Browsing by Author "Saydam, G"
Now showing 1 - 11 of 11
Results Per Page
Sort Options
Item Role of intercellular communications in breast cancer multicellular tumor spheroids after chemotherapyOktem, G; Bilir, A; Ayla, S; Yavasoglu, A; Goksel, G; Saydam, G; Uysal, ATumor 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.Item EPIGALLOCATECHIN-3-GALLATE TRIGGERS AUTOPHAGY MEDIATED CELL DEATH VIA UP-REGULATION OF TMEM74 GENE EXPRESSION IN CHRONIC MYELOID LEUKEMIA CELLSGoker, B; Caliskan, C; Mutlu, Z; Tepedelen, BE; Korkmaz, M; Saydam, G; Gunduz, C; Avci, CBItem Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cellsAydin, HH; Selvi, N; Saydam, G; Tobu, M; Uzunoglu, S; Uslu, R; Buyukkececi, F; Omay, SBSerine/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.Item The Effect of Cryotherapy on the Prevention of Oral Mucositis and on the Oral pH Value in Multiple Myeloma Patients Undergoing Autologous Stem Cell TransplantationBaysal, E; Sari, D; Vural, F; Cagirgan, S; Saydam, G; Töbü, M; Sahin, F; Soyer, N; Gediz, F; Acarlar, C; Timur, E; Güngör, AObjective: 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. (c) 2021 Elsevier Inc. All rights reserved.Item Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in TurkeySoyer, N; Ali, R; Turgut, M; Haznedaroglu, IC; Yilmaz, F; Aydogdu, I; Pir, A; Karakus, V; Özgür, G; Kis, C; Ceran, F; Ilhan, G; Özkan, M; Aslaner, M; Ince, I; Yavasoglu, I; Gediz, F; Sönmez, M; Güvenç, B; Özet, G; Kaya, E; Vural, F; Sahin, F; Töbü, M; Durusoy, R; Saydam, GBackground/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.Item Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia CellsKayabasi, C; Susluer, SY; Okcanoglu, TB; Yelken, BO; Mutlu, Z; Bagca, BG; Kurt, CC; Saydam, G; Durmuskahya, C; Kayalar, H; Ozbilgin, A; Avci, CB; Gunduz, COriganum 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 similar to 5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G(0)/G(1), 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.Item Evolution of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in turkey: a multicenter retrospective analysisKaradag, FK; Yenerel, MN; Yilmaz, M; Uskudar, H; Ozkocaman, V; Tuglular, TF; Erdem, F; Unal, A; Ayyildiz, O; Ozet, G; Comert, M; Kaya, E; Ayer, M; Salim, O; Guvenc, B; Ozdogu, H; Mehtap, O; Sonmez, M; Guler, N; Hacioglu, S; Aydogdu, I; Bektas, O; Toprak, SK; Kaynar, L; Yagci, M; Aksu, S; Tombak, A; Karakus, V; Yavasoglu, I; Onec, B; Ozcan, MA; Undar, L; Ali, R; Ilhan, O; Saydam, G; Sahin, FParoxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.Item Efficacy and Safety of Ibrutinib Use in Patients with Chronic Lymphocytic Leukemia in Real World Experiences: Results of a Prospective Multicenter StudyTombak, A; Tanrikulu, FP; Durusoy, SS; Gurkan, E; Kaya, E; Umit, EG; Yavasoglu, I; Mehtap, O; Deveci, B; Ozcan, MA; Terzi, H; Okay, M; Sayinalp, N; Yilmaz, M; Okan, V; Kizikli, A; Ozcan, O; Cetin, G; Demircioglu, S; Aydogdu, I; Saydam, G; Davulcu, EA; Ilhan, G; Ucar, MA; Ozet, G; Akpinar, S; Turgut, B; Berber, I; Kurtoglu, E; Sonmez, M; Batur, DS; Yildirim, R; Ozkocaman, V; Gunes, AK; Sahip, B; Ertop, S; Akay, M; Basturk, A; Dogu, MH; Akdeniz, A; Unal, A; Seyhanli, A; Ferhanoglu, BItem Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life DataTombak, A; Tanrikulu, FP; Durusoy, SS; Dinçyürek, HD; Kaya, E; Ümit, EG; Yavasoglu, I; Mehtap, Ö; Deveci, B; Özcan, MA; Terzi, H; Okay, M; Sayinalp, N; Yilmaz, M; Okan, V; Kizikli, A; Özcan, Ö; Çetin, G; Demircioglu, S; Aydogdu, I; Saydam, G; Davulcu, EA; Ilhan, G; Uçar, MA; Özet, G; Akpinar, S; Turgut, B; Berber, I; Kurtoglu, E; Sönmez, M; Batur, DS; Yildirim, R; Özkocamaz, V; Günes, AK; Sahip, B; Ertop, S; Akay, OM; Bastürk, A; Dogu, MH; Akdeniz, A; Ünal, A; Seyhanli, A; Gürkan, E; Çekdemir, D; Ferhanoglu, BObjective: 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.Item Evaluation of Patients with PNH Treated By Eculizumab: Real World Data from TurkeyKaradag, FK; Yenerel, MN; Mehmet, Y; Teke, HU; Ozkocaman, V; Tuglular, T; Erdem, F; Unal, A; Ayyildiz, O; Ozet, G; Ozkan, M; Kaya, E; Ayer, M; Salim, O; Güvenç, B; Ozdogu, H; Mehtap, Ö; Sönmez, M; Güler, N; Hacioglu, SK; Aydogdu, I; Bektas, O; Toprak, SK; Kaynar, L; Yagci, M; Aksu, S; Tombak, A; Karakus, V; Yavasoglu, I; Öneç, B; Özcan, MA; Ündar, L; Ali, R; Ustun, C; Ilhan, O; Saydam, G; Sahin, FItem Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine threonine protein phosphatase inhibitorsUzunoglu, S; Uslu, R; Tobu, M; Saydam, G; Terzioglu, E; Buyukkececi, F; Omay, SBTo 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.