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1.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414754

RESUMO

BACKGROUND: Prostate cancer is a common male cancer with poor prognosis, and to find molecular diagnostic markers for the early diagnosis of prostate cancer is urgently needed. The aim of this study is to investigate the diagnostic value of serum expression level of miR-494 for prostate cancer. METHODS: Ninety patients with prostate cancer and 90 patients with benign prostatic hyperplasia were enrolled in this study, and 90 healthy volunteers served as the control group. The serum of the participants was collected, and the expression level of miR-494 was measured by RT-PCR. Then the relationship between the expression of miR-494 and the clinical characteristics of the patients was analyzed. Moreover, the correlation between the expression of miR-494 and the Gleason score as well as serum level of prostate specific antigen (PSA) were analyzed. Finally, the diagnostic value of miR-494 for the early diagnosis of prostate cancer was analyzed by ROC curve. RESULTS: miR-494 was significantly increased in the prostatic hyperplasia group compared with the control group, and the level of miR-494 in the prostate cancer group was significantly higher than that in the prostatic hyperplasia group. The level of miR-494 in patients with prostate cancer was positively correlated with tumor size and tumor stage. Moreover, the level of miR-494 was positively correlated with the Gleason score (r = 0.3371, p = 0.0012) and serum level of PSA (r = 0.3485, p = 0.0008) in patients with prostate cancer. Finally, AUC of miR-494 was 0.8090 (95% confidence interval 0.7343 to 0.8837), suggesting that miR-494 is a sensitive biomarker for the diagnosis of prostate cancer. CONCLUSIONS: miR-494 was upregulated in the serum of the patients with prostate cancer and circulating miR-494 can be used as a biomarker for the early diagnosis of prostate cancer.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Curva ROC
2.
Anticancer Res ; 39(8): 4171-4177, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366502

RESUMO

BACKGROUND/AIM: Identification of prostatic stem cells in primary prostate tissue sections, organ cultures of prostate and cell lines requires a range of techniques that allows characterization of stem cells for their potential use in the treatment of patients. Isolated cells usually round-up and develop changes in shape, size and cellular characteristics. The aim of this study was to provide a range of methods for identifying prostatic stem cells and characterizing them with regard to ultrastructure, nuclear morphology, cytoplasmic organelles, and/or expression stem cell marker CD133. MATERIALS AND METHODS: Prostate biopsy and prostatectomy specimens were used for studying prostatic stem cells and their known marker CD133 in tissue sections by light and/or electron microscopy. Inverted capsule embedding was used to study archival metastatic prostate in pelvic nodes and Du145 cell line in a monolayer culture. RESULTS: Staining for CD133 positively identified stem cells that were found in benign prostatic hyperplasia, benign prostate, and prostate cancer cells. Paraffin embedded sections showed a single type of stem cells, whereas methylene blue-stained Epon sections showed both light and dark stem cells. Electron microscopy showed that both basal and stem cells were closely associated with the basement membrane (basal lamina). Stem cells had smooth plasma and nuclear membranes, a prominent nucleolus, small mitochondria, and few ribosomes. Du145 cells were separated by intercellular spaces in monolayer culture. CONCLUSION: The inverted capsule embedding method allowed the study of metastasized prostate cancer in pelvic lymph nodes. Our approach enabled the assessment of stem cells in tissue sections by light and electron microscopy.


Assuntos
Antígeno AC133/genética , Membrana Basal/ultraestrutura , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Membrana Basal/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Microscopia Eletrônica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/ultraestrutura , Próstata/metabolismo , Próstata/patologia , Próstata/ultraestrutura , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/ultraestrutura
3.
Clin Lab ; 65(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307177

RESUMO

BACKGROUND: Prostate cancer (PC) is considered the fifth most common cancer causing death worldwide. Many studies have pointed to dysregulated microRNA (miRNA) expression in PC and their use in early detection and follow-up of the disease. In addition, the Prostate Health Index (PHI) is the FDA-approved blood test joining total, free, and -2proPSA having greater specificity than free and total PSA for assessment of PC. METHODS: In this study, we evaluated the plasma levels of miR-21and miR-221 expression using quantitative real-time polymerase chain reaction (qRT-PCR) among 100 prostate cancer patients (50 localized and 50 metastatic cases) and 50 benign prostatic hyperplasia patients in comparison to 50 normal control subjects, as well as assess-ed its diagnostic and prognostic value and its correlation with the Prostate Health Index (PHI). RESULTS: To our knowledge, we are the first study to join PHI with miRNAs in assessing PC diagnosis and progno-sis. Our results showed that adding miR-21 to PHI for detecting patients with LPC, increased the sensitivity to 95.5% at a specificity 100% (p < 0.0001). Additionally, combining miR-221 and PHI for differentiating patients with MPC, increased the sensitivity to 96.4% at a specificity 100% (p < 0.0001). CONCLUSIONS: The potentials of circulating miR-21, miR-221, and PHI serum level as biomarkers for PC have been established not only as diagnostic factors but also as prognostic markers.


Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Hiperplasia Prostática/sangue , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/genética , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Curva ROC
4.
Mediators Inflamm ; 2019: 7894017, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360119

RESUMO

Investigations on prostate inflammation-related disorders, including acute and chronic prostatitis, chronic pelvic pain syndrome, benign prostate hyperplasia (BPH), and prostate cancer (PCa), are still ongoing to find new, accurate, and noninvasive biomarkers for a differential diagnosis of those pathological conditions sharing some common macroscopic features. Moreover, an ideal biomarker should be useful for risk assessment of prostate inflammation progression to more severe disorders, like BPH or PCa, as well as for monitoring of treatment response and prognosis establishment in carcinoma cases. Recent literature evidence highlighted that changes in the expression of transglutaminases, enzymes that catalyze transamidation reactions leading to posttranslational modifications of soluble proteins, occur in prostate inflammation-related disorders. This review focuses on the role specifically played by transglutaminases 4 (TG4) and 2 (TG2) and suggests that both isoenzymes hold a potential to be included in the list of candidates as novel diagnostic biomarkers for the above-cited prostate pathological conditions.


Assuntos
Biomarcadores Tumorais/metabolismo , Isoenzimas/metabolismo , Transglutaminases/metabolismo , Biomarcadores Tumorais/genética , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Humanos , Isoenzimas/genética , Masculino , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Processamento de Proteína Pós-Traducional , Transglutaminases/genética
5.
Prostate ; 79(11): 1199-1210, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31251827

RESUMO

BACKGROUND: With the popularity of serum prostate-specific antigen (PSA) screening, the number of newly diagnosed prostate cancer (PCa) patients is increasing. However, indolent or invasive PCa cannot be distinguished by PSA levels. Here, we mainly explored the role of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in the invasiveness of PCa. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis was used to detect the expressions of hnRNPM in PCa and benign prostate hyperplasia (BPH) tissues as well as in PCa cell lines. Immunohistochemistry was applied to detect the hnRNPM or Yin Yang 1 (YY1) expression in BPH, prostate adenocarcinoma (ADENO) and neuroendocrine prostate cancer (NEPC) tissues. After aberrant, the expression of hnRNPM in C4-2 and PC3 cells, the changes of cell migration and invasion were observed through wound-healing and transwell assays. We also predicted the transcription factor of hnRNPM through databases, then verified the association of hnRNPM and YY1 using chromatin immunoprecipitation (ChIP) and luciferase assays. RESULTS: The expression level of hnRNPM is gradually reduced in BPH, ADENO, and NEPC tissues and it is less expressed in more aggressive PCa cell lines. Overexpression of hnRNPM can significantly reduce Twist1 expression, which inhibits the migration and invasion of PCa cells in vitro. In PCa cells, overexpression of YY1 can promote epithelial-mesenchymal transition by reducing hnRNPM expression. Furthermore, this effect caused by overexpression of YY1 can be partially attenuated by simultaneous overexpression of hnRNPM. CONCLUSIONS: Our study demonstrates that hnRNPM negatively regulated PCa cell migration and invasion, and its expression can be transcriptionally inhibited by YY1. We speculated that hnRNPM may be a biomarker to assist in judging the aggressiveness of PCa.


Assuntos
Adenocarcinoma/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/metabolismo , Invasividade Neoplásica/genética , Neoplasias da Próstata/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/genética , Humanos , Masculino , Invasividade Neoplásica/patologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
6.
PLoS One ; 14(4): e0215003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970027

RESUMO

Urine of prostate cancer (PCa) carries miRNAs originated from prostate cancer cells as a part of both nucleoprotein complexes and cell-secreted extracellular vesicles. The analysis of such miRNA-markers in urine can be a convenient option for PCa screening. The aims of this study were to reveal miRNA-markers of PCa in urine and design a robust and precise diagnostic test, based on miRNA expression analysis. The expression analysis of the 84 miRNAs in paired urine extracellular vesicles (EVs) and cell free urine supernatant samples from healthy donors, patients with benign and malignant prostate tumours was done using miRCURY LNA miRNA qPCR Panels (Exiqon, Denmark). Sets of miRNAs differentially expressed between the donor groups were found in urine EVs and urine supernatant. Diagnostically significant miRNAs were selected and algorithm of data analysis, based on expression data on 24-miRNA in urine and obtained using 17 analytical systems, was designed. The developed algorithm of data analysis describes a series of steps necessary to define cut-off values and sequentially analyze miRNA expression data according to the cut-offs to facilitate classification of subjects in case/control groups and allows to detect PCa patients with 97.5% accuracy.


Assuntos
MicroRNAs/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Estudos de Casos e Controles , Interpretação Estatística de Dados , Vesículas Extracelulares/genética , Redes Reguladoras de Genes , Humanos , Masculino , MicroRNAs/urina , Pessoa de Meia-Idade , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/genética , Hiperplasia Prostática/urina , Neoplasias da Próstata/urina
7.
Oncol Rep ; 41(4): 2491-2501, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816510

RESUMO

Benign prostatic hyperplasia (BPH) is a common chronic disease in older males. The pathogenesis of BPH remains elusive but may be associated with chronic inflammation. Chemokines and chemokine receptors have been implicated as critical mediators in the immune response and inflammatory processes. In the present study, the aim was to evaluate the association of three polymorphisms in chemokine genes, namely C­C motif chemokine ligand (CCL)2 rs1024611, CC chemokine receptor 2 (CCR2) rs1799864 and CCL5 rs2107538, with BPH risk. These polymorphisms were genotyped in 109 patients with BPH and 160 control subjects, using the polymerase chain reaction and multiple ligase detection reaction method. The CCL5 rs2107538 polymorphism was identified to be associated with a significantly lower risk of BPH [A/G vs. G/G: odds ratio (OR)=0.37, 95% confidence interval (CI)=0.17­0.78; A/A + A/G vs. G/G: OR=0.39, 95% CI=0.19­0.79; A vs. G: OR=0.58, 95% CI=0.35­0.96). However, this polymorphism was also associated with the development of larger prostate volumes in patients with BPH (A/G vs. G/G: OR=3.02, 95% CI=1.28­7.11; AA + AG vs. GG: OR=2.83, 95% CI=1.28­6.26; A vs. G: OR=1.94, 95% CI=1.08­3.49). The CCR2 rs1799864 polymorphism was associated with lower International Prostate Symptom Score values (A/A + A/G vs. G/G: OR=0.39, 95% CI=0.17­0.91; A vs. G: OR=0.43, 95% CI=0.20­0.90) and low Qmax (A/G vs. G/G: OR=0.38, 95% CI=0.16­0.92; AA + AG vs. GG: OR=0.39, 95% CI=0.17­0.91) in the patients. No association was observed between the CCL2 rs1024611 polymorphism and BPH. These results suggest that the CCR2 and CCL5 genes may contribute to the occurrence and progression of BPH.


Assuntos
Quimiocina CCL2/genética , Quimiocina CCL5/genética , Predisposição Genética para Doença , Hiperplasia Prostática/genética , Receptores CCR2/genética , Idoso , Estudos de Casos e Controles , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Polimorfismo de Nucleotídeo Único , Próstata/patologia , Hiperplasia Prostática/patologia , Fatores de Risco
8.
Oncol Rep ; 41(3): 1789-1796, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30747213

RESUMO

Krüppel­like factor 4 (KLF4) is a transcription factor and putative tumor suppressor. However, little is known about its role in the progression of prostate cancer. The aim of the present study was to examine the expression and potential role of KLF4 in prostate cancer. KLF4 and E­cadherin expression in 60 prostate cancer tissues and 60 benign prostatic hyperplasia tissues was characterized by immunohistochemistry. The levels of KLF4 expression in prostate cancer cells were determined by reverse transcription­quantitative polymerase chain reaction and western blot analysis. LNCaP cells were transduced with lentivirus to induce KLF4 overexpression. The effects of KLF4 overexpression on proliferation, cell cycle and migration were determined by MTT, flow cytometry, wound healing and Transwell migration assays. KLF4 was identified to be primarily expressed in the cytoplasm of non­tumor prostate tissues. The percentage of KLF4+ tissues among prostate cancer tissues (16.67%) was significantly lower compared with that of non­tumor tissues (84.67%; P<0.05). Downregulated KLF4 expression was associated with higher stage, positive lymph node metastasis and higher Gleason scores of prostate cancer (all P<0.05). Induction of KLF4 overexpression significantly inhibited the proliferation, wound healing and migration of LNCaP cells and induced their cell cycle arrest at S phase. Furthermore, E­cadherin expression was downregulated in prostate cancer tissues and KLF4 overexpression enhanced the levels of E­cadherin expression in LNCaP cells. In conclusion, downregulated KLF4 expression was associated with aggressiveness of prostate cancer, and KLF4 overexpression inhibited the proliferation, wound healing and migration of prostate cancer cells by inducing cell cycle arrest and E­cadherin expression.


Assuntos
Regulação para Baixo/genética , Fatores de Transcrição Kruppel-Like/genética , Neoplasias da Próstata/genética , Caderinas/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Humanos , Masculino , Gradação de Tumores/métodos , Próstata/patologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia
9.
Indian J Pathol Microbiol ; 62(1): 99-102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30706868

RESUMO

Background: The expression of androgen (AR) and estrogen receptors (ER-A, ER-B) in Prostate cancer is well documented, but there are limited data about the same in patients with BPH. Hence the present study was designed to analyse the gene and protein expression of androgen and estrogen receptors in patients with BPH. Materials and Methods: Prostatic tissues were obtained from 27 BPH patients aged between 55 to 85 years by transurethral resection of prostate. Based on prostate volume, BPH patients were divided into two groups, Group A (≤30mL) and Group B (>30mL). The mRNA and protein expression of AR, ER-A and B were assessed by Quantitative real time PCR, Western blotting and Immunohistochemistry. Results: AR gene (P < 0.05) and protein expression (P = 0.03) and ER-A gene (P < 0.05) and protein expression (P = 0.02) was significantly higher in BPH patients with larger prostate size compared to smaller prostate size. Immunohistochemistry showed that AR expression was predominate in ductal cells of larger volume prostate tissues while AR expression in stromal tissue was the dominant finding in patients with smaller prostate size. Also serum estradiol was significantly increased in patients with larger prostate size (P = 0.03). Conclusion: Androgen and Estrogen receptor expression increases with increase in prostate volume in BPH cases.


Assuntos
Estudos de Associação Genética , Próstata/patologia , Hiperplasia Prostática/genética , Receptores Androgênicos/genética , Receptores Estrogênicos/genética , Idoso , Idoso de 80 Anos ou mais , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Próstata/cirurgia , Hiperplasia Prostática/etiologia , Neoplasias da Próstata , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real , Ressecção Transuretral da Próstata
10.
Gene ; 692: 22-25, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30641210

RESUMO

Prostate cancer (PCa) and benign prostate hyperplasia (BPH) as two prevalent age-related disorders in male have some shared genetic and immunological underlying mechanisms. However, researchers have aimed at identification of specific biomarkers with the ability to differentiate between these disorders. In the present study, we genotyped the rs4073, rs2227306 and rs1126647 single nucleotide polymorphisms within IL-8 gene in 530 individuals including 130 PCa patients, 200 BPH patients and 200 male controls. The rs2227306 alleles and genotypes were distributed equally in the three study groups. The frequency of the A allele of the rs4073 was significantly lower in PCa group compared with BPH group (OR (95% CI) = 0.62 (0.46-0.84), adjusted P value = 0.006). This allele was negatively associated with PCa risk in dominant model (OR (95% CI) = 0.53 (0.34-0.83), adjusted P value = 0.02). When comparing PCa and BPH groups, the rs1126647 was associated with PCa risk in recessive model (OR (95% CI) = 2.14 (1.23-3.72), adjusted P value = 0.02). The A T A haplotype (rs4073, rs2227306 and rs1126647 respectively) was less frequent in PCa group compared with BPH group (OR (95% CI) = 0.4 (0.22-0.75), adjusted P value = 0.03). Consequently, our data demonstrated significant differences in allele, genotype and haplotype frequencies of IL-8 variants between BPH and PCa patients which might imply distinct role for this chemokine in the pathogenesis of these disorders. Future studies are needed to elaborate the underlying mechanism of these observations.


Assuntos
Interleucina-8/genética , Polimorfismo de Nucleotídeo Único , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade
11.
World J Urol ; 37(4): 709-718, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30069579

RESUMO

PURPOSE: The enzyme 5-α reductase type 2 (5-AR 2) plays a key role in the development and maintenance of the prostate gland. We evaluated the level 5-AR 2 protein expression and the relationship between methylation of the 5-AR 2 gene-promoter and 5-AR 2 protein expression of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 37 prostate samples were evaluated. These included 22 samples from men undergoing transurethral prostate resections and 15 non-cancerous transition-zone human prostate tissue samples taken following radical prostatectomy. We quantified 5-AR 2 protein expression and gene-promoter methylation status using common assay procedures. Clinical variables included age, body mass index (BMI), prostate-specific antigen (PSA) levels, lipid profiles, and prostate volumes. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling. RESULTS: We were able to extract DNA from 36 of the 37 tissue samples and 10 of these (28%) did not express the 5-AR 2 protein. In total, 26 patients (72%) had methylated 5-AR 2 promoter-regions. There was a strong correlation between methylation of the 5-AR 2 promoter-regions and low-absent 5-AR 2 protein expression (p = 0.0003). Increasing age significantly predicted methylation status and protein expression level (p = 0.013). CONCLUSIONS: The level of 5-AR 2 protein expression varies among prostate tissue samples. Methylation of the 5-AR 2 gene-promoter may account for low or absent expression of 5-AR 2 in adult human prostate tissues. Increased age correlates with increased 5-AR 2 gene-promoter methylation and decreased protein expression in men with BPH.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Metilação de DNA , Proteínas de Membrana/genética , Regiões Promotoras Genéticas , Hiperplasia Prostática/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Modelos Logísticos , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Hiperplasia Prostática/metabolismo , Ressecção Transuretral da Próstata
12.
Urol J ; 16(2): 141-144, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-30251751

RESUMO

PURPOSE: Prostate cancer (PCa) and benign prostate hyperplasia (BPH) are two prevalent disorders among men with considerable mortality and morbidity. Several association studies have been conducted in different populations to find genetic loci linked with these disorders. Retinoic acid-receptor-related orphan receptor alpha (RORA) codes for a transcription factor which regulates expression of several cancer-related genes. Besides, RORA has been shown to be down-regulated in PCa tissues and cell lines. MATERIALS AND METHODS: In the present study we evaluated genotype and allele frequencies of rs11639084 and rs4774388 variants within RORA gene in PCa and BPH patients compared with healthy subjects. RESULTS: The rs11639084 and rs4774388 alleles were not different between PCa and normal groups 95% CI: 0.52-1.24, OR = 1.04, P = .34; 95% CI: 0.48-1.33, OR = .79, P = .39 respectively. Moreover, we did not detect any significant difference in allele, genotype or haplotype frequencies of these SNPs between the other study groups. CONCLUSION: The mentioned RORA variants are possibly not involved in the pathogenesis of PCa and BPH. Future studies are needed to assess the associations between other variant within this gene and PCa risk to suggest a putative mechanism for involvement of RORA in PCa.


Assuntos
Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Masculino , Fatores de Risco
13.
Eur J Hum Genet ; 27(3): 466-474, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30341416

RESUMO

Hereditary hearing loss (HHL) is an extremely heterogeneous disorder with autosomal dominant, recessive, and X-linked forms. Here, we described an Italian pedigree affected by HHL but also prostate hyperplasia and increased ratio of the free/total PSA levels, with the unusual and extremely rare Y-linked pattern of inheritance. Using exome sequencing we found a missense variant (r.206A>T leading to p.Asp69Val) in the TBL1Y gene. TBL1Y is homologous of TBL1X, whose partial deletion has described to be involved in X-linked hearing loss. Here, we demonstrate that it has a restricted expression in adult human cochlea and prostate and the variant identified induces a lower protein stability caused by misfolded mutated protein that impairs its cellular function. These findings indicate that TBL1Y could be considered a novel candidate for HHL.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo Y/genética , Perda Auditiva/genética , Hiperplasia Prostática/genética , Transducina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cóclea/metabolismo , Feminino , Doenças Genéticas Ligadas ao Cromossomo Y/patologia , Perda Auditiva/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Próstata/metabolismo , Hiperplasia Prostática/patologia , Estabilidade Proteica , Síndrome , Transducina/metabolismo
14.
Urol J ; 16(3): 267-273, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-30318571

RESUMO

PURPOSE: This study aims to investigate the expression level of mir-let7b-3p and mir-548, which are involved in PTEN expression in tissue samples of prostate cancer patients versus benign prostate hyperplasia (BPH) and normal adjacent tissue. MATERIALS AND METHODS: Prostate cancer tissues were obtained from patients after receiving informed consent. Total RNA extraction and cDNA synthesis were performed for determining gene expression. RESULTS: Ten patients were determined to have high Gleason scores (> 7), 36 and seven samples had intermediate Gleason scores (7?) and BPH, respectively, and 40 samples were derived from normal adjacent tissue. Downreg-ulation of mir-let7b and upregulation of mir-548 expression significantly correlated with high-risk Gleason scores. CONCLUSION: The present study showed that miR-let7b and/or mir-548 can be considered as potential targets in prostate cancer therapy.


Assuntos
MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia
15.
Prostate ; 79(3): 312-319, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30450670

RESUMO

BACKGROUND: Benign prostate hyperplasia (BPH) is the most common disease among aging males, but no reports have addressed the prevalence of BPH in Zhengzhou. Therefore, we aimed to understand the prevalence of BPH in men aged 40 years or older in Zhengzhou's rural areas through a cross-sectional study and analyzed the correlation with epidemiologic factors and the heritability of the disease. MATERIALS AND METHODS: A multistage sampling method was used to randomly select male respondents in Zhengzhou's rural areas. Men who were 40 years of age or older and their first-degree relatives were subjected to the International Prostate Symptom Score (IPSS) and related examinations. Heritability was calculated according to the prevalence of the first-degree relatives in the case and control groups. RESULTS: The prevalence of BPH was 10.04%. Its prevalence increased with age, from 2.17% in men aged 40-44 years to 31.11% in men aged 80 years or older. The average volume of the prostate was 17.16 ± 7.96 mL, and the average IPSS was 5.89 ± 5.91. The analysis of the correlation between the associated risk factors and BPH revealed that prostatitis and a history of prostatic hyperplasia were significant factors. Obesity, smoking, drinking, diabetes, and hypertension were not correlated with BPH. Of the 94 first-degree relatives of the cases, 53 had BPH (56.38%); of the 106 first-degree relatives of the controls, five had BPH (4.72%). Heritability appeared to account for 40.48% of BPH cases. The heritability of incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia was 43.28, 71.37, 9.67, 5.67, 2.70, 53.36, and 19.12%, respectively. CONCLUSION: The total prevalence of BPH in men aged 40 years or older in Zhengzhou's rural areas was 10.04%, and the heritability of prostatic hyperplasia was 40.48%.


Assuntos
Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/genética , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural/estatística & dados numéricos
16.
Cancer Genomics Proteomics ; 16(1): 29-58, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30587498

RESUMO

BACKGROUND/AIM: Periprostatic adipose tissue (PPAT) directs tumour behaviour. Microenvironment secretome provides information related to its biology. This study was performed to identify secreted proteins by PPAT, from both prostate cancer and benign prostate hyperplasia (BPH) patients. PATIENTS AND METHODS: Liquid chromatography-mass spectrometry-based proteomic analysis was performed in PPAT-conditioned media (CM) from patients with prostate cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or benign disease (CM-BPH). RESULTS: The highest number and diversity of proteins was identified in CM-T3. Locomotion was the biological process mainly associated to CMs-T and reproduction to CM-T3. Immune responses were enriched in CMs-T. Extracellular matrix and structural proteins were associated to CMs-T. CM-T3 was enriched in proteins with catalytic activity and CM-T2 in proteins with defense/immunity activity. Metabolism and energy pathways were enriched in CM-T3 and those with immune system functions in CMs-T. Transport proteins were enriched in CM-T2 and CM-BPH. CONCLUSION: Proteins and pathways reported in this study could be useful to distinguish stages of disease and may become targets for novel therapies.


Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteoma , Proteômica , Idoso , Cromatografia Líquida , Biologia Computacional/métodos , Meios de Cultivo Condicionados/metabolismo , Curadoria de Dados , Perfilação da Expressão Gênica , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Proteômica/métodos
17.
Int J Immunopathol Pharmacol ; 32: 2058738418812349, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30453799

RESUMO

Benign prostatic hypertrophy (BPH) has become a troublesome disease for elder men. Triptolide (TPL) has been reported to be a potential anticancer agent. However, the potential effects of TPL on BPH have not been shown out. BPH-1 cells were treated with different concentrations of TPL and/or transfected with microRNA-218 (miR-218) inhibitor, pc-survivin, sh-survivin, or their corresponding controls (NC). Thereafter, cell viability was determined by CCK-8 assay. Cell migration was accessed by modified two-chamber migration assay. Cell apoptosis was checked by propidium iodide (PI) and fluorescein isothiocyanate (FITC)-conjugated Annexin V staining. In addition, messenger RNA (mRNA) and protein levels were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. BPH-1 cell viability and migration were significantly decreased, while cell apoptosis and expression of miR-218 were statistically enhanced by TPL ( P < 0.05 or P < 0.01). However, downregulation of miR-218 increased cell viability and migration, while decreased cell apoptosis compared with the negative control group ( P < 0.05 or P < 0.01). Furthermore, the expression of cell cycle-related proteins and cell apoptosis-related proteins were also led to the opposite results with NC. In addition, we found that miR-218 negatively regulated the expression of survivin ( P < 0.01) and suppression of survivin significantly enhanced cell apoptosis ( P < 0.01). Moreover, the results demonstrated that TPL could inactivate mammalian target of rapamycin (mTOR) pathway, while inhibition of miR-218 alleviated the effects. TPL inhibits viability and migration of BPH-1 cells and induces cell apoptosis and also inactivates mTOR signal pathway via upregulation of miR-218. This study provides evidence for the further studies representing triptolide as a potential agent in the treatment of human BPH.


Assuntos
Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/farmacologia , Epitélio/efeitos dos fármacos , MicroRNAs/genética , Fenantrenos/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos , Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Epitélio/metabolismo , Compostos de Epóxi/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Próstata/efeitos dos fármacos , Próstata/metabolismo , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Survivina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ativação Transcricional/efeitos dos fármacos
18.
Proc Natl Acad Sci U S A ; 115(47): E11091-E11100, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30397150

RESUMO

Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR-183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of the Zn importer ZIP1 (target of miR-182), leading to a reduction of prostatic Zn. This inverse relationship between miR-182 and ZIP1 also occurs in human prostate cancer tissue, which is known for Zn loss. The discovery that the Zn-depleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold down-regulation of citric acid (P = 0.0003), links citrate reduction directly to prostatic Zn loss, providing the underlying mechanism linking dietary Zn deficiency with miR-183-96-182 overexpression, ZIP1 down-regulation, prostatic Zn loss, and the resultant citrate down-regulation, changes mimicking features of human prostate cancer. Thus, dietary Zn deficiency during rat middle age produces changes that mimic those of human prostate carcinoma and may increase the risk for prostate cancer, supporting the need for assessment of Zn supplementation in its prevention.


Assuntos
Adenocarcinoma/patologia , Proteínas de Transporte de Cátions/metabolismo , Próstata/patologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Zinco/deficiência , Adenocarcinoma/genética , Animais , Proliferação de Células , Ácido Cítrico/metabolismo , Dieta , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/biossíntese , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transdução de Sinais/genética , Transcrição Genética/genética , Células Tumorais Cultivadas , Zinco/metabolismo
19.
Nat Commun ; 9(1): 4568, 2018 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-30410027

RESUMO

Benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) are common conditions affecting the majority of elderly males. Here we report the results of a genome-wide association study of symptomatic BPH/LUTS in 20,621 patients and 280,541 controls of European ancestry, from Iceland and the UK. We discovered 23 genome-wide significant variants, located at 14 loci. There is little or no overlap between the BPH/LUTS variants and published prostate cancer risk variants. However, 15 of the variants reported here also associate with serum levels of prostate specific antigen (PSA) (at a Bonferroni corrected P < 0.0022). Furthermore, there is a strong genetic correlation, rg = 0.77 (P = 2.6 × 10-11), between PSA and BPH/LUTS, and one standard deviation increase in a polygenic risk score (PRS) for BPH/LUTS increases PSA levels by 12.9% (P = 1.6×10-55). These results shed a light on the genetic background of BPH/LUTS and its substantial influence on PSA levels.


Assuntos
Estudo de Associação Genômica Ampla , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/genética , Acetilação , Idoso , Biologia Computacional , Predisposição Genética para Doença , Histonas/metabolismo , Humanos , Islândia , Sintomas do Trato Urinário Inferior/sangue , Sintomas do Trato Urinário Inferior/genética , Lisina/metabolismo , Masculino , Metanálise como Assunto , Herança Multifatorial/genética , Mutação/genética , Fenótipo , Locos de Características Quantitativas/genética , Fatores de Risco , Reino Unido
20.
In Vivo ; 32(6): 1373-1379, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30348691

RESUMO

BACKGROUND/AIM: The banana flower is used for ameliorating urinary disturbance. However, there is limited evidence to support the efficacy or mechanism of action of banana flower against benign prostatic hyperplasia (BPH). In the present study, the anti-BPH activity and mechanisms of banana flower extracts were investigated in vitro and in vivo. MATERIALS AND METHODS: The banana flower extract is a water-soluble extract obtained by sonication. MTT assay was used to examine whether banana flower extract exhibited cytotoxic effects on BPH-1 cells. The effect of banana flower extract on cell-cycle distribution was examined by flow cytometry. The expression of cell-cycle-regulatory molecules was determined by western blot analysis. Testosterone propionate (TP)-induced rat model of BPH was used to evaluate the anti-BPH activity of banana flower extract in vivo. RESULTS: Banana flower extract reduced epithelial cell line BPH-1 cell viability through cell-cycle arrest at G1 phase. Moreover, banana flower extract reduced the expression of cyclin D1 and cyclin-dependent kinase 6, while it increased the expression of p53 and p27. Interestingly, banana flower extract suppressed BPH-related inflammatory responses through suppressing cyclo-oxygenase-2 expression and prostaglandin E2 production. Finally, banana flower extract administered orally to male rats reduced prostatic weight and serum dihydrotestosterone level, and improved prostate gland morphology. High-performance liquid chromatography revealed that banana flower extract contains citric acid, taurine, pantothenic acid and nicotinic acid components. In summary, banana flower extract may be used as a therapeutic agent for BPH via anti-proliferative and anti-inflammatory activities.


Assuntos
Anti-Inflamatórios/farmacologia , Flores/química , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Musa/química , Extratos Vegetais/farmacologia , Anti-Inflamatórios/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Humanos , Masculino , Extratos Vegetais/química , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia
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