Immunological characterization and clinical implication of cobalamin binding protein in human gastric cancer.

Cobalamin (vitamin B12) binding protein was purified from gastric cancer extracts and from serum-free culture medium of cancer cell line KATOH-III. The molecular weight, determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 70,000 and the pI was 2.8 to 3.2. From biochemical and immunological properties, this cobalamin binding protein was considered to be an isoprotein of cobalamin R binder. Monoclonal antibodies were produced against saliva R and cobalamin binding protein in culture medium to study their antigenic determinants. Monoclonal antibody 55-D reacted to an epitope of peptide in both binders, whereas WK-1 and H-12 reacted to determinants of a carbohydrate moiety, including sialic acid, in cancer cell-derived binder. In addition, we carried out an enzyme-linked immunoassay and examined plasma levels of immunoreactive R binder in patients with gastric cancer (n = 72), benign gastrointestinal disease (n = 30), and healthy individuals (n = 40). Even in patients without liver metastasis, the level of immunoreactive R binder detected by monoclonal antibody H-12 was elevated in some patients and decreased after excision of the tumor. R binder was also elevated in cancer tissue extract. Immunoreactive binder was histochemically detected in the cytosol of cancer cells and metaplastic cells of the gastric mucosa. The present findings suggest that cobalamin R binder is de novo synthesized in gastric cancer cells and that its plasma level increases in some patients. This binding protein may be a useful diagnostic and therapeutic parameter.

Effect of intraarterial active oxygen species on the rat pancreas.

To explore the role of active oxygen species in the development and progression of acute pancreatitis, we studied the direct toxic effect on the rat pancreas of active oxygen species: superoxide anions generated by xanthine/xanthine oxidase (X/XO), and hydrogen peroxide (H2O2). After a continuous injection of X (10(-3)M, 0.9 ml/hour)/XO (1 U/ml, 0.3 ml/hour) into the celiac artery supplying the pancreas, hemorrhages and extensive edema developed in the pancreas. The amylase and lipase concentrations in the peritoneal fluid rose to 10.3 and 13.8 times the control values, respectively. The subsequent infusion of superoxide dismutase (SOD, 3600 U/hour) into the external jugular vein completely suppressed hemorrhages, and reduced edema and the amylase and lipase concentrations in the peritoneal fluid. After continuous injection of H2O2 (100 microM, 1.2 ml/hour), via the celiac artery, marked hemorrhages and edema appeared in the pancreas, and the amylase and lipase concentrations in the peritoneal fluid were 11.1 and 17.3 times higher than the control values, respectively. These abnormalities were significantly suppressed by the intravenous infusion of catalase (10 mg/kg/hour) or gabexate mesilate (10 mg/kg/hour). These results indicate that active oxygen species have a direct toxic effect on the pancreas and that free radicals may play an important role in the development of acute pancreatitis.

[Imaging of somatostatin receptor using 111In-pentetreotide].

Recently radiolabeled somatostatin analog, [111In]pentetreotide, was developed and its usefulness for the diagnosis and localization of neuroendocrine tumors has been described. In this paper, we reported the results of [111In]pentetreotide scintigraphy in four patients with gastroenteropancreatic endocrine tumors. Two patients with metastatic gastrinoma, one patient with gastric carcinoid, and one patient suspected with gastrinoma, were injected with 119-156 MBq of [111In]pentetreotide. Planar and SPECT images were obtained 4, 24, and 48 hours postinjection. Both primary and metastatic tumors were well visualized in patients with metastatic gastrinoma. Especially in one patient small liver metastases which were not detected by CT or MRI were imaged. We could not obtain positive images in the other two patients. Four-hour or 24-hr images were better than 48-hr images because of higher count density and lower gut activity. No significant adverse effect were seen in any patient. [111In]pentetreotide scintigraphy is a useful procedure for the localization of gastroenteropancreatic endocrine tumors.