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Molecular Identity Changes of Tumor-Associated Macrophages and Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Mouse Glioblastoma Model

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机构: [1]Department of Radiology, Neuroradiology Division, Stanford University, Stanford, CA, USA [2]Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China [3]Acupuncture and Tuina School/Third Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China [4]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [5]Department of Diagnostic and Public Health, University of Verona, Verona, Italy [6]Department of Nuclear Medicine, Guangdong Provincial People’s Hospital, Guangzhou, China [7]In Vivo Imaging Facility, Luxembourg Institute of Health, Luxembourg [8]Department of Oncology, Luxembourg Institute of Health, Luxembourg [9]Department of Radiology, Molecular Imaging Program at Stanford, Stanford, CA, USA [10]Division of Pediatric Neurosurgery, Department of Neurosurgery, Lucile Packard Children’s Hospital, Stanford University School of Medicine, Stanford, CA, USA [11]Molecular Imaging Program at Stanford (MIPS), Canary Center for Cancer Early Detection, Department of Radiology, Stanford University, Stanford, CA, USA [12]Departments of Neuroscience and Neurosurgery and Center for Brain, Immunology, and Glia, School of Medicine, University of Virginia, Charlottesville, VA, USA [13]Department of Neuroradiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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An orthotopically allografted mouse GL26 glioma model (Ccr2RFP/wt-Cx3cr1GFP/wt) was used to evaluate the effect of transient, focal opening of the blood-brain barrier (BBB) on the composition of tumor-associated macrophages and microglia (TAMs). BBB opening was induced by magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) combined with microbubbles. CX3CR1-GFP cells and CCR2-RFP cells in brain tumors were quantified in microscopic images. Tumors in animals treated with a single session of MRgFUS did not exhibit significant changes in cell numbers when compared with tumors in animals not receiving FUS. However, tumors that received two or three sessions of MRgFUS had significantly increased amounts of both CX3CR1-GFP and CCR2-RFP cells. The effect of MRgFUS on immune cell composition was also characterized and quantified using flow cytometry. Glioma implantation resulted in increased amounts of lymphocytes, monocytes and neutrophils in the brain parenchyma. Tumors administered MRgFUS exhibited increased numbers of monocytes and monocyte-derived TAMs. In addition, MRgFUS-treated tumors exhibited more CD80+ cells in monocytes and microglia. In summary, transient, focal opening of the BBB using MRgFUS combined with microbubbles can activate the homing and differentiation of monocytes and induce a shift toward a more pro-inflammatory status of the immune environment in glioblastoma.Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 声学 3 区 核医学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 声学 3 区 核医学
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出版当年[2023]版:
Q2 ACOUSTICS Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
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Q2 ACOUSTICS Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

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第一作者机构: [1]Department of Radiology, Neuroradiology Division, Stanford University, Stanford, CA, USA
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通讯机构: [13]Department of Neuroradiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA [*1]Department of Neuroradiology, University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1482, Houston, TX 77030- 4009, USA
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