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Brain Sci 2022 May 31;12(6). Epub 2022 May 31.

Institute of Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.

: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). Read More

Cancers (Basel) 2022 Jun 20;14(12). Epub 2022 Jun 20.

Department of Neurosurgery, Gui de Chauliac Hospital, 34295 Montpellier, France.

Diffuse low-grade gliomas (LGG) commonly affect young adults and display a slow evolution, with a life expectancy that can surpass 15 years, thanks to multimodal therapeutic management. Therefore, preservation of quality of life (QoL), including sexual health, is mandatory. We systematically searched available medical databases of Pubmed, Cochrane, and Scopus for studies that reported data on sexual activity or dysfunction (SD) in LGG patients. Read More

Neuro Oncol 2022 Jun 23. Epub 2022 Jun 23.

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Background: Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site.

Methods: Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Read More

Neurooncol Adv 2022 Jan-Dec;4(1):vdac079. Epub 2022 May 24.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

Background: Diffuse midline gliomas (DMG) are highly malignant incurable pediatric brain tumors. A lack of effective treatment options highlights the need to investigate novel therapeutic strategies. This includes the use of immunotherapy, which has shown promise in other hard-to-treat tumors. Read More

Neuro Oncol 2022 Jun 21. Epub 2022 Jun 21.

Anhui Province Key Laboratory of Medical Physics and Technology; Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, Anhui, 230031, China.

Background: Glioblastoma multiforme and other solid malignancies are heterogeneous, containing subpopulations of tumor cells that exhibit stem characteristics. Oct4, also known as POU5F1, is a key transcription factor in the self-renewal, proliferation, and differentiation of stem cells. Although it has been detected in advanced gliomas, the biological function of Oct4, and transcriptional machinery maintained by the stemness of Oct4 protein-mediated glioma stem cells (GSC), has not been fully determined. Read More

Oper Neurosurg (Hagerstown) 2022 Jul 11;23(1):e58. Epub 2022 May 11.

Department of Neurosurgery, Rutgers Robert Wood Johnson Medical School & University Hospital, New Brunswick, New Jersey, USA.

Indian J Radiol Imaging 2022 Mar 19;32(1):71-80. Epub 2022 Apr 19.

Department of Neurosurgery, Bahçeşehir University School of Medicine, Göztepe Medical Park Training and Education Hospital, Istanbul, Turkey.

There are many types of neoplasms in or around the foramen of Luschka (FL), and definitive diagnosis in some cases requires knowledge of imaging findings. The uncommon and challenging neoplasms with FL involvement considered in this study are exophytic brainstem glioma, primary glioblastoma of the cerebellopontine angle (CPA), primary anaplastic ependymoma of the CPA, choroid plexus papilloma of the FL, solitary FL choroid plexus metastasis, extraskeletal myxoid chondrosarcoma of the jugular foramen, paraganglioma of the jugular foramen, exostosis of the jugular foramen, psammomatous meningioma in the lateral cerebellar medullary cistern, epidermoid tumor of the fourth ventricle, and a hypoglossal schwannoma. These neoplasms may have overlapping clinical and imaging features, but some have relatively distinct imaging features. Read More

Front Oncol 2022 26;12:924762. Epub 2022 May 26.

Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, Montpellier, France.

Awake surgery for brain gliomas improves resection while minimizing morbidity. Although intraoperative mapping was originally used to preserve motor and language functions, the considerable increase of life expectancy, especially in low-grade glioma, resulted in the need to enhance patients' long-term quality of life. If the main goal of awake surgery is to resume normal familial and socio-professional activities, preventing hemiparesis and aphasia is not sufficient: cognitive and emotional functions must be considered. Read More

Commun Biol 2022 Jun 16;5(1):593. Epub 2022 Jun 16.

Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do, Republic of Korea.

The heterogeneity of glioblastoma multiforme (GBM) leads to poor patient prognosis. Here, we aim to investigate the mechanism through which GBM heterogeneity is coordinated to promote tumor progression. We find that proneural (PN)-GBM stem cells (GSCs) secreted dopamine (DA) and transferrin (TF), inducing the proliferation of mesenchymal (MES)-GSCs and enhancing their susceptibility toward ferroptosis. Read More

J Clin Invest 2022 Jun 15;132(12). Epub 2022 Jun 15.

Cancer Cell 2022 Jun;40(6):639-655.e13

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Medicine II: Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, Medical Center - University of Freiburg, Freiburg, Germany.

Glioblastomas are malignant tumors of the central nervous system hallmarked by subclonal diversity and dynamic adaptation amid developmental hierarchies. The source of dynamic reorganization within the spatial context of these tumors remains elusive. Here, we characterized glioblastomas by spatially resolved transcriptomics, metabolomics, and proteomics. Read More

Mol Neurobiol 2022 Jun 13. Epub 2022 Jun 13.

Experimental Therapeutics and Molecular Imaging Unit, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

Gliomas are the most frequent type of tumor in the central nervous system, which exhibit properties that make their treatment difficult, such as cellular infiltration, heterogeneity, and the presence of stem-like cells responsible for tumor recurrence. The response of this type of tumor to chemoradiotherapy is poor, possibly due to a higher repair activity of the genetic material, among other causes. The DNA double-strand breaks are an important type of lesion to the genetic material, which have the potential to trigger processes of cell death or cause gene aberrations that could promote tumorigenesis. Read More

Ann Indian Acad Neurol 2022 Mar-Apr;25(2):274-275. Epub 2021 Oct 14.

Department of Neurology, Aster Medcity, Kochi, Kerala, India.

BMC Cancer 2022 Jun 11;22(1):642. Epub 2022 Jun 11.

Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults exhibiting infiltration into surrounding tissues, recurrence, and resistance to therapy. GBM infiltration is accomplished by many deregulated factors such as cell adhesion molecules (CAMs), which are membrane proteins that participate in cell-cell and cell-ECM interactions to regulate survival, proliferation, migration, and stemness.

Methods: A comprehensive bioinformatics analysis of CAMs (n = 518) in multiple available datasets revealed genetic and epigenetic alterations among CAMs in GBM. Read More

Comput Struct Biotechnol J 2022 30;20:2759-2777. Epub 2022 May 30.

Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech Republic.

Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Read More

Cancers (Basel) 2022 May 31;14(11). Epub 2022 May 31.

Institute of Anatomy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.

Glioblastoma multiforme is the most common and devastating form of brain tumor for which only palliative radio- and chemotherapy exists. Although some clinical studies on vaccination approaches have shown promising efficacy due to their potential to generate long-term immune surveillance against cancer cells, the evasion mechanisms preventing therapy response are largely uncharacterized. Here, we studied the response of glioblastoma-propagating cells (GPCs) to clinically relevant doses of γ radiation. Read More

Commun Biol 2022 Jun 9;5(1):569. Epub 2022 Jun 9.

Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON, M5T 2S8, Canada.

Spontaneous mouse models of medulloblastoma (MB) offer a tractable system to study malignant progression in the brain. Mouse Sonic Hedgehog (Shh)-MB tumours first appear at postnatal stages as preneoplastic changes on the surface of the cerebellum, the external granule layer (EGL). Here we compared traditional histology and 3DISCO tissue clearing in combination with light sheet fluorescence microscopy (LSFM) to identify and quantify preneoplastic changes induced by disrupting stromal Norrin/Frizzled 4 (Fzd4) signalling, a potent tumour inhibitory signal in two mouse models of spontaneous Shh-MB. Read More

Cell Death Dis 2022 Jun 8;13(6):536. Epub 2022 Jun 8.

Department of Neuro-oncological Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, P. R. China.

Glioblastoma multiforme (GBM) is the most aggressive and highly vascularized brain tumor with poor prognosis. Endothelial cell-dependent angiogenesis and tumor cell-dependent Vasculogenic mimicry (VM) synergistically contribute to glioma vascularization and progression. However, the mechanism underlying GBM vascularization remains unclear. Read More

ASN Neuro 2022 Jan-Dec;14:17590914221102065

Department of Translational Neuroscience, 526115University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocytes and neural stem cells, and their malignant analogues in glioma. Since the discovery of the protein 50 years ago, multiple alternative splice variants of the GFAP gene have been discovered, leading to different GFAP isoforms. In this review, we will describe GFAP isoform expression from gene to protein to network, taking the canonical isoforms GFAPα and the main alternative variant GFAPδ as the starting point. Read More

Theranostics 2022 16;12(9):4221-4236. Epub 2022 May 16.

Department of Neurosurgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

In the glioblastoma (GBM) microenvironment, tumor-associated macrophages (TAMs) are prominent components and facilitate tumor growth. The exact molecular mechanisms underlying TAMs' function in promoting glioma stem cells (GSCs) maintenance and tumor growth remain largely unknown. We found a candidate molecule, transforming growth factor beta-induced (TGFBI), that was specifically expressed by TAMs and extremely low in GBM and GSC cells, and meanwhile closely related to glioma WHO grades and patient prognosis. Read More

Front Immunol 2022 20;13:914236. Epub 2022 May 20.

Department of Biomedical Engineering, Yale University, New Haven, CT, United States.

Human glioblastoma (GBM), the most aggressive brain tumor, comprises six major subtypes of malignant cells, giving rise to both inter-patient and intra-tumor heterogeneity. The interaction between different tumor subtypes and non-malignant cells to collectively shape a tumor microenvironment has not been systematically characterized. Herein, we sampled the cellular milieu of surgically resected primary tumors from 7 GBM patients using single-cell transcriptome sequencing. Read More

Neurooncol Adv 2022 Jan-Dec;4(1):vdac049. Epub 2022 Apr 13.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Background: Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pediatric brain tumor biology, such as tumor cell invasiveness, have been difficult to study with currently available tools. Read More

Acta Neuropathol 2022 Jul 4;144(1):129-142. Epub 2022 Jun 4.

German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg, Germany.

Glioblastoma (GBM) derived from the "stem cell" rich subventricular zone (SVZ) may constitute a therapy-refractory subgroup of tumors associated with poor prognosis. Risk stratification for these cases is necessary but is curtailed by error prone imaging-based evaluation. Therefore, we aimed to establish a robust DNA methylome-based classification of SVZ GBM and subsequently decipher underlying molecular characteristics. Read More

Dev Cell 2022 Jun 3;57(12):1466-1481.e6. Epub 2022 Jun 3.

Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA; Division of Regenerative Medicine, School of Medicine, University of California San Diego, CA 92037, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA. Electronic address:

Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. Here, we demonstrate that platelet-derived growth factor (PDGF) signaling induces N-methyladenosine (mA) accumulation in glioblastoma (GBM) stem cells (GSCs) to regulate mitophagy. PDGF ligands stimulate early growth response 1 (EGR1) transcription to induce methyltransferase-like 3 (METTL3) to promote GSC proliferation and self-renewal. Read More

Cell Death Dis 2022 Jun 2;13(6):516. Epub 2022 Jun 2.

Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, PR China.

The current study aimed to investigate the effects associated with SNAI2 on the proliferation of glioma stem cells (GSCs) to elucidate its underlying molecular mechanism in the development of glioma. The expression of Snail family transcriptional repressor 2 (SNAI2) in glioma tissues was initially predicted via bioinformatics analysis and subsequently confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), which revealed that SNAI2 was highly expressed in glioma tissues as well as GSCs, with an inverse correlation with overall glioma patient survival detected. Loss- and gain- of-function assays were performed to determine the roles of SNAI2 and pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) on GSC viability, proliferation and apoptosis. Read More

Fluids Barriers CNS 2022 Jun 1;19(1):38. Epub 2022 Jun 1.

Human Health Therapeutics Research Centre, National Research Council of Canada, Building M-54, Montreal Road, ON, K1A 0R6, Ottawa, Canada.

Human blood brain barrier (BBB) models derived from induced pluripotent stem cells (iPSCs) have become an important tool for the discovery and preclinical evaluation of central nervous system (CNS) targeting cell and gene-based therapies. Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary form of gene-modified cell-based immunotherapy with potential for targeting solid tumors, such as glioblastomas. Crossing the BBB is an important step in the systemic application of CAR-T therapy for the treatment of glioblastomas and other CNS malignancies. Read More

Cell 2022 Jun 31;185(12):2184-2199.e16. Epub 2022 May 31.

Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA; Center for Biomedical Informatics and Information Technology & Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Read More

Brain 2022 May 30. Epub 2022 May 30.

Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, Montpellier, France.

Neuro Oncol 2022 May 26. Epub 2022 May 26.

Department of Cell Biology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor. Its cellular composition is very heterogeneous, with cells exhibiting stem-cell characteristics (GSCs) that co-determine therapy resistance and tumor recurrence. Bone Morphogenetic Protein (BMP)-4 promotes astroglial and suppresses oligodendrocyte differentiation in GSCs, processes associated with superior patient prognosis. Read More

Vet Pathol 2022 May 31:3009858221100433. Epub 2022 May 31.

Department of Agriculture, Food and the Marine, Celbridge, Ireland.

This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial tumors were reviewed and investigated by immunohistochemistry for S100, glial fibrillary acidic protein, synaptophysin, pancytokeratin, vimentin, neuron-specific enolase, oligodendrocyte transcription factor 2, and isocitrate dehydrogenase 1. Ages of affected cattle ranged from 6 months to 14 years (5. Read More