The stromal reaction in tumors was investigated for detecting conventional histopathological and histochemical patterns. The tumors examined consisted of expansively and diffusely invading types of several human tumors, and experimental tumors of epithelial and mesenchymal origin induced in mice by 20-methylcholanthrene. Stroma generally showed several patterns of responses for tumor growth depending on the type of invasion, but not closely related to malignancy grading. In diffusely invading tumors, cell infiltration and fibroblastic proliferation were very active while, in expansively invading tumors, cell infiltration was slight and fibroblastic connective tissue tended to encapsulate the tumor parenchyma. Alkaline phosphatase, aminopeptidase, β-glucuronidase, and oxidative enzymes were demonstrable in the fibroblastic stroma and in connective tissue capsules. Acid phosphatase was detected in stromal round cells which were suggestive of histiocytes, being increased in number with a diffuse type invasion. It is assumed that the mast cell has a function related to a defensive ability as in other stromal components. As far as the present study is concerned, the stroma is very likely to show a defensive reaction against tumor invasion, although the presence of promotive reaction cannot be absolutely denied.

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Antigenic constituents of the extracts from livers of normal rats and from those fed 4-dimethylaminoazobenzene (DAB) were analysed by the immunodiffusion methods, with a special reference to the histopathological findings of the liver.
1) The constituents of normal liver, showing numerous precipitin lines in the γ- and β-globulin regions by immunoelectrophoresis, decreased gradually in the course of DAB-feeding and showed a marked reduction in the hepatoma tissue.
2) Patterns of hepatoma extracts differed from those of normal or non-tumorous livers, indicating a reduction of components in the γ- and β-regions, and an increase of antigens in the α-region. With absorbed specific antisera, it was possible to detect four characteristic antigens in hepatoma extracts, which could not be found in normal materials.
3) In the sera of tumor-bearing rats. one abnormal antigenic constituent involved in the α₂-region was demonstrated with the absorbed antisera. It has been confirmed that one of the hepatoma antigens is released into the serum.

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An epidermoid lung carcinoma, antigenic to isologous hosts, was produced in a female rat of Buffalo strain by treatment with 4-nitroquinoline 1-oxide and transferred as a subcutaneous tumor. In a pedigree (Line V) produced by brother-sister matings from the female rat in which the tumor had arisen, the transplantation rate was significantly lower than that in other lines diverged from the same origin as Line V.
The second and subsequent tumor grafts were completely rejected in all rats used and an attempt was made to induce immunological unresponsiveness to the tumor graft in rats by inoculating tumor cells within 8 days after birth (within the adaptive period of rats). Progressive growth of repeated tumor grafts was demonstrated in this experiment.

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A series of systemic experiments have been made to induce neoplasia in rat kidneys with N-nitrosodimethylamine (DMN). Results showed that a high incidence of kidney tumors was induced by feeding rats with diets containing DMN at the level of 500p.p.m. for 2 weeks and then returning them to the basal diet. However, liver carcinomas were induced when DMN at the level of 100p.p.m. was administered for a long period. Autoradiographically, the number of ³H-labeled cells in the tubular epithelial cells of the kidney was greater when treated with 500p.p.m. DMN for a short period than when treated with 100p.p.m. DMN for a long period. These findings on the synthesis of deoxyribonucleic acid (DNA) agree with the fact that the incidence of kidney tumors was greater in rats treated with a high level of DMN for a short period than in those treated with a low level of DMN for a long period. Histologically the kidney tumors were divided into two types; one was renal cell type, and the other was anaplastic cell type. It was concluded that renal cell-type tumors might have been derived from tubular epithelial cells and anaplastic celltype tumors from the cells of the interstitial tissue of the kidney. The number of ³H-labeled cells in the pre-neoplastic areas of the kidneys showed a greater increase than that of the cells of the non-neoplastic areas.

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The influence of the serum of patients with various malignant tumors on HeLa cell culture was investigated in a simplified replicate tissue culture. In the culture medium containing their sera the cells grew better, less well, or unchanged than the control sera; namely, great differences existed in the growth behavior of HeLa cells in fresh serum of cancer patients. Therefore, the sera were divided into growthpromoting, growth-controlling, and unchanged groups.
The fraction of serum protein was measured, in addition to a series of studies to evaluate the changes in various serum protein during continuous cell cultivation in each group. Between the growth-promoting and the growth-controlling group, there existed little difference in the fraction of serum protein to affect growth of cells in cell culture, and there was found no difference in the capacity of the serum on cell growth between the patients with early cancer and advanced cancer. It was also clarified that the major property of the serum existed in the fraction of albumin.
In addition, the specific action of the patient's serum to the propagation of the cells was studied to learn if this specific action be related to the patient's own resistance to cancer, and also if they can be used for predicting the outcome of patients with cancer. As a result, those individuals whose sera inhibited the growth of the cells in tissue culture had a tendency to show a better survival rate than those whose sera did not, but the difference in the survival rate between the growth-promoting and gowth-controlling group was statistically not significant by the χ²-test. The importance of the rôle of individual human serum in the growth of cancer is stressed.

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1. Sixty lesions of minute, less than 2cm in the greatest diameter, well-differentiated adenocarcinoma or atypical epithelial focus, limited in the mucosa, were examined histologically. These lesions were obtained from 48 patients, 41 of which were incidentally discovered by routine histological examination and the remaining 7 were clinically diagnosed.
2. In comparison with minute well-differentiated adenocarcinoma and benign but atypical epithelial foci, histological criteria of malignancy have been presented as (1) the sharp borderline compressing the normal surrounding tissues, and (2) absence of normal Paneth cells in the affected mucosa. If an atypical epithelial focus cannot be diagnosed as malignant or benign at the cellular level and shows these above two evidences it is most likely to be malignant. Based on these proposed criteria, 27 of the total 60 lesions were classified as malignant and 33 benign.
3. The interrelationship of intestinal metaplasia and carcinoma occurrence of the gastric mucosa has been briefly discussed.

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The toxohormone effect, as represented by the decrease of liver catalase activity, was examined in mice bearing one of the two types of autochthonous tumors; either spontaneous mammary adenocarcinoma or 20-methylcholanthrene-induced primary sarcoma. A progressive decrease of liver catalase activity, roughly proportional to the weight of the tumors, was demonstrated in both cases, fully justifying the conclusion that the toxohormone concept, hitherto developed largely on the basis of studies on mice and rats bearing transplanted tumors, holds also in the autochthonous tumor-host system. Both spontaneous mammary adenocarcinomas and methylcholanthrene-induced primary sarcomas used in these experiments yielded active toxohormone fractions.

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Histochemical methods were presented for the demonstration of glucose metabolism of oxidative enzymes such as lactate, glucose-6-phosphate, and 6-phosphogluconate dehydrogenase in 83 cases of benign and malignant tumors.
Enzymatic activities for glucose-6-phosphate and 6-phosphogluconate dehydrogenase were generally confined to neoplastic epithelium and to normal epithelial elements, while lactate dehydrogenase activity was present in neoplastic cells and stromas. Activity levels of glucose-6-phosphate and 6-phosphogluconate dehydrogenases were variable from trace to high, and glucose-6-phosphate dehydrogenase activity in neoplasms was a little higher than 6-phosphogluconate dehydrogenase activity. Lactate dehydrogenase activity was generally high in tumor cells. Tumors showing a high glucose-6-phosphate dehydrogenase activity also exhibited a high lactate dehydrogenase activity, without relation to the grade of malignancy or differentiation.
Steroid-synthesizing tissues, i.e., the adrenal cortex, internal thecal cell, and corpus luteum, were characterized by the presence of the highest glucose-6-phosphate dehydrogenase activity and a comparatively high 6-phosphogluconate dehydrogenase activity. Adrenocortical adenoma and ovarian tumor were also highly reactive to both enzymes.

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Effect of prolactin injection on the established spontaneous mammary tumor growth was investigated using Swiss albino mice. There were no differences between injected and control animals in the mean growth rate per week, the whole growth rate, and the number of tumors which appeared.

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Isologous transplantation of macroscopic spleen foci of Friend's disease was attempted, and was successful on 7 different occasions, establishing 6 subcutaneously transplantable solid tumors. All were converted into ascites forms. One of the ascites strains provides tumor cells cytologically resembling proerythroblasts or basophilic erythroblasts as seen in spleen foci.

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