Development Of Prostate Carcinoma Research Articles

The Influence of Oral Health Care on Prevalence of Urinary Symptoms and mean plasma Prostatic Surface Antigen (PSA) concentration in a Population of Nigerian Adult Males

Background/Aims and Objectives: Inflammatory mediators from ongoing oral infection induce intense immune response that could lead to the carcinogenesis as well as progression of pathogenesis of systemic diseases. Development of prostatic carcinoma and presence of urinary symptoms may be linked to the presence of oral problems.

Opportunities for early detection of prostate cancer in young and middle-aged men

Prostate cancer (PCa) is a public health problem worldwide. Among all malignant tumors, PCa ranks second in prevalence (105 out of 185 countries) and fifth in cause of death in men in 46 countries. In some cases, this pathology is verified in men under the age of 50, including the advanced stage of the metastatic process. The review article provides information on the epidemiology and prevalence of PCa in young men obtained from the PubMed, CrossRef, and Scopus databases. The data on the probable causal relationship of a number of factors potentially affecting the development of prostate carcinoma are presented. Little-known and new molecular genetic changes are described, including those associated with prostate-specific antigen (PSA), with a proven role in the development of this disease, the use of which will make it possible to predict PCa development in the early stages in a timely manner. It has been determined that the common methods for diagnosing carcinoma in the population, assessing the level of serum PSA, are not always accurate and that the algorithm for their use has not been finally formed. The study of risk factors for the development of PCa in young patients will make it possible to formulate a new diagnostic approach based on considering personal molecular genetic information. The development of this direction is relevant and has an important social and economic importance, considering the study of the contingent of the able-bodied population.

Hsa-miR-149-5p Suppresses Prostate Carcinoma Malignancy by Suppressing RGS17.

BackgroundMicroRNAs (miRNAs) are key players in the progression of human cancers. While several miRNAs have been reported to regulate the development of tumors, the molecular mechanisms and roles of miR-149-5p in prostate carcinoma (PCa) remain unclear. Our aim was to investigate the interaction and functions of miR-149-5p and RGS17 in PCa.MethodsMicroarray analysis was performed to identify the key miRNA and gene involved in PCa progression. The expression levels of miRNA and mRNA in PCa tissues and cells were verified by qRT-PCR. MTT assay, BrdU proliferation assay and wound-healing assay were applied to assess the effect of miR-149-5p and RGS17 on PCa cells’ viability, proliferation, and migration ability. The association between RGS17 and miR-149-5p was identify using dual-luciferase reporter assay and Western blot assay.ResultsData analysis indicated the reduction of miR-149-5p expression in PCa tissues and cells. Experimental investigations also showed that this miRNA suppressed the viability, proliferation and migration ability of PCa cells. RGS17 was found to be the target of miR-149-5p, and the low expression of miR-149-5p upregulated RGS17 in PCa tissues and cells. The results of the cell-function assays showed that RGS17 acted as an oncogene in PCa even though its promotive effect could be reversed by miR-149-5p.ConclusionThis research confirmed that by targeting and inhibiting RGS17, miR-149-5p could suppress PCa development.

Androgen Receptor Signaling and the Emergence of Lethal Neuroendocrine Prostate Cancer With the Treatment-Induced Suppression of the Androgen Receptor: A Literature Review.

Androgen receptor signaling primarily influences both the normal growth and proliferation of the prostate gland and the development of prostatic carcinoma. While localized prostate cancers are typically managed with definitive therapies like surgery and radiotherapy, many patients have recurrences in the form of metastatic disease. Androgen deprivation therapy, by way of castration via orchiectomy or with drugs like luteinizing hormone-releasing hormone (commonly called gonadotropin-releasing hormone) agonists and luteinizing hormone-releasing hormone antagonists, is the primary mode of therapy for advanced castration-sensitive prostate cancer. Castration resistance invariably develops in these patients. Further treatment has shifted to newer anti-androgen drugs like enzalutamide or abiraterone and taxane-based chemotherapy. Prolonged inhibition of the androgen receptor signaling pathway causes androgen receptor-independent clonal evolution which leads to the development of treatment-emergent neuroendocrine prostate cancer.All prostate cancers at the initial presentation should undergo evaluation for the markers of neuroendocrine differentiation. Detection of serum biomarkers of neuroendocrine differentiation and circulating tumor cells is a prospective non-invasive method of detecting neuroendocrine transdifferentiation in patients undergoing treatment with androgen receptor pathway inhibitors. It is essential to perform a biopsy in the presence of red flags of neuroendocrine differentiation. Alisertib, an Aurora kinase inhibitor, showed promising clinical benefit in a subgroup of patients with certain molecular alterations. A thorough understanding of the molecular and clinical programming of treatment-emergent neuroendocrine prostate cancer can potentially lead to the development of drugs to prevent the development of this lethal variant of prostate cancer.

Loss of RBMS1 as a regulatory target of miR-106b influences cell growth, gap closing and colony forming in prostate carcinoma

Prostate carcinoma (PCa) is the second most commonly diagnosed cancer in males worldwide. Among hereditary genetic mutations and nutrient factors, a link between the deregulation of microRNA (miRNA) expression and the development of prostate carcinoma is assumed. MiRNAs are small non-coding RNAs which post-transcriptionally regulate gene expression and which are involved in tumour development and progression as oncogenes or tumour suppressors. Although many genes could be confirmed as targets for deregulated miRNAs, the impact of differentially expressed miRNA and their regulatory target genes on prostate tumour development and progression are not fully understood yet. We could validate RBMS1, a barely described RNA-binding protein, as a new target gene for oncogenic miR-106b, which was identified as an induced miRNA in PCa. Further analysis revealed a loss of RBMS1 expression in prostate tumours compared to corresponding normal tissue. Overexpression of RBMS1 in DU145 and LNCaP prostate cancer cells resulted in diminished cell proliferation, colony forming ability as well as in retarded gap closing. Our results demonstrate for the first time a miR-106b dependent downregulation of RBMS1 in prostate carcinoma. Additionally, we show new tumour suppressive properties of RBMS1 whose observed loss may further elucidate the development of PCa.

Induction of proliferative and mutagenic activity by benzo(a)pyrene in PC-3 cells via JAK2/STAT3 pathway

Environmental carcinogen benzo(a)pyrene (BaP) is a representative compound of polycyclic aromatic hydrocarbons (PAHs). BaP is strongly associated with prostate carcinogenesis. However, the molecular mechanism of BaP in development of prostate carcinoma remains largely unknown. The aim of this study was to investigate the effect and mechanism of BaP on the development in prostate cancer. PC-3 cells were exposed to different concentrations of BaP for 24, 48, 72 h, respectively. We analyzed the effect of BaP on PC-3 cell viability, cell cycle, DNA strand breaks, mutagenic activity, and migration. The expression of associated regulatory genes and the effect of JAK2/STAT3 signaling were also measured to explore the relationships among BaP metabolism, the JAK2/STAT3 pathway and proliferative activity in PC-3 cells. We observed significant effects on proliferation, DNA strand breaks and mutagenic activity after BaP exposure in PC-3 cells, and inhibitors of CYP1 and the AhR transcription factor α -naphthoflavone (ANF) and CH223191 treatment clearly reduced both cell survival and mutagenesis associated with BaP exposure. Reduction in G0-G1 phase population and elevation in S phase were observed after BaP exposure. Migratory cells for PC-3 were significantly increased. The results were further confirmed by the expression of mRNA levels in the significant increments of Snail, Slug, MMP-9, CYP1A1, CYP1B1, CycilnD1, CDK4 and significant reduction of E-cadherin. Significant enhancements were found in the expression of JAK2, STAT3 after BaP treatment. Additionally, activator IL-6 significantly enhanced the effect of BaP on cell survival, mutagenic activity, Cyclin D1, CDK4, Snail, and JAK2/STAT3 expression in PC-3 cells. Significant reductions in cell survival, mutagenic activity, Cyclin D1, CDK4, Snail, and JAK2/STAT3 expression were found after inhibitor AG490, ANF and CHJ223191 treatment. These findings reveal that BaP enhances the proliferative and mutagenic activity via JAK2-STAT3 pathway in PC-3 cells, and provide the additional evidence to understand the crucial role of BaP in prostate cancer carcinogenesis.

Immunohistochemical expression of androgen receptors in prostate carcinoma and benign prostatic hyperplasia

Background/Aim. Prostate carcinoma (PCa) and its parent organ are influenced by hormones, which is used for therapeutic purposes. Through androgen receptors (AR) androgens influence cell growth and function, proliferation, differentiation, apoptosis, lipid metabolism and secretory activity of the prostate, as well as development and progression of PCa. An antiandrogen therapy is carried out in patients with metastatic PCa, in order to block effects of androgens. By conducting immunohistochemical analysis of androgen receptors in the PCa tissue, we can assume how the tumour will react to an administered antiandrogen therapy, both in androgen-positive and androgen-negative, resistant tumours. Knowledge of the presence of AR in the tumour tissue may serve as a prognostic indicator in histopathological analysis. The aim of this study was to evaluate the expression of AR in patients with benign prostatic hyperplasia (BPH) and in those with PCa, before therapy. Methods. Immunohistochemical analysis was carried out by using anti-human AR monoclonal antibody AR441 (DAKO), and presence and intensity of AR were semi-quantitatively evaluated in 195 patients, 165 with BPH and 30 with PCa. Material for analysis was obtained by needle biopsy or transurethral resection of the prostate (TURP). Results. All secretory cells in patients with BPH were intensively androgen positive, while in patients with PCa they were mostly moderately to highly positive, but with foci of negativity. The observed negative correlation between AR and Gleason score and the International Society of Urologic Pathology (ISUP) grade group of PCa was not statistically significant. Conclusion. Study results indicate that PCa, before therapy, is androgen-dependent, with a high level of AR expression.

Differential immunohistochemical expression of AMACR and ERG in prostatic lesions

Introduction Alpha-methylacyl-CoA (AMACR) is an enzyme of the mitochondria and perixosomes. It was found that it showed great overexpression in prostatic adenocarcinoma, even with minimal foci. TMPRSS2/ERG fusion is one of the common genetic anomalies affecting PCa. A great correlation between positive immunohistochemical (IHC) expression for ERG and the state of fusion has been found, but the diagnostic and prognostic importance of ERG IHC remains undetected. This study aimed to evaluate the differential diagnostic and prognostic significance of both AMACR and ERG in PCa with correlation to the clinicopathological variables.Materials and methods TThe authors reviewed 70 prostatic lesions. Prostatic adenocarcinoma (50 cases), prostatic intraepithelial neoplasia (PIN) (15 with high-grade PIN, five with low-grade PIN), and benign prostatic hyperplasia (10 cases) that were used as a control. Immunohistochemical staining for AMACR and ERG was done. Follow-up of the cases for 18 months was also done.Results A statistically significant difference in the expression of ERG among the examined cases was found. It was negative in control benign prostatic hyperplasia and low-grade PIN cases), positive in 20% of high-grade PIN, and 74% of prostatic adenocarcinoma cases (P<0.01). No statistically significant correlation was found between ERG expression and tumor volume, Gleason sum score, stage, surgical margin, presence of lymphovascular invasion, perinural invasion, distant metastasis, and survival (P>0.05). Regarding AMACR expression, a statistically significant difference in the expression of AMACR among the examined cases was found (negative in benign prostatic hyperplasia, and low PIN cases) to be positive in 33.3% of high-grade PIN and in 62% of prostatic adenocarcinoma cases (P<0.01). A statistically significant correlation was found between AMACR expression and tumor volume, Gleason sum score, surgical margin, presence of lymphovascular invasion, and survival (P<0.05).Conclusion The study provides an additional evidence that IHC expression of AMACR has a role in prostatic carcinoma development. IHC expression of AMACR was absent in benign prostatic lesions. AMACR is an essential tumor marker for the diagnosis and prognosis of prostatic lesions. IHC expression of ERG may have a role in the diagnosis and biological stratification of prostate cancer.

Study of the expression of metastasis-associated in colon cancer 1, thymidine kinase 1 and the clinical significance of prostate carcinoma

Objective To investigate the expression of metastasis-associated in colon cancer 1 (MACC1), thymidine kinase 1 (TK1) in prostate carcinoma tissues and their effect on the development of prostate carcinoma. Methods The expression levels of MACC1 and TK1 in 70 cases of prostate carcinoma tissues and 20 cases of benign prostatic hyperplasia tissues were detected by using immunohistochemical method, the relationship between the levels of MACC1, TK1 and the clinicopathological features of prostate carcinoma were analyzed. Results The expression rate of MACC1 in prostate carcinoma tissues was higher than that of benign prostatic hyperplasia tissues (61.43% vs. 20.00%, t=10.700, P=0.000), the expressions of MACC1 were related prostate carcinoma to histology grade, Clinical stage and seminal vesicle invasion (Respectively, t=8.930, P=0.010, t=6.720, P=0.010, t=4.850, P=0.030); The expression rate of TK1in prostate carcinoma tissues was higher than that of benign prostatic hyperplasia tissues (64.29% vs. 15.00%, t=15.180, P= 0.000), the expressions of TK1 were related prostate carcinoma to histology grade and Clinical stage (Respectively, t=7.290, P=0.030, t=6.790, P=0.010). Conclusion MACC1 and TK1 might be play an important role in the invasion and metastasis in prostate carcinoma. Key words: Metastasis-associated in colon cancer 1; Thymidine kinase 1; Prostate carcinoma; Immunohistochemical method

Maternal Low-Protein Diet Impairs Prostate Growth in Young Rat Offspring and Induces Prostate Carcinogenesis With Aging.

Carcinogenesis is frequently linked to genetic background, however, exposure to environmental risk factors has gained attention as the etiologic agent for several types of cancer, including prostate. The intrauterine microenvironment has been described as a preponderant factor for offspring health; and maternal exposure to insult has been linked to chronic disease in older offspring. Using a model of maternal exposure to low-protein diet (LPD; 6% protein), we demonstrated that impairment of offspring rat prostatic growth on postnatal day (PND) 21 was associated with prostate carcinogenesis in older offspring (PND 540). One explanation is that maternal LPD consumption exposed offspring to an estrogenic intrauterine microenvironment, which potentially sensitized prostate cells early during glandular morphogenesis, increasing cellular response to estrogen in older rats. The onset of accelerated prostatic growth, observed on PND 21, associated with an unbalanced estrogen/testosterone ratio and increased circulating IGF-1 in older offspring appears to contribute to the development of prostate carcinoma in groups on gestational low protein and gestational and lactational low protein diets (33 and 50%, respectively). Our study strongly indicated maternal exposure to LPD as a potential risk factor for induction of slow-growing prostate carcinogenesis in rat offspring later in life.

Reduced Levels of ATP Synthase Subunit ATP5F1A Correlate with Earlier-Onset Prostate Cancer.

Switching of cellular energy production from oxidative phosphorylation (OXPHOS) to aerobic glycolysis occurs in many types of tumors. However, the significance of energy metabolism for the development of prostate carcinoma is poorly understood. We investigated the expression of OXPHOS complexes in 94 human prostate carcinomas and paired benign tissue using immunohistochemistry. Overall mitochondrial mass was upregulated in carcinomas compared to benign prostate tissue in all Gleason grades. A significant direct correlation between the expression of OXPHOS complexes I, II, and V and the Gleason score was observed. However, 17% of prostate carcinomas and 18% of benign prostate tissues showed isolated or combined deficiency of OXPHOS complexes (one deficiency in 12% of the tumors, combined deficiencies in 5%). Complex I was absent in 9% of the samples, with only parts of the tumor affected. ATP5F1A, a complex V protein, was the most frequently affected subunit, in 10% of tumors and 11% of benign prostate tissues (but not both tissues in any single patient). A possible role of complex V in prostate cancer development is suggested by the significant positive correlation of ATP5F1A levels with earlier-onset prostate cancer (age at diagnosis and at prostatectomy) and free PSA percentage. The relatively high percentage (17%) of prostate carcinomas with regional foci of partial OXPHOS complex deficiencies could have important therapeutic implications.

Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis.

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

Correlation analysis between sperm-associated antigen 9 and epithelial-mesenchymal transition, extracelluar matrix-associated protein in prostate cancer

Objective To study correlation between sperm-associated antigen 9 (SPAG9) and epithelial-mesenchymal transition (EMT), extracelluar matrix (ECM)-associated protein in prostate cancer. Methods The immunohistochermical analysis was used to detect the expression of SPAG9, E-cadherin, Vimentin and matrix metalloproteinase-2 (MMP-2) in 60 specimens of prostatic carcinoma (PCa) and 30 specimens of benign prostate hyperplasia (BPH). Statistical analyses were used to evaluate the relationship between SPAG9 and E-cadherin, Vimentin, MMP-2. Results The immunohistochermical analysis showed the average integral absorbance (IA) of each protein in metastatic PCa, nonmetastatic PCa and BPH as follows: for SPAG9 (466.34±13.52, 284.98±25.69 and 106.01±13.58, the differences were all statistically significant, P=0.000); for Vimentin (285.79±15.85, 184.20±21.31 and 79.56±7.96, the differences were all statistically significant, P=0.000); for MMP-2 (269.97±15.74, 175.82±21.81 and 87.86±17.61, the differences were all statistically significant, P=0.000). The IA values of these proteins were reduced successively in the three groups; however, the IA values of E-cadherin (148.62±28.31, 286.73±18.73 and 417.73±12.90, the differences were all statistically significant, P=0.000) were increased successively in the three groups. Pairwise comparisons of each protein’s IA within the three groups revealed the statistically significant differences. There was a positive correlation between SPAG9 and Vimentin (rs=0.443, P=0.014), MMP-2 (rs=0.443, P=0.001) while negative correlation was existed between SPAG9 and E-cadherin (rs=-0.431, P=0.017). Conclusion SPAG9 may promote the occurrence and development of PCa by regulating EMT, ECM-associated proteins. Key words: Sperm-associated antigen 9; Epithelial-mesenchymal transition; Extracelluar matrix; Prostatic carcinoma

Association of Vitamin D With Prostate Carcinoma: A Single Institutional Observational Study

Background: Recent studies highlight a role for vitamin D (VD) in the growth and differentiation of various cell types. The biologically active form of vitamin D3 is 1,25-dihydroxyvitamin D3. Most cells of the body including prostate cells have vitamin D receptor (VDR) and VD metabolizing enzymes, and can respond to 1,25-VD. Literature supports multipronged effects of 1,25-VD in the prevention of prostate carcinoma development and progression. However, the relationship between prostate carcinoma and VD is still not entirely understood. There are no studies conducted on the association of VD and prostate carcinoma among the Asian population and our study is the first of its kind in literature and hence the need for the same. Methods: All men more than 50 years of age who presented to our hospital between July 2015 and July 2017 with lower urinary tract symptom (LUTS), and had a suspicious digital rectal examination (DRE) and hypoechoic areas on transrectal ultrasound (TRUS), were considered for the study. Those patients whose biopsies came as malignancy were taken as study subjects and patients with a negative biopsy were taken as controls. VD and serum prostatic-specific antigen (PSA) was done for all patients undergoing biopsy. Results: Eighty-six men underwent prostate biopsy for suspicious DRE with hypoechoic areas on TRUS. Out of the 86 men, 66 men had a positive histopathology, suggestive of adenocarcinoma of the prostate gland (group A), and the remaining 20 men (group B) had a negative biopsy. All patients diagnosed with malignancy had severe VD deficiency and was found to be statistically significant. Conclusion: VD deficiency is a risk factor for development of prostate carcinoma and there is a strong correlation between them. Further trials are however required to study the effect of VD supplementation on the natural course of the disease. World J Nephrol Urol. 2017;6(3-4):21-24 doi: https://doi.org/10.14740/wjnu317w

Role of Human Papillomavirus Infection in the Development of Prostate Carcinoma and Benign Prostatic Hyperplasia

Role of Human Papillomavirus Infection in the Development of Prostate Carcinoma and Benign Prostatic Hyperplasia

New insights on the association between the prostate cancer and the small DNA tumour virus, BK polyomavirus.

In recent years the scientific literature in the field of the prostate carcinoma (PCa) pointed out on the genetic heterogeneity and mutations occurring in this tumour, while little attention was given to the causes of PCa onset, in particular infectiuos agents. In this brief commentary, we wish to point out recent advancements done on the role of the human polyomavirus BK (BKPyV) in the development of PCa by harnessing both humoral and cellular immune responses. Altogether, these new insights suggest that BKPyV is involved in the transforming activity during the multistep process of PCa development. Although these findings do not provide evidence for a causal relationship between BKPyV and PCa development, additional investigations with novel techniques will help to make it a concrete event.

ERG Expression in Prostate Needle Biopsy: Potential Diagnostic and Prognostic Implications.

To investigate the prognostic and diagnostic value of ERG immunohistochemistry (IHC) in prostate needle biopsy when combined with AMACR-CK5/6. ERG IHC was assessed in 119 consecutive prostate needle biopsies where the dual-stain AMACR-CK5/6 IHC was ordered and in 16 cases with a Gleason score (GS) ≥7. IHC results were evaluated in prostate carcinoma (PCA), high-grade prostatic intraepithelial neoplasia (HGPIN), HGPIN with adjacent atypical glands (PINATYP), atypical/suspicious (ASAP) foci, and benign PCA mimickers. GS, HGPIN, extraprostatic extension, perineural invasion, bilateralism of PCA, largest percent of core, and the overall percent of tissue involved by PCA were recorded. ERG was detected in 36% of PCA, 27% of HGPIN, 13% of ATYP/PINATYP, and none of benign mimickers. ERG-positive HGPIN was strongly associated with ERG-positive PCA in the same core compared with ERG-negative HGPIN (P<0.0001). Positive ERG expression in PCA was inversely related to GS and showed trends toward association with higher volume and bilateral disease. ERG was more specific for PCA than AMACR (0.87 vs. 0.23), but less sensitive (0.36 vs. 0.95). In conclusion, ERG IHC is of limited additional diagnostic value when added to AMACR and CK5/6. ERG expression is inversely related to GS and is associated with bilateral involvement and higher PCA tumor volume. ERG-positive HGPIN is strongly associated with the presence of PCA in the same core. Studies investigating the prognostic value of ERG in HGPIN should be implemented to address whether patients with ERG-positive HGPIN are at increased risk for subsequent PCA development.

Association Between Methylation of SHP-1 Isoform I and SSTR2A Promoter Regions with Breast and Prostate Carcinoma Development

Methylation pattern is presented here for first time as a potential molecular marker of changes on SSTR2A and SHP-1(I) gene promoter related to breast and prostate carcinoma. Our results have shown low concordances with SSTR2A and methylated state in prostate cancer and moderate relationship with unmethylated CpG-27 in breast cancer. We found significant concordances for both cancers and SHP-1(I) unmethylation, and increased HER2 expression and SSTR2A methylation in breast cancer. Moreover, we found a correlation between methylation patterns of two genes in normal breast tissue. These data might assist to select subgroups of patients for the administration of alternative therapies.

Possible relations between oxidative damage and apoptosis in benign prostate hyperplasia and prostate cancer patients

Cancer has been described as the twentieth century plague, and is a very common health problem. It has been reported that ROS and ROS products play a key role in cancer and that oxidative damage is effective in apoptosis initiation. In this study we aimed to evaluate the relationship between MDA (malondialdehyde), DNA damage (8-hydroxyguanine, 8-OH-dG), and caspase-3 in BHP and prostate cancer patients. Twenty male patients with prostate cancer and 20 male patients with benign prostate hyperplasia were included into this study. The MDA (nanomole), DNA damage (nanograms per millilitre), and caspase-3 (nanograms per millilitre) levels were measured in prostate cancer and benign prostate hyperplasia using Elisa kits (Millipore Corporation, Billerica, MA, USA). In the prostate cancer group, serum MDA (30.96 ± 9.25) and DNA damage (4.42 ± 0.36) levels were significantly raised (p < 0.05) when compared to the benign prostate hyperplasia group (24.05 ± 8.06, 3.99 ± 0.54). However, in the prostate cancer group, serum caspase-3 (2.36 ± 0.82) levels were statistically significantly lowered (p < 0.05) compared with the benign prostate hyperplasia group (3.15 ± 1.04). We observed that altered prooxidant, DNA damage levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that, although the triggering of these changes is unknown, changes in the levels of MDA, DNA damage, and caspase-3 in the blood are related to prostatic carcinoma development. In addition, it would be appropriate to conduct new studies with a large number of patients at different stages.

Liver X Receptors Protect from Development of Prostatic Intra-Epithelial Neoplasia in Mice

LXR (Liver X Receptors) act as “sensor” proteins that regulate cholesterol uptake, storage, and efflux. LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma (PCa) cell lines. This study shows that deletion of LXR in mouse fed a high-cholesterol diet recapitulates initial steps of PCa development. Elevation of circulating cholesterol in Lxrαβ-/- double knockout mice results in aberrant cholesterol ester accumulation and prostatic intra-epithelial neoplasia. This phenotype is linked to increased expression of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2), which results in the down-regulation of the tumor suppressors Msmb and Nkx3.1 through increased methylation of lysine 27 of histone H3 (H3K27) on their promoter regions. Altogether, our data provide a novel link between LXR, cholesterol homeostasis, and epigenetic control of tumor suppressor gene expression.