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1.
J Cell Mol Med ; 24(8): 4698-4706, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32168432

RESUMO

This study aimed to explore the association between LIM domain kinase 1 (LIMK1) expression in prostate cancer (PCa) tissues with advanced pathological features, lymph node metastases and biochemical recurrence. A total of 279 PCa specimens from patients who underwent radical prostatectomy and 50 benign prostatic hyperplasia (BPH) specimens were collected to construct tissue microarray, which were subjected to immunohistochemical staining for LIMK1 expression subsequently. Logistic and Cox regression analysis were used to evaluate the relationship between LIMK1 expression and clinicopathological features of patients with PCa. Immunohistochemical staining assay demonstrated that LIMK1 expression was significantly higher in PCa than BPH specimens (77.1% vs 26.0%; P < .001). LIMK1 expression was significantly higher in positive lymph node specimens than corresponding PCa specimens (P = .002; P < .001). Up-regulation of LIMK1 was associated with prostate volume, prostate-specific antigen, prostate-specific antigen density, Gleason score, T stage, lymph node metastases, extracapsular extension and seminal vesicle invasion, and positive surgical margin. Multivariate logistic regression analysis demonstrated that LIMK1 was an independent risk factor for PCa lymph node metastasis (P < .05). Multivariate Cox regression analysis revealed that the up-regulation of LIMK1 was an independent risk factor for biochemical recurrence. Kaplan-Meier analysis indicated that up-regulation LIMK1 was associated with shortened biochemical-free survival (BFS) after radical prostatectomy (P < .001). In conclusion, LIMK1 was significantly up-regulated in PCa and positive lymph node specimens and correlated with lymph node metastasis and shortened BFS of PCa. The underlying molecular mechanism of LIMK1 in PCa should be further evaluated.


Assuntos
Quinases Lim/genética , Metástase Linfática/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Próstata/genética , Idoso , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia , Análise de Sobrevida
2.
J Cell Biochem ; 121(1): 231-243, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31190401

RESUMO

The significance of actin-related protein 2/3 complex subunit 4 (ARPC4) expression in bladder cancer, and its potential role in the invasion and migration of bladder cancer cells, has yet to be determined. This study was to identify the correlation between ARPC4 and lymph node metastasis, and to determine the role of ARPC4 in the invasive migration of T24 bladder cancer cells. One hundred and ninety-eight bladder cancer tissues and 40 normal bladder and lymph node tissues were examined. Tissue microarrays were constructed and subjected to immunohistochemical stating for ARPC4. Multiple logistic analysis was used to determine risk factors associated with bladder cancer metastasis. ARPC4 expression in T24 bladder cancer cells was suppressed using small interfering RNA and changes in protein levels were determined by Western blot analysis. The proliferation of bladder cancer cells after knocking down of ARPC4 was determined by cell counting kit-8. The effects of ARPC4 knockdown on T24 cell invasion and migration was determined using transwell and wound healing assays. Immunofluorescence analysis was performed to examine changes in pseudopodia formation and actin cytoskeleton structure. The expression of ARPC4 was elevated in bladder cancer tissues than normal tissues (84.3% vs 27.5%, P < 0.001). The multivariate logistic analysis demonstrated that the level of ARPC4, as a risk factor, was correlated with lymphatic metastasis (P < 0.05). ARPC4 knockdown attenuated proliferation, migration, invasion, and pseudopodia formation in T24 cells. ARPC4 expression, as a risk factor, is associated with lymphatic metastasis and is upregulated in bladder cancer tissues in comparison with normal tissues. Inhibition of ARPC4 expression significantly attenuates the proliferation, migration, and invasion of bladder cancer cell, possibly due to defects in pseudopodia formation.


Assuntos
Actinas/metabolismo , Metástase Linfática , Neoplasias da Bexiga Urinária/metabolismo , Citoesqueleto de Actina/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , RNA Interferente Pequeno/metabolismo , Fatores de Risco , Análise Serial de Tecidos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Cicatrização
3.
Med Sci Monit ; 26: e920504, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32277695

RESUMO

BACKGROUND Evidence indicates that there is an important role for long non-coding RNAs (lncRNA) in numerous cellular processes and that lncRNAs dysregulation contributes to tumor progression. Improved insight into the molecular characteristics of bladder cancer is required to predict outcomes and to develop a new rationale for targeted therapeutic strategies. Bioinformatics methods, including functional enrichment and network analysis combined with survival analysis, are required to process a large volume of data to obtain further information about differentially expressed genes (DEGs) in bladder cancer. This study aimed to explore the role of lncRNAs and their regulation network in bladder cancer. MATERIAL AND METHODS We analyzed bladder cancer data by The Cancer Genome Atlas profiling to identify differentially expressed lncRNAs in bladder cancer. The genes involved in the circlncRNAnet database were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), evolutionary relationship analysis, and protein-protein interaction (PPI) networks. RESULTS Two new lncRNAs, ADAMTS9-AS1 and LINC00460, were shown to be differentially expressed in bladder cancer. Patients were divided into 2 groups (high expression and low expression) according to their median expression values. The overall survival and disease-free survival of patients with high ADAMTS9-AS1 bladder cancer were significantly shorter; the expression of LINC00460 had no significant correlation with survival. GO and KEGG analysis of the 2 lncRNA-related genes revealed that these lncRNAs played a vital role in tumorigenesis. Bioinformatics analysis showed that key genes related to LINC00460, including CXCL, CCL, and CSF2, may be related to the development of bladder cancer. The low expression of ADAMTS9-AS1 may influence the survival rate of bladder cancer with the hub gene as a target. CONCLUSIONS LncRNA, including LINC00460 and ADAMTS9-AS1, might play a crucial role in the biosynthesis network of bladder cancer. Differential expression results of ADAMTS9-AS1 suggests it may be correlated with a worse prognosis and a shorter survival time. We outlined the biosynthesis network that regulates lncRNAs in bladder cancer. Further experimental data is needed to validate our results.


Assuntos
RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Biomarcadores Tumorais/genética , Biologia Computacional , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Prognóstico , Mapas de Interação de Proteínas , Análise de Sobrevida , Transcriptoma , Neoplasias da Bexiga Urinária/diagnóstico
4.
J Cell Physiol ; 234(11): 19942-19950, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31187492

RESUMO

Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) in elderly man. However, the underlying molecular mechanisms of BPH have not been completely elucidated. We identified the key genes and pathways by using analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using edgeR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the DEGs by Database for Annotation, Visualization and Integrated Discovery (DAVID) database and ConsensusPathDB, respectively. Then, protein-protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Finally, we identified 660 DEGs ultimately including 268 upregulated genes and 392 downregulated genes. GO analysis revealed that DEGs were mainly enriched in extracellular exosome, identical protein binding, mitochondrial adenosine triphosphate (ATP) synthesis coupled proton transport, extracelluar matrix, focal adhesion, cytosol, Golgi apparatus, cytoplasm, protein binding, and Golgi membrane. Focal adhesion pathway, FoxO signaling pathway, and autophagy pathway were selected. Ubiquitin-conjugating enzyme E2 C (UBE2C), serine/threonine kinase (AKT1), mitogen-activated protein kinase 1 (MAPK1), cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) were filtrated as the hub genes according to the degree of connectivity from the PPI network. The five hub genes including UBE2C, AKT1, MAPK1, CCNB1, PLK1 may play key roles in the pathogenesis of benign prostatic hyperplasia (BPH). Focal adhesion pathway, FoxO signaling pathway, and autophagy pathway may be crucial for the progression of BPH.


Assuntos
Genes Neoplásicos , Hiperplasia Prostática/genética , Transdução de Sinais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Genoma , Humanos , Masculino , Mapas de Interação de Proteínas/genética
5.
Zhonghua Nan Ke Xue ; 20(1): 48-53, 2014 Jan.
Artigo em Zh | MEDLINE | ID: mdl-24527537

RESUMO

OBJECTIVE: To evaluate the long-term outcomes of hypospadias surgery relating to penile appearance, sexual function and sexual satisfaction, and analyze the influencing factors by comparing them with those of healthy male adults. METHODS: We conducted follow-up visits to 128 hypospadias patients surgically treated in our hospital between January 1990 and June 1994. We retrospectively analyzed their clinical data in comparison with 136 healthy male adults. RESULTS: The rate of satisfaction with penile appearance was significantly lower in the hypospadia patients than in the healthy men, and the main reason for the patients'dissatisfaction was inadequate penile size. There were no statistically significant differences between the two groups in sexual function and sexual satisfaction. The rate of sexual satisfaction was lower in the patients treated for proximal and middle shaft hypospadias but higher in those treated for distal shaft hypospadias than in the healthy adults, particularly high in those successfully treated by one-stage surgery at the age of < or = 3 years. The factors influencing postoperative sexual satisfaction included penile appearance, severity of hypospadias, surgical complications, surgical stage, age of surgery, and premature ejaculation. However, sexual satisfaction was not affected by surgical complications and surgical staging in those successfully treated by one-stage surgery at the age of < or = 3 years. CONCLUSION: Importance should be attached to the long-term follow-up of hypospadias patients after surgery. Sexual satisfaction could be achieved by successful one-stage urethroplasty at the age of < or = 3 years. Appropriate surgical procedures based on the characteristics of different cases may help the patients to establish confidence in their future sexual activities.


Assuntos
Hipospadia/fisiopatologia , Hipospadia/cirurgia , Pênis , Adolescente , Adulto , Estudos de Casos e Controles , Seguimentos , Humanos , Masculino , Satisfação do Paciente , Período Pós-Operatório , Estudos Retrospectivos , Comportamento Sexual , Inquéritos e Questionários , Adulto Jovem
6.
Urol Int ; 90(3): 354-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23548842

RESUMO

OBJECTIVE: Tubularized incised plate (TIP) urethroplasty is performed by many pediatric urologists and has been widely accepted for repair of distal and mid-shaft hypospadias. However, the role of urethral catheter placement in TIP repair remains controversial. In this study, the surgical outcomes of indwelling urethral catheter and non-catheter TIP repairs in boys with hypospadias were compared. METHODS: A total of 254 patients with primary distal and mid-shaft hypospadias underwent TIP repair and were evaluated retrospectively. A urethral catheter was placed in 103 patients (group A) and non-catheter repair was performed in 151 patients (group B). Information obtained included age, toilet training, chordee, type of hypospadias, presence or absence of a catheter, and postoperative complications. The complications recorded included wound infection, urinary tract infection, bladder spasm, urinary retention, urinary extravasation, meatal stenosis, urethral stricture, and urethrocutaneous fistula. RESULTS: There was no statistical difference in age, toilet training, chordee, hypospadias site, or performing surgeon between the two groups. The median follow-up time was 22 and 24 months for groups A and B, respectively. The rate of bladder spasms (10.7 vs. 0%, p < 0.001) and urinary tract infection (9.7 vs. 3.3%, p = 0.034) was significantly higher for group A than group B. Although the rate of urinary retention was higher in group B than in group A (4.0 vs. 0%), there was no statistically significant difference between the two groups (p = 0.084). Likewise, the incidence of urethrocutaneous fistula and meatal stenosis was not significantly different. CONCLUSION: Non-catheter TIP repair is feasible and positive outcomes can be achieved with minimal complications and less patient discomfort.


Assuntos
Hipospadia/cirurgia , Pênis/cirurgia , Uretra/cirurgia , Cateterismo Urinário/instrumentação , Cateteres Urinários , Procedimentos Cirúrgicos Urológicos Masculinos , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Pênis/anormalidades , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Uretra/anormalidades , Cateterismo Urinário/efeitos adversos , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos
7.
Cell Biosci ; 13(1): 38, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36814338

RESUMO

OBJECTIVE: This study aimed to identify potential biomarkers for prostate cancer (PCa) progression and metastasis, and to discern their biological functions. METHODS: Bioinformatics methods were used to screen for hub genes. The expression level of key hub genes in PCa was determined and their prognostic significance was examined. A series of functional assays were performed to investigate the function of the highest-ranking hub gene. RESULTS: Actin related protein 2/3 complex subunit 1A (ARPC1A) was identified as the hub gene. ARPC1A was highly expressed in PCa tissues and cell lines, and was an independent prognostic factor for predicting biochemical recurrence after radical prostatectomy and overall survival of PCa patients. Knockdown of ARPC1A inhibited PCa cell migration, invasion and cytoskeleton formation, but had no impact on cell proliferation and cell cycle progression. In vivo, ARPC1A overexpression promoted lung metastasis of PCa, but had no efffect on tumor growth. Additionally, glutamine metabolism was identified as an upstream regulator of ARPC1A, and promoted migration, invasion and cytoskeletal changes of PCa cell through ARPC1A. CONCLUSION: These findings suggested that ARPC1A, which correlates with poor prognosis in PCa, functions downstream of glutamine metabolism to regulate cytoskeletal changes, cellular migration and cellular invasion in this disease.

8.
Clin Nutr ; 40(12): 5792-5801, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34775222

RESUMO

OBJECTIVE: To investigate the predictors of response to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) patients. MATERIALS AND METHODS: We retrospectively analyzed the clinicopathological data of 184 intermediate and high risk NMIBC cases receiving transurethral resection of bladder tumor (TURBT) and intravesical BCG immunotherapy from December 2014 to April 2021 at our center. All patients were divided into BCG responders and non-responders. Multivariate Logistic regression analysis was performed to identify the independent predictors of response to intravesical BCG immunotherapy. Univariate and multivariate Cox regression analyses were applied to explore the independent prognostic factors of recurrence-free survival (RFS). Receiver operating characteristic (ROC) curve and Kaplan-Meier survival analysis were also utilized. RESULTS: The RFS of BCG responders was significantly increased compared with BCG non-responders. Multivariate Cox regression analysis demonstrated that low grade, pTa stage, non-CIS, lower relative visceral fat area (rVFA) and lower systemic immune inflammation index (SII) were independent prognostic factors of increased RFS after intravesical BCG immunotherapy. Multivariate Logistic regression analysis demonstrated that pTa stage, low grade, non-CIS, low rVFA, and low SII were independent predictors of response to intravesical BCG immunotherapy. Kaplan-Meier survival analysis indicated that the RFS of patients in low rVFA group or low SII group was significantly increased in comparison with those in high rVFA group or high SII group. ROC curve analysis showed that the area under ROC (AUC) of including SII and rVFA was significantly increased, indicating that the inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency. CONCLUSIONS: Low grade, pTa stage, non-CIS, preoperative lower rVFA and lower SII were vital independent predictors of response to intravesical BCG immunotherapy and were associated with preferable prognosis in NMIBC patients. The inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Imunoterapia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Gordura Abdominal/imunologia , Administração Intravesical , Idoso , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/imunologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Bexiga Urinária/patologia
9.
Asian J Surg ; 44(1): 80-86, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32291131

RESUMO

PURPOSE: To determine the risk factors of intraoperative cyst rupture in partial nephrectomy (PN) for a cystic renal mass (CRM) and their effect on the prognosis of patients. MATERIALS AND METHODS: Patients who underwent partial nephrectomy for CRMs from January 2009 to January 2015 were included. Uni/multivariate Logistic/Cox analysis and Kaplan-Meier analysis were performed. RESULTS: A total of 174 patients were included in this study. There were 27 (15.5%) intraoperative cyst ruptures. The median follow-up time was 60 months. Multivariate logistic analysis showed that the E component (P = 0.018) and N component (P = 0.022) of the R.E.N.A.L. nephrometry score, Bosniak category III (P = 0.044), and surgeon's experience (P = 0.030) were risk factors associated with intraoperative cyst rupture in PN for CRMs. The 5-year recurrence-free survival (RFS), cancer-free survival (CFS) and overall survival (OS) were 92.7%, 90.32% and 94.4%, respectively, in 124 cases of malignant CRM. Kaplan-Meier analysis demonstrated that 5-year RFS and 5-year CFS in patients with cyst rupture was worse than those without cyst rupture (P = 0.006 and 0.003, respectively). Multivariate Cox analysis revealed that intraoperative cyst rupture was independent risk factor for 5-year RFS and 5-year CFS (P = 0.039 and 0.013, respectively). However, there was no significant difference in OS between the two groups (P = 0.275). CONCLUSIONS: The prevalence of intraoperative cyst rupture is relatively high. Higher E and N scores, Bosniak category III, and lacking surgical experience (<20 cases) increase the risk of occurrence of intraoperative cyst rupture.


Assuntos
Complicações Intraoperatórias/etiologia , Doenças Renais Císticas/cirurgia , Nefrectomia/métodos , Ruptura Espontânea/etiologia , Adulto , Idoso , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Estimativa de Kaplan-Meier , Doenças Renais Císticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Ruptura Espontânea/epidemiologia , Taxa de Sobrevida
10.
Front Oncol ; 10: 1547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923401

RESUMO

OBJECTIVE: To explore the risk factors for postoperatively pathological lymph node metastasis in patients with clinical T2N0M0 stage prostate cancer (PCa). METHODS: We retrospectively analyzed clinicopathological data of 316 patients with clinical T2 stage PCa and preoperative negative lymph nodes [LN(-)] indicated by imaging (cT2N0M0) between January 2014 and May 2019. Multivariate logistic regression analysis was performed to determine risk factors for postoperatively pathological pLN(+) in patients with cT2N0M0 stage PCa. Spearman correlation analysis was used to explore the relationship between tumor burden and Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. RESULTS: A total of 45 patients (14.2%) were confirmed by postoperative pathology to have LN metastasis. Univariate analysis indicated that total prostate-specific antigen (tPSA), PI-RADS v2 score, postoperative Gleason grade group (GGG), intraductal carcinoma of the prostate (IDC-P), clinical T2 substaging, and postoperative pathological tumor burden were risk factors for pLN(+) in all patients. Multivariate analysis showed that tPSA and postoperative GGG were risk factors for pLN(+) in all patients. Univariate analysis revealed that tPSA, PIRADS v2 score, clinical T2 substaging, IDC-P, postoperative pathological tumor burden, and postoperative GGG were risk factors for pLN(+) in patients with GGG ≥ 3. Multivariate analysis suggested that tPSA, PI-RADS v2 score, clinical T2 substaging, postoperative pathological tumor burden, and GGG were risk factors for pLN (+) in patients with GGG ≥ 3. Spearman correlation analysis showed that PI-RADS v2 score was positively correlated with clinical T2 substaging and postoperative pathological tumor burden. CONCLUSION: There was a high risk of LN metastasis in patients with cT2 PCa if they had high preoperative tPSA or high postoperative GGG. Patients with cT2 PCa and GGG ≥ 3 had a high risk of LN metastasis if they had high PI-RADS v2 score, high preoperative clinical stage or high postoperative pathological tumor burden. PI-RADS v2 score predicted tumor burden well in patients with GGG ≥ 3.

11.
Pathol Res Pract ; 216(10): 153109, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853947

RESUMO

OBJECTIVE: To identify hub genes and pathways involved in castrate-resistant prostate cancer (CRPC). METHODS: The gene expression profiles of GSE70768 were downloaded from Gene Expression Omnibus (GEO) datasets. A total of 13 CRPC samples and 110 tumor samples were identified. The differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. Protein-protein interaction (PPI) network module analysis was constructed and performed in Cytoscape software. Weighted correlation network analysis (WGCNA) was conducted to determine hub genes involved in the development and progression of CRPC. The gene expression profiles of GSE80609 were used for validation. RESULTS: A total of 1738 DEGs were identified, consisting of 962 significantly down-regulated DEGs and 776 significantly upregulated DEGs for the subsequent analysis. GO term enrichment analysis suggested that DEGs were mainly enriched in the extracellular matrix organization, extracellular exosome, extracellular matrix, and extracellular space. KEGG pathway analysis found DEGs significantly enriched in the focal adhesion pathway. PPI network demonstrated that the top 10 hub genes were ALB, ACACB, KLK3, CDH1, IL10, ALDH1A3, KLK2, ALDH3B2, HBA1, COL1A1. Also, WGCNA identified the top 5 hub genes in the turquoise module, including MBD4, BLZF1, PIP5K2B, ZNF486, LRRC37B2. Plus, the Venn diagram demonstrated that HBA1 was the key gene in both GSE70768 and GSE80609 datasets. CONCLUSIONS: These newly identified genes and pathways could help urologists understand the differences in the mechanism between CRPC and PCa. Besides, it might be promising targets for the treatment of CRPC.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Neoplasias da Próstata/genética , Mapas de Interação de Proteínas/genética , Transcriptoma/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Masculino
12.
Aging (Albany NY) ; 11(21): 9478-9491, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672930

RESUMO

BACKGROUND: Numerous patients with clear cell renal cell carcinoma (ccRCC) experience drug resistance after immunotherapy. Regulatory T (Treg) cells may work as a suppressor for anti-tumor immune response. PURPOSE: We performed bioinformatics analysis to better understand the role of Treg cells in ccRCC. RESULTS: Module 10 revealed the most relevance with Treg cells. Functional annotation showed that biological processes and pathways were mainly related to activation of the immune system and the processes of immunoreaction. Four hub genes were selected: LCK, MAP4K1, SLAMF6, and RHOH. Further validation showed that the four hub genes well-distinguished tumor and normal tissues and were good prognostic biomarkers for ccRCC. CONCLUSION: The identified hub genes facilitate our knowledge of the underlying molecular mechanism of how Treg cells affect ccRCC in anti-tumor immune therapy. METHODS: The CIBERSORT algorithm was performed to evaluate tumor-infiltrating immune cells based on the Cancer Genome Atlas cohort. Weighted gene co-expression network analysis was conducted to explore the modules related to Treg cells. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was built. Samples from the International Cancer Genomics Consortium database was used as a validation set.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Linfócitos T Reguladores , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Feminino , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Masculino , Pessoa de Meia-Idade , Mapas de Interação de Proteínas , Proteínas Serina-Treonina Quinases/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Fatores de Transcrição/genética , Proteínas rho de Ligação ao GTP/genética
13.
Onco Targets Ther ; 12: 3683-3693, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190870

RESUMO

Background: Seminoma accounts for the most part of cases of testicular germ cell tumor, which is the most common malignancy among males between ages 15 and 44 years. Understanding the molecular mechanism of tumorigenesis is important for better clinical diagnosis and treatment. Purpose: We performed bioinformatics analysis to better understand seminoma at the genetic level and to explore potential candidate genes or molecules for diagnosis, treatment, and prognosis. Methods: A gene expression profile (GSE8607), containing 40 seminoma samples and three healthy testes samples, was analyzed to identify differentially expressed genes (DEGs) associated with the occurrence of seminoma. Functional annotation was then performed using gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Cytoscape with Search Tool for the Retrieval of Interacting Genes was used to construct a protein-protein interaction (PPI) network of the DEGs and select hub genes. Moreover, validation of expression level and Kaplan-Meier analysis for overall survival were conducted to those hub genes. Results: A total of 1,636 DEGs were identified between seminoma and healthy samples, including 701 up-regulated in seminoma that were enriched in the regulation of immune responses, defense responses, receptor activity, and signal transducer activity; 935 were down-regulated in seminoma and were associated with reproductive processes, kinase activity, and carbohydrate derivative binding. Five hub genes were selected from the PPI network according to the degree of connectivity: IL6, VEGFA, IL10, CCR5, and CXCR4. Among them, high expression levels of CCR5 and CXCR4 were associated with poor prognosis for seminoma patients. Four modules selected from the PPI network revealed that seminoma was connected with the Janus kinase-signal transducers and activators of transcription signaling pathway, chemokine signaling pathway, endocytosis, and cytokine-cytokine receptor interaction. Conclusion: These identified DEGs and hub genes facilitate our knowledge of the underlying molecular mechanism of seminoma and have the potential to be used as diagnostic biomarkers or therapeutic targets for seminoma.

14.
J Cancer Res Clin Oncol ; 144(5): 987-995, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29504080

RESUMO

PURPOSE: To explore the value of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) for predicting prostate biopsy results in patients with prostate specific antigen (PSA) levels of 4-10 ng/ml. METHODS: We retrospectively reviewed multi-parameter magnetic resonance images from 528 patients with PSA levels of 4-10 ng/ml who underwent transrectal ultrasound-guided prostate biopsies between May 2015 and May 2017. Among them, 137 were diagnosed with prostate cancer (PCa), and we further subdivided them according to pathological results into the significant PCa (S-PCa) and insignificant significant PCa (Ins-PCa) groups (121 cases were defined by surgical pathological specimen and 16 by biopsy). Age, PSA, percent free PSA, PSA density (PSAD), prostate volume (PV), and PI-RADS score were collected. Logistic regression analysis was performed to determine predictors of pathological results. Receiver operating characteristic curves were constructed to analyze the diagnostic value of PI-RADS v2 in PCa. RESULTS: Multivariate analysis indicated that age, PV, percent free PSA, and PI-RADS score were independent predictors of biopsy findings, while only PI-RADS score was an independent predictor of S-PCa (P < 0.05). The areas under the receiver operating characteristic curve for diagnosing PCa with respect to age, PV, percent free PSA, and PI-RADS score were 0.570, 0.430, 0.589 and 0.836, respectively. The area under the curve for diagnosing S-PCa with respect to PI-RADS score was 0.732. A PI-RADS score of 3 was the best cutoff for predicting PCa, and 4 was the best cutoff for predicting S-PCa. Thus, 92.8% of patients with PI-RADS scores of 1-2 would have avoided biopsy, but at the cost of missing 2.2% of the potential PCa cases. Similarly, 83.82% of patients with a PI-RADS score ≤ 3 would have avoided biopsy, but at the cost of missing 3.3% of the potential S-PCa cases. CONCLUSIONS: PI-RADS v2 could be used to reduce unnecessary prostate biopsies in patients with PSA levels of 4-10 ng/ml.


Assuntos
Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico/análise , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Humanos , Biópsia Guiada por Imagem/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Próstata/patologia , Neoplasias da Próstata/patologia , Curva ROC , Estudos Retrospectivos
15.
J Cancer ; 9(6): 959-967, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29581775

RESUMO

Purpose Paxillin regulates cell-cell adhesion, and altered Paxillin expression has been associated with human carcinogenesis. This study analyzed the association between Paxillin expression in prostate cancer (PCa) tissues with clinicopathological features, lymph node metastasis and biochemical PCa recurrence. Methods A total of 386 tissue specimens from PCa patients who received radical prostatectomy and 60 tissue specimens from benign prostatic hyperplasia (BPH) cases were collected to construct tissue microarrays, which were subsequently immunostained for Paxillin expression. Thirty positive lymph node tissue specimens and 10 healthy prostate tissue specimens were randomly selected for Paxillin immunostaining. Results The association between Paxillin expression, lymph node metastasis and biochemical PCa recurrence was analyzed. Paxillin expression was significantly higher in PCa than both normal and BPH tissues (P<0.001) and was correlated with preoperative prostate-specific antigen level, Gleason score, clinical tumor stage, lymph node metastasis, positive surgical margin, extracapsular extension and seminal vesicle invasion (P<0.05 for all). Logistic regression analysis showed that Paxillin and Gleason score were independent risk factors for PCa lymph node metastasis (P<0.05). The receiver operating characteristic (ROC) curve indicated that Paxillin expression (AUC=0.723) more accurately predicted PCa lymph node metastasis than Gleason score (AUC=0.692). Kaplan-Meier curve analysis showed that increased Paxillin expression was associated with shortened biochemical-free survival (BFS) after radical prostatectomy (P<0.001). Conclusion Paxillin was significantly upregulated in PCa compared with BPH and normal tissues and associated with lymph node metastasis and shortened BFS of PCa. Further study will investigate the underlying molecular mechanism and the role of Paxillin in PCa.

16.
Infect Drug Resist ; 11: 1491-1497, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271182

RESUMO

OBJECTIVE: To explore risk factors of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUSPB). METHODS: We retrospectively analyzed 1,203 patients with suspected prostate cancer who underwent TRUSPB at our center between December 2012 and December 2016. Demographics, clinical characteristics, and data regarding complications were collected, and then univariate and multivariate logistic regression analyses were used to identify independent risk factors for infectious complications after prostate biopsy. RESULTS: Multivariate logistic analysis demonstrated that body mass index (BMI) (OR=2.339, 95% CI 2.029-2.697, P<0.001), history of diabetes (OR=2.203, 95% CI 1.090-4.455, P=0.028), and preoperative catheterization (OR=2.303, 95% CI 1.119-4.737, P=0.023) were risk factors for infection after prostate biopsy. The area under the receiver operating characteristics curve for infectious complications was 0.930 (95% CI 0.907-0.953, P<0.001). BMI=28.196 kg/m2 was the best cut-off threshold for predicting infection after TRUSPB. CONCLUSION: BMI >28.196 kg/m2, history of diabetes, and preoperative catheterization are independent risk factors for infection after prostate biopsy.

17.
Biomed Res Int ; 2017: 6923290, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28466017

RESUMO

Background. To investigate the factors associated with the occurrence of and recovery from stress urinary incontinence (SUI) after plasmakinetic enucleation of the prostate (PKEP). Materials and Methods. This retrospective study enrolled 1,288 patients with benign prostatic hyperplasia treated with plasmakinetic enucleation from January 2008 to January 2015, collecting demographics and clinical parameters. SUI was defined as a patient complaint of involuntary urine leak, including stress or mixed urinary incontinence. Logistic regression analysis was used to investigate the factors associated with the occurrence of SUI. Results. SUI after PKEP occurred in 80 of 1,288 patients (6.2%), 73 of whom (91.3%) recovered within 3 months and 78 of whom (97.5%) recovered within 6 months. In multivariate regression analysis of factors that were significant in univariate analysis, the factors that were significantly associated with postoperative SUI were age ≥ 70 years (odds ratio [OR] = 9.239; 95% confidence interval [CI] = 4.616-18.495; P < 0.001) and prostate volume on transrectal ultrasound ≥ 90 mL (OR = 15.390; 95% CI = 8.077-29.326; P < 0.001). Conclusions. SUI occurred in 6.2% patients after PKEP and was associated with older age and larger prostate volume. We suggest that age and prostate volume be considered in preoperative candidate selection before PKEP to reduce the occurrence of postoperative SUI.


Assuntos
Próstata/patologia , Hiperplasia Prostática/patologia , Incontinência Urinária por Estresse/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Estudos Retrospectivos , Ressecção Transuretral da Próstata/métodos , Incontinência Urinária por Estresse/cirurgia
18.
J Cancer ; 8(18): 3725-3732, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29151960

RESUMO

Objective: The purpose of this study was to evaluate the efficacy and feasibility of the R.E.N.A.L. Nephrometry Score to postoperatively predict high-grade clear-cell renal carcinoma (ccRCC). Methods: The study included 288 patients diagnosed with ccRCC who had complete CT/CTA data and R.E.N.A.L. Nephrometry Scores and underwent renal surgery at our center between January 2012 and December 2015. The relationship between the pathological grade of renal masses and R.E.N.A.L. Nephrometry Score was evaluated. Results: Univariate analysis indicated that diagnostic modality, cystic necrosis, enlargement of the regional lymph node, distant metastasis, clinical T stage, TNM stage, surgical modality, tumor size, nearness of the tumor to the collecting system or sinus, total Nephrometry Score and individual anatomic descriptor components were significantly associated with postoperative tumor grade (P < 0.05). Multivariate analysis showed that tumor size, the maximal diameter (R score), exophytic/endophytic properties (E score) and the location relative to the polar lines (L score) were independent prognostic factors to preoperatively predicting ccRCC pathological grade. The areas under the ROC curve with respect to the multi-parameter regression model (0.935, 95%CI: 0.904-0.966), tumor size (0.901, 95%CI: 0.866-0.937), R score (0.868, 95%CI: 0.825-0.911), E score (0.511, 95%CI: 0.442-0.581) and L score (0.842, 95%CI: 0.791-0.892) were calculated and compared. Conclusion: Tumor size, as well as R, E, and L scores were independent prognostic factors for high-grade pathology. Lager tumor sizes and higher R, E and L scores were more likely to be associated with high-grade pathological outcomes. Thus, the R.E.N.A.L. Score is of practical significance in facilitating urologists to make therapeutic decisions.

19.
PLoS One ; 11(3): e0152463, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27019289

RESUMO

OBJECTIVE: To evaluate the efficacy of laparoscopic pyeloplasty relative to retrograde balloon dilatation for the treatment of ureteropelvic junction obstruction (UPJO). METHODS: This retrospective study enrolled UPJO patients with stricture length < 2 cm who had been treated with laparoscopic pyeloplasty (LP; 44 cases) or balloon dilatation (BD; 38 cases) from Jan 2010 to Jan 2012, according to patients' preference after consultation. Demographics and clinical parameters were collected. Patients were followed-up at 3, 6, 12, and 24 months. Ultrasonography, intravenous urography, and diuretic renography were applied to evaluate the remission of hydronephrosis. RESULTS: Both groups were comparable with respect to age, UPJO location, gender, and other baseline parameters. Compared to the LP group, patients receiving BD experienced significantly shorter operative time, analgesia time, hospital stay, and urethral catheter indwelling time, and less cost (P<0.001). Three and 6 months after their respective procedures, the success rates of the LP (97.7%, both) and BD (94.7% and 86.8%) groups were similar, and at 12 and 24 months the long-term success rate of LP (95.5%, both) was better than that of BD (78.9% and 71.0%). CONCLUSIONS: LP showed better long-term success rate than did BD in the management of UPJO with length of stricture < 2 cm. Considering that BD is more minimally invasive, simpler and easier to perform, and costs less, we recommend it for some selective UPJO patients as the first-line therapy.


Assuntos
Angioplastia com Balão , Laparoscopia , Obstrução Ureteral/cirurgia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Rim/fisiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Medicine (Baltimore) ; 95(45): e5372, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27828864

RESUMO

BACKGROUND: The aim of this meta-analysis was to compare the feasibility of en bloc transurethral resection of bladder tumor (ETURBT) versus conventional transurethral resection of bladder tumor (CTURBT). METHODS: Relevant trials were identified in a literature search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Google Scholar using appropriate search terms. All comparative studies reporting participant demographics, tumor characteristics, study characteristics, and outcome data were included. RESULTS: Seven trials with 886 participants were included, 438 underwent ETURBT and 448 underwent CTURBT. There was no significant difference in operation time between 2 groups (P = 0.38). The hospitalization time (HT) and catheterization time (CT) were shorter in ETURBT group (mean difference[MD] -1.22, 95% confidence interval [CI] -1.63 to -0.80, P < 0.01; MD -0.61, 95% CI -1.11 to -0.11, P < 0.01). There was significant difference in 24-month recurrence rate (24-month RR) (odds ratio [OR] 0.66, 95% CI 0.47-0.92, P = 0.02). The rate of complication with respect to bladder perforation (P = 0.004), bladder irritation (P < 0.01), and obturator nerve reflex (P < 0.01) was lower in ETURBT. The postoperative adjuvant intravesical chemotherapy was evaluated by subgroup analysis, and 24-month RR in CTURBT is higher than that in ETURBT in mitomycin intravesical irrigation group (P = 0.02). CONCLUSION: The first meta-analysis indicates that ETURBT might prove to be preferable alternative to CTURBT management of nonmuscle invasive bladder carcinoma. ETURBT is associated with shorter HT and CT, less complication rate, and lower recurrence-free rate. Moreover, it can provide high-qualified specimen for the pathologic diagnosis. Well designed randomized controlled trials are needed to make results comparable.


Assuntos
Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Estudos de Viabilidade , Humanos , Resultado do Tratamento , Uretra
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