Browsing by Author "Avcu, Ferit"

Now showing 1 - 7 of 7

Citation Count: 12
Bisphosphonate treatment and radiotherapy in metastatic breast cancer
(Humana Press inc, 2008) Ural, A. Ugur; Avcu, Ferit; Baran, Yusuf; Baran, Yusuf
Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and high risk of pathologic fractures due to osteolysis. The treatment of breast cancer patients with bone metastases requires a multidisciplinary approach. Radiotherapy is an established treatment for metastatic bone pain. It may be delivered either as a localized low dose treatment for localized bone pain or systemically for more widespread symptoms. Bisphosphonates have been shown to reduce morbidity and bone pain from bone metastases when given to patients with metastatic bone disease. In vivo studies indicate that early bisphosphonates administration in combination with radiotherapy improves remineralization and restabilization of osteolytic bone metastases in animal tumor models. This review focused on a brief discussion about biology of bone metastases, the effects of radiotherapy and bisphosphonate therapy, and possible mechanisms of combination therapy in metastatic breast cancer patients.
Citation Count: 6
Effect of cobalt-60 (γ radiation) on multidrug-resistant multiple myeloma cell lines
(Portland Press Ltd, 2011) Mutlu, Pelin; Baran, Yusuf; Ural, A. Ugur; Avcu, Ferit; Dirican, Bahar; Beyzadeoglu, Murat; Gunduz, Ufuk; Baran, Yusuf
Emergence of resistance to chemotherapy and radiotherapy is a major obstacle for the successful treatment of MM (multiple myeloma). Prednisone, vincristine and melphalan are commonly used chemotherapeutic agents for the treatment of MM. In the current study, we examined the presence of possible cross-resistance between these drugs and gamma (gamma) radiation. Prednisone, vincristine and melphalan resistant RPMI-8226 and U-266 MM cells were generated by stepwise increasing concentrations of the drugs. The sensitive and resistant cells were exposed to 200- and 800 cGy gamma radiation, and proliferation was examined by XTT {2,3-bis(2-methoxy-4-nitro-5-sulfopheny1)-5-Rphenylamino)carbonyl]-2H-tetrazolium hydroxide) assay. The results showed that Prednisone- and melphalan-resistant RPMI-8226 cells were also cross-resistant to 200 and 800 cGy gamma radiation application, while vincristine-resistant cells did not show resistance. On the other hand, Prednisone-, vincristine- and melphalan-resistant U-266 cells showed cross-resistance to 200- and 800 cGy gamma radiation application. These results demonstrated that MM cells resistant to anticancer agents respond to radiation in different levels. These findings may be important in the clinical applications of radiation therapy in the treatment of vincristine resistant MM.
Citation Count: 36
A novel mechanism of dasatinib-induced apoptosis in chronic myeloid leukemia; ceramide synthase and ceramide clearance genes
(Springer, 2011) Gencer, Emel B.; Ural, Ali U.; Avcu, Ferit; Baran, Yusuf; Baran, Yusuf
Sphingolipids are bioeffector molecules that control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramides, the central molecule of sphingolipid metabolism, are inducer of apoptosis and inhibitors of proliferation. Sphingosine-1-phosphate (S1P) and glucosyleceramide, converted from ceramides by sphingosine kinase-1 (SK-1) and glucosyleceramide synthase (GCS) enzymes, respectively, inhibit apoptosis and develop resistance to chemotherapeutic drugs. In this study, we examined the therapeutic potentials of bioactive sphingolipids in chronic myeloid leukemia (CML) alone and in combination with dasatinib in addition to investigate the roles of ceramide-metabolizing genes in dasatinib-induced apoptosis. Cytotoxic effects of dasatinib, C8:ceramide, PDMP, and SK-1 inhibitor were determined by XTT cell proliferation assay. Changes in caspase-3 enzyme activity and mitochondrial membrane potential (MMP) were measured using caspase-3 colorimetric assay and JC-1 MMP detection kit. Expression levels of ceramide-metabolizing genes were examined by qRT-PCR. Application of ceramide analogs and inhibitors of ceramide clearance genes decreased cell proliferation and induced apoptosis. Targeting bioactive sphingolipids towards generation/accumulation of ceramides increased apoptotic effects of dasatinib, synergistically. It was shown for the first time that dasatinib induces apoptosis through downregulating expression levels of antiapoptotic SK-1 but not GCS, and upregulating expression levels of ceramide synthase (CerS) genes, especially CerS1, in K562 cells. On the other hand, dasatinib downregulates expression levels of both GCS and SK-1 and upregulate apoptotic CerS2, -5 and -6 genes in Meg-01 cells. Increasing endogenous ceramide levels and decreasing prosurvival lipids, S1P, and GC, can open the way of more effective treatment of CML.
Citation Count: 0
Optimization of transfection of green fluorescent protein in pursuing mesenchymal stem cells in vivo
(2008) Avcu, Ferit; Baran, Yusuf; Ural, Uğur; Elçi̇, Pınar; Sarper, Meral; Baran, Yusuf
Amaç: Yeşil floresan proteini (YFP), günümüzde hücre biyolojisi çalışmalarında tanımlayıcı gen ve hücre işaretleyici olarak kullanılmaktadır. YFP’nin oldukça önemli kullanım alanları farklı genlerin içerisine eklenerek bu genlerin farklı organizmalardaki ekspresyonlarının miktar tayininde ve canlı hücreler içerisinde işaretleyici olarak kullanılabilmesidir. Bu çalışmamızda doku tamiri amacıyla ve hayvanlara aktardığımız mezankimal kök hücrelerini (MKH) in vivo takip edebilmek amacı ile YFP genini içeren plazmid vektörünün MKH’lara aktarılmasını optimize etmeye çalıştık. Yöntem ve Gereçler: Bu amaçla YFP geni taşıyan phM-YFP plazmid vektörü ve MKH’lara plazmid vektörün aktarılması amacı ile Effectene Transfeksiyon kiti kullanılmıştır.Bulgular: Elde edilen sonuçlar, MKH’ların phM-YFP ile iki defa transfekte edilmelerinin tek bir defa transfekte edilmelerine göre daha yüksek oranda ve daha uzun süreli YFP ekspresyonu sağladığını göstermiştir.Sonuç: MKH’ların YFP ile işaretlenmesi çalışmalarında transfeksiyon kimyasallarının yeterli bir inkübasyondan sonra uzaklaştırılmasının ve transfeksiyon işleminin 48 saat arayla iki defa yapılmasının MKH’ların aktarıldığı doku veya canlılarda daha uzun süreli ve daha etkin bir şekilde takibine olanak sağlayacağı gösterilmiştir
Citation Count: 16
Roles of ceramide synthase and ceramide clearence genes in nilotinib-induced cell death in chronic myeloidleukemia cells
(Taylor & Francis Ltd, 2011) Camgoz, Aylin; Gencer, Emel Basak; Ural, Ali Ugur; Avcu, Ferit; Baran, Yusuf; Baran, Yusuf
In this study, we aimed to increase the sensitivity of human K562 and Meg-01 chronic myeloid leukemia (CML) cells to nilotinib by targeting bioactive sphingolipids, in addition to investigating the roles of ceramide metabolizing genes in nilotinib induced apoptosis. Cytotoxic effects of nilotinib, C8:ceramide, glucosyle ceramide synthase (GCS) and sphingosine kinase-1 (SK-1) inhibitors were determined by XTT cell proliferation assay and synergism between the agents was determined by isobologram analysis. Also, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) results demonstrated that expression levels of longevity assurance (LASS) genes in response to nilotinib were correlated with sensitivity to nilotinib. For the first time, The results of this study showed for the first time that nilotinib induces apoptosis through upregulating ceramide synthase genes and downregulating SK-1 in CML cells in addition to inhibition of BCR/ABL. On the other hand, manipulating bioactive sphingolipids toward generation/accumulation of ceramides increased the apoptotic effects of nilotinib in CML cells.
Citation Count: 1
A study of multiple drug resistance mechanisms improved against Bortezomib on multiple myeloma cell lines in vitro
(Amer Soc Hematology, 2007) Uyuklu, Tolga; Ural, A. Ugur; Sarper, Metal; Avcu, Ferit; Baran, Yusuf; Elci, Pinar; Akar, Nejat; Baran, Yusuf
[No Abstract Available]
Citation Count: 35
Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance
(Maney Publishing, 2007) Baran, Yusuf; Guer, Bala; Kaya, Pelin; Ural, Ali Ugur; Avcu, Ferit; Guenduez, Ufuk; Baran, Yusuf
The major problem in the treatment of acute myeloid leukemia (AML) patients results from multidrug resistance to administered anticancer agents. Drug resistance proteins, MDR1 and MRP1, which work as drug efflux pumps, can mediate the multidrug resistance of human leukemia cells. In this study, the mechanisms of resistance to doxorubicin-induced cell death in human HL60 AML cells were examined. Continuous exposure of cells to step-wise increasing concentrations of doxorubicin resulted in the selection of HL60/DOX cells, which expressed about 10.7-fold resistance as compared to parental sensitive cells. The expression analyses of MRP1 and MDR1 drug efflux proteins in doxorubicin-sensitive and -resistant HL60 cells revealed that there was an upregulation of MRP1 gene in HL60/DOX cells as compared to parental sensitive cells. On the other hand, while there was no expression of MDR1 gene in parental cells, the expression of MDR1 gene was upregulated in HL60/DOX cells. HL60/DOX cells also showed cross-resistance to cytosine arabinoside (Ara-c). This resistance was reversed by a combination therapy of Ara-c and cyclosporine A. However, the expression levels of CD15 and CD16 surface markers were significantly decreased in HL60/DOX cells.