A large dose of Mitomycin-C was given during gastrectomy and on the first postoperative day in 489 gastric cancer patients. Both from the analysis of the postoperative complications and from the post-operative mortality, the harmlessness of this method was shown. The intermediate results of gastrectomy were investigated in 515 non-curative gastrectomy cases. The cases in which a large-dose administration of Mitomycin-C was carried out during gastrectomy showed an excellent survival rate at 6, 12, and 18 months after the operation as compared with the control group. The transplantation of homologous bone marrow cells seems to diminish the possibility of recurrence in enhancing the effect of chemotherapy, and its mechanism was discussed.

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The present study was carried out to ascertain the mitotic activity of human gastroduodenal epithelium, by estimating the percentage of epithelial cells which undergo division at any moment, and the renewal times were determined with the aid of the Colcemid technique.
In order to ascertain mitotic activity, at least 2000 cells were counted in each of the gastro-duodenal tissues removed by surgery from 29 male and 21 female patients. The results were compared among different disease groups.
The mitotic activity of gastro-duodenal epithelium of gastric cancer patients was significantly lower than that of the group of non-cancer patients (peptic ulcer, gastritis, etc.). The pathological significanceso f these findings were discussed.
In order to obtain high mitotic values and turnover time of human gastro-duodenal epithelium, the Colcemid technique was employed. Fifty-one male and twentyone female patients with various gastro-intestinal lesions were injected with 0.15mg/kg of Colcemid intravenously 3 to 7 hours before gastrectomy.
Difference in mitotic values between gastric cancer and non-cancer group was statistically highly significant.
On the basis of the mitotic values obtained by the Colcemid technique, the turnover rates were calculated. In gastric cancer group, it was 7 days in the body mucosa, 4.7 days in the pyloric mucosa, and 4.5 days in the duodenal mucosa.
From this observation, it is known that the whole epithelial lining of human stomach body, pylorus, and duodenum are completely renewed at least once about every 6.5 days, 2.4 days, and 2 days, respectively.

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Low mitotic activity of gastric and duodenal mucosa observed in the cancer stomach has been reported in the preceding paper, in comparison with the noncancer stomach. The cell renewal rate of digestive tract has also been discussed which was capable of estimating by means of the Colcemid technique.
Further study of this problem was carried out as to the buccal mucosa instead of the gastro-intestinal epithelium. The experimentation was performed on the materials obtained from the patients with a variety of diseases including cancer.
As a result, a conspicuous difference was observed in the mitotic rate of the buccal mucosa between cancer and non-cancer groups. The rate from the cancer group appeared lower than that from the non-cancer group, and each of them was strictly divided by a borderline of 2.0% level.
From this result, it is suggested that the mitotic activity of tissues may be suppressed in the cancer-bearing individuals by a certain unknown factor.
Three interesting cases were reported, all of which had been difficult to diagnose whether it was cancer or not at the first biopsy, and finally was able to confirm the exact diagnosis by the use of this technique.

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A study was made on the in vitro interactions between tumor cells and fibroblasts derived from the connective tissue adjacent to the tumor in the same individual, and of the influence of various stroma-affecting agents (ascorbic acid, hyaluronidase, heparin, chondroitinsulfate, and hydrocortisone) on those interactions. For this purpose, cell strains derived from Walker-256 rat carcinoma, T241 mouse sarcoma, and adjacent connective tissue were subcultured.
The five stroma-affecting agents in the concentrations used did not show any promoting effect on fibroblast growth. On the other hand, the growth of both strains of tumor cells was promoted by ascorbic acid and inhibited by hyaluronidase, heparin, and chondroitinsulfate. The effect of these agents on the interactions between tumor cells and fibroblasts varied from case to case.
Different results from in vitro interactions were obtained in experiments performed at different times of subculture or by different methods.
In general, however, the growth of Walker tumor cells was limited by the network of fibroblasts. In contrast, T241 tumor cells were able to grow into a meshwork of growing fibroblasts, and a large number of T241 tumor cells showed a marked ability to cause the dissolution of fibroblasts.
The effects of cell-free fluids from fibroblasts or tumor-cell cultures on the growth of tumor cells or fibroblasts, respectively, were also studied. In particular, effect on fibroblast multiplication.
On the basis of the present study, it appears that the in vitro interactions between tumor cells and fibroblasts in combined cultures depends on population density, the malignant potency of the tumor cells, and the time of subcultivation.
The relative importance of these factors is often different in different cases.

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The simple and partial correlations between either two of the following characters were investigated using Swiss Albino mice; primiparous age, litter number, breeding period till mammary tumor incidence, and tumor age, and the relative importances of primiparous age and litter number on the breeding period till tumor incidence or tumor age.
It was found that the primiparous age, not to say the litter number, played an important rôle in determining the appearance of mammary tumor.

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1) The effect of 4-nitroquinoline 1-oxide and its derivative, 4-hydroxyaminoquinoline 1-oxide, on incorporation of ¹⁴C-labeled lysine, phenylalanine, proline, and glycine, stimulated by addition of calf thymus DNA, was investigated in the nuclear ribosome system in vitro.
2) The stimulatory activity of heat-denatured DNA was not affected by the pre-treatment of DNA with 4-hydroxyaminoquinoline 1-oxide.
3) The treatment of native DNA with 4-hydroxyaminoquinoline 1-oxide, followed by heat-denaturation, did not change the stimulatory activity of the DNA.
4) The addition of 4-nitroquinoline 1-oxide or 4-hydroxyaminoquinoline 1-oxide to the incubation mixture did not result in any significant alteration of the ¹⁴C-labeled amino acid incorporation stimulated by heat-denatured calf thymus DNA.
5) In contrast, the treatment of calf thymus DNA with nitrous acid resulted in a significant alteration of ¹⁴C-glycine incorporation stimulated by the DNA.
6) These results indicate that 4-nitroquinoline 1-oxide and 4-hydroxyaminoquinoline 1-oxide cause neither detectable codon-misreading nor impairing of the proper codon properties in the nuclear ribosome system in vitro.

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The incidence of leukemia in the RF mice exposed to a single whole-body irradiation of 350 R X-ray was 77.4%, 41 out of 53 mice. Of those, 20 animals developed the thymic type and 20 others the non-thymic type lymphocytic leukemia, while only one developed myelogenous leukemia. The spontaneous incidence of leukemia in RF mice was 0.7%, 2 out of 300 mice.
By inoculating the cell-free filtrates from the leukemic RF mice, induced by a single whole-body X-irradiation of newborn mice of the same strain less than 16 hours old, 4 (25%) of 16 inoculated animals developed leukemia 12-22 months after the inoculation.
In the serial cell-free transmission, the development of leukemia was observed in 60%, 6 out of 10 in the second passage, and in 17%, 1 out of 6 in the third passage. In the inoculation of the cell-free filtrates from normal mice to 20 newborn mice of the same strain, not a single case of leukemia developed. On the basis of these findings, a discussion was made on the rôle of virus in the induction of leukemia by X-ray irradiation.

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Alkaline phosphatase activity was studied in 409 malignant and 225 benign human neoplasms employing a simultaneous azo-dye coupling technique. The enzymatic activity was not demonstrated in about 80% of malignant epithelial tumors. The neoplastic epithelium of oral squamous-cell carcinoma was completely devoid of the activity. In uterine cancers, endometrial adenocarcinoma showed an intense activity, and only about 4% of cervical cancers was positive. In gastric cancers, the enzymatic activity was negative in malignant epithelia in 78% of the cases, but there was no activity in other cancers of the digestive tract. In breast tumors, smalllobular type of fibroadenoma showed higher activity in periacinar aspects, whereas malignant epithelia in breast cancers hardly showed the activity. It seemed to be impossible for this study to establish a correlation between enzymatic activity and histopathologic pattern of tumors except for a few kinds of neoplasms. However, it is accepted that the occurrence of alkaline phosphatase in stromas of carcinomas was associated with inflammation, but the stromal activity appeared under a condition of little inflammation or none in some cancers; oral epidermoid carcinoma and adenocarcinoma in the stomach, the small and large intestine, the rectum, and the breast.

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Electron microscopic observations on two lines of transplantable Friend ascites tumors (refered to as Friend tumors) are described. Friend viruses were frequently observed intercellularly in the Friend tumor, and the course of development of the virus from the membranous surface of the tumor cell was observed. Friend virus was roughly 900Å in diameter and was considered to be Bernhard's type-C particles. It is evident that the Friend tumor cell is a host cell for Friend virus production while continuing to proliferate as a malignant tumor.

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The relationship between calcium content and mutual adhesiveness of tumor cells was studied by utilizing microincineration technique in ascites hepatoma AH-130, AH-7974, and AH-602, and in human carcinoma, especially gastric carcinoma. In the ascites hepatoma, calcium content in the tumor ascites and invasive tumor of the omentum was very high in AH-602, medium in AH-7974, and very low in AH-130. The tumor strain which forms smaller "islands" had a low calcium content and that with large "islands" had a high calcium content. In human gastric carcinoma, calcium content decreases in the descending order of squamous cell carcinoma, adenocarcinoma, and scirrhous adenocarcinoma. Calcium content was extremely low in the region where cancer cells involve muscle layer and further decreased in the cancer nests involving lymphatic vessels. The decrease of calcium content reduces mutual adhesiveness of the cells, produces anaplastic picture in histology, and increases invasive growth and metastatic spread of the tumor cells.

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Effect of cigarette smoke on the experimental induction of lung cancer in mice by 4-nitroquinoline 1-oxide was examined. When mice received 0.5mg of the carcinogen, the incidence of lung cancer in mice was not significantly different, between those with and without inhalation of cigarette smoke but the incidence of lung cancer in the smoke inhaled mice after receiving 0.25mg of the carcinogen was much higher than that in mice without inhalation of cigarette smoke, The cigarette smoke, though not strongly carcinogenic in itself, may play an accessory role in the incidence of cancers of the lung in mice.

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Newborn dd strain mice were given a single subcutaneous injection of 4-nitroquinoline 1-oxide in lecithin. Not a single mouse showed manifest lesion in the lung during the first 45 days. Adenomas of the lung appeared at 60 days, and lung cancers after 120 days, their incidence becoming higher with time from that day. No tumor was found in the controls. The process of induction of lung cancers could be divided into three phases; Phase I, with no manifest lesion, II, with nodules of adenoma, and III, with cancer. Considering the established fact that the cells in the lung are renewed every 30-50 days, the three phases in the lung cancer development may roughly correspond in the relative length of time to the cell renewal in the lung. Our experimental results actually showed that after cells are attacked by the carcinogen at birth, the submanifestational, adenomatous, and cancerous states in the lung follow by steps in the course of the induction, corresponding to this time schedule. Thus the manifestation of the tumors may be closely related to the renewal of tissue cells.

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Five brands of bourbons, eight brands of Scotch, and two brands of Japanese whisky were analyzed for polycyclic aromatic hydrocarbons and a Japanese whisky for phenols by means of column and paper chromatography, ultraviolet absorption spectroscopy, and gas chromatography. Presence of small amounts of phenanthrene, pyrene, or fluoranthene was noted for all the brands of whisky analyzed. Benz[a]-anthracene and chrysene were detected in two kinds of whisky, a Japanese and a Scotch, while benzo[a]pyrene, benzo[b]fluoranthene, and benzo[e]pyrene only in a Scotch. The concentration of these hydrocarbons was extremely low, ranging from 0.03 to 0.08μg/L. Phenol and several alkylphenols were also identified in a Japanese whisky and their concentration was estimated to be 1-23μg/L.

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Incidence of lung cancer is very high when lecithin is used as a vehicle for subcutaneous injection of 4-nitroquinoline 1-oxide. Lecithin is recommended as the most suitable vehicle for experimental induction of lung cancer.

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