ABSTRACTS â ORAL PRESENTATIONS - AMCA, spol. s r.o.

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cell survival, resistance to anticancer therapy and disease progression (Srinivasula and Ashwell, 2008). Based on these findings we considered XIAP and survivin as factors with potentially negative impact on efficiency of hypericin-mediated photodynamic therapy (HY-PDT). Impact of specific XIAP and survivin inhibition on human colorectal adenocarcinoma HT- 29 cells themselves and after their exposition to HY-PDT were the primary objectives of presented study. In our experimental system, specific inhibitors embelin (XIAP) and YM155 (survivin) were applied as pre-treatment as well as post-treatment to HY-PDT. We observed that inhibition of XIAP and survivin resulted in significant decrease in the metabolic activity of HT-29 cells. Further, inhibition of XIAP and survivin in combination with HY-PDT decreased percentage of cells with normal mitochondrial membrane potential, increased the number of death cells and caused accumulation of cells in G2 phase of cell cycle. Considering our results, we may suggest that application of IAPs antagonists stimulates HY-PDT efficiency, therefore it may contribute to a more favorable outcome than the use of single-modality HY-PDT. Acknowledgements This work was supported by the Slovak Research and Development Agency under the contract No. APVV-0040-10; the Scientific Grant Agency of the Ministry of Education of the Slovak Republic under the contract No. VEGA 1/0626/11. References Agostinis, P., Vantieghem, A., Merlevede, W., and de Witte, P. A.: Hypericin in cancer treatment: more light on the way. - International Journal of Biochemistry & Cell Biology 34: 221-241, 2002. Dougherty, T. J., Gomer, C. J., Henderson, B. W., Jori, G., Kessel, D., Korbelik, M., Moan, J., and Peng, Q.: Photodynamic therapy. - Journal of the National Cancer Institute 90: 889-905, 1998. Srinivasula, S. M., and Ashwell, J. D.: IAPs: what´s in a name? - Molecular Cell 30: 123- 135, 2008. Viktorsson, K., Lewensohn, R., and Zhivotovsky, B.: Apoptotic pathways and therapy resistance in human malignancies. - Advances in Cancer Research 94: 143-196, 2005. P6. L-ASPARAGINASE STRONGLY AFFECTS BIOENERGETICS IN LEUKEMIC CELLS Ivana Hermanova 1 , Hana Nuskova 2 , Karel Valis 3 , Karel Fiser 1 , Sonia Fernandez 4 , Josef Houstěk 2 , Arkaitz Carracedo 4 , Jan Trka 1 and Julia Starkova 1 1 Childhood Leukaemia Investigation Prague, Department of Pediatric Hematology/ Oncology, 2 nd Faculty of Medicine, Charles University Prague, Czech Republic, Ivana. hermanova@lfmotol.cuni.cz 2 Department of Bioenergetics, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic 3 Laboratory of Molecular Structure Characterization Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic Analytical Cytometry VII 93
4 CIC bioGUNE Technology Park of Bizkaia, Derio, Bizkaia, Spain L-asparaginase (L-asp) is an important component of childhood acute lymphoblastic leukemia (ALL) therapy. Its cytotoxic effect is based on the depletion of extracellular asparagine and glutamine. Leukemic cells are sensitive to this depletion due to the lower ability to synthesize asparagine compared to healthy cells. However, the exact mechanism of cytotoxic effect and resistance development remains unclear. We established cell lines resistant to L-asp derived from the B-cell precursor ALL REH (TEL/ AML1[+]; very sensitive) and NALM6 (TEL/PDGFRB[+]; medium sensitive) cells by longterm incubation with L-asp. We used the GEP data published by Holleman (Holleman et al, 2004) of ALL patients´ samples sensitive/resistant to L-Asp. Pathway analysis of GEP data from the cell lines and patient samples revealed that protein translation and glucose/lipid metabolic pathways are strongly involved in the effect of L-asp. Next to glucose, glutamine is the other major cellular energy source, it is also important for the activation of PI3K/Akt/mTOR pathway - the key regulator of translation. Since L-asp has also glutaminase activity we focused on the effect of L-asp treatment on translation and bioenergetics in leukemic cells. The amount of p-P70S6K expression fell in REH and NALM6 after treatment with L-asp. Therefore we were interested whether PI3K/mTOR inhibition affects the sensitivity of resistant cell lines. We measured the cytostatic effect of co-treatment: L-asp with mTORC1 inhibitor (rapamycin); with dual inhibitor of mTORC1 and PI3K (LY294002); and with specific inhibitor of PI3K (PX866) on REH, res-REH, NALM6 and res-NALM6. The MTS assay proved the L-asp/rapamycin combination is the most effective. It strongly diminished viability of all cell lines. The effect was even more eminent in resistant cells. Next we determined the impact of L-asp on metabolism of leukemic cells. The protein level of c-myc, the activator of glucose and glutamine catabolism, and glucose transporter 1 (Glut-1) was decreased in REH and NALM6 after L-asp treatment. The inhibition of glycolysis was confirmed by decrease of glucose uptake and decrease of lactate production in cells treated with L-asp. Beside glutamine and glucose metabolism, fatty acids are next substrates for ATP production. Fatty acid oxidation (FAO) was significantly increased in both cell lines after L-asp. The capacity of cell respiration was also increased. Our results indicate that leukemic cells, which normally depend on glycolysis, are able to switch to fatty acid oxidation followed by activation of respiratory chain under amino acid deprivation stress. Respiration of healthy lymphocytes was not changed after incubation with L-asp. L-asp inhibits mTORC1, glycolysis and activates FAO and respiration. We believe that these changes are mainly caused by the effort of the cells to mobilize metabolism with the aim to supply depleted amino acids. We conclude from these data that resistance of the cells is caused by better biochemical adaptability to the nutrient deprived environment. Acknowledgements This work was supported by IGA NT/12429-5, UNCE204012, GAUK 632513 References Holleman A, Cheok MH, den Boer ML, et al.: Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med. 2004;351:533–542 94 Analytical Cytometry VII
Page 1 and 2: ABSTRACTS - ORAL PRESENTATIONS 14.
Page 3 and 4: and (iii) siRNA-mediated knockdown
Page 5 and 6: 25. PROFILING OF CHILDHOOD ACUTE LE
Page 7 and 8: more dominantly than Th1 and CD4 ce
Page 9 and 10: 29. INFLUENCE OF THE LEVEL OF CD133
Page 11 and 12: 36. B-CELL IMMUNOPHENOTYPING OF LAR
Page 13 and 14: possible mechanism behind risk alle
Page 15 and 16: isotype controls and FMO for CD14 a
Page 17 and 18: NEP developmental stages were disti
Page 19 and 20: 50. THE PROGRESSION OF HIV INFECTIO
Page 21 and 22: 52. PRŮKAZ REGULAČNÍCH T LYMFOCY
Page 23 and 24: values when analysing paediatric ly
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Page 27 and 28: for application of proton therapy,
Page 29 and 30: effects will be also characterized
Page 31 and 32: Although multiple signalling pathwa
Page 33 and 34: an ability to recreate the tumour f
Page 35 and 36: incubated with non-filtered superna
Page 37 and 38: approaches how to detect and isolat
Page 39 and 40: progress in development of automate
Page 41 and 42: tissues is characteristic for a num
Page 43 and 44: kappaB. Beside that, we found OANO
Page 45 and 46: therapy in patients (Calderwood et
Page 47: difference in the effect caused eit
Page 51 and 52: P8. PROADIFEN (SKF-525A) ATTENUATES
Page 53 and 54: models. As manifested by compromise
Page 55 and 56: P11. NEW BIOACTIVE AND FLUORESCENT
Page 57 and 58: Acetylation of histones, along with
Page 59 and 60: stimulated cells. The physiological
Page 61 and 62: h induced very minor manifestations
Page 63 and 64: chemotherapeutic drug LA-12. These
Page 65 and 66: aberrant expression, localization a
Page 67 and 68: P21. ASSESSMENT OF MITOCHONDRIAL FU
Page 69 and 70: P23. PTEROSTILBENE: COMPARISON OF A
Page 71 and 72: Fam123b. Amer1 has been shown very
Page 73 and 74: In summary, we described different
Page 75 and 76: this process. Combined treatment wi
Page 77 and 78: Homolog 1) gene; previously identif
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Page 81 and 82: was harmful neither alone nor in co
Page 83 and 84: P34. PHARMACOLOGICAL INHIBITION OF
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Page 87 and 88: P38. EVIDENCE OF ABNORMAL PERIPHERA
Page 89 and 90: acid to 5-lipoxygenase. Similarly t
Page 91 and 92: P41. WHY CAN WE SEE DIFFERENT RADIO
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Page 95 and 96: P44. INSTRUMENT SETTINGS FOR EUROFL
Page 97 and 98: e used to cultivate endothelial cel
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concentrations 0.15, 0.2, 0.3 and 0
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P49. NEW ANALOGS OF RHODAMINE Jiři
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P51. FLUORESCENCE-LABELED FERROMAGN
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could be achieved via the activatio
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28. Pp. 1565-1570. 2008. Dearden C:
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cells (SFC) using IFN-γ Elispot in
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FACSCantoII flow cytometer (Becton
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P59. EARLY DIAGNOSTICS OF CARTILAGE
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cross-reacting group (CREG) and sha
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the frequency of autoimmune disease
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non-covalent bonds. For a solution
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P65. OVULATION STIMULATION PROTOCOL
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Acknowledgements This work was supp
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P68. SUBPOPULATIONS OF B LYMPHOCYTE
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triggers a process of normal blood
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3 Department of Internal Medicine -
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P73. THE V-ATPASE-INHIBITOR BAFILOM
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P75. 5-FLUOROURACIL-SELECTED TUMOUR
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We conclude that decrease in the po
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Acknowledgements This work was supp
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P79. NEW TYPE OF PHOTOSENSITIZER IS
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LD11015, from GAČR 13-29358S, and
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P83. DIFFERENTIATION OF NEURAL CRES
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given cell type are missing and the
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Our results show that both p38α +/
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P90. TOLL-LIKE RECEPTOR 2 TRACKS TH
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for chemokines in attracting “inf
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in immune organs (Bursa of Fabricii
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