Browsing by Author "Saydam, Güray"

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Expression levels of JAK/STAT signaling genes in newly diagnosed, drug sensitive and resistant chronic myeloid leukemia patients
(Izmir Institute of Technology, 2014) Kiraz, Yağmur; Baran, Yusuf; Saydam, Güray
JAK/STAT signaling pathway has a role in transmission of information carried by cytokines, from outside of the cell to the nucleus. The system is run by the proteins known as Janus kinases (JAK) located on the cell membrane and STAT proteins acting as signal transducer and activator of transcription. JAK proteins activated by cytokines, phosphorylates and initiates the dimerization of STATs, which become active, move into nucleus and regulate expression of target genes. Previous studies demonstrated that there is overexpression of JAK/STAT genes in various types of cancer. The aim of this study is to examine the relationship between expression levels of JAK/STAT genes and clinical outcome of chronic myeloid leukemia (CML) patients. In this study expression levels of Jak/STAT pathway genes were analyzed in 23 different patients (1 patient responded positively, 1 only imatinib and 1 both imatinib and nilotinib resistant patients, 1 patient lost molecular response, 5 imatinib treated, and 14 newly diagnosed CML patients). The results showed that expression levels of Jak3, STAT1, STAT2, STAT3, STAT4 and STAT5A genes were overexpressed in TKI resistant patients. Expression levels of STAT5B, Jak1, Jak2 and Tyk2 genes were higher in newly diagnosed patients compared to resistant patients while STAT1 was lower in imatinib-treated patients. It was demonstrated for the first time that there is a relation between the clinical outcome of CML patients and expression levels of JAK-STAT genes that could make this signaling pathway a new target for more effective treatment of CML.
Synergistic apoptotic effects of bortezomib and methylstat inhibitor on different multiple myeloma cell lines
(Izmir Institute of Technology, 2015) Kacı, Fatma Necmiye; Baran, Yusuf; Saydam, Güray
Multiple myeloma is one of the common hematological malignancies that affects plasma cells. Bortezomib, proteasome inhibitor, is an anticancer agent used for the treatment of multiple myeloma while methylstat is a demethylase inhibitor having anticancer potential. In this study, we investigated antiproliferative and apoptotic effects of methylstat alone or in combination with bortezomib. We also examined the genes involved in methylstat induced apoptosis. Cytotoxic effects of bortezomib and methylstat on U266 and ARH77 cells were demonstrated by MTT cell proliferation assay. To understand the apoptotic effects of these agents, loss of mitochondrial membrane potential was investigated by JC-1 method while phosphatidylserine localization was investigated by Annexin V assay. Cell cycle analysis in response to Bortezomib and Methylstat alone or in their combination were measured by flow cytometry. Changes in expression profiles of 84 genes underlying apoptosis, cell cycle control, DNA damage repair, and invasion and metastasis in response to Methylstat were determined by PCR Array. Our results demonstrated that both bortezomib and methylstat have antiproliferative and aoptotic effects in a time and dose dependent manner. Combination of bortezomib and methylstat induced apoptosis significantly as compared to any agent alone. In conclusion, we suggest methylstat as candidate agent for the treatment of MM after in vivo analyses.