RESUMO
BACKGROUND: The relationship between obesity and cancer has become of particular interest due to the rapidly growing prevalence of overweight individuals. Obesity predisposes individuals to the development of hepatic steatosis and is an independent risk factor for several neoplasms. Toll-like receptor 4 (TLR4) is the innate receptor for endotoxin, and steatotic livers are known to be sensitive to endotoxin. TLR4 signaling has been shown to have proneoplastic effects in vitro due to its effect on immune surveillance. Thus far, studies have predominantly focused on the effect of tumor-cell-derived TLR4 without regard to host TLR4 signaling. RESULTS: In the present study we show that steatotic livers have increased expression of TLR4. Obese animals developed higher metastatic tumor burden in the liver than lean controls regardless of the presence or absence of intact host TLR4. After silencing TLR4 expression using RNAi in the mouse colon cancer cell line MC38, there was a significant decrease in metastatic tumor burden within the liver of obese animals. CONCLUSIONS: These findings demonstrate that steatotic livers have increased susceptibility to metastatic tumor growth and that silencing tumor cell TLR4 reduces metastatic tumor burden in steatotic liver.
Assuntos
Neoplasias Colorretais/genética , Fígado Gorduroso/metabolismo , Inativação Gênica , Neoplasias Hepáticas/genética , Receptor 4 Toll-Like/genética , Carga Tumoral/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/secundário , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/secundário , Masculino , Camundongos , Obesidade/complicações , Obesidade/genética , Obesidade/imunologia , Receptor 4 Toll-Like/biossínteseRESUMO
BACKGROUND: The reported patient and graft survivals among adults post-orthotopic liver transplantation (OLT) are variable, with an apparent discrepancy between ethnic groups. The aim of this study was to evaluate the impact of ethnicity on patient and graft survivals among adult and pediatric patients. METHODS: A retrospective analysis from the UNOS/OPTN databank between January 1995 and December 2006 was performed on adult and pediatric liver transplant recipients. Patients were divided into 4 groups based on ethnicity: African Americans, Hispanic, Caucasians, and other. Kaplan-Meier (KM) analysis was used to calculate patient and graft survival. Log-rank tests were used to compare survival rates between groups. RESULTS: In our study 42,710 OLT patients were included in the analysis, 90% of whom were adults. Of the 38,639 adult recipients, 29,432 (76.1%) were Caucasian, 4369 (11.3%) were Hispanic, 2963 (7.7%) were African American, and the remaining 1875 (4.9%) were of other ethnicities. KM estimates and Cox regression analyses demonstrated that there was a significant ethnic difference in both patient and graft survivals at 1, 3, 5, and 10 years. African Americans showed a lower rate (P<.001). Of the 4341 pediatric recipients, 2461 (56.7%) were Caucasian, 797 (18.4%) were Hispanic, 824 (18.9%) were African American, and the remaining 259 (5.9%) were of other ethnicities. Unlike the adults, there were no significant differences among ethnic groups in terms of patient (P=.31) and graft (P=.33) survival at 1, 3, 5, and 10 years after OLT. CONCLUSION: These results showed that adult African American OLT patients have a reduced transplantation rate and a worse survival rate when compared with other ethnicities in the adult but not in the pediatric population. This information suggests that further studies are indicated to identify the causes of racial differences in transplant access and outcomes in the adult patient population.
