RESUMO
The in vitro predictive evaluation of chemical carcinogenicity based on hepatic premalignance has so far not been established. Here, we report a novel approach to investigate the premalignant events triggered by human carcinogen aristolochic acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6 phenotypic characteristics. Hepatocytes expressed STAT3/p-STAT3, c-Myc and Lin28B in parallel. Some of them displayed the dedifferentiation characteristics, such as full of α-fetoprotein granules, increase in size, and nucleocytoplasmic shuttle of Oct4. When these cells were injected into mice, the xenografts mostly displayed the uniform area of hepatic-like tissue with malignant nuclei. The hepatic malignant markers, α-fetoprotein, cytokeratin 7 and cytokeratin 19, were co-expressed in albumin-positive areas, respectively. In conclusion, we established an approach to predict the hepatic premalignance triggered by carcinogen AAI. This premalignant assay system might aid to evaluate the effects of potential carcinogens in liver, and probably to screen the protecting against hepatocarcinogenic efficacy of pharmaceuticals in vitro.
Assuntos
Ácidos Aristolóquicos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Hepatócitos/efeitos dos fármacos , Neoplasias Hepáticas/induzido quimicamente , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Albuminas/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Desdiferenciação Celular/efeitos dos fármacos , Linhagem Celular , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Hepatócitos/metabolismo , Hepatócitos/patologia , Interleucina-6/metabolismo , Queratina-19/metabolismo , Queratina-7/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/patologia , Comunicação Parácrina/efeitos dos fármacos , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas de Ligação a RNA , Transdução de Sinais/efeitos dos fármacos , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: Laparoscopic splenectomy (LS) shows many advantages compared with open surgery except for the high cost. This study was aimed to recommend secondary pedicle division strategy as a method with high cost-effectiveness. METHODS: From January 2003 to June 2005, 14 consecutive patients underwent laparoscopic splenectomy. The splenic pedicle was controlled by secondary pedicle division strategy in 8 cases and by Endo-GIA in the other 6 cases. A retrospective study was carried out to evaluate the operative time, blood loss, time to diet, operative morbidity, postoperative stay, and operative cost. RESULTS: LS was performed successfully in a total of 14 cases. There was no significant difference between the two strategies in operative time, blood loss, time to diet, operative morbidity and postoperative stay. The operative cost of secondary pedicle division strategy group (RMB 8354.38 +/- 752.10) was significantly lower than that of Endo-GIA group (RMB 11053.33 +/- 602.27) (P < 0.01). CONCLUSIONS: Laparoscopic splenectomy by secondary pedicle division strategy is a safe, effective and economical procedure with the value of popularization in developing countries.
