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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
    Coexistence of different tissue tumourigenesis in an N-methyl-N-nitrosourea-induced mammary carcinoma model: a histopathological report in Sprague-Dawley rats
    (Royal Soc Medicine Press Ltd, 2009) Esendağlı, Güneş; Yılmaz, G.; Canpınar, Hande; Günel-Özcan, Ayşen; Güç, M. Oğuz; Güç, Dicle
    N-methyl-N-nitrosourea (MNU), a highly potent carginogen, is widely used to generate mammary tumours in murine species. In a model of MNU-induced mammary carcinogenesis using immature female Sprague-Dawley rats, large mammary tumours (largest dimension >= 0.5 cm) were obtained within a very short period of time. In addition, in the rats bearing MNU-induced mammary carcinomas, there were a number of tumours whose origins were not from mammary tissue but from several different tissues and from mammary non-epithelial tissue. The tumours were of mesenchymal or epithelial origin and they were located in the inguinal region. These tumours were diagnosed as fibroadenoma, combined tubular adenoma and fibroadenoma, hyperkeratotic papilloma, keratinous cyst and malignant peripheral nerve sheath tumour (MPNST) with smooth muscle differentiation. The occurrence of these other tumours in addition to the development of the mammary carcinomas may be attributed to a direct local effect of the intraperitoneal administration of MNU during the sexual development of the immature rats. In the MNU-induced mammary tumour model, coexistence of tumourigenesis in various non-mammary tissues should be considered an important factor that may interfere with experimental procedures and results and also the quality of life of the tumour-bearing animals.
  • Küçük Resim
    Öğe
    HFE H63D mutation frequency shows an increase in Turkish women with breast cancer
    (Bmc, 2006) Günel-Özcan, Ayşen; Alyılmaz-Bekmez, Sibel; Güler, Emine Nilüfer; Güç, Dicle
    Background: The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls. Methods: Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP. Results: All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176) in the breast cancer patients, and 14% (28/200) in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers ( P = 0.02). Conclusion: Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios ( odds ratio = 2.05) computed in this study suggest that H63D has a positive association with breast cancer.
  • Küçük Resim
    Öğe
    Molecular and functional analysis of a novel recombinant clone of rat (Rattus norvegicus) CD40 ligand (CD40L) gene
    (Springer, 2009) Esendağlı, Güneş; Günel-Özcan, Ayşen; Canpınar, Hande; Güç, Dicle
    Genetic material obtained from various individuals may contain certain polymorphisms which may conflict with the predetermined DNA sequence and consequently, may modulate the function of gene products. In this study, coding sequence of rat CD40 ligand (CD40L, CD154) was obtained from activated splenocytes, amplified, and cloned into a eukaryotic expression vector by using directional cloning method. Sequence of the recombinant rat CD40L DNA, pCD40L-IRES2-EGFP (pCD40L), was compared with the previously reported rat CD40L cDNA sequences and a 99% identity was found. Differing nucleotides were on the positions; 122-T/C, 341-G/A, 476G/A, 762-T/A. Further alignment analysis showed that pCD40L was collectively carrying the nucleotides each previously reported by different groups. The sequence was submitted to NCBI GenBank and nucleotide database accession number EF066490 was obtained. Following transfection of the construct into NIH/3T3 cell line, novel CD40L clone was functionally expressed de novo, increasing the expression of CD80 and CD86 costimulatory molecules and augmenting the proliferation rate of effector splenocytes in immune reactions ex vivo. Based on these data, here we report a novel recombinant clone of the rat CD40L gene which may represent a potential polymorphic variant.
  • 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.
  • [ X ]
    Öğe
    Salmonella typhimurium aroB-encoding murine IL-18 or CD40L: evaluation for gene therapy
    (Blackwell Publishing, 2006) Aydın, Duygu; Guünel-Özcan, Ayşen; Menager, N.; Esendağlı, Güneş; Güç, M. O.; Hayran, M.; Güç, Dicle
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