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Öğe Alterations in the activity and expression of serine/threonine protein phosphatases during all trans retinoic acid-induced apoptosis in breast cancer cells(Professor D A Spandidos, 2003) Sanli, UA; Uslu, R; Karabulut, B; Sezgin, C; Selvi, N; Aydin, HH; Saydam, G.; Goker, E; Omay, SBRetinoids exert different effects on malignant cells with various phenomena. They can induce differentiation and apoptosis in various cancer cells. However, the underlying mechanism of these effects is not clear. There are data related to the role of protein phosphatases during retinoid-induced leukemic cell differentiation. The aim of this study was to evaluate effects of the All trans retinoic acid (ATRA) on protein/serine phosphatases during ATRA induced apoptosis in the breast cancer cells. The MTT assay was used to determine drug-mediated cytotoxicity. A cell death detection ELISA kit was used for detection of the DNA fragments. The activity of serine/threonine protein phosphatases was assayed by the serine/threonine phosphatase system. The expression of serine/threonine protein phosphatases was evaluated by Western blot. During ATRA treatment, a significant decrease in the activity of serine/threonine phosphatases 2A, B and C occurred. The decreased activity of PP2A correlated with the up-regulation of PP2A catalytic and PP2A/B gamma, PP2A/B alpha regulatory subunits. The decrease in activity of the PP2B correlated with down-regulation of PP2B catalytic and up-regulation of PP2B regulatory subunit expression. In addition, there was an up-regulation in PP4C and down regulation in PP2C alpha/beta subunits protein expression. We demonstrated clear alteration in the activity and expression of serine/threonine protein phosphatases in breast cancer cells during ATRA treatment, and we suggest that the ATRA-induced apoptosis of the MCF-7 cells is significantly related to the phosphorylation dynamics.Öğe Alterations in the activity and expression of serine/threonine protein phosphatases during all trans retinoic acid-induced apoptosis in breast cancer cells(Professor D A Spandidos, 2003) Sanli, UA; Uslu, R; Karabulut, B; Sezgin, C; Selvi, N; Aydin, HH; Saydam, G.; Goker, E; Omay, SBRetinoids exert different effects on malignant cells with various phenomena. They can induce differentiation and apoptosis in various cancer cells. However, the underlying mechanism of these effects is not clear. There are data related to the role of protein phosphatases during retinoid-induced leukemic cell differentiation. The aim of this study was to evaluate effects of the All trans retinoic acid (ATRA) on protein/serine phosphatases during ATRA induced apoptosis in the breast cancer cells. The MTT assay was used to determine drug-mediated cytotoxicity. A cell death detection ELISA kit was used for detection of the DNA fragments. The activity of serine/threonine protein phosphatases was assayed by the serine/threonine phosphatase system. The expression of serine/threonine protein phosphatases was evaluated by Western blot. During ATRA treatment, a significant decrease in the activity of serine/threonine phosphatases 2A, B and C occurred. The decreased activity of PP2A correlated with the up-regulation of PP2A catalytic and PP2A/B gamma, PP2A/B alpha regulatory subunits. The decrease in activity of the PP2B correlated with down-regulation of PP2B catalytic and up-regulation of PP2B regulatory subunit expression. In addition, there was an up-regulation in PP4C and down regulation in PP2C alpha/beta subunits protein expression. We demonstrated clear alteration in the activity and expression of serine/threonine protein phosphatases in breast cancer cells during ATRA treatment, and we suggest that the ATRA-induced apoptosis of the MCF-7 cells is significantly related to the phosphorylation dynamics.Öğe Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines(Amer Assoc Cancer Research, 2000) Uslu, R; Sanli, UA; Sezgin, C; Karabulut, B; Terzioglu, E; Omay, SB; Goker, EWe studied the effect of arsenic trioxide (As2O3) on prostate and ovarian carcinoma cell lines. As2O3 has been shown to be effective in leukemia, and acute promyelocytic leukemia in particular, both in vitro and in vivo. As model cell lines, we used DU145 and PC-3 for prostate cancer and MDAH 2774 for ovarian cancer. New modalities of treatment are essential in these kinds of cancers, which produce a high death toll. The 3-(4,5-dimethyl-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to evaluate cytotoxicity. Flow cytometric analysis and mono-oligo nucleosome detection-based ELISA were used to determine the apoptosis. Isobologram analysis was used to evaluate synergism and/or the additive effects of As2O3 and conventional chemothtrapeutic agents. We clearly demonstrated that As2O3 has significant cytotoxic effect on both prostate and ovarian carcinoma cell lines. The dose range of As2O3 in all three cell lines was similar to 10(-6) at. The mechanism underlying cytotoxicity of As2O3 was shown to be apoptosis. The experiments by butylated hydroxyanisole showed that the cytotoxic effect of As2O3 was not through superoxide generation. There was no synergism, but the additive effects of As2O3 were demonstrated with cisplatin, adriamycin, and etoposide. We strongly suggest that As2O3 alone or in combination with conventional chemotherapeutic agents be evaluated further as a new agent for the treatment of prostate and ovarian cancers.Öğe Arsenic trioxide-mediated cytotoxicity in prostate and ovarian carcinoma lines.(Amer Assoc Cancer Research, 1999) Uslu, R; Sezgin, C; Karabulut, B; Sanli, UA; Tobu, M; Saydam, G.; Buyukkececi, F; Omay, SB; Goker, EÖğe The cytotoxic effect of chalcons on myeloid leukemia cell lines.(Amer Soc Hematology, 2001) Omay, SB; Saydam, G.; Sahin, F; Kucukoglu, O; Erciyas, E; Terzioglu, E; Aydin, HH; Goker, E; Buyukkececi, FÖğe Detection of mutant p53 in hepatocellular cancer from turkey and its correlation with clinicopathologic parameters(Kluwer Academic/Plenum Publ, 2003) Cengiz, C; Akarca, US; Goker, E; Yuce, GThe samples of hepatocellular carcinoma from Turkey, a country with a high prevalence of hepatitis B virus and hepatitis C virus, but low dietary exposure to aflatoxin B1, were examined in order to detect the frequency of mutant p53 and its association with clinical and pathological data. Fifty-two samples of hepatocellular cancer from the patients who were diagnosed in our clinic were included in this study. The mutant p53 protein was searched for by specific enzyme-linked immunosorbent assay. Of 52 patients with hepatocellular carcinoma, 26 (50%) had the mutant p53. The incidence of p53 mutation in hepatocellular cancer patients with chronic liver disease due to hepatitis B virus infection was significantly higher than in those with chronic liver disease due to alcohol, indicating that not alcohol but hepatitis B virus, in fact induces the mutations in p53 gene. In addition, it has been shown that the p53 mutation was significantly associated with the diameter of tumor nodule and the degree of cellular differentiation in hepatocellular cancer. The p53 mutation rate found in our study is concordant for a geography where hepatitis B virus and hepatitis C virus are common. Hepatitis B virus and possibly hepatitis C virus, but not alcohol, should be responsible, to a degree, for the mutational change in p53 protein in hepatocellular cancer patients with chronic liver disease. The p53 mutation is a late event in hepatocarcinogenesis because it is related with cellular differentiation and tumor diameter. The specific ELISA can be a useful screening test in future studies to select the patients for gene therapy using wild-type p53.Öğe Detection of mutant p53 in hepatocellular cancer from turkey and its correlation with clinicopathologic parameters(Kluwer Academic/Plenum Publ, 2003) Cengiz, C; Akarca, US; Goker, E; Yuce, GThe samples of hepatocellular carcinoma from Turkey, a country with a high prevalence of hepatitis B virus and hepatitis C virus, but low dietary exposure to aflatoxin B1, were examined in order to detect the frequency of mutant p53 and its association with clinical and pathological data. Fifty-two samples of hepatocellular cancer from the patients who were diagnosed in our clinic were included in this study. The mutant p53 protein was searched for by specific enzyme-linked immunosorbent assay. Of 52 patients with hepatocellular carcinoma, 26 (50%) had the mutant p53. The incidence of p53 mutation in hepatocellular cancer patients with chronic liver disease due to hepatitis B virus infection was significantly higher than in those with chronic liver disease due to alcohol, indicating that not alcohol but hepatitis B virus, in fact induces the mutations in p53 gene. In addition, it has been shown that the p53 mutation was significantly associated with the diameter of tumor nodule and the degree of cellular differentiation in hepatocellular cancer. The p53 mutation rate found in our study is concordant for a geography where hepatitis B virus and hepatitis C virus are common. Hepatitis B virus and possibly hepatitis C virus, but not alcohol, should be responsible, to a degree, for the mutational change in p53 protein in hepatocellular cancer patients with chronic liver disease. The p53 mutation is a late event in hepatocarcinogenesis because it is related with cellular differentiation and tumor diameter. The specific ELISA can be a useful screening test in future studies to select the patients for gene therapy using wild-type p53.Öğe Docetaxel concomitant with radiotherapy in patients with nonsmall cell lung cancer unresponsive to platinum-based induction chemotherapy(Elsevier Ireland Ltd, 2005) Ozkok, S; Yalman, D; Goker, E; Parvizi, M; Cok, G; Goksel, T; Haydaroglu, AÖğe The effect of Taxol treatment on serum interleukln-8 (IL-8) levels in patients with ovarian carcinoma.(Amer Assoc Cancer Research, 1999) Uslu, R; Ozsaran, A; Sanli, UA; Dikmen, Y; Goker, ENT; Goker, EÖğe Endobronchial metastasis from osteosarcoma of bone - Treatment with intraluminal radiotherapy(Amer Coll Chest Physicians, 1999) Mogulkoc, N; Goker, E; Atasever, A; Veral, A; Ozkok, S; Bishop, PWLung parenchymal metastases are common manifestations in patients with osteosarcoma; however, spread to the major airway itself is extremely rare. We present a young man who had been previously treated with surgical resection following preoperative chemotherapy and immediate postsurgical adjuvant chemotherapy for proximal tibial osteosarcoma. He developed metastasis to the major airways. The patient was treated with intraluminal radiotherapy (ILT) for the endobronchial metastasis. This is the first report of an endobronchial osteosarcoma that was treated with ILT with a complete endoscopic response. ILT provided excellent palliation in this particular case.Öğe Gemcitabine treatment in patients with inoperable locally advanced/metastatic pancreatic cancer and prognostic factors(Taylor & Francis Ltd, 2005) Sezgin, C; Karabulut, B; Uslu, R; Sanli, UA; Goksel, G; Yuzer, Y; Goker, EObjective. Most patients with pancreatic cancer show an inoperable locally advanced/ metastatic tumour at the time of diagnosis. The present study was aimed at determining the prognostic factors in patients with advanced pancreatic carcinoma treated with gemcitabine. Material and methods. Sixty- seven unresectable or metastatic pancreatic cancer patients treated with gemcitabine were included in the study and a total of 258 cycles of treatment were applied. Results. The overall response rate was 5%. Thirty- one percent of the patients had stable disease, whereas progressive disease was seen in 49%. Clinical benefit response rate was 15%. The median duration of response was 7.3 months. Median progression- free survival was 3 months, while median overall survival was 9 months. Univariate analysis revealed that worse results were found in patients with performance status ( PS) = 2, and in patients with primary tumour location in the body or tail of the pancreas ( p < 0.05). Multivariate analysis of data revealed that the most important factor was PS of the patient, as the patients with PS = 2 had worse results than the patients with PS = 0 - 1 ( p < 0.05). Conclusions. Low PS is a negative predictive factor for the survival of patients with advanced pancreatic carcinoma treated with gemcitabine.Öğe Randomized phase 3 trial of irinotecan (CPT-11)+5FU/folinic acid (FA) vs CDDP+5FU in 1(st)-line advanced gastric cancer patients(Amer Soc Clinical Oncology, 2005) Dank, M; Zaluski, J; Barone, C; Valvere, V; Peschel, C; Wenczl, M; Goker, E; Risse, ML; Awad, L; Bugat, RÖğe Successful treatment of liver transplant-associated Kaposi's sarcoma with long-term vincristine(Elsevier Science Inc, 2005) Akay, S; Karasu, Z; Akyildiz, M; Tokat, Y; Goker, EKaposi's sarcoma has a higher incidence in organ transplant recipients. We report on a 41-year-old Turkish man with liver transplantation-associated Kaposi's sarcoma that involved the skin and the gut. Immediately after discontinuation of immunosuppressive medication, there was an acute rejection episode. After controlling the acute rejection with steroids, the immunosuppressive treatment was continued together with vincristine, which resulted in disease remission. After 6 months, withdrawal of vincristine lead to relapse of the disease, prompting commencement of vincristine again, which has maintained the patient in remission for more than 3 years without any significant side effects. In conclusion, long-term vincristine may be an effective, safe treatment option for Kaposi's sarcoma.Öğe Therapy, outcome and analysis of c-kit expression in patients with extrapulmonary small cell carcinoma(Blackwell Publishing Ltd, 2005) Kurt, E; Sezgin, C; Evrensel, T; Yalcinkaya, U; Kanat, O; Veral, A; Demiray, M; Arslan, M; Karabulut, B; Ercan, I; Goker, E; Manavoglu, OIn this study, we aimed to investigate the clinicopathological characteristics with special emphasis on c-kit expression and the treatment results of patients with extrapulmonary small cell carcinoma (EPSCC). The medical records of the patients with EPSCC were reviewed, and the data regarding patient and tumour characteristics, treatment and clinical outcome were retrieved and analysed. A total of 28 patients with the diagnosis of EPSCC were identified. There were 19 males and 9 females, with a mean age of 56.5 years. Patients with limited disease (LD) (n = 13) were treated with surgery, chemotherapy (CT) and radiotherapy with different sequences. Patients with extensive disease (ED) (n = 15) were mainly treated with combination CT. The median overall survival was 14.5 months in patients with LD compared to 11 months in those with ED (p = 0.029). Ten patients (36%) showed c-kit overexpression. There was no significant difference between the survival of c-kit-positive and c-kit-negative patients (p = 0.367). In conclusion, our study demonstrates that the prognosis of EPSCC is poor despite currently available treatments. C-kit may be considered as a potential target for novel therapeutical approaches.Öğe Which dosing scheme is suitable for the taxanes? An in vitro model(Pharmaceutical Society Korea, 2002) Sanli, UA; Uslu, R; Karabulut, B; Sezgin, C; Saydam, G.; Omay, SB; Goker, EThe discovery and development of the taxane class of antitumor compounds represent significant advances in the treatment of patients with a variety of malignancies. These drugs are effectively used in the treatment of breast cancer. In this study we evaluated the efficacy of fractionated usage of both paclitaxel and docetaxel as a single agent in the breast cancer cell line MCF-7. It has been shown that the cytotoxic effect of paclitaxel was increased when the divided IC50 concentrations were used sequentially and in contrast to paclitaxel, cytotoxic effect of docetaxel was decreased with the same schema and the single dose Of IC50 concentration was optimal. The cause of the difference between the cytotoxic effects of two agents with this schedule is obscure. Demonstrating mechanisms, which are responsible for these differences, will be important for more rational use of taxoids and to provide basis for the following clinical trials.
