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1.
Nature ; 580(7801): 93-99, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238934

RESUMO

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.


Assuntos
Povo Asiático/genética , Epigênese Genética , Epigenômica , Genoma Humano/genética , Genômica , Mutação , Neoplasias da Próstata/classificação , Neoplasias da Próstata/genética , Proteínas de Transporte/genética , Transformação Celular Neoplásica/genética , China , Estudos de Coortes , DNA Helicases/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Masculino , Proteínas do Tecido Nervoso/genética , Neoplasias da Próstata/patologia , RNA-Seq , Transcriptoma/genética
3.
J Transl Med ; 22(1): 608, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956589

RESUMO

BACKGROUND: Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. METHODS: The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. RESULTS: We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4-94.1%) and specificity of 90.0% (95% CI: 81.9-95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. CONCLUSION: TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Recidiva Local de Neoplasia , Humanos , Metilação de DNA/genética , Masculino , Feminino , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/diagnóstico , Idoso , Urotélio/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Estudos de Coortes , Neoplasias Urológicas/genética , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/urina , Reprodutibilidade dos Testes , Proteínas de Membrana , Proteínas de Neoplasias
4.
Urol Int ; 106(9): 884-890, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34818262

RESUMO

INTRODUCTION: Prostate biopsy (PB) is a typical daily practice method for the diagnosis of prostate cancer (PCa). This study aimed to compare the PCa detection rates and peri- and postoperative complications of PB among 3 residents and a consultant. PATIENTS AND METHODS: A total of 343 patients who underwent PB between August 2018 and July 2019 were involved in this study. Residents were systematically trained for 2 weeks by a consultant for performing systematic biopsy (SB) and targeted biopsy (TB). And then, 3 residents and the consultant performed PB independently every quarter due to routine rotation in daily practice. The peri- and postoperative data were collected from a prospectively maintained database (www.pc-follow.cn). The primary outcome and secondary outcome were to compare the PCa detection rates and complications between the residents and consultant, respectively. RESULTS: There was no significant difference between the residents and consultant in terms of overall PCa detection rates of SB and TB or further stratified by prostate-specific antigen value and prostate imaging reporting and data system (PI-RADS) scores. We found the consultant had more TB cores (175 cores vs. 86-114 cores, p = 0.043) and shorter procedural time (mean 16 min vs. 19.7-20.1 min, p < 0.001) versus the residents. The complication rate for the consultant was 6.7% and 5%-8.2% for the residents, respectively (p = 0.875). CONCLUSIONS: The residents could get similar PCa detection and complication rates compared with that of the consultant after a 2-week training. However, the residents still need more cases to shorten the time of the biopsy procedure.


Assuntos
Próstata , Neoplasias da Próstata , Consultores , Humanos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos Prospectivos , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção , Urologistas
5.
Environ Toxicol ; 37(6): 1495-1508, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35213076

RESUMO

In most bladder cancer (BC) patients, cancer cells will eventually develop chemical resistance causing increased mortality. This study aimed to explore the mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating doxorubicin (ADM) resistance of BC cells. We observed that PVT1 expression was upregulated in ADM-resistant BC cells compared with ADM-sensitive BC cells. Downregulation of PVT1 suppressed ADM-resistant BC cell proliferation and invasion, promoted apoptosis, and increased sensitivity to ADM, while PVT1 overexpression promoted ADM-sensitive BC cell growth and their resistance to ADM. Further study uncovered that PVT1 could interact with and promote mouse double minute 2 (MDM2) expression, and upregulated MDM2-mediated Aurora kinase B (AURKB). Furthermore, Nutlin-3, an inhibitor of MDM2, could counteract the promotive effects of PVT1 overexpression on ADM resistance of ADM-sensitive BC cell, the expression of multidrug-resistance-related proteins, and the inhibition of p53-mediated tumor suppressor genes. And, overexpression of MDM2 or AURKB reversed the promotive effects of PVT1 silence on the ADM sensitivity of ADM-resistant BC cell, and the inhibitory effect on expression multidrug resistance proteins. Mechanically, AURKB increased MDM2-mediated p53 ubiquitination. Taken together, PVT1 promoted BC cell proliferation and drug resistance via elevating MDM2 expression and AURKB-mediated p53 ubiquitination.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Animais , Apoptose/genética , Aurora Quinase B/genética , Aurora Quinase B/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
6.
Nanomedicine ; 34: 102370, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33713859

RESUMO

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with poor prognosis. Therapeutic drugs for RCC can easily develop resistance or have unignorable toxicity or limited efficiency. Here, the thermosensitive mitochondrial metabolism-interfering anticancer drug lonidamine (LND) was combined with the photothermal material polydopamine (PDA) to treat RCC. To delivery drugs accurately to RCC site, LND and PDA were loaded in stellate mesoporous silica nanoparticles (MSNs) with a large surface area and cloaked with RCC membranes (MLP@M). The results showed that MLP@M exhibited excellent tumor targeting ability. The synergistic effects of LND and PDA in MLP@M were greatly enhanced when triggered by an 808 nm laser. Moreover, the antiproliferative and tumor suppressing abilities were enhanced with good biocompatibility after MLP@M + laser treatment. Additionally, 80% of RCC tumor-bearing mice treated with MLP@M + laser did not relapse. Our study provides a potential therapeutic approach for RCC treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Indazóis/uso terapêutico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Terapia Fototérmica , Polímeros/uso terapêutico , Animais , Antineoplásicos/farmacologia , Carcinoma de Células Renais/metabolismo , Humanos , Indazóis/farmacologia , Indóis/farmacologia , Neoplasias Renais/metabolismo , Camundongos , Mitocôndrias/metabolismo , Polímeros/farmacologia , Dióxido de Silício/química , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Cell Physiol ; 234(10): 18763-18772, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30953370

RESUMO

DNA methylation can regulate gene expression and is pivotal in the occurrence and development of bladder cancer. In this study, we analyzed whole-genome DNA methylation on the basis of data from The Cancer Genome Atlas to select epigenetic biomarkers predictive of survival and further understand the molecular mechanisms underlying methylation patterns in bladder cancer. We identified 540 differentially methylated genes between tumor and normal tissues, including a number of independent prognostic factors based on univariate analysis. Genes (MIR6732, SOWAHC, SERPINI1, OR10W1, OR7G3, AIM1, and ZFAND5) were integrated to establish a risk model for prognostic assessment based on multivariate Cox analysis. The methylation of SOWAHC was negatively correlated with its messenger RNA expression, and together these were significantly correlated with prognosis. This study took advantage of high-throughput data mining to provide new bioinformatics evidence and ideas for further study into the pathogenesis and prognosis of bladder cancer.


Assuntos
Metilação de DNA/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias da Bexiga Urinária/genética , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Análise de Regressão , Fatores de Risco , Urotélio/patologia
8.
BMC Cancer ; 19(1): 604, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31216997

RESUMO

BACKGROUND: The prognosis of bladder urothelial carcinoma (BLCA) varies greatly among patients, and conventional pathological predictors are generally inadequate and often inaccurate to predict the heterogeneous behavior of BLCA. This study aims to investigate the prognostic value and function of TOP2A in BLCA. METHODS: TOP2A expression level was examined by RNA-sequencing, quantitative real time polymerase chain reaction and immunohistochemistry from 10, 40 and 209 BLCA samples, respectively. Public databases were analyzed for validation. Cell proliferation, migration, invasion assays were performed to explore potential functions of TOP2A in BLCA. Flow cytometry was performed for cell cycle and apoptosis analysis. Univariable and multivariable Cox regression models were performed to identify independent risk factors for the prognosis of BLCA. RESULTS: We found TOP2A was significantly upregulated in BLCA samples, especially for high-grade and advanced stage tumors, compared with matched normal epithelial tissue. Univariable COX regression analysis revealed high TOP2A expression was significantly associated with poorer cancer-specific, progression-free and recurrence-free survival, but not independently of clinical characteristics in the multivariable models. Knockdown of TOP2A remarkably inhibited the proliferation of BLCA cells and non-cancerous urothelial cells. Furthermore, migration and invasion capacity of BLCA cells were strongly suppressed after TOP2A knockdown. Moreover, flow cytometry suggested TOP2A had anti-apoptotic function, and knockdown of TOP2A could induce resistance to doxorubicin in J82 cells. CONCLUSIONS: In our study, TOP2A was overexpressed in BLCA and could serve as a prognostic biomarker for BLCA. Moreover, TOP2A is functionally important for the proliferation, invasion and survival of BLCA cells.


Assuntos
Carcinoma/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células , DNA Topoisomerases Tipo II/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose/genética , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sequência de RNA , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
9.
Cochrane Database Syst Rev ; 2: CD012305, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30789676

RESUMO

BACKGROUND: Cystoscopy is commonly performed for diagnostic purposes to inspect the interior lining of the bladder. One disadvantage of cystoscopy is the risk of symptomatic urinary tract infection (UTI) due to pre-existing colonization or by introduction of bacteria at the time of the procedure. However, the incidence of symptomatic UTI following cystoscopy is low. Currently, there is no consensus on whether antimicrobial agents should be used to prevent symptomatic UTI for cystoscopy. OBJECTIVES: To assess the effects of antimicrobial agents compared with placebo or no treatment for prevention of UTI in adults undergoing cystoscopy. SEARCH METHODS: We comprehensively searched electronic databases of the Cochrane Library, PubMed, Embase, LILACS, and CINAHL. We searched the WHO ICTRP and ClinicalTrials.gov for ongoing trials. We used no language or date restrictions in the electronic searches. We searched the reference lists of identified articles and contacted authors for related information. The last search of the electronic databases was 4 February 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) or quasi-RCTs that compared any prophylactic antibiotic versus placebo, no treatment, or other non-antibiotic prophylaxis in adults undergoing cystoscopy. There was no restriction on the dose, frequency, formulation, duration, or mode of administration of the antibiotics. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were systemic UTI, symptomatic UTI (composite of systemic and/or localized UTI), and serious adverse events. Secondary outcomes were minor adverse events, localized UTI, asymptomatic bacteriuria, and bacterial resistance. We assessed the quality of evidence using GRADE. MAIN RESULTS: We included 20 RCTs and two quasi-RCTs with 7711 participants, all of which compared antibiotic prophylaxis with placebo or no treatment control. We found no studies comparing antibiotic prophylaxis with non-antibiotic prophylaxis.Primary outcomesSystemic UTI: antibiotic prophylaxis may have little or no effect on the risk of systemic UTI compared with placebo or no treatment (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.38 to 3.32; 5 RCTs; 504 participants; low-quality evidence); this corresponds to two more people (95% CI 12 fewer to 46 more) per 1000 people developing a systemic UTI. We downgraded the quality of the evidence for study limitations and imprecision.Symptomatic UTI: antibiotic prophylaxis may reduce the risk of symptomatic UTI (RR 0.49, 95% CI 0.28 to 0.86; 11 RCTs; 5441 participants; low-quality evidence); this corresponds to 30 fewer people (95% CI 42 fewer to 8 fewer) per 1000 people developing a symptomatic UTI when provided with antibiotic prophylaxis. We downgraded the quality of the evidence for study limitations and potential publication bias.Serious adverse events: the studies reported no serious adverse events in either the intervention group or control group and no effect size could be calculated. Antibiotic prophylaxis may have little or no effect on serious adverse events (4 RCTs, 630 participants; very low-quality evidence), but we are very uncertain of this finding. We downgraded the quality of the evidence for study limitations and very serious imprecision.Secondary outcomesMinor adverse events: prophylactic antibiotics may have little or no effect on minor adverse events when compared with placebo or no treatment (RR 2.82, 95% CI 0.54 to 14.80; 4 RCTs; 630 participants; low-quality evidence). We downgraded the quality of the evidence for study limitations and imprecision.Localized UTI: prophylactic antibiotics may have little or no effect on the risk of localized UTI (RR 1.0, 95% CI 0.06 to 15.77; 1 RCT; 200 participants; very low-quality evidence), but we were very uncertain of this finding. We downgraded the quality of the evidence for study limitations and very serious imprecision.Bacterial resistance: prophylactic antibiotics may increase bacterial resistance (RR 1.73, 95% CI 1.04 to 2.87; 38 participants; 2 RCTs; very low-quality evidence), but we were uncertain of this finding. We downgraded the quality of the evidence for study limitations, indirectness, and imprecision.We were able to perform few secondary analyses; these did not suggest any subgroup effects. AUTHORS' CONCLUSIONS: Antibiotic prophylaxis may reduce the risk of symptomatic UTI but not systemic UTIs. Serious and minor adverse events may not be increased with the use of antibiotic prophylaxis. The findings are informed by low- and very low-quality evidence ratings for all outcomes.


Assuntos
Anti-Infecciosos Urinários/uso terapêutico , Antibioticoprofilaxia , Cistoscopia/efeitos adversos , Infecções Urinárias/prevenção & controle , Adulto , Anti-Infecciosos Urinários/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Farmacorresistência Bacteriana , Humanos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Urinárias/etiologia
10.
Int J Cancer ; 143(2): 396-407, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29441565

RESUMO

Genetic alterations drive metabolic reprograming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa. Significant accumulation of metabolic intermediates and enrichment of genes in the tricarboxylic acid (TCA) cycle were observed in tumor tissues, indicating TCA cycle hyperactivation in PCa tissues. In addition, the levels of fumarate and malate were highly correlated with the Gleason score, tumor stage and expression of genes encoding related enzymes and were significantly related to the expression of genes involved in branched chain amino acid degradation. Using an integrated omics approach, we further revealed the potential anaplerotic routes from pyruvate, glutamine catabolism and branched chain amino acid (BCAA) degradation contributing to replenishing metabolites for TCA cycle. Integrated omics techniques enable the performance of network-based analyses to gain a comprehensive and in-depth understanding of PCa pathophysiology and may facilitate the development of new and effective therapeutic strategies.


Assuntos
Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Metabolômica/métodos , Neoplasias da Próstata/patologia , Ciclo do Ácido Cítrico , Fumaratos/análise , Cromatografia Gasosa-Espectrometria de Massas , Regulação Neoplásica da Expressão Gênica , Humanos , Malatos/análise , Masculino , Gradação de Tumores , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Análise de Sequência de RNA
11.
World J Urol ; 36(1): 41-50, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29080948

RESUMO

PURPOSE: Enhanced recovery after surgery (ERAS) has played an important role in recovery management for radical cystectomy with ileal urinary diversion (RC-IUD). This study is to evaluate ERAS compared with the conventional recovery after surgery (CRAS) for RC-IUD. METHODS: From October 2014 and July 2016, bladder cancer patients scheduled for curative treatment from 25 centers of Chinese Bladder Cancer Consortium were randomly assigned to either ERAS or CRAS group. Primary endpoint was the 30-day complication rate. Secondary endpoints included recovery of fluid and regular diet, flatus, bowel movement, ambulation, and length of stay (LOS) postoperatively. Follow-up period was 30-day postoperatively. RESULTS: There were 144 ERAS and 145 CRAS patients. Postoperative complications occurred in 25.7 and 30.3% of the ERAS and CRAS patients with 55 complications in each group, respectively (p = 0.40). There was no significant difference between groups in major complications (p = 0.82), or type of complications (p = 0.99). The ERAS group had faster recovery of bowel movements (median 88 versus 100 h, p = 0.01), fluid diet tolerance (68 versus 96 h, p < 0.001), regular diet tolerance (125 versus 168 h, p = 0.004), and ambulation (64 versus 72 h, p = 0.047) than the CRAS group, but similar time to flatus and LOS. CONCLUSIONS: ERAS did not increase 30-day complications compared with CRAS after RC. ERAS may be better than CRAS in terms of bowel movement, tolerance of fluid and regular diet, and ambulation.


Assuntos
Cistectomia , Cuidados Pós-Operatórios/métodos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária , China , Cistectomia/métodos , Feminino , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica
12.
Mol Cell Proteomics ; 15(1): 154-63, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26545398

RESUMO

Prostate cancer is a highly prevalent tumor affecting millions of men worldwide, but poor understanding of its pathogenesis has limited effective clinical management of patients. In addition to transcriptional profiling or transcriptomics, metabolomics is being increasingly utilized to discover key molecular changes underlying tumorigenesis. In this study, we integrated transcriptomics and metabolomics to analyze 25 paired human prostate cancer tissues and adjacent noncancerous tissues, followed by further validation of our findings in an additional cohort of 51 prostate cancer patients and 16 benign prostatic hyperplasia patients. We found several altered pathways aberrantly expressed at both metabolic and transcriptional levels, including cysteine and methionine metabolism, nicotinamide adenine dinucleotide metabolism, and hexosamine biosynthesis. Additionally, the metabolite sphingosine demonstrated high specificity and sensitivity for distinguishing prostate cancer from benign prostatic hyperplasia, particularly for patients with low prostate specific antigen level (0-10 ng/ml). We also found impaired sphingosine-1-phosphate receptor 2 signaling, downstream of sphingosine, representing a loss of tumor suppressor gene and a potential key oncogenic pathway for therapeutic targeting. By integrating metabolomics and transcriptomics, we have provided both a broad picture of the molecular perturbations underlying prostate cancer and a preliminary study of a novel metabolic signature, which may help to discriminate prostate cancer from normal tissue and benign prostatic hyperplasia.


Assuntos
Perfilação da Expressão Gênica/métodos , Redes e Vias Metabólicas/genética , Metabolômica/métodos , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Cromatografia Líquida , Estudos de Coortes , Humanos , Masculino , Espectrometria de Massas , Metaboloma/genética , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcriptoma/genética
13.
Biochem Biophys Res Commun ; 474(1): 213-219, 2016 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-27109471

RESUMO

MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3'UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer.


Assuntos
Arrestinas/genética , Integrina beta4/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Androgênicos/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Transdução de Sinais/genética
14.
Anal Bioanal Chem ; 408(24): 6741-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27473428

RESUMO

Bladder cancer (BC) is a fatal malignancy with considerable mortality. BC urinary metabolomics has been extensively investigated for biomarker discovery, but few BC blood metabolomic studies have been performed. Hence, a plasma pseudotargeted metabolomic method based on gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was developed to study metabolic alterations in BC. The analytical performance of the developed method was compared with that of a nontargeted method. The relative standard deviation (RSD) values of 89 and 70.7 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, were less than 20 %. The Pearson correlations of 90.7 and 78.3 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, exceeded 0.90 in the linearity evaluation. Compared with the nontargeted method, the signal-to-noise ratios (S/N) of 97.9 and 69.3 % of the peaks increased two- and fivefold, respectively. The developed method was fully validated, with good precision, recovery, and stability of the trimethylsilyl (TMS) derivatives. The method was applied to investigate BC. Significant increases in the contents of metabolites involved in, for example, the pentose phosphate pathway (PPP) and nucleotide and fatty acid synthesis were found in the high-grade (HG) BC group compared to the healthy control (HC) group. These differences imply that the activated PPP may regulate BC cell proliferation by promoting lipid and nucleotide biosynthesis and the detoxification of reactive oxygen species (ROS). These results illustrate that the plasma pseudotargeted method is a powerful tool for metabolic profiling. Graphical abstract The plasma pseudotargeted metabolic profiling suggested the metabolic alterations in bladder cancer (BC) and the significantly differential metabolites for BC discrimination.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Metaboloma , Metabolômica/métodos , Neoplasias da Bexiga Urinária/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/metabolismo
15.
Zhonghua Nan Ke Xue ; 22(7): 626-629, 2016 Jul.
Artigo em Zh | MEDLINE | ID: mdl-28965381

RESUMO

OBJECTIVE: To investigate the treatment of azoospermia induced by iatrogenic injury to the bilateral vas deferens. METHODS: We retrospectively analyzed 11 cases of azoospermia caused by iatrogenic injury to bilateral vas deferens. The patients were aged 20-33 years, all diagnosed with azoospermia preoperatively and none with a history of pelvic operation. Seven of them had received bilateral inguinal hernia repair and the other 4 undergone bilateral orchidopexy in the childhood. RESULTS: Intraoperative exploration of the bilateral inguinal region was performed in all the patients. Bilateral vas deference atresia was found in the inguinal canal in 6 cases, which was treated by microscopic vasovasostomy following removal of the atresic segment. Vas deferens residual was observed in or near the deep inguinal ring in the other 5 cases, with the distal vas deferens inaccessible, which was treated by bilateral vasovasostomy in 3 cases and unilateral vasovasostomy in 2 (for longer defect segment than could be anastomosed) following combined laparoscopic exploration of the abdominal cavity. The patients were followed up for 3-12 months postoperatively, during which sperm were detected in 7 cases, with sperm concentration ranging from 0.4×106/ml to 35×106/ml and grade a+b sperm from 15% to 46%. CONCLUSIONS: For the diagnosis of azoospermia, especially in patients with no history of pelvic operation, special attention should be paid to iatrogenic injury to the vas deferens. For the treatment of the disease, non-tension vasovasostomy is essential and, when necessary, the vas deferens can be reconstructed by changing its anatomical path and shortening its length.


Assuntos
Azoospermia/cirurgia , Doença Iatrogênica , Ducto Deferente/lesões , Adulto , Hérnia Inguinal/cirurgia , Humanos , Laparoscopia , Masculino , Microcirurgia , Pelve/cirurgia , Estudos Retrospectivos , Contagem de Espermatozoides , Vasovasostomia , Adulto Jovem
16.
Prostate ; 75(6): 653-61, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25597901

RESUMO

BACKGROUND: Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). METHODS: Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. RESULTS: 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. CONCLUSIONS: FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis.


Assuntos
Biópsia , Próstata/patologia , Neoplasias da Próstata/diagnóstico , RNA Longo não Codificante/urina , Idoso , Biomarcadores Tumorais/urina , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/urina
17.
BJU Int ; 115(3): 437-45, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24731125

RESUMO

OBJECTIVES: To compare the peri-operative and early renal functional outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for kidney tumours. MATERIALS AND METHODS: A total of 237 patients fulfilling the selection criteria were included, of whom 146 and 91 patients were treated with LPN and RAPN, respectively. To adjust for potential baseline confounders, propensity-score matching was performed. A favourable outcome was defined as a warm ischaemia time (WIT) of ≤20 min, negative surgical margins, no surgical conversion, no Clavien ≥3 complications and no postoperative chronic kidney disease (CKD) upstaging. Descriptive statistics and multivariable logistic regression analyses were performed before and after propensity-score matching. RESULTS: Within the propensity-score-matched cohort, the RAPN group was associated with significantly lower estimated blood loss (EBL; 156 vs 198 mL, mean difference [MD] = -42; P = 0.025), a shorter WIT (22.8 vs 31 min, MD = -8.2; P < 0.001) and a higher proportion of malignant lesions (88.4 vs 67.5%; odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.2-5.67; P = 0.023). With regard to early renal functional outcomes, the mean last estimated glomerular filtration rate was 95.8 and 89.4 mL/min per 1.73 m(2) (MD = 6.4; P = 0.01), with a mean ± sd percentage change of -4.8 ± 17.9 and -12.2 ± 16.6 (MD = 7.4; P = 0.018) in the RAPN and LPN groups, respectively. The intra-operative complication rate was significantly lower in the RAPN group (1.3 vs 11.7%; OR 0.1, 95% CI 0.01-0.81; P = 0.018). On multivariable analysis, surgical approach (RAPN vs LPN, OR 5.457, 95% CI 2.075-14.346; P = 0.001), Charlson Comorbidity Index (OR 0.223; 95% CI 0.062-0.811; P = 0.023), diameter-axial-polar score (OR 0.488, 95% CI 0.329-0.723; P < 0.001) and preoperative CKD stage (OR 3.189, 95% CI 1.204-8.446; P = 0.020) were found to be independent predictors of obtaining a favourable outcome. CONCLUSIONS: After adjusting for potential treatment selection biases, RAPN was found to be superior to LPN for peri-operative outcomes (EBL, WIT and intra-operative complications) and early renal functional preservation.


Assuntos
Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
18.
J Sex Med ; 12(2): 567-71, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25471258

RESUMO

INTRODUCTION: Sexual curiosity and the quest for sexual excitement are the most frequent reasons for patients to introduce foreign bodies into the urethra or the bladder. Imagination and surgical skill are essential for urologists to retrieve such vesical foreign bodies. AIM: The aim of this study was to describe a novel method for retrieving vesical magnetic beads, which were inserted for autoeroticism by a male adolescent, with a self-made "magnetic sheath." METHODS: A 21-year-old young man inserted more than one hundred small magnetic beads into his urethra for sexual excitement, which lately caused symptoms of gross hematuria, frequent urination, and acute lower abdominal pain when walking or urinating. We invented a magnetic sheath by fixing a magnetic bead on the tip of an F9.5 ureteral access sheath to remove the foreign bodies in a minimally invasive way. MAIN OUTCOME MEASURE: The feasibility of using magnetic sheath to remove vesical foreign bodies; and operation duration. RESULTS: Under direct visualization of an F8/9.8 ureteroscope, the magnetic sheath could firmly attach to the magnetic bead inside the bladder and could easily pull out 5 to 15 beads each time. It took about 5 minutes to remove all of the 125 magnetic beads by utilizing our magnetic sheath. CONCLUSIONS: The self-made magnetic sheath can make the task of removal of magnetic foreign bodies easy to urologists, requiring less time and surgical skills. The new equipment provides a new method for urologists to deal with the challenging task of removing metal vesical foreign bodies which were self-inserted for masturbation.


Assuntos
Corpos Estranhos/complicações , Corpos Estranhos/cirurgia , Migração de Corpo Estranho/complicações , Prepúcio do Pênis/lesões , Fenômenos Magnéticos , Imãs/efeitos adversos , Uretra/lesões , Doenças da Bexiga Urinária/etiologia , Adolescente , Migração de Corpo Estranho/cirurgia , Humanos , Masculino , Masturbação , Procedimentos Cirúrgicos Minimamente Invasivos , Comportamento Sexual , Resultado do Tratamento , Doenças da Bexiga Urinária/cirurgia , Adulto Jovem
19.
Phytother Res ; 29(5): 633-47, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25641408

RESUMO

The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti-nociceptive, antiinflammatory, anti-tumor, anti-oxidant, insecticidal, antimicrobial, anti-androgenic, anti-osteoporotic, anti-cataract, hepatoprotective and anti-hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure-activity relationship and their molecular mechanisms of action.


Assuntos
Extratos Vegetais/farmacologia , Plantas Medicinais/química , Vitex/química , Animais , China , Flavonoides , Humanos , Índia , Japão , Lignanas , Fitoterapia , Esteroides , Terpenos
20.
J Cell Physiol ; 229(7): 834-44, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24243035

RESUMO

Castration-resistant prostate cancer (CRPC) and its treatment are challenging issues in prostate cancer management. Here, we report that miR-663 is upregulated in CRPC tissues. Overexpression of miR-663 in prostate LNCaP cells promotes cell proliferation and invasion, neuroendocrine differentiation, and reduction in dihydrotestosterone-induced upregulation of prostate-specific antigen expression. Furthermore, results of in situ hybridization show that miR-663 expression is correlated with Gleason score and TNM stage and is an independent prognostic predictor of clinical recurrence. Together, these findings suggest that miR-663 is a potential oncomiR for CRPC and may serve as a tumor biomarker for the early diagnosis of CRPC.


Assuntos
MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Detecção Precoce de Câncer , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/biossíntese , Invasividade Neoplásica/genética , Recidiva Local de Neoplasia/patologia , Neoplasias de Próstata Resistentes à Castração/patologia
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