Browsing by Subject "Sulfides"

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    Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy
    (Public Library of Science, 2011) Zerbini, Luiz F; Tamura, Rodrigo E; Correa, Ricardo G; Czibere, Akos; Cordeiro, Jason; Bhasin, Manoj; Simabuco, Fernando M; Wang, Yihong; Gu, Xuesong; Li, Linglin
    Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 ( mda -7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda -7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda -7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda -7/IL-24 by small interfering RNA abrogates apoptosis. mda -7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda -7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.
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    Fine-grained pyroxenites from the Gansfontein kimberlite, South Africa: Evidence for megacryst magma-mantle interaction
    (Geological Society of South Africa, 2004) Doyle, P M; Bell, D R; Le Roex, A P
    The Gansfontein kimberlite contains a suite of fine-grained xenoliths dominated by orthopyroxene, and containing ilmenite, phlogopite, and occasional garnet, with minor quantities of olivine and sulphide. Lamellar intergrowths of orthopyroxene and ilmenite were observed in one sample. The fine grained orthopyroxenite assemblages were observed as discrete xenoliths as a vein in lherzolite, and as a zone margin surrounding a megacrystic dunite. The minerals are characterized by intra- and inter-grain chemical heterogeneity, but are on the whole compositionally similar to those in the abundant, highly evolved Cr-poor megacryst suite at Gansfontein. However, they differ to varying degrees from megacrysts in the concentration of minor elements such as Cr, Al and Ti. Mineral compositions in a pyroxenite vein in lherzolite are higher Cr and Mg#, and lower in Fe3+ than the discrete fine-grained pyroxenites, indicating chemical interaction with peridotite. A single zircon-bearing mica-clinopyroxenite has mineral compositions similar to MARID xenoliths. Fine-grained orthopyroxenites, recognized previously from the Weltevreden and Mzongwana kimberlites and interpreted as rapidly crystallized magmas, are here suggested to result from a reaction between megacryst magma and solid mantle peridotite. Mica-clinopyroxenite may represent the liquid end-product of this reaction. Chemical and modal differences of orthopyroxenites from megacrysts result from reaction with peridotitic components, lack of buffering by typical megacryst mineral assemblages, and possibly shallower origins. Textures and fine-scale chemical disequilibrium indicate that reaction postdates some episodes of megacryst formation and was probably underway when the xenoliths were sampled by ascending kimberlite. Orthopyroxene-garnet thermobarometry indicates an origin of one Gansfontein pyroxenite at ∼1215°C and ∼3.3 GPA, similar to the locus of megacryst crystallization under East... [ABSTRACT FROM AUTHOR]