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Deciphering Adverse Drug Reactions: In Vitro Priming and Characterization of Vancomycin-Specific T Cells From Healthy Donors Expressing HLA-A*32:01.
Toxicol Sci
August 2021
Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK.
Drug rash with eosinophilia with systemic symptoms (DRESS) is a serious adverse event associated with use of the glycopeptide antibiotic vancomycin. Vancomycin-induced drug rash with eosinophilia with systemic symptoms is associated with the expression of human leukocyte antigen (HLA)-A*32:01, suggesting that the drug interacts with this HLA to activate CD8+ T cells. The purpose of this study was to utilize peripheral blood mononuclear cell from healthy donors to: (1) investigate whether expression of HLA-A*32:01 is critical for the priming naïve of T cells with vancomycin and (2) generate T-cell clones (TCC) to determine whether vancomycin exclusively activates CD8+ T cells and to define cellular phenotype, pathways of drug presentation and cross-reactivity.
View Article and Find Full Text PDFSuppression of Hepatocellular Carcinoma by Mycophenolic Acid in Experimental Models and in Patients.
Transplantation
May 2019
Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
Background: Tumor recurrence is a major complication following liver transplantation (LT) as treatment for hepatocellular carcinoma (HCC). Immunosuppression is an important risk factor for HCC recurrence, but conceivably may depend on the type of immunosuppressive medication. Mycophenolic acid (MPA) is a currently widely used immunosuppressant.
View Article and Find Full Text PDFFrom epidemiology to treatment: Aspirin's prevention of brain and breast-cancer and cardioprotection may associate with its metabolite gentisic acid.
Chem Biol Interact
August 2018
Department of Medical Biochemistry, Acibadem University, Istanbul, Turkey.
Background: Epidemiological studies indicate that aspirin consumption reduces the risk of tumors, which is especially relevant for colonic adenoma and carcinoma. Similar observations were made for glial brain tumors and breast cancers, yet the results are inconsistent. Gentisic acid (GA) is a minor catabolite of aspirin; yet humans carrying CYP2C9-variants incapable to catabolize aspirin to GA do not benefit from aspirin in prevention against colonic adenoma.
View Article and Find Full Text PDFClinical Correlation of the Histoculture Drug Response Assay for Head and Neck Cancer.
Methods Mol Biol
January 2019
AntiCancer Inc., San Diego, CA, USA.
Gelfoam histoculture was utilized to develop the histoculture drug response assay (HDRA) for head and neck cancer. Specimens of head and neck tumors were evaluated for sensitivity to the following drugs: cisplatinum (CDDP), 5-fluorouracil (5-FU), and the combination of CDDP and 5-FU. In the first clinical study at UCSD, 10 of 12 patients with tumors that were drug sensitive in Gelfoam histoculture had either complete or partial response clinically.
View Article and Find Full Text PDFFenfluramine-Phentermine is Associated with an Increase in Cellular Proliferation Ex Vivo and In Vitro.
J Heart Valve Dis
July 2017
Division of Biochemistry and Molecular Biology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
Background And Aim Of The Study: Fenfluraminephentermine (FenPhen) has been implicated in accelerated valvular heart disease, characterized by valvular regurgitation and thickening, and resembling the histopathologic lesions found in carcinoid. The study aim was to determine whether cellular proliferation is present in FenPhen-exposed valves, by utilizing an in-vitro model to test whether FenPhen has a direct mitogenic effect on cardiac valvular cells, as compared to serotonin.
Methods: Ex-vivo valves were tested for proliferation in surgically removed FenPhen-exposed valves (n = 10) and compared to proliferation levels in normal human cardiac valves removed at autopsy (n = 10).
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