Demirci, S. | Doğan, A. | Türkmen, N.B. | Telci, D. | Rizvanov, A.A. | Şahin, Fikrettin

Article | 2017 | Biomedicine and Pharmacotherapy86 , pp.492 - 501

Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II)Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration . . . and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the anti-inflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro. © 2016 Elsevier Masson SA Daha fazlası Daha az

Yılmaz, SG | Yencilek, F | Yildirim, A | Yencilek, E | İşbir, Turgay

Article | 2017 | IN VIVO31 ( 2 ) , pp.205 - 208

Background: Prostate cancer is one of the most common solid tumors and the second leading cause of the death due to malignancy in men. Caspase 9 (CASP9) is a member of the intrinsic pathway and plays a central role in the apoptosis. Patients and Methods: Genotyping of the CASP9 (rs1052576) polymorphism were performed using real-time polymerase chain reaction for blood samples of prostate cancer patients (n=69) and controls (n=76). Results: There were no significant differences between the groups in the frequency of CASP9 genotypes (chi 2 = 1.363; p=0.506). Patients with CASP9 (rs1052576) CT genotype were 12.8 fold higher in patholog . . .ical stage of pT2a compared to any other stages of cancer (OR=0.078, 95% CI= 0.009-0.062; p=0.004). Also TT genotype carriers were 11.3 times lower in pathological stage of pT2a (OR=11.33, 95% CI= 2.39-53.748; p=0.000). C allele carriers were 11.36 fold higher in pathological stage of pT2a compared to any other stages of cancer (OR=0.088, 95% CI= 0.019-0.418; p=0.002). Conclusion: CASP9 (rs1052576) C allele was decreasing the risk for pathological stage of patients with prostate cancer and also CT genotype had positive impact on pathological stage of patients with prostate cancer. CASP9 (rs1052576) TT genotype was seemed to be associated with higher risk of pathological stage. Those results implicated that CASP9 variations could be associated with severity of prostate cancer Daha fazlası Daha az

Küçükhüseyin, Ö. | Kurnaz, Ö. | Akadam-Teker, A.B. | Narter, F. | Yilmaz-Aydogan, H. | İşbir, Turgay

Article | 2011 | Asian Pacific Journal of Cancer Prevention12 ( 9 ) , pp.2275 - 2278

Prostate cancer is the most common malignancy and the second leading cause of cancer related deaths among men in many countries. Serum levels of prostate-spesific antigen (PSA) have attracted attention for prediction purposes. The methylenetetrahydrofolate reductase (MTHFR) gene play a critical role in cancer development, but its potential impact on prostate cancer has not been well studied. The C677T variant lies in exon 4 at the folate binding site of the MTHFR gene and results in substitution of an alanine by a valine residue. The present study was carried out 55 cases with prostate cancer and 50 healthy men. Polymerase chain rea . . .ction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were employed to determine MTHFR C677T mutation. The frequencies of the CT genotype (p= 0.025) and T allele (p= 0.023) was found to be higher in control subjects when compared with patients group. No statistical difference was found between the alleles of MTHFR and PSA levels after (PSA-BT)/ before (PSA-AT) antiandrogen treatment or tumor stages. We suggest that the heterozygote CT genotype and the 677T allele of the MTHFR polymorphism might be associated with an decreased prostate cancer risk Daha fazlası Daha az

Onay, A. | Ertas, G. | Vural, M. | Colak, E. | Esen, T. | Bakir, B.

Article | 2020 | Abdominal Radiology , pp.2275 - 2278

Purpose: Extraprostatic extension (EPE) is an unfavorable prognostic factor and the grade of EPE is also shown to be correlated with the prognosis of prostate cancer. The current study assessed the value of prostate magnetic resonance imaging (MRI) in measuring the radial distance (RD) of EPE and the role of T2 WI signs in predicting the grade of EPE. Materials and methods: A total of 110 patients who underwent prostate MRI before radical prostatectomy are enrolled in this retrospective study. Eighty-four patients have organ confined disease and the remaining twenty-six patients have EPE all verified by histopathology. Prostate MRI . . .examinations were conducted with 3T MRI scanner and phased array coil with the following sequences: T2 WI, T1 WI, DCE, DWI with ADC mapping, and high b-value at b = 1500 s/mm2. The likelihood of EPE with 5-point Likert scale was assigned, several MRI features were extracted for each dominant tumor identified by using T2 WI. Tumors with Likert scales 4–5 were evaluated further to obtain MRI-based RD. The relationship between pathological and MRI-determined RD was tested. Univariate and multivariate logistic regression models were developed to detect the grade of pathological EPE. The inputs were among the 2 clinical parameters and 4 MRI features. Results: There is a moderate correlation between pathological RD and MRI-determined RD (? = 0.45, P < 0.01). In univariate and multivariate models, MRI features and clinical parameters possess varying significance levels (univariate models; P = 0.048–0.788, multivariate models; P = 0.173–0.769). Multivariate models perform better than the univariate models by offering fair to good performances (AUC = 0.69–0.85). The multivariate model that employs the MRI features offers better performance than the model employs clinical parameters (AUC = 0.81 versus 0.69). Conclusion: Co-existence of T2 WI signs provide higher diagnostic value even than clinical parameters in predicting the grade of EPE. Combined use of clinical parameters and MRI features deliver slightly superior performance than MRI features alone. © 2020, Springer Science+Business Media, LLC, part of Springer Nature Daha fazlası Daha az

Ozen, M. | Karatas, O.F. | Gulluoglu, S. | Bayrak, O.F. | Sevli, S. | Guzel, E. | Ittmann, M.

Article | 2015 | Cancer Investigation33 ( 6 ) , pp.251 - 258

We aimed to perform functional analysis of miR-145-5p in prostate cancer (PCa) cells and to identify targets of miR-145-5p for understanding its role in PCa pathogenesis. PC3, DU145, LNCaP PCa, and PNT1a nontumorigenic prostate cell lines were utilized for functional analysis of miR-145-5p. Its overexpression caused inhibition of proliferation through apoptosis and reduced migration in PCa cells. SOX2 expression was significantly decreased in both mRNA and protein level in miR-145-5p-overexpressed PCa cells. We proposed that miR-145-5p, being an important regulator of SOX2, carries a crucial role in PCa tumorigenesis. © 2015 Informa . . . Healthcare USA, Inc Daha fazlası Daha az

Ozdemir, A.T. | Altinova, S. | Koyuncu, H. | Serefoglu, E.C. | Cimen, I.H. | Balbay, D.M.

Article | 2014 | Central European Journal of Urology67 ( 1 ) , pp.19 - 24

Introduction Our aim was to examine the incidence and risk factors of postoperative ileus among patients who underwent robot-assisted radical prostatectomy (RARP). Material and methods We retrospectively reviewed 239 patients who underwent RARP transperitoneally between February 2009 and December 2011. Patients switched to open surgery were excluded. We defined postoperative ileus as intolerance of a solid diet continued until the third postoperative day and beyond. By Clavien classification, we evaluated the perioperative complications that cause or contribute to postoperative ileus. Similarly, we analyzed the impact of anesthesia . . .risk score on the incidence of postoperative ileus. Results The study included 228 patients. The mean period to tolerate solid food was 1.24 days. Only 6 patients experienced postoperative ileus, all of whom were treated with a conservative approach. The two groups differed significantly in the duration of abdominal drainage, hospital stay, modified Clavien classification, and the presence of comorbidity diabetes mellitus (P Daha fazlası Daha az

Kabasakal, L. | AbuQbeitah, M. | Aygün, A. | Yeyin, N. | Ocak, M. | Demirci, E. | Toklu, T.

Article | 2015 | European Journal of Nuclear Medicine and Molecular Imaging42 ( 13 ) , pp.1976 - 1983

Purpose: 177Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of 177Lu-labeled PSMA ligand. Methods: The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer . . .uptake at the lesions. The injected 177Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. Results: The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Conclusion: Our first results suggested that 177Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory. © 2015, Springer-Verlag Berlin Heidelberg Daha fazlası Daha az

Lin, X. | Aslam, A. | Attar, Rukset | Yaylim, I. | Qureshi, M.Z. | Hasnain, S. | Farooqi, A.A.

Review | 2016 | Cellular and Molecular Biology62 ( 1 ) , pp.45 - 50

Research over the decades has gradually and sequentially shown that both intratumor heterogeneity and multifocality make prostate cancer difficult to target. Different challenges associated with generation of risk-stratification tools that correlate genomic landscape with clinical outcomes severely influence clinical efficacy of therapeutic strategies. Androgen receptor mediated signaling has gained great appreciation and rewiring of AR induced signaling cascade in absence of androgen, structural variants of AR have provided near complete resolution of genomic landscape and underlying mechanisms of prostate cancer. In this review we . . . have attempted to provide an overview of most recent advancements in our knowledge related to different signaling cascades including TGF, SHH, Notch, JAK-STAT in prostate cancer progression and development. © 2016 by the C.M.B. Association Daha fazlası Daha az

Doğan, A. | Demirci, S. | Apdik, H. | Apdik, E.A. | Şahin, Fikrettin

Article | 2017 | Tissue and Cell49 ( 6 ) , pp.711 - 718

Cancer as a multistep and complicated disease is regulated by several molecular and cellular events. Cancer treatment could be managed at the early stages when the tumor is confined in the tissue. However, disseminated cancer cells metastasize to other body parts and generate new tumors resulting in mortality. Mesenchymal stem cells (MSCs) are found in different body parts and helps adult tissue regeneration. The role of MSCs in cancer progression has emerged as one of the important aspects in cancer biology and is the aim of interest in recent years. In the current study, effects of Dental Pulp Stem Cells (DPSCs) on PC-3 prostate c . . .ancer cell proliferation and migration were conducted by cell proliferation, apoptosis, gene expression and cell migration analysis in vitro. Condition medium (CM) obtained from DPSCs increased cell proliferation of PC-3 cells and decreased apoptosis. Either administration of CM or trans well co-culture of DPSCs increased cell migration in scratch assay, confirmed by gene expression analysis of migratory genes including fibronectin, laminin and collagen type I (Col I). Furthermore, DPSCs participated in a self-organized structure with PC-3 cells in co-culture conditions. Overall, results indicated that DPSCs could promote PC-3 cancer cell proliferation and metastasis in co-culture conditions in vitro. © 201 Daha fazlası Daha az

Kabasakal, L. | Toklu, T. | Yeyin, N. | Demirci, E. | Abuqbeitah, M. | Ocak, M. | Selçuk, N.A.

Article | 2017 | Molecular Imaging and Radionuclide Therapy26 ( 2 ) , pp.62 - 68

Objective: The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177) prostate-specific membrane antigen (PSMA)-617. Methods: For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h. The stability was also calculated in blood and urine samples. Post-therapeutic dosimetry was performed based on whole body and single photo . . .n emission computed tomography/computed tomography (SPECT/CT) scans on dual-headed SPECT/CT system. Results: The radiochemical yield of Lu-177-PSMA-617 was >99%. It remained stable in saline up to 48 h. Analyses of the blood and urine samples showed a single radioactivity peak even at 24 hours after injection. Half-life of the distribution and elimination phases were calculated to be 0.16±0.09 and 10.8±2.5 hours, respectively. The mean excretion rate was 56.5±8.8% ranging from 41.5% to 65.4% at 24 h. Highest radiation estimated doses were calculated for parotid glands and kidneys (1.90±1.19 and 0.82±0.25 Gy/GBq respectively). Radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands ( Daha fazlası Daha az

Ertas, G.

Article | 2018 | Magnetic Resonance Imaging50 , pp.125 - 133

Purpose: To assess the value of joint evaluation of diffusion tensor imaging (DTI) measures by using logistic regression modelling to detect high GS risk group prostate tumors. Materials and methods: Fifty tumors imaged using DTI on a 3 T MRI device were analyzed. Regions of interests focusing on the center of tumor foci and noncancerous tissue on the maps of mean diffusivity (MD) and fractional anisotropy (FA) were used to extract the minimum, the maximum and the mean measures. Measure ratio was computed by dividing tumor measure by noncancerous tissue measure. Logistic regression models were fitted for all possible pair combinatio . . .ns of the measures using 5-fold cross validation. Results: Systematic differences are present for all MD measures and also for all FA measures in distinguishing the high risk tumors [GS ? 7(4 + 3)] from the low risk tumors [GS ? 7(3 + 4)] (P < 0.05). Smaller value for MD measures and larger value for FA measures indicate the high risk. The models enrolling the measures achieve good fits and good classification performances (R 2 adj = 0.55–0.60, AUC = 0.88–0.91), however the models using the measure ratios perform better (R 2 adj = 0.59–0.75, AUC = 0.88–0.95). The model that employs the ratios of minimum MD and maximum FA accomplishes the highest sensitivity, specificity and accuracy (Se = 77.8%, Sp = 96.9% and Acc = 90.0%). Conclusion: Joint evaluation of MD and FA diffusion tensor imaging measures is valuable to detect high GS risk group peripheral zone prostate tumors. However, use of the ratios of the measures improves the accuracy of the detections substantially. Logistic regression modelling provides a favorable solution for the joint evaluations easily adoptable in clinical practice. © 201 Daha fazlası Daha az

Yencilek, F. | Yildirim, A. | Yilmaz, S.G. | Altinkilic, E.M. | Dalan, A.B. | Bastug, Y. | İşbir, Turgay

Article | 2015 | Anticancer Research35 ( 11 ) , pp.6057 - 6061

Background: Cytokine-mediated immune and inflammatory responses are considered to play an important role in the pathogenesis of prostate cancer. The present study investigated certain interleukin-1? (IL1?) polymorphisms and their association with prostate cancer. Materials and Methods: Genotyping of the IL1B-31(rs 1143627 G>A) and IL1B-511(rs 16944 A