Browsing by Author "Saydam G."

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    Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine/threonine protein phosphatase inhibitors
    (1999) Uzunoglu S.; Uslu R.; Tobu M.; Saydam G.; Terzioglu E.; Buyukkececi F.; Omay S.B.
    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 Cal-A on the proliferation/differentiation of HL60 and K562 cells. Okadaic acid and Cal-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.
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    Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cells
    (2000) Aydin H.H.; Selvi N.; Saydam G.; Tobu M.; Uzunoglu S.; Uslu R.; Buyukkececi F.; Omay S.B.
    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 PP2 A upregulation.
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    Role of intercellular communications in breast cancer multicellular tumor spheroids after chemotherapy
    (Tech Science Press, 2006) Oktem G.; Bilir A.; Ayla S.; Yavasoglu A.; Goksel G.; Saydam G.; Uysal A.
    Tumor heterogeneity is an important feature that is especially involved in tumor aggressiveness. Multicellular tumor spheroids (MTS) may provide some benefits in different steps for investigation of the aggregation, organization, differentiation, and network formation of tumor cells in 3D space. This model offers a unique opportunity for improvements in the capability of a current strategy to detect the effect of an appropriate anticancer agent. The aim of this study was to investigate the cellular interactions and morphological changes following chemotherapy in a 3D breast cancer spheroid model. Distribution of the gap junction protein "connexin-43" and the tight junction protein "occludin" was investigated by immunohistochemistry. Cellular interactions were examined by using transmission and scanning electron microscopies as well as light microscopy with Giemsa staining after treating cells with doxorubicin, docetaxel, and doxorubicin/docetaxel combination. Statistical analyses showed significant changes and various alterations that were observed in all groups; however, the most prominent effect was detected in the doxorubicin/docetaxel combination group. Distinct composition as a vessel-like structure and a pseudoglandular pattern of control spheroids were detected in drug-administered groups. Immunohistochemical results were consistent with the ultrastructural changes. In conclusion, doxorubicin/ docetaxel combination may be more effective than the single drug usage as shown in a 3D model. The MTS model has been found to be an appropriate and reliable method for the detection of the changes in the expression of cellular junction proteins as well as other cellular proteins occurring after chemotherapy. The MTS model can be used to validate the effects of various combinations or new chemotherapeutic agents as well as documentation of possible mechanisms of new drugs. Copyright © 2006 Cognizant Comm. Corp.
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    Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes
    (Zerbinis Publications, 2014) Goker B.; Caliskan C.; Caglar H.O.; Kayabasi C.; Balci T.; Tepedelen B.E.; Aygunes D.; Susluer S.Y.; Mutlu Z.; Gunell N.S.; Korkmaz M.; Saydam G.; Gunduz C.; Avci C.B.
    Purpose: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that inhibition of BCR-ABL fusion protein by ponatinib induces apoptosis of CML cells. Epigallocatechin-3-gallate (EGCG), which is a polyphenol in green tea, induces apoptosis in different types of cancer cells. The purpose of this study was to determine the cytotoxic and apoptotic effects of ponatinib and EGCG combination in K562 CML cell line. This study also aimed to detect alterations of the expression levels of cell cycle-regulation related genes after ponatinib and EGCG combination in K562 CML cell line. Methods: The cytotoxic effects of the compounds on K562 cells were determined in a time- and dose-dependent manner by using WST-1 analysis. The combination index (CI) isobologram was used to analyze the data. Apoptotic effects of P-EGCG were defined by flow cytometry and gene expressions were detected by RT-qPCR. Results: IC50 values of ponatinib and EGCG were 87.13 nM and 50μM, respectively. CI value of the P-EGCG was 0.658 and the combination showed synergistic effect (ED90 value: 28.39 nM ponatinib, 117.12 μg/ml EGCG). Ponatinib, EGCG and P-EGCG induced apoptosis compared to control cells. CyclinDl and CDC25A were downregulated by P-EGCG by 2.49 and 2.63-fold, respectively. TGF-β2 was upregulated by 4.57-fold. Conclusion: EGCG possesses cytotoxic and apoptotic properties and may cooperate with the growth inhibiting activity of ponatinib synergistically against CML cells. P-EGCG mediated apoptosis might be associated with upregulation of TGF-β2 gene and downregulation of cyclinDl and CDC25A genes.
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    The Effect of Cryotherapy on the Prevention of Oral Mucositis and on the Oral pH Value in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
    (Elsevier Inc., 2021) Baysal E.; Sari D.; Vural F.; Çağırgan S.; Saydam G.; Töbü M.; Şahin F.; Soyer N.; Gediz F.; Acarlar C.; Timur E.; Güngör A.
    Objective: The aim of this study was to evaluate the effectiveness of cryotherapy on the prevention of oral mucositis (OM) and on the oral pH value in patients with multiple myeloma undergoing autologous stem cell transplantation. Data Sources: This nonrandomized controlled clinical trial was carried out in Bone Marrow Transplant Centers of three hospitals with total 32 patients. In addition to standard oral care, a total of 80 minutes of cryotherapy was applied to the experimental group. OM was assessed according to the World Health Organization's Oral Toxicity Scale before chemotherapy and for 21 days after chemotherapy (every day in the first 14 days, then every other day until the 21st day [if not discharged]). Conclusion: According to the findings, cryotherapy did not change the incidence of oral OM, and neither affected the severity of nor decreased the duration of it. Oral pH value was found to be significantly different between the patient groups only before and 1 day after chemotherapy. Implications for Nursing Practice: Cryotherapy is an inexpensive, easy-to-use method with no side effects; it would be beneficial to continue cryotherapy to prevent the development of OM in patients with cancer receiving drugs with a short half-life such as melphalan. It is also recommended to conduct further studies with different chemotherapy drugs with short half-lives to determine its effect on the prevention of OM development. © 2021 Elsevier Inc.
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    Efficacy and safety of ruxolitinib in patients with myelofibrosis: A retrospective and multicenter experience in turkey
    (Turkiye Klinikleri, 2021) Soyer N.; Ali R.; Turgut M.; Haznedaroğlu İ.C.; Yilmaz F.; Aydoğdu İ.; Pir A.; Karakuş V.; Özgür G.; Kiş C.; Ceran F.; Ilhan G.; Özkan M.; Aslaner M.; Ince İ.; Yavaşoğlu İ.; Gediz F.; Sönmez M.; Güvenç B.; Özet G.; Kaya E.; Vural F.; Şahin F.; Töbü M.; Durusoy R.; Saydam G.
    Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28–87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10–40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1–55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment. © TÜBİTAK.
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    Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data; [Kronik Lenfositik Lösemili Hastalarda İbrutinib Tedavisinin Etkililiği ve Güvenilirliği: Gerçek Hayat Verilerinin Retrospektif Analizi]
    (Turkish Society of Hematology, 2021) Tombak A.; Tanrıkulu F.P.; Durusoy S.S.; Dinçyürek H.D.; Kaya E.; Ümit E.G.; Yavaşoğlu İ.; Mehtap Ö.; Deveci B.; Özcan M.A.; Terzi H.; Okay M.; Sayınalp N.; Yılmaz M.; Okan V.; Kızıklı A.; Özcan Ö.; Çetin G.; Demircioğlu S.; Aydoğdu İ.; Saydam G.; Davulcu E.A.; İlhan G.; Uçar M.A.; Özet G.; Akpınar S.; Turgut B.; Berber İ.; Kurtoğlu E.; Sönmez M.; Batur D.S.; Yıldırım R.; Özkocamaz V.; Güneş A.K.; Sahip B.; Ertop Ş.; Akay O.M.; Baştürk A.; Doğu M.H.; Akdeniz A.; Ünal A.; Seyhanlı A.; Gürkan E.; Çekdemir D.; Ferhanoğlu B.
    Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes. © 2021 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.
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    Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells
    (Taylor and Francis Ltd., 2022) Kayabasi C.; Yilmaz Susluer S.; Balci Okcanoglu T.; Ozmen Yelken B.; Mutlu Z.; Goker Bagca B.; Caliskan Kurt C.; Saydam G.; Durmuskahya C.; Kayalar H.; Ozbilgin A.; Biray Avci C.; Gunduz C.
    Origanum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose ∼5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G0/G1, S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML. © 2022 Taylor & Francis Group, LLC.