DISTRIBUTION OF IMMUNOGLOBULIN-CONTAINING CELLS AND LOCALIZATION OF SECRETORY COMPONENT IN GASTRIC MUCOSA BEARING CARCINOMA

Surgical materials of gastric carcinoma were studied immunohistochemically in terms of the distribution of immunoglobulin-containing cells and the localization of secretory component (SC). There was no convincing evidence suggesting that the secretory immune system surrounding carcinoma was responding to the carcinoma. But in some cases, increase of IgG-containing cells was observed in the stroma of carcinoma suggesting the presence of some kind of tumor immunity. In the non-carcinomatous mucosa, SC was observed strongly in cells of intestinal metaplasia except for the goblet cells, but weakly in the normal foveolar epithelium. The presence of SC in carcinoma cells was observed in 45 percent of the total cases of gastric carcinoma [36/80] and was especially porminent in signet-ring cell carcinoma [78%]. IgA was observed in about 50 percent of these SC-positive carcinoma cases. SC was also frequently positive in group III atypical epithelium

LONGER SURVIVAL AND FEWER METASTASES BY LEVAMISOLE AND TEGAFUR IN 1, 2-DIMETHYLHYDRAZINE-INDUCED MURINE COLONIC CANCERS

The anticancer effects of levanisole, tegafur and their combination were experimentally compared in rats on the 1, 2-dimethylhydrazine (DMH)-induced colonic cancers. DMH at 20 mg/kg of body weight was injected subcutaneously to Donryu rats once a week for 24 weeks long. Nineteen weeks after the start of DMH administration, early colonic cancers were induced and, 28 weeks after, they developed into advanced cancers with distant metastases. From 19 weeks after the start of DMH injection, subcutaneous administration of levamisole at the dose of 2 mg/kg, oral administration of tegafur at 90 mg/kg and their combination were given to the rats daily for nine weeks. The animals were sacrificed 28 weeks after the start of DMH administration. Tegafur was effective, but levamisole with or without tegafur was not effective against early cancer. From 28 weeks after the start of DMH injection, levamisole, tegafur and their combination were administered to the rats daily for four weeks. All of the rats were necropsied when they died. The survival rate and mean survival days were significantly higher and longer in the levamisole groups than in the control rats (p<0.05). The incidence of distant metastases was also significantly lower in the levamisole groups than in the control group

Pharmacological profile of the novel mammalian tachykinin, hemokinin 1

1. The effects of the novel mammalian tachykinin, hemokinin 1 (HEK-1), have been investigated by radioligand binding and functional in vitro and in vivo experiments. 2. Similar to SP (K(i)=0.13 nM), HEK-1 inhibited in a concentration-dependent manner and with high affinity [(3)H]-substance P (SP) binding to human NK(1) receptor (K(i)=0.175 nM) while its affinity for [(125)I]-neurokinin A (NKA) binding at human NK(2) receptor was markedly lower (K(i)=560 nM). 3. In isolated bioassays HEK-1 was a full agonist at tachykinin NK(1), NK(2) and NK(3) receptors. In the rat urinary bladder (RUB) HEK-1 was about 3 fold less potent than SP. In the rabbit pulmonary artery (RPA) HEK-1 and in the guinea-pig ileum (GPI), HEK-1 was about 500 fold less potent than NKA and NKB, respectively. 4. The responses to HEK-1 were antagonized by GR 82334 in RUB (pK(B)=5.6±0.07), by nepadutant in RPA (pK(B)=8.6±0.04) and by SR 142801 in GPI (pK(B)=9.0±0.2) with apparent affinities comparable to that measured against tachykinin NK(1), NK(2) and NK(3) receptor-selective agonists, respectively. 5. Intravenous HEK-1 produced dose-related decrease of blood pressure in anaesthetized guinea-pigs (ED(50)=0.1 nmol kg(−1)) and salivary secretion in anaesthetized rats (ED(50)=6 nmol kg(−1)) with potencies similar to that of SP. All these effects were blocked by the selective tachykinin NK(1) receptor antagonist, SR 140333. 6. We conclude that HEK-1 is a full agonist at tachykinin NK(1), NK(2) and NK(3) receptors, possesses a remarkable selectivity for NK(1) as compared to NK(2) or NK(3) receptors and acts in vivo experiments with potency similar to that of SP