The lymphocyte distribution into the tumor-draining node was studied with AH-130 hepatoma cells and Donryu strain rats in relation to the adjuvant activity of the oil-attached BCG whole cell wall.
The mixed inoculation of the oil-attached BCG cell wall with tumor cells resulted initially in further augmentation of increased distribution of ⁵¹Cr-labeled lymphocytes into the draining-node induced by inoculation of the tumor cells alone, and secondarily in the systemic stimulation of response of the lymph node lymphocytes to phytohemagglutinin. Suppression of the inoculated tumor growth and lymph node metastasis was finally observed. These results were discussed in connection with the therapeutic effect of BCG and its cell wall fraction.

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A first case of malignant melanoma treated with oil-attached BCG cell-wall skeleton (BCG-CWS) is reported. The patient, a 70-year-old farmer, with metastatic malignant melanoma was treated intralesionally with oil-attached BCG-CWS or was given intradermally with oil-attached BCG-CWS together with irradiated autologous and allogeneic tumor cells. Four months after the start of the immunotherapy with oil-attached BCG-CWS, primary tumor and metastatic inguinal lymph nodes regressed markedly without any significant complications. Lymphocytosis in the peripheral blood was usually observed after injection of oil-attached BCG-CWS.

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PS-K, a protein-bound polysaccharide from a basidiomycetes, was found to suppress tumor growth after grafting of sarcoma-180 or Ehrlich tumor in ICR mice. In the present study, effect of PS-K on antibody-forming capacities was examined in tumor-bearing mice and normal controls.
1) PS-K did not enhance the capacities of normal mice to produce antibodies against sheep erythrocytes (SRBC), hamster erythrocytes (HRBC), and trinitrophenyl group (TNP).
2) The capacities of mice to produce IgG antibody against SRBC, IgM antibody against HRBC, and IgG antibody against TNP were depressed after grafting of sarcoma-180. Intraperitoneal injection of PS-K restored these capacities to the normal levels.
3) Oral as well as intraperitoneal administration of PS-K restored the capacity of the mice bearing sarcoma-180 to produce IgG antibody against SRBC.
4) The capacity to produce IgG antibody against SRBC was depressed after grafting of Ehrlich tumor and it recovered to the normal level after intraperitoneal injection of PS-K.
These results showed that antibody-forming capacity of mice was depressed after tumor grafting and recovered after administration of PS-K.

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To investigate the metabolic fate of a 6S RNA (VA-RNA), which appears in human cell lines only after infection with adenovirus, various species of RNA from the cells at different stages of infection were tested for the presence of nucleotide sequence homologous to this RNA. RNA extracted from subcellular fractions of the cells was further fractionated by sucrose gradient centrifugation and analysed by acrylamide gel electrophoresis or by competition against ³²P-labeled VA-RNA in hybridization with adenovirus DNA. The results pointed to the following conclusions.
(1) VA-RNA is synthesized in the cells throughout the entire period after infections, starting before the onset of viral DNA synthesis. (2) VA-RNA does not participate in protein synthesis as a messenger RNA or a precursor of transfer RNA. (3) The nucleotide sequence homologous to VA-RNA exists as a part of certain species of nuclear high molecular weight RNA in the infected cells.

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Two cell lines of human hepatoma, HLE and HLF lines, were established in vitro from the hepatocellular carcinoma of a 68-year-old patient. One clone (HLEC) was obtained from a single HLE cell. The cells of HLE and HLEC were epithelial-like and both of these cells demonstrated glycogen granules in the cytoplasm when stained with periodic acid and Schiff reagent. Although HLF cells resembled fibroblasts in morphology, they appear to have originated from hepatoma cells, judging from epithelial characteristics in aggregates reconstituted by rotation culture and heterotransplantability. HLE cells produced α-fetoprotein until day 187 of culture, but HLF cells did not produce α-fetoprotein at any period examined. Chromosome number of both cell lines was distributed near the triploid range. HLF cells were transplantable into the cheek pouch of adult hamsters treated with cortisone acetate, but not HLE cells.

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Adenylate cyclase activities of untransformed hamster BHK 21/13 cells and their polyoma virus-transformed derivatives were compared using the cells cultured in low and high serum concentrations. The untransformed cells that were cultured in a medium containing 10% serum had a slightly higher activity than the transformed cells cultured under the same conditions. When the cells were cultured in a medium containing 0.5% serum that stopped proliferation of untransformed cells, more significant difference was observed in the adenylate cyclase activity; the untransformed cells had a two-fold higher activity than the transformed cells. The full activity measured in the presence of fluoride was two-fold higher in the untransformed than in the transformed cells. The low serum concentration increased the enzyme activity of both untransformed and transformed cells, but the enzyme activity of transformed cells in the presence of 0.5% serum did not exceed the activity of untransformed cells in 10% serum. Intracellular cyclic AMP levels were in parallel with the activity of adenylate cyclase, whereas no correlation was found between cyclic AMP levels and cyclic AMP phosphodiesterase activities.

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Aryl hydrocarbon hydroxylase activity in liver nuclei from C3H/He mice is apparently increased by the administration of 3-methylcholanthrene, but the enzyme activity from the DBA/2 mice is not. On the other hand, by treatment of the mice with phenobarbital sodium, the increased activity in liver nuclei was observed in both strains of mice. There are approximately the same levels of the apparent K_m for benzo[a]pyrene in liver nuclei from both strains of mice even after treatment with 3-methylcholanthrene, but different K_m values for NADPH and NADH are observed between the constitutive and induced enzyme, showing 0.032 and 0.091mM for NADPH, and 0.303 and 1.67mM for NADH, respectively. Both 5, 6- and 7, 8-benzoflavones enhance the activity in the constitutive enzyme, but inhibit it in the induced enzyme non-competitively. Nicotinamide inhibits both enzyme activities in liver nuclei. Cyclohexene oxide and 1, 1, 1-trichloropropane oxide enhance the activity in the induced enzyme, but not in the constitutive enzyme in liver nuclei. The differences in the properties between the constitutive and induced enzymes and between the enzymes in microsomes and in nuclei from mouse liver were discussed briefly.

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Relationship between the urinary excretion of steroids in premenopausal Japanese patients with advanced breast cancer and their response to oophorectomy was studied. The estrogen fractions were determined by radioimmunoassay and those who responded to oophorectomy showed higher levels of 17β-estradiol than the non-responders before surgery. The high levels of urinary 17β-estradiol of the responders dropped markedly after oophorectomy. On the contrary, the non-responders showed relatively low levels of urinary excretion of 17β-estradiol before oophorectomy and the levels appeared either unchanged or slightly elevated after surgery. No definite relation was found between changes in the urinary excretion of estrone or estriol and the clinical effect of oophorectomy. Excretion of 17-ketosteroids in the responders was lower than that of the non-responders.

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Ethanol-insoluble components were extracted from fresh garlic with 0.9% NaCl solution containing streptomycin and penicillin. This extract, containing approximately 10% sugar, 0.3% nitrogen, and 0.4% ash, was termed garlic sugar solution. This garlic sugar solution (Medium 1) was used as the suspending medium for Ehrlich ascites tumor cells attenuated with allicin, the main principle of garlic, and 0.9% NaCl solution containing streptomycin and penicillin (Medium 2) was also used as the suspending medium. Mice of DDD strain were immunized with the attenuated tumor cells suspended in Medium 1 or 2. After immunization, the immunized and control mice were challenged intraperitoneally with viable Ehrlich ascites tumor cells.
Animals immunized with the attenuated tumor cells suspended in Medium 1 acquired significantly stronger resistance against the tumor cells than animals immunized with those suspended in Medium 2.

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One of five gastro-entero-pancreatic hormones, gastrin, serotonin, histamine, glucagon, and insulin, was intraperitoneally administered for a long period to the rats that received N-methyl-N'-nitro-N-nitrosoguanidine. A frequent development of scirrhous carcinoma was demonstrated in the group treated with gastrin.

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Immunohistological studies, using the fluorescein isothiocyanate-labeled antibody against gastric mucosal glycoprotein, were made during the development of gastric cancer, induced in dogs and rats by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In an early stage, the regenerative glands were lined by fluorescent mucus cells. Carcinoma cells of orderly glandular structure, produced in dogs, were devoid of fluorescence. Carcinoma cells of less differentiation, produced in rats during further advanced stage, were well fluorescent. The immunofluorescent profiles of such experimentally induced gastric carcinoma were found to be the same as those of human gastric adenocarcinoma.

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Cell-wall skeleton of Nocardia rubra and of Mycobcterium bovis BCG in the oilattached form, when injected mixed with autografts of spontaneous mammary adenocarcinoma or of methylcholanthrene-induced sarcoma of mice, suppresses the growth of tumor autografts to a demonstrable extent. The BCG whole cell wall showed no effect. The local destruction of tumor autografts did not induce recognizable systemic immunity to the respective tumors.
These findings are commented upon from immunological and chemical points of view.

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The carcinogenic effect of bracken fern (Pteris aquilina) to the urinary bladder of mice was studied. Powdered bracken fern mixed with a basic commercial diet (1:4 by weight) was fed to a group of 40 ICR strain mice for 20 weeks after the implantation of a glass bead into the bladder. A total experimental period was 70 weeks. Fifteen mice survived 40 or more weeks and 4 mice (27%) developed urinary bladder tumors. No urinary bladder tumor was found in the group of mice fed a similar bracken fern diet mixture without a glass bead in their bladder and in the control group of mice fed a normal diet after the implantation of a glass bead. The result of this experiment may indicate that there is a metabolite(s) in the urine of bracken-fed mice carcinogenic to the bladder.

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In an attempt to quantitate DNA repair induced by Neocarzinostatin, the incorporation of labeled thymidine into the human peripheral lymphocytes after exposure to the agent was studied by autoradiography. The exposure of lymphocytes to Veocarzinostatin for 60min at the concentrations as low as 0.05μg/ml caused a significant increase in the number of grains per cell within 2hr of incubation with 10μCi/ml of ³H-thymidine in the presence of 2mM of hydroxyurea. The number of grains increased with the increasing dose of the agent up to the concentration of around 2.5μg/ml and then fell at higher concentrations. The extent of maximum incorporation induced by Neocarzinostatin was found to be almost comparable to that induced by 100erg/mm² of UV irradiation. Hydroxyurea or caffeine in the labeling medium showed little or no effect on the grain count, but acriflavine at 0.1mM reduced the grain count by a factor of about 6.
These results indicate that relatively high level of repair synthesis occurred in human lymphocytes after exposure to Neocarzinostatin and provide further evidence for the direct damage of cellular DNA induced by the antibiotic.

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Urinary polyamines in patients with gastric cancer were determined and changes in their content due to gastrectomy were studied. Total polyamines (spermine plus spermidine) in patients with gastric cancer of either stage II or III decreased significantly after the operation, the mean values before and after operation being 8.35 and 2.71mg/day, respectively. The mean value of total polyamines in normal cases has been reported to be 4.02±1.35mg/day, so that the value in these patients after the operation is within the normal range.

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Sprague-Dawley rats were given gastric intubation of cycad extract (group 1), rectal infusion of cycasin (group 2), or rectal infusion of cycad extract after external colostomy at 1/3 proximal portion of the large intestine (group 3). In group 1, intestinal tumors developed in any portion of the intestinal tract ranging from the duodenum to the rectum. In group 2, tumors developed in mucosa of the large intestine. In group 3, however, tumors arose from both sites of intestinal mucosa which were in contact and not in contact directly with the cycad extract infused. Possible hypothesis for intestinal tumor development by cycad extract and cycasin was presented.

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Pretreatment with OK-432 showed marked suppresive effect on splenomegaly induced by Friend leukemia virus in mice. Post-treatment was less effective than pretreatment. OK-432 did not inactivate the virus infectivity by in vitro contact.

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Several α-acetoxy-dialkylnitrosamines raelated to dibutylnitrosamine were synthesized and the mutagenic action of dialkynitrosamine derivatives on microorganisms, without using any metabolic activation system, is described.

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Fractions obtained from cell-free Ehrlich carcinoma ascites based on the molecular weight revealed various kinds of activity affecting the antibody production, ability of carbon clearance, delayed-type hypersensitivity, tumor graft regression, etc., to various extent in mice.

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Administration of the herb extract of Capsella bursa-pastoris prevented the liver catalase activity from being reduced in the rats fed 3'-methyl-4-(dimethylamino)azobenzene. This finding was associated with the inhibitory effect of the herb extract on the azo-dye carcinogenesis.

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