FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.1.1

Title of the proposal

Apoptosis and cell necrosis

Institute

Slovak Acaemy of Sciences, Cancer Research Institute
Vlarska 7, 833 91 Brastislava, Slovak Republic

Contact

Research subject for a potential FP6 project

The project aim is to analyze apoptosis and cell necrosis, their relationship and regulation in cells with defined mechanisms of resistance. The in vitro model of human leukemic and carcinoma cell lines as well as leukemia patients’ cells versus isolated cord blood hematopoietic stem cells and healthy donor peripheral blood lymphocytes will be used. Cell response to external stimulation is controlled by a number of signaling pathways functioning in an integrated rather than sequential or parallel fashion. We propose, with the aid of flow cytometry, cytogenetic, biochemical and immunological methods to monitor cell treatment response to some possible chemopreventive agens, chemo- or radioresistance modulators in combination with known target structure drugs. Markers involved are cell cycle kinetics, mitochondrial respiratory chain activity, cell redox potential, intracellular pH, reactive oxygen species generation, activities of pro- and antiapoptotic regulatory proteins. Final efforts are modulation of drug- and radioresistance, correlation of in vitro cell lines and leukemia patients’ cells results, and selection of markers with possible predictive value for individual patient.

Recent international cooperation of the research team

Prof. R. Zeillinger, University of Vienna, Department of Obstetrics and Gynecology,Molecular Oncology Group, Vienna, Austria
Prof. T. Szekeres, Klinisches Institut f. Med. & Chem. Labordiagnostik AKH-Wien, Vienna, Austria

Proposer´s relevant publications related to the research subject

J. Jakubikova, J. Duraj, X. Takacsova, L. Hunakova, B. Chorvath, J. Sedlak: Non-steroidal anti-inflammatory agent ibuprofen-induced apoptosis, cell necrosis and cell cycle alterations in human leukemic cells in vitro. Neoplasma 2001;48(3):208-13.

L. Hunakova, J. Bies, J. Sedlak, J. Duraj, J. Jakubikova, X. Takacsova, L. Novotny, B. Chorvath: Differential sensitivity of ovarian carcinoma cell lines to apoptosis induced by the IMPDH inhibitor benzamide riboside. Neoplasma 2000;47(5):274-9

Sedlak J, Hunakova L, Duraj J, Sulikova M, Chovancova J, Novotny L, Chorvath B.: Detection of apoptosis in a heterogenous cell population using flow cytometry. Gen Physiol Biophys. 1999 Oct;18 Spec No:147-54.

Sedlak J, Hunakova L, Chorvath M, Sulikova M, Novotny L, Boljesikova E, Zeillinger R, Chorvath B.: Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radio-sensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833. Anticancer Res. 1998 Jul-Aug;18(4C):3099-105.