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Viaclieková rezistencia leukemických buniek na rôzne terapeutiká
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Vedúci projektu: Zdena SulováTrvanie: január 2013 – december 2016
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Anotácia:P-glykoproteín je transportná ATP-áza plazmatickej membrány, ktorá zabezpečuje efektívne odstraňovanie látok z intracelulárneho priestoru buniek. Expresia P-glykoproteínu (P-gp) v neoplastických bunkách vedie k rozvoju viacliekovej rezistencie. Nadexpresia P-gp je sprevádzaná zmenami v morfológii buniek, mení sa zloženie sacharidov na povrchu plazmatickej membrány, čo sa prejavuje rozdielmi vo väzbe lektínov na bunky.Prítomnosť P-gp v bunke je mimo iného sprevádzaná poklesom v senzitivite buniek aj na také látky, ktoré nie sú substrátom P-gp (cisplatina, tunikamycín thapsigargín, konkanavalín A). Tento fakt súvisí so zmenami v metabolizme nádorových buniek ako druhotná bunková odpoveď na masívnu nadexpresiu P-gp. V poslednej dobe sa v literatúre zjavujú názory, že P-gp popri svojej transportnej funkcii, hrá rolu aj ako bunkový regulátor, kde zasahuje do procesov apoptózy a expresie niektorých proteínov. Projekt bude zameraný na štúdium javov, ktoré sprevádzajú nadexpresiu P-gp v leukemických bunkách. |
Kľúčové slová:Viaclieková rezistencia, P-glykoproteín, leukémia, myelodysplastický syndróm |
Ciele:
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Publikácie: |
Messingerova L, Imrichova D, Coculova M, Zelina M, Pavlikova L, Kavcova H, Seres M, Bohacova V, Lakatos B, Sulova Z, Breier A: Different Mechanisms of Drug Resistance in Myelodysplastic Syndromes and Acute Myeloid Leukemia. (Chapter 7), In Myelodysplastic Syndromes (Ota Fuchs Ed.), InTech, ISBN 978-953-51-2586-0, 2016, pp 181-200 | |
Pavlikova L, Seres M, Imrichova D, Hano M, Rusnak A, Zamorova M, Katrlik J, Breier A, Sulova Z. The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin. Gen Physiol Biophys. 35 (2016) 497-510 | |
Coculova M, Imrichova D, Seres M, Messingerova L, Bohacova V, Sulova Z., Breier A. The expression of P-glycoprotein in leukemia cells is associated with the upregulated expression of nestin, a class 6 filament protein. Leuk Res. 36 (2016) 32-39. | |
Messingerova L, Imrichova D, Kavcova H, Seres M, Sulova Z., Breier A. A decrease in cellular microRNA-27a content is involved in azacytidine-induced P-glycoprotein expression in SKM-1 cells. Toxicol In Vitro. 36 (2016) 81-88. | |
Imrichova D, Messingerova L, Seres M, Kavcova H, Pavlikova L, Coculova M, Breier A, Sulova Z. Selection of resistant acute myeloid leukemia SKM-1 and MOLM-13 cells by vincristine-, mitoxantrone- and lenalidomide-induced upregulation of P-glycoprotein activity and downregulation of CD33 cell surface exposure. Eur J Pharm Sci. 77 (2015):29-39. | |
Messingerova L, Imrichova D, Kavcova H, Turakova K, Breier A, Sulova Z. Acute myeloid leukemia cells MOLM-13 and SKM-1 established for resistance by azacytidine are crossresistant to P-glycoprotein substrates. Toxicol In Vitro. 29 (2015) 1405-15. | |
Messingerova L, Jonasova A, Barancik M, Polekova L, Seres M, Gibalova L, Breier A, Sulova Z. Lenalidomide treatment induced the normalization of marker protein levels in blood plasma of patients with 5q-myelodysplastic syndrome. Gen Physiol Biophys. 34 (2015) 399–406 | |
Turakova K, Pavlikova L, Messingerova L, Lakatos B, Breier A, Sulova Z. Reduced udp-glucose levels are associated with p-glycoprotein over-expression in l1210 cells and limit glucosylceramide synthase activity Anticancer Research 35 (2015) 2627-2634 | |
Breier A, Stetka J, Bohacova V, Macejova D, Brtko J, Sulova Z. Effect of 9-cis retinoic acid and all-trans retinoic acid in combination with verapamil on P-glycoprotein expression in L1210 cells. Neoplasma. 61 (2014) 553-565 | |
Imrichova D, Coculova M, Messingerova L, Sulova Z, Breier A. Vincristine-induced expression of P-glycoprotein in MOLM-13 and SKM-1 acute myeloid leukemia cell lines is associated with coexpression of nestin transcript. Gen Physiol Biophys. 33 (2014) 425-431. | |
Breier A, Imrichova D, Paulikova H, Barancik M, Sulova Z: Vincristine as an inductor of drug resistance marker expression in neoplastic cells. In Vincristine: Clinical Uses, Pharmacokinetics and Impacts on Health, (Coello, J. M.; Sabres, Y. D., eds.) NOVA Science Publishers, 2013, pp 1-31 |