Nur Ozten

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

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

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.

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 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 ...

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-thymid...

Glutathione S‐transferases (GSTs) are phase II enzymes that detoxify hazardous xenobiotics including carcinogens. Inter‐individual variations in GSTM1 and GSTT1 loci have been associated with several types of cancer, including leukemias. In this study, we investigated the possible association between GSTM1 and GSTT1 polymorphisms and susceptibility to chronic myeloid leukemia (CML) in a Turkish population. In a case‐control study, 106 CML patients and 190 healthy controls were evaluated for GSTM1 and GSTT1 polymorphisms. GSTM1 null (GSTM1‐) genotype frequencies in CML cases and controls were 45.3% and 42.6%, respectively. GSTT1 null (GSTT1‐) genotype frequencies were 44.3% and 18.4%, respectively. The frequency of the GSTT1‐ genotype among CML patients was significantly higher than in controls [odds ratio (OR) 3.53, 95% confidence interval (CI) 2.08‐6.00; P < 0.0001]. Individuals with the GSTM1‐ genotype did not have increased risk of CML [OR: 1.11; 95% CI: 0.69‐1.80; P = 0.714]....

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

B225 Dietary selenium (Se) supplementation has been reported to be associated with a decreased incidence of some human cancers such as prostate cancer. Se has therefore been suggested to be a promising chemopreventive agent for prostate cancer, but the biological effects of Se on normal or malignant prostate cells have not been well established. Thioredoxin reductase (TR) is a seleno-enzyme responsible for maintaining thioredoxin (Trx)in its reduced form. Because Trx is involved in manycellular processes, TR is likely to be an importantregulatory protein for both normal and transformed cells. Trx is overexpressed in a number of human tumors, and experimental studies have shown that Trx contributes to the growth and the transformed phenotype of some human cancer cells. Thus, TR, by reducing Trx, could play a role in regulating the growth of normal and cancer cells. Our objective was to investigate whether Se affects TrxR activity and whether this is associated with alterations in cel...

Genome sequencing methods have basically similar algorithms, although they show a few differences between the platforms. The human genome contains approximately three billion base pairs, and this amount is huge and therefore impossible to sequence at one step. However, this amount is not a problem for developed technology. Researchers break DNA into small random pieces and then sequence and reassemble. Library preparation, sequencing, bioinformatic approaches and reporting. High-quality library preparation is critical and the most important part of the next-generation sequencing workflow. Successful sequencing directly requires high-quality libraries. Sequencing is second step and all high-throughput sequencing approaches are generally based on conventional Sanger sequencing. After preparation of library and sequencing, later steps are completely computer-based (in silico) approaches called as bioinformatics.

Lichens are stable symbiotic associations between fungus and algae and/or cyanobacteria that have different biological activities. Around 60% of anti-cancer drugs are derived from natural resources including plants, fungi, sea creatures, and lichens. This project aims to identify the apoptotic effects and proliferative properties of extracts of Bryoria capillaris (Ach.) Brodo & D.Hawksw, Cladonia fimbriata (L.) Fr., Evernia divaricata (L.) Ach., Hypogymnia tubulosa (Schaer.) Hav., Lobaria pulmonaria (L.) Hoffm., and Usnea florida (L.) Weber ex Wigg. lichen species on prostate cancer cells. Lichen extracts were performed by ethanol, methanol, and acetone separately by using the Soxhlet apparatus and the effects of the extracts on cell viability, proliferation, and apoptosis were measured with the utilization of MTT, LDH assay, Annexin V assay, and Western Blot. Findings of our study revealed a positive correlation between the elevation of cell sensitivity and the increase in the treatment doses of the extract in that higher doses applied reverberate to higher cell sensitivity. A similar correlation was also identified between cell sensitivity elevation and the duration of the treatment. Evidence in our study have shown the existence of an anti-proliferative effect in the extracts of Bryoria capillaris, Evernia divaricata (L.) Ach., Hypogymnia tubulosa (Schaer.) Hav., Lobaria pulmonaria (L.) Hoffm., and Usnea florida (L.) Weber ex Wigg., while a similar effect was not observed in the extracts of Cladonia fimbriata. Evernia divaricata induced anti-proliferative and apoptotic effects in PC-3 cells, which induced apoptotic cell death by both extrinsic and intrinsic pathways. Hypogymnia tubulosa has been shown to have anti-proliferative and apoptotic effects in all extractions methods and our findings identified that both the percentage of the apoptotic cells and apoptotic protein expressions recorded an increase at lower treatment concentrations. Although Lobaria pulmonaria is known to have significant cytotoxic effects, we did not observe a decrease in cell proliferation. Indeed, proliferation marker proliferating cell nuclear antigen (PCNA) protein expression levels have shown an increase in all extracts, while Usnea florida exhibited apoptosis induction and slight proliferation reduction in extract treatments with lower concentrations. We tested 18 extracts of six lichen species during our study. Of these, Evernia divaricata and Hypogymnia tubulosa demonstrated significant apoptotic activity on prostate cancer cells including at low concentrations, which implies that it is worth pursuing the biologically active lead compounds of these extracts on prostate cancer in vitro. Further corroboratory studies are needed to validate the relative potential of these extracts as anti-metastatic and anti-tumorigenic agents.

Soy consumption may prevent prostate cancer (PCa) and be beneficial for patients with this malignancy. However, there are contradictory data on the anticancer effects of the soy isoflavone genistein, which has antioxidant properties and can affect cell proliferation and apoptosis of cancer cells through multiple mechanisms, including estrogen receptor-β mediation. Genistein also affects the expression of the manganese superoxide dismutase (MnSOD) gene and polymorphisms in this gene are related to risk of PCa. This study addressed the hypothesis that the effects of physiological concentrations of genistein on PCa cell proliferation and apoptosis are dependent on their MnSOD genotype and ER-β status, as well as on oxidative stress levels. In addition, we determined the effects of genistein on PCa cell proliferation and apoptosis at varying input levels of reactive oxygen species (O2.-), while controlling ER-β status and MnSOD genotype. PC-3 PCa cells transfected with different MnSOD genotypes (Ala/Ala and Val/Val) were cultured and treated with genistein at physiological concentrations (0, 0.01, 0.1, 0.5, 1, 5, 10 and 50 μM). After 24, 48 and 72 hours of incubation, we determined cytotoxicity, cell proliferation, apoptosis, and ER-β expression. Cell proliferation was induced at 0,5 μM genistein in PC-3 cells with MnSOD Val genotype and decreased at 2.5 μM in Ala genotype cells at 48 hours of treatment, which suggests 30-40% lower activity of Val genotype cells compared with the Ala variant, possibly increasing susceptibility to oxidative stress. ER-β expression levels were elevated by 48 hours of genistein treatment at 0.5 μM in Val genotype cells and were decreased at 2.5 μM in Ala cells. PARP protein expression levels, determined to investigate genistein’s effect on apoptosis in these cells, started to increase at 0.5 μM in Val cells and to decrease at 2.5 μM in Ala cells. These results suggest that PC-3 cells with Val genotype have increased oxidative stress and genistein at 0.5 μM induced proliferation in these cells. By contrast, genistein decreased proliferation of PC-3 cells with Ala genotype which have higher detoxification activity of superoxide radicals. Thus, genistein causes differential responses of cells with MnSOD variants, ER-β expression, and oxidative stress potential. This study help to understand the mechanisms of genistein9s effects on PCa cells under physiological conditions and assess the impact of interactions of MnSOD genotype, ER-β presence, and ROS environment in the context of non-linear dose-response relationships contrasting potential benefit with possible harm of genistein. The results of this study may have important implications for PCa patients who consume soy in therapeutic and chemopreventive settings. Citation Format: Sule Terzioglu Usak, Maarten C. Bosland, Nur Ozten Kandas. Differential response to genistein on prostate cancer cells expressing different MnSOD variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-168. doi:10.1158/1538-7445.AM2017-LB-168

Cold ischemia protects organs and tissues by slowing their metabolism, but it also causes ischemic injury. Minimizing cold ischemia has been an important goal in parathyroid auto- and allotransplantation, as well as the transplantation of other major organs. Parathyroid glands are responsible for calcium homeostasis by releasing parathormone (PTH) into the blood circulation. Functionality of a new parathyroid transport solution (NPTS) and effects on cell viability, PTH secretion, and calcium-sensing receptor (CaSR) levels during cold ischemia were evaluated. A NPTS was prepared, and the pH was adjusted to a range of 7.2-7.4 and kept at +4°C until use. Seven patients with parathyroid hyperplasia secondary to chronic renal failure who were scheduled to undergo subtotal parathyroidectomy were enrolled in the study. Glands were cold-preserved in NPTS with different time intervals (0, 6, 12, 18, and 24 hours), and then parathyroid cell viability before and after cryopreservation, PTH sec...

Permanent hypoparathyroidism is a serious problem and requires medications indefinitely. Parathyroid allotransplantation (PA) with short-term immunosuppression is definitive choice but long-term results are not clear. We performed PA from two donors to two recipients. Both recipients were 39-year-old females. Donors were a 32-year-old female and a 36-year-old male, who both have chronic kidney disease. Routine tests, viral markers, and cross-matches were analyzed individually. The parathyroid glands were resected from the living donors, fragmented quickly in the operation room and injected into the left deltoid muscles of the two recipients. Methylprednisolone was administered on post-PA day one and two. Recipients were discharged from the hospital without complications. Calcium and PTH levels were observed throughout 1 year. We did not observe any complications during the follow-up period. Medications ceased in post-transplantation week 1 for Case 1 and after 1 month for Case 2. Fresh tissue PA with short-term immunosuppression appears to be a promising technique that is easy to perform, is cost-effective, has low risk of side effects and minimal complications with compatibility for HLA conditions. A longer follow-up period and more case studies are needed to determine the risks and benefits of this procedure for future cases.

Oral mucositis (OM) induces severe pain and limits fundamental life behaviors such as eating, drinking, and talking for patients receiving chemotherapy or radiotherapy. In addition, through opportunistic microorganisms, OM frequently leads to systemic infection which then leads to prolonged hospitalization. Severe lesions often adversely affect curative effects in cancer cases. Therefore, the control of OM is important for oral health quality of life and prognosis. Low-level laser therapy (LLLT) and ozone may be useful to accelerate wound healing. In this study, 24 Sprague-Dawley rats were divided into three groups as control, ozone, and laser groups. All groups received 5-fluorouracil intraperitoneally and trauma to the mouth pouch with a needle. After the formation of OM in the mouth, the control group had no treatment; the ozone group was administered ozone, and the laser group, LLLT. Then, all groups were sacrificed and basic fibroblast growth factor (bFGF), transforming growth ...

The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of nonsmall cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify 2 major lessons from the outcomes of these trials: 1) the antioxidant hypothesis was tested in wrong subjects or patient populations, and 2) the selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essen...

In this perspective, modifiable carcinogenic factors for the prostate are summarized. This is followed by a discussion of how current knowledge about causation of prostate cancer and chemoprevention of prostate cancer can be used to develop preventive strategies. Prostate cancer is a slowly developing cancer which offers opportunities for preventive interventions. Only a few randomized clinical trials of prostate cancer prevention have been completed. The SELECT study with selenium and vitamin E did not find protective effects, but in two trials with 5α-reductase inhibitors risk was reduced about 25 %, showing that chemoprevention is possible and indicating that the androgen receptor is a suitable target. Besides smoking cessation and reduction of obesity, there are no known dietary or life style interventions that will have a major impact on prostate cancer risk. Inflammation of the prostate is an attractive target, and aspirin may be a promising candidate agent, but has not been a...