Browsing by Author "Omay, SB"

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    Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine threonine protein phosphatase inhibitors
    Uzunoglu, S; Uslu, R; Tobu, M; Saydam, G; Terzioglu, E; Buyukkececi, F; Omay, SB
    To elucidate the roles of serine/threonine protein phosphatases type 1 (PP1) and type 2A (PP2A) in methylprednisolone-induced differentiation of HL60 cells into granulocytes and K562 cells into monocytes, we examined the effect of serine/threonine protein phosphatase inhibitors, okadaic acid and Gal-A on the proliferation/ differentiation of HL60 and K562 cells. Okadaic acid and Gal-A augmented methylprednisolone induced granulocytic differentiation and cell death of HL60 cells and monocytic differentiation and cell death of K562 cells in different dose ranges, respectively. These data suggest an important role of PP1 and PP2A in the mechanism leading to differentiation of leukemic cells. (C) 1999 Elsevier Science Ltd. AU rights reserved.
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    Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cells
    Aydin, HH; Selvi, N; Saydam, G; Tobu, M; Uzunoglu, S; Uslu, R; Buyukkececi, F; Omay, SB
    Serine/threonine protein phosphatase 2A (PP2A) may play a role in leukaemic cell differentiation of the HL 60 myeloid leukaemic cell-line after methylprednisolone induction. We have investigated the specific enzyme activity and expression of catalytic and regulatory subunits of PP2A. The resulting specific enzyme activity and immunoblots showed an increase in enzyme activity and the expression of regulatory subunits after methylprednisolone treatment. There was no change in the expression of PP2A catalytic subunits. It is suggested that the effect of methylprednisolone on leukaemic differentiation may be the result of PP2A upregulation.
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    Chemotherapy influences inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) activity on 3D breast cancer cell line
    Öktem, G; Bilir, A; Selvi, N; Yurtseven, ME; Vatansever, S; Ates, U; Uysal, A; Omay, SB
    Multicellular tumor spheroids (NITS) are three-dimensional structural forms of tumors grown in vitro in the laboratory. In this study, the aim was to determine the regulation of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expressions on NITS in response to treatment with the commonly used anti-cancer drugs Doxorubicin and Docetaxel. The spheroids were generated using the liquid overlay technique. The distribution of both iNOS and eNOS was detected using indirect immunohistochemistry, while the expression of both iNOS and eNOS was measured using Western blots. Additionally, S-phase analysis using 5-bromo-2'-deoxyuridine (BrdU) was done on the MTS after treatment with doxorubicin, docetaxel, and a combination of the two. The Griess method was used to measure nitric oxide (NO) production in the cells. An increase in iNOS immunoreactivity and a decrease in eNOS immunoreactivity were observed after doxorubicin treatment, when compared with the other groups. Furthermore, upregulation of iNOS and downregulation of eNOS were detected in doxorubicin-treated cells using Western blotting. Insignificant iNOS expression was observed in all of the groups, and it was particularly low in the control and drug combination groups. NO production was also found to be significantly high after docetaxel treatment, and cell proliferation decreased after doxorubicin treatment. In conclusion, chemotherapy influences NOS activity differently with the presence of different drugs. The results with iNOS show that doxorubicin is a more effective drug than docetaxel, and a drug combination may play a helpful role in the suppression of tumorigenicity and cancer metastasis. Interestingly, eNOS expression increased after the addition of both docetaxel and the drug combination, and it was found to negatively correlate with the histological grade of the tumor. Therefore, analyzing the expression of both iNOS and eNOS might be very useful for targeting the treatment of breast carcinoma and obtaining better information on prognosis.