RESUMEN
BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy. METHODS: Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression. RESULTS: Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group. CONCLUSION: Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias del Colon/mortalidad , Reparación de la Incompatibilidad de ADN , Proteínas de Unión al ADN/metabolismo , Endonucleasas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
1. Unlike mammals, uricotelic species, such as the duck, cannot synthesise endogenous arginine (Arg). This study was conducted to test the hypothesis that dietary L-Arg supplementation might regulate body fat deposition in ducks without affecting their fast growth rate. 2. A total of 160 21-d-old male and female White Pekin ducks were assigned randomly to two treatments: a non-supplemented control and supplementation at 10 g/kg L-Arg of a maize and soybean meal-based diet. 3. The 3-week feeding trial showed that the addition of L-Arg had no significant effect on feed intake, but significantly increased body weight gain by 5·2 %, breast muscle weight relative to live body weight by 9·9%, carcase crude protein content by 9·2%, ether extract content in breast muscle by 11·9%. Arg supplementation significantly decreased skin with fat and abdominal fat pad contents by 7·6% and 4·9% respectively and the ether extract content of carcase by 7·2%. 4. The results of this study indicate that a diet with 10 g/kg supplemental L-Arg could reduce the fat deposition of carcase and abdominal adipose cell size (diameter and volume), enhance intramuscular fat in breast muscles, as well as increase muscle and protein gain. The decreased fat depot in the carcase may be attributed to a reduction of hepatic lipogenic enzyme activity.