In her PhD dissertation with a title »Study of biochemical and genetic factors in individualization of thiopurine therapy« Alenka Šmid has presented results of studies which importantly contribute to the improvement of optimization of thiopurine therapy - the backbone of maintenance treatment of childhood acute lymphoblastic leukemia (ALL). The main purpose of the doctoral dissertation was to contribute to understanding of metabolism and toxicity of thiopurines and to translate the acquired knowledge into clinical practice in terms of therapy individualization. The research was focused on studies of biochemical and genetic factors influencing thiopurine S-methyltransferase (TPMT) activity. Identification of novel factors influencing TPMT is of great importance for the improvement of prediction of response to thiopurine therapy, which would lead to improved drug dosing. Scientific achievements of assist. Alenka Šmid, PhD contribute to the development of pharmacogenomics both at the home Faculty and beyond in Slovenia and are a part of the world treasury of knowledge and reflects the international integration through cooperation with experts from the Estonian genome centre at the Tartu University , the University of Tel - Aviv , a spin-off company Genialis d.o.o. and others. In addition to scientific excellence the socioeconomic and social importance of her achievements should not be overlooked. Excellent cooperation with the Pediatric Clinic in Ljubljana has facilitated optimization of thiopurine therapy in the treatment of childhood ALL and thereby allowed for more efficient and safer therapy.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 279654656Sulfasalazine (SZ) belongs to the first line drug therapy in initiation and remission phases in mild to moderate inflammatory bowel disease (IBD). While, thiopurines, 6 mercaptopurine (6 MP) and azathioprine, are particularly used in maintaining phase. It has been shown that SZ inhibits one of the main enzymes responsible for thiopurine catabolism – thiopurine S methyltransferase (TPMT). Clinical trials have demonstrated that concomitant therapy of the two drugs leads to higher plasma concentrations of active thiopurine metabolites and thus enhanced therapeutic response. However, the exact underlying mechanisms of co- treatment remain unclear due to poor study designs and wide variability of analysed parameters. The aim of our study was to confirm the stated observations and to find new elements that could contribute to synergistic behaviour of SZ and 6 MP. We based our experiments on in vitro Caco 2 cell model. Effects of 6 MP and SZ co administration were determined by measuring metabolic activity of cells using MTS. As inflammation can vastly modify gene expressions, we quantified the change in the expression of two efflux transporters for SZ (ABCG2 and ABCC2) against two house-keeping genes (RPLP0 and GAPDH) with Syber dye qPCR. IL 1β reduced ABCG2 expression in Caco 2 cells for 10 % after an 8-hour exposure (p=0,02). We also observed significant decrease of ABCC2 expression: for 10 % (p(0,01) and for 24 % (p(0,001) after 8 and 24 hour treatment with IL 1β, respectively. Our study suggests that SZ enhances 6 MP toxicity and may consequently improve the efficacy of thiopurine therapy. The possible triggering process lies in the TPMT inhibition with SZ which is especially pronounced under inflammatory conditions. The finding can be explained by modified expression of efflux transporters by IL 1β that enables SZ to remain in the cell. Further in vitro and in vivo studies are needed to evaluate the actual impact of joined pharmacological and pathophysiological factors in 6 MP and SZ co treatment of IBD.
B.04 Guest lecture
COBISS.SI-ID: 3910001Organization of postgraduate Certified Course in Radiopharmaceutical Chemistry/Radiopharmacy (http://www.ffa.uni-lj.si/en/mednarodna-dejavnost/joint-educational-programes.html http://www.radiochem.pharma.ethz.ch/) The postgraduate certified course in Radiopharmaceutical Chemistry/Radiopharmacy is co-organized by three Universities : Ljubljana (Slovenia), Zurich (Switzerland) and Leipzig (Germany). The course contents follow the guidelines of the European Association of Nuclear Medicine EANM. Training program is designed for chemists and pharmacists, involved in the small-batch manufacture or quality control of radioactive drugs as well as in the research and development of such products. Modules and Dates Module I "Pharmacy I and Legislation" Module II "Radiopharmaceutical Chemistry" Module III "Pharmacy II and Nuclear Medicine" Modul I is co-organized by Assit. prof. dr. Tanja Gmeiner Stopar, and prof. dr. Irena Mlinarič-Raščan
B.01 Organiser of a scientific meeting
COBISS.SI-ID: 280928000