Microglia/Brain Macrophages as Central Drivers of Brain Tumor Pathobiology

Publication date: 6 November 2019Source: Neuron, Volume 104, Issue 3Author(s): David H. Gutmann, Helmut KettenmannOne of the most common brain tumors in children and adults is glioma or astrocytoma. There are few effective therapies for these cancers, and patients with malignant glioma fare poorly, even after aggressive surgery, chemotherapy, and radiation. Over the past decade, it is now appreciated that these tumors are composed of numerous distinct neoplastic and non-neoplastic cell populations, which could each influence overall tumor biology and response to therapy. Among these noncancerous cell types, monocytes (microglia and macrophages) predominate. In this Review, we discuss the complex interactions involving microglia and macrophages relevant to glioma formation, progression, and response to therapy.
Source: Neuron - Category: Neuroscience Source Type: research

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Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Astroblastoma is an extremely rare CNS tumor. Morphological diagnosis is difficult, as the typical astroblastic rosettes may be present also in other CNS tumors, including some gliomas and ependymomas. In fact, AB can be considered as a morphologic pattern, which can be associated with a spectrum of molecular entities. Total resection is the best treatment; the precise role of chemotherapy and radiotherapy is still debated, particularly for high-grade tumors. We believe that DNA-methylation profiles represents an important instrument for confirming diagnosis, predicting prognosis and better defining the molec...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In this study, to improve our understanding of the role of ATP1A1 in the malignant phenotype and pathogenesis of GSCs, we evaluated ATP1A1 expression in GBMs of different grades and in two primary GSC lines established from human GBM tissues. We evaluated the role of ATP1A1 in GSC growth, its interactions with Src, and the activation of the ERK1/2 and AKT pathways. Our results revealed that ATP1A1 acts as an oncogene in our GSC models and targeting ATP1A1/Src may suppress GSC proliferation and growth. Materials and Methods Cell Isolation and Culture Human brain GBM tissues were from pathologically confirmed surgical spe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Chiu-Min Lin1†, Ching-Fang Yu2,3†, Hsueh-Ya Huang1,4, Fang-Hsin Chen2,3,5, Ji-Hong Hong2,3,5 and Chi-Shiun Chiang1,6,7* 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan 2Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan 3Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 4Education &Medical Research National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan 5Department of Medical Imaging an...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Alkylating agents have been used since the 60ties in brain cancer chemotherapy. Their target is the DNA and, although the DNA of normal and cancer cells is damaged unselectively, they exert tumor-specific killing effects because of downregulation of some DNA repair activities in cancer cells. Agents exhibiting methylating properties (temozolomide, procarbazine, dacarbazine, streptozotocine) induce at least 12 different DNA lesions. These are repaired by damage reversal mechanisms involving the alkyltransferase MGMT and the alkB homologous protein ALKBH2, and through base excision repair (BER). There is a ...
Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we have shown the safety and efficacy of Vemurafenib in a pediatric patient with DS affected by PXA. Ethics Statement This study was carried out in accordance with the recommendations of the Internal Review Board of the Bambino Gesù Children's Hospital with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Internal Review Board of the Bambino Gesù Children's Hospital. Informed Consent The authors declare that written informed consent was obtained from the pat...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, CuE inhibited cell proliferation and induced mitosis delay in cancer cells, suggesting its potential applicability as an antitumour agent. PMID: 30912292 [PubMed - as supplied by publisher]
Source: Molecular Medicine - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
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