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Background and aims: Activation of the vanilloid receptor subtype 1 (VR-1) results in release of proinflammatory peptides which initiate an inflammatory cascade known as neurogenic inflammation. We investigated its role in an acute model of surgically induced oesophagitis. Methods: Oesophagitis was induced by pyloric ligation in wild-type and VR-1 deficient mice. A subset of animals were administered the VR-1 antagonist capsazepine, famotidine, or omeprazole one hour before surgery. Five hours after surgery, myeloperoxidase activity (MPO), histological damage scores, intragastric pH, and immunocytochemical analysis of substance P (SP) receptor endocytosis were determined. Results: Oesophagitis induced knockout mice exhibited significantly lower levels of MPO activity, histological damage scores, and SP receptor endocytosis than wild-type mice. Inflammatory parameters were significantly reduced by acid inhibition and capsazepine in wild-type mice. Conclusions: We conclude that acute acid induced oesophagitis is reduced in animals lacking VR-1. This suggests that acid induced oesophagitis may act through VR-1 and that inhibition of the receptor may reduce inflammation.

Introduction-Osteopontin (OPN) mediates cancer metastatis. Mechanisms regulating OPN expression in human colorectal cancer are unknown. Using SW480 colon adenocarcinoma cells, we hypothesized that transcription determines OPN expression.

Rho family GTPases play a pivotal role in the regulation of numerous cellular functions associated with malignant transformation and metastasis. To evaluate the role of these GTPases in colorectal cancer, the protein expression levels and activities of these proteins in matched sets of tumor and non-tumor tissues of surgical specimens were analyzed. The relationship between the protein levels and activities in tumor tissues to the clinicopathological features was also assessed. The expression levels of RhoA, active RhoA, Rac1, and active Rac1 in tumor tissues were higher than in normal tissues. The amounts of active RhoA protein in primary tumors correlated with lymph nodes metastasis. No relationship was noted between the protein expression levels and other clinicopathological findings. These findings suggest that the Rho family small GTPases are related to malignant transformation and progression of colorectal cancer and the activation of RhoA is associated with the lymph node metastasis.