Nur Ozten - Academia.edu (original) (raw)

Papers by Nur Ozten

Prostate cancer is one of the most commonly diagnosed cancer types in US men. Consequently, there... more Prostate cancer is one of the most commonly diagnosed cancer types in US men. Consequently, there is an urgent need to identify preventive agents which can inhibit the prostate carcinogenesis process. 9-cis-retinoic acid (9cRA) is a naturally occurring retinol metabolite and pan retinoic acid receptor agonist which is of interest as a potential chemopreventive compound. Previous studies have demonstrated preventive activity against breast and prostate cancer in animal models and inhibitory effects on growth of cancer cell lines of this retinoid, but the mechanisms by which 9cRA can influence growth of prostate cancer cells remains unclear. In this study we used LNCaP cells to investigate the effects of 9cRA on cell proliferation, differentiation, and apoptosis. Cells were cultured with and without 10−10 or 10−9M dihydrotestosterone and treated with 9cRA at non-cytotoxic concentrations ranging from 10−8M to 10−5M. After 3 and 6 days of incubation, we determined cell growth, 3H-thymidine incorporation, and secretion of prostate specific antigen (PSA), and performed cell cycle analysis and apoptosis assays. Cell growth assessed by cell counts was inhibited on 3 and 6 days in a dose-dependent manner by treatment with 9cRA, and 3H-thymidine incorporation was reduced, reaching a maximum at day 3. PSA secretion was increased in a dose-related fashion after 6 days of treatment, suggesting a differentiation effect. Treatment with 9cRA increased the number of apoptotic cells observed microscopically by staining with H33258 by 3 to 7-fold peaking on day 3. When apoptosis was measured using flow cytometry and staining with PI and FITC-Annexin V, a maximal increase of apoptotic cells was observed on day 6. A cell cycle analysis by flow cytometry revealed up to a 70% increase in cells in S-phase and a decrease in cells in G0/G1 after 3 and 6 days of 9cRA treatment. The results suggest that 9cRA acts on LNCaP cells by interfering with the completion of S-phase or S to G2-phase transition and inducing cellular differentiation and apoptosis. These observations together indicate that the growth inhibitory mechanism of 9cRA on LNCaP prostate human cancer cells is a combination of the ability of 9cRA to inhibit cell proliferation, promote differentiation, and induce apoptosis. Although these findings suggest that 9cRA may be an attractive treatment for option for the prevention of prostate cancer development, this is limited by its human toxicity. A search for 9cRA analogues or other selective retinoid acid receptor modulators with similar anti-prostate cancer activity is thus warranted. Citation Format: Jillian N. Eskra, Maarten C. Bosland, Nur Ozten. Effects of 9-cis-retinoic acid on proliferation, differentiation, and apoptosis of LNCaP prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2585. doi:10.1158/1538-7445.AM2013-2585

Cancer Prevention Research, Mar 1, 2010

Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have bee... more Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have been negative, but these models may not involve oxidative stress mechanisms. In this study, we examined the potential of selenomethionine and α-tocopherol to modulate prostate cancer development in the testosterone plus estradiol-treated NBL rat, a model that does involve sex hormone-induced oxidative stress mechanisms and prostatic inflammation. One week following the implantation with hormone-filled Silastic implants, rats were fed diets containing L-selenomethionine (1.5 or 3.0 mg/kg), DL-α-tocopherol acetate (2,000 or 4,000 mg/kg), or a natural ingredient control diet (NIH-07). The development of prostate carcinomas was not affected by dietary treatment with either agent. Food intake, body weight, and mortality were also not affected. The high dose of selenomethionine reduced the severity of epithelial dysplasia in the lateral prostate that was not associated with inflammation, and α-tocopherol reduced in a doserelated fashion the incidence of marked inflammation and marked epithelial dysplasia in the lateral prostate, regardless of whether these lesions were associated with inflammation. α-Tocopherol significantly increased the incidence of adenocarcinomas of the mammary glands at both dietary concentrations. Collectively, our findings suggest that selenomethionine and α-tocopherol supplementation does not prevent prostate cancer in rats fed diets with nutritionally adequate levels of selenium and vitamin E. Importantly, the results of the current animal studies and those reported previously were fully predictive of the outcome of the Selenium and Vitamin E Cancer Prevention Trial. Cancer Prev Res; 3(3); 371-80. ©2010 AACR.

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Previous studies with se... more Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have been negative, but these models may not involve oxidative stress mechanisms. Selenium and vitamin E have been the subject of one of the largest trials ever conducted, SELECT, which was discontinued because there was no difference between the study arms and there were side effects, including an increased chance of developing diabetes mellitus with the use of selenium. We previously found that selenomethionine supplementation did not prevent prostate cancer in NBL rats treated with testosterone plus 17 beta-estradiol (T+E2), a model that does involve sex-hormone induced oxidative stress mechanisms and prostatic inflammation; this result was fully predictive of the outcome of the SELECT trial. Based on the outcomes of SELECT and our NBL rat study, we hypothesized that selenium has no protective effect against T+E2-induced prostate cancer development because it does not protect against oxidative stress. In the present study, we examined the potential of selenomethionine to modulate prostatic oxidative stress and induction of dysplasia and inflammation in the T+E2-treated NBL rat. Nbl/Crl rats were treated for 16 weeks with T+E2 by Silastic implants and were fed a natural ingredient control diet (NIH-07) with or with L-selenomethionine at a concentration of 1.5 or 3.0 mg/kg (as selenium). These diets were initiated one week post hormone implantation. T+E2 significantly increased immunohistochemical staining for 8-hydroxy-deoxyguanosine (8-OHdG) in prostatic ducts, and in the lateral and dorsal prostate which are the main sites of T+E2-induced inflammation and preneoplasia after 16 weeks of hormone treatment, and in the seminal vesicles. However, selenomethionine did not reduce these effects and did not, by itself, change 8OHdG staining. There was a lobe-specific differential response and modulation of antioxidant enzymes. Glutathione peroxidase activity and protein expression level of manganese superoxide dismutase were induced by T+E2, which effects were counteracted by selenomethionine in the dorsolateral prostate, which is the main site of T+E2-induced inflammation and preneoplasia occurring after 16 weeks of hormone treatment. However, selenomethionine did not influence the induction by T+E2 of marked inflammation and dysplasia in the lateral prostate. These findings partially explain the negative outcome of our previous NBL rat study and is consistent with the negative results of the SELECT trial. (Supported in part by Grant No. CA104334) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5579. doi:10.1158/1538-7445.AM2011-5579

Turkish Journal of Medical Sciences, Aug 30, 2021

Background/aim: MicroRNAs (miRNAs) are known up-to-date candidate biomarkers for several diseases... more Background/aim: MicroRNAs (miRNAs) are known up-to-date candidate biomarkers for several diseases. In addition, obtaining miRNA from different body fluids such as serum, plasma, saliva, and urine is relatively easy to handle. Herein we aimed to detect miRNAs as biomarkers for early stage prostate cancer (PC). For this purpose, we used urine and serum samples to detect any significant differences in miRNA profiles between patients and healthy controls. Materials and methods: Total ribonucleic acid (RNA) in urine and serum samples were isolated from eight untreated PC patients, thirty healthy individuals were screened for miRNA profile, and candidate miRNAs were validated. Whole urinary and serum miRNA profile was analyzed using Affymetrix GeneChip miRNA 4.0 Arrays. Candidate miRNAs were investigated by stem-loop reverse transcriptionpolymerase chain reaction. Results: When we analyzed the urinary samples of PC patients, 49 miRNAs were detected to be upregulated and 14 miRNAs were found to be downregulated when compared with healthy controls. According to the serum samples, 19 miRNAs were found to be upregulated, and 21 miRNAs were found to be downregulated when compared with healthy individuals as well. Interestingly, we detected only four overlapping miRNAs (MIR320A, MIR4535, MIR4706, MIR6750) that commonly increase or decrease in both serum and urine samples. Among them, MIR320A was found to be downregulated, and MIR4535, MIR4706, and MIR6750 were found to be upregulated for urine samples. However, only MIR6750 was upregulated and the other three miRNAs were downregulated for serum samples. Conclusion: Notably, the expression profile of MIR320A was significantly altered in urine specimens of prostate cancer patients. We considered that MIR320A has been evaluated as a valuable biomarker that can be used in the early diagnosis of PC.

Nutrition and Cancer, Feb 21, 2009

We examined the hypothesis that nontoxic concentrations of selenium induce apoptosis and growth i... more We examined the hypothesis that nontoxic concentrations of selenium induce apoptosis and growth inhibition selectively in prostate cancer cells but not in benign prostate cells. Nontumorigenic BPH-1 prostate epithelial cells, androgen-sensitive LNCaP, and androgen-independent PC-3 prostate cancer cells were exposed to sodium selenite at 1 to 10 μmol/l for 24 to 72 h. Cell proliferation, viability, and apoptosis were assessed by MTT assay, trypan blue exclusion, flow cytometry, DNA laddering, and caspase activation. BPH-1 cells were more sensitive for cytotoxic selenium effects than malignant prostate cells, whereas LNCaP cells were more sensitive than PC-3 cells. At noncytotoxic selenium concentrations, there was no apoptosis in BPH-1 and PC-3 cells and no growth inhibition of LNCaP and BPH-1 cells. PC-3 cells were refractory to apoptosis induction but were growth inhibited at non-cytotoxic concentrations. LNCaP cells were growth stimulated at 1 μmol/l and sensitive to apoptosis induction at higher noncytotoxic concentrations. Thus, noncytotoxic selenite concentrations did not induce growth inhibition or apoptosis selectively in prostate cancer cells. Growth stimulation of LNCaP cells by low concentrations suggests the possibility of adverse effects of selenium supplementation on hormone sensitive prostate cancer, whereas inhibition of PC-3 cell proliferation at noncytotoxic concentrations suggests potential benefit of selenium in advanced prostate cancer.

Arabian Journal of Chemistry, 2020

Current therapies to treat gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), an... more Current therapies to treat gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and other acid-related diseases either prevent stimulation of the parietal cell (H 2-receptor antagonists) or inhibit gastric H ? / K ?-ATPase (proton pump inhibitors). The inhibition of acid production by proton pump inhibitors (PPI's) provides more effective relief of symptoms and healing. A series of novel 4-substituted-2-(1H-benzimidazol-2-yl)methylsulfinylpyrimidines were synthesized as target compounds and antiulcer activity was done using parameters like total acidity, pH, and total gastric acid volume by pylorus ligation method on Wistar rats. Three different dose levels were employed for testings. The target compounds 4-substituted-2-(1H-benzimidazol-2-yl)methylsulfinylpyrimidines were effective for ulcer treatment and among them compounds 10c, 10d, 8b, and 8c exhibited potent antisecretory activity. Overall, compounds 10c, 10d, 8b, and 8c can be looked upon as potential leads for further development and investigations. Keywords Antiulcer agents Á H ? /K ?-ATPase Á Omeprazole Á pH Á Total acidity Á Total gastric acid volume Kishor S. Jain, Vikas K. Raskar contributed equally for the research work.

Nutrition and Cancer, Apr 28, 2014

Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not sh... more Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including one study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T+E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3.0 mg selenium/kg in NIH-07 diet in Nbl/Crl rats treated with T+E2 for 16 weeks. Hormone treatment increased immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) in the prostatic sites of T+E2-induced preneoplasia (p<0.05), but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity and mRNA expression were induced by T+E2 (p<0.05-p<0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathioneperoxidase and MnSOD, except for a reduction of MnSOD protein expression in the lateral prostate (p<0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (p<0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T+E2 occurred in the lateral and dorsal prostate, explaining why T+E2 induces lesions selectively in the lateral lobe of NBL rats.

European Journal of Cancer Prevention, 2017

9-cis-Retinoic acid (9cRA), which binds to both retinoic acid receptors and retinoic X receptors,... more 9-cis-Retinoic acid (9cRA), which binds to both retinoic acid receptors and retinoic X receptors, inhibits prostate cancer induction in rats and reduces growth of prostate cancer cells. However, the nature of this growth inhibition and the interactive influence of androgens are not well defined and are the subject of this report. LNCaP and PC-3 cells were cultured and treated with a range of 9cRA concentrations for 3-6 days in the absence or presence of 5α-dehydrotestosterone. 9cRA inhibited cell proliferation in a dose-dependent manner, plateauing at 10 mol/l. Treatment of cells with 10 mol/l 9cRA inhibited 5α-dihydroxytestosterone (DHT)-stimulated proliferation, the effect of which was maximal at 10 mol/l DHT. Treatment of DHT (10 mol/l)-exposed cells with 9cRA caused a dose-dependent increase in prostate-specific antigen in the medium after 6 days, but not 3 days. 9cRA caused a dose-dependent increase in apoptotic cells stained with H33258 after 3 days, but not 6 days; however, on using flow cytometry, apoptosis was apparent at both 3 and 6 days. Flow cytometry also revealed interference of G0/G1 to S phase transition by 9cRA. Inhibition by 9cRA of anchorage-independent growth of PC-3 cells was also found; LNCaP cells did not grow colonies in soft agar. 9cRA inhibited growth and induced differentiation of human LNCaP prostate cancer cells in vitro and inhibited anchorage-independent growth of PC-3 cells. Because 9cRA and 13-cis-retinoic acid, which is retinoic acid receptor-selective, prevent prostate carcinogenesis in rats, and 13-cis-retinoic acid also inhibits growth of human prostate cancer cells, the RAR is a potential molecular target for prostate cancer prevention and therapy.

Serum prostat spesifik antijeni (PSA) prostat kanserli hastaların tanımlanmasında kliniğe çok öne... more Serum prostat spesifik antijeni (PSA) prostat kanserli hastaların tanımlanmasında kliniğe çok önemli katkı sağlamıştır. Bununla birlikte PSA'nın bazı limitasyonları bulunmaktadır. Bu durum erken tanı ve tedavide yeni biomarkerların tanımlanması ihtiyacını doğurmuştur. Klinik çalışmalara göre, selenyumun ileri ve agresif prostat kanserinde potansiyel önleyici etkisinin olduğu gösterilmiştir. Ancak bu etki mekanizmasının daha çok düşük selenyuma sahip erkeklerde etkili olduğu gösterilmiştir. Bu çalışmanın amacı, yeni tümör markerlarının araştırılması ve selenyumla indüklenen değişikliklerin proteomiks teknolojisiyle saptanmasıdır. Selenyumla muamale edilmiş BPH-1 ve LNCaP hücrelerinin bulunduğu besiyerindeki proteinler iki boyutlu elektroforez yapılmış ve MALDI-TOF-MS ile tanımlanmıştır. MALDI-TOF-MS kullanılarak ve veri tabanı araştırılması yapılarak besiyerinde eksprese olan 9 farklı protein tanımlanmıştır. Proteomikse dayalı bir yöntemle yeni tümör markerlarının araştırılması için uygun ve etkin bir yol olarak prostat kanseri ve benign prostatik hipertrofi hücrelerinin ayırımında 9 aday protein bir kemopreventif ajan olan selenyum kullanımına yanıt vermesine bağlı olarak tanımlanmıştır.

International Journal of Molecular and Cellular Medicine, 2022

Human Immunology

BACKGROUND Basic and clinical studies about parathyroid allotransplantation have to be utilized w... more BACKGROUND Basic and clinical studies about parathyroid allotransplantation have to be utilized with more definitive criteria for longer graft survival. Several reports demonstrated different isolation and cultivation methods for parathyroid cells to minimize their immunogenicity. In this study, we aim to compare and evaluate the clinical characteristics and the status of HLA class II expression changes in parathyroid tissue. METHODS A total of 22 parathyroid hyperplasia tissue donors was included in this study. Clinical characteristics were evaluated and compared with the HLA-DR, -DP, -DQ mRNA, and protein expression levels which were determined by qRT-PCR and Western blot. RESULTS We have compared the clinical characteristics (age, dialysis duration, frequency, recurrency of hyperparathyroidism and, calcimimetic usage) and HLA class II expression. HLA class II mRNA and protein levels showed varied expression patterns between tissues. Only, the HLA-DP has high mRNA expression levels without affecting the protein level when compared with the ages of the tissue donors. In addition, the HLA-DR, HLA-DP, and HLA-DQα1 protein expression levels showed a permanent and varied expression rate between tissues. CONCLUSION Expression of HLA class II molecules in parathyroid cells appears to constitute a decisive factor. Despite the lack of clinical outcomes, present data proposes new insight with a detailed understanding of parathyroid immunogenicity. In the future, randomized controlled clinical trials are needed for the accurate assessment of the effect of the varied HLA class II expression profiles in parathyroid tissue.

Serum prostat spesifik antijeni (PSA) prostat kanserli hastalarin tanimlanmasinda klinige cok one... more Serum prostat spesifik antijeni (PSA) prostat kanserli hastalarin tanimlanmasinda klinige cok onemli katki saglamistir. Bununla birlikte PSA’nin bazi limitasyonlari bulunmaktadir. Bu durum erken tani ve tedavide yeni biomarkerlarin tanimlanmasi ihtiyacini dogurmustur. Klinik calismalara gore, selenyumun ileri ve agresif prostat kanserinde potansiyel onleyici etkisinin oldugu gosterilmistir. Ancak bu etki mekanizmasinin daha cok dusuk selenyuma sahip erkeklerde etkili oldugu gosterilmistir. Bu calismanin amaci, yeni tumor markerlarinin arastirilmasi ve selenyumla induklenen degisikliklerin proteomiks teknolojisiyle saptanmasidir. Selenyumla muamale edilmis BPH-1 ve LNCaP hucrelerinin bulundugu besiyerindeki proteinler iki boyutlu elektroforez yapilmis ve MALDI-TOF-MS ile tanimlanmistir. MALDI-TOF-MS kullanilarak ve veri tabani arastirilmasi yapilarak besiyerinde eksprese olan 9 farkli protein tanimlanmistir. Proteomikse dayali bir yontemle yeni tumor markerlarinin arastirilmasi icin ...

Akdeniz Medical Journal, 2018

Hipotiroidi tüm yaş gruplarında görülebilen, bireylerin sağlıklarının genel olarak bozulmasına ne... more Hipotiroidi tüm yaş gruplarında görülebilen, bireylerin sağlıklarının genel olarak bozulmasına neden olan klinik bir tablodur. Tedavisi genellikle yaşam boyu ilaç kullanımıdır. Bu tedaviye rağmen hormon yetmezliğine bağlı semptomlar görülmekte ve uzun dönem ilaç kullanımına bağlı yan etkiler ortaya çıkmaktadır. Hastalardaki yetersiz tiroid hormon miktarını optimum sınırlara çekmek ve hastaların yaşam kalitesini yükseltmek için tiroid dokusu transplantasyonu alternatif bir yöntem olarak önem taşımaktadır. Sunulan çalışmada, transplantasyonda immün redden etkilenmemek için hem doku kültürü hem de biyouyumlu polimerle kapsüle edilmiş tiroit dokusunun in vitro optimizasyonu amaçlanmıştır. Gereç ve Yöntemler: Mekanik yollarla kültüre edilen tiroid dokusu 2 grupta takip edilmiştir; doku kültürü ve kapsülasyon kültürü. In vitro ortamda 60 gün boyunca takip edilen kapsüllerin morfolojileri ışık mikroskopu ile birlikte T3 ve T4 hormon değerleri ise biyokimyasal olarak değerlendirilmiştir.

Cancer Research, 2013

Nutrition and Cancer, 2009

Nutrition and Cancer, 2014

Journal of Carcinogenesis, 2011

Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of d... more Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1) Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2) chemoprevention drugs including agents interfering with androgen action, and (3) antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.