MACROPHAGE AND MICROGLIAL ACTIVATION IN GLIOMA-ASSOCIATED INFLAMMATION
Nalin Gupta, Associate Professor
University Of California San Francisco, 3333 California St., Ste 315, San Francisco, Ca 94143-0962
Grant 5K08NS055061-05 from National Institute Of Neurological Disorders And Stroke
Keywords: 0-11 years old; 21+ years old; Address; Adult; Anaplastic Astrocytic Neoplasm; Anaplastic Astrocytic Tumor; Anaplastic astrocytoma; Animals; Astrocytes; Astrocytoma, Grade III; Astrocytus; Astroglia; Attenuated; Binding; Binding (Molecular Function); Blood Vessels; Blood monocyte; Body Tissues; Bone Marrow; Bone Marrow Transplant; Bone Marrow Transplantation; Brain; Brain Neoplasia; Brain Neoplasms; Brain Tumors; C-C Chemokines; CCL2; CCL2 gene; CCR2 receptor; CNS Diseases; CNS Tumor; CNS disorder; CNS neoplasm; Cachectin; Cachectin-Tumor Necrosis Factor; California; Cancer Genes; Cancer of Brain; Cancer-Promoting Gene; Cell/Tissue, Immunohistochemistry; Cells; Central Nervous System Diseases; Central Nervous System Disorders; Central Nervous System Neoplasms; Chemokines, CC; Child; Child Youth; Childhood; Children (0-21); Chronic; Classification; Clinical; Clinical Research; Clinical Study; Cytofluorometry, Flow; Cytokine Receptors; Cytokines, Chemotactic; Data; Demyelinations; Development; Disease; Disorder; Drugs; Ectopic Expression; Encephalon; Encephalons; Endothelial Cells; Environment; Extracellular Matrix, Integrins; Family; Flow Cytofluorometries; Flow Cytometry; Flow Microfluorimetry; G-Proteins; GDCF-2; GDCF-2 HC11; GTP-Binding Proteins; GTP-Regulatory Proteins; Generalized Growth; Genetic; Glial Cell Tumors; Glial Neoplasm; Glial Tumor; Glioma; Goals; Grade III Astrocytic Neoplasm; Grade III Astrocytic Tumor; Grafting, Bone Marrow; Growth; Guanine Nucleotide Coupling Protein; Guanine Nucleotide Regulatory Proteins; HC11; Hematogenous; Histologic; Histologically; Homologous Chemotactic Cytokines; Hortega cell; Human; Human, Adult; Human, Child; Human, General; Hypoxia; Hypoxic; IHC; INFLM; Immunity; Immunohistochemistry; Immunohistochemistry Staining Method; Immunology; Immunology (Including BRMP); Immunology (NCI Program); Immunosuppression Effect; Immunosuppressions (Physiology); Immunosuppressive Effect; Implant; In Vitro; Inbred Strains Mice; Incidence; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Injury; Integrins; Intercrines; Investigators; Israel; Knock-out; Knockout; Knockout Mice; Label; Ligands; MCAF; MCP-1; MCP1; MGC9434; MS (Multiple Sclerosis); Malignant Astrocytoma; Malignant Tumor of the Brain; Malignant neoplasm of brain; Mammals, Mice; Man (Taxonomy); Man, Modern; Marrow Transplantation; Marrow monocyte; Measures; Mediating; Medication; Mentors; Metastasis; Metastasize; Metastatic Neoplasm; Metastatic Tumor; Mice; Mice, Inbred Strains; Mice, Knock-out; Mice, Knockout; Mice, Transgenic; Microfluorometry, Flow; Microglia; Molecular Interaction; Monocyte Chemoattractant Protein-1; Monocyte Chemotactic Protein-1; Monocyte Chemotactic and Activating Factor; Monocyte Chemotactic and Activating Protein; Monocyte Secretory Protein JE; Multiple Sclerosis; Murine; Mus; Natural immunosuppression; Necrosis; Necrotic; Neoplasm Metastasis; Neoplasms of Neuroglia; Nervous System, Brain; Neuroglial Neoplasm; Neuroglial Tumor; Neurosurgeon; Nomenclature; Normal Tissue; Normal tissue morphology; Null Mouse; Oncogenes; Oxygen Deficiency; Pathogenesis; Patients; Pharmaceutic Preparations; Pharmaceutical Preparations; Play; Primary Brain Neoplasms; Process; Programs (PT); Programs [Publication Type]; R01 Mechanism; R01 Program; RPG; Radiation; Receptor Protein; Receptors, Cytokine; Recruitment Activity; Research; Research Grants; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Research Specimen; Researchers; Resistance; Reticuloendothelial System, Bone Marrow; Role; SCYA2; SIS cytokines; SMC-CF; SUBGP; SYS-TX; San Francisco; Sclerosis, Disseminated; Secondary Neoplasm; Secondary Tumor; Secondary to; Signal Pathway; Small Inducible Cytokine A2; Specimen; Stimulus; Subgroup; System; System, LOINC Axis 4; Systematics; Systemic Therapy; TNF-alpha; Target Populations; Testing; Therapeutic Agents; Tissue Growth; Tissues; Training; Transforming Genes; Transgenic Mice; Tumor Biology; Tumor Cell; Tumor Cell Migration; Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Tumor-Derived; Tumors of Neuroglia; Tumors, Central Nervous System; Universities; Viral Diseases; Virus Diseases; adult human (21+); angiogenesis; antitumor agent; beta-Chemokines; cancer metastasis; career; chemoattractant cytokine; chemokine; chemokine receptor; children; clinical relevance; clinically relevant; cytokine; disease/disorder; drug/agent; experience; flow cytophotometry; gitter cell; immunosuppression; implantation; inhibitor; inhibitor/antagonist; insular sclerosis; interest; local drug delivery; loss of function; macrophage; malignant astrocyte; mesoglia; microglial cell; microgliocyte; migration; monocyte; monocyte chemoattractant protein 1 receptor; mouse model; neoplastic cell; neuro-oncology; oligodendroglioma; ontogeny; overexpression; pediatric; perivascular glial cell; programs; public health relevance; ray (radiation); receptor; receptor, MCP-1; recruit; resistant; response; small molecule; social role; surgeon, neuro-; tissue processing; tumor; tumor growth; tumors in the brain; tumors in the central nervous system; v erbB; v-erbB Gene; v-erbB Oncogenes; vascular; viral infection; virus infection; youngster
Project start date: 2006-04-19
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-00-003
5K08NS055061-05 (2010): $161406
Sponsored Links Excellgen http://Excellgen.com
Macrophage And Microglial Activation In Glioma-Associated Inflammation
Nalin Gupta
Neurological Surgeryuniversity Of California San Francisco
Grant 5K08NS055061-04 from National Institute Of Neurological Disorders And Stroke IRG: NST
Keywords: glioma, inflammation, leukocyte activation /transformation, neoplasm /cancer G protein, Israel, angiogenesis, astrocyte, astrocytoma, biology, birth, bone marrow, bone marrow transplantation, brain, career, cell, cell migration, chemoattractant, chemokine, chemokine receptor, children, clinical research, cytokine, cytokine receptor, environment, experience, family, genetically modified animal, genetics, human, hypoxia, immunity, immunocytochemistry, immunology, immunosuppression, implant, infection, injury, integrin, laboratory mouse, ligand, macrophage, microglia, model, monocyte, monocyte chemoattractant protein 1, motivation, multiple sclerosis, myelinopathy, necrosis, neoplasm /cancer blood supply, neoplastic cell, neoplastic growth, nomenclature, oncogene, oncology, osteocyte, play, protein, public health, radiation, receptor, role, small molecule, therapy, tissue, training, tumor necrosis factor alpha, university
Project start date: 2006-04-19
Project end date: 2011-02-28
5K08NS055061-02 (2007): $161406
Grants awarded to Nalin Gupta
Macrophage And Microglial Activation In Glioma-Associated Inflammation
Nalin Gupta
University Of California San Francisco 3333 California St., Ste 315 San Francisco, Ca 941430962
Grant 1K08NS055061-01 from National Institute Of Neurological Disorders And Stroke IRG: NST
Abstract: The goal of this project is to provide , Nalin Gupta, with the necessary expertise to develop an independent research career at the University of California San Francisco by building on his previous experience and training. This will be accomplished through a mentored research project supervised by Dr. Israel F. Charo, and additional training in immunology and use of transgenic mouse models. Dr. Gupta is a pediatric neurosurgeon with a clinical and research interest in neuro-oncology. His project, Macrophage and microglial activation in glioma-associated inflammation addresses an understudied aspect of brain tumor biology The interactions between inflammatory cells and tumor cells. The hypothesis of this project is that macrophages and microglia are recruited to high-grade gliomas by over-expression of a specific chemokine, monocyte chemoattractant protein-1 (MCP-1), and that this process facilitates tumor growth. The Specific Aims that will test this hypothesis are 1) determine the origin of tumor-associated macrophages, 2) measure the effect of loss of the CCR2 cytokine receptor on glioma growth in mice developing oligodendrogliomas, and 3) determine the contribution of tumor and host-derived MCP-1 on glioma growth. The importance of MCP-1 is suggested by its ubiquity in high-grade gliomas, its correlation with infiltrating macrophages, and data supporting a role for this cytokine in angiogenesis and tumor cell migration. The effect of macrophages and microglia on glioma growth will be directly examined using a genetic approach in transgenic mice. Mice expressing the v-erbB oncogene in a heterozygous ink4a/arf background develop high-grade tumors with a predictable incidence. These tumors recapitulate many of the features of human high-grade tumors. For Specific Aim 1, animals will receive bone marrow transplants with fluorescently labeled cells so that bone- marrow derived cells can be identified precisely. The effect of cytokine activity upon glioma growth will be measured in Aim 2 by crossing v-erbB expressing mice with mice that lack CCR2, the cellular receptor for MCP-1. Macrophage and microglia will be measured using immunohistochemistry and flow cytometry. The final Aim will use intracranial implantation of transformed astrocytes to study the effect of either tumor- or host-derived MCP-1 on tumor growth. If the expected results are achieved, we would next evaluate inhibitors of the MCP-1/CCR2 signaling pathway as potential anti-tumor agents. Public Health Relevance Inflammation accompanying malignant brain tumors results in complications for patients, and may promote the growth of tumors. Identifying the role of inflammation in brain tumors would provide a rationale to develop drugs to target this process. Another possible benefit of such drugs is that normal tissue injury associated with treatments such as radiation may also be reduced.
Keywords: glioma, inflammation, leukocyte activation /transformation, neoplasm /cancer, brain, macrophage, neoplastic growth
Project start date: 2006-04-19
Project end date: 2011-02-28
1K08NS055061-01 (2006): $161406