61 research outputs found
Novel sulfasalazine analogues with enhanced NF-kB inhibitory and apoptosis promoting activity
No full textThe NF-kB transcription factor plays a key role in the regulation of apoptosis by modulating expression of a wide range of cell death control molecules. NF-kB also plays an important role in human diseases by promoting inappropriate cell survival. Small molecule inhibitors of NF-kB are therefore likely to provide novel therapeutic opportunities. Sulfasalazine (SFZ) is a synthetic anti-inflammatory comprising an aminosalicylate, 5-amino salicylic acid (5-ASA), linked to an antibiotic, sulfapyridine (SPY). SFZ, but not 5-ASA or SPY, inhibits activation of NF-kB. We synthesised a small number of SFZ analogues and determined their ability to inhibit NF-kB activity and promote apoptosis in chronic lymphocytic leukaemia and hepatic stellate cells, where NF-kB plays an important role in cell survival. Remarkably, 3 of the 6 analogues synthesised were significantly more effective (up to 8-fold) inhibitors of NF-kB dependent transcription and this increased activity was associated with enhanced apoptosis. Therefore, it is possible to readily improve the NF-kB inhibiting activity of SFZ and analogues of SFZ may be attractive therapeutic agents for malignancies and chronic liver disease where NF-kB is thought to play a significant role
Synthesis and analysis of spiruchostatin A, a potent bicyclic tetrapeptide histone deacetylase inhibitor
No full textDistinct promoters mediate constitutive and inducible Bcl-X-L expression in malignant lymphocytes
No full textBcl-X-L is a Bcl-2-related survival protein that is essential for normal development. Bcl-X-L expression is rapidly induced by a wide range of survival signals and many cancer cells constitutively express high levels. The Bcl-X gene has a complex organization with multiple promoters giving rise to RNAs with alternate 5' non-codingexons. Here we have investigated the mechanisms that control basal and induced expression of Bcl-X-L in B-lymphoma cells. Antisense experiments demonstrated that Bcl-X-L was essential for survival of Akata6 B-lymphoma cells. The levels of RNAs containing the IB Bcl-X non-coding exon, derived from the distal 1B promoter, correlated with basal expression of Bcl-X-L in primary malignant B cells and this promoter was highly active in B-cell lines. The activity of this promoter was largely dependent on a single Ets binding site and Ets family proteins were bound at this promoter in intact cells. CD40 ligand (CD40L)-induced cell survival was associated with increased Bcl-X-L expression and accumulation of exon IA-containing RNAs, derived from the proximal 1A promoter. Nuclear factor-kappaB (NF-kappa B) inhibition prevented induction of Bcl-X-L protein and exon IA-containingRNAs by CD40L. Therefore, the distal Bcl-X 1B promoter plays a critical role in driving constitutive expression-mediated via Ets family proteins in malignant B cells, whereas NF-kappa B plays a central role in the induction of Bcl-X-L in response to CD40 signalling via the proximal 1A promoter
Novel synthetic analogues of the natural product histone deacetylase inhibitor FK2286289
No full textTítulo: Sermones de tempore et de sanctis totius anni
No full text"D. IOannis Thauleri conuersionis vitaeque historia ..." -- Conciones de tempore" -- "Conciones de Sanctis" -- "Tractatus de veris virtutibus, institutionisbusque diuinis habens capita XXXIX ..."Copia digital : Google BooksSign.: *\p4\s, a-f\p4\s, A-Z\p4\s, 2A-2Z\p4\s, 3A-3Z\p4\s, 4A-4Z\p4\s, 5A-5Y\p4\sPortada con grabado xilográficoSign.: [asterisco], a-f, A-F, 2A-2Z, 3A-3Z, 4A-4Z, 5A-5YPort. con grav. xilPort. con grab. xilContiene : D. Ioannis Thauferi conuersionis vitaeque historia...Conciones de temporeConciones de SanctisTractatus de veris virtutibus, institutionibusque diuinis habens capita XXXI
Johannes Beleth , De officiis ecclesiasticis. II
No full textNumérisation effectuée à partir d'un document de substitution.F. 98v-100 Notes sur l'octave des fêtes (98v), la messe (99), les trois Marie (99v) et les Apôtres (99v). F. 100 PETRUS PICTAVENSIS, Poenitentiale (incompl. de la fin) : « Conpilatio presens materiam habens confessionem... — ... tamen modo probabile. » Cf. Moore, Works of Peter of Poitiers, 168.F. 1. Ex-libris gratté du président Jacques-Auguste de Thou
Pharmacological inhibitors of NF-kappa B accelerate apoptosis in chronic lymphocytic leukaemia cells
No full textNuclear factor-kappaB NF-kappa B) is a transcription factor that plays a critical role in the inappropriate survival of various types of malignant cells. Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the Western world. Although overexpression and regulation of NF-kappa B has been described in CLL, its function remains unclear. Exposure of CLL cells to BAY117082 or Kamebakaurin, potent pharmacological inhibitors of the NF-kappa B pathway, accelerated apoptosis in approximately 70% of cases. Sensitivity to NF-kappa B pathway inhibitors was not related to the prognostic markers VH status, CD38 or Zap70 expression, or to the levels of nuclear NF-kappa B. Normal peripheral B cells were resistant to the apoptosis-inducing effects of these compounds. Cell death induced by the inhibitors was associated with activation of caspase-9 and -3, and loss of mitochondrial membrane polarization, but did not involve changes in the expression of Bcl-2 or Mcl-1. Inhibitors caused an increase in c-jun NH2-terminal kinase activity in CLL, but this did not appear to be important for apoptosis. Microarray analysis identified some potential novel NF-kappa B target genes, including interleukin-16- and the Bcl-2- related survival protein Bcl-w. These results demonstrate that a substantial proportion of CLL are dependent on NF-kappa B for enhanced survival and suggest that inhibition of NF-kappa B may have therapeutic potential
Habens, Sophia J (Death, 1908-01-01)
No full textAddress: 1241 Plum St.Age at death: 52 Yrs. 7-176/Pg.2./1908/F W M/B.P.-City/Dr. S.J. D. Meade/John J. Radel Co. - Undertaker/Walnut Hills Cem.Original record filed in drawer labeled 'GUR-HAGEL'
Turbinaria turbinata Kuntze
No full textFucus turbinatus Linnaeus, Species Plantarum 2: 1160. 1753. "Habitat in America rupibus marinis." RCN: 8282, 8307. Lectotype (Irvine in Spencer & al. in Taxon, in press): [icon] " Fucus marinus vesiculas habens membranis extantibus alatas" in Sloane, Voy. Jamaica 1: 58, t. 20, f. 6. 1707. - Typotype: Herb. Sloane 1: 6 (BMSL). Current name: Turbinaria turbinata (L.) Kuntze (Sargassaceae).Published as part of Jarvis, Charlie, 2007, Chapter 7: Linnaean Plant Names and their Types (part F), pp. 516-528 in Order out of Chaos. Linnaean Plant Types and their Types, London :Linnaean Society of London in association with the Natural History Museum on page 526, DOI: 10.5281/zenodo.29197
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