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Öğe Alveolar rhabdomyosarcoma originating from the uterine cervix(I R O G Canada, Inc, 2011) Cakar, B.; Muslu, U.; Karaca, B.; Junushova, B.; Uslu, R.; Goker, E.Cervical alveolar rhabdomyosarcoma is a rare condition associated with poor prognosis. An 18-year-old patient presented with vaginal bleeding and a protruding mass from the vagina. Biopsy of the mass revealed alveoler rhabdomyosarcoma (ARMS), and radiological evaluation demonstrated that it originated from the uterine cervix. First, Wertheim's operation was carried out followed by four cycles of vincristine, actinomycine-D, ifosfamide (VAI) chemotherapy. However, the disease relapsed within three months, and the patient died of disease progression. Despite combination treatment, we could not achieve a desirable survival advantage in ARMS. Future studies may unveil the genomic profile of this rare condition, leading to invention of targeted therapies, which is the emerging trend in the treatment of sarcomas.Öğe AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells(Springer, 2018) Yurekli, B. S.; Karaca, B.; Kisim, A.; Bozkurt, E.; Atmaca, H.; Cetinkalp, S.; Ozgen, G.; Yilmaz, C.; Uzunoglu, S.; Uslu, R.; Saygili, F.Purpose Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.Öğe A DIVERSE INDUCTION OF APOPTOSIS BY TRABECTEDIN IN MCF-7 (HER2-/ER+) AND MDA-MB-453 (HER2+/ER-) BREAST CANCER CELLS(Oxford Univ Press, 2013) Atmaca, H.; Bozkurt, E.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe A DIVERSE INDUCTION OF APOPTOSIS BY TRABECTEDIN IN MCF-7 (HER2-/ER+) AND MDA-MB-453 (HER2+/ER-) BREAST CANCER CELLS(Oxford Univ Press, 2013) Atmaca, H.; Bozkurt, E.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells(Wiley, 2009) Karabulut, B.; Erten, C.; Gul, M. K.; Cengiz, E.; Karaca, B.; Kucukzeybek, Y.; Gorumlu, G.; Atmaca, H.; Uzunoglu, S.; Sanli, U. A.; Baran, Y.; Uslu, R.Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.Öğe Does the tumor localization in advanced pancreatic cancer have an influence on the management of symptoms and pain?(Imprimatur Publications, 2010) Eyigor, C.; Karaca, B.; Kuzeyli-Yildirim, Y.; Uslu, R.; Uyar, M.; Coker, A.Purpose: The symptoms and survival of patients with advanced pancreatic cancer show great variability according to tumor localization. The main purpose of this study was to see for any differences between the intensity of symptoms, mainly pain, and the need for analgesic treatment in advanced pancreatic cancer patients with different (head vs. body-tail) tumor localizations. Methods: Ninety-six patients with histologically confirmed pancreatic cancer were enrolled in the study. The patients were divided into 2 subgroups according to tumor localization: group 1 (n=50) with head tumors and group 2 (n=46) with body and tail tumors. The demographic features of the patients as well as disease stages, onset of symptoms and necessity and consumption of analgesics were recorded. Patients were followed-up until death, and survival data was also analysed. Results: At the time of diagnosis, patients with body and tail tumors had more advanced disease stages compared to head tumors (p=0.006). While jaundice was the most common initial symptom in head tumors (p<0.0001), it was pain in body and tail tumors (p<0.001). Patients with body and tail tumors had more analgesics consumption as compared to those with head tumors (p=0.009). No statistically significant difference in survival was detected between the 2 groups (p>0.05). Conclusion: We believe that pancreatic cancer should be accepted as two diverse disease types according to tumor localization, and pain and symptom management should be organized based on this fact.Öğe Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients(Wiley, 2013) Ergun, M.; Eyigor, S.; Karaca, B.; Kisim, A.; Uslu, R.The aim of this study was to explore the effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in patients who completed breast cancer treatment. Sixty breast cancer patients were randomised into three groups, as supervised exercise group, home exercise group and education group. Angiogenesis and apoptosis-related cytokine levels and quality of life (EORTC QOL-C30: European Organisation for Research and Treatment of Cancer Quality of Life C30), fatigue (Brief Fatigue Inventory) and depression (BDI: Beck Depression Inventory) scores were compared before and after a 12-week exercise programme. After the exercise programme, statistically significant decreases were found in interleukin-8 and neutrophil activating protein-78 levels in the home exercise group (P < 0.05). The education group showed a statistically significant increase in monocyte chemoattractant protein-1 level (P < 0.05). Functional score and global health score of EORTC QOL-C30 in the supervised exercise group and functional score of EORTC QOL-C30 in the home exercise group increased significantly after exercise programme (P < 0.05). BDI score was significantly lower in the supervised exercise group after the exercise programme (P < 0.05). Changes in angiogenesis and apoptosis-related molecules in the study groups suggest a possible effect of exercise on these parameters. Exercise programmes are safe and effective on quality of life and depression in breast cancer patients whose treatments are complete.Öğe Efficacy and safety of bevacizumab plus capecitabine and irinotecan regimen for metastatic colorectal cancer(Humana Press Inc, 2010) Degirmenci, M.; Karaca, B.; Gorumlu, G.; Durusoy, R.; Piskin, G. Demir; Bozkurt, M. T.; Cirak, Y.; Tunali, D.; Karabulut, B.; Sanli, U. A.; Uslu, R.Recent phase III trials have proven the fact that adding bevacizumab to irinotecan plus infusional 5-fluorouracil (5-FU)/leucovorin (LV) should be preferred as a first-line treatment for metastatic colorectal cancer (mCRC). But, since the data regarding bevacizumab administered together with capecitabin, an oral fluoropyrimidine, and irinotecan in patients with mCRC is limited, we aimed to analyse the efficacy and safety of bevacizumab with capecitabine plus irinotecan (BEV-CAPIRI) regimen in mCRC patients. Records of patients treated with BEV-CAPIRI regimen between January 2005 and March 2008 were reviewed. Efficacy data regarding response rates (RR) as well as safety data were collected. Progression free survival (PFS) and overall survival (OS) analyses were done by using the Kaplan-Meier method. A total number of 53 metastatic colorectal cancer patients were treated with BEV-CAPIRI regimen. The median age of this population was 57.3 +/- 11.5 (range 29-78). The treatment was well tolerated. The RR was 43.3%, while 30.1% of the patients achieved stable disease (SD). Median PFS and OS were 12.6 +/- 1.4 and 20.6 +/- 1.7 months, respectively. However, median OS was 21.3 months for male and 14.6 months for female patients. In addition, median OS and PFS was 25.3 months and 16.2 months for the patients who received BEV-CAPIRI as first-line treatment, respectively, and for the other patients it was 15.2 months and 10.2 months, respectively. In conclusion, BEV-CAPIRI is an effective and well-tolerated alternative regimen for mCRC, leading to disease control in a vast majority of patients with mCRC.Öğe Enhancement of taxane-induced cytotoxicity and apoptosis by gossypol in human breast cancer cell line MCF-7(Imprimatur Publications, 2009) Karaca, B.; Atmaca, H.; Uzunoglu, S.; Karabulut, B.; Sanli, U. A.; Uslu, R.Purpose: Gossypol is a natural polyphenolic compound extracted from cotton plant (Gossypium species) which has shown potent inhibitory effect on cell growth of many types of cancers. In this study, we aimed to evaluate the interaction of gossypol with some conventional drugs known to be effective in the treatment of breast cancer like taxanes, doxorubicin, gemcitabine, cisplatin and vinorelbine, in MCF-7 breast cancer cells. Materials and methods: The XTT viability assay was used to evaluate the cytotoxicity of various cytotoxic agents alone and in combination with gossypol in MCF-7 breast cancer cells. The combination effect analysis of Chou and Talalay was used to identify the most synergistic drug combinations. The possible synergistic effects of the combination of drugs on apoptosis were also evaluated by using two different apoptosis assays. Results: We identified strong synergistic cytotoxic and apoplotic activity of gossypol with taxanes among all other studied cytotoxic drugs. Conclusion: This study provides proof that gossypol combined with taxanes may have potential as a novel future treatment for breast cancer.Öğe Environmentally Benign Alternatives: Plasma and Enzymes to Improve Moisture Management Properties of Knitted PET Fabrics(Korean Fiber Soc, 2010) Karaca, B.; Demir, A.; Ozdogan, E.; Ismal, O. E.Effects of enzymatic and atmospheric plasma treatments individually and their combinations on knitted PET fabrics were investigated in terms of hydrophilicity, surface modification and moisture management properties. Cutinase from Humicola Insolens, lipase from Candida SP and atmospheric plasma with air and argon gases were applied to PET fabrics. To evaluate results, moisture management tester (MMT) and scanning electron microscopy (SEM) were utilized. Wicking heights of samples were measured by wicking test method. Improved moisture management properties were observed with environmentally benign processes compared to the untreated ones. Especially combined treatments have given the same or slightly better results than those of conventional alkaline treatments. Fabrics treated with plasma and then followed by enzymatic incubations have significantly improved the wetting time, absorption rates and spreading speed results.Öğe Evaluation of the efficacy of adjuvant chemotherapy in patients with high-risk stage II colon cancer(Imprimatur Publications, 2013) Cakar, B.; Varol, U.; Junushova, B.; Muslu, U.; Oner, P. Gursoy; Surmeli, Z. Gokhan; Cirak, Y.; Karaca, B.; Sezgin, C.; Karabulut, B.; Uslu, R.Purpose: This study aimed at comparing the disease-free survival (DFS) in high-risk TNM stage II colon cancer patients who had been subjected to adjuvant chemotherapy and TNM low-risk stage II patients who did not receive chemotherapy. Methods: : We retrospectively reviewed the medical records of stage II colon cancer patients between January 2006 and December 2011. High-risk patients were defined those with any colonic obstruction/perforation, mucinous histology, inadequate lymph node sampling, T4 disease, lymphatic/vascular or perineural invasion, preoperatively elevated carcinoembryonic antigen (CEA) and high-grade tumor. All patients with high-risk features received adjuvant chemotherapy. Results: There were 42 patients in the high-risk treatment group and 21 patients in the non-treatment (observation) group. There were no significant differences in terms of gender, tumor size, tumor localization, or the number of excised lymph nodes between the groups. The median follow-up time was 33.9 months in the treatment group and 29.3 months in the non-treatment group. Recurrence developed in 4 patients (6.3%), 3 of which were in the treatment group. DFS in both groups was statistically similar. Conclusion: Adjuvant chemotherapy in the high-risk patients resulted in similar DFS as that in the low-risk patients. Although the role of adjuvant chemotherapy for stage II colon cancer is unclear, it is rational to offer adjuvant chemotherapy to patients with high-risk stage II colon cancer.Öğe FIBROBLAST GROWTH FACTOR RECEPTOR 2 (FGFR2) POLYMORPHISM STATUS OF TURKISH BREAST CANCER PATIENTS(Oxford Univ Press, 2010) Uslu, R.; Karaca, B.; Atmaca, H.; Kisim, A.; Cakar, B.; Karabulut, B.; Sezgin, C.; Uzunoglu, S.Öğe THE IMPRESSION WE GIVE TO PATIENTS WHEN BREAKING BAD NEWS: A MULTICENTER STUDY IN A TURKISH CANCER POPULATION(Oxford Univ Press, 2010) Yaman, E.; Yamac, D.; Turhal, S.; Karaca, B.; Coskun, H. S.; Komurcu, S.; Yavuzsen, T.; Dane, F.; Nalca, M.; Akmansu, M.Öğe Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K-AKT pathway(Springer-Verlag Italia Srl, 2015) Dirican, A.; Atmaca, H.; Bozkurt, E.; Erten, C.; Karaca, B.; Uslu, R.The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways. We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC.Öğe P53 MODULATES TRABECTEDIN MEDIATED CYTOTOXICITY IN GLIOBLASTOMA MULTIFORME CELLS (U-87MG AND T98G)(Oxford Univ Press, 2013) Bozkurt, E.; Atmaca, H.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe P53 MODULATES TRABECTEDIN MEDIATED CYTOTOXICITY IN GLIOBLASTOMA MULTIFORME CELLS (U-87MG AND T98G)(Oxford Univ Press, 2013) Bozkurt, E.; Atmaca, H.; Uzunoglu, S.; Uslu, R.; Karaca, B.Öğe A potent enantiomer of gossypol, AT-101: Screening of anti-angiogenic protein targets in glioblastoma multiforme cells(Elsevier Sci Ltd, 2013) Surmeli, Z.; Bozkurt, E.; Karaca, B.; Karabulut, B.; Sezgin, C.; Sanli, U. A.; Uslu, R.Öğe PREVALANCE AND CLINICOPATHOLOGICAL ASSESSMENT OF INFLAMMATORY BREAST CANCER PATIENTS DIAGNOSED BETWEEN 2000 AND 2008(Oxford Univ Press, 2009) Karaca, B.; Tunali, D.; Gorumlu, G.; Degirmenci, M.; Goker, E.Öğe Radiosensitization of hormone-refractory prostate cancer cells by gossypol treatment(Zerbinis Medical Publ, 2010) Akagunduz, O.; Karaca, B.; Atmaca, H.; Uzunoglu, S.; Karabulut, B.; Sanli, U. A.; Haydaroglu, A.; Uslu, R.Purpose: Many drugs have been tested to increase the sensitivity of prostate cancer cells to radiotherapy Gossypol, a natural polyphenolic compound extracted from the cotton plant, is one of the agents the efficacy of which has been investigated in the treatment of prostate cancer for this purpose. The main aim of this study was to investigate the best gossypol application with irradiation, when gossypol was applied either sequentially (24 h before and after irradiation) or concurrently in PC-3 hormone-refractory and radioresistant prostate cancer cells. Methods: The XTT viability assay was used to evaluate the cytotoxicity of different concentrations of gossypol in PC-3 cells. Irradiation was applied to PC-3 cells via 6 MV photon linear accelerator and delivered 24 h before, 24 h after radiation or at the same time with gossypol administration. Results: Gossypol caused radiosensitization of PC-3 cells that are known to be radioresistant, with high Bcl-2 levels. Among different applications of gossypol and irradiation (before, after and concurrent) in prostate cancer cells, the best results were observed by the application of gossypol 24 h before irradiation. Conclusion: Our study suggests that gossypol represents a promising novel anticancer treatment for radiosensitization of human hormone-refractory prostate cancer cells.Öğe Retrospective analysis of patients with relapsed or refractory testicular nonseminous germ cell tumors treated with autologous stem cell transplantation(Wolters Kluwer Medknow Publications, 2017) Yilmaz, F.; Soyer, N.; Uslu, R.; Erdogan, A. P.; Karaca, B.; Saydam, G.; Sahin, F.; Vural, F.BACKGROUND AND AIM: About 20-25% of the testicular germ cell tumors (TGCT) are relapsed or refractory after first line therapy and optimal treatment for this group is poorly defined. We aimed to analyze the efficacy and safety of autologous stem cell transplantation (ASCT) in this patient group. Material and METHODS: 19 patients with 28 ASCT were retrospectively analyzed. All the patients were treated with BEP (Bleomycin, etoposide, cisplatin) as first line therapy and TIP(paclitexalifosfamide, cisplatin) was given as salvage chemotherapy. Stem cell collection was performed with TIP and granulocyte stimulating factor. ASCT was performed with carboplatin(700mg/m2) and etoposite(750mg/m2). The results were provided as median(min-max). P< 0.05 was accepted as statistical significant level. RESULTS: After ASCT, complete(CR) and partial remission (PR) rates were 47.3% and 31.5% respectively. The median overall survival(OS) and progression free survival (PFS) were 18(0-37.4 months) and 7(0-15months) months respectively. Estimated 2-year OS was 47.4% and PFS was 35.3%. Grade 3/4 toxicities including diarrhea, mucositis, and toxic hepatitis were observed in 5 patients. Only one patient died due to complication of transplantation. CONCLUSION: Although the number of the patients in this study is limited, ASCT seems to be a safe and effective treatment modality in relapsed refractory non-seminomatousTGCT with an acceptable OS, PFS and mortality rates.
