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1.
Onco Targets Ther ; 10: 5551-5559, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200870

RESUMO

Bladder cancer (BC) is a common urinary system tumor with high aggressiveness, and it results in relatively high mortality due to a lack of precise and suitable biomarkers. In this study, we applied the weighted gene coexpression network analysis method to miRNA expression data from BC patients, and screened for network modules associated with BC progression. Hub miRNAs were selected, followed by functional enrichment analyses of their target genes for the most closely related module. These hub miRNAs were found to be involved in several functional pathways including pathway in cancer, regulation of actin cytoskeleton, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, proteoglycans in cancer, focal adhesion and p53 signaling pathway via regulating target genes. Finally, their prognostic significance was tested using analyses of overall survival. A few novel prognostic miRNAs were identified based on expression profiles and related survival data. In conclusion, several miRNAs that were critical in BC initiation and progression have been identified in this study. These miRNAs, which may contribute to a comprehensive understanding of the pathogenesis of BC, could serve as potential biomarkers for BC prognosis or as new therapeutic targets.

2.
Cell Physiol Biochem ; 44(3): 1213-1223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29179219

RESUMO

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim , RNA Longo não Codificante/sangue , Doença Aguda , Área Sob a Curva , Biomarcadores/sangue , Estudos de Coortes , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Curva ROC , Transcriptoma , Transplante Homólogo
3.
Oncotarget ; 8(45): 79323-79336, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108311

RESUMO

Objective: We conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon. Methods: Pubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively. Results: A total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months. Conclusion: RIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.

4.
J Cancer ; 8(13): 2643-2652, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900502

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

5.
Yi Chuan ; 39(3): 177-188, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28420614

RESUMO

The emergence of genome editing tools, such as the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has enabled researchers to achieve somatic and germline genomic manipulations in cell lines and model organisms. Within a couple of years, genome editing is now being rapidly developed for multiple applications and widely used in biomedical researches, including creation of disease models with desired genetic mutations, screening in a high-throughput manner for drug resistance genes, and making appropriate editions to genes in vivo for disease treatment. All these applications have been facilitating the development of precision medicine research. In this review, we describe the use of genome editing technologies for a variety of research and translational applications in the precision medicine field. We also highlight some of the existing limitations or challenges as well as future directions.


Assuntos
Edição de Genes , Medicina de Precisão/métodos , Animais , Pesquisa Biomédica , Sistemas CRISPR-Cas/genética , Humanos
6.
Tumour Biol ; 36(10): 8159-66, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25990459

RESUMO

Bladder cancer ranks the second most common genitourinary tract cancer, and muscle-invasive bladder cancer (MIBC) accounts for approximately 25 % of all bladder cancer cases with high mortality. In the current study, with a total of 202 treatment-naïve primary MIBC patients identified from The Cancer Genome Atlas dataset, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in MIBC, with the aim to investigate the relationship of miRNA expression with the progression and prognosis of MIBC, and generate a miRNA signature of prognostic capabilities. In the progression-related miRNA profiles, a total of 47, 16, 3, and 84 miRNAs were selected for pathologic T, N, M, and histologic grade, respectively. Of the eight most important progression-related miRNAs, four (let-7c, mir-125b-1, mir-193a, and mir-99a) were significantly associated with survival of patients with MIBC. Finally, a four-miRNA signature was generated and proven as a promising prognostic parameter. In summary, this study identified the specific miRNAs associated with the progression and aggressiveness of MIBC and a four-miRNA signature as a promising prognostic parameter of MIBC.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Musculares/genética , Neoplasias Musculares/mortalidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Carcinoma Papilar/genética , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
7.
Int J Clin Exp Pathol ; 8(2): 1128-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25972999

RESUMO

BACKGROUND: Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO). METHODS: Male Sprague-Dawley rats were randomly divided into five groups after right-side nephrectomy: Sham group (surgery without vascular clamping); IRI group (the left renal artery was clamped for 45 min); IPC group (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L-arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC). The renal and systemic hemodynamic parameters, renal function and morphology, as well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the indicated time points after reperfusion. RESULTS: IPC rats exhibited significant improvements in renal function, morphology, and renal artery blood flow (RABF), without obvious influence on the systemic hemodynamics and renal vein blood flow. Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully abolished by the administration of L-NAME. CONCLUSIONS: The results suggest that IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated NO production, thereby alleviating the renal dysfunction and histological damage caused by IRI.


Assuntos
Precondicionamento Isquêmico/métodos , Rim/irrigação sanguínea , Traumatismo por Reperfusão/fisiopatologia , Animais , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
8.
Sci Rep ; 5: 10328, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-25981392

RESUMO

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of kidney cancers. In the present study, we identified 58 treatment-naïve primary chRCC patients from The Cancer Genome Atlas dataset and analyzed the genome-wide microRNA (miRNA) expression profiles, with the aim to assess the relationship of miRNA expression with the progression and prognosis of chRCC. Overall, a total of 105 miRNAs were found to be differentially expressed between tumor and the adjacent normal tissues from 22 chRCC patients. In the unpaired condition (58 chRCC vs. 22 normal tissues), 77 (96.3%) samples were distinguished correctly by the signatures. In the progression-related profiles, 27 miRNAs were selected for pathologic T and 9 for lymph node involvement. In the survival analyses, the expression levels of mir-191, mir-19a, mir-210, and mir-425 were significantly associated with both recurrence-free survival (RFS) and overall survival, while mir-210 was proven as an independent prognostic factor in terms of RFS. In summary, miRNAs are expressed differentially in chRCC, and unique expression of miRNAs is associated with the progression and prognosis of chRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/genética , Transcriptoma , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Análise por Conglomerados , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
9.
Medicine (Baltimore) ; 94(16): e767, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25906110

RESUMO

Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC.A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan-Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda).In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways.Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/biossíntese , Fatores Etários , Idoso , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores Sexuais
10.
J Cancer Res Clin Oncol ; 141(7): 1291-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25633718

RESUMO

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers in adults, and microRNAs (miRNAs) differentially expressed in ccRCC tumors have been identified and proposed to predict prognosis. In the present study, we comprehensively analyzed the genome-wide miRNA expression profiles in ccRCC, with the aim to generate a tumor-specific miRNA signature of prognostic values. METHODS: The miRNA profiles in tumor and the adjacent normal tissue were analyzed, and the association of the differentially expressed miRNAs with patient survival was examined with univariate Cox regression analysis. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate, and multivariate Cox regression analyses. RESULTS: A total of 147 miRNAs were found differentially expressed between tumor and matched non-tumor tissues from 58 ccRCC patients. The prognostic values of these differentially expressed miRNAs were subsequently analyzed in the 411 ccRCC patients, and 22 miRNAs were found significantly correlated with patient survival. Finally, a tumor-specific miRNA signature of 22 miRNAs was generated and validated as an independent prognostic parameter. CONCLUSIONS: A tumor-specific miRNA signature consisting of 22 miRNAs was identified and validated as an independent prognostic factor, which could serve as a novel biomarker for ccRCC prognostication and help in predicting treatment outcome.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , MicroRNAs/genética , Transcriptoma , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/diagnóstico , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Especificidade de Órgãos/genética , Prognóstico , Análise de Sobrevida
11.
Med Oncol ; 32(1): 332, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25428376

RESUMO

Human cancers are endowed with sustained vascularization capability, and their growth, invasion, and metastasis are vascularization dependent. Recently, accumulated body of evidence suggests that endothelial progenitor cells (EPCs) can support vasculogenesis and induce angiogenesis through paracrine mechanisms. In addition, numerous clinical studies have revealed the increase in the number of EPCs in the peripheral blood of cancer patients and demonstrated the correlation of circulating EPCs (CEPCs) with the clinical outcomes. This review highlights current enrichment procedures and methods for the detection of CEPCs and different biomarkers to identify CEPCs as well as the functions of EPCs in tumor vascularization. Furthermore, we systematically review available studies on the clinical relevance of CEPCs in cancer patients to explore the potential diagnostic and prognostic values of CEPCs. Although several contrasting results exist, CEPCs can conceivably serve as a promising biomarker for the early diagnosis, prognosis prediction, and treatment response indication in the future. Additionally, further well-designed clinical studies with larger sample size and unique, specific enumeration procedures are warranted to achieve further insight into the clinical implications of CEPCs.


Assuntos
Biomarcadores Tumorais/sangue , Células Progenitoras Endoteliais , Neoplasias/sangue , Neovascularização Patológica/sangue , Humanos , Oncologia/métodos , Oncologia/tendências
12.
Gene ; 551(1): 86-91, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25168891

RESUMO

The wide application of prostate-specific antigen (PSA) has contributed to the early diagnosis and improved management of prostate cancer (PCa). Accumulating evidence has suggested the involvement of genetic components in regulating serum PSA levels, and several single nucleotide polymorphisms (SNPs) have been identified by genome-wide association studies (GWASs). However, the GWASs' results have the limited power to identify the causal variants and pathways. After the quality control filters, a total of 330,540 genotyped SNPs from one GWAS with 657 PCa-free Caucasian males were included for the identify candidate causal SNPs and pathways (ICSNPathway) analysis. In addition, the genotype-phenotype association analysis has been conducted with the data from HapMap database. Overall, a total of four SNPs in three genes and six pathways were identified by ICSNPathway analysis, which in total provided three hypothetical mechanisms. First, CYP26B1 rs2241057 polymorphism (nonsynonymous coding) which leads to a Leu-to-Ser amino acid shift at position 264, was implicated in the pathways including meiosis, proximal/distal pattern formation, and M phase of meiotic cell cycle. Second, CLIC5 rs3734207 and rs11752816 polymorphisms (regulatory region) to the 2 iron, 2 sulfur cluster binding pathway through regulating expression levels of CLIC5 mRNA. Third, rs4819522 polymorphism (nonsynonymous coding) leads to a Thr-to-Met transition at position 350 of TBX1 and involves in the pathways about gland and endocrine system development. In summary, our results demonstrated four candidate SNPs in three genes (CYP26B1 rs2241057, CISD1 rs2251039, rs2590370, and TBX1 rs4819522 polymorphisms), which were involved in six potential pathways to influence serum PSA levels.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Proteínas Mitocondriais/genética , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/genética , Proteínas com Domínio T/genética , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Grupo com Ancestrais do Continente Europeu , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Projeto HapMap , Humanos , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Proteínas Mitocondriais/metabolismo , Polimorfismo de Nucleotídeo Único , Ácido Retinoico 4 Hidroxilase , Proteínas com Domínio T/metabolismo
13.
Hum Immunol ; 75(8): 827-32, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24952208

RESUMO

BACKGROUND: Human leukocyte antigen-G (HLA-G) is involved in the development and progression of human cancers, and numerous molecular epidemiological studies have been conducted to explore the potential relationship of HLA-G 14-bp insertion/deletion (ins/del) polymorphism with cancer risk. However, results from published studies were inconclusive. METHODS: Both PUBMED and EMBASE databases were searched comprehensively to identify eligible studies investigating the association of HLA-G 14-bp ins/del polymorphism with cancer risk. Statistical analysis was performed by using STATA 12.0 and Review Manager 5.0. RESULTS: Fourteen eligible studies with 2340 cancer patients and 3967 controls were included and analyzed with odds ratio (OR) and its corresponding 95% confidence interval (CI). Overall, no significant association between HLA-G 14-bp ins/del polymorphism and overall cancer risk was detected in all comparison models. Further subgroup analyses based on ethnicity and cancer types demonstrated the significant association among Asians (ins/del vs. del/del: OR = 0.80, 95% CI, 0.66-0.95; ins/ins+ins/del vs. del/del: OR = 0.80, 95% CI, 0.65-0.97) and for breast cancer (ins allele vs. del allele: OR = 0.76, 95% CI, 0.61-0.96; ins/ins vs. del/del: OR = 0.57, 95% CI, 0.37-0.87; and ins/ins vs. ins/del+del/del: OR = 0.60, 95% CI, 0.42-0.87). CONCLUSION: This study suggested that HLA-G 14-bp ins/del polymorphism might contribute to breast cancer susceptibility and overall cancer risk among Asians. Further well-designed studies with larger sample size are warranted to validate our conclusion.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Antígenos HLA-G/genética , Mutação INDEL , Neoplasias/genética , Polimorfismo Genético , Alelos , Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/etnologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Antígenos HLA-G/imunologia , Humanos , Masculino , Neoplasias/etnologia , Neoplasias/imunologia , Neoplasias/patologia , Razão de Chances , Risco
14.
Asian J Androl ; 16(5): 710-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24875819

RESUMO

Reactive stromal changes in prostate cancer (PCa) are likely involved in the emergence of castration-resistant PCa (CRPC). This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic significance. Prostate needle biopsies obtained from 148 patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade (Masson stain 82.8% vs 45.6%, P < 0.001) and vimentin expression (P = 0.005) were significantly higher, and desmin expression (P = 0.004) significantly lower, in reactive stroma of tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan-Meier analysis showed a significant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 (P = 0.009). Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease-free period. In multivariate analysis, only vimentin expression was a significant predictor of tumor relapse (hazard ratio 1.78, 95% confidence interval 1.12-10.26, P = 0.012). These findings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6-7, and may serve as a new prognostic marker in daily practice.


Assuntos
Carcinoma/patologia , Recidiva Local de Neoplasia , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , Células Estromais/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/metabolismo , Carcinoma/terapia , Desmina/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Estadiamento de Neoplasias , Prognóstico , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/terapia , Células Estromais/metabolismo , Vimentina/metabolismo
15.
Tumour Biol ; 35(7): 6405-14, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24671824

RESUMO

Interferon gamma (IFN-γ) is a potent proinflammatory cytokine which plays a pivotal role in the antiviral, antiproliferative, and antitumor activities. A T-to-A transition at the position +874 of human IFN-γ gene (IFNG) has been reported to influence the secretion of IFN-γ and affect cancer susceptibility. However, results from published studies on the association between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even controversial. In order to derive a more precise estimation of the association, a meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI). Overall, no significant association was detected in allelic model (A allele vs. T allele-OR = 0.96, 95 % CI, 0.86-1.08), homozygote comparison (AA vs. TT-OR = 0.97, 95 % CI, 0.79-1.21), heterozygote comparison (AT vs. TT-OR = 1.03, 95 % CI, 0.87-1.23), dominant model (AA + AT vs. TT-OR = 1.00, 95 % CI, 0.87-1.15), nor recessive model (AA vs. AT + TT-OR = 0.93, 95 % CI, 0.78-1.12). Further subgroup analyses based on ethnicity, cancer types, and Hardy-Weinberg equilibrium status failed to demonstrate any significant relationship except in African population under recessive model (AA vs. AT + TT-OR = 0.68, 95 % CI, 0.47-0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A polymorphism may not contribute to cancer susceptibility, and further well-designed studies with large sample size are warranted to validate our conclusion.


Assuntos
Predisposição Genética para Doença , Interferon gama/genética , Neoplasias/genética , Alelos , Estudos de Associação Genética , Humanos , Fatores de Risco
16.
J Assist Reprod Genet ; 31(5): 601-11, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24647635

RESUMO

PURPOSE: Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive. METHODS: To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95 % confidence intervals (95 % CI). RESULTS: Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods. CONCLUSIONS: This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.


Assuntos
Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Infertilidade Masculina/genética , Polimorfismo Genético , Grupo com Ancestrais do Continente Asiático/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances
17.
Tumour Biol ; 35(4): 3881-90, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24353088

RESUMO

Ras-associated domain family 1A (RASSF1A) is a putative tumor suppressor gene located at 3p21.3, and the epigenetic inactivation of RASSF1A by hypermethylation of CpG islands within the promoter region has been observed in various cancer types, including prostate cancer (PCa). However, results from published studies on the association between RASSF1A promoter methylation and PCa risk are conflicting and inconclusive. Hence, we conducted a meta-analysis of 19 eligible studies with odds ratio (OR) and its corresponding 95% confidence intervals (95% CI) in order to investigate the strength of relationship of RASSF1A promoter methylation with PCa risk and its clinicopathological variables. Overall, the RASSF1A promoter methylation was significantly associated with PCa risk (OR = 9.58, 95% CI 5.64-16.88, P heterogeneity <0.001) and Gleason score (GS) (OR = 2.58, 95% CI 1.64-4.04, P(heterogeneity) = 0.019). In addition, subgroup analysis by testing material demonstrated the significant association between RASSF1A methylation and GS (OR = 3.09, 95% CI 1.92-4.97, P heterogeneity =0.042), PSA level (OR = 2.75, 95% CI 1.67-4.52, P(heterogeneity) = 0.639), and tumor stage (OR = 1.74, 95% CI 1.05-2.87, P(heterogeneity) = 0.026) in tissue rather than urine samples. In conclusion, this meta-analysis suggested that RASSF1A promoter methylation was significantly associated with an increased risk for PCa; furthermore, the RASSF1A methylation status in tissue rather than urine was positively correlated with GS, serum PSA level, and tumor stage, which can be utilized for the early detection and prognosis prediction of PCa.


Assuntos
Metilação de DNA , Predisposição Genética para Doença , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Proteínas Supressoras de Tumor/genética , Humanos , Masculino , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/etiologia , Neoplasias da Próstata/patologia , Viés de Publicação , Risco
18.
Asian Pac J Cancer Prev ; 13(4): 1639-44, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22799381

RESUMO

The aim of this study was to investigate the expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer (PCa). Immunohistochemistry was performed on paraffin-embedded sections with rabbit polyclonal against mPGES-1 and Beclin-1 in 40 PCa, 40 benign prostatic hyperplasia (BPH) and 10 normal prostate specimens for this purpose. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for mRNA expression of mPGES-1 and Beclin-1, while MTT assays were used to ascertain the best working concentration of the mPGES-1 inhibitor (CAY10526). The effect of CAY10526 treatment on expression of Beclin-1 in DU-145 cells was studied using Western blot analysis. Localization of Beclin-1 and mPGES-1 was in endochylema. Significant differences in expression was noted among PCa, BPH and normal issues (P<0.05). Beclin-1 expression inversely correlated with mPGES-1 expression in PCa tissue (P<0.05). CAY10526 could significantly block mPGES-1 expression and the proliferation of DU-145 cells (P<0.05), while increasing Beclin-1 levels (P<0.05). Overexpression of mPGES-1 could decrease the autophagic PCa cell death. Inhibiting the expression of mPGES-1 may lead to DU-145 cell death and up-regulation of Beclin-1. The results suggest that inhibition of mPGES-1 may have therapeutic potential for PCa in the future.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Proteínas Reguladoras de Apoptose/metabolismo , Oxirredutases Intramoleculares/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Proteína Beclina-1 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Distribuição de Qui-Quadrado , Humanos , Oxirredutases Intramoleculares/antagonistas & inibidores , Masculino , Proteínas de Membrana/efeitos dos fármacos , Microssomos/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prostaglandina-E Sintases , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Tiofenos/farmacologia , Regulação para Cima
19.
Zhonghua Yi Xue Za Zhi ; 91(30): 2135-8, 2011 Aug 16.
Artigo em Chinês | MEDLINE | ID: mdl-22093992

RESUMO

OBJECTIVE: To investigate the effects of transplanted endothelial progenitor cells (EPCs) on the spermatogenic functions in testicular detorsion. METHODS: Bone-marrow-derived EPCs were obtained from rats and transfected by enhanced green fluorescent protein adenovirus (Ad-eGFP). The rats were divided into 3 groups (n = 6 each). In the sham group, left testis was not twisted. In the ischemia reperfusion injury (IRI) group, 1 ml saline was injected into the femoral vein of each rat after testicular detorsion. In the EPCs group, 1 ml EPCs suspension (1.0 × 10(6) EPCs) was injected into each rat after testicular detorsion. The Ad-eGFP transfected EPCs were injected into the 3 additional rats of testicular torsion-detorsion. At Day 5 post-transplantation, the characteristics of transplanted EPCs homing were detected. And the pathological changes and apoptotic cells/seminiferous tubules in left testis were examined. RESULTS: When the value of multiplication of infection (MOI) was at 50, the transfection rate of EPCs by Ad-eGFP exceeded 73.7%. At Day 5 post-treatment, the cells exhibiting green fluorescence were detected in left testis. The germ cells in rats of the sham group were normal. And the ratio of apoptotic cells to seminiferous tubules was 0.09 ± 0.02. The germ cells in rats of the IRI group were much fewer. And the ratio of apoptotic cells to seminiferous tubules was 2.82 ± 0.81. As compared with the IRI group, seminiferous epithelium was thicker in the EPCs group. And the ratio of apoptotic cells to seminiferous tubules was 0.32 ± 0.09 in the EPCs group. It was much smaller than that in the IRI group. There was significant difference (P < 0.01). CONCLUSION: The transplantation of EPCs is effective for treating the spermatogenic dysfunctions caused by testicular torsion so as to greatly enhance the spermatogenic functions.


Assuntos
Células Endoteliais/transplante , Torção do Cordão Espermático/fisiopatologia , Transplante de Células-Tronco , Células-Tronco , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Epitélio Seminífero , Torção do Cordão Espermático/metabolismo , Espermatogênese , Testículo/metabolismo , Testículo/fisiopatologia
20.
Zhonghua Nan Ke Xue ; 17(10): 894-6, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22049791

RESUMO

OBJECTIVE: To evaluate the efficacy of tadalafil in the treatment of ED after transurethral resection of the prostate (TURP). METHODS: A total of 113 patients with ED after TURP received 3 months of tadalafil treatment and were followed up for 6 months. The IIEF-5 scores of the patients and the number of successful penile intromissions and sustained penile erections in the patients' sexual life diary were compared before and after the treatment. RESULTS: The IIEF-5 scores were 9.83 +/- 3.96 before the medication, 20.23 +/- 3.25 after it, and 17.28 +/- 3.03 at 6 months after drug withdrawal, with statistically significant differences between pre- and post-treatment (P < 0.05). The patients' success rates of penile intromission and sexual intercourse were increased from 44.8% and 7.5% before the medication to 81.7% and 63.2% after it. CONCLUSION: Tadalafil can be used as a first-line drug for the treatment of ED after TURP.


Assuntos
Carbolinas/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Inibidores de Fosfodiesterase/uso terapêutico , Ressecção Transuretral da Próstata/efeitos adversos , Idoso , Disfunção Erétil/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tadalafila , Resultado do Tratamento
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