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  • Küçük Resim
    Öğe
    Adhesion of beta 1 integrin to fibronectin regulates CAM-DR phenotype via p21 in HL60 acute myeloid leukemia (AML) cells
    (2008) Canpınar, Hande; Esendağlı, Güneş; Kansu, Emin; Özcan, Ayşen Günel; Güç, Dicle
    Genel Bilgiler: İlaç direnci, kanser tedavisinin başarısında büyük zorluktur. Hücre adezyon aracılı ilaç direnci (CAM-DR), kanser hücrelerinin mikroçevre ile ilişkisiyle gelişen, çeşitli tümörlerde gösterilen yeni bir ilaç direncidir. Bu çalışma da, HL60 AML hücrelerinde CAM-DR fenotipi analiz edildi. Yöntem: HL60 hücrelerin fibronektine bağlanması kolorimetrik adezyon deneyi ile yapıldı. Doksorubisin ile indüklenen apoptozis ve hücre siklusu akım sitometrik analiz ile belirlendi. [3H]-timidin inkorporasyon deneyi ile proliferasyon hızı değerlendirildi. Hücre siklusunu kontrol eden proteinler, western blot ve RT-PCR analizi ile belirlendi. Bulgular: HL60 hücrelerinin a4pM and oc5pi integrin aracılığı ile fibronektine bağlanmasıyla CAM-DR fenotipi oluşmuştur, aderent HL60 hücreleri doksorubisin ile tetiklenen apoptozise dirençli hale geçmiştir. Fibronektine aderan/yapışan HL60 hücrelerinde hücre siklusunun GQ/G, fazında birikimi ile hücre proliferasyonu durmuştur. Buna karşılık, fibronektinden" sökülen hücreler 8 saat sonra tekrar sentez fazına girerek apoptozise duyarlı hale gelmiştir. Hücre siklusunun GQ/G, kontrol noktalarının analizi, CAM-DR fenotipinin p21waf/cıp proteini ile düzenlendiğini göstermiştir. Sonuç: Bu çalışmada, CAM-DR fenotipininin AML blastlarında apoptozisi azaltan ve proliferasyonu durduran geri dönüşümlü bir ilaç direnci mekanizması olabileceğini gösterdik.
  • Küçük Resim
    Öğe
    Adhesion of beta1 integrin to fibronectin regulates CAM-DR phenotype via p21(WAF1/cip1) in HL60 acute myeloid leukemia (AML) cells
    (Tubitak Scientific & Technical Research Council Turkey, 2008) Canpinar, Hande; Esendagli, Gunes; Kansu, Emin; Ozcan, Aysen Gunel; Guc, Dicle
    Aims: Drug resistance is a major obstacle for a successful cancer therapy. Cell adhesion mediated drug resistance (CAM-DR) is a novel type of drug resistance and generated via interaction of cancer cells with the microenvironment. In this study, CAM-DR phenotype was analyzed in HL60 acute myeloid leukemia (AML) cells. Materials and Methods: Fibronectin (FN) adherence of HL60 cells was tested by a colorimetric adhesion assay. Flow cytometry analyses were performed to evaluate doxorubicin-incluced apoptosis and to determine cell cycle status. Proliferation rate was evaluated by [H-3]-thymidine incorporation assay. Western blot and RTPCR were used for analysis of the factors involved in cell cycle control. Results: Binding of HL60 to FN via alpha 4 beta 1 and alpha 5 beta 1 integrins exerted a CAM-DR phenotype, which shows resistance to apoptosis triggered by doxorubicin. FN-adherent HL60 cells accumulated in the G(0)/G(1) phase of cell cycle and stopped proliferation. However, after detachment from FN, cells entered S phase, proliferated, and became sensitive to apoptosis. The analysis of the factors involved in the G(0)/G(1) cell cycle checkpoint showed that CAM-DR phenotype might be regulated mainly by p21(waf/cip). Conclusions: Here we showed that CAM-DR may also represent a reversible drug resistance mechanism that decreases apoptosis and causes growth arrest in AML blasts.
  • Küçük Resim
    Öğe
    Primary tumor cells obtained from MNU-induced mammary carcinomas show immune heterogeneity which can be modulated by low-efficiency transfection of CD40L gene
    (Taylor & Francis Inc, 2009) Esendağlı, Günşs; Canpınar, Hande; Yılmaz, Güldal; Gunel-Ozcan, Aysen; Güç, M. Oğuz; Kansu, Emin; Güç, Dicle
    The presence of CD40 on carcinoma cells is an important factor for the generation of tumor-specific responses induced by CD40 ligation. In an N-methyl-N-nitrosourea (MNU)-induced autochthonous mammary tumor model, we analyzed the immune features of primary tumor cells. Here, CD40 was frequently detected on the primary tumor cultures and selectively expressed on the malignant mammary tissue in vivo. On the other hand, every mammary tumor cell culture had a heterogeneous and reduced expression of proinflammatory TNF alpha, IL-1 beta, IL-6 and CXCL1 cytokines compared to normal mammary epithelial cells. Low-efficiency transfection of CD40 ligand (CD40L) gene enhanced the expression of proinflammatory cytokines in the tumor cells, and strengthened allogeneic immune reactions and costimulatory activity which may help overwhelming suppressive features of the tumor.