A case of carcinoid of the stomach with metastases to the liver is described in which the simultaneous occurrence of α₁-fetoprotein (110μg/ml) and carcinoembryonic antigen (25ng/ml) was demonstrated in the circulation by immunochemical methods. By means of the indirect fluorescence method α₁-fetoprotein was detected in the cytoplasm of some tumorous cells both in the primary tumour and in liver metastases. On the other hand, the abnormal variant of alkaline phosphatase isoenzymes-the Regan isoenzyme-was not detected in the patient's serum though the total activity of alkaline phosphatase in serum was increased (150U/L). The patient's serum also contained "hepatitis B-associated" antigen.
This case provides a further evidence of another pathologic occurrence of α₁-fetoprotein in tumours of the digestive tract; it also shows the possibility of the simultaneous incidence of two "onco-fetal antigens" in one type of the tumour.

View full abstract

The cell-free Ehrlich carcinoma ascites blocked immune adherence produced on Ehrlich carcinoma cells by anti-Ehrlich antiserum. The molecular weights of the blocking factors in the ascites were >100, 000, 100, 000-10, 000, and 1, 000-500. Similar activities were found in the ascites produced in sarcoma-180, in leukemia SN-36, or by complete Freund's adjuvant. These blocking factors in the carcinoma ascites may explain the development of ascites type of the carcinoma which often regresses spontaneously when transplanted subcutaneously. The blocking factors in the ascites seem to be different from the blocking activities in the serum of tumor-bearers which Hellström and Hellström described.

View full abstract

An aqueous solution of 60μg/ml of N-methyl-N'-nitro-N-nitrosoguanidine was administered to 6 dogs once a day in place of drinking water, for 22.5 months to 3 dogs, and 27 months to the remainder. The animals were observed until moribund. At autopsy numerous protrusions were observed on the anterior wall of the upper stomach body, with irregularity of the surface of the mucosa around them in 4 dogs.
Histopathologically the area with protrusions and irregularity of the mucosal surface showed severe atrophy of the fundic glands. Where the severe atrophy of the fundic mucosa was found, there were many "atypical glandular lesions", which varied in the degree of atypism.
Atypical glandular lesions found in the stomach were classified histologically into 5 grades. Lesions with milder atypia were found more frequently than those with severe atypia. Lesions with high atypia were often accompanied with other lesions of different grades. Four lesions suspected to be cancer and two lesions judged as cancer were found in two of the dogs studied.
Relationship between severe atrophy and neoplastic changes in stomach was also discussed.

View full abstract

Clinicopathological findings of four cases of yolk sac tumor (endodermal sinus tumor), arising from the anterior abdominal wall, the testis, and the ovaries, are presented. Irrespective of the differences in age and sex of the patients and in the site of primary tumors, the four cases showed common biological and morphological properties. The sera obtained from the patients were all positive for α-fetoprotein in agar immunodiffusion test and radioimmunoassay. Histological appearances of the four tumors are essentially similar showing mucinous loose stroma mimicking the magma reticulare, structure resembling the endodermal sinus of Duval, polyvesicular vitelline structure, and periodic acid-Schiff reaction-positive, diastase-resistant hyaline globules. Immunofluorescence study carried out on two cases of tumors of the ovary clearly demonstrated th presence of intra- and extracytoplasmic α-fetoprotein granules in the tumor tissues. Further, these α-fetoprotein granules demonstrated by immunofluorescence was found to show similar distribution with the periodic acid-Schiff reaction-positive hyaline globules. Electron microscopic studies also revealed basically similar ultrastructural features, epithelial cell cords, tubules and cysts lined with basemement membrane, luminal microvilli, and well-developed Golgi complexes which indicate close similarity to the yolk sac endoderm. These findings suggest that yolk sac tumor is a peculiar germ cell tumor having a property to differentiate to yolk sac which is able to synthesize α-fetoprotein.

View full abstract

Three groups of Donryu rats of both sexes were given continuously 400, 200, or 100ppm solution of N-butyl-N-nitrosourethan (BNUR) as their drinking water. A high incidence of squamous cell carcinomas, 126 out of 150 rats (84%), and papillomas, 149 out of 150 rats (99%), arising from the upper digestive tract, was found in all three groups. Mean survival time of tumor-bearing rats was as short as 200 days in the group that received 400ppm BNUR solution, and the earliest development of squamous cell carcinoma was found in the forestomach of a rat killed on the 112th experimental day.
The study on the morphogenesis of squamous cell tumors arising from the esophagus and forestomach was made in rats that were killed on the 4th, 8th, 12th, 16th, and 20th experimental week of the BNUR treatment. The result showed that the majority of these tumors developed either directly or from papillary down-growths of the squamous cell epithelium.

View full abstract

Effect of Daunomycin and its new analog, Adriamycin, on nucleic acid biosynthesis was compared in L-1210 leukemia cells and in human leukemic leucocytes in vitro by the use of labeled adenine incorporation. Daunomycin was demonstrated to be significantly more effective than Adriamycin in inhibiting RNA and DNA synthesis in leukemic cells at the same concentration studied. On the other hand, the reaction catalysed in vitro by DNA polymerase activity in 100, 000g supernatant prepared from L-1210 leukemia cells was quite equally inhibited in the presence of Daunomycin and Adriamycin, suggesting their same effect on template activity of primer DNA. In fact, interaction of both antibiotics with calf thymus DNA in vitro, which was determined by using Sephadex G-25 column chromatography, showed no appreciable difference between Daunomycin and Adriamycin in binding affiinity to calf thymus DNA.
Studies on cell-drug interaction, however, revealed that the uptake of Daunomycin by leukemia cells was considerably greater than that of Adriamycin. Both Daunomycin and Adriamycin were judged rather stable in leukemic cells and in the medium during incubation from the analysis of metabolites using a thin-layer chromatography, indicating that neither activation nor inactivation plays any rôle in the different effects of these antibiotics.
Since the essential mechanism of action of both antibiotics, such as binding to DNA and inhibiton of DNA polymerase reaction, was found to be quantitatively similar in the cell-free system, better accessibility of Daunomycin to DNA in leukemic cells due to the greater cellular uptake may account for the superiority of Daunomycin to Adriamycin in inhibiting the nucleic acid metabolism in leukemia cells in vitro.

View full abstract

The ultrastructure of cholangiofibrosis in a rat liver induced by short-term feeding with 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) was investigated. The feeding of 3'-Me-DAB for as short a period as 2 weeks was sufficient to induce cholangiofibrosis. After cessation of the feeding of the carcinogen, lesions of cholangiofibrosis continued to grow for up to 25 weeks. Hyalinization of the lesions was seen from 8 weeks after stopping of the dye feeding. However, the newly proliferated lining epithelial cells at the peripheral zone of the hyalinized lesions could always be seen. The ultrastructure of the epithelial lining cells in the lesion of cholangiofibrosis showed a typical intestinal cell metaplasia including goblet cells, enterochromaffin cells, and Paneth cells. A variation in the fine structure of the striated border was often observed.

View full abstract

δ-Aminolevulinic acid (ALA) synthetase in a culture line of Friend leukemia cells (T-3-Cl-1) was assayed by a newly devised micro-assay method. When the cells were grown in a medium containing dimethyl sulfoxide (Me₂SO) or human placental extract (HPE) for 4 days, ALA synthetase activity increased to maximal levels of 4 and 8 times that of control cells. When transferred to a fresh medium without these materials, the ALA synthetase activity of these cells increased 4-fold on the first day, but decreased to the initial level again during subsequent culture for 3 to 4 days. In contrast, when transferred to a medium containing 1.5% Me₂SO, the ALA synthetase activity of the cells increased 4-fold on the first day and this level was maintained during the subsequent culture, while when transferred to a medium containing 2.5% HPE, the enzyme activity increased 11-fold on the first day and then decreased gradually to 6 times the initial level during the next 4 days. Heme synthesis also increased in the cells grown in a medium containing 1.5% Me₂SO for 3 to 4 days. Differentiation of these leukemia cells in culture is discussed in relation to other phenotypic markers.

View full abstract

Immunosuppressive principles were purified from Ehrlich ascites tumor cells. One of the principles, D3-1 with molecular weight of 76, 000, showed a single protein band on polyacrylamide gel electrophoresis. Immunosuppression was assayed by counting 19S antibody plaque-forming cells against sheep red blood cells in mouse spleen.

View full abstract

In 19 out of 24 rats which survived oral administration of 23 to 47g/kg of a synthetic compound, 3-benzylsydnone-4-acetamide, during 8 to 16 weeks, hepatocellular carcinomas developed between 126 and 251 days of experiment, 17 with liver cirrhosis. Hepatomas were mostly of trabecular type of varied differentiation.

View full abstract

The spontaneous gastric corcinoid of mastomys produced histamine but not serotonin at the primary tumor stage. Homogenate of the carcinoid tissue produced 8.5 to 14.8 nmoles of histamine/hr/mg protein in vitro, and these values were 60 times higher than those of the normal gastric mucosa.

View full abstract

4-Hydroxyaminoquinoline 1-oxide-activating enzyme was found in baker's yeast as well as rat ascites hepatoma cells. Enzymes from both sources required heated extract of the ascites cells in addition to ATP and Mg²⁺ for their maximal activity. The main active component in the extract was identified as L-serine.

View full abstract

Pigeon-egg sized V₂ carcinoma and its lymph node metastasis of the rabbit legs were completely regressed by the present perfusion-circulation stop chemotherapy using Carbazilquinone glucose solution. Normal surrounding tissues of the legs were fairly intact.

View full abstract