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1.
J Rheumatol ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941803

RESUMO

OBJECTIVE: Bidirectional relationships between some autoimmune diseases and non- Hodgkin's lymphoma (NHL) may exist. We conducted this nationwide populationbased study in Taiwan to investigate whether there is a bidirectional relationship between primary Sjögren's syndrome (pSS) and non-Hodgkin's lymphoma (NHL). METHODS: Using the National Health Insurance Research Database of Taiwan, we identified 15,636 patients with new-onset pSS without previous cancer and 25,074 patients with new-onset NHL without previous pSS as two non-overlapping cohorts from 1998-2012, and followed them until 2013. Standardized incidence ratio (SIR) for NHL in the patients with pSS and SIR for pSS in the patients with NHL were compared with the general population. RESULTS: Among the 15,636 patients with pSS, 741 developed cancers, including 51 with NHL. The highest SIR of specific cancer risk in patients with pSS was that for NHL (SIR 4.6, 95% CI 3.4-6.0). Among the 25,074 patients with NHL, 49 developed pSS; the SIR was also increased (SIR 3.2, 95% CI 2.4-4.2). The risk was highest within one year after the diagnosis of each disease. CONCLUSION: This nationwide population-based study is the first study to report a bidirectional relationship between pSS and NHL. Our findings may suggest being alert for the patients with pSS or NHL who have early signs of the other disease in the clinical care. The underlying mechanisms of the bidirectional relationship merit further investigation.

2.
Genes Chromosomes Cancer ; 59(2): 73-83, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31408253

RESUMO

Hypoxia-induced epithelial-mesenchymal transition (EMT) involves the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5. The histone mark histone 3 lysine 4 acetylation (H3K4Ac) is observed in the promoter regions of various EMT marker genes (eg, CDH1 and VIM). To further define the genome-wide location of H3K4Ac, a chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) analysis was performed using a head and neck squamous cell carcinoma (HNSCC) FaDu cell line under normoxia and hypoxia. H3K4Ac was found to be located mainly around the transcription start site. Coupled with analysis of gene expression by RNA sequencing and using a HDAC3 knockdown cell line, 10 new genes (BMI1, GLI1, SMO, FOXF1, SIRT2, etc) that were labeled by H3K4Ac and regulated by HDAC3 were identified. Overexpression or knockdown of GLI1/SMO increased or repressed the in vitro migration and invasion activity in OECM-1/FaDu cells, respectively. In HNSCC patients, coexpression of GLI1 and SMO in primary tumors correlated with metastasis. Our results identify new EMT marker genes that may play a significant role in hypoxia-induced EMT and metastasis and further provide diagnostic and prognostic implications.

3.
Huan Jing Ke Xue ; 41(1): 166-172, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854917

RESUMO

We use 84 rainfall samples collected during June to September 2017 from the Dongkemadi basin, source region of the Yangtze River, China, to analyze the characteristics and influencing factors of stable isotopes in groundwater, and further discuss the groundwater recharge sources. The results showed that the range of groundwater δ18 O values in this permafrost region varied from -15.3‰ to -12.5‰ (mean -14.0‰). The range of δD values in groundwater varied from -108.9‰ to -91.7‰ (mean -100.2‰). Compared with local atmospheric precipitation, groundwater isotopes were relatively enriched. The slope and intercept of the groundwater line (GL) in the study area were both lower than of those of the global and local meteoric water lines (GMWL and LMWL), thus indicating that groundwater in the study area was subjected to evaporation during rainfall recharge of groundwater. The d-excess values of groundwater varied from 4.9‰ to 25.0‰ (mean 11.6‰), which was close to the average d-excess value determined for global average rainfall (10‰), but lower than that of rainfall in the study area (15.1‰). The influencing factors on the composition and variation of groundwater isotopes were different in different periods. The permafrost active layer was relatively thin during periods of increasing air temperature, and groundwater isotopes were significantly affected by air temperature. A temperature decrease during the latter part of the sampling period, when the thickness of the permafrost active layer was still increasing, further increased the retention time of infiltrating rainfall in the soil, thereby eventually leading to evaporation that strengthened the enrichment of heavy isotopes in the groundwater. According to the topographic characteristics of the Dongkemadi basin, the isotopic characteristics of the groundwater, and the factors influencing the isotopic composition, we conclude that rainfall was the main source of groundwater recharge. The results of this study provide a scientific basis for studying water cycle processes in the permafrost regions of the source region of the Yangtze River.

4.
Huan Jing Ke Xue ; 40(6): 2615-2623, 2019 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854652

RESUMO

Based on the stable isotopes of 73 precipitation samples continuously collected from May to October 2014 and related meteorological statistics in the Dongkemaldi Basin, the characteristics of δD, δ18O, and d-excess of precipitation, as well as the correlations between δ18O and the rainfall amount and air temperature were analyzed. The moisture sources were tracked by the HYSPLIT model to further estimate the contribution of different water vapor sources to the rainfall amount. The results showed that the range of δ18O and δD values varied from -26.5‰ to 1.9‰ and -195.2‰ to 34.0‰, respectively; meanwhile, the δ18O and δD values in precipitation fluctuated greatly with time in response to water vapor transport from different moisture sources of the Qinghai-Tibet Plateau. The slope and intercept of the Local Meteoric Water Line (LMWL) were both higher than those of the Global Meteoric Water Line (GMWL) and close to the LMWL in the northern area of the Qinghai-Tibet Plateau. The relationship between δ18O and δD in different precipitation types showed significant differences, which were mainly related to the source of water vapor and meteorological conditions during the process of precipitation formation. Because of the influence of local evaporation and the transport process of water vapor, the d-excess values of atmospheric precipitation were relatively large; the δ18O in precipitation had a significant amount effect, but had no temperature effect, thus indicating that the rainfall amount was more effective in controlling the stable isotope content of atmospheric precipitation than temperature. The modeled trajectory of vapor sources showed that water vapor of precipitation was mainly derived from the marine vapor carried by the southwest monsoon, local moisture, and the westerly water vapor, and their contributions to the rainfall amount were 43%, 36%, and 21%, respectively. The results of this study can contribute to further understanding of the atmospheric circulation characteristics and water cycle process of the Dongkemadi basin in the headwaters of the Yangtze River.

5.
Huan Jing Ke Xue ; 40(10): 4431-4439, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854810

RESUMO

Using 64 precipitation samples collected from June to September 2013 in the Dongkemadi Basin in the source region of the Yangtze River, the pH, conductivity, and main ionic concentration characteristics of precipitation were analyzed. The main ionic sources of precipitation and their relationships with atmospheric circulation were examined using factor analysis, correlation analysis, enrichment factor analysis, and backward trajectory analysis. The results showed that the range of precipitation pH values varied from 5.26 to 9.25 with a weighted average of 6.70, and conductivity ranged from 0.23 to 28.70 µS·cm-1 with a weighted average of 3.45 µS·cm-1. The conductivity of precipitation was lower than for the Mt. Waliguan basin (China Global Atmosphere Watch baseline observatory). The total ionic concentrations in the precipitation ranged from 7.0 to 376.9 µeq·L-1 with a weighted average of 40.8 µeq·L-1. The ranked order of ionic concentrations was HCO3- > NH4+ > Ca2+ > NO3- > SO42- > Na+ > Cl- > K+ > Mg2+. HCO3-, NH4+,Ca2+, and NO3- were the dominant ions, which accounted for 74.75% of the total ionic concentration. Fractional acidity (FA) analysis showed that 97.8% of the precipitation acidity was neutralized by alkaline constituents. Neutral factor (NF) analysis indicated that NH4+ and Ca2+ were the dominant neutralization constituents in the precipitation. The precipitation ions in this study area were mainly derived from terrestrial material, while input from marine sources was relatively low. Backward trajectory analysis revealed that the total ionic concentrations varied significantly between the different sources, which followed the order of local sources>westerly sources>monsoon sources. This indicates that different atmospheric circulation conditions and air mass sources have a significant influence on the chemical composition of precipitation in this area. To some extent, the chemical characteristics of precipitation could reflect the air quality and background values for remote areas due to the limited effect of human activities. The results of this study provide a scientific basis for the protection of water quality and the assessment of the impact of human activities on the atmospheric environment in the source region of the Yangtze River.

6.
J Nanosci Nanotechnol ; 19(12): 7943-7946, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196313

RESUMO

A facile synthesis approach of urchin-like and bouquet-like silver nanoparticles (AgNPs) using gas assisted wet chemistry method with silver nitride as source materials, ascorbic acid as reducing agent, polyvinylpyrrolidone (PVP) as passivator and NO2/O2 as ventilation mixture is proposed It was demonstrated that the urchin-like and bouquet-like AgNPs evolved from spherical nanoparti cles and/or clusters of Ag as a result of strong adsorption and passivation of newly-formed Ag {100} facets by PVP, which effectively boost preferential growth. The NO2/O2 as the ventilation mixture provides an equilibrium of aggregation and detachment of Ag atoms on the surface, thus confining the shapes of AgNPs generated. This study provides an alternative approach for synthesis AgNPs in specific shapes and facilitates their applications.

7.
Acta Biomater ; 92: 205-218, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31071475

RESUMO

This study aimed to evaluate the performance of cisplatin-loaded polymeric micelles (CDDP-PMs) with different drug/copolymer ratios of 1:1, 1:3 and 1:6 (w/w) prepared by coordinated complexation and self-assembly method. The mass ratio influenced the self-assembly behaviors and the complex degree, where both single- and double- complexation existed in CDDP-PMs. With the increase of CDDP/copolymer ratio, the particle size and drug loading increased, while encapsulation efficiency decreased. The PEG density of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 were 0.20, 0.61 and 0.38 PEG/nm2, respectively. CDDP-PM1-3 and CDDP-PM1-6 had similar sustained release behavior, while CDDP-PM1-1 showed burst release. Pharmacokinetics showed the AUC of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 was 27.2, 76.6 and 13.0 fold higher than CDDP solution. Tissue distribution presented the platinum concentration of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 was 1.03, 0.80 and 0.48 times of CDDP solution in kidney at 10 min, and 17.61, 28.63 and 16.6 times in tumor at 48 h respectively, indicating CDDP-PMs significantly reduced nephrotoxicity and increased tumor-targeting accumulation. In vivo antitumor test showed that CDDP-PMs exhibited an improved antitumor efficacy and lower systemic toxicity compared with CDDP solution. From CDDP-PM1-1 to CDDP-PM1-6, the toxicity decreased with the increase of copolymer ratio, but the tumor inhibition rate also decreased. CDDP-PM1-3 had relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM1-3 could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot. This work provides an effective strategy by modulating drug/copolymer ratio of CDDP-PMs to balance the antitumor efficacy and toxicity for better payoff. STATEMENT OF SIGNIFICANCE: Cancer chemotherapy always exists a contradiction between antitumor efficacy and toxicity. Higher efficacy against tumor often associated with larger toxicity for normal tissues. This work provides an important strategy by modulating the drug/copolymer ratios to balance the antitumor efficacy and toxicity to obtain better payoff. The cisplatin-loaded polymeric micelles (CDDP-PMs) based on the complexation between CDDP and copolymer with different mass ratios make differences in vitro and in vivo because of the single- or double-complexation degree. Most importantly, we found the balance at CDDP/copolymer ratio of 1:3, which has relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM1-3 could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot.

8.
Rheumatology (Oxford) ; 58(7): 1245-1249, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30726952

RESUMO

OBJECTIVES: We conducted this nationwide population-based study in Taiwan to investigate whether there is a bidirectional relationship between SLE and non-Hodgkin's lymphoma (NHL). METHODS: Using the National Health Insurance Research Database of Taiwan, we identified 16 417 patients with new-onset SLE without previous cancer and 25 069 patients with new-onset NHL without previous SLE as two non-overlapping cohorts from 1998-2012, and followed them until 2013. Standardized incidence ratio (SIR) for NHL in the patients with SLE and SIR for SLE in the patients with NHL were compared with the general population. RESULTS: Among the 16 417 patients with SLE, 512 developed cancers, including 34 with NHL. The highest SIR was that for NHL (SIR 4.2, 95% CI 2.9, 5.9) in site-specific cancer risk analysis. Among the 25 069 patients with NHL, 14 developed SLE, and the SIR was also increased (SIR 2.0, 95% CI 1.1, 3.4). The SIRs of the patients with SLE to develop NHL and the patients with NHL to develop SLE were both highest within the first year after the diagnosis of each disease. CONCLUSION: This nationwide population-based study is the first study to report a bidirectional relationship between SLE and NHL. This finding may suggest being alert for the patients with SLE or NHL who have early sings of the other disease in clinical care.

9.
J Gastroenterol Hepatol ; 34(9): 1563-1570, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30597598

RESUMO

BACKGROUND AND AIM: Salivary characteristics are altered in gastrointestinal diseases and related to oral taste disorder. However, specific salivary biochemical characteristics and their relationships with oral taste disturbances in chronic non-atrophy gastritis (CNAG) remain uncertain. METHODS: Seventy patients with CNAG and 70 subjects in healthy control group (HCG) were enrolled in our study. The levels of salivary flow rate (SFR), pH, salivary α-amylase (sAA) activity, total protein density (TPD), chloride concentration, and calcium concentration were determined before and after citric acid stimulation and compared between CNAG with and without oral taste disturbances. RESULTS: Average body mass index (BMI) of CNAG (17.75 ± 2.08) was lower than that of HCG (21.96 ± 1.72, P < 0.01). Compared with HCG, CNAG showed increased TPD and calcium concentration but decreased SFR both before and after acid stimulation (P < 0.01), as well as reduced sAA and salivary chloride responses to acid stimulation (P < 0.01). Compared with CNAG with normal BMI (24.29%, 17/70), sAA activity response to acid stimulation was reduced in those with low BMI (75.71%, 53/70, P < 0.05). Under resting condition, CNAG with dry mouth (55.71%, 39/70) showed increased SFR and decreased TPD (P < 0.05), as compared with CNAG without dry mouth (44.29%, 31/70). Compared with CNAG without bitter taste (57.14%, 40/70), pH was decreased in those with bitter taste (42.86%, 30/70) under both resting and stimulated conditions (P < 0.05). CONCLUSION: Decreased sAA activity may reflect malnutrition state and be one potential marker of poor digestion, decreased salivary pH may contribute to bitter taste perception, and reduced TPD might be a cause of dry mouth in CNAG.

10.
Cell Physiol Biochem ; 51(6): 2647-2693, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30562755

RESUMO

Cancer is a disease caused by the accumulation of genetic and epigenetic changes in two types of genes: tumor suppressor genes (TSGs) and proto-oncogenes. Extensive research has been conducted over the last few decades to elucidate the role of TSGs in cancer development. In cancer, loss of TSG function occurs via the deletion or inactivation of two alleles, according to Knudson's two-hit model hypothesis. It has become clear that mutations in TSGs are recessive at the level of an individual cell; therefore, a single mutation in a TSG is not sufficient to cause carcinogenesis. However, many studies have identified candidate TSGs that do not conform with this standard definition, including genes inactivated by epigenetic silencing rather than by deletion. In addition, proteasomal degradation by ubiquitination, abnormal cellular localization, and transcriptional regulation are also involved in the inactivation of TSGs. This review incorporates these novel additional mechanisms of TSG inactivation into the existing two-hit model and proposes a revised multiple-hit model that will enable the identification of novel TSGs that can be used as prognostic and predictive biomarkers of cancer.


Assuntos
Genes Supressores de Tumor , Neoplasias/genética , Proteínas Supressoras de Tumor/genética , Alelos , Animais , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação , Neoplasias/metabolismo , Proteólise , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/metabolismo , Ubiquitinação
11.
PLoS One ; 13(2): e0192361, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466390

RESUMO

Rhabdomyolysis (RM) may cause kidney damage and results primarily in acute kidney injury (AKI). Complement is implicated in the pathogenesis of renal diseases and ischemia-reperfusion injury (IRI), but the role of complement, especially its activation pathway(s) and its effect in RM-induced AKI, is not clear. This study established a rat model of AKI induced by RM via intramuscular treatment with glycerol. Cobra venom factor (CVF) was administered via tail vein injection to deplete complement 12 h prior to intramuscular injection of glycerol. We found that the complement components, including complement 3 (C3), C1q, MBL-A, factor B(fB), C5a, C5b-9, and CD59, were significantly increased in rat kidneys after intramuscular glycerol administration. However, the levels of serum BUN and Cr, renal tubular injury scores, and the number of TUNEL-positive cells decreased significantly in the CVF+AKI group. These results suggest that complement plays an important role in RM-induced AKI and that complement depletion may improve renal function and decrease renal tissue damage by reducing the inflammatory response and apoptosis.


Assuntos
Lesão Renal Aguda/etiologia , Ativação do Complemento , Modelos Animais de Doenças , Rabdomiólise/complicações , Animais , Glicerol/administração & dosagem , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
12.
Exp Cell Res ; 362(1): 72-82, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29155365

RESUMO

Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients. Here, we investigated the mechanisms underlying these findings. DSF/Cu reversed the microtubule inhibitor resistance in A549/Taxol and KB/VCR cells in vitro, and had anti-tumor effects in A549/Taxol and KB/VCR xenograft mice. DSF/Cu and DSF reduced the cancer stem cell (CSC) characteristics of drug-resistant A549/Taxol and KB/VCR cells, including sphere formation, colony generation and migration, and DSF/Cu was more effective than DSF alone. DSF/Cu also decreased the aldehyde dehydrogenase (ALDH) activity and the expression of P-gp and stem cell transcription factors in A549/Taxol and KB/VCR cells. Knockdown of ALDH2 attenuated the CSC characteristics of resistant cancer cells and enhanced their sensitivity to Taxol or VCR. Importantly, DSF/Cu treatment inhibited the expression of ALDH2 in vitro and in vivo. Our findings suggest that DSF/Cu reverses microtubule inhibitor resistance in cancer cells by suppressing ALDH2 expression, and Cu improves the activity of DSF.


Assuntos
Aldeído-Desidrogenase Mitocondrial/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cobre/administração & dosagem , Dissulfiram/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Moduladores de Tubulina/uso terapêutico , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular/métodos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Surg Endosc ; 32(1): 536-543, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28664437

RESUMO

BACKGROUND AND OBJECTIVE: Endoscopic mucosa-sparing lateral dissection (EMSLD) was developed by our group, and is used to remove gastric submucosal tumor (SMT). This study aims to evaluate the feasibility and safety of this method. METHODS: This retrospective study included 25 patients who underwent EMSLDs at an endoscopy center as a national key unit in china from October 2015 to July 2016. The main data collected were the size of the gastric SMT, its location and origin, en bloc resection rate, operating time, intraoperative and postoperative complications, hospitalization expense, hospital days, and follow-up after hospital discharge. RESULTS: The mean (SD) size of the gastric SMTs was 18.3 (5.9) mm; 96% (24/25) of the tumors originated in the muscularis propria; and 64% (16/25) and 28% (7/25) were located in the gastric fundus and gastric body, respectively. The rate of en bloc resection was 96% (24/25), and the rate of intraoperative perforations due to endoscopic full-thickness resection was 48% (12/25). All wounds and perforations were effectively closed using endoscopic clips combined with the retained mucosa. The mean operative time was 74.2 (38.0) min. Delayed bleeding and perforation were not observed. CONCLUSION: Endoscopic mucosa-sparing lateral dissection is safe and feasible for the removal of gastric SMTs. The wound can be effectively closed using the retained mucosa and endoscopic clips, even if perforation has occurred. EMSLD provides an alternative to the resection of gastric SMTs, especially for tumors with a risk of intraoperative perforation.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Mucosa Gástrica/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Adulto Jovem
14.
Minim Invasive Ther Allied Technol ; 27(3): 127-137, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28681655

RESUMO

AIMS: To evaluate the effectiveness and safety of endoscopic resection for gastric gastrointestinal stromal tumors (GISTs). MATERIAL AND METHODS: The effectiveness and safety of endoscopic resection were mainly assessed by complete resection rate, postoperative adverse event rate, and recurrence rate. Moreover, a comparison of endoscopic with laparoscopic resection for gastric GISTs was made through weighted mean difference by STATA 12.0 with regard to operation time, blood loss, and length of stay after including patients who underwent endoscopic or laparoscopic resection for gastric GISTs in the comparative studies. RESULTS: Eleven studies investigating endoscopic resection for GISTs were included. For stromal tumors <2 cm in average diameters the pooled rates of complete resection, postoperative adverse events and recurrence were 0.97, 0.08, and 0.03, respectively. Only five retrospective studies directly compared endoscopic with laparoscopic resection for gastric GISTs with average diameters from 1.1 cm to 3.8 cm, and endoscopic resection had a shorter operation time than laparoscopic resection, but there were no significant differences in intraoperative blood loss, length of stay, postoperative complications, and postoperative recurrence rates between the two approaches. CONCLUSIONS: Endoscopic resection is predominantly tried for gastric GISTs of relatively small size. It seems effective and safe for gastric GISTs <2 cm in average diameter, with relatively short operation times.


Assuntos
Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Neoplasias Gástricas/cirurgia , Gastroscopia , Humanos , Laparoscopia , Resultado do Tratamento
15.
J Cell Mol Med ; 22(1): 439-451, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29148232

RESUMO

Late-stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)-dependent anticancer properties in vitro and in vivo. The present work aims to explore the anti-metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both in vitro and in vivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti-metastatic activity of DSF, while Cu alone had no effect. Furthermore, DSF/Cu inhibited both NF-κB and TGF-ß signalling, including the nuclear translocation of NF-κB subunits and the expression of Smad4, leading to down-regulation of Snail and Slug, which contributed to phenotype epithelial-mesenchymal transition (EMT). Finally, DSF/Cu inhibited the lung metastasis of Hep3B cells not only in a subcutaneous tumour model but also in an orthotopic liver metastasis assay. These results indicated that DSF/Cu suppressed the metastasis and EMT of hepatic carcinoma through NF-κB and TGF-ß signalling. Our study indicates the potential of DSF/Cu for therapeutic use.


Assuntos
Carcinoma Hepatocelular/patologia , Cobre/farmacologia , Dissulfiram/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , NF-kappa B/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/genética , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Fenótipo , Transdução de Sinais , Proteína Smad4/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Oncotarget ; 8(49): 85252-85262, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29156717

RESUMO

Hypoxia-inducible factor-1 (HIF-1) is over-expressed in gliomas and has become one of the most compelling tumor targets. In this study, we found that oligomer procyanidins (F2) can suppress the expressions of HIF-1α and its target genes in U87 cells, and also down-regulate the EGFR/PI3K/AKT/mTOR and MAPK/ERK1/2 pathways in vitro and in vivo. Furthermore, hypoxia-induced formation of tubular structures by human umbilical vascular endothelial cells and the migration and invasion of U87 cells could be inhibited by F2 in a HIF-1 dependent manner. Moreover, in a U87 xenograft tumor model, F2 significantly reduced intra-tumor vessel density and cell proliferation and finally retarded tumor growth, indicating that F2 may be a potential HIF-1 inhibitor and serve as one of candidates for glioma therapy.

17.
Med Sci Monit ; 23: 5176-5183, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29084195

RESUMO

BACKGROUND Prostate cancer (PCa) is the second most commonly diagnosed cancer in males worldwide. This study aimed to identify differentially expressed genes and to investigate the potential correlation between gene abnormalities and clinical features in PCa to evaluate disease progression and prognosis. MATERIAL AND METHODS A total of 4 independent microarrays of PCa patients from the Oncomine database were used to identify differences in expression of genes contributing to cancer progression. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis was used to evaluate the mRNA expression of the target in human prostate cancer cells. To explore the relationship between the DNA copy number alteration and mRNA expression changes, dataset containing copy number alteration, DNA methylation, and gene expression in PCa were obtained from the cBioPortal online platform (n=273). RESULTS We identified 40 genes that were significantly dysregulated in PCa from 4 independent microarrays. Among these, 3 genes showed a consistent change of over 2-fold in the 4 microarrays. The mRNA expression of C10orf116 showed consistent expression in prostate cancer cells compared with that in prostate gland cells as assessed by RT-qPCR. Moreover, C10orf116 loss was associated with poor distant relapse-free survival (DFS) by analyzing data of 273 PCa patients, but it was not identified as an independent prognostic risk factor for DFS. In addition, we found that C10orf116 loss was associated with higher pathological stage, higher clinical stage, and lymph node metastasis in PCa, and that C10orf116 copy number was highly correlated with PTEN copy number and mRNA expression. CONCLUSIONS As a predictive indicator, C10orf116 loss contributes to our understating of the biology of aggressive changes in PCa and also helps evaluate the prognosis of patients.


Assuntos
Dosagem de Genes , Proteínas Nucleares/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Biologia Computacional , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Proteínas Nucleares/metabolismo , PTEN Fosfo-Hidrolase/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
18.
Psychiatry Res ; 256: 59-65, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28623769

RESUMO

We examined the relationship between bully victimization experience and depression in rural adolescents and analyzed the moderating roles of peer support and active coping in male and female students. The sample comprised N=755 adolescents (376 females) with a mean age of 13.52 years. Through structural model and multi-group analysis, the results indicated: (1) a significant gender difference on the positive association between bullying victimization and depression; (2) peer support had a directly negative effect on depression among all boarding adolescents; and (3) significant moderating effect of active coping on the association between victimization and depression, without significant gender difference. We discuss enhancing active coping and peer support as a prevention strategy to reduce adverse mental health outcomes in adolescents due to bullying victimization.


Assuntos
Bullying , Vítimas de Crime/psicologia , Depressão/psicologia , Apoio Social , Estudantes/psicologia , Adaptação Psicológica , Adolescente , Grupo com Ancestrais do Continente Asiático/psicologia , China , Feminino , Humanos , Masculino , Grupo Associado , Fatores Sexuais
19.
Int J Oncol ; 50(1): 272-282, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27922669

RESUMO

SMAD4 is a tumor suppressor that is frequently inactivated in many types of cancer. The role of abnormal expression of SMAD4 has been reported in developmental processes and the progression of various human cancers. The expression level of SMAD4 has been related to the survival rate in gastric cancer patients. However, the molecular mechanism underlying transcriptional regulation of SMAD4 remains largely unknown. In the present study, we characterized the promoter region of SMAD4 and identified myeloid zinc finger 1 (MZF1), as a putative transcription factor. MZF1 directly bound to a core region of the SMAD4 promoter and stimulated transcriptional activity. We also found that the expression of MZF1 influences the migration ability of gastric adenocarcinoma cells. Collectively, our results showed that MZF1 has a role in cellular migration of gastric cancer cells via promoting an increase in intracellular SMAD4 levels. This study might provide new evidence for the molecular basis of the tumor suppressive effect of the MZF1-SMAD4 axis, a new therapeutic target in advanced human gastric cancer.


Assuntos
Fatores de Transcrição Kruppel-Like/genética , Regiões Promotoras Genéticas , Proteína Smad4/biossíntese , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo , Neoplasias Gástricas/patologia , Ativação Transcricional/genética
20.
Sensors (Basel) ; 16(11)2016 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-27834849

RESUMO

Trypsin is important during the regulation of pancreatic exocrine function. The detection of trypsin activity is currently limited because of the need for the substrate to be labeled with a fluorescent tag. A label-free fluorescent method has been developed to monitor trypsin activity. The designed peptide probe consists of six arginine molecules and a cysteine terminus and can be conjugated to DNA-stabilized silver nanoclusters (DNA-AgNCs) by Ag-S bonding to enhance fluorescence. The peptide probe can also be adsorbed to the surface of graphene oxide (GO), thus resulting in the fluorescence quenching of DNA-AgNCs-peptide conjugate because of Förster resonance energy transfer. Once trypsin had degraded the peptide probe into amino acid residues, the DNA-AgNCs were released from the surface of GO, and the enhanced fluorescence of DNA-AgNCs was restored. Trypsin can be determined with a linear range of 0.0-50.0 ng/mL with a concentration as low as 1 ng/mL. This label-free method is simple and sensitive and has been successfully used for the determination of trypsin in serum. The method can also be modified to detect other proteases.


Assuntos
DNA/química , Grafite/química , Nanopartículas Metálicas/química , Prata/química , Tripsina/metabolismo , Técnicas Biossensoriais , Transferência Ressonante de Energia de Fluorescência , Fluorometria/métodos , Tripsina/química
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