The SAS proposals for participation in FP6 projects
are listed in blocks according to the FP6 priority theme structure
FP6 priority |
1.1.1 Genomics and Biotechnology for Health
1.1.1 Advanced genomics and its applications for health |
Title of the proposal |
Apoptosis and its modulation |
Institute |
Slovak Academy of Sciences, Cancer Research Institute
Vlarska 7, 833 91 Bratislava, Slovak Republic
www.exon.sav.sk |
Contact |
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Research subject for a potential FP6 project
The project is aimed at the study of:
I. - viability, immunophenotype, cell cycle and the relationship of these changes to programmed cell death (expression anti- and proapoptotic proteins) in human multidrug resistant leukemia and cacinoma (ovarian, breast) cells expressing MDR-1 gene coded for P-glycoprotein and MRP gene coded for p190 glycoprotein after induction with:
a/ anticancer drugs (taxanes, anthracyclins) ,
b/ vitamins (vitamin D3)
c/ retinoids (all-trans retinoic acid, 9-cis-retinoid acid, 13-cis-retinoid acid),
d/ inhibitors of histone deacetylase (trichostatin A, trapoxin A),
e/ platinum complexes (cisplatin, carboplatin),
epidophilotoxins (etoposide),
f/ modulators of multidrug resistance (inhibitors of protein kinases (staurosporine, N-benzoylstaurosporine CGP 41251, genistein), calcium channel blockers (verapamil), agonists of calmodulin (R24571), antiestrogens (tamoxifen), nonimmu-nosuppressive substances (SDZ-PSC 833), neuroleptics (ligand of peripheral benzodiazepine receptor PK11195).
II. - cell cycle and expression of MMR (mismatch-repair) proteins (hMLH1, hMSH2, HMSH6..) in human tumor MMR-deficient- and proficient tumor cells (lymphoblastoid, colon carcinoma, ovarian carcinoma) after induction with antimetabolite agents (6-thioguanine), methylating agents (temozolomide), anthracyclins (doxorubicin), platinum complexes (cis- and carboplatin), epidophylotoxins (etoposide) and potential apoptotic cell attributes monitored by the expression of anti- and proapoptotic proteins. |
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, AustriaProf. Vincent Castronovo, Metastasis Research Laboratory, University of Liege, Sart-Tilman, Liege, Belgium |
Proposerīs relevant publications related to the research subject
1.HUNAKOVA L., SEDLAK J., KLOBUSICKA M., DURAJ J., CHORVATH B.: Tyrosine kinase inhibitor-induced differentiation of K-562 cells: alterations of cell cycle and cell surface phenotype. Cancer Lett., 81, 1994, 81-87.
2. DURAJ J., KOVACIKOVA M., SEDLAK J., KOPPEL J., SOBEL A., CHORVATH B.: Phosphorylation of stathmin during TPA-induced growth inhibition of human pre-B leukemia REH6 cells. Leukemia Res., 19, 1995, 457-461.
3. SEDLAK J., HUNAKOVA L., SULIKOVA M., CHORVATH B.: Protein kinase inhibitor-induced alterations of drug uptake, cell cycle and surface antigen expression in human multidrug-resistant (Pgp and MRP) promyelocytic leukemia (HL-60) cells. Leukemia Res., 21, 1997, 449-458.
4. CHORVATH B., SEDLAK J., NOVOTNY L., HUNAKOVA L., SEVCIKOVA L., BOLJESIKOVA E., CHORVATH M.: Non-immunosuppressive cyclosporine derivative PSC 833 abolishes the resistance of human multidrug-resistant ovarian carcinoma cells in vitro to paclitaxel and paclitaxel-induced radiosensitisation . Int. J. Cancer, 72, 1997, 916-917.
5. 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 radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833. Anticancer Res., 16, 1998, 3099-3106.
6. 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. 18, 1998, 3099-105.
7. 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. 18, 1999, 147-54.
8. HUNAKOVA L., BIES J., SEDLAK J., DURAJ J., JAKUBIKOVA J., TAKACSOVA X., NOVOTNY L.,. CHORVATH B: Differential sensitivity of ovarian carcinoma cell lines to apoptosis induced by the IMPDH inhibitor benzamide riboside. Neoplasma 47, 2000, 274-9 |
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