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1.
Int J Biochem Cell Biol ; 90: 1-8, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28694105

RESUMO

Centrosomal proteins have been implicated in the progression of human diseases. CEP131 plays important roles in centrosome duplication and genome stability, but its role in cancers remains largely unknown. Here, we showed that CEP131 expression was increased in hepatocellular carcinoma (HCC), compared to the paracarcinoma tissues, at both mRNA and protein levels. High CEP131 expression was closely associated with tumor size (P=0.020), tumor capsule (P=0.043), TNM stage (P=0.007) and tumor differentiation (P=0.019). Furthermore, patients with high expression of CEP131 were accompanied with worse overall and disease-free survivals in our and TCGA cohorts consisting of a total of 802 cases. The prognostic value of CEP131 was further confirmed by stratified survival analysis. Multivariate cox regression model indicated that CEP131 was an independent factor for overall survival (hazard ratio=1.762, 95% confident interval: 1.443-2.151, P<0.001). In vitro data demonstrated that nucleophosmin (NPM) physically bound to CEP131 and maintained its protein stability. Overexpression of CEP131 in HCC cell lines enhanced cell proliferation and migration, whereas the knockdown of CEP131 led to the opposite phenotypes. Further studies demonstrated that CEP131 exhibited oncogenic activity via activation of PI3K/AKT signaling pathway. Taken together, our findings suggest CEP131 serves as a potential prognostic biomarker in HCC, and functions as an oncogene in this deadly disease.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Movimento Celular , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Proteínas dos Microtúbulos/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas do Citoesqueleto , Ativação Enzimática , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Nucleofosmina , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
2.
Oncotarget ; 7(25): 38052-38063, 2016 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-27191260

RESUMO

HEY2, a bHLH transcription factor, has been implicated in the progression of human cancers. Here, we showed that HEY2 expression was markedly increased in HCC, compared with the adjacent nontumorous tissues. High HEY2 expression was closely correlated with tumor multiplicity, tumor differentiation and TNM stage. Kaplan-Meier analyses revealed that HEY2 expression was significantly associated with poor overall and disease-free survival in a training cohort of 361 patients with HCC. The prognostic implication of HEY2 was validated in another cohort of 169 HCC patients. Multivariate Cox regression model indicated HEY2 as an independent factor for overall survival in HCC (Hazard ratio = 1.645, 95% confident interval: 1.309-2.067, P<0.001). We also demonstrated that HEY2 expression was inhibited by miR-137. In clinical samples, HEY2 expression was reversely associated to miR-137 expression. Furthermore, overexpression of HEY2 increased cell viabilities, colony formation and cell migration, whereas knockdown of HEY2 resulted in the opposite phenotypes. Collectively, our data suggest HEY2 as a promising biomarker for unfavorable outcomes and a novel therapeutic target for the clinical management of HCC.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Repressoras/metabolismo , Resultado do Tratamento
3.
Eur J Oncol Nurs ; 19(2): 136-41, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25465773

RESUMO

PURPOSE OF THE RESEARCH: To compare the efficacy of dioctahedral smectite and iodine glycerin (DSIG) cream with topical mouth rinse (composed of saline, gentamicin and Vitamin B12) in treatment of chemotherapy induced oral mucositis (OM). METHODS AND SAMPLE: A total of 130 intensive chemotherapy or stem cells transplantation induced OM patients were recruited. Among these patients, 67 patients received topical mouth rinse and 63 patients received DSIG cream treatment. The OM would be treated on the OM appearance and sustained for 5 days. OM severity was measured daily using The American Oncology Nursing Society recommended Oral Assessment Guideline (OAG) score system. KEY RESULTS: Compared with topical mouth rinse treatment, a significant lower OAG score was observed in DSIG cream treated patients. Specifically, the OAG scores were respectively 12.1 ± 1.1, 12.0 ± 1.2, 11.3 ± 1.3 and 10.4 ± 1.3 from day 2 to day 5 in topical mouth rinse treatment subgroup. Correspondingly, the OAG scores were respectively 10.2 ± 1.0, 9.3 ± 0.9, 8.5 ± 0.6 and 8.0 ± 0.2 for DSIG cream treatment subset (all P < 0.05). Importantly, compared with topical mouth rinse treatment, the DSIG cream significantly shortened OM repair time (4.68 ± 0.98 vs. 8.76 ± 1.80 days, P < 0.001). After 5 days treatment, 54 patients (85.7%) obtained complete regression with an OAG score ≤8, and 7 patients (11.1%) had partial regression with an OAG score of 9-10 in DSIG cream treatment subgroup. However, only 2 patients (3.0%) obtained completed regression and 32 patients (47.8%) had partial regression in topical mouth rinse treatment cohort. Moreover, no serious side-effect was observed in both cohorts. CONCLUSIONS: Compared with topical mouth rinse, DSIG cream significantly lowered the OAG score and shortened OM duration.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Antineoplásicos/efeitos adversos , Compostos de Iodo/uso terapêutico , Silicatos/uso terapêutico , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Feminino , Glicerol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Projetos Piloto , Creme para a Pele , Solventes/uso terapêutico , Estomatite/patologia , Adulto Jovem
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