Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714.
AuthorsFeng B, Xu JJ, Bi YA, Mireles R, Davidson R, Duignan DB, Campbell S, Kostrubsky VE, Dunn MC, Smith AR, Wang HF,
JournalToxicol Sci
PubMed ID19223659
'CP-724,714, a potent and selective orally active HER2 tyrosine kinase inhibitor, was discontinued from clinical development due to unexpected hepatotoxicity in cancer patients. Based on the clinical manifestation of the toxicity, CP-724,714 likely exerted its hepatotoxicity via both hepatocellular injury and hepatobiliary cholestatic mechanisms. The direct cytotoxic effect, hepatobiliary disposition ... More
Isolation of carbohydrate-specific CD4(+) T cell clones from mice after stimulation by two model glycoconjugate vaccines.
AuthorsAvci FY, Li X, Tsuji M, Kasper DL,
JournalNat Protoc
PubMed ID23196974
Here we describe how to isolate carbohydrate-specific T cell clones (for which we propose the designation 'Tcarbs') after stimulation by two glycoconjugate vaccines. We describe how to prepare, purify and characterize two model glycoconjugate vaccines that can be used to generate Tcarbs. These glycoconjugate vaccines (GBSIII-OVA and GBSIII-TT) are synthesized ... More
Ceramide mediates age-associated increase in macrophage cyclooxygenase-2 expression.
Authors Claycombe Kate J; Wu Dayong; Nikolova-Karakashian Mariana; Palmer Helen; Beharka Alison; Paulson K Eric; Meydani Simin Nikbin;
JournalJ Biol Chem
PubMed ID12072440
Previously, we showed that macrophages (MØ) from old mice have significantly higher levels of lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)) production than young mice, due to increased cyclooxygenase-2 (COX-2) mRNA levels. The aim of the current study was to determine the underlying mechanisms of age-associated increase in COX-2 gene expression. The ... More