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Stat3 is a signaling molecular and oncogene activated frequently in many human malignancies including the majority of prostate, breast, and head and neck cancers; yet, no current chemotherapeutic approach has been implemented clinically that specifically targets Stat3. We recently developed G-rich oligodeoxynucleotides, which form intramolecular G-quartet(More)
BACKGROUND/AIMS IL-6, an inducer of the acute-phase response, is linked with the development of vascular disease and atherosclerosis. One mechanism likely involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6 can induce VSMC proliferation and the release of monocyte chemoattractant protein-1 (MCP-1). We hypothesized that this(More)
Signal transducer and activator of transcription 3 (Stat3) is a critical mediator of oncogenic signaling activated frequently in many types of human cancer where it contributes to tumor cell growth and resistance to apoptosis. Stat3 has been proposed as a promising target for anticancer drug discovery. Recently, we developed a series of G-quartet(More)
Recently, we have described the design and characterization of oligonucleotides containing only G and T bases, i.e. T30695 and T30177, that are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in culture (Jing, N., Rando, R. F., Pommier, Y., and Hogan, M. E. (1997) Biochemistry 36, 12498-12505). To understand that observation and(More)
Stat3 is constitutively activated in many human cancers where it functions as a critical mediator of oncogenic signaling through transcriptional activation of genes encoding apoptosis inhibitors (e.g. Bcl-x(L), Mcl-1 and survivin), cell-cycle regulators (e.g. cyclin D1 and c-Myc) and inducers of angiogenesis (e.g. vascular endothelial growth factor). This(More)
Lung cancer is the leading cause of cancer mortality in the United States. Despite advances made over the past decades, the overall survival of patients with lung cancer remains dismal. Here we report novel G-quartet oligodeoxynucleotides (GQ-ODN) that were designed to selectively target signal transducer and activator of transcription 3 (Stat3), in the(More)
The G-tetrad-forming oligonucleotides and have been identified as potent inhibitors of human immunodeficiency virus type 1 integrase (HIV-1 IN) activity (Rando, R. F., Ojwang, J., Elbaggari, A., Reyes, G. R., Tinder, R., McGrath, M. S., and Hogan, M. E. (1995) J. Biol. Chem. 270, 1754-1760; Mazumder, A., Neamati, N., Ojwang, J. O., Sunder, S., Rando, R. F.,(More)
The ability of certain DNA sequences to form G-quartet structures has been exploited recently to develop novel anti-cancer agents including small molecules that promote G-quartet formation within the c-MYC promoter thereby repressing c-MYC transcription and introducing G-quartet-forming oligodeoxynucleotides (GQ-ODN) into cancer cells resulting in(More)
Stat3 is an oncogene that is activated in many human cancer cells. Genetic approaches that disrupt Stat3 activity result in inhibition of cancer cell growth and enhanced cell apoptosis supporting the development of novel drugs targeting Stat3 for cancer therapy. G-quartet oligodeoxynucleotides (ODNs) were demonstrated to be potent inhibitors of Stat3 DNA(More)
Previously, we have described inhibition of HIV-1 infection by T30177, 5'-(GTGGTGGGTGGGTGGGT)-3', an oligonucleotide that is a potent inhibitor of HIV-1 integrase in vitro (Mazumder et al. (1996) Biochemistry 35, 13762). Here a family of oligonucleotides, analogs of T30177, has been studied. On the basis of thermal denaturation, we show that a folded(More)