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1.
Artigo em Inglês | MEDLINE | ID: mdl-31304803

RESUMO

Objective: To examine the clinical characteristics of fluid collections after pancreatic surgery and evaluate the safety and effectiveness of CT-guided percutaneous catheter drainage (CT-PCD). Material and methods: A retrospective, cross-sectional study was carried out. 51 patients enrolled in this study underwent CT-PCD for collections after pancreatic surgery. The clinical and imaging data were collected and analysed. Results: In all 51 cases, CT scans showed that the samples were collected from the upper abdomen in 94.1% (48/51) of the patients. Apparent clinical symptoms before puncture manifested in 88.2% (45/51) of the patients. The average interval between surgery and puncture was 14.3 ± 7.9 days. In 76.4% (39/51) of the patients, the abdominal drainage catheter inserted during surgery was still not removed during CT-PCD. Amylase levels in drainage fluid were more than three times that of serum amylase in 66.7% (24/36) of the patients. The drainage fluid of 37 patients was sent for bacterial cultures; of these, 64.9% (24/37) tested positive. Full recovery after single puncture procedure occurred in 84.3% (43/51) of the patients. The incidence of puncture-related complications was 3.9%. Conclusions: Pancreatic postoperative collections requiring clinical puncture were mostly located in the upper abdomen. CT-PCD is a safe technique with good therapeutic effects in patients with collections.

2.
Abdom Radiol (NY) ; 44(9): 3019-3029, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201432

RESUMO

BACKGROUND: Controversy still exists on the optimal surgical resection for potentially curable gastric cancer (GC). Use of radiologic evaluation and machine learning algorithms might predict extent of lymphadenectomy to limit unnecessary surgical treatment. We purposed to design a machine learning-based clinical decision-support model for predicting extent of lymphadenectomy (D1 vs. D2) in local advanced GC. METHODS: Clinicoradiologic features available from routine clinical assignments in 557 patients with GCs were retrospectively interpreted by an expert panel blinded to all histopathologic information. All patients underwent surgery using standard D2 resection. Decision models were developed with a logistic regression (LR), support vector machine (SVM) and auto-encoder (AE) algorithm in 371 training and tested in 186 test data, respectively. The primary end point was to measure diagnostic performance of decision model and a Japanese gastric cancer treatment guideline version 4th (JPN 4th) criteria for discriminate D1 (pT1 + pN0) versus D2 (≥ pT1 + ≥ pN1) lymphadenectomy. RESULTS: The decision model with AE analysis produced highest area under ROC curve (train: 0.965, 95% confidence interval (CI) 0.948-0.978; test: 0.946, 95% CI 0.925-0.978), followed by SVM (train: 0.925, 95% CI 0.902-0.944; test: 0.942, 95% CI 0.922-0.973) and LR (train: 0.886, 95% CI 0.858-0.910; test: 0.891, 95% CI 0.891-0.952). By this improvement, overtreatment was reduced from 21.7% (121/557) by treat-all pattern, to 15.1% (84/557) by JPN 4th criteria, and to 0.7-0.9% (4-5/557) by the new approach. CONCLUSIONS: The decision model with machine learning analysis demonstrates high accuracy for identifying patients who are candidates for D1 versus D2 resection. Its approximate 14-20% improvements in overtreatment compared to treat-all pattern and JPN 4th criteria potentially increase the number of patients with local advanced GCs who can safely avoid unnecessary lymphadenectomy.

3.
J Hepatol ; 70(6): 1133-1144, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30876945

RESUMO

BACKGROUND & AIMS: Microvascular invasion (MVI) impairs surgical outcomes in patients with hepatocellular carcinoma (HCC). As there is no single highly reliable factor to preoperatively predict MVI, we developed a computational approach integrating large-scale clinical and imaging modalities, especially radiomic features from contrast-enhanced CT, to predict MVI and clinical outcomes in patients with HCC. METHODS: In total, 495 surgically resected patients were retrospectively included. MVI-related radiomic scores (R-scores) were built from 7,260 radiomic features in 6 target volumes. Six R-scores, 15 clinical factors, and 12 radiographic scores were integrated into a predictive model, the radiographic-radiomic (RR) model, with multivariate logistic regression. RESULTS: Radiomics related to tumor size and intratumoral heterogeneity were the top-ranked MVI predicting features. The related R-scores showed significant differences according to MVI status (p <0.001). Regression analysis identified 8 MVI risk factors, including 5 radiographic features and an R-score. The R-score (odds ratio [OR] 2.34) was less important than tumor capsule (OR 5.12), tumor margin (OR4.20), and peritumoral enhancement (OR 3.03). The RR model using these predictors achieved an area under the curve (AUC) of 0.909 in training/validation and 0.889 in the test set. Progression-free survival (PFS) and overall survival (OS) were significantly different between the RR-predicted MVI-absent and MVI-present groups (median PFS: 49.5 vs. 12.9 months; median OS: 76.3 vs. 47.3 months). RR-computed MVI probability, histologic MVI, tumor size, and Edmondson-Steiner grade were independently associated with disease-specific recurrence and mortality. CONCLUSIONS: The computational approach, integrating large-scale clinico-radiologic and radiomic features, demonstrates good performance for predicting MVI and clinical outcomes. However, radiomics with current CT imaging analysis protocols do not provide statistically significant added value to radiographic scores. LAY SUMMARY: The most effective treatment for hepatocellular carcinoma (HCC) is surgical removal of the tumor but often recurrence occurs, partly due to the presence of microvascular invasion (MVI). Lacking a single highly reliable factor able to preoperatively predict MVI, we developed a computational approach to predict MVI and the long-term clinical outcome of patients with HCC. In particular, the added value of radiomics, a newly emerging form of radiography, was comprehensively investigated. This computational method can enhance the communication with the patient about the likely success of the treatment and guide clinical management, with the aim of finding drugs that reduce the risk of recurrence.

4.
Eur Radiol ; 29(7): 3725-3735, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30915561

RESUMO

OBJECTIVES: This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its prognostic value. METHODS: For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients. RESULTS: The radiomics signature comprised eight LN-status-related features and showed significant association with LN metastasis in both cohorts (p < 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both p < 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival. CONCLUSIONS: Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making. KEY POINTS: • The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup. • Prognosis of high-risk patients remains dismal after curative-intent resection. • The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Colangiocarcinoma/secundário , Linfonodos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Colangiocarcinoma/diagnóstico , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
5.
J Am Coll Radiol ; 16(7): 952-960, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30733162

RESUMO

PURPOSE: The aim of this study was to develop and validate a computational clinical decision support system (DSS) on the basis of CT radiomics features for the prediction of lymph node (LN) metastasis in gastric cancer (GC) using machine learning-based analysis. METHODS: Clinicopathologic and CT imaging data were retrospectively collected from 490 patients who were diagnosed with GC between January 2002 and December 2016. Radiomics features were extracted from venous-phase CT images. Relevant features were selected, ranked, and modeled using a support vector machine classifier in 326 training and validation data sets. A model test was performed independently in a test set (n = 164). Finally, a head-to-head comparison of the diagnostic performance of the DSS and that of the conventional staging criterion was performed. RESULTS: Two hundred ninety-seven of the 490 patients examined had histopathologic evidence of LN metastasis, yielding a 60.6% metastatic rate. The area under the curve for predicting LN+ was 0.824 (95% confidence interval, 0.804-0.847) for the DSS in the training and validation data and 0.764 (95% confidence interval, 0.699-0.833) in the test data. The calibration plots showed good concordance between the predicted and observed probability of LN+ using the DSS approach. The DSS was better able to predict LN metastasis than the conventional staging criterion in the training and validation data (accuracy 76.4% versus 63.5%) and in the test data (accuracy 71.3% versus 63.2%) CONCLUSIONS: A DSS based on 13 "worrisome" radiomics features appears to be a promising tool for the preoperative prediction of LN status in patients with GC.

6.
FEBS Lett ; 593(4): 406-413, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30604502

RESUMO

Recent studies have demonstrated that ubiquitin-specific protease 10 (USP10) plays a catalytic role in tumour suppression mainly by deubiquitinating its target proteins to enhance their stabilities. However, we found that USP10 could interact with and regulate the expression of oncogenic factor Musashi-2 (MSI2). We investigated whether USP10 positively regulates the expression of MSI2 by deubiquitination and confirmed the type of polyubiquitin chain that is linked to MSI2. We also explored the role of USP10 in regulating the proliferation of colon cancer through different experiments. This study provides a completely new perspective in understanding the role of USP10 in deubiquitination. In the future, USP10 may serve as a target for colon cancer treatment.

7.
Cell Death Dis ; 9(10): 1009, 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262880

RESUMO

Little is known about the function of Keratin 80 (KRT80), an epithelial keratin, in cancer. This study investigated the role of KRT80 in the prognosis of colorectal carcinoma (CRC) and the underlying mechanisms involved in CRC migration and invasion. We analyzed the expression of KRT80 using The Cancer Genome Atlas and Oncomine databases. Higher expression of KRT80 was found to be significantly associated with multiple pathological parameters, lower disease-free survival, and overall survival in CRC patients. Also, KRT80 was an independent prognostic indicator for CRC. Furthermore, altered KRT80 expression impacted migration and invasion of CRC cells, as well as the expression of epithelial-mesenchymal transition (EMT)-related markers and cell morphology via the AKT pathway. Inhibiting the expression of AKT could reverse these phenomena. Liquid Chromatograph Mass Spectrometer/Mass Spectromete, Co-immunoprecipitation, and laser scanning confocal microscopy techniques showed that KRT80 could interact with protein kinase, DNA-activated, catalytic polypeptide (PRKDC). Suppressing PRKDC could inhibit the expression of AKT and EMT, as well as the migration and invasion of CRC cells. Taken together, these results demonstrated that KRT80 was an independent prognostic biomarker for CRC and promoted CRC migration and invasion by interacting with PRKDC via activation of the AKT pathway.

8.
J Exp Clin Cancer Res ; 37(1): 54, 2018 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-29530061

RESUMO

BACKGROUND: Diabetic patients have a higher risk factor for colorectal cancer (CRC) metastasis. Stearoyl-CoA desaturase 1 (SCD1), the main enzyme responsible for producing monounsaturated fatty acids(MUFA) from saturated fatty acids, is frequently deregulated in both diabetes and CRC. The function and mechanism of SCD1 in metastasis of CRC and its relevance to glucose remains largely unknown. METHODS: SCD1 expression levels were analyzed in human CRC tissues and the Cancer Browser database ( https://genome-cancer.ucsc.edu/ ). CRC cell lines stably transfected with SCD1 shRNAs or vector were established to investigate the role of SCD1 in modulating migration and invasion of CRC cells. A glucose concentration gradient was set to investigate regulation of SCD1 in CRC relevant to diabetic conditions. RESULTS: The clinical data analysis showed high expression of SCD1 in CRC tissues with a negative correlation with the prognosis of CRC. In vitro experiments revealed that SCD1 increased CRC progression through promoting epithelial-mesenchymal transition (EMT). Lipidomic analysis demonstrated that SCD1 increased MUFA levels and MUFA administration could rescue migration and invasion defect of CRC cells induced by SCD1 knockdown. Furthermore, SCD1-mediated progression of CRC was promoted by carbohydrate response-element binding protein (ChREBP) in response to high glucose. Mechanistically, hyperglycemia-SCD1-MUFA induced CRC cell migration and invasion by regulating PTEN. CONCLUSIONS: Our findings show that SCD1 promotes metastasis of CRC cells through MUFA production and suppressing PTEN in response to glucose, which may be a novel mechanism for diabetes-induced CRC metastasis.

9.
J Cancer Res Clin Oncol ; 144(6): 1049-1063, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29560517

RESUMO

PURPOSE: Recent studies have determined that cartilage oligomeric matrix protein (COMP) plays a vital role in carcinogenesis. We sought to clarify the role of COMP in colon cancer. METHODS: We investigated gene expression data from The Cancer Genome Atlas (TCGA) dataset. Tissue microarrays (TMA) containing paired samples from 253 patients with colon cancer were subjected to immunostaining. COMP levels in serum of colon cancer patients and healthy donors were measured with ELISA. We established COMP-knockout cells using the CRISPR/Cas9 system and COMP-overexpressing cells using lentiviral vectors to detect the effects of COMP on colon cancer cells using Cell Counting Kit-8 (CCK8), colony formation, apoptosis detection kit, and tumorigenesis assays in nude mice. RESULTS: The analysis of TCGA dataset and the results of the TMA suggested that COMP expression levels were significantly higher in cancer tissues than in adjacent normal tissues. Moreover, high COMP expression was correlated with the poor outcome of colon cancer patients. COMP levels in the sera of preoperative patients with colon cancer were much higher than those in healthy donors and were significantly reduced after colectomy. Colon cancer cells without COMP were defective with respect to the ability to proliferate, colony formation, the ability to resist 5-Fluorouracil-induced apoptosis and the growth of xenograft tumors in mice. Contrasting results were observed in COMP overexpressed cells. COMP promoted colon cancer cell proliferation partially through the activation of PI3K/ Akt/ mTOR/ p70S6K pathway. CONCLUSIONS: COMP may be a novel prognostic indicator and biomarker and also a potential therapeutic target for colon cancer.


Assuntos
Proteína de Matriz Oligomérica de Cartilagem/biossíntese , Neoplasias do Colo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Idoso , Animais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Células CACO-2 , Proteína de Matriz Oligomérica de Cartilagem/sangue , Proteína de Matriz Oligomérica de Cartilagem/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Neoplasias do Colo/sangue , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Bases de Dados Genéticas , Intervalo Livre de Doença , Feminino , Células HCT116 , Células HEK293 , Células HT29 , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transdução de Sinais , Taxa de Sobrevida , Análise Serial de Tecidos , Transcriptoma , Regulação para Cima
10.
Mol Cancer Ther ; 17(1): 290-296, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29133619

RESUMO

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of digestive tract. In the past, tissue biopsy was the main method for the diagnosis of GISTs. Although, circulating tumor DNA (ctDNA) detection by next-generation sequencing (NGS) may be a feasible and replaceable method for diagnosis of GISTs. We retrospectively analyzed the data for ctDNA and tissue DNA detection from 32 advanced GIST patients. We found that NGS obviously increased the positive rate of ctDNA detection. ctDNA detection identified rare mutations that were not detected in tissue DNA detection. Tumor size and Ki-67 were significant influencing factors of the positive rate of ctDNA detection and concordance between ctDNA and tissue DNA detection. In all patients, the concordance rate between ctDNA and tissue DNA detection was 71.9%, with moderate concordance, but the concordance was strong for patients with tumor size > 10 cm or Ki-67 > 5%. Tumor size, mitotic figure, Ki-67, and ctDNA mutation type were the significant influencing factors of prognosis, but only tumor size and ctDNA mutation type, were the independent prognostic factors for advanced GIST patients. We confirmed that ctDNA detection by NGS is a feasible and promising method for the diagnosis and prognosis of advanced GIST patients. Mol Cancer Ther; 17(1); 290-6. ©2017 AACR.

11.
AJR Am J Roentgenol ; 209(5): 1081-1087, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28834443

RESUMO

OBJECTIVE: The purpose of this study was to investigate whether diffusion kurtosis imaging (DKI) is useful for predicting upgrades in Gleason score (GS) in biopsy-proven prostate cancer with a GS of 6. MATERIALS AND METHODS: A total of 46 patients with biopsy-proven GS 6 prostate cancer, 3-T DWI results, and surgical pathologic results were retrospectively included in the study. DWI data were postprocessed with monoexponential and DK models to quantify the apparent diffusion coefficient (ADC), apparent diffusion for gaussian distribution (Dapp), and apparent kurtosis coefficient (Kapp). The volume of the lesions, prostate-specific antigen (PSA) level, and diffusion variables (ADCmin, Dappmin, Kappmax, ADCmean, Dappmean, and Kappmean) were evaluated. PSA and DKI were combined as a parameter in a logistic regression model. The utility of these parameters in predicting an upgrade in GS was analyzed with ROC regression. RESULTS: The rate of GS upgrade was 50.0% (23/46). The GS upgrade group had significantly lower ADCmin (p = 0.007), ADC mean (p = 0.003), D appmin (p < 0.001), and Dappmean (p = 0.001) values and significantly higher Kappmax (p = 0.003), Kappmean (p = 0.005), and PSA (p = 0.004) values than the group that did not have an upgrade. Among single parameters, Kappmax had the highest ROC AUC value (0.819, p < 0.05), and among all the parameters and models, PSA-Kappmax had the highest AUC (0.868, p < 0.05) and Youden index (0.6522). CONCLUSION: The results showed that DKI may help in prediction of GS upgrade in biopsy-proven GS 6 prostate cancer. The comprehensive consideration of DKI and PSA may be a promising approach to predicting GS upgrade.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Antígeno Prostático Específico , Estudos Retrospectivos
12.
Mol Cancer ; 16(1): 12, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28095858

RESUMO

BACKGROUND: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. METHODS: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGFß pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. RESULTS: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGFß signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/Smad7/TGFß in vitro and in vivo. CONCLUSION: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGFß signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Proteína Smad7/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Transdução de Sinais
13.
Cancer Lett ; 389: 11-22, 2017 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-28043911

RESUMO

We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , MicroRNAs/fisiologia , Proteínas Monoméricas de Ligação ao GTP/fisiologia , Neoplasias Gástricas/etiologia , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Humanos , Invasividade Neoplásica , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
14.
J Magn Reson Imaging ; 45(2): 586-596, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27654116

RESUMO

PURPOSE: To assess a magnetic resonance imaging (MRI)-based nomogram in the prediction of prostate cancer (PCa) biochemical recurrence (BCR) within 3 years after prostatectomy. MATERIALS AND METHODS: Between 2009 and 2013, 205 patients with biopsy-confirmed PCa had MRI before prostatectomy. BCR was defined as a PSA failure (>0.2 ng/ml) after prostatectomy. MR features (cancer location, diameter, apparent diffusion coefficients [ADCs], PI-RADS v2 score, dynamic contrast-enhanced [DCE] type, and MR T-stage) were retrospectively evaluated for predicting 3-year BCR based on partial least square regression analysis. Second, imaging features were added to a popularized D'Amico and CAPRA scheme to determine imaging contribution to published nomograms. Lastly, a multivariable Cox regression analysis was employed to determine the independent risk factors of time to BCR. RESULTS: Three-year BCR rate (median follow-up of 44.9 mo) was 25.4% (52/205). The area under receiver operating characteristic (ROC) curve (Az) for MR nomogram (0.909, 95% confidence interval [CI]: 0.861-0.944) was higher than popularized D'Amico (0.793, 95% CI: 0.731-0.846, P = 0.001) and CAPRA (0.809, 95% CI: 0.748-0.860, P = 0.001). The performance of D'Amico (Az: 0.901, 95% CI: 0.852-0.938, P < 0.001) and CAPRA (Az: 0.894, 95% CI: 0.843-0.932, P = 0.004) was significantly improved by adding MR findings. Tumor ADCs (hazard ratio [HR] = 1.747; P = 0.011), PI-RADS score (HR = 4.123; P = 0.039), pathological Gleason score (HR = 3.701; P = 0.004), and surgical-T3b (HR = 6.341; P < 0.001) were independently associated with time to BCR. CONCLUSION: Multiparametric MRI, when converted into a prognostic nomogram, can predict the clinical outcome in patients with PCa after prostatectomy. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:586-596.


Assuntos
Interpretação Estatística de Dados , Imagem por Ressonância Magnética/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Idoso , China/epidemiologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Incidência , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento
15.
J Magn Reson Imaging ; 45(1): 291-302, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27367527

RESUMO

PURPOSE: To investigate the physiopathological effects of low- and iso-osmolar contrast media (CM) on renal function with physiologic MRI and histologic-gene examination. MATERIALS AND METHODS: Forty-eight rats underwent time-course DWI and DCE-MRI at 3.0 Tesla (T) before and 5-15 min after exposure of CM or saline (Iop.370: 370 mgI/mL iopromide; Iod.320: 320 mgI/mL iodixanol; Iod.270: 270 mgI/mL iodixanol; 4 gI/kg body weight). Intrarenal viscosity was reflected by apparent diffusion coefficient (ADC). Renal physiologies were evaluated by DCE-derived glomerular filtration rate (GFR), renal blood flow (RBF), and renal blood volume (RBV). Potential acute kidney injury (AKI) was determined by histology and the expression of kidney injury molecule 1 (Kim-1). RESULTS: Iop.370 mainly increased ADC in inner-medulla (△ADCIM : 12.3 ± 11.1%; P < 0.001). Iod.320 and Iod.270 mainly decreased ADC in outer-medulla (△ADCIM ; Iod.320: 16.8 ± 7.5%; Iod.270: 18.1 ± 9.5%; P < 0.001) and inner-medulla (△ADCIM ; Iod.320: 28.4 ± 9.3%; Iod.270: 30.3 ± 6.3%; P < 0.001). GFR, RBF and RBV were significantly decreased by Iod.320 (△GFR: 45.5 ± 24.1%; △RBF: 44.6 ± 19.0%; △RBV: 35.2 ± 10.1%; P < 0.001) and Iod.270 (33.2 ± 19.0%; 38.1 ± 15.6%; 30.1 ± 10.1%; P < 0.001), while rarely changed by Iop.370 and saline. Formation of vacuoles and increase in Kim-1 expression was prominently detected in group of Iod.320, while rarely in Iod.270 and Iop.370. CONCLUSION: Iso-osmolar iodixanol, given at high-dose, produced prominent AKI in nonhydrated rats. This renal dysfunction could be assessed noninvasively by physiologic MRI. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:291-302.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Ácidos Tri-Iodobenzoicos/administração & dosagem , Ácidos Tri-Iodobenzoicos/efeitos adversos , Lesão Renal Aguda/patologia , Animais , Meios de Contraste/química , Relação Dose-Resposta a Droga , Imagem por Ressonância Magnética/métodos , Masculino , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Ácidos Tri-Iodobenzoicos/química
16.
Sci Rep ; 6: 37240, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27845412

RESUMO

Adjuvant chemotherapy is considered the standard of care for patients with colorectal cancer after curative resection. Although current guidelines provide clear instructions for chemotherapy for stage II high-risk and stage III colorectal cancer, it is insufficient to individualize therapy. We analyzed the outcomes of 902 patients with colorectal cancer treated with or without chemotherapy in our hospital. We found Chinese survival benefit for chemotherapy was consistent with current guidelines. Moreover, our data added to the evidence that chemotherapy might be used for elderly patients with stage II high-risk colorectal cancer. Pathological markers could predict response to individualize therapy in a convenient, fast and inexpensive way. We compared survivals of patients with stage II high-risk and stage III colorectal cancer with chemotherapy in different pathological markers expression, and furthermore used 458 colon adenocarcinoma samples from The Cancer Genome Atlas to verify our preliminary results. We confirmed TOPIIα, EGFR and P170 may be sufficiently predictive markers to individualize chemotherapy. FOLFOX was the optimal adjuvant chemotherapy for patients with stage II high-risk and stage III colorectal cancer when TOPIIα was positive or EGFR or P170 was negative.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Medicina de Precisão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto
17.
Am J Cancer Res ; 6(8): 1636-49, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27648355

RESUMO

Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.

18.
Oncotarget ; 7(29): 45199-45213, 2016 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-27286257

RESUMO

BACKGROUND: Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. RESULTS: miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. METHODS: Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. CONCLUSIONS: miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.


Assuntos
Neoplasias Colorretais/patologia , MicroRNAs/fisiologia , Proteína Smad4/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Regulação para Baixo , Transição Epitelial-Mesenquimal , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Modelos de Riscos Proporcionais , Proteína Smad4/antagonistas & inibidores
19.
AJR Am J Roentgenol ; 207(2): 330-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27187062

RESUMO

OBJECTIVE: The purpose of this article was to investigate whether a new readout segmentation of long variable echo-trains (RESOLVE)-based diffusional kurtosis imaging (DKI) with reduced b value technique can affect image quality and diagnostic effectiveness in MRI-visible prostate cancer (PCA). SUBJECTS AND METHODS: Prostatic RESOLVE DKI (0-1400 s/mm2) was prospectively performed for 12 volunteers. The optimal protocol was then performed in 108 MRI-visible PCAs to determine whether it can compete against a preferred b-value set (0-2000 s/mm(2)) regarding image quality and diagnostic effectiveness. Images were interpreted by two independent radiologists using the prostate imaging reporting and data system (PI-RADS). Readers' concordance and diagnostic effectiveness were tested with the Fleiss kappa and area under the ROC curve (Az) analyses. RESULTS: A b value of 1400 s/mm(2) generated a larger apparent diffusion coefficient of gaussian distribution (Dapp) (1.35 ± 0.31 vs 1.30 ± 0.30 mm(2)/s; p < 0.001) and apparent kurtosis coefficient (Kapp) (1.11 ± 0.26 vs 1.00 ± 0.21; p < 0.001) in PCA than did a b value of 2000 s/mm(2). Interreader agreement using PI-RADS was relatively low when Dapp and Kapp maps were excluded from image interpretations (κ = 0.39-0.41 vs κ = 0.66-0.68 with Dapp and Kapp maps). Interreader agreement in staging PCA was relatively high (κ > 0.80) and was not influenced by reducing the b value. The power of Dapp and Kapp to differentiate PCA from normal tissue (Az = 0.97-0.98), tissue with a Gleason score less than or equal to 3 + 4 from tissue with a Gleason score greater than 3 + 4 (Az = 0.77-0.82), and PCA stage lower than pT3 from stage pT3 and higher PCA (Az = 0.70-0.75) was not significantly degraded by reducing the b value. CONCLUSION: We found that b values significantly influenced image quality, PI-RADS score, and DKI outputs but did not degrade the diagnostic effectiveness of DKI parameters to detect and classify PCA.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Biópsia , Meios de Contraste , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade
20.
Oncol Rep ; 35(5): 2801-10, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26986234

RESUMO

Several members of the sirtuin family (SIRT1-7), which are a highly conserved family of NAD+-dependent enzymes, play an important role in tumor formation. Recent studies indicate that SIRT4 acts as a tumor suppressor by regulating glutamine metabolism. In the present study, we investigated the expression and activity of SIRT4 in colorectal cancer. Using a tissue microarray of 89 colorectal cancer cases, we found that SIRT4 was significantly downregulated in colorectal cancer tissues compared with that noted in the corresponding normal tissue (P<0.001). Lower SIRT4 levels were associated with worse pathological differentiation (P=0.031) and poorer post-operative overall survival rate (P=0.041). We found that SIRT4 overexpression inhibited the proliferation of colorectal cancer cells in vitro and in vivo. SIRT4 inhibited the glutamine metabolism of colorectal cancer cells and synergistically with glycolysis inhibitors induced cell death. SIRT4 also increased the sensitivity of colorectal cancer cells to chemotherapeutic drug 5-fluorouracil by inhibiting the cell cycle. Together, these results highlight the prognostic value of SIRT4 in colorectal cancer and the potential application of SIRT4 in colorectal cancer treatment.


Assuntos
Neoplasias Colorretais/enzimologia , Proteínas Mitocondriais/metabolismo , Sirtuínas/metabolismo , Idoso , Animais , Antimetabólitos Antineoplásicos/farmacologia , Sobrevivência Celular , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/farmacologia , Expressão Gênica , Glutamina/metabolismo , Células HT29 , Humanos , Concentração Inibidora 50 , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Análise Multivariada , Transplante de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Sirtuínas/genética
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