The RNA had been also hybridized to Affymetrix rat genome array 230 two. 0, which represents 28,000 rat cDNAs. Worldwide modifications in gene expres sion had been analyzed by cluster evaluation and expression analysis of process atic explorer. 33 and 303 genes were dysregulated by CPA twelve hrs and 72 hrs after injection in the virus, respectively. An EASE evaluation for microclusters selelck kinase inhibitor of dysregulated genes by CPA immediately after twelve and 72 hrs revealed that genes involved in immune response, defense response, and response to biotic stimuli were overrepresented. EASE is a potent device for swiftly converting the outcomes of practical genomics studies from genes to themes. The outcomes of real time quantitative PCR confirmed that the observed dif ferences in expression were real and important. Future experiments would elucidate the position of each of these functions in suppressing the host response to viral infection, and suppression of these functions could lead to ways to improve the therapeutic efficacy of OV infection.
ET 23. SYSTEMIC DELIVERY OF ANTI HGF NEUTRALIZING MONOCLONAL ANTIBODY DOWNREGULATES C MET SIGNALING PATHWAYS IN GLIOMA XENOGRAFTS Bachchu Lal,one David E. Gerber,1 Jin Kim,2 and John Laterra1, 1Johns Hopkins University and MN029 Kennedy Krieger Institute, Baltimore, MD, and two Galaxy Biotech, Inc, Mountain See, CA, USA Most glioblastomas express hepatocyte growth issue, and all express its transmembranous receptor tyrosine kinase c Met. Expression amounts of HGF and c Met are associated with malignant progression in gli oma and in medulloblastoma. Experimental proof indicates that c Met activation contributes to glioma malignancy by improving tumor mitogenic ity, motogenicity, angiogenesis, and resistance to cytotoxic therapies.
We showed that inhibition of expression amounts of HGF and c Met are associ ated with tumor cell growth inhibition in vivo and in vitro. c Met activa tion by HGF activates numerous cell signaling pathways that mechanistically contribute to the biologic response to receptor activation.

PI3K AKT and RAS MAPK are 2 pathways potently activated by c Met. We recently reported that systemic delivery of mL2G7, a murine monoclonal antibody that inhibits HGF binding to c Met, inhibited the growth of established intracranial U87MG xenografts and prolonged ani mal survival. We now report that inhibition of intracranial U87MG glioma development via systemic delivery of mL2G7 is dose dependent, with anti tumor activity using doses as low as 0. 625 mg/kg body weight delivered I. P. twice/ week. The systemic delivery of mL2G7 also had modest anti tumor activity against pre established subcutaneous primary human glioblastoma xenografts that express 30 fold less HGF than the U87MG glioma model. Humanized anti HGF antibody, admin istered by I. P. injections biweekly to scid mice bearing pre established intracranial U87MG glioma xenografts, also showed substantial tumor development inhibition compared with animals treated with control IgG.