Browsing by Author "Sezgin C."
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Item Potential predictive factors for response to weekly paclitaxel treatment in patients with metastatic breast cancer(E.S.I.F.T. srl, 2005) Sezgin C.; Karabulut B.; Uslu R.; Sanli U.A.; Goksel G.; Zekioglu O.; Ozdemir N.; Goker E.The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS. © E.S.I.F.T. srl - Firenze.Item Increasing antimicrobial resistance in Escherichia coli isolates from community-acquired urinary tract infections during 1998-2003 in Manisa, Turkey(National Institute of Health, 2005) Kurutepe S.; Surucuoglu S.; Sezgin C.; Gazi H.; Gulay M.; Ozbakkaloglu B.Urinary tract infections are among the most common infections with an increasing resistance to antimicrobials. The aim of this study was to determine the change in antimicrobial susceptibility of Escherichia coli isolates from patients with community-acquired urinary tract infection (UTI) for the years 1998 through 2003 and to suggest that the current empirical antibiotic therapy used for these patients is inappropriate. During the study period, 7,335 community urine samples of which 1,203 (16.4%) grew bacterial isolates were analyzed. Among the total of 1,203 isolates, 880 (73.2%) were E. coli. The range of resistance of E. coli to ampicillin was 47.8 to 64.6% and that to trimethoprim-sulfamethoxazole was 37.1 to 44.6% during the study period. The susceptibility pattern of E. coli to nitrofurantoin and cefuroxime did not vary significantly over the 6-year period. There was a significant increase in the susceptibility of E. coli to ciprofloxacin (11.3-26.7%), amoxicillin-clavulanate (18.4-29.2%) and gentamicin (7.0-25.6%) (P < 0.05). Empirical initial treatment with ampicillin and trimethoprim-sulfamethoxazole was thus inadequate in approximately half of UTI cases in our region.Item Gemcitabine treatment in patients with inoperable locally advanced/metastatic pancreatic cancer and prognostic factors(2005) Sezgin C.; Karabulut B.; Uslu R.; Sanli U.A.; Goksel G.; Yuzer Y.; Goker E.Objective. Most patients with pancreatic cancer show an inoperable locally advanced/ metastatic tumour at the time of diagnosis. The present study was aimed at determining the prognostic factors in patients with advanced pancreatic carcinoma treated with gemcitabine. Material and methods. Sixty-seven unresectable or metastatic pancreatic cancer patients treated with gemcitabine were included in the study and a total of 258 cycles of treatment were applied. Results. The overall response rate was 5%. Thirty-one percent of the patients had stable disease, whereas progressive disease was seen in 49%. Clinical benefit response rate was 15%. The median duration of response was 7.3 months. Median progression-free survival was 3 months, while median overall survival was 9 months. Univariate analysis revealed that worse results were found in patients with performance status (PS) =2, and in patients with primary tumour location in the body or tail of the pancreas (p <0.05). Multivariate analysis of data revealed that the most important factor was PS of the patient, as the patients with PS =2 had worse results than the patients with PS =0-1 (p <0.05). Conclusions. Low PS is a negative predictive factor for the survival of patients with advanced pancreatic carcinoma treated with gemcitabine. © 2005 Taylor & Francis.Item The effect of racemic gossypol and AT-101 on angiogenic profile of OVCAR-3 cells: A preliminary molecular framework for gossypol enantiomers(2009) Varol U.; Karaca B.; Tunali D.; Degirmenci M.; Cirak Y.; Purcu D.U.; Uzunoglu S.; Sezgin C.; Karabulut B.; Sanli U.A.; Uslu R.Aim: To compare the effect of racemic gossypol with its (-)/(-) enantiomer (AT-101) on expression profiles of angiogenic molecules by mRNA levels in human ovarian cancer cell line OVCAR-3. Methods: Cell viability assay (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) was used to detect cytotoxicity of gossypol enantiomers. DNA fragmentation by an enzyme-linked immunosorbent (ELISA) assay was used to evaluate the rate of apoptosis. The mRNA expression levels of angiogenic molecules were investigated by Human Angiogenesis RT2 Profiler™ PCR Array (SuperArray, Frederick, MD). Results: Both racemic form and AT-101 resulted in a significant cytotoxicity and induced apoptosis. This effect was observed in a dose- and time dependent manner. However, AT-101 was much more potent. In addition, the treatment of 10 μM of racemic gossypol alone and 3 μM of AT-101 alone resulted in significant down-regulation (≥ 3 fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3, but altered gene profiles were different by the treatment of each enantiomer. Conclusion: The efficacy of two gossypol enantiomers in OVCAR-3 cells showed distinction. AT-101 was much more potent than racemic gossypol, not only by means of cell death and apoptosis, but also by modulation of angiogenic molecules released from OVCAR-3 cells. Further studies with endothelial cells should be done to verify the anti-angiogenic effect of gossypol enantiomers in cancer treatment.Item Apoptosis-mediated cytotoxic effects of ibandronic acid on hormone-and drug-refractory prostate cancer cells and human breast cancer cells(SAGE Publications Ltd, 2010) Kucukzeybek Y.; Gorumlu G.; Cengiz E.; Karabulut B.; Sezgin C.; Atmaca H.; Sanli U.A.; Uzunoglu S.; Uslu R.Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immuno sorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 μM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings. © 2010 Field House Publishing LLP.Item Comparison of XTT and Alamar blue assays in the assessment of the viability of various human cancer cell lines by AT-101 (-/- gossypol)(2010) 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 2.540 M for 24, 48, and 72h. The AB assay was slightly more sensitive than the XTT assay in the evaluation of AT-101 at 24h, 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. © 2010 Informa Healthcare USA, Inc.Item Regulation of apoptosis-related molecules by synergistic combination of all-trans retinoic acid and zoledronic acid in hormone-refractory prostate cancer cell lines(2011) 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. © 2010 Springer Science+Business Media B.V.Item 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(2012) Kisim A.; Atmaca H.; Cakar B.; Karabulut B.; Sezgin C.; Uzunoglu S.; Uslu R.; Karaca B.Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. © Springer-Verlag 2012.Item 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(2012) 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 enzymelinked immunosorbent assay (ELISA) using a Cell Death Detection ELISA Plus Kit and verifi ed 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 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 andprotein levels, which was more overt with the ZA/CA combination. CONCLUSION • Results from our study increase the translational potential of our in vitro fi ndings 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. © 2012 B J U I N T E R N A T I O N A L.Item Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells(2013) Karaca B.; Atmaca H.; Bozkurt E.; Kisim A.; Uzunoglu S.; Karabulut B.; Sezgin C.; Sanli U.A.; 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. © 2012 Springer Science+Business Media Dordrecht.Item Zoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell lines(Kluwer Academic Publishers, 2015) Varol U.; Degirmenci M.; Karaca B.; Atmaca H.; Kisim A.; Uzunoglu S.; Sezgin C.; Sanli U.A.; Uslu R.Our aim was to investigate the possible synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and zoledronic acid (ZA), in PC-3 hormone-refractory prostate cancer cells (HRPC), as well as their docetaxel-resistant sublines. We established a docetaxel-resistant cell line (PC-3R) from PC-3 prostate cancer cells, by intermittent exposure to increasing concentrations of docetaxel in vitro. We then examined the effect of ZA and docetaxel on cell proliferation in both PC-3 and PC-3R prostate cancer cells. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 enzyme activity were measured to verify apoptosis. According to our results, docetaxel and ZA were found to be synergistically cytotoxic and apoptotic in both PC-3 and docetaxel-resistant PC-3R cells, in a dose- and time-dependent manner. Combined treatment with docetaxel and ZA synergistically inhibited PC-3 cell growth in vitro through an enhanced induction of cell death, compared with either agent alone; this result was also evident on PC-3R cells. Moreover, we have also demonstrated that apoptosis was induced in prostate cancer cells exposed to these drugs by a concentration-dependent increase in DNA fragmentation and caspase 3/7 enzyme activity. We concluded that ZA, either with docetaxel or not, might still exert some cytotoxicity even in docetaxel-resistant cells. From the clinical perspective, when the clinician decided to change the treatment in the post-docetaxel setting, continuing or combination with ZA may be an effective therapeutic approach for the treatment of HRPC patients. © 2014, International Society of Oncology and BioMarkers (ISOBM).Item 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(Springer Science and Business Media B.V., 2016) Surmeli Z.; Gursoy P.; Erdogan A.P.; Bozkurt E.; Atmaca H.; Uzunoglu S.; Sezgin C.; Şanlı U.A.; 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. © 2015, International Society of Oncology and BioMarkers (ISOBM).Item Contribution of Open Mouth Technique in18F-FDG PET/CT Imaging in Patients with Malignant Lip Neoplasm; [Dudak Malign Neoplazmı Tanılı Hastaların18F-FDG PET/BT Görüntülemesinde Ağız Açık Pozisyonlamanın Katkısı](Galenos Publishing House, 2022) Mütevelizade G.; Sezgin C.; Parlak Y.; Gümüşer G.; Sayit E.Objectives:18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating head and neck cancers. However, localization and size evaluation in this region can be rough due to the multitude of the anatomic structures and physiologic uptakes. The aim of this study was to evaluate malignant lip lesions with the contribution of open mouth (OM) imaging technique at PET/CT. Methods: Fifty-six patients with malignant lip neoplasm underwent18F-FDG PET/CT imaging. Each patient was imaged twice as whole-body PET/ CT with routine closed mouth (CM) position; and OM head and neck image, standardized with a special device. Lesion maximum standard uptake value (SUVmax), localization, size, and involvement of lymph nodes were evaluated. Results: Lesion localization was correctly detected in 100% of the OM images. Lesion size in PET/CT was compared with clinical, radiological (magnetic resonance imaging and CT) and/or histopathological results and the size measurement was coherent at 47.1% and 95.6% for CM and OM images, respectively. It was observed that OM acquisition did not contribute additionally in detecting regional lymph node metastasis. Forty-one PET/CT scans with CT artifacts due to dental amalgams were evaluated and 46.3% dimensional and 53.7% localization errors were detected in the CM position. There was no statistically significant difference between OM and CM SUVmax (p>0.05). Conclusion: We concluded that additional OM head and neck imaging is useful and necessary to accurately determine the localization and size of the tumor, thus enhancing the value of PET/CT in staging, treatment response assessment, and restaging of patients with malignant lip cancer with or without dental amalgam. © 2022 by Turkish Society of Nuclear Medicine Molecular Imaging and Radionuclide Therapy published by Galenos Yayınevi.Item Unexpected Metastatic Localizations of Prostate Cancer Determined by68Ga PSMA PET/CT: Series of Four Cases; [68 Ga PSMA PET/BT’de Saptanan Prostat Kanserinin Nadir Metastaz Lokalizasyonları: Dört Olgu](Galenos Publishing House, 2022) Mütevelizade G.; Sezgin C.; Gümüşer G.; Sayit E.Prostate-specific membrane antigen (PSMA) is a transmembrane protein with overexpression in most prostate cancer cells. Gallium-68-(68Ga) 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 as68Ga PSMA PET/CT have led to the possibility to make more determination of rare metastase sites in prostate cancer patients. © 2022 by Turkish Society of Nuclear Medicine Molecular Imaging and Radionuclide Therapy published by Galenos Yayınevi.Item Radiolabeling fingolimod with technetium-99 m and evaluating its biological affinity by in vitro method(Springer Science and Business Media B.V., 2023) Uygur E.; Parlak Y.; Karatay K.B.; Sezgin C.; Gümüşer F.G.; Biber Müftüler F.Z.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 [99mTc]Tc and the biological affinity of [99mTc]Tc-FTY-720 was assessed using in vitro methods. The radiochemical yield and stability of [99mTc]Tc-FTY-720 was over 95% during 4 h. [99mTc]Tc-FTY-720 showed uptake on the SH-SY5Y cell line. © 2023, Akadémiai Kiadó, Budapest, Hungary.Item Inguinoscrotal Bladder Hernia Mimicking Testicle Tumor(SAGE Publications Ltd, 2023) Sezgin C.; Duzgun F.; Mutevelizade G.; Gumuser G.; Sayit E.Bladder hernias usually begin asymptomatically and are discovered incidentally at the time of discovery. Preoperative diagnosis of bladder hernias is important to reduce the risk of bladder injury during surgery. Although F-18 FDG PET/CT is applied for oncological purposes, benign conditions should also be taken into account when evaluating the implants. In this article, a case of bladder hernia, which can be confused with pathological cancer involvement, with the diagnosis of F-18 FDG PET/CT performed in a 73-year-old male patient with renal cell carcinoma is presented. © The Author(s) 2023.Item Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson’s Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods(Springer, 2024) Uygur E.; Karatay K.B.; Derviş E.; Evren V.; Kılçar A.Y.; Güldü Ö.K.; Sezgin C.; Çinleti B.A.; Tekin V.; Muftuler F.Z.B.Parkinson’s disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99 m ([99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography–mass spectrometry (LC–MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [99mTc]Tc radiolabeled compounds ([99mTc]Tc-MA, [99mTc]Tc-MA-L-DOPA, [99mTc]Tc-MA-PLGA and [99mTc]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague–Dawley rats and a Parkinson’s disease experimental model to evaluate the compounds’ bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [99mTc]Tc-L-DOPA-PLGA were above 95% and had stability over 6 h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [99mTc]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research. © The Author(s) 2024.Item The radiolabeling of [161Tb]Tb-PSMA-617 by a novel radiolabeling method and preclinical evaluation by in vitro/in vivo methods(Akademiai Kiado ZRt., 2024) Uygur E.; Sezgin C.; Parlak Y.; Karatay K.B.; Arıkbaşı B.; Avcıbaşı U.; Toklu T.; Barutça S.; Harmanşah C.; Sözen T.S.; Maus S.; Scher H.; Aras O.; Gümüşer F.G.; Biber Muftuler F.Z.Prostate cancer (PC) is the most prevalent cancer in elderly men, exhibiting a positive correlation with age. As resistance to treatment has developed, particularly in the progressive stage of the disease and in the presence of microfocal multiple bone metastases, new generation radionuclide therapies have emerged. Recently introduced for treating micrometastatic foci, Terbium-161 ([161Tb]) has shown great promise in prostate cancer treatment. This study investigated the in vitro and in vivo cytotoxicity of Terbium-161 ([161Tb])-radiolabeled prostate-specific membrane antigen (PSMA)-617. [161Tb]Tb-PSMA-617 (7.4 MBq/nmol) demonstrated a radiochemical yield of 97.99 ± 2.01% and hydrophilicity. [161Tb]Tb-PSMA-617 was also shown to have good stability, with a radiochemical yield of over 95% up to 72 h. In vitro, [161Tb]Tb-PSMA-617 exhibited cytotoxicity on LNCaP cells but not on PC3 cells. In vivo, scintigraphy imaging visualized the accumulation of [161Tb]Tb-PSMA-617 in the prostate, kidneys, and bladder. The results suggest that [161Tb]Tb-PSMA-617 can be an effective radiolabeled agent for the treatment of PSMA positive foci in prostate cancer. © Akadémiai Kiadó, Budapest, Hungary 2024.Item Predicting thyroid cancer ablation success: Pre-ablative 99mTc-Pertechnetate and post-ablative 131I scan comparison; [Prédiction du succès de l'ablation dans le cancer de la thyroïde : une comparaison de la scintigraphie pré-ablative à la 99mTc-pertechnétate et de la scintigraphie post-ablative au 131I](Elsevier Masson s.r.l., 2024) Mutevelizade G.; Parlak Y.; Bozdemir B.C.; Sezgin C.; Gumuser G.; Sayit E.Introduction: The purpose of this study was to evaluate the relationship between pre-ablative 99mTc-pertechnetate scintigraphy, and therapeutic iodine-131 (131I) whole-body scan (TxWBS), with ablation status and to investigate the possible predictive factors for successful ablation in differentiated thyroid carcinoma (DTC) patients. Materials and methods: A total of 330 DTC patients underwent 99mTc-pertechnetate scintigraphy after thyroidectomy. Uptake values were determined using the region-of-interest technique. All patients had neck ultrasonography and TxWBS. Both scintigraphic scans were interpreted visually and qualitatively. The ablation status was evaluated with a diagnostic 131I whole-body scan. Results: The success rate for residual thyroid ablation was 88.8%. The sensitivity, specificity, accuracy, PPV, and NPV of 99mTc-Pertechnetate scintigraphy were 82.4%, 87.5%, 82.7%, 99.2%, and 20.2%, respectively. Pre-ablative TG values and 99mTc uptake (%) were significantly lower in successfully ablated patients. The 99mTc uptake was determined as a significant predictive factor for ablation success (P = 0.000). The optimal 99mTc uptake cut-off value of 0.75% was demonstrated for successful ablation. There were significant positive correlations between the visual and the calculated uptake (%) of residual tissues on both scintigraphic scans, Considering the number of remnant tissue foci, significant positive correlations were found between 99mTc-Pertechnetate scintigraphy, TxWBS, and USG. Conclusion: Pre-ablative 99mTc-Pertechnetate uptake (%) value of the remnant tissue can predict the ablation status in DTC patients. 99mTc-Pertechnetate scintigraphy, which is an easily applicable and accessible imaging method, has maintained its place in the postoperative and pre-ablative period in DTC patients over the years and has not lost any of its value. © 2024 Elsevier Masson SASItem Splenosis imaging with 99mTc nano-colloid as a different mimicker in a lymphoma patient on 18F- FDG PET/CT; [Scintigraphie aux nanocolloïdes-33mTc pour différencier une splénose d'un ganglion lymphatique fixant le 18F-FDG](Elsevier Masson s.r.l., 2024) 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. © 2024 Elsevier Masson SAS