Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1.
The selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains was examined using the SOS response as an end point of DNA damage.
Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease.
- Changtao Jiang, Cen Xie, F. Gonzalez
- Biology, MedicineJournal of Clinical Investigation
- 2 January 2015
It is demonstrated that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota-associated NAFLD development, linking the microbiome, nuclear receptor signaling, andNAFLD.
Induction of lung and exocrine pancreas tumors in F344 rats by tobacco-specific and Areca-derived N-nitrosamines.
- A. Rivenson, D. Hoffmann, B. Prokopczyk, S. Amin, S. Hecht
- Medicine, BiologyCancer research
- 1 December 1988
The observation of benign and malignant tumors of the lung and pancreas of rats treated with the tobacco-specific nitrosamines NNK and NNAL is discussed in respect to the causal association between cigarette smoking and cancer of the Lung and Pancreas.
Autophagosomal Membrane Serves as Platform for Intracellular Death-inducing Signaling Complex (iDISC)-mediated Caspase-8 Activation and Apoptosis*
- Megan M. Young, Yoshinori Takahashi, Hong-Gang Wang
- Biology, ChemistryJournal of Biological Chemistry
- 23 February 2012
An autophagy-dependent mechanism of caspase-8 activation and initiation of the apoptotic cascade in response to SKI-I, a pan-sphingosine kinase inhibitor, and bortezomib, a proteasome inhibitor is demonstrated.
Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells.
The results of the present study indicate that SFN administration inhibits prostate cancer progression and pulmonary metastasis in TRAMP mice by reducing cell proliferation and augmenting NK cell lytic activity.
Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction
Treatment of mice with glycine-β-muricholic acid (Gly-MCA) inhibits FXR signalling exclusively in intestine, and improves metabolic parameters in mouse models of obesity, suggesting that Gly-M CA may be a candidate for the treatment of metabolic disorders.
The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma.
It is found that 4-HNE-DNA adducts are preferentially formed at the third base of codon 249 in the p53 gene, a mutational hotspot in human cancers, particularly hepatocellular carcinoma.
Glucuronidation of Active Tamoxifen Metabolites by the Human UDP Glucuronosyltransferases
- Dongxiao Sun, Arun K. Sharma, P. Lazarus
- Biology, MedicineDrug Metabolism And Disposition
- 1 November 2007
Characterization of the glucuronidating activities of human UDP glucuronosyltransferases (UGTs) against isomers of 4-OH-TAM and endoxifen suggests that several UGTs, including UGTS 1A10, 2B7, and 1A8 play an important role in the metabolism of4-OH,N-desmethyl-tamox ifen and endxifen.
Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites.
Functional polymorphisms in TAM-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in TAM metabolism and response to TAM therapy.