ABSTRACT
We investigated the effect of TNBS administration using TNF-receptor knockout mice to elucidate the role of TNF receptors in chronic inflammation of the colon. Histologically, inflammatory cell scores showed no significant differences among TNBS-administered groups, while tissue damage scores were significantly lower in TNFR-1KO and TNFR-1,2KO than in WT. The apoptotic indexes of lamina propria mononuclear cells (LPMC) of all TNBS-administered groups were significantly lower than that of controls. TNF-alpha mRNA expression in the colon was significantly higher in all TNBS-administered groups than in controls. And NF-kappa B activities were enhanced in WT and TNFR-2KO compared with controls. Our data indicate that the TNF/TNFR-1 signaling system mediates mucosal damage through the enhancement of NF-kappa B activity and that continuous infiltration of TNF-producing cells, probably a key pathogeneses of colitis, may be closely associated with defective apoptosis of LPMC, which is possibly independent of the TNF/TNFR signaling system in TNBS-induced colitis.
Subject(s)
Colitis/chemically induced , Colitis/immunology , Receptors, Tumor Necrosis Factor, Type I/physiology , Trinitrobenzenesulfonic Acid/pharmacology , Trinitrobenzenesulfonic Acid/toxicity , Animals , Apoptosis , Colitis/veterinary , Female , Inflammation , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/physiology , Receptors, Tumor Necrosis Factor, Type I/genetics , Signal Transduction , Tumor Necrosis Factor-alpha/physiologyABSTRACT
A 60-year-old man was admitted to our hospital suffering from discomfort in the epigastrium. Endoscopic examination revealed stenosis from the fornix to the body of the stomach. The lesion had invaded the lower esophagus. Biopsy specimens confirmed poorly differentiated adenocarcinoma. An abdominal CT scan showed the lesion was a single mass in the stomach and swollen lymph nodes at the fornix, and revealed slight ascites and left hydronephrosis. The patient received oral administration of TS-1. No adverse effect was seen after 3 courses of treatment, and the lesion was reduced so that it was only found in the fornix. During the 1 year and 3 months of treatment with TS-1, this patient worked as mountain guide in the Hida area and was able to travel to the Himalayas in Nepal for the New Year of 2001. To preserve the quality of life of cancer patients, it is worth considering outpatient treatment with TS-1.
