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1.
Int J Exp Pathol ; 102(3): 157-162, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33993564

RESUMO

Xeroderma Pigmentosum group D (XPD) gene has been shown to suppress hepatocellular carcinoma (HCC) progression, but its mechanism remains not fully understood. ETS-related gene (ERG) is generally known as an oncogenic gene. This study aimed to explore whether XPD regulated HCC cell proliferation, apoptosis and cell cycle by inhibiting ERG expression via the PPARγ pathway. The human hepatoma cells (HepG2) were transfected with the XPD overexpression vector (pEGFP-N2/XPD) or empty vector (pEGFP-N2). The PPARγ inhibitor GW9662 was used to determine whether XPD effects were mediated by activation of PPARγ pathway. Cell cycle and apoptosis were ascertained by flow cytometry, and cell viability was measured by MTT assay. Reverse transcription-polymerase chain reaction and Western blot were performed to determine the mRNA and protein levels. Overexpression of XPD significantly enhanced the expression of PPARγ and p-PPARγ, whereas it downregulated that of ERG and cdk7. Furthermore, XPD overexpression notably inhibited proliferation, promoted apoptosis and decreased the percentage of cells in the S + G2 phase of HepG2 cells. However, these effects of XPD overexpression were abrogated by GW9662. Collectively, XPD suppresses proliferation and promotes apoptosis of HepG2 cells by downregulating ERG expression via activation of the PPARγ pathway.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , PPAR gama/metabolismo , Proteína Grupo D do Xeroderma Pigmentoso/metabolismo , Apoptose/fisiologia , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/fisiologia , Regulação para Baixo , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Transdução de Sinais/fisiologia , Regulador Transcricional ERG/metabolismo
2.
Int J Oncol ; 48(3): 1218-28, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26780944

RESUMO

Activated ras genes are found in a large number of human tumors, and therefore are one of important targets for cancer therapy. This study investigated the antitumor effects of a novel single chain fragment variable antibody (scFv) against ras protein, p21Ras. The anti-p21Ras scFv gene was constructed by phage display library from hybridoma KGHR1, and then subcloned into replication-defective adenovirus vector to obtain recombinant adenovirus KGHV100. Human tumor cell lines with high expression of p21Ras SW480, MDA-MB­231, OVCAR-3, BEL-7402, as well as tumor cell line with low expression of p21Ras, SKOV3, were employed to investigate antitumor effects in vitro and in vivo. Fluorescence microscopy demonstrated that KGHV100 was able to express intracellularly anti-p21Ras scFv antibody in cultured tumor cells and in transplantation tumor cells. MTT, Transwell, colony formation, and flow cytometry analysis showed that KGHV100 led to significant growth arrest in tumor cells with high p21Ras expression, and induced G0/G1 cell cycle arrest in the studied tumor cell lines. In vivo, KGHV100 significantly inhibited tumor growth following intratumoral injection, and the survival rates of the mice were higher than the control group. These results indicate that the adenovirus-mediated intracellular expression of the novel anti-p21Ras scFv exerted strong antitumoral effects, and may be a potential method for therapy of cancers with p21Ras overexpression.


Assuntos
Adenoviridae/genética , Inibidor de Quinase Dependente de Ciclina p21/imunologia , Neoplasias/tratamento farmacológico , Anticorpos de Cadeia Única/química , Proteínas ras/imunologia , Animais , Apoptose , Sítios de Ligação , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular , Feminino , Citometria de Fluxo , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Invasividade Neoplásica , Transplante de Neoplasias , Biblioteca de Peptídeos , Fosforilação
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-976363

RESUMO

@#ObjectiveTo observe the effect of equilibrium therapy of decontamination living creature of blood dilution (ETBD) on acute cerebral infarction.Methods124 inpatients were divided randomly into the treatment group and control group with 62 cases in each group. The patients of the treatment group were treated with routine medicine and ETBD. The patients of the control group were treated only with routine medicine. The blood-lipid and blood viscosity were tested and nerve function evaluation was performed before and on the 15th day after the treatment in two groups.ResultsAfter treatment, the levels of blood-lipid, blood viscosity and nerve functions of all patients in two groups were better than that before the treatment, but the effect of the treatment group was better than that of the control group ( P<0.05), and no obvious adverse reaction was found.ConclusionETBD is a safe, effect, simply and convenient therapeutic method for acute cerebral infarction and it is suitable for primarily medical units.

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