination. Read More

Sci Rep 2020 Jul 6;10(1):11065. Epub 2020 Jul 6.

Department of General Pathology, Institute of Biological Sciences, Federal University, Minas Gerais, Av. Pres. Antônio Carlos, 6627, Belo Horizonte, 31270-901, Brazil.

For atypical brainstem lesions, histological diagnosis can have an impact on treatment, especially in cases where diffuse glioma is not found. Since radiotherapy is the only therapeutic modality that has shown clinical and radiographic improvement in patients with diffuse glioma, the misdiagnosis of diffuse glioma can have drastic consequences, particularly in patients with nontumorous lesions. Thus, the purpose of this study was to evaluate the impact of histological diagnosis on the treatment of atypical brainstem lesions. Read More

J Cancer 2020 22;11(16):4683-4691. Epub 2020 May 22.

Departments of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR 72205, USA.

As a highly aggressive pediatric brainstem tumor, diffuse intrinsic pontine glioma (DIPG) accounts for 10% to 20% of childhood brain tumors. The survival rate for DIPG remains very low, with a median survival time as less than one year even under radiotherapy, the current standard treatment. Moreover, over than 250 clinical trials have failed when trying to improve the survival compared to radiotherapy. Read More

Nat Commun 2020 Jul 3;11(1):3288. Epub 2020 Jul 3.

Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.

The prognostic and therapeutic relevance of molecular subtypes for the most aggressive isocitrate dehydrogenase 1/2 (IDH) wild-type glioblastoma (GBM) is currently limited due to high molecular heterogeneity of the tumors that impedes patient stratification. Here, we describe a distinct binary classification of IDH wild-type GBM tumors derived from a quantitative proteomic analysis of 39 IDH wild-type GBMs as well as IDH mutant and low-grade glioma controls. Specifically, GBM proteomic cluster 1 (GPC1) tumors exhibit Warburg-like features, neural stem-cell markers, immune checkpoint ligands, and a poor prognostic biomarker, FKBP prolyl isomerase 9 (FKBP9). Read More

Sci Rep 2020 Jul 2;10(1):10937. Epub 2020 Jul 2.

Unaffiliated, Los Angeles, CA, 90017, USA.

Grade 4 glioma or GBM has poor prognosis and is the most aggressive grade of glioma. Accurate diagnosis and classification of tumor grade is a critical determinant for development of treatment pathway. Extensive genomic sequencing of gliomas, different cell types, brain tissue regions and advances in bioinformatics algorithms, have presented an opportunity to identify molecular markers that can complement existing histology and imaging methods used to diagnose and classify gliomas. Read More

Acta Biomed 2020 Jun 30;91(7-S):5-17. Epub 2020 Jun 30.

Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, Uni-versity of Pavia, Pavia, Italy.

Background: Immune tolerance, immune escape, neoangiogenesis, phenotypic changes, and glioma stem cells are all responsible for the resistance of malignant brain tumors to current therapies and persistent recurrence. The present study provides a panoramic view of innovative therapies for malignant brain tumors, especially glioblastoma, aimed at achieving a tailored approach.

Methods: PubMed/Medline and ClinicalTrials. Read More

J Clin Invest 2020 Jun 30. Epub 2020 Jun 30.

Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Immunotherapeutic strategies are increasingly important in neuro-oncology and the elucidation of escape mechanisms which lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing wildtype and Pd-1-/- mice survived significantly longer than immunodeficient Pfp-/- Rag2-/- mice. Read More

Neuro Oncol 2020 Jun 27. Epub 2020 Jun 27.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Background: The tumorigenic potential of glioma stem cells (GSCs) is associated with multiple reversible molecular alternations, but the role of post-translational protein sumoylation in GSCs has not been elucidated. The development of GSC-targeting drugs relies on the discovery of GSC-preferential molecular modifications and the relevant signaling pathways. In this work, we investigated the protein sumoylation status, the major sumoylated substrate and the key regulatory enzyme in GSCs to explore the therapeutic potential of disrupting protein sumoylation for glioblastoma (GBM) treatment. Read More

Neuro Oncol 2020 Jun 27. Epub 2020 Jun 27.

Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio, USA.

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor and has a dismal prognosis. Previously, we identified that junctional adhesion molecule-A (JAM-A), a cell adhesion molecule, is highly elevated in human GBM cancer stem cells and predicts poor patient prognosis. While JAM-A is also highly expressed in other cells in the tumor microenvironment, specifically microglia and macrophages, how JAM-A expression in these cells affects tumor growth has yet to be determined. Read More

Curr Neuropharmacol 2020 Jun 26. Epub 2020 Jun 26.

Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Centre (CIBM), University of Granada. Spain.

Temozolomide (TMZ), an oral alkylating prodrug which delivers a methyl group to purine bases of DNA (O6- guanine; N7-guanine and N3-adenine), is frequently used together with radiotherapy as part of the first-line treatment of high-grade gliomas. The main advantages are its high oral bioavailability (almost 100% although the concentration found in the cerebrospinal fluid was approximately 20% of the plasma concentration of TMZ), its lipophilic properties, and small size that confer the ability to cross the blood-brain barrier. Furthermore, this agent has demonstrated activity not only in brain tumors but also in a variety of solid tumors. Read More

Cancer Sci 2020 Jun 26. Epub 2020 Jun 26.

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Transgenic green fluorescent protein (GFP) gene mice are widely used. And for the unique advantages of immunodeficient animals in the field of oncology research, we aim to establish a nude mouse inbred strain, which stably expresses EGFP (enhanced-GFP) for the use of transplanted tumor microenvironment (TME) research. Female C57BL/6-Tg(CAG-EGFP) mice were backcrossed with male BALB/c nude mice for eleven generations. Read More

Clin Neuropathol 2020 Jun 26. Epub 2020 Jun 26.

Aims: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients.

Materials And Methods: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). Read More

Pediatr Blood Cancer 2020 Jun 26:e28468. Epub 2020 Jun 26.

Doctoral Program, Department of Radiology, Hanoi Medical University, Ha Noi, Vietnam.

Background: Differentiation between cerebellar medulloblastoma and brainstem glioma is necessary for certain clinical circumstances. We aimed to evaluate the function of diffusion tensor imaging (DTI) metrics in the differentiation between cerebellar medulloblastomas and brainstem gliomas in children.

Procedure: The institutional review board approved this prospective study. Read More

Cancers (Basel) 2020 Jun 22;12(6). Epub 2020 Jun 22.

Brain Tumor Research Laboratory, Department of Neurological Surgery, University of California, Irvine, CA 92617, USA.

The history of modern oncology started around eighty years ago with the introduction of cytotoxic agents such as nitrogen mustard into the clinic, followed by multi-agent chemotherapy protocols. Early success in radiation therapy in Hodgkin lymphoma gave birth to the introduction of radiation therapy into different cancer treatment protocols. Along with better understanding of cancer biology, we developed drugs targeting cancer-related cellular and genetic aberrancies. Read More

Rev Assoc Med Bras (1992) 2020 Apr;66(4):445-451

. Department of Neurosurgery, Linyi People's Hospital, Linyi, 276000, Shandong, China.

Objective: Glioblastoma (GBM) is a common type of cancer with high mortality. Epithelial to mesenchymal transition (EMT) plays a vital role in the development of glioblastoma. The aim of this study is to evaluate the role of miR-125a-5p in glioblastoma and in the tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. Read More

Glia 2020 Jun 23. Epub 2020 Jun 23.

Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Glioblastomas (GBMs) are incurable brain tumors with a high degree of cellular heterogeneity and genetic mutations. Transcription factors that normally regulate neural progenitors and glial development are aberrantly coexpressed in GBM, conferring cancer stem-like properties to drive tumor progression and therapeutic resistance. However, the functional role of individual transcription factors in GBMs in vivo remains elusive. Read More

Cancer Drug Resist 2020 11;3(2):199-208. Epub 2020 Mar 11.

Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

Aim: Improved treatment strategies are desperately needed for eradicating cancer stem cells (CSCs), which drive malignancy and recurrence in glioblastoma multiforme. Hypoxic regions within the tumor microenvironment help maintain and promote the proliferation of CSCs. Here, we explored the effects of silencing hypoxia inducible factor-2α (HIF-2α) because of its specificity for CSCs within the hypoxic environment. Read More

Nat Commun 2020 Jun 17;11(1):3077. Epub 2020 Jun 17.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Lu 119, Fengtai District, 100070, Beijing, China.

Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on a large cohort of brainstem gliomas, including Diffuse Intrinsic Pontine Gliomas. Here we report, from DNA methylation data, distinct clusters termed H3-Pons, H3-Medulla, IDH, and PA-like, each associated with unique genomic and clinical profiles. Read More

Nat Commun 2020 Jun 15;11(1):3015. Epub 2020 Jun 15.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.

The interplay between glioma stem cells (GSCs) and the tumor microenvironment plays crucial roles in promoting malignant growth of glioblastoma (GBM), the most lethal brain tumor. However, the molecular mechanisms underlying this crosstalk are incompletely understood. Here, we show that GSCs secrete the Wnt-induced signaling protein 1 (WISP1) to facilitate a pro-tumor microenvironment by promoting the survival of both GSCs and tumor-associated macrophages (TAMs). Read More

Neurol Med Chir (Tokyo) 2020 Jun 15. Epub 2020 Jun 15.

Ludwig Institute for Cancer Research, University of California San Diego.

Genome engineering using programmable nucleases such as transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeat-associated protein nine facilitated the introduction of genetic alterations at specific genomic sites in various cell types. These tools have been applied to cancer modeling to understand the pathogenic effects of the growing catalog of mutations found in human cancers. Pertaining to brain tumors, neural progenitor cells derived from human induced pluripotent stem cells (iPSCs) engineered with different combinations of genetic driver mutations observed in distinct molecular subtypes of glioblastomas, the most common form of primary brain cancer in adults, give rise to brain tumors when engrafted orthotopically in mice. Read More

Cell Rep 2020 Jun;31(10):107738

Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstrasse 1, 40225 Düsseldorf, Germany. Electronic address:

Glioblastoma (GBM) possesses glioma stem cells (GSCs) that exhibit aggressive invasion behavior in the brain. Current preclinical GBM invasion assays using mouse brain xenografts are time consuming and less efficient. Here, we demonstrate an array of methods that allow rapid and efficient assaying of GSCs invasion in human brain organoids. Read More

Adv Biosyst 2020 Jun 9:e1900312. Epub 2020 Jun 9.

M. W. Schweiger, M. Li, A. Giovanazzi, Dr. R. L. Fleming, E. I. Tabet, Dr. T. Tian, Prof. B. A. Tannous, Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, Boston, MA, 02129, USA.

Glioblastoma (GBM) is the most common primary malignant brain tumor and despite optimal treatment, long-term survival remains uncommon. GBM can be roughly divided into three different molecular subtypes, each varying in aggressiveness and treatment resistance. Recent evidence shows plasticity between these subtypes in which the proneural (PN) glioma stem-like cells (GSCs) undergo transition into the more aggressive mesenchymal (MES) subtype, leading to therapeutic resistance. Read More

Cells 2020 Jun 5;9(6). Epub 2020 Jun 5.

Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain.

Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor in adults with a median overall survival of 15 months. Tumor recurrence and poor prognosis are related to cancer stem cells (CSCs), which drive resistance to therapies. A common characteristic in GBM is gene loss, located close to the cluster of genes at Ch9p21. Read More

Cell Biosci 2020 29;10:74. Epub 2020 May 29.

Institute for Translational Medicine, Qingdao University, Qingdao, China.

The capacities for neural stem cells (NSCs) self-renewal with differentiation are need to be precisely regulated for ensuring brain development and homeostasis. Recently, increasing number of studies have highlighted that long non-coding RNAs (lncRNAs) are associated with NSC fate determination during brain development stages. LncRNAs are a class of non-coding RNAs more than 200 nucleotides without protein-coding potential and function as novel critical regulators in multiple biological processes. Read More

Am J Cancer Res 2020 1;10(5):1429-1441. Epub 2020 May 1.

Department of Anatomy, Ajou University School of Medicine Suwon, South Korea.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, and current standard therapy provides modest improvements in progression-free and overall survival of patients. Innate tumor resistance and presence of the blood-brain barrier (BBB) require the development of multi-modal therapeutic regimens. Previously, cytosine deaminase (CD)-expressing mesenchymal stem cells (MSC/CD) were found to exhibit anticancer activity with a wide therapeutic index by converting 5-fluorocytosine (5-FC), a nontoxic prodrug into 5-fluorouracil (5-FU), a potent anticancer drug. Read More

Cell Mol Life Sci 2020 Jun 6. Epub 2020 Jun 6.

Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, FL, USA.

The metabolic complexity and flexibility commonly observed in brain tumors, especially glioblastoma, is fundamental for their development and progression. The ability of tumor cells to modify their genetic landscape and adapt metabolically, subverts therapeutic efficacy, and inevitably instigates therapeutic resistance. To overcome these challenges and develop effective therapeutic strategies targeting essential metabolic processes, it is necessary to identify the mechanisms underlying heterogeneity and define metabolic preferences and liabilities of malignant cells. Read More

Cells 2020 06 3;9(6). Epub 2020 Jun 3.

Department of Neurosurgery, Division of Experimental Neurosurgery, Heidelberg University Hospital, 69120 Heidelberg, Germany.

The discovery of the isocitrate dehydrogenase (IDH) mutation in glioma led to a paradigm shift on how we see glioma biology. Difficulties in cultivating IDH mutant glioma stem cells (IDH GSCs) resulted in a paucity of preclinical models in IDH glioma, limiting the discovery of new effective chemotherapeutic agents. To fill this gap, we used six recently developed patient-derived IDH GSC lines and performed a large-scale drug screening with 147 Food and Drug Administration (FDA)-approved anticancer drugs. Read More

Lancet Oncol 2020 06;21(6):e317-e329

Department of Pediatric Oncology, Dana- Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute, Boston, MA, USA.

Response criteria for paediatric high-grade glioma vary historically and across different cooperative groups. The Response Assessment in Neuro-Oncology working group developed response criteria for adult high-grade glioma, but these were not created to meet the unique challenges in children with the disease. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. Read More

Lancet Oncol 2020 06;21(6):e305-e316

Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute, Boston, MA, USA.

Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and biological features that are distinct from adult low-grade gliomas, and the developing paediatric brain is more susceptible to toxic late effects of the tumour and its treatment. Therefore, response assessment in children requires additional considerations compared with the adult Response Assessment in Neuro-Oncology criteria. Read More

CNS Neurosci Ther 2020 Jun 2. Epub 2020 Jun 2.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

Aims: To reveal the effects of intra- and inter-tumoral heterogeneity on characteristics of primary IDH-wild type glioblastoma cells.

Methods: Single-cell RNA-seq data were acquired from the GEO database, and bulk sample transcriptome data were downloaded from the TCGA database with clinical information. Neoplastic subtype and glioma stem-like cells (GSCs) were identified by matching 5000 random virtual samples based on ssGSEA. Read More

Cell Death Dis 2020 Jun 2;11(6):417. Epub 2020 Jun 2.

Cellular Oncology group, Biodonostia Health Research Institute, San Sebastian, Spain.

Histone deacetylase 6 (HDAC6) is an epigenetic modifier that is an attractive pharmacological target in cancer. In this work, we show that HDAC6 is elevated in glioblastoma, the most malignant and common brain tumor in adults, in which its high levels correlate with poor patient survival and is more abundant in glioma stem cell subpopulation. Moreover, we identified a new small-molecule inhibitor of HDAC6, which presents strong sensitivity for HDAC6 inhibition and exerts high cytotoxic activity, alone or in combination with temozolomide. Read More

Fluids Barriers CNS 2020 Jun 2;17(1):37. Epub 2020 Jun 2.

Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Univ. Artois, UR 2465, 62300, Lens, France.

Background: Pediatric diffuse intrinsic pontine glioma (DIPG) represents one of the most devastating and lethal brain tumors in children with a median survival of 12 months. The high mortality rate can be explained by the ineligibility of patients to surgical resection due to the diffuse growth pattern and midline localization of the tumor. While the therapeutic strategies are unfortunately palliative, the blood-brain barrier (BBB) is suspected to be responsible for the treatment inefficiency. Read More

Neuro Oncol 2020 May 27. Epub 2020 May 27.

Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.

Background: Diffuse Midline Glioma, formerly Diffuse Intrinsic Pontine Glioma (DIPG), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated 1) whether direct delivery of adenovirus expressing CD40L (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and, 2) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem.

Methods: Syngeneic gliomas in the brainstems of immune competent mice were treated with Ad-CD40L and survival, toxicity and immune profiles determined. Read More

Front Cell Dev Biol 2020 8;8:306. Epub 2020 May 8.

Department of Biology, University of Dayton, Dayton, OH, United States.

Glioblastoma Multiforme (GBM) is the most common form of malignant brain tumor with poor prognosis. Amplification of Epidermal Growth Factor Receptor (EGFR), and mutations leading to activation of Phosphatidyl-Inositol-3 Kinase (PI3K) pathway are commonly associated with GBM. Using a previously published glioma model generated by coactivation of PI3K and EGFR pathways [by downregulation of Pten and overexpression of oncogenic Ras] in glial cells, we showed that the Tep1 gene (ortholog of human CD109) regulates Yki (the ortholog of human YAP/TAZ) via an evolutionarily conserved mechanism. Read More

Aging (Albany NY) 2020 May 25;12(10):9151-9172. Epub 2020 May 25.

Brain Tumor Lab, Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

Mesenchymal stromal/stem cells (MSCs) are promising carriers in cell-based therapies against central nervous system diseases, and have been evaluated in various clinical trials in recent years. However, bone marrow-derived MSCs (BMSCs) are reportedly involved in tumorigenesis initiated by glioma stem-like cells (GSCs). We therefore established three different orthotopic models of GSC-MSC interactions using dual-color fluorescence tracing. Read More

J Mol Neurosci 2020 May 26. Epub 2020 May 26.

Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Glioma is the most common primary brain tumor in humans and the most deadly. Stem cells, which are characterized by therapeutic resistance and self-renewal, play a critical role in glioma, and therefore the identification of stem cell-related genes in glioma is important. In this study, we collected and evaluated the epigenetically regulated-mRNA expression-based stemness index (EREG-mRNAsi) of The Cancer Genome Atlas (TCGA, http://www. Read More

Int Rev Neurobiol 2020 13;151:253-279. Epub 2020 May 13.

Department of Fundamental Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; Laboratory of Pharmacology, National Scientific Center of Marine Biology, Far East Branch of the Russian Academy of Sciences, Vladivostok, Russia; Medical Center, Far Eastern Federal University, Vladivostok, Russia. Electronic address:

Rationale: Glioblastoma multiforme (GBM) is one of the most aggressive human brain tumors. The prognosis is unfavorable with a median survival of 15 months. GBM aggressive nature is associated with a special phenotype of cancer cells that develops because of the transforming growth factor β (TGF-β). Read More

Int Rev Neurobiol 2020 13;151:111-138. Epub 2020 May 13.

School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch of Russian Academy of Sciences, Vladivostok, Russia. Electronic address:

Glioblastoma is the most common malignant tumor of the brain, but its treatment outcomes can be improved by new therapeutic techniques using biocompatible materials. Utilizing controllable alkaline de-esterification we obtained pectin preparation with 27.4% esterification degree and used it for bio-artificial matrix production. Read More

Int J Mol Sci 2020 May 20;21(10). Epub 2020 May 20.

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.

Glioblastoma (GBM) is the most aggressive and prevalent form of a human brain tumor in adults. Several data have demonstrated the implication of microRNAs (miRNAs) in tumorigenicity of GBM stem-like cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. Read More

J Neurosurg Pediatr 2020 May 22:1-7. Epub 2020 May 22.

1Department of Neurological Surgery, Vanderbilt University Medical Center.

Objective: The subventricular zone (SVZ), housed in the lateral walls of the lateral ventricles, is the largest neurogenic niche in the brain. In adults, high-grade gliomas in contact or involved with the SVZ are associated with decreased survival. Whether this association holds true in the pediatric population remains unexplored. Read More