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1.
Clin Transl Gastroenterol ; 11(11): e00262, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33259161

RESUMO

OBJECTIVES: To establish and verify a simple noninvasive model based on the left gastric vein (LGV) to predict the grade of esophageal varices (EV) and high-risk EV (HEV), to facilitate clinical follow-up and timely treatment. METHODS: We enrolled 320 patients with B-viral cirrhosis. All patients underwent endoscopy, laboratory tests, liver and spleen stiffness (SS), and ultrasonography. HEV were analyzed using the χ test/t test and logistic regression in the univariate and multivariate analyses, respectively. EV grades were analyzed using the variance/rank-sum test and logistic regression. A prediction model was derived from the multivariate predictors. RESULTS: In the training set, multivariate analysis showed that the independent factors of different EV grades were SS, LGV diameter, and platelet count (PLT). We developed the LGV diameter-SS to PLT ratio index (LSPI) and LGV diameter/PLT models without SS. The area under the receiver operating characteristic curve of the LSPI for diagnosis of small EV, medium EV, large EV, and HEV was 0.897, 0.899, 0.853, and 0.954, respectively, and that of the LGV/PLT was 0.882, 0.890, 0.837, and 0.942, respectively. For the diagnosis of HEV, the negative predictive value was 94.07% when LSPI < 19.8 and the positive predictive value was 91.49% when LSPI > 23.0. The negative predictive value was 95.92% when LGV/PLT < 5.15, and the positive predictive value was 86.27% when LGV/PLT > 7.40. The predicted values showed similar accuracy in the validation set. DISCUSSION: Under appropriate conditions, the LSPI was an accurate method to detect the grade of EV and HEV. Alternatively, the LGV/PLT may also be useful in diagnosing the varices when condition limited.

2.
Eur J Radiol ; 124: 108827, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31951892

RESUMO

PURPOSE: The aim of this study was to noninvasively explore pancreatic morphological and mechanical changes in diabetic patients with or without microangiopathy and to investigate the clinical correlations of pancreatic stiffness or size with diabetic microangiopathy. METHODS: A total of 213 type 2 diabetic patients with / without microangiopathy (91/122) were prospectively enrolled. Microangiopathy included diabetic retinopathy, diabetic nephropathy and diabetic peripheral neuropathy. Each subject underwent pancreatic ultrasonography and elastography. The shear wave velocity (SWV) and thickness of the head, body and tail were measured and compared. Receiver operating characteristic (ROC) curves was performed in the diagnosis of microangiopathy. Risk factors of the occurrence of more microvascular complications were explored. RESULTS: The SWV in pancreas increased significantly in patients with microangiopathy (P < 0.01) while the thickness was similar in all patients. The area under ROC curve for the SWV in pancreatic body was greatest (0.747) and the sensitivity, specificity were 73.0, 70.9 %. There was a significant shift towards the occurrence of more microvascular complications for patients with increasing of the SWV in pancreatic body (OR 39.25), long duration of diabetes (OR 1.077), aging (OR 1.039) and elevation of microalbuminuria (OR 1.004). CONCLUSIONS: The SWV in pancreatic body was significantly high in diabetic patients with microangiopathy and was prominently correlated with the number of microvascular complications. The SWV in pancreatic body may be considered as a potential marker for diabetic microangiopathy and its occurrence.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Angiopatias Diabéticas/complicações , Angiopatias Diabéticas/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Pancreatopatias/complicações , Pancreatopatias/diagnóstico por imagem , Adulto , Idoso , China , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/irrigação sanguínea , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Pancreatopatias/patologia , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
3.
PLoS One ; 15(1): e0227358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940395

RESUMO

BACKGROUND: Acoustic radiation force impulse (ARFI) imaging is an ultrasound-based elastography method that has been studied in the staging of hepatic fibrosis, especially in chronic hepatitis. However, the diagnostic accuracy of ARFI in non-viral hepatopathies, such as autoimmune hepatitis and non-alcoholic fatty liver disease, has not been systematically determined. AIM: To systematically assess the diagnostic accuracy of ARFI in non-viral hepatopathies. METHODS: The databases of PubMed, Embase, Cochrane Library and clinicaltrials.gov were systematically searched for candidate studies reporting the diagnostic accuracy of ARFI for hepatic fibrosis. The pooled estimates of the sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios were calculated with the summary receiver operating curve (sROC) performed using STATA software. RESULTS: In detail, a total of 29 diagnostic studies were included for further analysis. The quality of the included studies was relatively high using QUADAS method. The pooled sensitivity and specificity were 0.79 (0.73, 0.83) and 0.81 (0.75, 0.86), with AUROC 0.87 (0.83, 0.89) for the staging of significant fibrosis (F≥2). Meanwhile, for the staging of severe fibrosis (F≥3), the pooled sensitivity and specificity were 0.92 (0.87, 0.95) and 0.85 (0.80, 0.89), with AUROC 0.94 (0.92, 0.96). Furthermore, the pooled sensitivity and specificity were 0.89 (0.79, 0.95) and 0.89 (0.85, 0.92), with AUROC 0.94 (0.92, 0.96) for ARFI in staging cirrhosis (F = 4), which were similar to the data for severe fibrosis. No significant publication bias was present in this study. CONCLUSION: This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in staging non-viral hepatic fibrosis, especially severe fibrosis (F≥3) and cirrhosis (F = 4).


Assuntos
Técnicas de Imagem por Elasticidade , Fibrose/diagnóstico , Cirrose Hepática/diagnóstico , Hepatopatias/diagnóstico , Fibrose/diagnóstico por imagem , Fibrose/patologia , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia
4.
Eur J Radiol ; 118: 58-64, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31439259

RESUMO

PURPOSE: To summarize the published literature on microwave ablation (MWA) for the treatment of benign thyroid nodules and papillary thyroid microcarcinomas, and to evaluate the effectiveness and safety of MWA as a novel treatment strategy. METHODS: Two independent authors carried out the literature search using four databases, including PubMed, Embase, Cochrane, and Web of Science. The meta-analysis included prospective and retrospective data that compared pre-treatment values to post-treatment outcomes. RESULTS: From the 33 original articles, seven studies met the inclusion criteria for this meta-analysis. Of these, five were retrospective studies, two were prospective trials, one was controlled study, and one was a multi-center study. The results showed significant improvements in nodule volume, clinical symptom scores, and beauty scores between the baseline and final follow-up visits. In all of the studies, the most common adverse effects were hematomas, unbearable pain, and transient or permanent voice change in 3.8%, 2.2%, and 4.6% of patients, respectively. None of these incidents resulted in hospitalization or death. CONCLUSIONS: MWA is effective and safe for the treatment of benign thyroid nodules and papillary thyroid microcarcinomas. However, future studies should compare the efficacy of MWA, RFA, and surgical intervention.


Assuntos
Técnicas de Ablação/métodos , Carcinoma Papilar/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/cirurgia , Técnicas de Ablação/efeitos adversos , Bases de Dados Factuais , Hospitalização/estatística & dados numéricos , Humanos , Micro-Ondas/uso terapêutico , Glândula Tireoide/cirurgia , Resultado do Tratamento
5.
Biomed Pharmacother ; 116: 108932, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108351

RESUMO

Circular RNAs (circRNAs), a novel subgroup of non-coding RNAs (ncRNAs), have been reported in human cancers due to their significant regulatory roles. CircRNA Hippocampus Abundant Transcript 1 (circHIAT1) has been studied in clear cell renal cell carcinoma. However, whether it can regulate the tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The expression level of circHIAT1 in HCC samples and cell lines was measured by qRT-PCR analysis. CircHIAT1 was expressed at a significantly low level in cancerous samples. Based on Kaplan-Meier survival analysis, we determined a positive correlation between the downregulation of circHIAT1 and the poor overall survival of HCC patients. Using subcellular fractionation and RNA FISH assay, we identified the predominant cytoplasmic localization of circHIAT1. Both in vitro and in vivo experiments demonstrated the suppressive effect of circHIAT1 on the HCC cell growth. Mechanistically, circHIAT1 acted as the miR-3171 sponge to upregulate PTEN in HCC. Finally, rescue assays demonstrated the role of circHIAT1/miR-3171/PTEN pathway in regulating HCC cell growth. Taken together, this study revealed the novel mechanism of circHIAT1 in HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Circular/metabolismo , Transdução de Sinais , Animais , Sequência de Bases , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Modelos Biológicos , Prognóstico , RNA Circular/genética
6.
Technol Health Care ; 27(4): 407-415, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829623

RESUMO

BACKGROUND: The mechanical stretch injury imposed by the intravascular intervention contributes to neointimal hyperplasia. Lessening of this damage without the compromise of luminal dilation could be an alternative way to alleviate restenosis. OBJECTIVE: We aimed to assess the relationship of lumen diameter and neointimal hyperplasia with inflation pressure using color Doppler ultrasound-guided balloon dilation. METHODS: The anteroposterior diameter of the given aortic segment in rabbits was measured by ultrasonography to ensure the similar original diameter. Then they were assigned into three groups with the inflation force at 1, 5, 10 atmosphere pressure (atm), respectively. Balloon dilation and injury of the given aortic segment were performed. Two weeks later, all rabbits were euthanized for histologic evaluation. RESULTS: After operation, the lumen diameter of each group enlarged significantly (P< 0.05) with a similar rate of change. However, neointimal area, circumference and hepatocyte growth factor (HGF) positive cells in group with 1 atm were significantly less than those of the other two (P< 0.05). Maximal neointima thickness increased significantly with the elevation of the inflation pressure (P< 0.05). CONCLUSIONS: Based on sufficient dilation of the balloon, the balloon inflated with the less pressure caused the similar increase in lumen diameter as the higher pressure but the less neointimal hyperplasia and HGF positive cells.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Estenose Coronária/terapia , Vasos Coronários/patologia , Neointima/patologia , Estresse Mecânico , Angioplastia Coronária com Balão/métodos , Animais , Biópsia por Agulha , Estenose Coronária/diagnóstico por imagem , Modelos Animais de Doenças , Humanos , Hiperplasia/patologia , Imuno-Histoquímica , Coelhos , Distribuição Aleatória , Sensibilidade e Especificidade , Ultrassonografia Doppler em Cores
7.
Endocrine ; 65(1): 121-131, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30830584

RESUMO

OBJECTIVES: (1) To compare the American College of Radiology (ACR) thyroid imaging reporting and data system (TIRADS) and American Thyroid Association (ATA) guidelines for thyroid nodules with regard to diagnostic performance and effectiveness at reducing the number of fine-needle aspiration (FNA) biopsies and to preliminarily discuss the reasons for the differences and (2) to compare the diagnostic performance of the two guidelines in the subgroup of nodules <1 cm in diameter. MATERIALS AND METHODS: In the present study, 1000 thyroid nodules in 894 consecutive patients with final diagnoses were included; these thyroid nodules were investigated via FNA biopsies in our hospital. The ultrasound (US) features of the thyroid nodules were reviewed and stratified according to the categories defined by the ACR TIRADS and ATA guidelines. RESULTS: Compared with the ACR TIRADS guidelines, the ATA guidelines had a higher sensitivity (93.4% (P < 0.001)) and a larger negative predictive value (NPV) (85.3% (P= 0.034)). Compared with the ATA guidelines, the ACR TIRADS guidelines had a higher specificity (66.0% (P < 0.001)), a greater PPV (73.6% (P= 0.001)), and greater accuracy (75.5% (P= 0.017)). Compared with the ATA guidelines, the ACR TIRADS guidelines resulted in significantly fewer unnecessary FNA biopsies (P= 0.007). CONCLUSIONS: This study suggests that both the ACR TIRADS and ATA guidelines have unique strengths with regard to their diagnostic performance. In terms of reducing the number of FNA biopsies, the ACR TIRADS guidelines were superior to the ATA guidelines.


Assuntos
Técnicas de Diagnóstico Endócrino/normas , Guias de Prática Clínica como Assunto , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina/normas , China/epidemiologia , Estudos de Coortes , Diagnóstico Diferencial , Humanos , Guias de Prática Clínica como Assunto/normas , Valor Preditivo dos Testes , Dados Preliminares , Estudos Retrospectivos , Sensibilidade e Especificidade , Sociedades Médicas/normas , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , Carga Tumoral , Ultrassonografia/métodos , Estados Unidos
8.
Endocrine ; 64(1): 109-117, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30771153

RESUMO

PURPOSE: To assess the safety and efficacy of microwave ablation (MWA) for primary papillary thyroid microcarcinoma (PTMC) with a large sample of 185 patients. METHODS: A total of 185 patients underwent MWA for 206 primary PTMC nodules. They received ultrasound follow-up at 1, 3, 6, and 12 months after MWA and every 6 months thereafter. Nodule volumes were calculated at each follow-up and compared with those before MWA. Additionally, the volume reduction rate (VRR) of the nodules was calculated. Patients' thyroid functions were tested before and 1 month after MWA. RESULTS: The mean follow-up time of the 185 patients was 20.7 ± 8.8 months (range 12-36 months). During the follow-up period, the mean volume of the 206 nodules was 100.1 ± 92.9 mm3 (range 3.6-423.9) before MWA, which decreased to 2.2 ± 5.6 mm3 (range 0-20.3 mm3) after MWA (P = 0.000). The mean VRR of the nodules was 98.65 ± 3.60% after MWA (range 83.85-100%). One hundred and seventy four of 206 nodules (84.5%) were fully absorbed. Compared with the preoperative results, no significant variation in thyroid function was observed 1 month after MWA. Thirty-eight patients (20.5%) had different types of complications, ranging from minor to major. Five patients (2.7%) had hoarseness, 11 patients (5.9%) had bleeding, 21 patients (11.4%) had earache or toothache, and one patient had another lesion 1 month after MWA. CONCLUSIONS: This preliminary study suggests that MWA is safe and effective in the treatment of primary PTMC and offers a new alternative for clinical treatment.


Assuntos
Técnicas de Ablação/métodos , Carcinoma Papilar/terapia , Neoplasias da Glândula Tireoide/terapia , Adolescente , Adulto , Idoso , Carcinoma Papilar/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
9.
Int J Biol Sci ; 15(3): 617-627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30745848

RESUMO

Metformin, a common therapeutics for type 2 diabetics, was recently demonstrated to possess antitumor activity in various cancer types. However, its therapy effect in renal cell carcinoma (RCC) still remains controversial. In this study, we found that metformin treatment in RCC cells lead to activation of AMPK, which suppressed the cell proliferation under normal condition, but enhanced cell proliferation under glucose deprivation (GD) condition. Depletion of AMPK by siRNA abolished the proliferation effect of MF under GD condition. Mechanistic investigations revealed that the effect of AMPK on cell proliferation under GD condition is dependent on its nuclear translocation. Moreover, the nuclear AMPK recruits PKM2 and ß-Catenin to form a complex, which promotes the transcription of cell proliferation related genes, including CCND1 and c-Myc. Furthermore, depletion of PKM2 or ß-Catenin abrogated the proliferative effects of metformin under GD condition. And inhibition of PKM2 also re-sensitized the A498 xenograft in response to metformin treatment. Together, our results suggested that combined of AMPK activation and PKM2 depletion or inhibition can achieve better therapeutic effect for RCC patients.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Renais/metabolismo , Proteínas de Membrana/metabolismo , Metformina/farmacologia , Hormônios Tireóideos/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
10.
J Ultrasound Med ; 38(9): 2305-2314, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30609088

RESUMO

OBJECTIVES: To analyze the clinical significance of using hepatic transit time (HTT) to evaluate portal vein pressure in gastroesophageal varices patients. METHODS: For the observation group, we enrolled 50 gastroesophageal varices patients who had received esophagogastric variceal embolization in our hospital between January 2015 and February 2018. Patients without liver disease populated the control group and were recruited during the same time period. All patients underwent contrast-enhanced sonography. In the observation group, free portal pressure (FPP) was detected during esophagogastric variceal embolization with ultrasound guidance. Differences in hepatic artery-hepatic vein transit time (HA-HVTT), portal vein-hepatic vein transit time (PV-HVTT), and parenchyma-hepatic vein transit time (PA-HVTT) were compared between groups. Correlations between HA-HVTT, PV-HVTT, PA-HVTT, and FPP in the observation group were analyzed using the Pearson coefficient and linear regression analysis. RESULTS: HA-HVTT (t = 5.078; P < .001), PV-HVTT (t = 12.163; P < .001), and PA-HVTT (t = 2.649; P = .009) within the observation group were significantly lower than those of the control group. The areas under the curve of HTT were 0.771 (HA-HVTT), 0.951 (PV-HVTT), and 0.652 (PA-HVTT), and the sensitivity and specificity of PV-HVTT at 7.99 seconds were 86.0% and 88.0%, respectively. The HA-HVTT (r = -0.799; P < .001), PV-HVTT (r = -0.554; P < .001), and PA-HVTT (r = -0.735; P < .001) negatively correlated to FPP in the observation group. Linear regression analysis showed y = -0.410x + 7.254 (HA-HVTT and FPP), y = -0.335x + 4.983 (PV-HVTT and FPP), and y = -0.566x + 4.997 (PA-HVTT and FPP) in the observation group. CONCLUSION: Compared with the control patients, the HTT of patients with portal hypertension-esophagogastric varices was significantly shorter, and showed an inverse relationship with FPP.


Assuntos
Varizes Esofágicas e Gástricas/fisiopatologia , Artéria Hepática/fisiopatologia , Veias Hepáticas/fisiopatologia , Pressão na Veia Porta/fisiologia , Ultrassonografia/métodos , Meios de Contraste , Feminino , Artéria Hepática/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Veia Porta , Sensibilidade e Especificidade , Fatores de Tempo
11.
Clin Exp Pharmacol Physiol ; 46(2): 144-152, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353914

RESUMO

YWHAZ (14-3-3ζ) plays crucial roles in regulating proliferation, apoptosis, migration, and invasion of gastric cancer (GC) cells. However, its extensive roles and potential mechanisms in GC cells remain unknown, and need to be researched deeply. In this study, we focus on the role of miR-375/YWHAZ axis in migration, invasion and epithelial-to-mesenchymal transition (EMT) of GC cells. YWHAZ level was assessed by western blot and qPCR assays in GC cells. Scratch and transwell assays were used to determine the migration and invasion of GC cells. The protein levels of correlative molecules were detected by western blot. The regulation of miR-375 on the expression of its target gene YWHAZ was verified by dual-luciferase report system. According to the results, knockdown of YWHAZ inhibited the migration, invasion and EMT of GC cells. Moreover, silencing of YWHAZ restrained the activation of wnt/ß-catenin signalling pathway. YWHAZ was confirmed to be a target gene of miR-375, and its expression was regulated by miR-375 in GC cells. Transfection of miR-375 inhibitor promoted the migration, invasion, EMT and activation of wnt/ß-catenin pathway in GC cells, which was suppressed by inhibition of YWHAZ. Taken together, this study suggests that miR-375/YWHAZ axis may be served as a novel therapeutic target for GC patients.


Assuntos
Proteínas 14-3-3/metabolismo , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Neoplasias Gástricas/patologia , beta Catenina/metabolismo , Proteínas 14-3-3/deficiência , Proteínas 14-3-3/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Invasividade Neoplásica , Via de Sinalização Wnt/genética
12.
Biomater Sci ; 7(1): 196-210, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30422139

RESUMO

Currently, multifunctional nanotechnology is strongly expected to improve the prospect of treatment and diagnosis. In this study, we synthesized epidermal growth factor (EGFR)-targeted phase-changeable polymer nanoparticles (C-HPNs) loaded with two drugs (C225 and 10-HCPT) for specific tumor targeting, synergistic chemotherapy, and ultrasound imaging under low-intensity focused ultrasound (LIFU). Cetuximab (C225), an EGFR-targeted monoclonal antibody, was conjugated on the surface of the nanoparticles, leading to a significantly high binding affinity to EGFR-overexpressing anaplastic thyroid C643 cells both in vitro and in vivo. As expected, an increase of more than 3- to 4-fold in the release rates of 10-HCPT was observed after LIFU irradiation in vitro, demonstrating that LIFU could enhance the release of drugs from the nanoparticles. Combined treatment with C-HPNs and LIFU showed excellent inhibition of cell proliferation in vitro, as well as a remarkable therapeutic effect in vivo. Moreover, the combined treatment simultaneously enhanced ultrasound imaging by LIFU-induced acoustic droplet vaporization (ADV). In conclusion, C225-modified and phase-changeable nanoparticles combined with LIFU exhibited great promise for concurrent targeted ultrasound molecular imaging and effective synergistic antitumor therapy.


Assuntos
Antineoplásicos/uso terapêutico , Cetuximab/uso terapêutico , Preparações de Ação Retardada/química , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Cetuximab/administração & dosagem , Cetuximab/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Receptores ErbB/metabolismo , Humanos , Camundongos Nus , Imagem Óptica/métodos , Transição de Fase , Carcinoma Anaplásico da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Ultrassonografia/métodos
13.
Hum Gene Ther ; 29(7): 816-827, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29382231

RESUMO

Hepatic growth factor (HGF) has been widely used in studies on arterial remodeling after injury, and results turn out to be inconsistent. The changes of endogenous HGF expression after injury also remain controversial. This study clarified the role of exogenous human HGF (hHGF) gene transfer in neointimal hyperplasia and investigated the associated alterations of endogenous HGF and c-Met expressions under endothelial denudation with or without hHGF gene transfer using a balloon-injured rabbit aorta model. Sixty-one rabbits were randomly divided into normal controls, endothelial injury, endothelial injury with hHGF, or the control vector gene transfer groups. On weeks 1, 2, 4, and 8 after injury, neointimal hyperplasia and endothelialization were evaluated by the ratio of neointimal area to medial area (N/M ratio), CD31-positive staining, α-smooth muscle actin, and endothelial nitric oxide synthase expressions using histological analysis, immunohistochemistry staining, or real-time quantitative reverse transcriptase polymerase chain reaction. Endogenous rabbit HGF (rHGF) and c-Met expressions were detected with immunohistochemistry staining and quantitative reverse transcriptase polymerase chain reaction. It was found that expressions of endogeneous rHGF and c-Met in endothelial injury upregulated with peak levels on week 2 or week 4 after injury (p < 0.01). On week 1 after hHGF transfer, neointimal hyperplasia was significantly inhibited (p < 0.001), with decreased α-smooth muscle actin expression (p < 0.05) and improved endothelial cells regeneration and function (p < 0.01). More remarkable overexpression of endogenous rHGF and c-Met mRNAs were detected, and lowered positive staining of rHGF and c-Met was shown in the neointima (p < 0.05). These results demonstrated hHGF gene transfer induced further overexpression of endogenous rHGF and c-Met mRNAs but lowered immunoreactivities of rHGF and c-Met in the neointima, thus leading to significant attenuation of neointimal hyperplasia.


Assuntos
Terapia Genética , Fator de Crescimento de Hepatócito/administração & dosagem , Hiperplasia/terapia , Neointima/terapia , Proteínas Proto-Oncogênicas c-met/genética , Actinas/genética , Animais , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/genética , Vetores Genéticos/administração & dosagem , Fator de Crescimento de Hepatócito/genética , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Neointima/genética , Neointima/patologia , RNA Mensageiro/genética , Coelhos
14.
Mol Med Rep ; 16(4): 5203-5210, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849185

RESUMO

The present study investigated the effects of in vivo gene transfer of human hepatocyte growth factor (hHGF) on neointima formation in rabbit abdominal aortae following ultrasound­guided balloon injury. New Zealand white rabbits were randomly divided into four groups: endothelium injury alone (EI), endothelium injury with control vector transfection (EI­V), endothelium injury with hHGF transfection (EI­HGF), and hHGF transfection alone without endothelium injury (HGF). Endothelial injury was established by scraping the abdominal aortic wall using a balloon catheter under the guidance of a transabdominal ultrasound. hHGF gene transfer was performed 7 days following injury. hHGF mRNA and protein expression levels were determined at 3, 7, 14 and 21 days following transfection. Neointima formation was assessed by histopathological analysis at 14 and 28 days following injury. hHGF mRNA and protein expression levels were detected in the target abdominal aortae in EI­HGF and HGF groups with the greatest levels observed 3 days following transfection, and their levels dropped below detection limits at 21 days following transfection. hHGF was not detectable in the EI and EI­V groups throughout the experiment. The neointimal area and the neointima to media ratio in the EI­HGF group were significantly decreased compared with those in the EI or EI­V group at 14 days following injury. However, no differences were observed at 28 days following injury. The present study demonstrated that in vivo hHGF gene transfer inhibits the early formation of neointima in balloon­injured rabbit abdominal aortae.


Assuntos
Abdome/patologia , Aorta/patologia , Fator de Crescimento de Hepatócito/farmacologia , Neointima/patologia , Ultrassom , Abdome/diagnóstico por imagem , Animais , Aorta/diagnóstico por imagem , Aorta/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Masculino , Neointima/diagnóstico por imagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Transfecção
15.
AJR Am J Roentgenol ; 209(4): 775-780, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28705067

RESUMO

OBJECTIVE: The purposes of this study were to compare pancreatic shear-wave velocity (SWV) in subjects with and those without diabetic microvascular complications and to investigate the feasibility of pancreatic SWV in evaluating diabetic microangiopathy. SUBJECTS AND METHODS: SWV measurements were prospectively performed in 115 patients with diabetes mellitus and 115 healthy persons by use of acoustic radiation force impulse imaging. Patients with diabetes were divided into subgroups with and without microangiopathy. Pancreatic SWV was compared in three groups. Factors associated with increased SWV were studied. RESULTS: Pancreatic SWV increased significantly in the subgroups with diabetes mellitus compared with the control group (p < 0.01). Especially, the SWV in the pancreatic body was significantly higher when microangiopathy was present (p < 0.01). In patients with diabetes, microangiopathy (standardized ß = 0.208, p = 0.022), age (standardized ß = 0.265, p = 0.004), and total cholesterol level (standardized ß = 0.223, p = 0.011) were positively and markedly correlated with high SWV in the pancreatic body. CONCLUSION: The increased SWV in the pancreatic body was significantly related to the presence of microangiopathy. It is feasible to use SWV in the pancreatic body to evaluate diabetic microangiopathy.


Assuntos
Angiopatias Diabéticas/diagnóstico por imagem , Técnicas de Imagem por Elasticidade , Pâncreas/diagnóstico por imagem , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Clin Ultrasound ; 45(2): 116-120, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27492650

RESUMO

Extracranial internal carotid artery aneurysms (EICAA) are rare and can elicit various neurologic symptoms. Here, we present a case of a saccular EICAA compressing its proximal parent internal carotid artery (ICA). Ultrasonography demonstrated the proximal ICA stenosis and the "tardus-parvus" Doppler waveform downstream. The patient underwent aneurysmectomy and graft interposition. The histologic analysis highly supported an atypical fibromuscular dysplasia. Although this patient only showed a neck mass, the reduced ipsilateral cerebral blood supply was a potential cause for neurologic symptoms. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:116-120, 2017.


Assuntos
Aneurisma/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Ultrassonografia Doppler , Adulto , Aneurisma/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/etiologia , Feminino , Humanos
17.
Gastroenterol Res Pract ; 2015: 970940, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25918525

RESUMO

Objectives. The presence of motilin receptor in the GI tract of different animal species has been verified. However, the quantitation of motilin receptor expression in different regions of the GI tract remains unclear. The aim of this study was to investigate the expression of motilin receptor in the GI tract and semiquantitatively compare the expression difference in different GI regions in dogs. Methods. Antrum, duodenum, jejunum, ileum, proximal colon, middle colon, and distal colon were obtained from various parts of the GI tract of six sacrificed dogs. The distribution of motilin receptor was determined by immunohistochemistry. The expression levels of motilin receptor mRNA in different regions were measured by RT-PCR. Results. Motilin receptor was expressed throughout the GI tract in dogs. Multiple comparisons of the mean motilin receptor mRNA expression among various regions were significant (P < 0.05). Motilin receptor mRNA was extensively expressed in duodenum, followed by ileum, jejunum, proximal colon, antrum, middle colon, and distal colon. Immunohistochemistry revealed that motilin receptor immunoreactivity was observed only in the enteric nervous system. Conclusion. Motilin receptor is expressed differentially along the GI tract in dogs. The significantly high expression of motilin receptor mRNA is found in the duodenum.

18.
Am J Physiol Cell Physiol ; 303(8): C815-24, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22895259

RESUMO

To define the stoichiometry and molecular identity of the Cl(-)/HCO(3)(-) exchanger in the apical membrane of pancreatic duct cells, changes in luminal pH and volume were measured simultaneously in interlobular pancreatic ducts isolated from wild-type and Slc26a6-null mice. Transepithelial fluxes of HCO(3)(-) and Cl(-) were measured in the presence of anion gradients favoring rapid exchange of intracellular HCO(3)(-) with luminal Cl(-) in cAMP-stimulated ducts. The flux ratio of Cl(-) absorption/HCO(3)(-) secretion was ∼0.7 in wild-type ducts and ∼1.4 in Slc26a6(-/-) ducts where a different Cl(-)/HCO(3)(-) exchanger, most likely SLC26A3, was found to be active. Interactions between Cl(-)/HCO(3)(-) exchange and cystic fibrosis transmembrane conductance regulator (CFTR) in cAMP-stimulated ducts were examined by measuring the recovery of intracellular pH after alkali-loading by acetate prepulse. Hyperpolarization induced by luminal application of CFTRinh-172 enhanced HCO(3)(-) efflux across the apical membrane via SLC26A6 in wild-type ducts but significantly reduced HCO(3)(-) efflux in Slc26a6(-/-) ducts. In microperfused wild-type ducts, removal of luminal Cl(-), or luminal application of dihydro-4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid to inhibit SLC26A6, caused membrane hyperpolarization, which was abolished in Slc26a6(-/-) ducts. In conclusion, we have demonstrated that deletion of Slc26a6 alters the apparent stoichiometry of apical Cl(-)/HCO(3)(-) exchange in native pancreatic duct. Our results are consistent with SLC26A6 mediating 1:2 Cl(-)/HCO(3)(-) exchange, and the exchanger upregulated in its absence, most probably SLC26A3, mediating 2:1 exchange.


Assuntos
Antiporters/deficiência , Antiporters/genética , Bicarbonatos/farmacocinética , Cloretos/farmacocinética , Fibrose Cística/metabolismo , Ductos Pancreáticos/metabolismo , Animais , Fibrose Cística/genética , Modelos Animais de Doenças , Deleção de Genes , Camundongos , Camundongos Endogâmicos CFTR , Camundongos Knockout , Ductos Pancreáticos/citologia , Transportadores de Sulfato
19.
Pancreas ; 28(3): e80-5, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15084988

RESUMO

OBJECTIVES: Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with chronic pancreatitis in Caucasians. We developed a simple method for measuring finger sweat chloride concentration to test whether CFTR dysfunction underlies chronic pancreatitis in Japan where cystic fibrosis (CF) is rare. METHODS: We studied 25 patients with chronic (21 alcoholic and 4 idiopathic) pancreatitis and 25 healthy volunteers. Sweat chloride concentrations were measured by a finger sweat chloride test. We analyzed DNA for 20 common CFTR mutations in Europeans, 9 CF-causing mutations in Japanese, and 2 polymorphic loci, a poly-T tract and (TG) repeats, at intron 8. RESULTS: Thirteen patients (52%) had sweat chloride levels >60 mmol/L, a level consistent with CF, while only 4 (16%) healthy subjects exceeded this level. The 29 CF mutations and the 5T allele were detected in neither the patients nor controls. The (TG) 12 allele was common in both the patients (58%) and controls (48%). The (TG) 12/12 genotype was common in alcoholic pancreatitis (29%) compared with the (TG) 11/11 (10%). Patients with the (TG) 12/12 genotype had significantly higher sweat chloride concentrations than the controls. CONCLUSION: CFTR dysfunction as evidenced by a finger sweat chloride test is present in about half of Japanese patients with chronic pancreatitis, suggesting that this test may be useful for detecting the high-risk group. A higher proportion of the (TG) 12 allele may be a genetic background for elevated sweat chloride concentrations in Japanese patients.


Assuntos
Cloretos/análise , Pancreatite/diagnóstico , Suor/química , Adulto , Idoso , Doença Crônica , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Dedos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação , Pancreatite/genética , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico , Fatores de Risco
20.
Gastroenterology ; 123(5): 1578-87, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12404232

RESUMO

BACKGROUND & AIMS: Gastric blood flow exhibits cyclical increases in phase with the interdigestive contractions and secretion of the stomach in dogs. The aim of this study is to clarify the regulatory role of motilin in interdigestive gastric blood flow in dogs. METHODS: Blood flow of the left gastric (LGA) and superior mesenteric (SMA) arteries were measured by ultrasound transit-time blood-flow meters in 5 conscious dogs. Motilin was infused intravenously with or without Phe-cyclo[Lys-Tyr(3-tBu)-betaAla-]. trifluoroacetate (GM-109; motilin antagonist), granisetron (5-HT3 antagonist), atropine, hexamethonium (C6), phenoxybenzamine, propranolol, or cimetidine. RESULTS: Motilin (12.5, 25, 50, and 100 pmol x kg(-1) x h(-1)) induced LGA blood-flow responses, consisting of a sustained increase and a rapid phasic change coupled with a contraction, without affecting the blood pressure, heart rate, and SMA blood flow. GM-109 completely abolished the LGA, motility, and secretory responses to motilin (100 pmol x kg(-1) x h(-1)). Atropine abolished motilin-induced gastric contractions, secretion, and phasic changes of LGA blood flow but failed to affect the sustained flow increase. However, atropine partially inhibited the LGA responses to lower doses of motilin. The LGA flow responses to motilin were not inhibited by granisetron, C6, alpha-adrenergic, beta-adrenergic, or H2 blockers. Motilin induced significantly larger gastric vasodilatation than the equivalent doses of VIP. CONCLUSIONS: Motilin has a potent and selective gastric vasodilator effect, which appears to be mediated by both cholinergic and noncholinergic mechanisms. Motilin plays an important role in the regulation of interdigestive gastric blood flow in dogs.


Assuntos
Digestão/fisiologia , Motilina/fisiologia , Estômago/irrigação sanguínea , Antagonistas Adrenérgicos/farmacologia , Animais , Artérias/fisiologia , Antagonistas Colinérgicos/farmacologia , Cães , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Motilidade Gastrointestinal/fisiologia , Granisetron/farmacologia , Artérias Mesentéricas/fisiologia , Peptídeos Cíclicos/farmacologia , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores , Receptores de Neuropeptídeos/antagonistas & inibidores , Receptores de Serotonina/efeitos dos fármacos , Receptores 5-HT3 de Serotonina , Fluxo Sanguíneo Regional/fisiologia , Antagonistas da Serotonina/farmacologia , Peptídeo Intestinal Vasoativo/farmacologia
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