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1.
Artigo em Inglês | MEDLINE | ID: mdl-31679810

RESUMO

The anticancer effects of the omega-3 long chain polyunsaturated fatty acids (LCPUFA), EPA and DHA may be due, at least in part, to conversion to their respective endocannabinoid derivatives, eicosapentaenoyl-ethanolamine (EPEA) and docosahexaenoyl-ethanolamine (DHEA). Here, the effects of EPEA and DHEA and their parent compounds, EPA and DHA, on breast cancer (BC) cell function was examined. EPEA and DHEA exhibited greater anti-cancer effects than EPA and DHA in two BC cells (MCF-7 and MDA-MB-231) whilst displaying no effect in non-malignant breast cells (MCF-10a). Both BC lines expressed CB1/2 receptors that were responsible, at least partly, for the observed anti-proliferative effects of the omega-3 endocannabinoids as determined by receptor antagonism studies. Additionally, major signalling mechanisms elicited by these CB ligands included altered phosphorylation of p38-MAPK, JNK, and ERK proteins. Both LCPUFAs and their endocannabinoids attenuated the expression of signal proteins in BC cells, albeit to different extents depending on cell type and lipid effectors. These signal proteins are implicated in apoptosis and attenuation of BC cell migration and invasiveness. Furthermore, only DHA reduced in vitro MDA-MB-231 migration whereas both LCPUFAs and their endocannabinoids significantly inhibited invasiveness. This finding was consistent with reduced integrin ß3 expression observed with all treatments and reduced MMP-1 and VEGF with DHA treatment. Attenuation of cell viability, migration and invasion of malignant cells indicates a potential adjunct nutritional therapeutic use of these LCPUFAs and/or their endocannabinoids in treatment of breast cancer.

2.
J Agric Food Chem ; 67(43): 12037-12043, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31581772

RESUMO

Despite remarkable contribution of green fluorescent protein and its variants for better understanding of various biological functions, its application for anaerobic microorganisms has been limited because molecular oxygen is essential for chromophore formation. To overcome the limitation, we engineered a plant-derived light, oxygen, or voltage (LOV) domain containing flavin mononucleotide for enhanced spectral properties. The resulting LOV variants exhibited improved fluorescence intensity (20 and 70% higher for SH3 and 70% for BR1, respectively) compared to iLOV, an LOV variant isolated in a previous study, and the quantum yields of the LOV variants (0.40 for SH3 and 0.45 for BR1) were also improved relative to that of iLOV (Q = 0.37). In addition to fluorescence intensity, the identified mutations of SH3 enabled an improved thermostability of the protein. The engineered LOV variants with enhanced spectral properties could provide a valuable tool for fluorescent molecular probes under anaerobic conditions.

3.
Regul Toxicol Pharmacol ; 109: 104485, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568817

RESUMO

D-allulose is considered an ideal substitute for sucrose, because it has 70% of the sweetness of sucrose and ultra-low energy. Chemical and biotechnological methods have been developed to produce Dallulose from D-fructose because D-allulose exists in extremely small quantities in nature. In this study, we performed a 90-day repeated oral dose toxicity test on rats using D-allulose produced from Microbacterium foliorum-a non-GMO species isolated from salad ginseng-in dosages of 0, 1250, 2500 and 5000 mg/kg/day. We developed a toxicity determination criterion based on the significant change caused by the administration of the substance to estimate the NOEL, NOAEL, and LOAEL of the substance applied in this study. This test found only minor compound-related changes in both male and female rats in the high dose group and no important compound-related changes. Thus, we determined the NOAEL of Dallulose in both sexes to be 5,000 mg/kg/day. This study's finding of a NOAEL of 5,000 mg/kg/day should ensure that D-allulose produced from Microbacterium foliorum is classified as a safe and ordinary substance.

5.
J Prosthet Dent ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31307800

RESUMO

To simulate the current oral status of patients, including maxillofacial defects, the digital method described uses a method based on multisource data. These include data recorded from scans made with and without wearing an obturator and data obtained by scanning the surgical or interim obturator. This method eliminates the need for preliminary impressions and complex border-molding steps during the process of creating a definitive obturator, thereby greatly simplifying the fabrication process.

6.
J Prosthet Dent ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31307802

RESUMO

During production of an immediate interim implant-supported fixed restoration with interim cylinders, the formation of an access hole in the dentures is critical. Traditional access hole formation involves repeated prosthesis insertion and removal in the oral cavity, primarily through trial and error, to adjust the hole position and size. The presented technique simulates the interim cylinder position based on the healing abutment position, enabling confirmation of the access hole position and ensuring more precise seating of the interim implant-supported fixed restoration.

7.
Drug Deliv ; 26(1): 622-628, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31210056

RESUMO

Intranasal delivery of insulin is an alternative approach to treat diabetes, as it enables higher patient compliance than conventional therapy with subcutaneously injected insulin. However, the use of intranasal delivery of insulin is limited for insulin's hydrophilicity and vulnerability to enzymatic degradation. This limitation makes optimization of formulation intranasal insulin for commercial purpose indispensable. This study evaluated bioavailability (BA) of various formulations of insulin intranasally delivered with protein transduction domain (PTD) derived from translationally controlled tumor protein. The therapeutic efficacy of newly formulated intranasal insulin + PTD was compared in vivo studies with normal and alloxan-induced diabetic rats, to those of free insulin and subcutaneously injected insulin. BA of insulin in two new formulations was, respectively, 60.71% and 45.81% of subcutaneously injected insulin, while the BA of free insulin was only 3.34%. Histological analysis of tissues, lactate dehydrogenase activity in nasal fluid, and biochemical analysis of sera revealed no detectable topical or systemic toxicity in rats and mice. Furthermore, stability analysis of newly formulated insulin + PTD to determine the optimal conditions for storage revealed that when stored at 4 °C, the delivery capacity of insulin was maintained up to 7 d. These results suggest that the new formulations of intranasal insulin are suitable for use in diabetes therapy and are easier to administer.

8.
Medicine (Baltimore) ; 98(22): e15867, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145342

RESUMO

The aim of the study was to introduce our in-house software to measure the muscle and adipose area on axial computed tomography (CT) scans and to compare with various quantification methods.Our institutional review board approved this retrospective study and informed consent was waived. We developed in-house software to identify body composition analysis on CT scan, which semiautomatically operates 3 image processing steps. Abdominal images were obtained using multidetector row CT (MDCT). Two radiologists analyzed the same cross-sectional areas of subcutaneous fat, muscle, and visceral fat using the following techniques: manual measurements, Aquarius, ImageJ, and our newly developed software. We calculated an intraclass correlation coefficient (ICC) for comparison of muscle and fat areas quantified by various measurement methods using a 2-way random model. Interobserver agreement between the radiologists was also evaluated.Agreements in the measurement of subcutaneous fat and muscle areas were excellent among the methods (ICC = 0.962 and 0.897, respectively), and that of the visceral fat area was good (ICC = 0.822). In the subgroup analysis, ICC of the visceral fat area in the female group and in subjects with ascites was slightly lower than the other group (ICC = 0.742 and 0.787, respectively). The correlation coefficients between our software and other methods were relatively high (r = 0.854-0.996). Additionally, ICCs between both observers of our program for quantification of subcutaneous fat, muscle, and visceral fat areas were 0.999, 0.980, and 0.999, respectively.In conclusion, our method showed be reliable in quantifying muscle and adipose tissue using cross-sectional areas of MDCT with high reproducibility.


Assuntos
Gordura Abdominal/diagnóstico por imagem , Músculos Abdominais/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada Multidetectores/métodos , Software , Adulto , Idoso , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estatísticas não Paramétricas , Gordura Subcutânea/diagnóstico por imagem
9.
Abdom Radiol (NY) ; 44(9): 3115-3126, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31134313

RESUMO

PURPOSE: To determine the imaging features that help differentiate hypervascular primary hepatic tumors showing hepatobiliary hypointensity on gadoxetic acid MRI. METHODS: This study comprised 148 patients with pathologically proven hypervascular hepatic tumors who underwent gadoxetic acid MRI. Tumors included 23 atypical focal nodular hyperplasias (FNHs), 11 hepatocellular adenomas (HCAs), 15 neuroendocrine tumors (NETs), 25 intrahepatic cholangiocarcinomas (ICCs), and 74 hepatocellular carcinomas (HCCs). MRIs were analyzed for morphologic features, signal intensity, and enhancement pattern of the tumors to determine the differential features using multivariate logistic regression analysis. We evaluated the diagnostic performance of the MRI features for differentiating the five tumor types upon review by two observers. RESULTS: Multivariate analysis revealed that reverse target sign on hepatobiliary phase in FNHs (p = 0.009), iso or hyperintensity on ADC map in FNHs and HCAs (p = 0.009, < 0.001, respectively), central hypointensity on arterial phase in NETs (p = 0.001), hepatobiliary target sign in ICCs (p = 0.002), the presence of septum and capsule in HCCs (all p < 0.001) were significant independent features of each tumor group over other tumor groups. Diagnostic accuracy for both observers was 98-98.6% for FNHs, 96.6-98% for HCAs, 97.3-98.6% for NETs, 90.5-94.6% for ICCs, and 85.8-93.2% for HCCs. CONCLUSIONS: Ancillary MRI features established in our study can be helpful in the differentiation of hypervascular and hepatobiliary hypointense primary hepatic tumors on gadoxetic acid MRI.

10.
J Microbiol Biotechnol ; 29(5): 704-712, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-30982316

RESUMO

Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <1 µm in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of TNF-α and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of NF-κB in a dose-dependent manner. Oral administration of MHT-LM1004 (4 × 109 or 4 × 1011 cells/kg mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/NF-κB signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.


Assuntos
Temperatura Alta , Lactobacillus plantarum/imunologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Proliferação de Células , Citocinas/sangue , Citocinas/metabolismo , Feminino , Imunidade Inata , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/biossíntese , Células RAW 264.7 , Receptor 2 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Clin Imaging ; 55: 132-139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30818163

RESUMO

BACKGROUND: Accurate differentiation between pancreatic adenocarcinoma and focal pancreatitis is challenging. PURPOSE: To investigate the usefulness of non-contrast MRI by comparing with multidetector row CT (MDCT) and gadoxetic acid-enhanced MRI in the discrimination of pancreatic ductal adenocarcinoma (PDAC) and focal pancreatitis (FP). MATERIALS AND METHODS: This retrospective study included 187 patients (116 with PDACs and 71 with FP) who underwent gadoxetic acid-MRI and MDCT prior to surgical resection or biopsy. The MRI features of PDAC and FP were compared by two radiologists. Then, two observers independently reviewed the three imaging sets: MDCT, non-contrast MRI (T1-, T2-weighted, and diffusion-weighted images), and MRI with and without gadoxetic acid to determine the diagnostic performances of each imaging modality in the discrimination of PDAC and FP. RESULTS: The significant features on non-contrast MRI for diagnosis of PDAC included peritumoral cyst, pancreatic duct cut-off, clear hypointensity on T1WI, and bile duct dilatation (P < 0.05). Presence of peritumoural cyst showed the highest odds ratio for predicting PDAC. Non-contrast MRI was superior to MDCT in differentiating PDAC from FP with regard to accuracy (84.5% vs 95.5% for observer 1; 85.8% vs. 96.0% for observer 2), sensitivity (83.6% vs. 98.3%; 84.5% vs 97.8%), and negative predictive value (76.3% vs. 97.0%; 77.6% vs 96.4%) (P < 0.05). We found similar diagnostic values between the non-contrast MRI and MRI with and without contrast (P > 0.05) for both observers. CONCLUSION: Non-contrast MRI is better than MDCT and comparable to MRI with and without gadoxetic acid in differentiating PDAC from FP.

12.
Abdom Radiol (NY) ; 44(7): 2366-2376, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30847566

RESUMO

PURPOSE: To compare the efficacy of magnetic resonance imaging (MRI) with hepatobiliary agents (HBA-MRI) and MRI with extracellular contrast agents (ECA-MRI) for detection of recurrent hepatocellular carcinoma (HCC) after multiple treatments. METHODS: The institutional review board approved this retrospective study and waived the requirement for informed patient consent. A total of 135 patients with suspected HCC recurrence after 2-5 treatments (surgery, transarterial chemoembolization, and/or radiofrequency ablation) underwent both HBA-MRI and ECA-MRI within a 1 month interval. HBA-MRI and ECA-MRI were analyzed for HCC detection by two observers using a five-point scale. The diagnostic performances according to MRI modality were compared. RESULTS: A total of 136 liver lesions (121 HCCs and 15 benign lesions; median size, 1.9 cm) were identified. ECA-MRI showed greater sensitivity (90.9% vs. 76.9% for observer 1; 91.7% vs. 78.5% for observer 2) and accuracy (91.2% vs. 78.7% for observer 1; 91.9% vs. 80.2% for observer 2) than HBA-MRI for both observers (P = 0.002, 0.003). Fifteen (12.4%) HCCs were correctly diagnosed with ECA-MRI but not with HBA-MRI by both observers. Interobserver agreement was excellent (0.885) for ECA-MRI and substantial (0.749) for HBA-MRI. CONCLUSIONS: For detection of recurrent HCC, ECA-MRI was superior to HBA-MRI in terms of sensitivity and accuracy. Therefore, ECA-MRI could be the preferred imaging modality over HBA-MRI for assessing HCC recurrence following multiple treatments.

13.
Food Chem ; 275: 282-291, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30724198

RESUMO

In the present study, the influence of production systems (net-house and open-field) on volatile profiles of three Texas A&M University (TAMU) and five commercial tomato varieties was investigated. Forty metabolites were determined using headspace solid phase microextraction (HS-SPME) equipped with gas chromatography and mass spectrometry (GC-MS). The data was evaluated by multivariate analyses to discriminate the effects of genotype and production system, and to identify potential biomarker(s). The levels of hexanal, p-cymene, and (E)-2-hexenal from TAMU varieties were distinct from those of commercial tomato varieties. Similarly, 16 metabolites were considerably affected by the production systems, and majority of these volatiles were significantly higher in the net-house-grown tomatoes. Multivariate analysis also allowed identifying geranylacetone and d-limonene as potential biomarkers to classify tomatoes according to production systems. These findings underline the importance of the selection of variety and production system to preserve or improve desirable aroma traits in tomatoes.


Assuntos
Lycopersicon esculentum/química , Compostos Orgânicos Voláteis/análise , Aldeídos/análise , Análise de Alimentos/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Lycopersicon esculentum/crescimento & desenvolvimento , Metabolômica/métodos , Monoterpenos/análise , Análise Multivariada , Odorantes/análise , Microextração em Fase Sólida/métodos , Terpenos/análise
14.
Phytomedicine ; 55: 40-49, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668442

RESUMO

BACKGROUND AND PURPOSE: Glycosylation of phenolic compounds has been reported to increase water-solubility, reduce toxicity, and sometimes give improved or novel pharmacological activities. Present study was aimed to evaluate and compare the beneficial effects of quercetin aglycone (Quer) and its glycosylated derivative, quercetin 3-O-xyloside (Quer-Xyl), against acute pancreatitis (AP). METHODS: The cellular acute pancreatitis model was established by treating the rat pancreatic acinar cells (AR42J) with lipopolysaccharide (10 µg/ml) and cerulein (10-7 M). The cytotoxicity of Quer or Quer-Xyl on AR42J cells was assessed by MTT assay. Calcium and ROS levels were fluorometrically determined. The ER stress levels (PERK, GRP78), expression levels of amylase and lipase, and apoptotic markers (caspase-3 and -9) were measured by RT-PCR, western blotting, or fluorometric assay. RESULTS: While Quer increased the mRNA expressions of AP marker enzymes, amylase and lipase, Quer-Xyl dose-dependently reversed their expressions. Quer-Xyl suppressed intracellular ROS production and both mRNA and protein levels of GRP78 and PERK, which were significantly elevated in cerulein and LPS-treated AR42J cells. Further, RT-PCR and fluorescence assay revealed that Quer-Xyl dose-dependently augmented the mRNA expressions and activities of caspase-3 and -9. CONCLUSION: These results showed that Quer-Xyl, but not Quer, has a significant anti-pancreatitis activity through attenuating intracellular ROS production and ER stress response and enhancing apoptotic cell death, suggesting that it might be useful as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat AP.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glicosídeos/farmacologia , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Quercetina/análogos & derivados , Células Acinares/citologia , Células Acinares/efeitos dos fármacos , Amilases/metabolismo , Animais , Linhagem Celular , Ceruletídeo , Relação Dose-Resposta a Droga , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Lipase/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Pancreatite/induzido quimicamente , Quercetina/farmacologia , Ratos , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
15.
Vasc Endovascular Surg ; 53(3): 212-215, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30618346

RESUMO

OBJECTIVE:: Patients with critical limb ischemia (CLI) and gangrene have a 10% to 38% rate of major amputation at 6 months. The purpose of this study is to report short- and mid-term major and minor amputation rates for patients who underwent tibial and pedal revascularization in addition to quality-of-life (QoL) scores. METHODS:: All patients who presented to a single institution with CLI (defined as rest pain or nonhealing wounds) and underwent antegrade or retrograde tibial access, atherectomy and angioplasty of the tibial circulation, and angioplasty of pedal circulation (antegrade or retrograde) from June 2016 to September 2017 were included. The Stark QoL questionnaire was used at each visit. Patients were scored at 1, 3, and 6 months postprocedure. Amputation rates were recorded. RESULTS:: Forty-two patients with CLI and gangrene underwent 57 peripheral interventions for limb salvage between June 2016 and September 2017. Thirty-two limbs had dry gangrene along the dorsalis pedis angiosome, 14 limbs had dry gangrene along the posterior tibial angiogram, and 11 limbs had a combined disease pattern. Twelve limbs underwent angioplasty of the superficial femoral artery (SFA), 18 limbs underwent angioplasty and stenting of the SFA, and 14 limbs underwent atherectomy, angioplasty, and stenting of the SFA. All patients had 1 or 2 tibial vessel runoff and high-grade stenosis of the pedal circulation. Immediate technical success defined as 3-vessel outflow to the foot occurred in 49 limbs (86%) with zero 30-day complications (30-day readmission, major amputation, or sepsis). Major amputation rate at 1, 3, and 6 months was 0%, 2%, and 4%, respectively. Patient satisfaction in terms of QoL increased over the 6-month follow-up period. CONCLUSION:: Aggressive tibial and pedal revascularization may improve freedom from minor and major amputation at 6 months and may be associated with a short- and mid-term higher QoL.


Assuntos
Amputação , Angioplastia , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Qualidade de Vida , Idoso , Angioplastia/efeitos adversos , Angioplastia/instrumentação , Estado Terminal , Feminino , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Intervalo Livre de Progressão , Fatores de Risco , Stents , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Cicatrização
16.
Clin Imaging ; 54: 63-70, 2019 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30551027

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) is a reliable imaging tool for evaluating gallbladder carcinoma, but it is costly and time-consuming. PURPOSE: To compare noncontrast MRI with multidetector row CT (MDCT) and gadoxetic acid-enhanced whole MRI in distinguishing gallbladder carcinoma from benign disease. MATERIALS AND METHODS: 101 patients (36 with gallbladder carcinoma and 65 with benign disease) with mild focal gallbladder wall thickening were included. Two radiologists reviewed the MDCT and MRI to determine the differential features between malignancy and benignity. Then, the diagnostic performance of MDCT and MRI (T1-, T2- and diffusion-weighted images) with and without gadoxetic acid enhancement in the diagnosis of gallbladder carcinoma was evaluated. RESULTS: The benign group more often showed T2 necklace sign or T2 hyperintensity within the thickened wall (P < 0.0001) and T1 hyperintensity within the wall or gallbladder lumen (P = 0.0002). Meanwhile, malignancy more frequently showed T2 moderate hyperintensity of the thickened wall, papillary appearance, and diffusion restriction (all P < 0.0001). There were significant differences in sensitivity (79.2% vs 98.6% for observer 1; 84.7% vs 100% for observer 2) and specificity (80.7% vs 96.9%; 79.2% vs 95.4%) between the MDCT and noncontrast MRI (P < 0.05). We found similar diagnostic values between the noncontrast MRI and whole MRI (P = 0.479-1.000) for both observers. CONCLUSION: Noncontrast MRI could be a useful alternative to gadoxetic acid-enhanced MRI in the diagnosis of gallbladder carcinoma that presents as mild gallbladder wall thickening on MDCT.


Assuntos
Carcinoma/diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Vesícula Biliar/patologia , Imagem por Ressonância Magnética/métodos , Carcinoma/diagnóstico por imagem , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Feminino , Gadolínio DTPA , Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Radiologistas , Sensibilidade e Especificidade
17.
Abdom Radiol (NY) ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30515535

RESUMO

PURPOSE: To determine the differential features of inflammatory myofibroblastic tumor (IMT) and intrahepatic cholangiocarcinoma (ICC) manifesting as target appearance on gadoxetic acid-enhanced MRI. METHODS: Twenty-seven patients with 36 IMTs (1.2-6.0 cm) and 34 patients with 34 ICCs (1.5-6.0 cm) who underwent gadoxetic acid-enhanced MRI were enrolled in this study. Two reviewers evaluated morphology, signal intensity, and enhancement features of tumors on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and gadoxetic acid-enhanced imaging. RESULTS: As for 32 IMTs with target appearance, IMTs most commonly demonstrated early target appearance characterized by a peripheral hypointense rim on unenhanced T1WI (n = 27, 84.4%), central enhanced area with a hypointense rim on arterial phase (AP) and portal venous phase (PVP) (n = 29, 90.6%), and transitional phase (TP) (n = 28, 87.5%). Meanwhile, most of the ICCs showed homogeneous hypointensity on T1WI (100%), a hyperenhancing rim on AP, late target appearance on TP (n = 32, 94.1%) and HBP (n = 32, 94.1%). Target appearance on DWI appearing as hyperintensity with central hypointense area was seen in 2 IMTs and 32 ICCs. On T2WI, 24 IMTs (n = 24, 75.0%) displayed central iso- and peripheral hyperintensity and 27 ICCs (84.4%) showed layered hyperintensity with either brighter or darker area in center. The remaining six IMTs with no target were observed as cystic appearing nodules (n = 3) or ill-defined hypovascular nodules (n = 2) and fibrotic mass (n = 1). CONCLUSION: IMTs often show early target appearance on unenhanced T1WI, and early dynamic phases of gadoxetic acid-enhanced MRI. Target appearance on later phases, such as TP and HBP, and DWI target appearance were commonly in ICCs, but rare in IMTs.

18.
Int J Biol Macromol ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30521889

RESUMO

Colorectal cancer is the third most diagnosed cancer and a leading cause of cancer death. Dissatisfaction with currently available anti-colorectal cancer drugs caused by unwanted side effects and low efficacy necessitates new therapeutic agents. In the present study, a sulfated glucuronorhamnoxylan polysaccharide (named SPS-CF) purified from a green alga Capsosiphon fulvescens was evaluated for its anti-cancer activity in vitro and in vivo against colorectal cancer. The SPS-CF treatment resulted in a dose-dependent inhibition of the HT-29 human colon cancer cell growth up to 40% at 500 µg/mL. This inhibitory activity was shown to be mediated by upregulation of the cleavage of caspase-8, -9, -3 and poly (ADP-ribose) polymerase (PARP), induction of DNA fragmentation, and disruption of mitochondrial membrane potential (MMP), demonstrating that SPS-CF causes apoptotic death of HT-29 cancer cells though activation of caspase-dependant pathway. Administration of SPS-CF to BALB/c-nude mice bearing HT-29 cell-xenograft tumor also reduced the tumor growth. The results of this study demonstrated that the SPS-CF effectively inhibits the colorectal tumor growth both in vitro and in vivo by induction of apoptotic death of tumor cells, suggesting that it can be a potent ingredient for health-beneficial foods or anti-cancer agents to prevent or ameliorate human colon cancer.

19.
Sci Rep ; 8(1): 13924, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30224681

RESUMO

Despite the development of advanced therapeutic regimens such as molecular targeted therapy and immunotherapy, the 5-year survival of patients with lung cancer is still less than 20%, suggesting the need to develop additional treatment strategies. The molecular chaperone heat shock protein 90 (Hsp90) plays important roles in the maturation of oncogenic proteins and thus has been considered as an anticancer therapeutic target. Here we show the efficacy and biological mechanism of a Hsp90 inhibitor NCT-50, a novobiocin-deguelin analog hybridizing the pharmacophores of these known Hsp90 inhibitors. NCT-50 exhibited significant inhibitory effects on the viability and colony formation of non-small cell lung cancer (NSCLC) cells and those carrying resistance to chemotherapy. In contrast, NCT-50 showed minimal effects on the viability of normal cells. NCT-50 induced apoptosis in NSCLC cells, inhibited the expression and activity of several Hsp90 clients including hypoxia-inducible factor (HIF)-1α, and suppressed pro-angiogenic effects of NSCLC cells. Further biochemical and in silico studies revealed that NCT-50 downregulated Hsp90 function by interacting with the C-terminal ATP-binding pocket of Hsp90, leading to decrease in the interaction with Hsp90 client proteins. These results suggest the potential of NCT-50 as an anticancer Hsp90 inhibitor.

20.
Mar Biotechnol (NY) ; 20(6): 813-828, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30159630

RESUMO

Low molecular weight mannogalactofucans (LMMGFs) prepared by enzymatic degradation of high molecular weight Undaria galactofucan (MF) were evaluated for their anti-cancer effects against human prostate cancer. Correlation NMR and linkage analyses confirmed that LMMGFs consist mainly of α-fucose and ß-galactose units: α-fucose units are 1,3-linked; ß-galactose units are terminal, 1,3- and/or 1,6-linked; both sugars are partially sulphated, fucose at positions O-2 and/or O-4 and galactose at O-3. Mannose residue, as a minor sugar, presents as the 1,4-linked terminal units. LMMGFs more significantly induced cell cycle arrest at the G0/G1 phase and cell death via suppression of the Akt/GSK-3ß/ß-catenin pathway than MF in human PC-3 prostate cancer cells. LMMGFs upregulated mRNA expression of death receptor-5 (DR-5), the ratio of Bax to Bcl-2, the cleavage of caspases and PARP, the depolarisation of mitochondrial membrane potential, and ROS generation. LMMGFs (200-400 mg/kg) effectively reduced both tumour volume and size in a xenografted mouse model. These results demonstrated that LMMGFs attenuate the growth of human prostate cancer cells both in vitro and in vivo, suggesting that LMMGFs can be used as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat androgen-independent human prostate cancer. Graphical Abstract.

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