Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - Scopus: 1Prognostic Significance of the Igvh Mutation Status and Immunohistochemical Analysis of Zap70 and Cd38 in Bone Marrow Biopsies in Chronic Lymphocytic Leukemia(Türkiye Klinikleri Journal of Medical Sciences, 2014) Kahraman Çetin, Nesibe; Kaçar Döger, Füruzan; Kurtgöz, Serkan Erkan; Rusçuklu, Dane; Yavaşoğlu, İrfanObjective: Chronic lymphocytic leukemia (CLL) is one of the most common leukemia type among adults in the industrialized countries. Due to the nature of CLL, it is important to recognize patients with a more rapid course of disease. The goal of our study was to study ZAP70 and CD38 antibodies along with immunglobulin heavy chain variable region (IgVH) mutation status, which have been associated with rapid progression and aggressive clinical course in CLL, and to correlate the expression of these molecules with patterns of bone marrow infiltration. Material and Methods: We included 84 bone marrow biopsy samples into the study to determine ZAP70 and CD38 status using immunohistochemistry. Expression patterns for both antibodies were then correlated with the bone marrow infiltration patterns. We also analyzed IgVH mutations in 20 patients using DNA obtained from paraffin-embedded formalin-fixed bone marrow biopsies. These findings were then correlated with immunohistochemical results. Results: We identified a positive correlation between the expression patterns of ZAP70 and CD38, factors that were previously identified as poor prognostic factors (p<0.001). However, there was no correlation between these two markers and IgVH mutation status (p=1.000 and p=0.931). In addition, we showed a statistically significant positive correlation with ZAP70 immunostaining, and the necessity for an early intervention (p=0.046). ZAP70 and CD38 expressions were statistically significantly correlated with the diffuse pattern infiltration of bone marrow (p<0.001 and p<0.001, respectively). Conclusion: Despite small number of our patients, the findings of our study suggested that ZAP70 and CD38 expression patterns as well as IgVH mutation status might be helpful to determine the course of the disease, and the risk of progression. Particularly ZAP70 immunopositive patients appear to have a faster disease progression, and may require earlier intervention and a closer follow up.Article Citation - WoS: 6Citation - Scopus: 6Bioactive Sphingolipids in Response To Chemotherapy: a Scope on Leukemias(Bentham Science Publishers B.V., 2011) Ekiz, Hüseyin Atakan; Baran, YusufSphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that have important roles in the regulation of cell death, survival and chemotherapeutic resistance. Some of those species are known to accumulate in the cells upon chemotherapy while some others are known to exhibit an opposite pattern. Even though the length of fatty acid chain has a deterministic effect, in general, upregulation of ceramides and sphingosine is known to induce apoptosis. However, S1P, C1P and GluCer are proliferative for cells and they are involved in the development of chemoresistance. Therefore, sphingolipid metabolism appears as a good target for the development of novel therapeutics or supportive interventions to increase the effectiveness of the chemotherapeutic drugs currently in hand. Some approaches involve manipulation of the synthesis pathways yielding the increased production of apoptotic sphingolipids while the proliferative ones are suppressed. Some others are trying to take advantage of cytotoxic sphingolipids like short chain ceramide analogs by directly delivering them to the malignant cells as a distinct chemotherapeutic intervention. Numerous studies in the literature show the feasibility of those approaches especially in acute and chronic leukemias. This review compiles the current knowledge about sphingolipids and their roles in chemotherapeutic response with the particular attention to leukemias. © 2011 Bentham Science Publishers Ltd.Article Citation - WoS: 4Citation - Scopus: 7The Importance of Protein Profiling in the Diagnosis and Treatment of Hematologic Malignancies(Galenos Yayıncılık, 2011) Şanlı Mohamed, Gülşah; Turan, Taylan; Ekiz, Hüseyin Atakan; Baran, YusufProteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemiaassociated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high-throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed.Article Citation - WoS: 31Citation - Scopus: 36Quercetin-Induced Apoptosis Involves Increased Htert Enzyme Activity of Leukemic Cells(Taylor and Francis Ltd., 2011) Avcı, Çığır Biray; Yılmaz, Sunde; Doğan, Zeynep Özlem; Saydam, Güray; Dodurga, Yavuz; Ekiz, Hüseyin Atakan; Kartal, Melis; Şahin, Fahri; Baran, Yusuf; Gündüz, CumhurWe aimed to examine the growth suppressive effects of quercetin on acute promyelocytic and lymphoblastic leukemia and chronic myeloid leukemia, and to find out whether the growth suppression is related to the blocking of telomerase enzyme activity. Cytotoxic effects of quercetin were shown by trypan blue analyses. Apoptotic effects of quercetin were examined by acridine orange and ethidium bromide staining by fluorescence microscopy. The effects of quercetin on telomerase enzyme activity were shown by hTERT Quantification Kit. Our results demonstrated that quercetin has antiproliferative and apoptotic effects on T-cell acute lymphoblastic leukemia (ALL), acute promyelocytic leukemia, and chronic myeloid leukemia (CML) cells. We also showed for the first time by this study that quercetin suppresses the activity of telomerase in ALL and CML cells. The results of this study show the importance of quercetin for its therapeutic potential in treatment of leukemias.Article Citation - WoS: 23Citation - Scopus: 25Role of Autophagy in the Progression and Suppression of Leukemias(Elsevier Ltd., 2012) Ekiz, Hüseyin Atakan; Can, Geylani; Baran, YusufAutophagy is a physiological process in which cellular components are degraded by the lysosomal machinery. Thereby, organelles are recycled and monomers are produced in order to maintain energy production. Current studies indicate autophagy might suppress or augment survival of cancer cells. Therefore, by elucidating the role of autophagy in cancer pathogenesis, novel therapeutic intervention points may be revealed. Leukemia therapy has advanced in recent years; but a definitive cure is still lacking. Since autophagy often is deregulated in this particular type of cancer, it is clear that future findings will have clinical implications. This review will discuss the current knowledge of autophagy in blood cancers. © 2011 Elsevier Ireland Ltd.Article Citation - WoS: 32Citation - Scopus: 34Therapeutic Applications of Bioactive Sphingolipids in Hematological Malignancies(John Wiley and Sons Inc., 2010) Ekiz, Hüseyin Atakan; Baran, YusufSphingolipids are sphingosine-based lipid molecules that have important functions in cellular signal transduction and in a variety of cellular processes including proliferation, differentiation, programmed cell death (apoptosis) and responses to stressful conditions. Ceramides, dihydroceramide, sphingosine and sphingosine-1-phosphate are examples of those bioactive sphingolipids. They have a major impact on determination of the cell fate by contributing to the cell survival or cell death through apoptosis. Despite the number of carbon atoms in the fatty acid chain changes the physiological role; ceramides generally exert suppressive roles on the cell proliferation. There have been several enzymes identified in this pathway that are responsible for the conversion of ceramide into other sphingolipid derivatives. Those derivatives also have differential roles on those cellular processes. Sphingosine-1-phosphate is an example of such sphingolipid derivatives which has antiapoptotic effects. As they have significant impacts particularly on the cell death and survival, bioactive sphingolipids have a great potential to be targets in cancer therapy. Increasing number of studies indicates that sphingolipid derivatives are important in the progression of hematological malignancies, and they are also involved in the resistance to current chemotherapeutic options. This review compiles the current knowledge in this area for enlightening the therapeutic potentials of bioactive sphingolipids in various leukemias. © 2010 UICC.