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BACKGROUND: Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain. METHODS: Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1. RESULTS: CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression. CONCLUSIONS: CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.
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Neoplasias da Próstata , RNA Circular , Microambiente Tumoral , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CCL20 , Quimiocinas CC , Humanos , Hibridização in Situ Fluorescente , Ligantes , Masculino , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Circular/genética , Receptores CCR6/genética , Transdução de Sinais , Microambiente Tumoral/genética , Macrófagos Associados a TumorRESUMO
BACKGROUND: More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. RESULTS: Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. CONCLUSIONS: Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.
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Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Próstata/genética , Interferência de RNA , RNA Circular/genética , Proteínas de Ligação a RNA/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estabilidade de RNA , Proteínas de Ligação a RNA/metabolismoRESUMO
Objective: To investigate the protective effect of long-term consumption of hydrogen-rich water (HRW) on the percentage of progressively motile sperm (PMS) in male rats. METHODS: Twenty normal healthy male SD rats were equally randomized into an HRW and a control group, the former given HRW (1.2 ppm) and the latter normal saline, both intragastrically at 2 ml/d for 9 months. Then, the bilateral epididymides of the rats were harvested for preparation of sperm suspension and detection of the percentage of PMS. The testis tissue was isolated for HE staining and determination of the expressions of the Ki67, CYBB, eNOS, CLDN3 and SRD5A2 proteins using the streptavidin-peroxidase (SP) immunohistochemical method. RESULTS: The percentage of PMS was significantly higher in the HRW than in the control group (ï¼»64.3 ± 4.7ï¼½% vs ï¼»55.3 ± 9.5ï¼½%, P < 0.05), and so was the expression of Ki67 in the testicular tissue (P < 0.01). Compared with the controls, the rats in the HRW group showed markedly decreased oxidative stress-related index CYBB (P < 0.01), increased eNOS level (P < 0.01), and upregulated expressions of sperm development-related proteins CLDN3 and SRD5A2 (P < 0.01 and P < 0.05). CONCLUSIONS: Hydrogen not only regulates the expressions of some oxidative stress-related indicators, but also increases the expressions of the molecules promoting sperm maturation and motility, which provides a theoretical basis and experimental support for the application and studies of hydrogen in asthenospermia.
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OBJECTIVE: To investigate the application of a simplified technique for reconstruction of vesicourethral support (RVUS) in laparoscopic radical prostatectomy (LRP). METHODS: From January 2017 to August 2019, 122 patients with localized prostate cancer underwent extraperitoneal LRP, 65 with RVUS (the RVUS group) and 57 without RVUS (the non-RVUS group). We compared the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, incidence of urethrovesical anastomotic urinary leakage (UVAUL), postoperative urinary continence, postoperative hospital stay, intraperitoneal drainage tube removal time, and urethral catheter removal time between the two groups of patients. RESULTS: No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, or urethral catheter removal time (P > 0.05). The incidence rate of UVAUL was lower in the non-RVUS than in the RVUS group (8.8% vs 0%, P < 0.05), and so were the rates of postoperative urinary continence immediate after (0% vs 32.3%, P < 0.05) and at 1 month (38.6% vs 56.9%, P < 0.05), 3 months (59.6% vs 80%, P < 0.05), 6 months (78.9% vs 84.6%, P > 0.05) and 12 months after catheter removal (87.7% vs 92.3%, P > 0.05). The postoperative hospital stay was dramatically longer in the non-RVUS than in the RVUS group (ï¼»9.1 ± 4.3ï¼½ vs ï¼»6.7 ± 1.8ï¼½ d, P < 0.01) and so was the intraperitoneal drainage tube removal time (ï¼»6.9 ± 4.5ï¼½ vs ï¼»4.8 ± 1.5ï¼½ d, P < 0.01). CONCLUSIONS: The simplified technique for reconstruction of vesicourethral support in laparoscopic radical prostatectomy improves early urinary continence, especially immediate continence, decreases the incidence rate of urethrovesical anastomotic urinary leakage, and shortens the intraperitoneal drainage tube removal time and postoperative hospital stay.?
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Laparoscopia , Prostatectomia , Humanos , MasculinoRESUMO
Recently, novel therapies of prostate cancer, such as immunotherapy, endothelin receptor antagonists, novel androgen receptor antagonist and novel taxanes, and others have been introduced into clinical practice. This study was performed to summarize these results of immunotherapy and endothelin receptor antagonists in the treatment of castration-resistant prostate cancer (CRPC) and derive a more precise estimation of their effect on future treatment. The PubMed database, references of published trials, and review articles were searched. Two reviewers independently extracted data of these trials. We used hazard ratios (HRs) to assess the effects on overall survival (OS), progression-free survival (PFS), or time to disease progression (TTP), and relative risk (RR) for the different types of toxicity. In addition, 95% confidence intervals (CIs) give a sense of the precision of the estimate. Nine randomized controlled trials were ultimately identified. The pooled HR showed that immunotherapy could prolong OS significantly in patients with CRPC compared to placebo (HR = 0.70, 95% CI: 0.58-0.83, p < 0.001). Endothelin receptor antagonists also had modest benefits (HR = 0.90, 95% CI: 0.82-1.00, p = 0.046). Nevertheless, there were no significant benefits from both therapies on PFS or TTP. In addition, immunotherapy led to more fatigue, pyrexia, chills, and endothelin receptor antagonists led to more peripheral edema, anemia, and dyspnea. Our article suggested that the very acceptable toxicity and improving OS in patients with CRPC made immunotherapy an attractive option for such patients. However, future studies with thoughtful clinical trial designs are warranted.
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Antagonistas dos Receptores de Endotelina , Imunoterapia/métodos , Neoplasias da Próstata/terapia , Atrasentana , Intervalo Livre de Doença , Humanos , Masculino , Orquiectomia , Modelos de Riscos Proporcionais , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Extratos de Tecidos/efeitos adversos , Extratos de Tecidos/uso terapêuticoRESUMO
The suppressor of variegation enhancer of zeste-trithorax (SET) domain methyltransferases have been reported to function as key regulators in multiple tumor types by catalyzing histone lysine methylation. Nevertheless, our understanding on the role of these lysine methyltransferases, including SETD4, in prostate cancer (PCa) remains limited. Hence, the specific role of SETD4 in PCa was investigated in this study. The expression of SETD4 in PCa cells and tissue samples was downregulated in PCa cells and tissue specimens, and decreased SETD4 expression led to inferior clinicopathological characteristics in patients with PCa. knockdown of SETD4 facilitated the proliferation of PCa cells and accelerated cell cycle progression. Mechanistically, SETD4 repressed NUPR1 transcription by methylating H3K27 to generate H3K27me3, subsequently inactivated Akt pathway and impeded the tumorigenesis of PCa. Our results highlight that SETD4 prevents the development of PCa by catalyzing the methylation of H3K27 and suppressing NUPR1 transcription, subsequently inactivating the Akt signaling pathway. The findings suggest the potential application of SETD4 in PCa prognosis and therapeutics.
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Histonas , Neoplasias da Próstata , Humanos , Masculino , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Histonas/genética , Histonas/metabolismo , Lisina/metabolismo , Metiltransferases/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Background: BAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC. Methods: Raw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence in situ hybridization (FISH) assays were used to confirm the ceRNA network. Results: Nuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels. Conclusions: In BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.
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Interferon gamma (IFN-γ) plays a pivotal role in antiproliferative, antitumor and antiviral activities. The +874 polymorphism in IFN gene region reportedly affects cancer risk. However, pertinent studies offer conflicting results. To derive a more precise estimation, we performed a meta-analysis based on 1,929 cases and 2,830 controls from 17 published case-control studies, assessing the strength of the association using odds ratios with 95% confidence intervals. Our meta-analysis showed the evidence that IFN-γ +874 T/A was not associated with increased cancer risk in ethnicity and source of controls. However, stratified analysis by cancer type indicated a significantly increased risk of cervical cancer (AT vs. TT: OR = 1.10, 95% CI = 1.02-1.19, P = 0.961 for heterogeneity). Further prospective researches with a larger single study are required to evaluate any association with other types of cancer or in other populations.
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Predisposição Genética para Doença , Interferon gama/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Humanos , Viés de Publicação , Fatores de RiscoRESUMO
Polymorphisms in the endoribonuclease L (RNASEL) gene have been hypothesized to increase the incidence of cancer. The common sequence variation in RNASEL, -1385G/A (rs486907) has been involved in several types of cancer risk. However, results of the related published studies remained conflicting rather than conclusive. To clarify the role of RNASEL -1385G/A genotype in global cancer, we performed a meta-analysis of all the available published studies involving 8,732 cancer patients and 8,748 control subjects. The overall results indicated that there was no major influence of the variant on cancer risk. However, stratified analysis by ethnicity showed that the RNASEL -1385G/A polymorphism has an increased cancer risk in African descendents in the homozygote comparison (OR = 2.59, 95% CI = 1.27-5.27), although no association was found in the analysis stratified by cancer type (OR = 1.12, 95% CI = 0.94-1.35). This meta-analysis suggested that the RNASEL -1385G/A polymorphism is associated with cancer risk in African descendents. To draw more comprehensive conclusions, further prospective studies with larger numbers of participants worldwide are still required to examine associations between RNASEL -1385G/A polymorphism and cancer risk.
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Endorribonucleases/genética , Predisposição Genética para Doença , Neoplasias/enzimologia , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Humanos , Fatores de RiscoRESUMO
Interleukin-6 (IL-6) is a multifunctional cytokine involved in different physiologic and pathophysiologic processes and plays important roles in the etiology of cancer. The -174G>C polymorphism of the IL-6 gene influences IL-6 transcription and has been implicated in cancer risk. However, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 29,377 cancer cases and 37,739 controls from 50 published case-control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between -174G>C polymorphism and cancer risk. Overall meta-analysis indicated that no association was found between -174G>C genotypes and cancer risk. However, the positive association was found in bladder cancer (OR=4.33, 95% CI: 1.93-9.71 for CC vs. GC, OR=2.81, 95% CI: 1.39-5.68 for CC vs. GG, and OR=2.19, 95% CI: 1.32-3.64 for CC vs. GG/GC), and among Asians (OR=2.08, 95% CI: 1.07-4.06 for CC vs. GG, and OR=2.20, 95% CI: 1.02-4.74 for CC vs. GG/GC) and Africans (OR=1.61, 95% CI: 1.07-2.42 for GC vs. GG). This meta-analysis showed the evidence that the -174G>C of the IL-6 gene was a low-penetrance susceptibility gene for bladder cancer. Further larger, preferably prospective studies are needed to confirm this relationship.
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Predisposição Genética para Doença/genética , Interleucina-6/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , População Negra/genética , Feminino , Humanos , Masculino , Razão de Chances , População Branca/genéticaRESUMO
OBJECTIVE: To investigate the correlation between the polymorphism of the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and the genetic susceptibility to prostate cancer (PCa) in the Chinese Han population in Nanjing. METHODS: We performed a case control study on 187 cases of PCa and 237 cancer-free healthy controls. Peripheral blood genome DNA was extracted from the subjects for analysis of the polymorphism of the TRAIL-716 locus by polymerase chain reaction-ligase detection reaction (PCR-LDR). The correlations between the susceptibility to PCa and different genotypes were compared. RESULTS: An SNP (-716A/G) was found in the promoter of the TRAIL gene. AA, AG and GG genotypes were identified. Logistic regression analysis suggested that AG, GG and AG + GG genotypes had no significant correlation with the risk of PCa (OR = 0.89, 95% CI = 0.54 -1.47; OR = 0.94, 95% CI = 0.69 -1.27; OR = 0.87, 95% CI = 0.54 - 1.41). CONCLUSION: The TRAIL-716 polymorphism is not directly related with the genetic susceptibility to PCa in the Chinese Han population of Nanjing.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Ligante Indutor de Apoptose Relacionado a TNF/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Estudos de Casos e Controles , China , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A G > C polymorphism (rs2910164) which is located in the sequence of miR-146a precursor, results in a change from a G:U pair to a C:U mismatch in its stem region. To explore whether rs2910164 plays any role in prostate cancer (CaP), we analyzed the association between miR-146a polymorphism and risk of CaP and the expression of miR-146a with different genotypes in CaP tissues in southern Chinese Han population. MATERIALS AND METHODS: Two hundred fifty-one CaP and 280 control subjects were included in the cancer association study, and 15 CaP tissue samples were used to test the expression of the miRNA precursors by real-time quantitative reverse transcription PCR. RESULTS: We found that subjects carrying CC homozygotes had a 0.65-fold reduced risk (95% CI = 0.43-0.99) than those carrying GG/GC genotypes (P = 0.03), and the C allele displayed a lower prevalence of CaP compared with the G allele (OR = 0.73, 95% CI = 0.57-0.94, P = 0.01). Moreover, hsa-miR-146a quantification showed that homozygous carriers of the C-variant had significantly decreased miRNA levels compared to the carriers of the GG/GC genotype. CONCLUSIONS: The natural genetic variation in pre-miR-146a affects the amount of mature miR-146a, contributes to the genetic predisposition to CaP.
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Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Adulto , Idoso , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/etiologia , RiscoRESUMO
INTRODUCTION: Alterations in P53 and murine double minute 2 (MDM2) genes appear to be important in the development of many human tumors. We investigated the potential prognostic roles of p53 codon 72 and MDM2 309 and 1797 polymorphisms in prostate cancer after radical prostatectomy. PATIENTS AND METHODS: Fifty southern Chinese with prostate cancer undergoing radical prostatectomy were included in this study. All polymorphisms were detected by PCR-RFLP. Their prognosis on biochemical recurrence was assessed using Kaplan-Meier analysis and Cox regression model. RESULTS: p53 codon 72 GG genotype was associated with increased biochemical recurrence compared with CG+CC genotypes and poorer PSA-free survival. It was also noted that GG genotype was an independent risk factor for biochemical recurrence after radical prostatectomy on multivariate analysis. No statistical difference was observed in MDM2 polymorphisms and prostate cancer prognosis. CONCLUSION: Our data revealed that p53 codon 72 GG genotype carriers more frequently show biochemical recurrence than CG+CC genotypes carriers.
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Povo Asiático/genética , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Proteína Supressora de Tumor p53/genética , Idoso , Distribuição de Qui-Quadrado , China , Códon , Intervalo Livre de Doença , Frequência do Gene , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/etnologia , Estadiamento de Neoplasias , Fenótipo , Projetos Piloto , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/etnologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effect of in utero exposure to di-n-butyl phthalate (DBP) on the protein expression in the penile tissue of hypospadiac rats, isolate and identify differentially expressed proteins, and determine the role of the differential expression of Annexin A3 in the development of hypospadia in the rat offspring after maternal exposure to DBP. METHODS: Twenty pregnant SD rats were randomly assigned to an experimental group, intragastrically administered DBP at 800 mg/kg, and a control group, given soybean oil at 5 ml/kg, both for 5 days. Three days after birth, the penises of the newborn rats were removed, and the total protein extracted for 2D-electrophoretic separation and image analysis. Differentially expressed protein spots were screened and identified by mass spectrometry, and the changes in the expression of Annexin A3 detected by Western blotting and immunohistochemistry. RESULTS: Thirty-one differentially expressed protein spots were screened, of which 17 were identified by mass spectrometry and the SwissProt database, including pyruvate kinase M2, alpha-enolase, and Annexin A3. Western blot showed that Annexin A3 was mainly located in the urethral epithelia and had a lower expression in the hypospadiac rats (1.851 +/- 0.014, n = 10) than in the controls (2.603 +/- 0.012, n = 10) (P < 0.05). CONCLUSION: A pedigree of differentially expressed proteins in the penises of DBP-induced hypospadia and normal rats was established by the proteomic method. The differential expression of Annexin A3 may play an important role in the development of hypospadia.
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Anexina A3/metabolismo , Hipospadia/metabolismo , Pênis/metabolismo , Proteoma/análise , Animais , Animais Recém-Nascidos , Dibutilftalato/efeitos adversos , Epispadia , Feminino , Masculino , Exposição Materna , Gravidez , Proteômica , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To evaluate the clinical significance of prostate-specific antigen (PSA) screening in early detection of prostate cancer in Chinese men. METHODS: PSA screening was performed in 8562 asymptomatic men who had been enrolled for health checkup and all were > or = 50 years old. Prostate biopsy was recommended for those with a serum PSA level > or = 4.0 ng/ml. The pathological and clinical features of the patients with prostate cancer detected by the PSA screening were compared with that of 82 clinically diagnosed prostate cancer patients during the same period. RESULTS: Of the 8562 asymptomatic men, 719 had PSA levels > or = 4.0 ng/ml and biopsy was performed in 295 of them. Fifty-eight prostate cancers were detected. The biopsy rate was 41.0% and positive detection rate was 19.7%. The overall age distribution in the screening group and the clinical groups was not significantly different (P = 0.176). However, 41.4% (24/58) of the patients in screening group were > 75 years old, and significantly more than that in the clinical group (25.6%, P = 0.0491). The proportion of the patients with PSA levels > or = 20 ng/ml in the screening group was significantly less than that in the patients of the clinical group (44.8% vs. 75.6%, P = 0.0002). Whether in the patients whose age was > 75 years old (P < 0.05) or < or = 75 years old (P = 0.0002), the patients in the screening group had significantly lower Gleason scores < 7 (60.3% vs. 34.1%, P = 0.002), more T1 or T2 tumor (87.9% vs. 26.8%, P < 0.0001) and more chance to receive radical prostatectomy (50.0% vs. 18.3%, P < 0.0001) than the patients in the clinical group did. However, the distributions of PSA levels at diagnosis and biopsy Gleason scores were not significantly different between the above mentioned two groups (P > 0.05). CONCLUSION: Prostate-specific antigen (PSA) screening is useful for early detection of prostate cancer in Chinese men aged > or = 50 years. The patients detected by PSA screening usually show a lower PSA level, Gleason scores and early clinical stage disease, and have more chance for radical prostatectomy than the clinically diagnosed patients.
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Detecção Precoce de Câncer/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: To investigate the association of the risk of prostate cancer (PCa) with the polymorphism of the CYP2E1 gene, smoking and drinking, and to explore the joint role of genes and living habits in PCa pathogenesis. METHODS: We conducted a case-control study on 109 PCa patients and 202 age-matched non-PCa male controls, and detected the polymorphisms of CYP2E1 Rsa I and Pst I sites by PCR-RFLP using DNA from peripheral blood lymphocytes. RESULTS: The history of deep smoking (OR = 2.29, 95% CI: 1.28 - 4.09) or heavy smoking (OR = 1.81, 95% CI: 1.02 - 3.22) was a risk factor. The CYP2E1 C1/C1 genotype significantly increased the risk of PCa (OR = 1.71, 95% CI: 1.04 - 2.82) and apparently interacted with drinking (OR = 2.21, 95% CI: 1.06 - 4.59). Heavy smokers with the C1/C1 genotype showed an increased risk of PCa (OR = 2.80, 95% CI: 1.20 - 6.56), as compared with non-smokers carrying the genotype of C1/C2 or C2/C2. CONCLUSION: The risk of PCa obviously increases in individuals with both the CYP2E1 C1/C1 genotype and the habit of smoking or drinking, and it has a significant positive correlation with the dose of tobacco exposure.
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Consumo de Bebidas Alcoólicas/genética , Citocromo P-450 CYP2E1/genética , Neoplasias da Próstata/genética , Fumar/genética , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Neoplasias da Próstata/epidemiologia , Fumar/epidemiologiaRESUMO
AIM: To study the molecular mechanism of epididymal protease inhibitor (Eppin) modulating the process of prostate specific antigen (PSA) digesting semenogelin (Sg). METHODS: Human Sg cDNA (nucleotides 82-849) and Eppin cDNA (nucleotides 70-723) were generated by polymerase chain reaction (PCR) and cloned into pET-100D/TOPO. Recombinant Eppin and Sg (rEppin and rSg) were produced by BL21 (DE3). The association of Eppin with Sg was studied by far-western immunoblot and radioautography. In vitro the digestion of rSg by PSA in the presence or absence of rEppin was studied. The effect of anti-Q20E (N-terminal) and C-terminal of Eppin on Eppin-Sg binding was monitored. RESULTS: Eppin binds Sg on the surface of human spermatozoa with the C-terminal of Eppin (amino acids 75-133). rSg was digested with PSA and many low molecular weight fragments were produced. When rEppin is bound to rSg, then digested by PSA, incomplete digestion and a 15-kDa fragment results. Antibody binding to the N-terminal of rEppin did not affect rSg digestion. Addition of antibodies to the C-terminal of rEppin inhibited the modulating effect of rEppin. CONCLUSION: Eppin protects a 15-kDa fragment of rSg from hydrolysis by PSA.
Assuntos
Antígeno Prostático Específico/metabolismo , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Sêmen/metabolismo , Animais , Anticorpos/farmacologia , Autorradiografia , Humanos , Hidrólise , Masculino , Proteínas Secretadas Inibidoras de Proteinases/genética , Proteínas Secretadas Inibidoras de Proteinases/imunologia , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sêmen/citologia , Proteínas Secretadas pela Vesícula Seminal/metabolismo , Espermatozoides/metabolismoRESUMO
OBJECTIVE: To explore the clinical significance of azoospermia factor (AZF) region deletion. METHODS: Detection of the Y-link sequence tagged sites in AZF region was conducted by means of 2 multiplex polymerase chain reactions among 80 patients with severe oligozoospermia and 63 patients with azoospermia, totally 143. RESULTS: Twenty-one cases of microdeletion were found among the 143 infertile patients with a prevalence of 14.7%. PCR analysis showed that deletion of the portions of Yq in 12 of the 62 idiopathic infertility patients, 3 being with severe oligozoospermia and 9 with azoospermia, and in 9 out of the 81 patients with non-idiopathic infertility. PCR analysis of 40 normal fertile men did not detect any abnormality. The results of the microdeletion showed that 1 patient had a microdeletion in the AZFa region with sY84 and sY86 (1/21, 4.8%), 2 patients presented a large deletion involving sY127 and sY143 from AZFb, and sY254 and sY255 from AZFc (1/21, 9.5%). Two patients had the deletions located in AZFb region (2/21, 9.5%), and 16 patients had a deletion on the AZFc region involving the DAZ (deleted in azoospermia) gene (16/21, 76.2%) Among the 21 infertile men 4 showed a testicular cytologic picture of maturation arrest, 6 patients had severe hypospermatogenesis, and 11 had Sertoli cell-only syndrome. There were not significant differences in location and extent of deletions between the patients with idiopathic infertility and those with non-idiopathic infertility. CONCLUSION: It is recommended to carry out screening of microdeletion of Y chromosome among the patients with idiopathic and non-idiopathic infertility, especially the candidates for intracytoplasmic sperm injection.
Assuntos
Azoospermia/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Infertilidade Masculina/genética , Oligospermia/genética , Adulto , Pré-Escolar , Humanos , Lactente , Masculino , Reação em Cadeia da PolimeraseRESUMO
Congenital agenesis of the seminal vesicle (CASV) is frequently associated with congenital absence of the vas deferens (CAVD) or ipsilateral congenital vasoureteral communication. We reported two cases of a rare condition that the vas deferens open ectopically into Mullerian duct cyst associated with agenesis of the ipsilateral seminal vesicle. The diagnosis was confirmed by vasography. Transurethral unroofing of the Mullerian duct cyst was performed in both patients with favourable results, however, assisted reproductive technology (ART) was still necessary for them to father children.