Looks like the NCI is following Duke in choosing panzem over YC-1....note "nitric oxide" under publications......... Giovanni Melillo, M.D. SAIC FrederickNational Cancer Institute-FrederickAddress: Building 432, Rm 218Frederick, MD 21702-1201Phone:301-846-5050Fax:301-846-6081Email:melillo@dtpax2.ncifcrf.govNovel therapeutic strategies related to Hypoxia inducible factor-1 (HIF-1).Current interests of the DTP-Tumor Hypoxia Laboratory include the development of pharmacological and molecular strategies targeting hypoxia-inducible factor-1 (HIF-1) activity. In vitro and in vivo studies support a role for the HIF-1 in angiogenesis and tumor progression. Therefore, HIF-1 is a novel molecular target for development of cancer therapeutics and anti-angiogenic drugs. To identify novel HIF-1 inhibitors we are developing a screening system based on a luciferase reporter assay. A second interest of the laboratory is to identify and characterize novel hypoxia and HIF-1-inducible genes and to study the molecular mechanisms by which hypoxia promotes gene expression in the tumor microenvironment. To fully elucidate the gene expression profile under hypoxic conditions we are using the microarray technique. We are interested in studying hypoxic induction of novel genes in normal cells infiltrating the tumor (i.e. human monocytes) as well as in cancer cell lines. Interactive possibilities and available reagents include: hypoxia-inducible reporter gene vectors. CredentialsDr. Giovanni Melillo obtained his medical doctor degree from the University of Naples, Italy in 1981. He had his residency and fellowship in Medical Oncology at the National Tumor Institute in Naples. In 1991 he was awarded a CNR-NATO international fellowship and he joined the Laboratory of Molecular Immunoregulation at the NCI-FCRDC as a visiting scientist. He then joined the Laboratory of Experimental Immunology at the NCI-FCRDC where he characterized the role of a hypoxia-responsive element in the promoter of the inducible nitric oxide synthase gene. In July 1996 he became a Clinical associate at the Clinical Oncology Program of the NCI in Bethesda where he became interested in the role of hypoxia-induced angiogenesis in tumor progression. In July 1999 he became a Senior Investigator with the DTP-Tumor Hypoxia Laboratory at the NCI-Frederick. His current interests are to develop novel therapeutic strategies to target hypoxia inducible factor-1 (HIF-1) activity and to identify and characterize novel hypoxia and HIF-1-inducible genes. Recent PublicationsNCBI PubMed listing of publications by Giovanni Melillo. 1. Melillo, G., Musso, T., Sica, A., Taylor, L.S., Cox, G.W., and Varesio, L.: A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J. Exp. Med. 182:1683-1693, 1995. 2. Melillo, G., Brooks, A., Musso, T., Taylor, L.S., Cox, G.W., and Varesio, L.: Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase (iNOS) promoter by the iron chelator desferrioxamine. J. Biol. Chem. 272: 12236-12243, 1997.3. Melillo, G., Sausville, E. A., Cloud, K., Lahusen, T., Varesio, L., and Senderowicz, A.M.: Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of VEGF expression in human monocytes. Cancer Res. 59: 5433-5437, 1999.4. Carta, L., Pastorino, S., Melillo, G., Bosco, M.C., Massazza, S., and Varesio, L.: Engineering of Macrophages to Produce IFN-g in Response to Hypoxia. J. Immunol. 166:5374-5380, 2001.5. Shoemaker, R.H., Scudiero, D.A., Melillo, G., Currens, M.J., Monks, A.P., Rabow, A.A., Covell, D.G., and Sausville, E.A.: Application of high-throughput, molecular-tageted screening to anticancer drug discovery. Current Topics in Medicinal Chemistry 2:229-246, 2002.6. Rapisarda A., Uranchimeg B., Scudiero D.A., Selby M., Sausville E.A., Shoemaker R.H., and Melillo G: Identification of Small Molecule Inhibitors of Hypoxia Inducible Factor 1 (HIF-1) Transcriptional Activation Pathway. Cancer Res. 62: 4316-4324, 2002.7. Tan, A.R., Messmann, R.A., Sausville, E.A., Headlee, D., Arbuck, S.G., Murgo, A.J., Melillo, G., Zhai S., Figg W.D., Swain S.M., and Senderowicz A.M.: Phase I Clinical and Pharmacokinetic Study of Flavopiridol Administered as a Daily 1-Hour Infusion in Patients with Advanced Neoplasms. J. Clin. Oncol. 20(19): 4074-4082, 2002.8. Rybak SM, Sanovich E, Hollingshead MG, Borgel SD, Newton DL, Melillo G, Kong D, Kaur G, and Sausville EA: "Vasocrine" formation of tumor cell-lined vascular spaces: Implications for rationale design of antiangiogenic therapies. Cancer Res. 63: 2812-2819, 2003.[ DTP Home ] [DTP Pathways ] [DTP Discovery ] [DTP Development ] [DTP Site Search ] [DTP Data Search ]
