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The increased worldwide awareness of seasonal and pandemic influenza, including pandemic H1N1 virus, has stimulated interest in the development of economic platforms for rapid, large-scale production of safe and effective subunit vaccines. In recent years, plants have demonstrated their utility as such a platform and have been used to produce vaccine(More)
The high rate of clinical response to protein-kinase-targeting drugs matched to cancer patients with specific genomic alterations has prompted efforts to use cancer cell line (CCL) profiling to identify additional biomarkers of small-molecule sensitivities. We have quantitatively measured the sensitivity of 242 genomically characterized CCLs to an Informer(More)
The health and economic burden of infectious diseases in general and bioterrorism in particular necessitate the development of medical countermeasures. One proven approach to reduce the disease burden and spread of pathogen is treatment with monoclonal antibodies (mAb). mAbs can prevent or reduce severity of the disease by variety of mechanisms, including(More)
PURPOSE We used human stem and progenitor cells to develop a genetically accurate novel model of MYC-driven Group 3 medulloblastoma. We also developed a new informatics method, Disease-model Signature versus Compound-Variety Enriched Response ("DiSCoVER"), to identify novel therapeutics that target this specific disease subtype. EXPERIMENTAL DESIGN Human(More)
The microsomal metabolism of eight methyl alkyl nitrosamines (nitrosotrifluoroethylamine, nitrosomethylpropylamine, nitrosomethylpentylamine, nitrosomethylneopentylamine, nitrosomethylhexylamine, nitrosomethylheptylamine, nitrosomethylcyclohexylamine and nitrosomethylbenzylamine) was studied. All the nitrosamines produced formaldehyde during metabolism but(More)
H5N1 avian influenza continues to be a potential pandemic threat. Several vaccine candidates based on potentially pandemic influenza strains and antiviral drugs have been tested in preclinical and clinical studies. The data obtained so far have shown some promise, but have also revealed some shortcomings with both of these approaches. We have identified and(More)
With the use of rat liver preparations, the in vitro microsomal metabolism of methylethylnitrosamine, methyl-n-butylnitrosamine, and methyl(2-phenylethyl)nitrosamine labeled with deuterium in the methyl and alpha-methylene positions has been compared with that of the parent (unlabeled) compounds. All three forms of the liver carcinogen(More)
Nitrosodiallylamine has been reported to be non-carcinogenic in rats while nitrosodipropylamine and nitrosodiethanolamine are liver carcinogens. That nitrosodipropylamine is metabolized at the alpha-position by liver microsomes from Fischer-344 rats supports the widely held contention that such metabolism is responsible for the carcinogenicity of(More)
Nitrosopyrrolidine (NO-PYR), an hepatocellular carcinogen, is rapidly metabolized to CO2 by hepatocytes freshly isolated from the livers of male Fischer rats. Using CO2 evolution as a measure of NO-PYR metabolism, we observed two kinetic constants; a high affinity component (Km = 0.11 mM), and a lower affinity component (K m = 3.2 mM). The high affinity(More)
Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that(More)