Recently developed experiment selleck chemicals Calcitriol approaches, such as interference of RNA, could be useful to help answer this question and support additional investigation on the mechanisms and proteins involved in liver fibrosis. In summary, the present study demonstrates that the AhR has an endogenous role in the development of liver fibrosis. Indeed, AhR-null mice showed hepatic portal fibrosis with hypertrophy of the portal vasculature and overproduction of fibrosis markers such as collagen, the fibroblasts marker proteins ��-actin and vimentin and the ECM proteins LTBP-1 and TGF-��. TGF-�� and LTBP-1 mRNAs were not coregulated in this animal model, suggesting that the absence of AhR increased TGF-�� activity without affecting its mRNA levels.

This study provides a new insight on the putative endogenous role for the AhR that could represent a new therapeutic target for liver degenerative diseases. Acknowledgments We are very grateful to Dr Manuel Ramirez for the use of the fluorescence microscope. This work has been funded by Grants from the Spanish Ministry of Science and Technology (SAF2002-0034) and from the Consejer��a de Sanidad y Consumo, Junta de Extremadura (Ref. 08�C12).
The current global standard adjuvant treatment for Dukes’ C (stage III) colon cancer is intravenous (i.v.) administration of bolus 5-fluorouracil (5-FU) and leucovorin (LV), either weekly or monthly, over a period of 6�C8 months (Van Cutsem et al, 2002). Adjuvant 5-FU/LV reduces the risk of relapse and prolongs survival in patients with resected colon cancer (IMPACT, 1995; O’Connell et al, 1997; Haller et al, 1998; Wolmark et al, 1999; Porschen et al, 2001; Arkenau et al, 2003).

Although the clinical benefits associated with adjuvant 5-FU/LV are significant, it is clear that more effective, convenient and better-tolerated treatments are required. Capecitabine (Xeloda?, F Hoffmann-La Roche, Basel, Switzerland) is a convenient oral fluoropyrimidine that generates 5-FU preferentially in tumour tissue through a three-step enzymatic cascade (Miwa et al, 1998). As first-line therapy for metastatic colorectal cancer, oral capecitabine achieved improved response rates (26 vs 17%, respectively), and equivalent progression-free and overall survival compared with monthly bolus i.v. 5-FU/LV (Van Cutsem et al, 2004).

Capecitabine was also better tolerated than 5-FU/LV and its administration was associated with a reduced consumption of medical resources (Twelves et al, 2001). These results led to the approval of capecitabine in 2001 as a first-line alternative to 5-FU/LV in metastatic colorectal cancer. The effectiveness of capecitabine in the metastatic setting provided a rationale for its use as adjuvant therapy for colon cancer. A large, randomised phase III study (X-ACT) was undertaken to compare the efficacy and tolerability of adjuvant oral capecitabine vs bolus i.v. 5-FU/LV (Mayo Clinic regimen) over 24 weeks in 1987 patients with Dukes’ C colon cancer (Twelves AV-951 et al, 2005).