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1.
ACS Appl Mater Interfaces ; 12(7): 8016-8029, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31997633

RESUMO

Arsenic trioxide (ATO) is effective in the treatment of hematological malignancies and solid tumors. However, its toxicity and side effects are severe, posing an obstacle in its clinical application. A controlled-release ATO carrier with mitochondrial targeting was constructed in this study. The safety and efficacy in vitro were investigated using a hemolysis test, cytotoxicity, proliferation, migration, apoptosis, and other changes in cell behavior. The safety and efficacy were further evaluated in vivo by hematoxylin-eosin staining, terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling staining, and blood testing in tumor-bearing mice. Immunohistochemically and western blotting experiments were conducted to explore the mechanism of combination therapy of material-based chemotherapy and microwave hyperthermia in vitro. We demonstrated that the nano-zirconia (ZrO2) loading platform may be used to administer the ATO, with local precision-controlled release and mitochondrial targeting. Furthermore, we showed the safety of this approach for delivering high doses of ATO. In addition, we explored this new method in combination with in vitro microwave heat therapy, providing a potentially novel intravenous approach to chemotherapy. We described a new non-invasive treatment that improved the efficacy of ATO chemotherapy against hepatocellular carcinoma through nano-ZrO2 carriers.

2.
Cancer ; 126(4): 840-849, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31714592

RESUMO

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

3.
Cancer Cell Int ; 19: 295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807117

RESUMO

The potent pleiotropic lipid mediator sphingosine-1-phosphate (S1P) participates in numerous cellular processes, including angiogenesis and cell survival, proliferation, and migration. It is formed by one of two sphingosine kinases (SphKs), SphK1 and SphK2. These enzymes largely exert their various biological and pathophysiological actions through one of five G protein-coupled receptors (S1PR1-5), with receptor activation setting in motion various signaling cascades. Considerable evidence has been accumulated on S1P signaling and its pathogenic roles in diseases, as well as on novel modulators of S1P signaling, such as SphK inhibitors and S1P agonists and antagonists. S1P and ceramide, composed of sphingosine and a fatty acid, are reciprocal cell fate regulators, and S1P signaling plays essential roles in several diseases, including inflammation, cancer, and autoimmune disorders. Thus, targeting of S1P signaling may be one way to block the pathogenesis and may be a therapeutic target in these conditions. Increasingly strong evidence indicates a role for the S1P signaling pathway in the progression of cancer and its effects. In the present review, we discuss recent progress in our understanding of S1P and its related proteins in cancer progression. Also described is the therapeutic potential of S1P receptors and their downstream signaling cascades as targets for cancer treatment.

4.
J Vasc Interv Radiol ; 30(12): 2026-2035.e2, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31590966

RESUMO

PURPOSE: To evaluate the effect of transarterial infusion of iRGD-modified and doxorubicin-loaded zirconia-composite nanoparticles (R-DZCNs) with lipiodol in the improvement of the distribution of doxorubicin (DOX) in liver tumors and its antitumor efficacy. MATERIALS AND METHODS: The effect of R-DZCNs was evaluated in vitro by tumor cellular uptake and cytotoxicity assays. For the in vivo study, DOX distribution and antitumor efficiency were assessed. In the DOX distribution study, VX2 tumor-bearing rabbits received transarterial infusion of lipiodol with DOX, doxorubicin-loaded zirconia-composite nanoparticles (DZCNs), or R-DZCNs, respectively. DOX distribution was assessed by immunofluorescence. In the antitumor study, tumor-bearing rabbits received transarterial infusions of lipiodol with DOX, DZCNs, R-DZCNs, or saline respectively. Tumor volume was measured using magnetic resonance imaging, and the expression of apoptosis-related factors (caspase-3, Bax, Bcl-2) was analyzed by immunohistochemistry and Western blotting. RESULTS: R-DZCNs increased cellular uptake and caused stronger cytotoxicity. Compared with the DOX + lipiodol or DZCNs + lipiodol group, the R-DZCNs + lipiodol group showed more DOX fluorescence spots (2,449.15 ± 444.14 vs. 3,464.73 ± 632.75 or 5,062.25 ± 585.62, respectively; P < .001) and longer penetration distance (117.58 ± 19.36 vs 52.64 ± 8.53 or 83.37 ± 13.76 µm, respectively; P < .001). In the antitumor study, the R-DZCNs + lipiodol group showed smaller tumor volumes than the DOX + lipiodol or DZCNs + lipiodol group (1,223.87 ± 223.58 vs. 3,695.26 ± 666.25 or 2281.06 ± 457.21 mm3, respectively; P = .005).The greatest extent of tumor cell apoptosis was observed in R-DZCNs + lipiodol group immunohistochemistry and Western blotting results. CONCLUSIONS: Transarterial infusion of R-DZCNs with lipiodol improved the distribution of DOX and enhanced its antitumor efficacy.

5.
Front Pharmacol ; 10: 833, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402864

RESUMO

Resveratrol (Res) is a multi-functional polyphenol compound that has protective functions in acute kidney diseases. Here, we examined whether the resveratrol could ameliorate post-contrast acute kidney injury (PC-AKI) following diabetic nephropathy (DN), and explored any underlying mechanism(s) in vivo and in vitro. Twenty-four rabbits with DN were randomly divided into four groups: control (Cont), resveratrol (Res), iohexol (PC-AKI), and resveratrol plus iohexol (Res+PC-AKI) groups. Functional magnetic resonance imaging, renal histology, blood and urinary biomarkers, silent information regulator l (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), hypoxia-inducible transcription factor-1α (HIF-1α), and apoptosis-associated protein expression were assessed ex vivo. For in vitro experiments, renal tubular epithelial (HK-2) cells subjected to high glucose conditions were treated with resveratrol, Ex527, an SIRT1 inhibitor, or 2-methoxyestradiol (2-MeOE2), HIF-1α inhibitor, before treatment with iohexol. With regard to the rabbit model of acute renal injury in DN, compared to the PC-AKI group, the Res+PC-AKI group showed decreased levels of cystatin C and urinary neutrophil gelatinase-associated lipocalin, increased pure molecular diffusion (D) and the fraction of water flowing in capillaries (f), a decreased apparent relaxation rate (R2*), renal injury score and apoptosis rate, increased protein expression levels of SIRT1 and PGC-1α, and decreased levels of HIF-1α and apoptosis-associated protein. In addition, iohexol decreased HK-2 cell survival and increased the cell apoptosis rate; results were reversed after treating cells with resveratrol. Resveratrol reduced renal hypoxia, mitochondrial dysfunction and renal tubular cell apoptosis by activating SIRT1-PGC-1α-HIF-1α signaling pathways in PC-AKI with DN.

6.
ACS Omega ; 4(4): 6486-6491, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31459781

RESUMO

We report water-splitting application of chemically stable self-grown nickel sulfide (Ni x S y ) electrocatalysts of different nanostructures including rods, flakes, buds, petals, etc., synthesized by a hydrothermal method on a three-dimensional Ni foam (NiF) in the presence of different sulfur-ion precursors, e.g., thioacetamide, sodium thiosulfate, thiourea, and sodium sulfide. The S2- ions are produced after decomposition from respective sulfur precursors, which, in general, react with oxidized Ni2+ ions from the NiF at optimized temperatures and pressures, forming the Ni x S y superstructures. These Ni x S y electrocatalysts are initially screened for their structure, morphology, phase purity, porosity, and binding energy by means of various sophisticated instrumentation technologies. The as-obtained Ni x S y electrocatalyst from sodium thiosulfate endows an overpotential of 200 mV. The oxygen evolution overpotential results of Ni x S y electrocatalysts are comparable or superior to those reported previously for other self-grown Ni x S y superstructure morphologies.

7.
Virol J ; 16(1): 61, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064399

RESUMO

BACKGROUND: Hepatitis B e antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. METHODS: We have studied whether levels of serum hepatitis B virus ribonucleic acid (HBV RNA) during pegylated interferon alfa-2a treatment might be helpful for predicting HBeAg seroconversion. 61 HBeAg-positive chronic hepatitis B (CHB) patients treated with pegylated interferon alfa-2a alone or in combination with adefovir (10 mg/day) for 48 weeks were included in this retrospective analysis. Response was defined as HBeAg seroconversion at 24 weeks posttreatment. Receiver operating characteristic analyses were used to identify baseline and on-treatment HBV RNA levels associated with response. RESULTS: Twenty-two of 61 (36.1%) patients achieved a response. Baseline HBV RNA levels were lower in responders than in nonresponders (4.55 ± 1.19 and 5.90 ± 1.13 copies/mL, respectively, P = 0.001). Baseline HBV RNA cut off level (200,000 copies/mL) provided a positive predictive value (PPV) of 56.0% and a negative predictive value (NPV) of 77.8%. HBV RNA level (3000 copies/mL) at week 12 provide a PPV of 75.0% and a NPV of 82.8%. Moreover, HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in patients with HBV RNA ≤ 200,000 copies/mL at baseline and HBV RNA ≤ 3000 copies/mL at week 12 (92.9%) versus others (12.5%) (All P < 0.05). CONCLUSIONS: In Conclusions, serum HBV RNA levels may serve as a novel tool for prediction of HBeAg seroconversion during therapy with pegylated interferon alfa-2a in HBeAg-positive CHB patients.


Assuntos
Antivirais/uso terapêutico , DNA Viral/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Curva ROC , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Soroconversão , Adulto Jovem
8.
Cancer Manag Res ; 11: 3813-3828, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118799

RESUMO

Purpose: CADM1-AS1 (cell adhesion molecule 1 antisense RNA 1, long non-coding RNA), was firstly characterized in renal clear cell carcinoma, and exhibits a tumor suppressor role. However, its clinical relevance and exact effects in hepatocellular carcinoma (HCC) remain unknown. Therefore, in this study, we aimed to assess the clinical significance and function of CADM1-AS1 in HCC. Methods: We detected CADM1-AS1 expression in liver cancer tissue samples and cell lines, and analyzed the association between CADM1-AS1 expression and clinical parameters in 90 liver cancer patients. Moreover, we conducted gain-of-function and loss-of-function studies in liver cancer cell to explore the biological function and molecular mechanism of CADM1-AS1. Results: CADM1-AS1 expression was reduced in HCC. Clinical data showed that this downregulation was associated with advanced tumor stage, high TNM stage and reduced survival in HCC patients. CADM1-AS1 overexpression inhibited HCC cells proliferation, migration and invasion, while inducing G0/G1 phase arrest. Meanwhile, we revealed that CADM1-AS1 inhibited the phosphorylation of AKT and GSK-3ß. Furthermore, our study showed that CADM1-AS1 decreased the cell cycle associated proteins expression of cyclinD, cyclinE, CDK2 CDK4, CDK6, and enhanced the levels of p15, p21 and p27. More importantly, SC79, a specific activator for AKT;, apparently attenuated the effects of CADM1-AS1 on above cell-cycle associated proteins, confirming that CADM1-AS1 inhibited cell cycles through the AKT signaling pathway. And we also found the CADM1-AS1 has antitumor effect in vivo by a xenograft HCC mouse model. In conclusion, the present findings show that the CADM1-AS1 inhibits proliferation of HCC by inhibiting AKT/GSK-3ß signaling pathway, then upregulate p15, p21, p27 expression and downregulate cyclin, CDK expression to inhibit the G0/G1 to S phase transition both in vitro and in vivo. Conclusion: CADM1-AS1 functions as a tumor-suppressive lncRNA. This study reveals a molecular pathway involving PTEN/AKT/GSK-3ß which regulates HCC cell-cycle progression.

9.
Clin Transl Gastroenterol ; 10(5): 1-12, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31033506

RESUMO

OBJECTIVES: Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications. METHODS: A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI). RESULTS: A total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis. CONCLUSIONS: The Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.

10.
Biomed Res Int ; 2019: 1621627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30937309

RESUMO

It is still vague for chronic hepatitis B (CHB) patients with normal or mildly increasing alanine aminotransferase (ALT) level to undergo antiviral treatment or not. The purpose of our study was to establish a noninvasive model based on routine blood test to predict liver histopathology for antiviral therapy. This retrospective study enrolled 258 CHB patients with liver biopsy from the First Hospital of Quanzhou (training cohort, n=126) and Huashan Hospital (validation cohort, n=132). Histologic grading of necroinflammation (G) and liver fibrosis (S) was performed according to the Scheuer scoring system. A novel model, ATPI, including aspartate aminotransferase (AST), total bilirubin (TBil), and platelets (PLT), was developed in training cohort. The area under ROC curves (AUC) of ATPI for predicting antiviral therapy indication was 0.83 in training cohort and was 0.88 in the validation cohort, respectively. Similarly, ATPI also displayed the highest AUC in predicting antiviral therapy indication in CHB patients with normal or mildly increasing ALT level. In conclusion, ATPI is a novel independent model to predict liver histopathology for antiviral therapy in CHB patients with normal and mildly increased ALT levels.


Assuntos
Hepatite B Crônica/patologia , Fígado/patologia , Alanina Transaminase/sangue , Antivirais/farmacologia , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Biomarcadores/metabolismo , Plaquetas/patologia , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Fígado/efeitos dos fármacos , Modelos Biológicos , Análise Multivariada , Curva ROC , Reprodutibilidade dos Testes
11.
Aliment Pharmacol Ther ; 49(4): 448-456, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30689258

RESUMO

BACKGROUND: Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear. AIMS: To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response. METHODS: Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG-IFN. RESULTS: Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82). CONCLUSIONS: PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843).


Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , DNA Viral , Quimioterapia Combinada , Feminino , Guanina/administração & dosagem , Antígenos E da Hepatite B/sangue , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Masculino , Polietilenoglicóis/química , Adulto Jovem
12.
ACS Appl Mater Interfaces ; 11(4): 4551-4559, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30601660

RESUMO

Sulphur source-inspired self-grown polycrystalline and mesoporous nickel sulfide (Ni xS y) superstructures with vertically aligned nanomorphologies viz. rods, flakes, buds, and petals, synthesized at elevated temperatures and moderate pressures by a facile one-pot hydrothermal method on a three-dimensional Ni foam demonstrate remarkable areal specific capacitances of 7152, 4835, and 2160 F cm-2 at current densities of 1, 2, and 5 mA cm-2, respectively, with a cycling stability of 94% for a battery-type electrochemical supercapacitor when used as an electrode material in a supercapacitor. The Ni xS y//Bi2O3 asymmetric supercapacitor assembly exhibits an energy density of 41 W h·kg-1 at a power density of 1399 W kg-1 for 1 A g-1 and was used in a three-cell series combination to operate a "GFHIM" display panel (our research institute name, Global Frontier R & D Center for Hybrid Interface Materials) composed of nearly 50 differently colored light-emitting diodes with high intensity in 1 M KOH water-alkali electrolyte. The electrochemical supercapacitor results obtained for the Ni xS y superstructures because of a combination of catalytically active amorphous and high mobility polycrystalline are highly comparable to those reported previously for salt-mediated and self-grown Ni xS y structures and morphologies.

13.
J Viral Hepat ; 26(1): 109-117, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30187612

RESUMO

Addition of peginterferon alpha (PEG-IFN add-on) to entecavir (ETV) treatment after a short lead-in phase results in more response than ETV monotherapy in HBeAg-positive chronic hepatitis B infection (CHB). This study is the first to assess long-term efficacy of this treatment strategy. Patients who received ETV ± 24 weeks of PEG-IFN add-on in a global trial (ARES study) and completed follow-up were eligible to participate in this observational LTFU study if they had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA <200 IU/mL) at LTFU. In total, 48 patients treated with PEG-IFN add-on and 48 patients treated with ETV monotherapy were included. The median follow-up duration was 226 (IQR 51) weeks, and 86/96 (90%) patients were initial non-responders. At LTFU, combined response was present in 13 (27%) vs 11 (23%) patients (P = 0.81), and 1 log10  HBsAg decline in 59% vs 28% (P = 0.02) for PEG-IFN add-on and ETV monotherapy, respectively. In 41 initial non-responders who continued ETV therapy, combined response at LTFU was present in 9 patients (PEG-IFN add-on: 5/22 [23%]; ETV monotherapy: 4/19 [21%]). Beyond week 96 of follow-up, rates of serological response became comparable between PEG-IFN add-on and ETV monotherapy. Although in this LTFU study initial non-responders were overrepresented in the add-on arm, PEG-IFN add-on possibly leads rather to accelerated HBeAg loss than to increased long-term HBeAg loss rates.

14.
Cancer Manag Res ; 10: 5261-5271, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464623

RESUMO

Background: Resistance to radiation therapy is still a challenge for treatment of pancreatic cancer(PC). Long non-coding RNAs (lncRNA) HOTAIR has been found to play a oncogenic role in several cancers. However, the correlation between HOTAIR and radiotherapy in PC is still unclear. Methods: TCGA data was collected to analyze the expression of HOTAIR and its relationship with PC progression. A series of functional experiments were conducted to explore the role of HOTAIR in PC radiosensitivity and its underlying molecular mechanisms. Results: By the analysis of the TCGA data, we found HOTAIR expression in PC tissues was significantly higher than normal tissues and associated with tumor progression. The function analysis showed HOTAIR was enriched in biological regulation and response to stimulus. And in vitro study, the expression of HOTAIR was increased in PANC-1 and AsPC-1 cells after radiation. We identified that HOTAIR knockdown could enhance radiosensitivity and influence autophagy by up-regulating ATG7 expression in PC cells. By futher rescue experiments using rapamycin, activation of autophagy could reversed the the inhibition of cell proliferation and colony formation, as well as promotion of apoptosis mediated by HOTAIR knockdown, indicating that HOTAIR knockdown promoted radiosensitivity of PC cells by regulating autophagy. Conclusion: Our finding revealed the the regulatory role of HOTAIR in radiosensitivity and provided a a new sight to improve radiotherapy effciency in PC.

15.
Biosci Rep ; 38(6)2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30355653

RESUMO

Sialic-acid-binding immunoglobulin-like lectin (siglec) regulates cell death, anti-proliferative effects and mediates a variety of cellular activities. Little was known about the relationship between siglecs and hepatocellular carcinoma (HCC) prognosis. Siglec gene expression between tumor and non-tumor tissues were compared and correlated with overall survival (OS) from HCC patients in GSE14520 microarray expression profile. Siglec-1 to siglec-9 were all down-regulated in tumor tissues compared with those in non-tumor tissues in HCC patients (all P < 0.05). Univariate and multivariate Cox regression analysis revealed that siglec-2 overexpression could predict better OS (HR = 0.883, 95%CI = 0.806-0.966, P = 0.007). Patients with higher siglec-2 levels achieved longer OS months than those with lower siglec-2 levels in the Kaplan-Meier event analysis both in training and validation sets (P < 0.05). Alpha-fetoprotein (AFP) levels in siglec-2 low expression group were significantly higher than those in siglec-2 high expression group using Chi-square analysis (P = 0.043). In addition, both logistic regression analysis and ROC curve method showed that siglec-2 down-regulation in tumor tissues was significantly associated with AFP elevation over 300 ng/ml (P < 0.05). In conclusion, up-regulation of siglec-2 in tumor tissues could predict better OS in HCC patients. Mechanisms of siglec-2 in HCC development need further research.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Prognóstico , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Adulto , Antígenos CD/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Vírus da Hepatite B/patogenicidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , alfa-Fetoproteínas/genética
16.
Biomed Res Int ; 2018: 5859415, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30148168

RESUMO

Objective: This study aimed to evaluate the links between CYP450 family genes in tumor tissues and hepatocellular carcinoma (HCC) outcomes. Methods: Gene Expression Omnibus (GEO) databases GSE14520 and GSE36376 were used to identify differential expressed CYP450 genes between tumor and nontumor tissues and related to HCC clinicopathological features and survivals. Results: Seven CYP450 genes including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2E1, CYP3A4, and CYP4A11 were downregulated in tumor tissues, which were validated in both GSE14520 and GSE36376. HCC patients with CYP2A6 and CYP2C8 low levels in tumor tissues suffered from poorer overall survival (OS) compared to those with high CYP2A6 and CYP2C8 in GSE14520 profile (log ranks P = 0.01 and P = 0.006, respectively). In addition, HCC patients with lower CYP2A6 and CYP2C8 in tumors had worse recurrence-free survival (RFS) than those with higher CYP2A6 and CYP2C8 (log ranks P = 0.02 and P = 0.012, respectively). In GSE36376 validation dataset, HCC patients with lower CYP2A6 and CYP2C8 had worse OS and RFS than those with higher CYP2A6 and CYP2C8 (all P < 0.05), in line with results in GSE14520 dataset. Additionally, lower CYP2A6 and CYP2C8 are associated with advanced clinicopathological features including tumor staging, vascular invasion, intrahepatic metastasis, and high alpha fetoprotein (all P < 0.05). Conclusion: Downregulation of CYP2A6 and CYP2C8 in tumor tissues links to poorer OS and RFS in HCC patients.


Assuntos
Carcinoma Hepatocelular/metabolismo , Citocromo P-450 CYP2A6/metabolismo , Citocromo P-450 CYP2C8/metabolismo , Regulação para Baixo , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/mortalidade , Estadiamento de Neoplasias , Prognóstico , República da Coreia
17.
Mol Med Rep ; 18(2): 2061-2067, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29956789

RESUMO

The present study investigated the role of tissue inhibitor of matrix metalloproteinase­3 (TIMP­3) in regulating the proliferation, migration, apoptosis and activity of matrix metalloproteinase (MMP)­2 and ­9, during the development of an atherosclerotic abdominal artery aneurysm (AAA). Experiments were conducted using rabbit AAA neck (NA) smooth muscle cells (SMCs), to investigate the potential for TIMP­3 to be used as a novel stent coating in preventing aortic dilation adjacent to the AAA. The atherosclerotic AAA model was induced in New Zealand white rabbits via a 6­week high­cholesterol diet, followed by incubation of the targeted aortic region with elastase. SMCs were isolated from the aorta adjacent to the aneurysm 30 days after AAA model induction, and stimulated with 3, 10, 30 or 100 ng/ml TIMP­3. Cell proliferation was investigated using Cell Counting Kit­8 reagent, migration was examined using a Boyden chamber assay and apoptotic rate was analyzed using the Annexin V­fluorescein isothiocyanate Apoptosis Detection kit. Gelatin zymography and ELISA were used to measure the activity of MMP­2 and MMP­9, and the expression of tumor necrosis factor­α (TNF­α), respectively. Analysis of cell proliferation indicated that 10, 30 and 100 ng/ml TIMP­3 reduced cell viability. Cell migration was decreased by 10, 30 and 100 ng/ml TIMP­3. MMP­2 activity was inhibited by 10, 30 and 100 ng/ml TIMP­3, and MMP­9 activity was suppressed by 30 and 100 ng/ml TIMP­3. The protein levels of secreted TNF­α were reduced by 10, 30 and 100 ng/ml TIMP­3. The present study demonstrated the ability of 30 and 100 ng/ml TIMP­3 to attenuate migration and proliferation, and to inhibit the activity of MMP­2, MMP­9 and TNF­α secretion of NA SMCs. In conclusion, TIMP­3 may be considered a potential therapeutic drug for use in a novel drug­eluting stent, to attenuate the progressive dilation of the aortic NA.


Assuntos
Aorta/metabolismo , Aterosclerose/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Inibidor Tecidual de Metaloproteinase-3/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Aorta/patologia , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Movimento Celular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Coelhos
18.
Dalton Trans ; 47(26): 8676-8682, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29897071

RESUMO

The structure and morphology of titanium carbide (Ti3C2Tx) MXene, a new class of two dimensional (2D) materials, are investigated and reported. Ti3AlC2 MAX, treated with a hydrofluoric acid etching process, is used as a promising electrode material for electrochemical supercapacitor studies. The electrochemical supercapacitor performance of Ti3C2Tx as a negatrode in a natural seawater electrolyte solution, tested in a three-electrode system, demonstrated a specific capacitance of 67.7 F g-1 at a current density of 1 A g-1 which is in accordance with the volumetric specific capacitance of 121.8 F cm-3. A symmetric supercapacitor assembled with a Ti3C2Tx//Ti3C2Tx electrode configuration revealed a volumetric specific capacitance of 27.4 F cm-3 at 0.25 A g-1, and 96.6% capacitance retention even after 5000 cycles, which is superior to those reported previously in similar systems, suggesting the importance of abundant and cost-effective seawater as a natural electrolyte in developing energy storage devices.

19.
Dig Liver Dis ; 50(5): 482-489, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29396134

RESUMO

BACKGROUNDS: The evaluation of liver fibrosis stages is essential for the clinical management of chronic hepatitis B (CHB). AIMS: To develop and validate a novel noninvasive index for moderate to severe fibrosis (≥S2) in CHB patients. METHODS: A total of 401 CHB patients who underwent liver biopsy were divided into the training (n = 300) and validation (n = 101) cohort. Histological severity was scored using a modified Scheuer system. Clinical and laboratory assessments were collected. RESULTS: In the training cohort, PACG, a novel index combining the quantitative hepatitis B core antibody (qAnti-HBc), platelet count (PLT), and albumin globulin ratio (A/G), presented better diagnostic performance (AUROC = 0.814) than that of APRI (0.735, p = 0.007) and FIB-4 (0.749, p = 0.014). In the validation cohort, the AUROC of the PACG, APRI, FIB-4 and Fibroscan were 0.834, 0.806, 0.791 and 0.810, respectively. More importantly, a higher and lower cutoff of PACG for predicting ≥S2 fibrosis or not had a >90% sensitivity and specificity, with a diagnostic accuracy of 85.9%. CONCLUSION: PACG is a promising noninvasive alternative to liver biopsy in CHB patients for the evaluation of moderate to severe fibrosis.


Assuntos
Globulinas/metabolismo , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Albumina Sérica/metabolismo , Adulto , Fatores Etários , Alanina Transaminase/sangue , Área Sob a Curva , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Contagem de Plaquetas , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
20.
ACS Appl Mater Interfaces ; 10(13): 11037-11047, 2018 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-29485262

RESUMO

Superfast (≤10 min) room-temperature (300 K) chemical synthesis of three-dimensional (3-D) polycrystalline and mesoporous bismuth(III) oxide (Bi2O3) nanostructured negatrode (as an abbreviation of negative electrode) materials, viz., coconut shell, marigold, honey nest cross section and rose with different surface areas, charge transfer resistances, and electrochemical performances essential for energy storage, harvesting, and even catalysis devices, are directly grown onto Ni foam without and with poly(ethylene glycol), ethylene glycol, and ammonium fluoride surfactants, respectively. Smaller diffusion lengths, caused by the involvement of irregular crevices, allow electrolyte ions to infiltrate deeply, increasing the utility of inner active sites for the following electrochemical performance. A marigold 3-D Bi2O3 electrode of 58 m2·g-1 surface area has demonstrated a specific capacitance of 447 F·g-1 at 2 A·g-1 and chemical stability of 85% even after 5000 redox cycles at 10 A·g-1 in a 6 M KOH electrolyte solution, which were higher than those of other morphology negatrode materials. An asymmetric supercapacitor (AS) device assembled with marigold Bi2O3 negatrode and manganese(II) carbonate quantum dots/nickel hydrogen-manganese(II)-carbonate (MnCO3QDs/NiH-Mn-CO3) positrode corroborates as high as 51 Wh·kg-1 energy at 1500 W·kg-1 power and nearly 81% cycling stability even after 5000 cycles. The obtained results were comparable or superior to the values reported previously for other Bi2O3 morphologies. This AS assembly glowed a red-light-emitting diode for 20 min, demonstrating the scientific and industrial credentials of the developed superfast Bi2O3 nanostructured negatrodes in assembling various energy storage devices.

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