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“A key property of metallo-proteins and -enzymes is the affinity of metal ion M for protein ligand P as defined by the dissociation constant K(D) = [M][P]/[MP]. Its accurate determination is essential for a quantitative understanding of metal selection and speciation. However, the surfaces of proteins are defined by the sidechains of amino

acids and so abound in good metal ligands (e. g., imidazole of histidine, thiol of cysteine, carboxylate of aspartic and glutamic AZD8931 acids, etc.). Consequently, adventitious binding of metal ions to protein surfaces is common with K(D) values >= 10(-6) M. On the other hand, transport proteins responsible for ‘chaperoning’ essential metals to their cellular destinations appear to Fosbretabulin molecular weight bind the metal ions selectively (K(D) < 10(-7) M), both for speciation and to minimise the toxic effects of ‘free’ metal ions. These ions are normally bound with still higher affinities at

their ultimate destinations (the active sites of metallo-proteins and -enzymes). This review surveys possible approaches to estimation of these dissociation constants and pinpoints the various problems associated with each approach.”
“BACKGROUND: Cholangiocarcinoma (CCA) is a lethal cancer of the biliary epithelium, originating from the liver (intrahepatic), at the confluence of the right and left hepatic ducts (hilar) or in the extrahepatic bile ducts. It is a rare malignancy associated with poor prognosis.\n\nDATA SOURCES: We searched the PubMed/MEDLINE database for relevant articles published from 1989 to 2008. The search terms used were related to “cholangiocarcinoma”

and its “treatment”. Although no language restrictions were imposed initially, for the Selleck Compound C full-text review and final analysis, our resources only permitted the review of articles published in English. This review deals with the treatment of cholangiocarcinoma, the principles and the current trends.\n\nRESULTS: The risks and prognostic factors, symptoms and differential diagnosis are thoroughly discussed. In addition, the tools of preoperative diagnosis such as endoscopic retrograde cholangiopancreatography, digital image analysis, fluorescence in situ hybridization and magnetic resonance cholangiopancreatography are reviewed. Moreover, the treatment of CCA is discussed.\n\nCONCLUSIONS: The only curative treatment available is surgical management. Unfortunately, many patients present with unresectable tumors, the majority of whom die within a year of diagnosis. Surgical treatment involves major resections of the liver, pancreas and bile duct, with considerable mortality and morbidity. However, in selected cases and where indicated, appropriate management with aggressive surgery may achieve a good outcome with a prolonged survival expectancy.