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1.
Anal Chim Acta ; 1117: 18-24, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32408950

RESUMO

This study aimed to develop a novel and practical fluorescent method for GSH detection in complex biological samples. To this end, a series of coumarin-based fluorescent probes was designed and synthesized using various aliphatic halogens as the sensing group. By using a new evaluation method of GSH/Cys/Hcy coexisting conditions, the probe with chloropropionate (CBF3) showed a high selectivity, excellent sensitivity, good stability for GSH detection. The reaction mechanism is proposed as nucleophilic substitution/cyclization and intramolecular charge transfer (ICT), which was confirmed by LC-MS and NMR analysis, as well as density functional theory calculations. In addition, CBF3 was demonstrated to be competent not only for the quantitative detection of GSH in real serum samples, but also for sensing GSH changes in different oxidative stress models in living cells and nematodes. This study showed a practical strategy for constructing GSH-specific fluorescent probes, and provided a sensitive tool for real-time sensing of GSH in real biological samples. The findings would greatly facilitate further investigations on GSH-associated clinical diagnosis and biomedical studies.

2.
Phytomedicine ; 69: 153184, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32199253

RESUMO

BACKGROUND: ß-Elemene is a natural agent extracted from the traditional Chinese herbal medicine Curcuma wenyujin that is a promising novel plant-derived drug with broad-spectrum anticancer activity. Our previous study identified an enhanced capacity for metastasis in multidrug resistant (MDR) gastric cancer and breast cancer cells. However, the anti-metastatic effects of ß-Elemene on MDR cancer cells remain unknown. PURPOSE: In this study, we posit the hypothesis that ß-elemene possesses antimetastatic effects on MDR cancer cells. METHODS: Cell viability assay was used to assess the resistance of SGC7901/ADR cells and the cytotoxic effects of ß-Elemene. Wound healing, transwell assay and lung metastatic mice model were used to the anti-metastasis effects of ß-Elemene. MicroRNA microarray analysis was used to explore potential regulated miRNAs. Luciferase reporter assay was used to identify the direct target. Human MMP antibody array, western blot, immunoprecipitation, qRT-PCR analyses and immunohistochemistry were conducted to investigate the underlying anti-metastasis mechanism of ß-Elemene. RESULTS: In this study, we found that ß-Elemene significantly inhibited the metastatic capacity of MDR gastric cells in vivo and in vitro. Mechanistically, we found that ß-Elemene regulated MMP-2/9 expression and reversed epithelial-mesenchymal transition. Further studies showed that ß-Elemene upregulated Cbl-b expression, resulting in inhibition of the EGFR-ERK/AKT pathways, which regulate MMP-2/9. Additionally, we confirmed that ß-Elemene upregulated Cbl-b by inhibiting miR-1323 expression. Finally, we found that numbers of metastatic tumor nodules were significantly decreased in the lungs of nude mice after ß-Elemene treatment. CONCLUSION: Our results suggested that ß-Elemene inhibits the metastasis of MDR gastric cancer cells by modulating the miR-1323/Cbl-b/EGFR signaling axis.

3.
Oncol Rep ; 43(3): 965-974, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020211

RESUMO

Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 20­30% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.

4.
Int J Biochem Cell Biol ; 122: 105716, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32058048

RESUMO

G-protein-signaling modulator 2 (GPSM2) belongs to a protein family that regulates activation of G proteins and plays an important role in mitotic spindle orientation. However, the role of GPSM2 in lung adenocarcinoma (LUAD) is still unclear. In this study, it was found that GPSM2 correlates with clinicopathological features and patient's prognosis in LUAD. Knocking down GPSM2 promoted LUAD cell proliferation in vitro and in vivo. Mechanistically, it was demonstrated that GPSM2 knockdown accelerates cell proliferation via the EGFR pathway. These results confirmed that GPSM2 played an important role in LUAD. Moreover, GPSM2, as an independent prognostic factor, may serve as a potential drug target and prognostic biomarker in LUAD.

5.
Cancer Biomark ; 27(4): 519-524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32083572

RESUMO

BACKGROUND: Occludin/ELL domain containing 1 (OCEL1) is a novel discovered protein with its molecular functions remaining unknown and its role in lung cancer has not been directly explored. OBJECTIVES: This study focused on the role of OCEL1 in the progression and prognosis of non-small cell lung cancer (NSCLC). METHODS: A public database and tissue samples (80 NSCLC tissue samples and paired normal lung samples) were used to compare differences in OCEL1 expression and investigate its relationship with clinical characteristics and prognosis. RESULTS: Compared to adjacent normal lung tissue samples, OCEL1 expression was significantly down-regulated in tumor tissues. In addition, there was a negative correlation between OCEL1 and Ki67 expression levels. Low OCEL1 expression was significantly associated with lymph node metastasis, higher TNM stage, and poor prognosis. Importantly, multivariate analysis identified OCEL1 expression as an independent predictor for unfavorable NSCLC prognosis. CONCLUSIONS: These results indicated that OCEL1 protein may serve as a novel prognostic biomarker in NSCLC.

6.
ACS Nano ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32049482

RESUMO

Vibrations in the environment are usually distributed over a wide frequency spectrum in multiple directions and a weaker amplitude, which makes most of the current vibrational energy collectors limited in practical environmental applications. Herein, a triboelectric-electromagnetic hybridized nanogenerator (TEHG) for low-frequency random microvibrational energy harvesting in all directions and a wide working bandwidth is fabricated. The output peak power of a triboelectric nanogenerator (TENG) up to 3.65 mW is realized (θ = 0.4 rad, f = 1 Hz). In addition, a real self-powered seawater splitting system and electrochemical cathodic protection system are fabricated, directly converting blue energy to hydrogen energy, and the ships can achieve self-protection against corrosion. Furthermore, relying on the linear relationship between the number of peaks and the amplitude of vibration, a highly sensitive self-powered vibration amplitude sensor system based on LabVIEW software is achieved, which can be used as an amplitude detection of bridges and earthquake monitoring, etc. This work is an important development for harvesting low-frequency random multiple direction microvibrational energy over a wide working bandwidth and the bright future of blue energy. In addition, it has been successfully applied to the power supply of portable electronic equipment, environmental monitors, and self-powered systems.

7.
J Fluoresc ; 30(1): 121-129, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31930435

RESUMO

In this study, an imidazole-coumarin based fluorescent probe was developed for the selective and sensitive detection of Ag+ in aqueous solution. Using a combination of Job plot, NMR titrations, and DFT calculations, the binding properties between Ag+ and the probe were deeply investigated, and the results revealed a 1:1 binding stoichiometry between the probe and Ag+ with a binding constant of 1.02 × 106 M-1. The detection limit was found to be 150 nM, which satisfies the requirement for the quantitative detection of Ag+ in real water samples. Moreover, the new probe, Ic, was successfully applied to sense Ag+ in HeLa and HepG2 cells as well as in C. elegans, indicating that it could be a useful tool for the environmental monitoring of Ag+ pollution. These results demonstrated that Ic could serve as a high-efficiency and low-cost fluorescent probe for tracking Ag+ in an aquatic environment and biological organisms.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117435, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31400745

RESUMO

A novel two-photon pH probe, 3-benzimidazole-7-hydroxycoumarin (BHC), was designed and synthesized based on the structures of hydroxycoumarin and benzimidazole. BHC showed good linearity in the pH ranges of 3.30-5.40 (pKa = 4.20) and 6.50-8.30 (pKa = 7.20) at a maximum emission wavelength of 480 nm. BHC in acidic and alkaline media could be distinguished by an obvious spectral shift of the maximum absorption wavelength from 390 nm to 420 nm. In addition, BHC was well localized to mitochondria and successfully applied to one-photon and two-photon imaging of pH changes in the mitochondria of HeLa cells. The findings presented herein suggest that BHC can serve as an excellent fluorescent probe for selectively sensing mitochondrial pH changes with remarkable photostability and low cytotoxicity.


Assuntos
Benzimidazóis/química , Cumarínicos/química , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Mitocôndrias , Umbeliferonas/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Mitocôndrias/química , Mitocôndrias/fisiologia
9.
Ann Transl Med ; 7(20): 586, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807567

RESUMO

Background: Acute variceal bleeding is one of the critical complications in patients with liver cirrhosis. Severe renal vasoconstriction in consequence of low peripheral vascular resistance triggers the reduction of glomerular filtration rate (GFR), and thus induces acute kidney injury (AKI)/hepato-renal syndrome (HRS). Terlipressin and octreotide have been used in the management of cirrhotic patients with variceal bleeding. Also, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS. In addition, the use of renal functional magnetic resonance imaging (fMRI) has become increasingly prevalent in research and clinical applications. However, the renal function-protective effect of terlipressin and octreotide and the value of fMRI in monitoring renal function remains unclear in patients with cirrhosis undergoing acute variceal bleeding. Methods: This is a multicenter, randomized controlled trial (RCT). Participants will be 1:1 assigned randomly into either terlipressin or octreotide groups. Sixty participants with clinically and/or pathologically diagnosed cirrhosis and active gastroesophageal variceal bleeding (GVB) will be recruited in several sites in China. Participants will receive either the treatment of terlipressin or octreotide after assigned into each group. The primary end point for the trial is the renal function. The secondary end points are (I) renal perfusion; (II) renal blood oxygenation; (III) failure to control bleeding; (IV) intra-hospital rebleeding; (V) intra-hospital mortality; (VI) adverse events (AE); (VII) overall survival. Statistical analysis including multivariate Cox regression, Kaplan-Meier analysis with log-rank test, etc. will be conducted. Discussion: The study will provide new insight into the protection of renal function in the process of the treatment of variceal bleeding in patients with cirrhosis. Trial registration number: NCT04028323.

10.
Chem Commun (Camb) ; 55(96): 14482-14485, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31729511

RESUMO

The electrochemical nitrogen reduction reaction (NRR) is a promising but extremely challenging approach for ammonia synthesis under ambient conditions. Herein, we report the excellent NRR performance of gold nanoparticles (AuNPs) with multiple high-index facets, prepared by a modified seed-mediated method. At -0.3 V vs. RHE and in 0.1 M Li2SO4 aqueous solution, the AuNPs afford the highest faradaic efficiency (FE) of 73.32% reported so far, with a remarkable ammonia generation rate of 9.22 µg h-1 cm-2. Density functional theory (DFT) calculations reveal that the high-index faceted surfaces of the AuNPs have greater preference for the adsorption of NRR intermediates (*NNH) and significantly hinder the adsorption of competing hydrogen evolution intermediates (*H).

11.
Phytother Res ; 33(9): 2448-2456, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342604

RESUMO

Peritoneal metastasis is common in advanced gastric cancer patients and is typically associated with a worse prognosis. ß-Elemene is a natural compound that can be isolated from the Curcuma wenyujin plant and has been widely used in China to treat a variety of cancers. However, the anti-metastatic impacts of ß-elemene on gastric cancer remain unknown. In our study, we found that ß-elemene significantly inhibited the migration and invasive capacity of gastric cells in vitro and inhibited the capacity of gastric cancer cells to peritoneally diffuse and metastasize in vivo. Mechanistically, we demonstrated that the anti-metastatic effects of ß-elemene were exerted by downregulating the expression of Claudin-1. Furthermore, ß-elemene was found to inhibit the metastatic capacity of cells by downregulating FAK phosphorylation, which regulated Claudin-1. Overall, our result revealed that ß-elemene inhibited peritoneal metastases from gastric cancer by modulating the FAK/Claudin-1 pathway.


Assuntos
Claudina-1/metabolismo , Neoplasias Peritoneais/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica , Fosforilação , Sesquiterpenos/farmacologia , Transdução de Sinais , Neoplasias Gástricas/patologia
12.
Eur J Pharm Sci ; 136: 104944, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31163215

RESUMO

Compared with coumarin, 7-hydroxycoumarin could serve as a better hit for developing CYP2A6 inhibitors. In this study, a series of 7-hydroxycoumarin and its structural analogues were collected to study their structure-activity relationship (SAR) and isoform selectivity for inhibiting CYP2A6. All tested coumarins except a C4 phenyl derivative (11) showed higher inhibitory activities for CYP2A6 over the other CYP isoforms, including CYP1A2, CYP2D6, CYP2E1, CYP3A4, CYP2C8, and CYP2C9. Of these coumarins, 6,7-dihydroxycoumarin (1) and 7,8-dihydroxycoumarin (9) were found to be potent inhibitors of CYP2A6 with IC50/Ki value of 0.39/0.25 and 4.61/3.02 µM, respectively, compared to methoxalen as positive control (IC50/Ki = 0.43/0.26 µM). In contrast, other coumarins showed low or decreased CYP2A6-inhibiting activities. SAR analysis showed that hydroxy groups might be important for CYP2A6 inhibition, and the rank order of sites for hydroxy substitution was C6 > C7 > C8. In addition, either hydrophobic or hydrophilic substituents introduced into C4, C6 and C8 led to a reduction in CYP2A6-inhibiting activity, and the degree of influence was dependent on the size and electrical charge of substituents. Furthermore, inhibition kinetic analysis and docking simulations demonstrated that the 8-O-glucosylated coumarin derivative (17) exhibited noncompetitive inhibition against CYP2A6, while competitive inhibition patterns were noted for the other tested coumarins. The mechanisms underlying the inhibitors binding to CYP2A6 were further investigated by molecular docking study. The findings presented herein are very helpful for developing highly selective and more potent CYP2A6 inhibitors.


Assuntos
Citocromo P-450 CYP2A6/antagonistas & inibidores , Inibidores das Enzimas do Citocromo P-450/farmacologia , Isoformas de Proteínas/metabolismo , Umbeliferonas/farmacologia , Cumarínicos/farmacologia , Humanos , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
13.
Cancer Manag Res ; 11: 4971-4984, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213913

RESUMO

Purpose: The chr1p/19q co-deletion is a favorable prognostic factor in patients with lower grade glioma. The aim of this study was to reveal key genes for prognosis and establish prognostic gene signatures based on genes encoded by chr1p/19q. Materials and methods: The data was downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between lower grade glioma tissue and normal brain were identified. The univariate COX regression, robust likelihood-base survival analysis (rbsurv) and multivariate COX regression analysis were used to establish the 4-gene-signature based on the DEGs. The receiver operating characteristic (ROC) curve and the Kaplan-Mere curve were used to verify the prediction accuracy of the signature. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to explore the reasons for good prognosis in patients with chr1p/19q deletion. Results: A total of 1346 DEGs were identified between lower grade glioma samples and normal brain samples in GSE16011, including 56 up-regulated mRNAs located on chr1p and 20 up-regulated mRNAs located on chr19q. We established a 4-gene-signature that was significantly associated with survival based on the 76 gene. The AUC of the 4-gene-signature for 5-year OS in TCGA and CGGA was 0.837 and 0.876, respectively, which was superior compared to other parameters such as chr1p/19q co-deletion, IDH mutant, WHO grade and histology type, especially in chr1p/19q non-co-deletion patients. GSEA and KEGG analysis suggested that the prolongation of chr1p/19q in patients could be associated with cell cycle and DNA mismatch repairing. Conclusions: We established a robust 4-gene-signature based on the chr1p/19q and we explored the potential function of these newly identified survival-associated genes by bioinformatics analysis. The 4-gene from the signature are promising molecular targets to be used in the future.

14.
PeerJ ; 7: e6885, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119084

RESUMO

The limb-bud and heart development (LBH) gene is a highly conserved, tissue-specific transcription cofactor in vertebrates that regulates multiple key genes in embryonic development. The role of LBH in various cancer types is still controversial, and its specific role and molecular mechanism in the oncogenesis of gastric cancer (GC) remains largely unexplored. In the present study, the prognostic significance and clinicopathological characteristics of LBH in GC was determined. The LBH mRNA expression was first investigated in four independent public datasets (TCGA-STAD, GSE15459, GSE29272, and GSE62254) and then validated with our samples at the protein level. LBH was overexpressed at both the mRNA and protein levels in cancer compared with normal tissues. High LBH expression was correlated with advanced T, N, and M stages. Kaplan-Meier analysis and log-rank test indicated that higher LBH expression was statistically correlated with shorter overall survival (OS) in the public datasets and our study samples. Univariate and multivariate Cox regression analysis showed that LBH was an independent prognostic biomarker for survival in TCGA-STAD, GSE15459, GSE62254 cohorts, and our GC patients. In vitro experiments showed that knockdown of LBH can significantly inhibit the proliferation and invasion of HGC-27 cells, while overexpression of LBH can significantly enhance the proliferation and invasion of BGC-823 cells. Gene Set Enrichment Analysis (GSEA), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) indicated that high LBH expression is associated with the PI3K-Akt pathway, focal adhesion, and extracellular matrix (ECM)-receptor interaction. Western blot analysis showed that knockdown of LBH significantly inhibited the expression of integrin α5, integrin ß1, p-FAK, and p-Akt. Therefore, results from the present study indicate that LBH is a potential independent prognostic biomarker and promotes proliferation and invasion of GC cells by activating the integrin/FAK/Akt pathway.

15.
Cancer Sci ; 110(7): 2145-2155, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087525

RESUMO

Gastric cancer (GC) is a common cause of cancer-related death worldwide. As a result of the lack of reliable diagnostic or prognostic biomarkers for GC, patient prognosis is still poor. Therefore, there is an urgent need for studies examining the underlying pathogenesis of GC in order to find effective biomarkers. LRRN1 (leucine-rich repeat neuronal protein-1) is a type I transmembrane protein that plays an important role in the process of nerve development and regeneration. However, its role in cancer, especially in GC, remains unclear. In the present study, we found that LRRN1 expression is upregulated in GC tissues and that high LRRN1 expression is associated with poor prognosis. siRNA and shRNA-mediated knockdowns of LRRN1 expression promoted GC cell apoptosis and activation of the Fas/FasL pathway. LRRN1 knockdown also resulted in upregulation of JUN, a subunit of the transcription factor AP-1 (activator protein-1). This suggests that LRRN1 suppresses GC cell apoptosis by downregulating AP-1, resulting in inhibition of the Fas/FasL pathway. These results confirm that LRRN1 plays a significant role in GC pathogenesis. Moreover, LRRN1 may be a potential prognostic biomarker and therapeutic target for GC.


Assuntos
Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Regulação para Cima , Animais , Apoptose , Linhagem Celular Tumoral , Proteína Ligante Fas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Análise de Sobrevida , Fator de Transcrição AP-1/metabolismo , Receptor fas/metabolismo
16.
Angew Chem Int Ed Engl ; 58(21): 7035-7039, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-30895689

RESUMO

Atomically dispersed Zn-N-C nanomaterials are promising platinum-free catalysts for the oxygen reduction reaction (ORR). However, the fabrication of Zn-N-C catalysts with a high Zn loading remains a formidable challenge owing to the high volatility of the Zn precursor during high-temperature annealing. Herein, we report that an atomically dispersed Zn-N-C catalyst with an ultrahigh Zn loading of 9.33 wt % could be successfully prepared by simply adopting a very low annealing rate of 1° min-1 . The Zn-N-C catalyst exhibited comparable ORR activity to that of Fe-N-C catalysts, and significantly better ORR stability than Fe-N-C catalysts in both acidic and alkaline media. Further experiments and DFT calculations demonstrated that the Zn-N-C catalyst was less susceptible to protonation than the corresponding Fe-N-C catalyst in an acidic medium. DFT calculations revealed that the Zn-N4 structure is more electrochemically stable than the Fe-N4 structure during the ORR process.

17.
Chem Commun (Camb) ; 55(22): 3290-3293, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30810547

RESUMO

Here, we develop inert V2O3 oxide to enhance the HER activity of industrial Ni catalysts with the assistance of abundant metal/oxide interfaces. The as-synthesized Ni/V2O3 catalyst exhibits over 5 times the activity of a pure Ni sample due to the particle size control and metal/oxide interaction, and excellent durability as a result of oxide anchoring.

18.
Dig Dis Sci ; 64(1): 25-38, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30284136

RESUMO

Acute pancreatitis is a human disease with multiple causes that leads to autodigestion of the pancreas. There is sufficient evidence to support the key role of sustained increase in cytosolic calcium concentrations in the early pathogenesis of the disease. To clarify the mechanism of maintaining calcium homeostasis in the cell and pathological processes caused by calcium overload would help to research directly targeted therapeutic agents. We will specifically review the following: intracellular calcium homeostasis and regulation, the occurrence of calcium overload in acinar cells, the role of calcium overload in the pathogenesis of AP, the treatment strategy proposed for calcium overload.


Assuntos
Células Acinares/metabolismo , Pesquisa Biomédica/tendências , Sinalização do Cálcio , Cálcio/metabolismo , Pâncreas/metabolismo , Pancreatite/metabolismo , Células Acinares/efeitos dos fármacos , Células Acinares/patologia , Doença Aguda , Animais , Sinalização do Cálcio/efeitos dos fármacos , Homeostase , Humanos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/tratamento farmacológico , Pancreatite/etiologia , Pancreatite/patologia , Fatores de Risco
19.
Cell Physiol Biochem ; 47(1): 223-234, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29788015

RESUMO

BACKGROUND/AIMS: The transcription cofactor limb-bud and heart (LBH) is involved in embryonic development. However, its role in human lung cancer, especially lung adenocarcinoma (LUAD), remains unclear. METHODS: A public database and tissue microarray (TMA) were used to compare differences in LBH expression and its relationship with clinical characteristics. Tissue from an additional 70 LUAD patients with follow-up records was used to explore the correlation of LBH expression with prognosis. Cellular and molecular studies validated the role of LBH in LUAD growth and invasion. RESULTS: LBH was significantly down-regulated in lung cancer tissue samples and was correlated with the prognosis and clinical characteristics of lung cancer patients based on a public database and TMA. Survival analysis revealed that LBH-negative expression was associated with poor overall survival of LUAD patients (P = 0.021). Cox regression analysis showed that LBH expression status was a favorable independent prognostic factor (hazard ratio = 0.120, 95% confidence interval = 0.016-0.894, P = 0.039). LBH knockdown accelerated LUAD cell proliferation, migration, and invasion. Furthermore, bioinformatics analysis indicated that LBH was significantly related to the cell adhesion pathway. Western blot analysis confirmed that LBH could regulate the expression of integrin family members (integrin-α1, integrin-α2, integrin-α4, integrin-αv, and integrin-ß4). CONCLUSION: Our data suggest that LBH plays an important role in lung cancer. Importantly, LBH is an independent prognostic factor in LUAD and can attenuate cell growth and invasion. LBH may be a potential prognostic biomarker in LUAD patients.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/genética , Transativadores/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Análise de Sobrevida , Transativadores/análise
20.
Oncol Rep ; 39(3): 893-900, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328394

RESUMO

Tumor immunotherapy has been in development for more than a century. With the rapid developments in biotechnology research in recent years, immunotherapy has become a promising oncotherapy strategy after surgery, chemotherapy and radiotherapy. Cancer vaccines are a promising new treatment strategy and the application of nanotechnology in cancer vaccines, greatly enhances their effectiveness. Such applications indicate the bright prospects of tumor immunotherapy. The multifunctional nanomaterials used in cancer vaccines and their practical application in specific cancer vaccines are hereby reviewed. In addition, a preliminary analysis of the current and prospective use of nanotechnology with the purpose of providing solutions to cancer vaccine challenges is presented.


Assuntos
Vacinas Anticâncer/administração & dosagem , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Humanos
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