Browsing by Author "Sezgin, C"

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    Radiolabeling fingolimod with technetium-99 m and evaluating its biological affinity by in vitro method
    Uygur, E; Parlak, Y; Karatay, KB; Sezgin, C; Gümüser, FG; Müftüler, FZB
    Fingolimod (FTY-720) is the first oral medication approved by the food and drug administration (FDA) for the treatment of multiple sclerosis. It acts on the central nervous system by crossing the blood-brain barrier and binding to sphingosine-1-phosphate receptors (S1PRs). FTY-720 protects against neural damage caused by mitochondrial dysfunction and cytotoxicity by modulating S1PR1. In this study, FTY-720 was radiolabeled with technetium-99 m [Tc-99m]Tc and the biological affinity of [Tc-99m]Tc-FTY-720 was assessed using in vitro methods. The radiochemical yield and stability of [Tc-99m]Tc-FTY-720 was over 95% during 4 h. [Tc-99m]Tc-FTY-720 showed uptake on the SH-SY5Y cell line.
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    Splenosis imaging with 99mTc nano-colloid as a different mimicker in a lymphoma patient on 18F-FDG PET/CT
    Sezgin, C; Parlak, Y; Mutevelizade, G; Gumuser, G; Sayit, E
    Fluorodeoxyglucose (FDG) 18F-FDG PET/CT plays an important role in lymphoma staging and evaluation of treatment response. Mimics should be considered when evaluating 18F-FDG PET/CT images to perform correct staging and correct treatment response evaluation. Splenosis is one of the causes that may cause misinterpretation by mixing with lymph nodes in lymphoma patients. In our case report, we visualized splenosis mimicking lymph node in a 50-year-old lymphoma patient with 99mTc nano-colloid scintigraphy.
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    Paclitaxel in combination with AT-101 induces apoptosis via supressing Bcl-2, bcl-XL, mcl-1 proteins in human breast cancer cells.
    Cakar, B; Gursoy, P; Atmaca, H; Kisim, A; Bozkurt, E; Uzunoglu, S; Sezgin, C; Sanli, UA; Karabulut, B; Uslu, R; Karaca, B
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    FIBROBLAST GROWTH FACTOR RECEPTOR 2 (FGFR2) POLYMORPHISM STATUS OF TURKISH BREAST CANCER PATIENTS
    Uslu, R; Karaca, B; Atmaca, H; Kisim, A; Cakar, B; Karabulut, B; Sezgin, C; Uzunoglu, S
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    Investigation of the Radiolabelling Potential of the Aurora A Kinase Inhibitor Alisertib with Iodine-123 [123I]
    Uygur, E; Sezgin, C; Akdag, BY; Özbey, T; Parlak, Y; Karatay, KB; Gümüser, FG; Müftüler, FZB
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    New Theranostic Approach in the Treatment of Bone Metastases: 161Terbium-DOTAZOL
    Sezgin, C; Uygur, E; Parlak, Y; Karatay, K; Avcibasi, U; Muftuler, ZB; Gumuser, G
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    Comparison of XTT and Alamar blue assays in the assessment of the viability of various human cancer cell lines by AT-101 (-/- gossypol)
    Uzunoglu, S; Karaca, B; Atmaca, H; Kisim, A; Sezgin, C; Karabulut, B; Uslu, R
    This study compared the two different commercially available in vitro viability assays: XTT and Alamar blue (AB), to detect anti-proliferative effects of AT-101, a cotton plant extract, on six different human carcinoma cell lines including: prostate (PC-3 and DU-145), breast (MCF-7 and MDA-MB-231), and ovary (OVCAR-3 and MDAH 2774) in a time- and dose-dependent manner. Cells were exposed to AT-101 in the concentration range of 2.5-40 mu M for 24, 48, and 72 h. The AB assay was slightly more sensitive than the XTT assay in the evaluation of AT-101 at 24 h, suggesting that the AB assay might be used for detecting early changes in cell viability as compared to the XTT assay. Moreover, the AB assay showed less intra-assay variability as compared to the XTT. The non-toxic, non-radioactive AB metabolism assay allows rapid assessment of large numbers of samples, with simple equipment and at reduced cost for continuous monitoring of cancer cell viability, and, thus, should be accepted as a suitable alternative viability method.
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    Zoledronic acid in combination with serine/threonine phosphatase inhibitors induces enhanced cytotoxicity and apoptosis in hormone-refractory prostate cancer cell lines by decreasing the activities of PP1 and PP2A
    Cirak, Y; Varol, U; Atmaca, H; Kisim, A; Sezgin, C; Karabulut, B; Uzunoglu, S; Uslu, R; Karaca, B
    OBJECTIVES To investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the serine/threonine protein phosphatase inhibitors calyculin A (CA) and okadaic acid (OA) in hormone and drug refractory prostate cancer cells, PC-3 and DU-145. To discover the effect of these combination treatments on phosphatase 1 (PP1) and PP2A protein expression levels in prostate cancer cells. MATERIALS AND METHODS An XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by enzyme-linked immunosorbent assay (ELISA) using a Cell Death Detection ELISA Plus Kit and verified by measuring caspase 3/7 enzyme activity. The PP1 and PP2A enzyme activities were evaluated by serine/threonine phosphatase ELISA and expression levels of PP1 and PP2A proteins were then re-assessed by Western blot analysis. RESULTS Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis compared with any agent alone in both PC-3 and DU-145 prostate cancer cells. The combination of ZA with phosphatase inhibitors resulted in enhanced suppression of both PP1 and PP2A enzyme activity and protein levels, which was more overt with the ZA/CA combination. CONCLUSION Results from our study increase the translational potential of our in vitro findings and offer the basic rationale for the design of new combinatory strategies with ZA and phosphatase inhibitors for the treatment of prostate cancer, which may become resistant to conventional therapy.
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    The Imaging Performance of 89Zr in TOF PET/CT system
    Parlak, Y; Goksoy, D; Sezgin, C; Medine, I; Gumuser, G; Aras, O; Sayit, E
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    Pretreatment with AT-101 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of breast cancer cells by inducing death receptors 4 and 5 protein levels
    Kisim, A; Atmaca, H; Cakar, B; Karabulut, B; Sezgin, C; Uzunoglu, S; Uslu, R; Karaca, B
    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and has been shown to induce extrinsic pathway of apoptosis in many types of cancer cells. AT-101, an (-)-enantiomer of gossypol, is a potent anticancer agent that is shown to be an inhibitor of Bcl-2/Bcl-XL. In this study, we searched whether pretreatment with either of these drugs would result in the enhancement of apoptosis through induction of death receptors and activation of mitochondrial pathways within breast cancer cells. Human breast cancer (MCF-7 and MDA-MB-231) and normal breast cells (MCF-10A) were treated with drugs alone/in combination/sequentially. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were done. ELISA and Western blot analysis were done to assess DR4 and DR5 protein levels. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. The sequential treatment of AT-101 followed by TRAIL resulted in significant synergistic cytotoxicity and apoptosis. Moreover, pretreatment of breast cancer cells with AT-101 and then with TRAIL caused enhancement of the expression levels of DR4 and DR5 in both cancer cell lines, suggesting that these cells were under strong apoptotic stimuli. These findings all together, strongly suggest that pretreatment with AT-101 enhances TRAIL-induced death-inducing signaling complex resulting in the engagement of the mitochondrial pathway to apoptosis in breast cancer cells. These promising, preliminary results make AT-101 and TRAIL a novel combination treatment candidate for breast cancer.
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    Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells
    Karaca, B; Atmaca, H; Bozkurt, E; Kisim, A; Uzunoglu, S; Karabulut, B; Sezgin, C; Sanli, UA; Uslu, R
    We investigated the effects of AT-101/cisplatin combination treatment on the expression levels of apoptotic proteins and epigenetic events such as DNA methyltransferase (DNMT) and histone deacetylase (HDAC) enzyme activities in OVCAR-3 and MDAH-2774 ovarian cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were performed. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. DNMT and HDAC activities were evaluated by ELISA assay and mRNA levels of DNMT1 and HDAC1 genes were quantified by qRT-PCR. Combination of AT-101/cisplatin resulted in strong synergistic cytotoxicity and apoptosis in human ovarian cancer cells. Combination treatment reduced some pivotal anti-apoptotic proteins such as Bcl-2, HIF-1A, cIAP-1, XIAP in OVCAR-3 cells, whereas p21, Bcl-2, cIAP-1, HSP27, Clusterin and XIAP in MDAH-2774 cells. Among the pro-apoptotic proteins, Bad, Bax, Fas, phospho-p53 (S46), Cleaved caspase-3, SMAC/Diablo, TNFR1 and Cytochrome c were induced in OVCAR-3 cells, whereas, Bax, TRAILR2, FADD, p27, phospho-p53 (S46), Cleaved caspase-3, Cytochrome c, SMAC/Diablo and TNFR1 were induced in MDAH-2774 cells. Combination treatment also inhibited both DNMT and HDAC activities and also mRNA levels in both ovarian cancer cells. AT-101 exhibits great potential in sensitization of human ovarian cancer cells to cisplatin treatment in vitro, suggesting that the combination of AT-101 with cisplatin may hold great promise for development as a novel chemotherapeutic approach to overcome platinum-resistance in human ovarian cancer.
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    OCTREOTIDE IN COMBINATION WITH DOCETAXEL TRIGGERS APOPTOSIS BY INDUCING SSTR2 AND SSTR5 LEVELS IN HUMAN BREAST CANCER CELLS, MCF-7 AND MDA-MB-231
    Karaca, B; Muslu, U; Surmeli, ZG; Cakar, B; Atmaca, H; Asli, K; Sezgin, C; Uzunoglu, S; Karabulut, B; Uslu, R
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    Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway
    Surmeli, Z; Gursoy, P; Erdogan, AP; Bozkurt, E; Atmaca, H; Uzunoglu, S; Sezgin, C; Sanli, UA; Uslu, R; Karaca, B
    The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells.
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    A potent enantiomer of gossypol, AT-101: Screening of anti-angiogenic protein targets in glioblastoma multiforme cells
    Surmeli, Z; Bozkurt, E; Karaca, B; Karabulut, B; Sezgin, C; Sanli, UA; Uslu, R
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    Regulation of apoptosis-related molecules by synergistic combination of all-trans retinoic acid and zoledronic acid in hormone-refractory prostate cancer cell lines
    Karabulut, B; Karaca, B; Atmaca, H; Kisim, A; Uzunoglu, S; Sezgin, C; Uslu, R
    We report that all-trans retinoic acid (ATRA) in combination with zoledronic acid has strong synergistic cytotoxic and apoptotic effects against human hormone- and drug-refractory prostate cancer cells, PC-3 and DU-145, in a time- and dose-dependent manner. We further investigated the effect of the combination treatment on the apoptotic process by both oligoarray and protein array analysis in DU-145 cells, in which the drug combination shows much more strong synergistic effects, as compared to PC-3 cells. Moreover, we have also performed real time-PCR array analysis to validate oligoarray results. We demonstrated that the combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in human androgen-and drug refractory prostate cancer cells DU-145, at either transcriptional or translational levels. While expression of proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF), Bad, Bax, Fas, FADD are induced with the exposure of the combination, expression of antiapoptotic genes or proteins such as members of inhibitor apoptosis family (IAPs), MCL-1, LTBR, p53 and bcl-2 are reduced. Because this novel combination treatment has fewer side effects than is generally the case with conventional cytotoxic agents, this regimen may be a good option for treatment of elderly prostate cancer patients.
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    Unexpected Metastatic Localizations of Prostate Cancer Determined by 68Ga PSMA PET/CT: Series of Four Cases
    Mütevelizade, G; Sezgin, C; Gümüser, G; Sayit, E
    Prostate-specific membrane antigen (PSMA) is a transmembrane protein with overexpression in most prostate cancer cells. Gallium-68-(Ga-68) PSMA positron emission tomography/computed tomography (PET/CT) imaging is a game-changer in the management of prostate cancer. 68Ga PSMA PET/CT scan is advanced and a promising radioligand has high sensitivity in determining lesions of prostate cancer with a high tumor to background ratio. The most common areas of metastasis are the bone and pelvic lymph nodes. The prognosis of prostate cancer is mainly determined by the status of metastases. The presence and the localization of metastases affects treatment planning. In our cases, we presented some examples of uncommon sites of metastases such as the brain, adrenal glands, penis and orbit. Improvements in imaging techniques, such as Ga-68 PSMA PET/CT have led to the possibility to make more determination of rare metastase sites in prostate cancer patients.
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    Body Mass Index Assessment In PET/CT Imaging Patients
    Mutevelizade, G; Parlak, Y; Sezgin, C; Sayit, E; Gumuser, G
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    The Relationship Between Four Parameters: 68Ga PSMA PET/CT, Gleason Score, PSA Levels and Metastasis
    Sezgin, C; Mutevelizade, G; Parlak, Y; Gumuser, G; Sayit, E