The Experimental Glioma Tissue (EGT) Core Facility will provide a wide range of histologic, immunologic and in vivo animal testing services to the second and third Projects directly and to the first Project indirectly to assist in critical in vivo evaluation of genetically engineered herpes simplex viruses (HSV) for the treatment of human malignant gliomas. The objective will be to provide correlative evidence of both safety (lack of neurovirulence) and efficacy (anti-tumor activity) of in vitro selected genetically engineered HSV in normal or severe combined immune deficiency (scid) mice bearing syngeneic or xenogeneic (human) glioma grafts. We will evaluate virulence of selected HSV injected into normal or stab-wounded brain tissue of mice and, for highly selected viruses, subhuman primates (Aotus monkeys) by (a) clinical monitoring (b) microscopic examination of injected brain tissue for morphologic pathology; (c) immunohistochemical and immunofluorescent studies using a wide variety of immunologic reagents as described in the second and third Projects. The EGT core facility will also be responsible for developing and validating a new intracranial glioma model that can be used to test combined therapy involving extracranial radiation to activate expression of HSV-transduced genes intratumorally via x-irradiation promoters. Efficacy will be determined using prolongation of survival and regression of intracranial gliomas of mouse or human origin in immunocompetent (C57BL/6) or immunocompromised (C.B-17 scid)mice. The core will assist in assessment of tumorigenic potential and viral susceptibility of in situ recovered human malignant glioma cells that have survived HSV mutant virus exposure as described in the second Project. The goal will be to improve viral production and/or delivery to achieve a more efficacious result. In summary, the EGT Core will provide assistance to investigators in the second and third Projects to define the anti-tumor effects produced in vivo by selected HSV mutants by (a) immunohistochemical/immunofluorescent identification of viral, tumor cell and host immune related inflammatory cell components with engrafted murine and human gliomas, (b) functional examination of intratumoral immune-related cells, and (c) distribution of induced and transduced cytokine expression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA071933-02
Application #
6269783
Study Section
Project Start
1998-07-01
Project End
1999-06-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Jackson, Joshua D; Markert, James M; Li, Li et al. (2016) STAT1 and NF-?B Inhibitors Diminish Basal Interferon-Stimulated Gene Expression and Improve the Productive Infection of Oncolytic HSV in MPNST Cells. Mol Cancer Res 14:482-92
Shu, Minfeng; Du, Te; Zhou, Grace et al. (2015) Role of activating transcription factor 3 in the synthesis of latency-associated transcript and maintenance of herpes simplex virus 1 in latent state in ganglia. Proc Natl Acad Sci U S A 112:E5420-6

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