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1.
Aging (Albany NY) ; 11(24): 12568-12580, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881008

RESUMO

Previous studies investigated the prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with biliary tract cancer (BTC); however, the results remained controversial. Therefore, we conducted the current meta-analysis with the aim of clarifying the association between PD-L1 expression and prognosis as well as with several important clinicopathological features of BTC. We searched PubMed, Embase, and Web of Science for relevant studies. Studies that detected PD-L1 expression in tumor cells by using immunohistochemistry (IHC) were selected. Pooled hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the correlations. In total, 15 independent studies with 1,776 patients were included in this meta-analysis. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival (n=15, HR=1.79, 95% CI=1.55-2.07, p<0.001). The correlation between PD-L1 expression and disease-free survival was not significant (n=6, HR=1.38, 95% CI=1.00-1.91, p=0.051). In addition, no significant correlation was observed between PD-L1 expression and clinical features in patients with BTC. Our study results showed that PD-L1 expression could play a pivotal role as an effective factor of poor prognosis in patients with BTC.

2.
Am J Transl Res ; 11(5): 2765-2774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217852

RESUMO

Hepatitis B infection is a major global health problem and a primary cause of hepatocellular carcinoma (HCC). While various antiviral treatments have been explored, there is not yet a reliable method for preventing the progression of chronic hepatitis B infection into HCC. Hepatitis B virus X protein (HBx) plays a major role in viral replication, chronic inflammation and the pathogenicity of chronic liver disease. Modulation of purinergic receptors using their specific agonists has become a popular new strategy for modifying disease processes. In the present study, we investigated the involvement of the P2Y11 receptor using its specific antagonist NF157 in some key aspects of HBx-induced liver disease in human MIHA hepatocytes, including mitochondrial dysfunction due to compromised mitochondrial membrane potential (MMP), oxidative stress resulting from overproduction of reactive oxygen species (ROS) and decreased antioxidant glutathione (GSH), production of proinflammatory cytokines and chemokines such as interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and chemokine (C-X-C motif) ligand 2 (CXCL2), as well as activation of cellular signaling pathways including the p38/mitogen-activated protein kinase (p38/MAPK) and nuclear factor-κB (NF-κB) pathways. Our findings present a novel new strategy for the treatment and prevention of chronic liver infection and subsequent morbidities induced by HBx via specific antagonism of the P2Y11 purinergic receptor.

3.
Exp Ther Med ; 16(6): 5137-5143, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30546412

RESUMO

The aim of the present study was to analyze the clinicopathological characteristics presented in 9 cases of gastric calcifying fibrous tumor (CFT), and investigate the expressions and clinical implications of G protein-coupled estrogen receptor (GPER), estrogen receptor (ER) and vimentin in gastric CFTs. The clinical and pathological information of 9 patients with CFTs was investigated retrospectively. Subsequently, the expression of GPER, ER and vimentin were examined using immunohistochemistry, and a literature search for gastric CFT was conducted. The 9 patients were 40-71 years old with a mean age of 52.22 years, including 6 female and 3 male patients. Pathological features included dense hyalinized collagen fibers with a psammomatous body or dystrophic calcification, and the infiltration of scattered lymphocytes and plasma cells. Immunohistochemically, all cases expressed vimentin and GPER, whereas ER expression was negative. Using a database research, 25 studies regarding gastric CFT were identified, including 48 cases with a sex ratio (female:male) of 1.4:1. In addition, the number of female patients was twice the number of male patients in patients <50 years old, whereas the number was almost equal between women and men ≥50 years of age. Gastric CFT is a benign lesion with a good prognosis and a predilection for female patients, particularly premenopausal women. Estrogen may serve a role in this female predominance, and this may be mediated by GPER rather than ER.

4.
Exp Ther Med ; 10(4): 1311-1316, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26622484

RESUMO

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) has previously been demonstrated to be associated with the malignant transformation of numerous types of human cancer. The aim of the present study was to investigate the effect of EBP50 overexpression on pancreatic cancer and the underlying mechanism. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of EBP50 in human pancreatic cancer tissue specimens. Furthermore, pBK-CMV-HA-EBP50 and the pBK-CMV-HA vectors were transfected into pancreatic cancer cells and the effect of EBP50 upregulation on the proliferation and invasion of the cells was investigated. In addition, the effect of EBP50 overexpression on ß-catenin and E-cadherin expression was evaluated. The results revealed that overexpression of EBP50 suppressed cell growth and invasion in two human pancreatic cancer cell lines. Overexpression of EBP50 also suppressed ß-catenin expression and increased E-cadherin expression. Thus, the present study demonstrated that EBP50 inhibits pancreatic cancer cell growth and invasion through targeting the ß-catenin/E-cadherin pathway. The results suggest that EBP50 may function as a potential tumor suppressor and thus may serve as a potential therapeutic target.

5.
World J Gastroenterol ; 21(14): 4358-64, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25892887

RESUMO

AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer. METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients. Statistical analysis was performed by meta-analysis. Four randomized controlled trials met the inclusion criteria. RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80 (95%CI: 0.52-1.21, P = 0.29). The overall response rate of S-1 vs capecitabine was 0.94 (95%CI: 0.59-1.51, P = 0.93). Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia (OR = 0.99, 95%CI: 0.65-1.49, P = 0.94) and thrombocytopenia (OR = 0.72, 95%CI: 0.31-1.67, P = 0.44). The most frequent non-hematologic toxicities included nausea (OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome (OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001). CONCLUSION: The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Distribuição de Qui-Quadrado , Combinação de Medicamentos , Síndrome Mão-Pé/etiologia , Humanos , Razão de Chances , Ácido Oxônico/efeitos adversos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Taxa de Sobrevida , Tegafur/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
6.
Int J Clin Exp Med ; 8(1): 818-26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25785062

RESUMO

The major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism has been implicated in susceptibility to cancer. However, the results are inconsistent. The aim of this meta-analysis is to evaluate the association between the MICA-TM polymorphisms and cancer risk. All eligible case-control studies published up to August 20, 2014 were identified by searching PubMed, Web of Science, CNKI and Wanfang databases. The cancer risk associated with the MICA polymorphism was estimated for each study by odds ratios (OR) together with its 95% confidence interval (CI), respectively. 21 studies from 19 publications with 3620 cases and 4903 controls were included. Overall, no significant associations between the MICA-TM polymorphism and cancer risk were found (A4 allele: OR = 0.97, 95% CI: 0.88-1.07; A5 allele: OR = 0.91, 95% CI: 0.81-1.04; A5.1 allele: OR = 1.03, 95% CI: 0.89-1.18; A6 allele: OR = 1.05, 95% CI: 0.95-1.15; A9 allele: OR = 0.96, 95% CI: 0.80-1.14; A10 allele: OR = 0.88, 95% CI: 0.43-1.79; del: OR = 2.50, 95% CI: 0.73-8.58; A7 allele: OR = 0.93, 95% CI: 0.43-2.00). When stratified by ethnicity, similar results were observed among Asians; however, there were significant association in Caucasian population for A5 (OR = 0.77, 95% CI: 0.68-0.87) and A9 allele (OR = 0.75, 95% CI: 0.66-0.85). This meta-analysis suggests that the MICA-TM A5 and A9 alleles may be an important protective factor for cancer in Caucasian populations.

7.
PLoS One ; 9(10): e109625, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25286337

RESUMO

BACKGROUND: Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility. MATERIALS AND METHODS: Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models. RESULTS: Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11-1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08-1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR). CONCLUSION: This meta-analysis indicates that carriers of the STAT3 rs744166 'A' allele have a significantly greater risk of CD and UC, especially among Caucasians.


Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT3/genética , Humanos
8.
Exp Ther Med ; 8(3): 919-924, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25120624

RESUMO

Increasing evidence has demonstrated that ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) is involved in the malignant transformation of numerous human cancers. The present study investigated the involvement of EBP50 overexpression in the tumorigenicity of pancreatic cancer (PC). The results revealed that overexpression of EBP50 suppressed cell growth, promoted cell apoptosis and arrested G1-to-S phase progression in two human PC cell lines. Overexpression of EBP50 also suppressed B-cell lymphoma 2 (Bcl-2) expression. Furthermore, nude mouse tumor xenograft models were established by the subcutaneous injection of cell lines stably transfected with an EBP50-expressing plasmid. The in vivo data indicated that overexpression of EBP50 inhibited the growth of the PC tumors and induced cell apoptosis. Thus, the present study demonstrated that EBP50 overexpression induces growth inhibition and apoptosis in PC by decreasing Bcl-2 expression. The results suggest that EBP50 may function as a potential tumor suppressor in vivo and in vitro.

9.
World J Gastroenterol ; 19(26): 4127-36, 2013 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-23864775

RESUMO

AIM: To determine whether the human giant larvae homolog 1 gene (Hugl-1/Llg1/Lgl1) exerts tumor suppressor effects in esophageal cancer. METHODS: We constructed a Hugl-1 expression plasmid, pEZ-M29-Hugl1, for gene transfection. We transfected the pEZ-M29-Hugl1 plasmid into Eca109 esophageal cancer cell lines with Lipofectamine 2000 to overexpress Hugl-1. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the effects of the plasmid on Hugl-1 expression. In vitro cell proliferation and apoptosis were examined separately by cell counting Kit-8 (CCK-8) assay, flow cytometry, and Western blotting before and after the transfection of the plasmid into Eca109 cells. Cell cycle distribution was assessed with flow cytometry. The effect of Hugl-1 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice. Expression of Hugl-1 in xenograft tumor was analyzed by immunohistochemistry. The transferase-mediated dUTP nick end-labeling (TUNEL) technique was performed to detect and quantitate apoptotic cell. RESULTS: The transfection efficiency was confirmed with real-time RT-PCR and Western blotting. Our results show that compared with control groups the mRNA levels and protein levels of Hugl-1 in pEZ-M29-Hugl1-treated group were remarkably increased (P < 0.05). The CCK-8 assay demonstrated that the growth of cells overexpressing Hugl-1 was significantly lower than control cells. Cell cycle distribution showed there was a G0/G1 cell cycle arrest in cells overexpressing Hugl-1 (64.09% ± 3.14% vs 50.32% ± 4.60%, 64.09% ± 3.14% vs 49.13% ± 2.24%). Annexin V-fluorescein isothiocyanate revealed that apoptosis was significantly increased in cells overexpressing Hugl-1 compared with control group (17.33% ± 4.76% vs 6.90% ± 1.61%, 17.33% ± 4.76% vs 6.27% ± 0.38%). Moreover, we found that Hugl-1 changes the level of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax and the activation of both caspase-3 and caspase-9. With a TUNEL assay, we found that Hugl-1 markedly increased the apoptosis rate of Eca109 cells in vivo (60.50% ± 9.11% vs 25.00% ± 12.25%). It was shown that Hugl-1 represents a significantly more effective tumor suppressor gene alone in a xenograft tumor mouse model. This data suggest that Hugl-1 inhibited tumor growth and induced cell apoptosis in vivo. CONCLUSION: These results suggest that Hugl-1 induces growth suppression and apoptosis in a human esophageal squamous cell carcinoma cell line both in vitro and in vivo.


Assuntos
Apoptose , Carcinoma de Células Escamosas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Neoplasias Esofágicas/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Proteínas do Citoesqueleto/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fatores de Tempo , Transfecção , Carga Tumoral , Regulação para Cima
10.
World J Gastroenterol ; 19(8): 1306-13, 2013 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-23483729

RESUMO

AIM: To determine the effect and molecular mechanism of ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) in hepatocellular carcinoma (HCC). METHODS: Three human HCC cell lines, i.e., SM-MC7721, HepG2 and Hep3B, were used. We transfected the Pbk-CMV-HA-EBP50 plasmid into SMMC7721 cells with Lipofectamine 2000 to overexpress EBP50. Western blotting were performed to determine the effects of the plasmid on EBP50 expression and to detect the expression of ß-catenin and E-cadherin before and after the transfection of the plasmid into SMMC7721 cells. In vitro cell proliferation was assessed with a Cell Counting Kit-8 (CCK-8) assay. Cell cycle distribution was assessed with flow cytometry. Invasion and migration ability of before and after the transfection were determined with a transwell assay. Cell apoptosis was demonstrated with Annexin V-FITC. The effect of EBP50 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice. RESULTS: The transfection efficiency was confirmed with Western blotting (1.36 ± 0.07 vs 0.81 ± 0.09, P < 0.01). The CCK8 assay demonstrated that the growth of cells overexpressing EBP50 was significantly lower than control cells (P < 0.01). Cell cycle distribution showed there was a G0/G1 cell cycle arrest in cells overexpressing EBP50 (61.3% ± 3.1% vs 54.0% ± 2.4%, P < 0.05). The transwell assay showed that cell invasion and migration were significantly inhibited in cells overexpressing EBP50 compared with control cells (5.8 ± 0.8 vs 21.6 ± 1.3, P < 0.01). Annexin V-FITC revealed that apoptosis was significantly increased in cells overexpressing EBP50 compared with control cells (14.8% ± 2.7% vs 3.4% ± 1.3%, P < 0.05). The expression of ß-catenin was downregulated and E-cadherin was upregulated in cells overexpressing EBP50 compared with control cells (0.28 ± 0.07 vs 0.56 ± 0.12, P < 0.05; 0.55 ± 0.08 vs 0.39 ± 0.07, P < 0.05). In vivo tumor growth assay confirmed that up-regulation of EBP50 could obviously slow the growth of HCC derived from SMMC7721 cells (28.9 ± 7.2 vs 70.1 ± 7.2, P < 0.01). CONCLUSION: The overexpression of EBP50 could inhibit the growth of SMMC7721 cells and promote apoptosis by modulating ß-catenin, E-cadherin. EBP50 may serve as a potential therapeutic target in HCC.


Assuntos
Caderinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfoproteínas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , beta Catenina/metabolismo , Animais , Antígenos CD , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Fosfoproteínas/genética , Transdução de Sinais , Trocadores de Sódio-Hidrogênio/genética , Fatores de Tempo , Transfecção , Carga Tumoral
11.
Biochem Biophys Res Commun ; 421(3): 627-33, 2012 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-22546556

RESUMO

Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC(50)=75 µM). This cytotoxicity was reflected by cell cycle arrest at G(2)/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Noscapina/farmacologia , Animais , Antineoplásicos/uso terapêutico , Caspase 3/metabolismo , Caspase 9/metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Citocromos c/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Noscapina/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/metabolismo
12.
J Mol Histol ; 43(5): 517-26, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22622406

RESUMO

Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a putative tumor suppressor that is correlated with many human cancers. However, the function of EBP50 in pancreatic cancer (PC) has not been described. In this paper, the EBP50 expression level in PC tissues was characterized. In vitro, the effects of EBP50 down-regulation by siRNA in PC-2 and MiaPaCa-2 cells were evaluated. In addition, possible mechanisms that mediate the influence of EBP50 were examined. Our results show that the EBP50 expression pattern changes during transformation as there is a loss of the normal apical membrane distribution and an ectopic cytoplasmic over-expression of EBP50; furthermore, the EBP50 expression level is subsequently decreased during malignant progression. Down-regulation of EBP50 promoted cancer cell proliferation, increased the colony-forming ability of cells and accelerated the G1-to-S progression. Additionally, the loss of EBP50 accentuated ß-catenin activity, increased cyclin E and phosphorylated Rb expression, and attenuated p27 expression compared to control cells. Our results suggest that EBP50 may function as a potential tumor suppressor.


Assuntos
Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Neoplasias Pancreáticas , Fosfoproteínas , Trocadores de Sódio-Hidrogênio , Linhagem Celular Tumoral , Ciclina E/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Pontos Quânticos , RNA Interferente Pequeno , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , beta Catenina/metabolismo
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