RESUMEN
INTRODUCTION: Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy. MATERIAL AND METHODS: We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS. Survival analyses were performed for each allelic variant by using the log-rank test and Kaplan-Meier analysis. RESULTS: The CRC patients with the XPD Gln allelic variants had poorer survival than patients with the Lys/Lys genotype (HR â=1.38, 95% CI â=1.02-1.87), and rectal cancer patients had the poorest survival among them (HR â=1.87, 95% CI â=1.18-2.95). A significantly shorter OS was observed among stage II/III colon cancer patients with the XRCC1 Gln allelic variants (HR â=1.69, 95% CI â=1.06-2.71), compared to those with XRCC1 Arg/Arg genotype. In the combined analysis of the XRCC1 and XPD genes patients with stage II/III tumors, the poorest OS occurred in colon cancer patients with the XRCC1 Gln and XPD Gln allelic variants (HR â=2.60, 95% CI â=1.19-5.71) and rectal cancer patients with the XRCC1 Arg/Arg and XPD Gln allelic variants (HR â=2.77, 95% CI â=1.25-6.17). CONCLUSION: The XPD and XRCC1 allelic variants may be prognostic markers for CRC patients receiving 5-FU based chemotherapy. The contributions of the XPD and XRCC1 allelic variants to OS are tumor site- and/or stage-dependent.
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Alelos , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales , Reparación del ADN/genética , Fluorouracilo/uso terapéutico , Glutatión Transferasa/genética , Biomarcadores de Tumor , Estudios de Cohortes , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
PURPOSE: This retrospective cohort study investigated the association between epidermal growth factor receptor (EGFR) polymorphisms and clinical outcomes in colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU)-based chemotherapy. METHODS: We genotyped 3 EGFR polymorphisms including R497K, G-216T, and the (CA)n repeat, among 499 histologically confirmed CRC patients who had received 5-FU-based chemotherapy after surgery between 1995 and 2001. Survival analyses of EGFR polymorphisms were performed by the log rank test and Kaplan-Meier curves. We used the Cox proportional hazard model to evaluate the association between EGFR genotypes and clinical outcomes. Stratification analysis by gender, tumor stage, and subsite were also carried out. RESULTS: CRC patients with the EGFR (CA)n L/L genotype compared to those with the S/S+S/L genotype had a significantly better overall survival (L, ≥ 20 repeats; S, <20 repeats) (hazard ratio (HR) 0.74; 95 % confidence interval (CI) 0.57-0.95), particularly for patients who were male (HR 0.63; 95 % CI 0.44-0.90), who had stage IV disease (HR 0.70; 95 % CI 0.49-0.99), and who had rectal cancer (HR 0.62; 95 % CI 0.42-0.92). Better survival was prominent among patients with the combined genotypes of EGFR (CA)n L/L, G-216T G/G, and R497K K/K (HR 0.51; 95 % CI 0.30-0.87), compared to those with the most common genotypes of the EGFR (CA)n S allele, G-216T G/G, and R497K R allele. CONCLUSIONS: EGFR polymorphisms can serve as prognostic predictors for CRC patients receiving 5-FU-based chemotherapy.
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Antimetabolitos Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Receptores ErbB/genética , Fluorouracilo/uso terapéutico , Polimorfismo Genético/genética , Adyuvantes Inmunológicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Levamisol/uso terapéutico , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Antrodia camphorata (A. camphorata), well known in Taiwan as a traditional Chinese medicine, has been shown to exhibit antioxidant and anticancer effects. In the present study, therefore, we have examined the effects of the fermented culture broth of A. camphorata (25-100 microg/ml) in terms of lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in RAW 264.7 macrophages. Our results indicate concentration-dependent A. camphorata inhibition of LPS-induced NO and PGE2 production, without appreciable cytotoxicity on the RAW 264.7 cells. A. camphorata also attenuates the production of LPS-induced tumor necrosis factor (TNF-alpha) and interleukin (IL)-1beta. Furthermore, A. camphorata blocks the IkappaB-alpha degradation induced by LPS. These results indicate that A. camphorata inhibits LPS induction of cytokine, iNOS and COX-2 expression by blocking NF-kappaB activation. Therefore, we report the first confirmation of the anti-inflammatory potential of this traditionally employed herbal medicine in vitro.