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1.
Artigo em Inglês | MEDLINE | ID: mdl-32297413

RESUMO

A general and atom-economical synthesis of 1,1-diborylalkanes from alkenes and a borane without the need for an additional H2 acceptor is reported for the first time. The key to our success is the use of an earth-abundant zirconium-based catalyst, which allows a balance of self-contradictory reactivities (dehydrogenative boration and hydroboration) to be achieved. Our method avoids using an excess amount of another alkene as an H2 acceptor, which was required in other reported systems. Furthermore, substrates such as simple long-chain aliphatic alkenes that did not react before also underwent 1,1-diboration in our system. Significantly, the unprecedented 1,1-diboration of internal alkenes enabled the preparation of 1,1-diborylalkanes.

3.
Int J Clin Oncol ; 24(3): 296-305, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30334174

RESUMO

OBJECTIVES: To evaluate the survival benefits that lymph node dissection (LND) brought to clinically node-negative upper tract urothelial carcinoma (UTUC) patients. METHODS: Non-metastatic node-negative UTUC patients were identified from the Surveillance, Epidemiology and End Results database. N0 patients were naturally divided as cN0-pNx group (clinically diagnosed as N0 without LND performed) and cNx-pN0 group (pathologically diagnosed as node-negative no matter what clinical node status they have). RESULTS: Of the 2731 patients included, 2240 and 491 cases were cN0-pNx and cNx-pN0, respectively. The overall survival (OS) of cNx-pN0 patients was significantly better than that of cNx-pN0 patients (p = 0.022). After propensity score matching, the survival of cNx-pN0 patients was still significantly better than cN0-pNx group. Besides, multivariate analyses showed cNx-pN0 (received LND) was an independent favorable prognostic factor for OS and CSS compared with cN0-pNx (no LND). Survival advantages of pN0 group were more significant in ≥ T2 patients and patients with tumor size ≤ 5 cm. Even in N0 patients who received adjuvant treatment, LND still brought obvious survival improvement (HRos = 0.565, p = 0.013; HRcss = 0.607, p = 0.046). CONCLUSION: LND could improve survival outcomes in patients with clinically node-negative UTUC, especially for those with muscle-invasive diseases (T2-4 stages) or smaller tumor size (≤ 5 cm). Adjuvant treatment after nephroureterectomy is incapable of replacing the therapeutic role of LND.


Assuntos
Excisão de Linfonodo/métodos , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefroureterectomia , Prognóstico , Pontuação de Propensão , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/patologia , Neoplasias Ureterais/cirurgia , Neoplasias Urológicas/cirurgia , Urotélio/patologia
4.
Oncol Rep ; 40(5): 2445-2454, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30106121

RESUMO

Poor response and chemotherapy resistance to cisplatin (DDP)­based therapy frequently lead to treatment failure in advanced bladder cancer; however the underlying mechanism is extremely complex and unclear. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified human oncoprotein, has been shown to play important regulatory roles in cancer cell survival. The present study aimed to investigate the correlation of CIP2A with sensitivity to DDP in bladder cancer cells. In the present study, knockdown of CIP2A was performed using short hairpin­RNA. IC50 determination was used to estimate the chemosensitivity of cells to DDP. Apoptosis and DNA damage indicators were tested in vitro and in vivo to clarify the role of CIP2A in enhancing DDP sensitivity. We observed that CIP2A knockdown enhanced DDP sensitivity. CIP2A depletion accelerated the process of DNA damage caused by DDP treatment. Furthermore, DDP triggered inhibition of CIP2A by preventing AKT Ser473 phosphorylation. In vivo, CIP2A suppression increased the cytotoxicity of DDP, which resulted in a decrease in the subcutaneous tumor growth in a xenograft mouse model. Our findings revealed that the mechanism underlying the involvement of CIP2A in DDP sensitivity enhancement is that CIP2A mediates DDP­induced cell apoptosis and DNA damage. CIP2A is a potential target to improve the response to DDP­based therapy in bladder cancer patients.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autoantígenos/metabolismo , Cisplatino/farmacocinética , Proteínas de Membrana/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Apoptose/genética , Autoantígenos/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Cisplatino/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Concentração Inibidora 50 , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Morfolinas/farmacologia , Proteínas Oncogênicas/genética , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Serina/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Jpn J Clin Oncol ; 48(10): 942-949, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137442

RESUMO

Objective: To evaluate the prognostic value of lymph node (LN) involvement for patients with chromophobe renal cell carcinoma (chRCC) and ascertain the minimum number of LNs that need to be pathologically examined to reliably diagnose a patient with node negative chRCC. Methods: From 2004 to 2014, non-metastatic chRCC patients receiving radical nephrectomy together with lymphadenectomy were identified from the Surveillance, Epidemiology and End Results (SEER) database. The primary outcome was overall survival (OS). Results: Two hundred and forty-six patients received lymph node dissection during the surgery. Of the patients, 24 (10%) had pathologically confirmed positive LN. Multivariate Cox regression model showed that positive LN was an independent unfavorable predictor for OS (HR = 2.83, 95%CI = 1.14-6.98, P = 0.024). More importantly, LN(-) patients with at least three LNs dissected had significantly better OS compared with when 1-2 LNs were examined (P = 0.048). Multivariate analysis confirmed that in LN(-) patients, the examination of three or more LNs could independently predict better OS compared with patients with only 1-2 LNs dissected (HR≥3LNs = 0.362, 95% CI = 0.135-0.972, P = 0.044). Additionally, the likelihood of finding at least one positive LN was significantly higher on dissection of ≥3 LNs compared with examination of 1-2 LNs (15% vs 5%, P = 0.018). Decision curve analysis found a better clinical validity of the '3 LNs examined'-based classification compared with the traditional LN(-)/LN(+) classification. Conclusion: The proportion of positive LNs in chRCC was far from neglectable and LN metastasis could independently predict unfavorable OS. We recommended a minimum of three LNs should be pathologically examined in order to reliably determine node negative.


Assuntos
Carcinoma de Células Renais/patologia , Linfonodos/patologia , Adulto , Carcinoma de Células Renais/mortalidade , Estudos de Coortes , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
6.
J Cancer ; 9(7): 1152-1164, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29675096

RESUMO

Objectives: To develop reliable nomograms to estimate individualized overall survival (OS) and cancer specific survival (CSS) for patients with primary small cell carcinoma of the bladder (SCCB) and compare the predictive value with the AJCC stages. Patients and Methods: 582 eligible SCCB patients identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training (n=482) and validation (n=100) cohorts. Akaike information criterion was used to select the clinically important variables in multivariate Cox models when establishing nomograms. The performance of nomograms was bootstrapped validated internally and externally using the concordance index (C-index) with 95% confidence interval (95% CI) and calibration curves and was compared with that of the AJCC stages using C-index, Kaplan-Meier curves and decision curve analysis (DCA). Results: Two nomograms shared common indicators including age, tumor size, T stage, lymph node ratio, metastases, chemotherapy, radiation and radical cystectomy, while marriage and gender were only incorporated in the OS nomogram. The C-indices of nomograms for OS and CSS were 0.736 (95%CI 0.711-0.761) and 0.731(95%CI 0.704-0.758), respectively, indicating considerable predictive accuracy. Calibration curves showed consistency between the nomograms and the actual observation. The results remained reproducible when nomograms were applied to the validation cohort. Additionally, comparisons between C-indices, Kaplan-Meier curves and DCA proved that the nomograms obtained obvious superiority over the AJCC stages with wide practical threshold probabilities. Conclusions: We proposed the first two nomograms for individualized prediction of OS and CSS in SCCB patients with satisfactory predictive accuracy, good robustness and wide applicability.

7.
World J Surg Oncol ; 16(1): 61, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29562940

RESUMO

BACKGROUND: Previous researches pointed out that the measurement of urine fibronectin (Fn) could be a potential diagnostic test for bladder cancer (BCa). We conducted this meta-analysis to fully assess the diagnostic value of urine Fn for BCa detection. METHODS: A systematic literature search in PubMed, ISI Web of Science, EMBASE, Cochrane library, and CBM was carried out to identify eligible studies evaluating the urine Fn in diagnosing BCa. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with their 95% confidence intervals (CIs) were calculated, and summary receiver operating characteristic (SROC) curves were established. We applied the STATA 13.0, Meta-Disc 1.4, and RevMan 5.3 software to the meta-analysis. RESULTS: Eight separate studies with 744 bladder cancer patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and DOR were 0.80 (95%CI = 0.77-0.83), 0.79 (95%CI = 0.73-0.84), and 15.18 (95%CI = 10.07-22.87), respectively, and the area under the curve (AUC) of SROC was 0.83 (95%CI = 0.79-0.86). The diagnostic power of a combined method (urine Fn combined with urine cytology) was also evaluated, and its sensitivity and AUC were significantly higher (0.86 (95%CI = 0.82-0.90) and 0.89 (95%CI = 0.86-0.92), respectively). Meta-regression along with subgroup analysis based on various covariates revealed the potential sources of the heterogeneity and the detailed diagnostic value of each subgroup. Sensitivity analysis supported that the result was robust. No threshold effect and publication bias were found in this meta-analysis. CONCLUSIONS: Urine Fn may become a promising non-invasive biomarker for bladder cancer with a relatively satisfactory diagnostic power. And the combination of urine Fn with cytology could be an alternative option for detecting BCa in clinical practice. The potential value of urine Fn still needs to be validated in large, multi-center, and prospective studies.


Assuntos
Biomarcadores Tumorais/urina , Fibronectinas/urina , Neoplasias da Bexiga Urinária/diagnóstico , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/urina
8.
Cancer Manag Res ; 9: 611-626, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29180897

RESUMO

Background: We aimed to evaluate the prognostic value of site-specific metastases in patients with metastatic bladder cancer and analyze the roles that surgeries play in the treatment of this malignancy. Materials and methods: A population-based retrospective study using Surveillance, Epidemiology and End Results dataset was performed and metastatic bladder cancer patients were classified according to the sites of metastases (bone, brain, liver, lung and distant lymph nodes). Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). Results: A total of 1862 patients with metastatic bladder cancer from 2010 to 2014 were identified. Bone, lung and distant lymph nodes were the most common metastatic sites. Patients with bone, brain, liver and lung involvement had worse OS and CSS compared to patients without the corresponding sites of metastases. Multivariate analysis showed that bone, brain, liver and lung metastases were independent prognostic factors for both OS and CSS, while distant node metastasis was not. Moreover, patients with a single metastatic site had more favorable OS (p<0.001) and CSS (p<0.001) than patients with multisite metastases. Among single-site metastatic patients, distant nodes and liver metastases represented the best and the worst prognosis, respectively. Moreover, radical cystectomy was an independent predictor for better OS and CSS, while in patients with liver metastasis and multiple metastatic sites, RC did not bring benefits. Besides, in patients with a single metastatic site, metastasectomy seemed to be associated with favorable OS (p=0.042), especially for patients with age <65 years (p=0.006) and for muscle-invasive bladder cancer patients (p=0.031). Conclusion: Distant metastatic sites have differential impact on survival outcomes in patients with metastatic bladder cancer. Surgeries, including radical cystectomy and metastasectomy, might still lead to survival benefits for highly selected patients.

9.
Org Lett ; 19(12): 3139-3142, 2017 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-28561579

RESUMO

Chemoselective access to either γ-ketoesters with a quaternary all-carbon α-stereogenic center or γ-keto nitriles is described by copper-catalyzed aerobic reaction of styrenes with α-cyanoesters. Formal oxo-enolation or oxo-cyanomethylation of styrenes is achieved via a sequence of addition of enolate (or cyanomethyl) radical to olefin and oxidation of the resulting radical adduct. This method starts from abundant and cheap feedstock under aerobic conditions, without any prefunctionalization or the production of stoichiometric metal salts waste, making it very attractive for practical use.

10.
J Exp Clin Cancer Res ; 36(1): 70, 2017 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-28521777

RESUMO

BACKGROUND: Fibronectin (FN) is associated with tumorigenesis and progression in bladder cancer, however, the underlying mechanisms causing this remain largely unknown. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to play important regulatory roles in cancer proliferation. Here, we investigated whether FN regulates CIP2A expression to promote bladder cancer cell proliferation. METHODS: The correlations of stromal FN with CIP2A and proliferating cell nuclear antigen (PCNA) expression were analyzed in a cohort bladder cancer patients. The roles of FN and CIP2A in regulating bladder cancer cell proliferation were evaluated in cell and animal models. Cycloheximide treatment was used to determine the effects of CIP2A on ß-catenin stabilization. The CIP2A-ß-catenin interaction was confirmed by immunofluorescence staining and co-immunoprcipitation. RESULTS: In this study, we found that stromal FN expression correlated positively with the levels of CIP2A and PCNA in bladder cancer tissues. Meanwhile, in human bladder cancer cell lines (T24 and J82), exogenous FN significantly promoted cell proliferation, however, CIP2A depletion inhibited this process. Furthermore, the interaction between CIP2A and ß-catenin enhanced the stabilization of ß-catenin, which was involved in FN-induced cell proliferation. In vivo, CIP2A depletion repressed FN-accelerated subcutaneous xenograft growth rates. CONCLUSIONS: These data reveal that CIP2A is a crucial mediator of FN-induced bladder cancer cell proliferation via enhancing the stabilization of ß-catenin. Promisingly, FN and CIP2A could serve as potential therapeutic targets for bladder cancer treatment.


Assuntos
Autoantígenos/genética , Autoantígenos/metabolismo , Fibronectinas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , beta Catenina/metabolismo , Animais , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Feminino , Fibronectinas/genética , Expressão Gênica , Xenoenxertos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Estabilidade Proteica , RNA Interferente Pequeno/genética , Neoplasias da Bexiga Urinária/patologia
11.
Lipids Health Dis ; 16(1): 63, 2017 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-28335787

RESUMO

BACKGROUND: Few data exist that correlate lesion-related risk factors such as conventional cardiovascular risks or lipoprotein-associated phospholipase A2 (Lp-PLA2) with tissue types within atherosclerotic plaques in patients with single-vessel and intermediate coronary lesions. METHODS: One hundred and ninety-two patients with single-vessel and intermediate coronary lesions were enrolled in a cross-sectional study and divided into two groups: stable angina pectoris (SAP) and acute coronary syndrome (ACS) groups. Data regarding clinical characteristics and Lp-PLA2 mass were collected. Using iMAP-IVUS, lumen areas were manually traced to determine the minimum lumen area (MLA) at 1-mm intervals in diseased segments. At the minimum lumen lesion, areas of different types of atherosclerotic tissue [i.e., areas of fibrous plaque tissue (FP), fibro-fatty tissue (FF), dense calcium (DC) and necrotic core (NC)], vascular external elastic membrane (EEMCSA) and plaque and media (P&MCSA) were calculated using the built-in iMap algorithm. Plaque burden was computed as P&MCSA divided by EEMCSA. RESULTS: In a univariate analysis, glycosylated hemoglobin A1C (GHbA1C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hypertension, Lp-PLA2 and a history of taking statins predicted the degree of FP and NC area, as well as plaque burden, but were not significant predictors of FF or DC area. In a multivariate analysis, Lp-PLA2 and HbA1c remained independent predictors of plaque burden, FP and NC area. However, the results of the regression analyses were not identical when the SAP and ACS groups were analyzed separately. Lp-PLA2, diabetes and NC area were significant predictors of acute coronary lesions, and the predictive value of Lp-PLA2 was confirmed by the finding of a high area-under-the-curve in a ROC analysis (0.837, 95% CI:0.778-0.895, P = 0.000), as well as by the reasonable sensitivity and specificity of cut-off values. CONCLUSIONS: GHbA1C and Lp-PLA2 were strong independent predictors of plaque burden and FP and NC area at the minimum lumen lesion in patients with single-vessel and intermediate coronary lesions. Furthermore, Lp-PLA2 has a certain predictive value for acute coronary lesions.


Assuntos
Síndrome Coronariana Aguda/sangue , Aterosclerose/sangue , Colesterol/sangue , Doença da Artéria Coronariana/sangue , Diabetes Mellitus/sangue , Placa Aterosclerótica/sangue , Síndrome Coronariana Aguda/patologia , Idoso , Aterosclerose/patologia , Doença da Artéria Coronariana/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Curva ROC , Fatores de Risco
12.
Clin Exp Metastasis ; 34(8): 467-477, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29500709

RESUMO

To evaluate the prognostic roles of organ-specific metastases and analyze the impact of organ-specific metastases on surgical resection of the primary tumor for metastatic upper tract urothelial carcinoma (UTUC) patients. A population-based study using Surveillance, Epidemiology, and End Results database was carried out. Kaplan-Meier analysis were used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic organs on overall survival (OS) and cancer specific survival (CSS). 337 patients from 2010 to 2014 were included. Patients with brain metastasis had significantly worse OS (p = 0.012) and CSS (p = 0.004). Liver metastasis could only independently predict unfavorable OS rather than CSS. Multivariate analysis showed that patients with bone, lung or distant lymph node metastasis was not independent prognostic factor for patients' survival. Surgical resection of the primary tumor was an independent favorable predictor for both OS (p = 0.004) and CSS advantages (p = 0.006). In subgroup analysis, patients with multiple organs of metastasis or distant lymph node involvement could benefit from surgical resection of the primary tumor. However, the presence of liver or lung metastasis could make such surgery become meaningless from the point of survival benefits. Our study showed that brain metastasis independently predicted both unfavorable OS and CSS for metastatic UTUC patients while liver metastasis was only associated with worse OS. More importantly, surgical resection of the primary tumor might still lead to survival benefits for highly selected patients.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Neoplasias Urológicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/cirurgia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/cirurgia , China/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/cirurgia
13.
J Endourol ; 31(9): 893-909, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27305835

RESUMO

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) is increasingly being used for the surgical management of renal masses. The comparison of RAPN with open partial nephrectomy (OPN) has not yet led to a unified conclusion with regard to perioperative outcomes. PURPOSE: To conduct a systematic review and meta-analysis of the literature on the perioperative outcomes of RAPN compared with OPN. METHODS: We searched PubMed and EMBASE through January 31, 2016, to identify randomized controlled trials (RCTs) and observational comparative studies assessing the comparison of the two approaches (RAPN vs OPN). Primary outcomes were intraoperative complication rate and postoperative complication rate (including minor and major). Secondary outcomes were perioperative transfusion rate, positive surgical margin (PSM) rate, operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), length of hospital stay (LOS), and estimated glomerular filtration rate (eGFR) change. RESULTS: A total of 19 cohort studies with at least 3551 patients (RAPN, 1216; OPN, 2335) were included. Compared with OPN, RAPN had the advantages of (a) lower rates of postoperative complication (risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.46, 0.78, p = 0.0002), postoperative minor complication (RR = 0.73, 95% CI = 0.56, 0.96, p = 0.02), and postoperative major complication (RR = 0.50, 95% CI = 0.30, 0.84, p = 0.01); (b) lower need for transfusion (RR = 0.64, 95% CI = 0.41, 0.98, p = 0.04); (c) less EBL (weighted mean difference [WMD] = -98.82, 95% CI = -125.64, -72.01, p < 0.00001); and (d) shorter LOS (WMD = -2.64, 95% CI = -3.27, -2.00, p < 0.00001). Sensitivity analyses excluding studies with obvious selection bias based on tumor complexity confirmed all these advantages. RAPN had longer OT (WMD = 18.56, 95% CI = 2.13, 35.00, p = 0.03) and WIT (WMD = 3.65, 95% CI = 0.75, 6.56, p = 0.01) in the primary analyses. Sensitivity analyses, however, showed no differences between RAPN and OPN regarding OT and WIT. Intraoperative complication rate (RR = 0.61, 95% CI = 0.29, 1.27, p = 0.19), PSM rate (RR = 0.87, 95% CI = 0.56, 1.34, p = 0.52), and short-term eGFR change, including absolute eGFR change (WMD = -1.56, 95% CI = -3.41, 0.28, p = 0.10) and percentage eGFR change (WMD = 0.99, 95% CI = -0.52, 2.50), did not differ between the two approaches. CONCLUSIONS: Compared with OPN, RAPN appears to have lower morbidity and achieves similar short-term functional outcomes. However, evidence is limited regarding the long-term oncologic outcomes even though the PSM rate is similar between the two groups. Well-designed RCTs with large sample sizes and long-term follow-up are needed to confirm and update the findings of our study.


Assuntos
Carcinoma de Células Renais/cirurgia , Taxa de Filtração Glomerular , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Isquemia Quente/estatística & dados numéricos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Margens de Excisão , Duração da Cirurgia , Resultado do Tratamento
14.
Sci Rep ; 6: 35672, 2016 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-27782122

RESUMO

The development and progression of bladder pain syndrome/interstitial cystitis (BPS/IC) is closely related to bladder inflammation. Intercellular adhesion molecule 1 (ICAM-1) is associated with bladder inflammation in BPS/IC. We investigated the effect of specific inhibition of ICAM-1 using an anti-ICAM-1 antibody (AIA) on bladder inflammation in a rat model of severe non-bacterial cystitis (NBC) resembling BPS/IC by evaluating the bladder inflammation grade, mast cell infiltration and related cytokines and receptors. We also compared the effects of AIA with the COX-2 inhibitor celecoxib and the neurokinin-1 receptor (NK1R) inhibitor aprepitant. Our NBC model was established by intraperitoneal injection of cyclophosphamide combined with intravesical protamine/lipopolysaccharide, which resulted in severe bladder inflammation and increased mast cell infiltration, similar to the pathological changes of BPS/IC. Inhibition of ICAM-1 by AIA significantly decreased the bladder inflammation grade and mast cell counts, which was accompanied by a reduction of purinergic receptors (P2X2/P2X3), prostaglandin E2, EP1/EP2 receptors, TNF-α, NK1R, and ICAM-1. Moreover, AIA showed superior effects to those of celecoxib and aprepitant treatment in improving the bladder inflammatory response. Our results suggest that ICAM-1 may play a critical role in bladder inflammation in severe NBC and may be used as a novel therapeutic target in non-bacterial bladder inflammation such as BPS/IC.


Assuntos
Cistite Intersticial/patologia , Cistite Intersticial/terapia , Imunoterapia/métodos , Molécula 1 de Adesão Intercelular/metabolismo , Bexiga Urinária/patologia , Animais , Anticorpos/imunologia , Aprepitanto , Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclofosfamida , Cistite Intersticial/induzido quimicamente , Citocinas/imunologia , Feminino , Molécula 1 de Adesão Intercelular/imunologia , Lipopolissacarídeos , Mastócitos/imunologia , Morfolinas/farmacologia , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Protaminas , Ratos , Ratos Sprague-Dawley
15.
Int J Surg ; 30: 109-15, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27107660

RESUMO

PURPOSE: To compare the perioperative outcomes of the transperitoneal (TP) and retroperitoneal (RP) approaches in robot-assisted partial nephrectomy (RAPN). METHODS: A literature search of MEDLINE, EMBASE, SCOPUS and the Cochrane Library was performed to identify relevant studies up to March 2016. All studies with enough data comparing TP-RAPN with RP-RAPN were included. Outcomes of interest were complication, conversion, operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), and positive surgical margin (PSM). Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model. Publication bias was assessed by funnel plots. RESULTS: Four studies with the total number of 449 patients assessing TP-RAPN (n = 229) versus RP-RAPN (n = 220) were included. There was no significant difference between the two groups in any of demographic variables. There were also no significant differences between TP-RAPN and RP-RAPN groups regarding tumor size, tumor laterality, R.E.N.A.L. nephrometry score, and tumor pathology. There was marginally significant difference between the two groups regarding OT (p = 0.05, WMD: 28.03; 95% CI, 0.41-55.65). No significant differences were found regarding complication, conversion, WIT, EBL, and PSM. No obvious publication bias was observed. CONCLUSIONS: The present meta-analysis suggests that RP-RAPN appears to be equally safe and efficacious in terms of complication, conversion, WIT, EBL and PSM compared with TP-RAPN. In addition, RP-RAPN has marginally significant advantage of shorter OT. Randomized controlled trials and high-quality observational cohort studies with large sample size and long-term follow-up are needed to update our findings.


Assuntos
Neoplasias Renais/cirurgia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Laparoscopia , Cavidade Peritoneal/cirurgia , Espaço Retroperitoneal/cirurgia , Resultado do Tratamento
16.
Oncotarget ; 7(19): 27445-57, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27050274

RESUMO

Urothelial bladder cancer (UBC) is a common genitourinary malignancy. MiR-31, a well-identified miRNA, exhibits diverse properties in different cancers. However, the specific functions and mechanisms of miR-31 in UBC have not been investigated. In this study, tumor samples, especially invasive UBC, showed significantly reduced level of miR-31, as compared with normal urothelium. Prognostic analysis using the EORTC model showed that down-regulation of miR-31 correlated with higher risks of recurrence and progression in noninvasive UBC cases. Remarkably, overexpression of miR-31 mimics in UBC cell lines inhibited cell proliferation, migration and invasion. Integrin α5 (ITGA5), an integrin family member, was subsequently identified as a direct target of miR-31 in UBC cells. When treated with mitomycin-C (MMC), miR-31-expressing UBC cells displayed lower survival and higher apoptotic rates, and deactivated Akt and ERK. These effects arising from miR-31 overexpression were abrogated by ITGA5 restoration. Furthermore, miR-31 markedly inhibited tumor growth and increased the effectiveness of MMC in UBC xenografts. In summary, our data suggest that miR-31 is a prognostic predictor and can serve as a potential therapeutic target of UBC.


Assuntos
Integrina alfa5/genética , MicroRNAs/genética , Mitomicina/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular , Prognóstico , Distribuição Aleatória , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Drug Des Devel Ther ; 10: 1035-45, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27022243

RESUMO

BACKGROUND: It has been demonstrated that chloroquine (CQ) enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP) in the treatment of adrenocortical carcinoma (ACC). In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo. METHODS: The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62) and apoptosis relative protein (Bax and Bcl-2) levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy. RESULTS: The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P<0.05). In vitro concomitant therapy (DDP and CQ) was more effective in restraining SW13 cell proliferation. DDP could promote cell apoptosis and induce autophagy in SW13 cells. Concomitant therapy further promoted cell apoptosis by inhibiting autophagy. In vivo, we found that concomitant therapy was more potent than DDP monotherapy in inhibiting the growth of xenografted tumors and prolonging the survival of tumor-bearing mice. CONCLUSION: The antitumor ability of DDP was related to autophagy activity, and the concomitant therapy (DDP and CQ) could be an optimal strategy for treating ACC.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Cloroquina/farmacologia , Cisplatino/farmacologia , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Animais , Proteína Beclina-1/antagonistas & inibidores , Proteína Beclina-1/biossíntese , Proteína Beclina-1/genética , Sobrevivência Celular/efeitos dos fármacos , Cloroquina/química , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Células Tumorais Cultivadas
18.
Int J Med Robot ; 12(4): 686-693, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26443694

RESUMO

BACKGROUND: There have been only four cases of robot-assisted laparoscopic resection of retroperitoneal paraganglioma (PGL) in the literature. Here we present our experience on robot-assisted laparoscopic resection of large PGL in four patients to further evaluate its safety and efficacy. METHODS: From March 2013 to January 2015, four patients with large PGL underwent robot-assisted laparoscopic resection. The tumors were located on the left side and adjacent to the aorta. Patients' demographics, intraoperative and postoperative data were collected, including intraoperative hemodynamic outcomes. RESULTS: In all cases, the PGLs were successfully removed robotically without conversion to open surgery and no intraoperative or postoperative complication occurred. The operative time ranged from 58-113 min, and estimated blood loss ranged from 50-350 mL. There were no significant intraoperative hemodynamic instabilities. The postoperative hospital stay ranged from 4-6 days. CONCLUSIONS: With the advantages of robotic system, robot-assisted resection of large retroperitoneal PGL is feasible, safe and efficient. The robotic system has the potential to expand surgical treatment modalities for complex PGL. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Laparoscopia/métodos , Paraganglioma/cirurgia , Espaço Retroperitoneal/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , China , Feminino , Hemodinâmica , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Int Urol Nephrol ; 47(7): 1105-15, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25997594

RESUMO

OBJECTIVE: The aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1-Bcl-2 interaction, were investigated. METHODS: Male Sprague-Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson's trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum. RESULTS: Compared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-ß1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration. CONCLUSIONS: Castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1-Bcl-2 interaction.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Disfunção Erétil , Orquiectomia/efeitos adversos , Pênis , Testosterona , Androgênios/metabolismo , Androgênios/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Estimulação Elétrica/métodos , Disfunção Erétil/etiologia , Disfunção Erétil/metabolismo , Disfunção Erétil/patologia , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Óxido Nítrico Sintase/metabolismo , Pênis/patologia , Pênis/fisiopatologia , Ratos , Ratos Sprague-Dawley , Testosterona/metabolismo , Testosterona/farmacologia
20.
Int Urol Nephrol ; 47(7): 1135-41, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26009259

RESUMO

OBJECTIVE: To evaluate the impact of body mass on recurrence and progression in patients with Ta, T1 urothelial bladder cancer. METHODS: Data from 469 patients with Ta, T1 bladder cancer who were treated with transurethral resection of bladder tumor at our center during 2006-2014 were retrospectively studied. According to body mass index (BMI), patients were divided into three groups: normal weight (BMI < 24 kg/m(2)), overweight (24 kg/m(2) ≤ BMI < 28 kg/m(2)) and obesity (BMI ≥ 28 kg/m(2)). Clinicopathologic features were compared across groups. Kaplan-Meier curves and Cox proportional hazards regression analyses were employed to assess the association between body mass and oncologic outcomes. RESULTS: Compared with patients with normal weight, overweight and obese counterparts showed significantly shorter recurrence-free or progression-free survival. In multivariate analyses, being overweight was an independent factor for recurrence and obesity was for both recurrence and progression. The presence of diabetes mellitus (DM) was not a strong risk factor for the entire cohort, while it became a significant predictor for both recurrence and progression in the subgroup of overweight and obese patients. CONCLUSION: Excessive body mass seems to act as independent risk factors for worse oncologic outcomes of Ta, T1 bladder cancer. Further studies should be carried out to elucidate the exact impact of obesity, DM or even other metabolic disorders.


Assuntos
Grupo com Ancestrais do Continente Asiático , Carcinoma de Células de Transição , Cistectomia , Recidiva Local de Neoplasia/patologia , Obesidade , Neoplasias da Bexiga Urinária , Idoso , Índice de Massa Corporal , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , China/epidemiologia , Cistectomia/métodos , Cistectomia/estatística & dados numéricos , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/diagnóstico , Obesidade/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
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