Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Toxicol Lett ; 319: 49-57, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31693926

RESUMO

Blast lung injury is associated with high morbidity and mortality. Vaporized perfluorocarbon (PFC) inhalation has been reported to attenuate acute respiratory distress syndrome in humans and animal models. However, the effect of vaporized PFC on blast lung injury is still unknown. In this study, we investigated the protective effects and potential underlying mechanisms of action of vaporized PFC on blast lung injury in a canine model. This was a prospective, controlled, animal study in adult male hybrid dogs randomized to sham, blast (B), blast plus mechanical ventilation (B + M), and blast plus PFC (B + P) groups. All groups except for the sham were exposed to blast wave. The B + P group was treated with vaporized PFC for 1.5 h followed by 5.5 h mechanical ventilation. B + M group received 7.5 h mechanical ventilation and B group was observed for 7.5 h. Blast lung injury was induced using a shock tube. Blood gas, inflammatory cytokines, and oxidative stress were measured. Expression of nuclear factor (NF)-κB activation, mitogen-activated protein kinase (MAPK) and nuclear factor, erythroid 2 like 2 (Nrf2) were measured using western blot. Lung injury observed after blast exposure was marked by increased histopathological scores, ratio of lung wet to dry weight. PFC treatment attenuated blast lung injury as indicated by histopathological scores and ratio of lung wet to dry weight. PFC treatment downregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), and upregulated superoxide dismutase (SOD) activity. PFC also suppressed expression of MAPK/NF-κB and Nrf2 protein levels. Our results suggest that PFC attenuated blast-induced acute lung injury by inhibiting MAPK/NF-κB activation and inducing Nrf2 expression in dogs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31746308

RESUMO

BACKGROUND AND PURPOSE: Although limited by side effects and development of resistance, doxorubicin still represent the most common chemotherapy for breast cancer. Thus, the identification of critical molecules to alleviate doxorubicin resistance is crucial. Here, we provide a molecular rationale for the breast cancer patients potentially benefitting from doxorubicin based on the expression levels of SIRT1, a identified member of longevity genes. METHODS: SIRT1-overexpressed and SIRT1-knockdown breast cancer cells were established to investigate the functions of SIRT1 in regulating doxorubicin resistance both in vitro and in vivo. Cell proliferation was analyzed via CCK8 assay, cell apoptosis was studied by TUNEL anslysis. Molecule interaction was analyzed through co-immunoprecipitation and immunofluorescence techniques. Sensibility to doxorubicin was assessed in vivo through nude mice tumorigenicity experiment. RESULTS: First, SIRT1 was found higher-expressed in breast cancer doxorubicin-resistant cells MCF-7/ADR than that in doxorubicin- sensitive cells MCF-7. Moreover, SIRT1-knockdown MCF-7/ADR cells showed higher susceptible to doxorubicin both in vitro and in vivo models, whereas overexpressing of SIRT1 obviously inhibited this phenotype. Accordingly, SIRT1 was found interacted with Akt, consequently promoted the activity of Akt in MCF-7/ADR cells in vitro and positively correlated with the expression of P-Akt in vivo. Reversion the activity of Akt partially downturned the doxorubicin-resistant effects mediated by SIRT1. CONCLUSION: This investigation suggested the value of SIRT1 as biomarker of response to doxorubicin, leading to the development of new tools for the management of breast cancer patients.

3.
Oncol Lett ; 18(4): 3581-3590, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31516572

RESUMO

The sensitivity and utility of liquid biopsy in clinical practice requires some improvement. The aim of the present study was to improve the detection of epidermal growth factor (EGFR) and cellular tumor antigen p53 (TP53) mutations in liquid biopsies from patients with advanced non-small cell lung cancer (NSCLC) by combining plasma, sputum and urine samples under the same sequencing platform. Plasma, sputum and urine samples, and tumor tissues were obtained from 50 patients with NSCLC and were analyzed using next-generation sequencing. The sensitivity of EGFR-sensitive mutation detection was 84% in plasma, 63% in sputum, 28% in urine, and 91% when combining the three liquid samples (P<0.001). The sensitivity of TP53 mutation detection increased from 87% in plasma to 94% when the three samples were combined (P<0.001). The sensitivity of EGFR or TP53 mutations detection was higher in patients with multiple metastatic sites compared with patients ≤1 metastatic site. In addition, the progression free survival (PFS) rates obtained following analysis of the three samples independently in patients with EGFR sensitizing mutations were similar, and were 9.0 months in the tissue sample, 7.5 months in plasma, 7.9 months in the sputum and 7.3 months in urine (P=0.721). The PFS of patients with TP53 mutations was shorter compared with patients without TP53 mutations and was as follows: Tissue, 8.2 months compared with 10.2 months (P=0.412); plasma, 8.4 months compared with 10.2 months (P=0.466); sputum, 8.3 months compared with 9.1 months (P=0.904); and when combined, 8.8 months compared with 10.3 months (P=0.599). The combination of plasma, sputum and urine increased the detection of EGFR or TP53 mutation with higher sensitivity, and may improve the predictive value of personalized treatment.

4.
BMC Infect Dis ; 19(1): 694, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387539

RESUMO

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA. METHODS: The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit. RESULTS: A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5µg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively. CONCLUSIONS: The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis. TRIAL REGISTRATION: NCT03027089 . Registered 20 January 2017.


Assuntos
Isotipos de Imunoglobulinas/sangue , Aspergilose Pulmonar/diagnóstico , Adulto , Idoso , Anticorpos Antifúngicos/sangue , Aspergillus/imunologia , Doença Crônica , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Aspergilose Pulmonar/sangue , Aspergilose Pulmonar/etiologia , Curva ROC , Sensibilidade e Especificidade
5.
Tissue Cell ; 51: 39-48, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29622086

RESUMO

Karyopherin ß1 (Kpnß1), also known as importin-ß, is part of the karyopherin superfamily of nuclear transport proteins. Kpnß1 is an oncogene that is overexpressed in various human cancers. Recent studies have showed that Kpnß1 is one of the leading causes of cancer-related deaths in the world. However, the role of Kpnß1 in non-small cell lung cancer (NSCLC) remains uncertain. In this study, we used western blotting to show that Kpnß1 expression is higher in lung-cancer tissues and cells, and immunohistochemistry analysis revealed that Kpnß1 was significantly associated with the clinicopathological features of NSCLC. Kaplan-Meier analysis showed that elevated Kpnß1 expression correlated with a poor prognosis in NSCLC patients. Serum starvation-refeeding experiments and Kpnß1-shRNA transfection assays revealed that elevated Kpnß1 expression promoted cell proliferation and reduced sensitivity to cis-diamminedichloroplatinum. Immunoprecipitation assays showed that Kpnß1 interacts with PI3 K to activate the PI3-kinase/AKT pathway, leading to enhanced cell survival and drug resistance in NSCLC cells. Collectively, our findings suggest that Kpnß1 plays a significant role in NSCLC progression and chemoresistance. Our study provides new insights for targeted therapy to treat NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Pulmonares/patologia , beta Carioferinas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia
6.
Microb Drug Resist ; 24(9): 1259-1270, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29489445

RESUMO

Acinetobacter baumannii is an important pathogen of nosocomial infections. Nosocomial outbreaks caused by antibiotic-resistant A. baumannii remain a significant challenge. Understanding the antibiotic resistance mechanism of A. baumannii is critical for clinical treatment. The purpose of this study was to determine the whole-genome sequence (WGS) of an extensively drug-resistant (XDR) A. baumannii strain, XDR-BJ83, which was associated with a nosocomial outbreak in a tertiary care hospital of China, and to investigate the antibiotic resistance mechanism of this strain. The WGS of XDR-BJ83 was performed using single-molecule real-time sequencing. The complete genome of XDR-BJ83 consisted of a 4,011,552-bp chromosome and a 69,069-bp plasmid. The sequence type of XDR-BJ83 was ST368, which belongs to clonal complex 92 (CC92). The chromosome of XDR-BJ83 carried multiple antibiotic resistance genes, antibiotic efflux pump genes, and mobile genetic elements, including insertion sequences, transposons, integrons, and resistance islands. The plasmid of XDR-BJ83 (pBJ83) was a conjugative plasmid carrying type IV secretion system. These results indicate that the presence of multiple antibiotic resistance genes, efflux pumps, and mobile genetic elements is likely associated with resistance to various antibiotics in XDR-BJ83.


Assuntos
Acinetobacter baumannii/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , China , Cromossomos Bacterianos/genética , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Elementos de DNA Transponíveis/genética , Humanos , Plasmídeos/genética , Centros de Atenção Terciária , beta-Lactamases/genética
7.
Genet Test Mol Biomarkers ; 21(11): 649-657, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28872921

RESUMO

OBJECTIVE: Long noncoding RNAs (lncRNAs) are becoming promising biomarker candidates in various diseases as assessed via sequencing technologies. Sepsis is a life-threatening disease without ideal biomarkers. The aim of this study was to investigate the expression profile of lncRNAs in the peripheral blood of sepsis patients and to find potential biomarkers of sepsis. METHODS: A lncRNA expression profile was performed using peripheral blood from three sepsis patients and three healthy volunteers using microarray screening. The differentially expressed lncRNAs were validated by real-time quantitative polymerase chain reaction (qRT-PCR) in a further set of 22 sepsis patients and 22 healthy volunteers. RESULTS: Among 1316 differentially expressed lncRNAs, 771 were downregulated and 545 were upregulated. Results of the qRT-PCR were consistent with the microarray data. lncRNA ENST00000452391.1, uc001vji.1, and uc021zxw.1 were significantly differentially expressed between sepsis patients and healthy volunteers. Moreover, lncRNA ENST00000504301.1 and ENST00000452391.1 were significantly differentially expressed between sepsis survivors and nonsurvivors. CONCLUSION: The lncRNA expression profile in the peripheral blood of sepsis patients significantly differed from that of healthy volunteers. Circulating lncRNAs may be good candidates for sepsis biomarkers.


Assuntos
RNA Longo não Codificante/genética , Sepse/diagnóstico , Sepse/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , China , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Dados Preliminares , Prognóstico , RNA Longo não Codificante/fisiologia , RNA Mensageiro/genética , Sepse/metabolismo
8.
Mol Med Rep ; 16(4): 4159-4164, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765911

RESUMO

To win the war against lung cancer, the molecular mechanisms underlying its oncogenesis and metastasis must be identified in order to develop novel diagnosis and treatment strategies. We previously identified a novel gene, namely lung cancer metastasis related protein 1 (LCMR1; GenBank accession no. AY148462), which was demonstrated to be overexpressed in non­small­cell lung cancer. LCMR1 expression was significantly associated with clinical stage. To further understand the mechanism of LCMR1 in lung cancer, the present study screened a cDNA library from the lung cancer cell line 95D for proteins interacting with LCMR1 by yeast two­hybrid assay, and the protein DEK was identified. Co­immunoprecipitation and glutathione S­transferase pull­down assays were performed to confirm the interaction between LCMR1 and DEK in vivo and in vitro. The results demonstrated that the interaction was mediated primarily by the N­terminal region of DEK, suggesting that LCMR1 may be involved in the regulation of cell apoptosis. Using RNA interference, DEK and LCMR1 were demonstrated to cooperate in the inhibition of apoptosis in lung cancer cells, and this effect was associated with the induced myeloid leukemia protein cell differentiation protein 1 pathway. The present findings suggest that LCMR1 might serve as a potential molecular target for lung cancer therapy.


Assuntos
Apoptose , Proteínas Cromossômicas não Histona/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Complexo Mediador/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Ligação Proteica
9.
PLoS One ; 12(3): e0173884, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28323898

RESUMO

BACKGROUND AND OBJECTIVE: Blast lung injury is a common type of blast injury and has very high mortality. Therefore, research to identify medical therapies for blast injury is important. Perfluorocarbon (PFC) is used to improve gas exchange in diseased lungs and has anti-inflammatory functions in vitro and in vivo. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action. STUDY DESIGN AND METHODS: A549 alveolar epithelial cells exposed to blast waves were treated with and without PFC. Morphological changes and apoptosis of A549 cells were recorded. PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA or protein levels of IL-1ß, IL-6 and TNF-α. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels were detected. Western blot was used to quantify the expression of NF-κB, Bax, Bcl-2, cleaved caspase-3 and MAPK cell signaling proteins. RESULTS: A549 cells exposed to blast wave shrank, with less cell-cell contact. The morphological change of A549 cells exposed to blast waves were alleviated by PFC. PFC significantly inhibited the apoptosis of A549 cells exposed to blast waves. IL-1ß, IL-6 and TNF-α cytokine and mRNA expression levels were significantly inhibited by PFC. PFC significantly increased MDA levels and decreased SOD activity levels. Further studies indicated that NF-κB, Bax, caspase-3, phospho-p38, phosphor-ERK and phosphor-JNK proteins were also suppressed by PFC. The quantity of Bcl-2 protein was increased by PFC. CONCLUSION: Our research showed that PFC reduced A549 cell damage caused by blast injury. The potential mechanism may be associated with the following signaling pathways: 1) the signaling pathways of NF-κB and MAPK, which inhibit inflammation and reactive oxygen species (ROS); and 2) the signaling pathways of Bcl-2/Bax and caspase-3, which inhibit apoptosis.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Traumatismos por Explosões/tratamento farmacológico , Traumatismos por Explosões/metabolismo , Fluorcarbonetos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Lesão Pulmonar Aguda/patologia , Apoptose/efeitos dos fármacos , Traumatismos por Explosões/patologia , Caspase 3/metabolismo , Forma Celular/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Biológicos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
10.
Psychooncology ; 26(9): 1347-1353, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27862617

RESUMO

OBJECTIVE: Increasing evidence suggests that psychological factors are involved in tumor progression. This study investigated the influence of anxiety and serum catecholamines (CAs) on the prognosis of hepatocellular carcinoma (HCC). METHOD: We enrolled 110 HCC patients who underwent tumor resection at the Affiliated Hospital of Nantong University, China, in this long-term investigation between 2005 and 2009. We evaluated anxiety using the Hamilton Anxiety Rating Scale (HAMA) and analyzed CA levels using an ELISA kit. We then assessed the association of each of them with overall survival (OS) and time to recurrence (TTR), as well as with other clinical variables. RESULTS: The HAMA scores significantly correlated with metastasis (P = 0.015), hepatitis B surface antigens (HBsAg) (P = 0.045), and the tumor-node-metastasis stage (P = 0.032), whereas the CA levels also significantly associated with tumor differentiation (P < 0.001). Univariate and multivariate analyses revealed that HAMA scores and CA levels were significant predictors of OS and TTR in HCC patients, with high levels of each being strongly correlated with poor prognosis. CONCLUSION: The HAMA scores and the CA levels were elevated in HCC patients and correlated with OS and TTR, suggesting that they are candidate prognostic markers of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/psicologia , Catecolaminas/sangue , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos
11.
Dig Dis Sci ; 62(1): 133-142, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27921263

RESUMO

BACKGROUND: Protein phosphatase 1γ (PP1γ), as a member of the protein phosphatase 1 family, may be involved in regulation of multiple cellular processes, such as mitosis, cell survival, and apoptosis. However, little is known about the underlying mechanisms by which PP1γ regulates hepatocellular carcinoma development. AIM: We investigated the expression profile of PP1γ in hepatocellular carcinoma (HCC) cell lines and human HCC specimens, as well as its potential prognostic significance in HCC. METHODS: PP1γ expression profile was detected in 94 HCC specimens using immunohistochemistry. PP1γ levels in HCC cells were downregulated by small interfering RNA (siRNA) transfection. Cell cycle progression and proliferation status of HCC cells and the effectiveness of doxorubicin were evaluated by flow cytometry and CCK-8 assay. The levels of PP1γ, CyclinD1, PCNA, Mdmx, p53, p21, and active caspase-3 were evaluated by Western blot analysis. RESULTS: PP1γ was upregulated in tumorous specimens, compared with adjacent nontumorous tissues. Univariate and multivariate survival analyses were conducted to determine the prognostic significance of PP1γ in HCC. The expression pattern of PP1γ was positively correlated with tumor size, histological grade, Ki-67 expression, and poor prognosis in HCC. In addition, depletion of PP1γ by siRNA could inhibit cell proliferation, resulted in G1 phase arrest, and attenuated resistance to doxorubicin in Huh7 cells. CONCLUSIONS: PP1γ is upregulated in HCC cell lines and HCC specimens, promotes cancer cell proliferation through regulation of p53, and may be a potential target for treatment of HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Proteína Fosfatase 1/metabolismo , Adulto , Idoso , Antibióticos Antineoplásicos , Apoptose , Western Blotting , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas Nucleares/metabolismo , Prognóstico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Modelos de Riscos Proporcionais , Proteína Fosfatase 1/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA Interferente Pequeno , Ensaio Tumoral de Célula-Tronco , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
12.
Tumour Biol ; 37(11): 14615-14628, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27619678

RESUMO

Dysregulation of TRIM44 has been reported to be involved in tumorigenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the clinicopathological and biological significance of TRIM44 in HCC. We found that TRIM44 mRNA and protein expression was upregulated in HCC compared with matched normal tissues. Intriguingly, we also found that TRIM44 expression was significantly correlated with tumor size (P < 0.001), vascular invasion (P < 0.001), intrahepatic metastasis (P < 0.001), distant metastasis (P < 0.001), and Ki-67 expression (P < 0.001). Kaplan-Meier analysis showed that high TRIM44 staining was significantly correlated with shorter overall survival (P < 0.001). TRIM44 was an independent predictor of overall survival in patients with HCC. Furthermore, we found that ectopic expression of TRIM44 could promote cell proliferation via accelerating the G1/S-phase transition in HCC. Moreover, overexpression of TRIM44 could enhance the invasive and migratory capacity of HCC cells. Meanwhile, we found that high expression of TRIM44 could enhance resistance of HCC cells to doxorubicin via accelerating NF-κB activation. In conclusion, our results suggest that TRIM44 may be a novel prognostic indicator and potential therapeutic target of HCC.


Assuntos
Carcinoma Hepatocelular/secundário , Proteínas de Transporte/metabolismo , Movimento Celular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/patologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Ciclo Celular , Doxorrubicina , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais Cultivadas
13.
Exp Mol Pathol ; 101(2): 176-186, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27498047

RESUMO

OBJECTIVES: The receptor for activated protein kinase C (RACK1) is a scaffold protein involved in multiple intracellular signal pathways. Previous studies have shown that RACK1 is associated with the progression of multiple cancer types, including hepatocellular carcinoma and gastric cancer. However, the role of RACK1 in human pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: In this study, the expression of RACK1 was evaluated by Western blot analysis in 8 paired fresh PDAC tissues and immunohistochemistry on 179 paraffin-embedded slices. Then, we used Fisher exact test to analyze the correlation between RACK1 expression and clinicopathological characteristics. Starvation and re-feeding assay was used to assess cell cycle. Western blot, CCK8, flow cytometry assays, and colony formation analyses demonstrated that RACK1 played an essential role in PDAC development. Annexin-V/PI apoptotic assay and western blot showed that RACK1 was involved in regulating the apoptosis of PDAC cells. RESULTS: RACK1 was highly expressed in PDAC tissues and cell lines and was significantly associated with multiple clinicopathological factors. Univariate and multivariate analyses showed that high RACK1 expression was identified to be an independent prognostic factor for PDAC patients' survival. In vitro, serum starvation-refeeding experiment suggested that RACK1 was upregulated in proliferating PDAC cells, together with the percentage of cells at the S phase, and was correlated with the expression of Cyclin D1. Moreover, Overexpression of RACK1 facilitated the proliferation and cell cycle progression of PDAC cells, while downregulation of RACK1 induced growth impairment, G1/S cell cycle arrest and apoptosis in PDAC cells. Silencing RACK1 decreased bcl-2 expression, increased cleaved caspase3 expression level and induced the apoptosis of PDAC cells. CONCLUSIONS: Our results suggest that RACK1 could play an important role in the tumorigenesis of PDAC and serve as a potential therapeutical target in PDAC treatment.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Receptores de Superfície Celular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptores de Quinase C Ativada , Resultado do Tratamento , Regulação para Cima
14.
Hum Pathol ; 57: 182-192, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27498060

RESUMO

Disheveled-axin (DIX) domain containing 1 (DIXDC1), a protein containing a coiled-coil domain and a DIX domain, is involved in the progression of multiple cancers. However, the role of DIXDC1 in human pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we investigated the role and prognostic value of DIXDC1 in the development of human PDAC. Western blot analysis revealed that DIXDC1 was highly expressed in PDAC tissues and cell lines. Immunohistochemistry on 165 paraffin-embedded sections showed that high expression of DIXDC1 was significantly correlated with tumor size (P = .002), histological differentiation (P = .001), tumor node metastasis (TNM) stage (P = .001), and the proliferation marker Ki-67 (P = .000). Importantly, Kaplan-Meier analysis revealed that high expression of DIXDC1 was obviously correlated with worsened overall survival (P < .001). In vitro, using serum starvation-refeeding experiments, our results suggested that DIXDC1 was up-regulated in proliferating PDAC cells, together with the percentage of cells at the S phase, and was correlated with the expression of cyclin D1. In addition, depletion of DIXDC1 decreased PCNA and cyclin D1 levels. Accordingly, CCK-8, colony formation, and flow cytometry analyses revealed that knocking down DIXDC1 induced growth impairment and G1/S cell cycle arrest in PDAC cells, while overexpression of DIXDC1 led to accelerated cell proliferation and cell cycle progression. On the basis of these results, we propose that DIXDC1 could play an important role in the tumorigenesis of PDAC and serve as a potential therapeutical target to prevent PDAC progression.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Proliferação de Células , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/secundário , Diferenciação Celular , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Proteínas dos Microfilamentos/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Carga Tumoral , Regulação para Cima
15.
Exp Cell Res ; 346(2): 157-66, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27397581

RESUMO

YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/patologia , Proteína 1 de Ligação a Y-Box/metabolismo , Adesão Celular/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/farmacologia , Análise Multivariada , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo
16.
Leuk Res ; 45: 59-67, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27101149

RESUMO

The chaperonin containing t-complex polypeptide 1 (CCT) is known to mediate folding of proteins. CCT, subunit 8 (CCT8), is the θ subunit of CCT complex chaperonin. CCT8 has been reported to be dysregulated in several tumor tissues. In this study, we investigated the role of CCT8 in B-cell non-Hodgkin's lymphoma (NHL). Clinically, the expression levels of CCT8 in reactive lymphoid hyperplasia (RLH) and B-cell NHL specimens were investigated using immunohistochemical analysis. We found that CCT8 was highly expressed in proliferating germinal center cells compared with the quiescent cells of the follicular mantle zone. Furthermore, CCT8 was highly expressed in progressive lymphomas than in indolent lymphomas. Kaplan-Meier curve showed that high expression of CCT8 was significantly associated with shorter overall survival in patients with diffuse large B-cell lymphoma. Moreover, we demonstrated that CCT8 could promote the proliferation of B-cell NHL cells. In addition, we found that CCT8 could accelerate the G1/S transition in B-cell NHL. Finally, we demonstrated that overexpression of CCT8 could reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype. Our study may shed new insights into the important role of CCT8 in cancer development.


Assuntos
Chaperonina com TCP-1/fisiologia , Linfoma de Células B/química , Idoso , Adesão Celular , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Chaperonina com TCP-1/análise , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Centro Germinativo/química , Centro Germinativo/patologia , Humanos , Imuno-Histoquímica/métodos , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
17.
Mol Med Rep ; 13(4): 3700-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26935986

RESUMO

Acute lung injury (ALI)/ARDS is a critical clinical syndrome with high mortality, and the effective therapeutic methods for the treatment remain limited. Previous studies have indicated that liquid ventilation with perfluorocarbon (PFC) may be advantageous over conventional mechanical ventilation in the treatment of ALI/ARDS. Additionally, PFC inhibits the inflammatory response caused by ALI/ARDS. However, the anti-inflammatory mechanism remains to be completely elucidated. In the present study, the aim was to determine the anti­inflammatory mechanism of PFC and the association with microRNA (miR). PFC was used to modulate LPS­induced A549 cells, with the cells divided into four groups: Untreated control group; LPS group, treated with 10 µg/ml LPS; LPS+PFC group, treated with 10 µg/ml LPS and PFC; and PFC group, treated with PFC alone. The intercellular adhesion molecule­1 (ICAM­1) mRNA and protein expression levels of each group were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blotting, respectively. A549 cells were transfected with miR­17­3p mimics, miR­17­3p inhibitors or negative controls to observe the alterations in the anti­inflammatory effects of PFC. A dual luciferase reporter gene assay was used to determine whether ICAM­1 is a target gene of miR­17­3p. PFC was observed to attenuate the mRNA and protein expression levels of ICAM­1 in LPS­induced A549 cells, with no significant effect on the untreated A549 cells. miR­17­3p was demonstrated to be regulated by PFC. Transfection with miR­17­3p mimics enhanced the anti­inflammatory effects of PFC, whereas the miR­17­3p inhibitor weakened the anti­inflammatory effects of PFC at early time points. To conclude, the current study indicates that ICAM­1 was a target gene of miR­17­3p, and PFC has anti­inflammatory effects. Additionally, the present study is the first report, to the best of our knowledge, that PFC is able to attenuate ICAM-1 expression in LPS-induced A549 cells by increasing miR-17-3p expression.


Assuntos
Fluorcarbonetos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , Regiões 3' não Traduzidas , Células A549 , Western Blotting , Genes Reporter , Humanos , Molécula 1 de Adesão Intercelular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
18.
J Cancer Res Clin Oncol ; 142(3): 561-72, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26498772

RESUMO

BACKGROUND: The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin ß1 (Kpnß1) is a member of the Karyopherin ß superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnß1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnß1 in diffuse large B-cell lymphoma (DLBCL). METHODS: The prognostic value of Kpnß1 expression was evaluated using immunohistochemical staining. The role of Kpnß1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. RESULTS: We demonstrated that Kpnß1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnß1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnß1 was significantly associated with shorter overall survival. In addition, Kpnß1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnß1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. CONCLUSIONS: Patients with tumors highly expressing Kpnß1 have poorer overall survivals. Kpnß1 interacts with p65 and enhances CAM-DR.


Assuntos
Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , beta Carioferinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Adesão Celular/genética , Linhagem Celular Tumoral , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Regulação para Cima , beta Carioferinas/metabolismo
19.
Tumour Biol ; 37(1): 1369-78, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26298725

RESUMO

Recent studies have identified that thyroid hormone receptor-interacting protein 6 (TRIP6) is implicated in tumorigenesis. However, the functional role of TRIP6 in non-Hodgkin's lymphoma (NHL) has never been elucidated. In this study, we demonstrated that TRIP6 is reversely correlated with the clinical outcomes of NHL patients. Western blot and immunohistochemical analysis revealed that TRIP6 expression is lower in indolent lymphoma than in progressive lymphoma. Kaplan-Meier survival curves indicated that the upregulation of TRIP6 is significantly associated with poor overall survival. Moreover, patients with higher expression of TRIP6 are prone to shorter time to recurrence. Furthermore, we also found that TRIP6 can promote the proliferation of NHL cells via regulating cell cycle progression. In addition, adhesion of lymphoma cells to fibronectin (FN) decreased TRIP6 expression, which led to the upregulation of nuclear p27(Kip1) expression by decreasing phosphorylation of p27(Kip1) at T157. Importantly, overexpression of TRIP6 can reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype in NHL. In summary, these results suggest that TRIP6 is a novel prognostic indicator for NHL patients and may shed new insights into the important role of TRIP6 in cancer development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Proteínas com Domínio LIM/metabolismo , Linfoma não Hodgkin/metabolismo , Fatores de Transcrição/metabolismo , ATPases Associadas a Diversas Atividades Celulares , Idoso , Adesão Celular , Ciclo Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Citometria de Fluxo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Fenótipo , Prognóstico , Complexo de Endopeptidases do Proteassoma , Resultado do Tratamento
20.
Cell Physiol Biochem ; 37(5): 1830-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26584283

RESUMO

BACKGROUND/AIMS: Mesenchymal stem cell (MSC) based therapies may be useful for treating acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC) secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. METHODS: Human alveolar epithelial cells (AEC) and primary human small airway epithelial cells (SAEC) were subjected to lipopolysaccharide (LPS) with or without the presence of hUC-MSC-conditioned medium (CM). Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC). Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. RESULTS: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. CONCLUSION: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antracenos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/toxicidade , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Fosforilação/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Espectrometria de Massas em Tandem , Cordão Umbilical/citologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA