From observations of human tumors, attention has been drawn to the relationship existing from various angles, between certain aspects of malformation and growth of tumors. In the development of malformations many and varied conditions have been pointed out to exist, while recent experimental works in this field have succeeded in the artificial production of malformations. Similarly numerous factors have been said to influence the growth of tumors and the multiple nature of tumor growth has been confirmed. The presence of viral tumors has on one hand been definitely recognized. From observations on the growth of human tumors and results of experimental research, it has been found that certain viruses cause unbalanced proliferation of young immature cells which leads to the production of malformations.
We transplanted a viral tumor, chicken sarcoma, into developing chick embryo and succeeded in producing tumors and numerous varied malformations in them. We also transplanted chick sarcoma into egg laying hens and succeeded in demonstrating the occurrence of infection via the ova with resulting formation of congenital sarcoma in chicks. These chicks were also found to have varied malformations. Next, a mammalian tumor, Brown Pearce rabbit tumor, was similarly transplanted into developing chick embryo, and we found that according to the stage of development of the embryo many malformations are produced in the central nervous system and other parts of the embryo.
Among the viruses there are some that produce regressive changes and others that produce proliferation of tissues. Hence, of the malformations produced there are those that are due to regressions of tissue growth and others to excessive proliferation of tissues. The virus of chicken sarcoma belongs to the latter group, producing both tumors and malformations. When cancerogenic substances are employed there will be cases where tissue malformations are produced by anomalous action of these substances on proliferation of embryonal cells.

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In our previous feeding tests of the Yoshida tumor with albino rats we observed sub-line tumor growths in twenty per cent of the test animals. This may be interpreted as a carcinogenesis due to a subcellular agent which infected the rats through digestive canal by tumor feeding. This time by repeated feedings of Hirosaki sarcoma to mix bred rats new tumors were produced in about twenty-nine per cent of the test animals. The tumor growths, resembling those in the Yoshida tumor feedings, appeared mainly at the skull base and the cervical regions; and especially tumorization of the submaxillary lymphnode was marked. There was also a tendency of swelling of the submaxillary lymphnode and formation of necrotic foci prior to the tumorization. In the viscera of test animals an inflammatory picture having mesenchymalcell reaction as its basic change.
Tumorization potentiality is latent in such inflammatory tissues; and despite being no tumoral cells when transplanted subcutaneously in rats it is possible to produce a transplantable tumor. Moreover, the rate of sub-line sarcoma growth has been surprisingly accelerated by successive feeding tests.
Next, in feeding test of homogenate of the Hirosaki sarcoma to rats an omentum tumor developed in one out of twenty-one cases despite mechanical injury and digestion of gastric juice on tumor cells. From the fact that cell-nuclei can resist pepsin, it may be thought that there is a possibility of existence of carcinogenic factors in the portion of a few nuclei reaching as far as the intestine after escaping all obstacles on its way. In addition, the Hirosaki sarcoma agent has been successifully isolated from the sub-line sarcoma.

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Historical review on the International Staging of carcinoma of the cervix uteri, especially on Stage O (Intra-epithelial carcinoma) was introduced, and clinical evaluations in diagnosis of Stage O carcinoma with vaginal smear method, colposcopy and punch biopsy were discussed. During one year and four months, from January 1956 to April 1957, 18 patients with Stage O carcinoma were found among 7, 405 (0.24%) at the Outpatient Clinic of Obstetrical and Gynecological Departemnt of the Okayama University Hospital.
Ten patients out of 18 were examined histologically by so-called serial section method of specimens extirpated by cold knife conization or panhysterectomy.
Final decisions were as follows:
benign abnormality 3
intra-epithelial carcinoma 3
invasive carcinoma 4
So the patient whose punch biopsy specimen showed figure of intra-epithelial carcinoma was not always real Stage O carcinoma, and should not be hasty to treat definitively as a patient with Stage O carcinoma.
Repeated examinations by vaginal smear and multiple punch biopsy or rather by cold knife conization are necessary to get the final decision of this kind of disease.
The importance of follow-up examinations in patients who have had Stage O carcinoma of the cervix was exphasized.

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The metastasis of the gastric cancer in the lymphnodes is macro-scopically classified in three types; the small nodular sporadic type being commonly observed, the large nodular localized type relatively bengin and the false type in which swelled lymphnodes are microscopically not invated by cancer cells but merely inflammtaic.
Concerning the malignancy of the cancer, similar features have been macroscopically and microscopically observed in the metastasis of the lymphnodes as well as its original cancer of the stomach.
Our clinical and experimental studies have revealed the fact that the size of the nuclei of the cancer cells plays an important role in the metastasis-formation. That is, the cancer cells with the nuclei of smaller size develop a widespread metastasis, while those with bigger size make a localized one.
The gastric cancer with metastasis in the liver mostly shows the large nodular localized type.
On the other hand, many differences have been observed in gastric cancer between the greater and lesser curvatures. Macroscopically diffuse infiltration is always seen on the side of the lesser curvature, while it is never observed in the side of the greater culvature. The size of the nuclei of the cancer cells is bigger on the side of the greater curvature than that of the lesser. The rate of growth of the stroma being considered a vital defensive reaction is higher on the side of the greater curvature. The ribo-nucleic acid content is more in the cancer cells of the lesser curvature than in those of the greater.

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No systemic study to induce leukemia in the experimental animals with the internal irradiation with radioactive isotopes has ever been attempted. We set about experiments with this object in 1953 and succeeded in the induction of experimental leukemia in dt, ddF and ddN uniform strain mice treated with small frequent doses of P³², Sr⁸⁹ and Ce¹⁴⁴.
Single dosis of the isotopes ranged from 0.03 to 0.5 μc per gram body weight twice a week was administrated to mice with the methods of intravenous injection, intraperitoneal injection, intratracheal administration and intraesophageal dripping. The total administrations of the isotopes were 7-16 times.
The development of leukemia was confirmed in higher frequencies among mice which were administered with small frequent doses of P³². The highest incidence of leukemia throughout our experiments was about 42% in the experiment with P³² at 0.3-0.5 μc level.
The development of leukemia remains in lower frequencies among mice which were given small frequent doses of Sr⁸⁹ or Ce¹⁴⁴. In the former cases we confirmed the higher incidence of osteogenic sarcoma. In the latter cases the aplasia of the bone marrow were easily resulted.
Among the Beta-emitting radioisotopes the one which has the shorter halflife and more intensive energy such as P³² is more suitable to induce leukemia in mice so far we had experienced.
The excessive and at the same time partially abnormal regeneration preceed the development of leukemia after the administrations of small frequent doses of the radioisotopes.
The order of the intensity of the radioactivity in the bone after the administration of the radioisotope change from time to time. Such effect will also contribute to enforce the abnormal regeneration of the bone marrow.
For the development of leukemia in mice after the administration of the frequent small doses of the radioisotope we should not overlook the most intensive regenerative hematopoietic activity in the bone marrow corresponding middle portion of the long bone such as the femur.

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Many investigators have reported lymphoid tumor in mice. The authors will describe in the present report the pathology of transplantable lymphoid tumors which were induced in na2 uniform strain of mice by the continuous administration of new synthetic estrogens belonging to triphenylethylene derivatives. These tumors occurred from the thymus or superficial lymph nodes situated in the cervical, axillar and mediastinal regions. The hematological and pathological features differ from each other. The incidence of these tumors was some 20%. By the histological examination it was revealed that the adrenal cortex showed interesting changes apparentaly related to the induction of tumor. Eight cases of tumors were transplanted through many tumor generations subcutaneously, intraperitoneally and intraveneously. These trans-plantable lymphoid tumors were called MN sarcoma. The pathological features and the cytology of tumor cells of each line of MN sarcoma, had their specific characters and were maintained during the period of transplantation for 30 to 100 generations. In the case of lymphatic leucosarcomatosis the transplantation and transformation from subcutan solid tumor to ascites tumor were both very easy; on the contrary, they were relatively difficult in the case of aleukemic lymphosarcoma. When the method of transplantation was limited to a definite one, no variation was found in the hematological and post-mortem pattern among mice with the same line of MN sarcoma. But the marked change in the transplantation method resulted in different patterns. The fact that there existed some variation of pattern accompanied by the different methods of transplantation was exactly related to the systemic reaction, including the reaction of serum protein, of the whold body, of animals inoculated with MN sarcoma and that had no connection with the character of MN sarcoma cells.

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The 1st report in the 57th Japanese Surgical General Association announced that we had proved biologically that there were substances like androgen in the hilus of the ovary of a adult cow.
Namely, by dividing the ovary into three parts and applying two kinds of emulsion salve, which were made of the hilus and body tissue of the ovary, to the comb of two groups of cocks which were castrated, it was made clear that the comb to which the salve of hilus was applied grew more remarkably.
Consequently, it was found that substances like androgen were being secreted from the hilus of the ovary.
In addition to the 1st report, the results of comparing the histological figure of the comb which showed more growth by applying the salve of hilus with that of the one to which the salve of body was applied were as follows; the smooth muscle fibre is more in the corium layer of the comb to which the salve of hilus was applied than in that of the one to which the salve of body was applied, and therefore the combe to which the salve of hilus was applied is scanty of the subcutaneous tissue.
The wrinkles of the epithelium to which the salve of hilus was applied were scarce, besides it's horny layer is thin.
To sum up the above mentioned, the differences in quality was not noticed at all between the histological figure of the comb to which the salve of hilus and that of the one to which the salve of body was applied, but only the differences in quantity was noticed.
In other words, some substances are being secreted which stimulate the normal cells of the comb to increase in number.
Moreover, according to the results of the above experiments, we, criticizing the old cast ration in the breast cancer at the last stage, dilated on the theoretical ground that the selective castration we bring forward was excellent.

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所謂網膜膠腫は幼児を好んで侵し,網膜に発生する悪性の腫瘍として眼科領域に於て臨床的に良く知られている.併し本腫瘍の本態に関しては病理形態学的或は組織発生学的に種々論議のある所である.
我々は最近3才の男児で全身の骨及びリンパ節に極めて多発性の転移を起し,対側眼球に併発巣を有する網膜膠腫(Retinoblastoma)の1例を剖検した.本例は患児を含め同胞2人共に両側性網膜膠腫で死亡しており,家族的発生が窺える.
本例に於て剖検時に右側眼球網膜に併発している極めて初期の腫瘍を発見し興味ある所見を観察した.即ち腫瘍組織と網膜の移行部に於て網膜の内顆粒層が漸時腫大して腫瘍組織に移行し,その部の腫瘍細胞は内顆粒層を構成している神経細胞に酷似して,この腫瘍細胞が内顆粒層の神経細胞を母細胞とすることを暗示する像を示していた.
本腫瘍のhistogenesisを究明する上に於てこの症例は貴重な資料を提供するものである.

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The so-called hibernoma is a peculiar fatty tumor arising from the residue of embryonal brown fat tissue. The present case is 10 years old female infant, who had been conscious of small lump at left submaxillar area for the past several years.
The tumor, recently enlarged to the size of a hen's egg, was excised surgically, and surmised as lipoma.
Microscopically, it showed a multilobulated figure consisted of nearly uniform multilocural fat cells, 15 to 25 μ in diameter. The tumor cell was entangled with dense network of capillaries showing no distinct boundary between cellular membrane and capillary wall as found in normal embryonal brown fat or hibernating gland of animals, which is considered to be a feature characteristic to this tumor.
As the nomenclature, “hibernoma” by Gery seems not appropriate for the human tumor, the authors propose the term “lipoma fuscum”.

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This report deals with a rare case of neoplasm in a 16-year-old male patient who succumbed to recurrent extra-renal nephroblastoma (Wilms's tumor) with a huge metastatic tumor in the retroperitoneal cavity.
Clinically, his initial complaint was slight swelling of the left hypochondrium in April 1956. He was operated for the removal of a retroperitoneal tumor and the left kidney. He died of general cachexia due to the enlargement of the recurrent tumor. The kidney contained no neoplasm.
At autopsy, the most remarkable findings was the existence of two soft, huge tumor masses in the retroperitoneal and pelvic cavities nearly filling these spaces. The recurrent tumor mass was in the left hypochondrium and consisted of a dark reddish, ovoid, soft tissue mass not unlike a hematoma. The cut surface revealed that it contained a greyish-white, ovoid, soft, parenchymatous tumor tissue, and it measured 7.0cm. in diameter. The metastasized tumor mass consisted of irregularly-shaped, greyish-white, soft tissue. The cut surface revealed many scattered areas of hemorrhage. Metastases were also seen in the liver and in the serosa of the ileum.
Histologically, the findings of recurrent tumor were almost the same as that of the metastatic and surgically removed tumors. Their structure varied greatly according to areas. In these tumors, epithelial structures showing a great diversity of form, including undifferentiated epithelial clumps, tubules in all stages of formation, and pro-glomeruli, predominated. Sarcomatous structures, mesenchymal and undifferentiated tissue were also seen. Smooth muscle and fat tissue were observed occasionally.

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1) Two cases of leukemoid reaction, one, male 55 yearsold and the other, female 41 years of age, are reported herewith.
Peripheral blood picture of both cases was that of leukemia, but the growing modus of explanted bone marrow tissue in the “tissue culture of the bone marrow” revealed that these cases were of leukemoid reaction.
Malignant tumor cells were recognized in the vital observation and the smear preparations of the bone marrow cells. X-ray examination of the stomach, examination of gastric juice and other findings indicated gastric cancer, and this was confirmed at autopsy.
Thus these two cases were suspected to be the leukemoid reaction induced by the bone marrow metastasis of gastric cancer.
In later histological examinations, however, the male case proved to be endothelioma of the bone marrow accidentally associated with cancer of the stomach.
2) In these two cases it has been proved that the tissue cultur of ethe bone marrow initiated in our department is truly beneficial for differenciating leukemoid reaction from leukemia.

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There had been no precendent where the isolation of viruses from tumors was attempted by the conventional method usually employed in isolating viruses from acute infectious diseases, namely, by passage through a heterogeneous species of animals, until Prof. Hamazaki first emphasized the necessity of applying the same method in isolation of viruses from tumors several years ago. Since then, it has already been proven in this laboratory that a filtrable agent can be isolated from such various transplantable tumors as the Yoshida tumor, chicken sarcoma, rabbit myxoma, etc. numbering well over 16 kinds.
Recently similar studies are being carried out on the tumors of human beings, and this time the authors have attempted isolation experiments of filtrable agents from coelothelioma, uterine cancer, gastric cancer, and leukemia. The results of our studies are presented in the following.
As the experimental animals, guinea-pigs were used. Successive inoculation revealed interalveolitis in the parenchyma of the lung, proliferative, granulative inflammation around the blood vessels and bronchi in the interstitium, and in the liver diffuse proliferation of stellate cells, diffuse or nodular infiltration of round cells.
These finding resemble those found in the case of such viruses as the HST virus, Brown-Pearce virus, n. n. chicken sarcoma virus, and Takeda sarcoma agent, and others; and therefore, it may be possible to assume the existence of a filtrable agent in the malignant tumor of human beings.

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A case was reported of dysgerminoma of the mediastinum. A twenty-three years old male was admitted to the hospital with a complaint of easy fatigability of four month's duration. A mass, size of fist, was found in the anterior mediastinum on chest roentgenogram.
No abnormality was noted in testes. No recurrence or metastasis have been found for four years since surgical extirpation of the mediastinal mass.
Brief review of the histogenesis of mediastinal teratoma was given and hypothesis of extragonadal germ cell (Friedman) was discussed.

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A number of literatures have been reported on the metastasis of uterine cancer. The metastatic lesions are most frequently found in the liver, lungs and pelvic organs at autopsy. It is believed, however, that metastasis is seldom in the bone.
Most of the clinical studies of uterine cancer have been directed to the lymphnodes which have been considered to be an possible site of metastasis and carefully removed in the radical operation. Little attention has been paid to the treatment of advanced stage of uterine cancer with metastasis.
Recently we have experienced 6 cases of ossal metastasis of uterine cancer in our clinic. In four cases, the metastasis occurred following the operation and in two cases the radical operation was not performed. During their hospitalization severe pain tortured them all day long. The metastasis was found in lumbal vertebrae in 3 cases, sacral bone in one case, cranial bone in one case. and right side femur and os tibiae in one case. The metastatic lesions found in cranial bones and os tibiae are remote metastasis, and they are perhaps due to haematogenious way.
The first X-ray examination revealed no significant findings, but subsequent X-ray check-ups gave abnormal shadow which made us suspect the bone metastasis. The repeated examination by X-ray photography made the diagnosis decisive.
From these experience it is our impression that the ossal metastasis is more frequent than it is generally believed to be. And if this is the case, it may be due to the progresses of operation techinique, radiation therapy, and chemotherapy against the uterine cancer which consequently have prolonged the average life of the patients.
It must be stressed that early X-ray examination of those suffering from pain may detect abnormal shadow in the bone to which hitherto no attention has been paid.
With the recent advancement of the treatment of cancer, it has become more and more important to prevent the metastasis of cancer and to detect the metastasis. if it has occurred, and to treat the metastatic lesions earlier stage.

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As, from clinical experience, chemotherapeutic agents were suspected to have some influence on the growth of the malignant tumor, their effects on the experimentally developed carcinoma and on the rate of its development were investigated. Chemotherapeutic agent used Streptmycin (SM), Penicillin (PC), and other antituberculous agents.
1. SM, SM with PC, PAS and INAH showed facilitating effects on the increase in ascites and the growth of subdermal nodes due to Ehrlich ascites carcinoma. On the contrary, PC showed no such effects.
2. SM, PC, and SM with PC also slightly facilitated the growth of Yoshida sarcoma.
3. Effects on experimental development of azo-dye hepatoma. The group administered with PC and SM showed almost the same rate of development of the carcinoma as that of the control group. However, decisive conclusion was difficult because both group was too few cases. The following observations may be said to be noteworthy: the experimental group showed a slightly lower liver index; judging from the increase in body weight the growth of the experimental group was facilitated in the first 200 days of the experiment; histollogically, the new growth of bile ducts and the increase of stellate cells seemed more remarkable in the experimental group.

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For the purpose of revelation of the regulatory mechanism of cell growth and reproduction, various cells including protozoa and tumor cells were observed under the varied oxygen tensions.
Blepharisma undurans japonicus cultured in the hay infusion fluid showed a changed division rate under the changed rate of O₂ to CO₂ in the atmosphere contacting to the cultured media; the cell division occurred most actively under the atmosphere in which the gas tension was kept in the rate of CO₂:O₂=6:4, and the cell death occurred in the atmospere having the O₂ tension higher than O₂:CO₂=8:2 or lower than O₂:CO=2:8, whereas the cells proceed to survive for a long period without cell division in the point O₂:CO₂=8:2 or 2:8. Electron microscipic observation proved that the swelling of mitochondria and the demolition of cristae brought about by the high oxygenation.
Fibroblasts from the heart of chick embryo proved the most active growth in vitro under such gas tension as O₂:N₂=5:5. The growth stopped when the rate of O₂ to N₂ reached 8:2.
Tumor cells, the Yoshida sarcoma, were suppressed of their cell division under the high oxygenated environments, but they still grew forming tumors.
The depression of the activity of succinic dehydrogenase was proved in the normal liver cells of mice by exposing to pure O₂ gas. The same dehydrogenase activity of DAB hepatoma cells was markedly low comparing to that of normal rat liver cells.
From these observations it was concluded that the depressing effect of O₂ on the cell division will be the result of demolition of the structure of mitochondria and the subsequent inactivation of their function, sggesting that O₂ tension in the environments may play an important role for the regulation of cell growth and cell division in the normal tissue.

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In examining the affinity of various cell components for porphyrin, we noticed the very marked affinity of extracellular small bodies in cancer tissues for protoporphyrin III, and we also ascertained that the substance in normal tissues which has an affinity for protoporphyrin III, and which occurs in mitochondria and myelin sheaths, is sphingomyelin. Investigation of the chemical nature of the extracellular small bodies in cancer tissues with the marked affinity for protoporphyrin III has led to the discovery of a new phospholipid.
This new phospholipid, malignolipin, has been shown to be composed of choline, spermine, phosphoric acid, and fatty acid.
Malignolipin is specific to malignant tumors. It is always found in malignant tumors, but never in normal tissues nor in pathological tissues other than malignant tumors.
We have devised a method to detect malignolipin in blood or ascites. This test is all positive in the blood of 129 patients bearing a malignant tumor, and is negative without exception in the blood of 48 normal persons as well 114 patients suffering from diseases other than a malignant tumor. This blood test is stated to serve for the early diagnosis of cancers. Further, malignolipin is ascertained to enhance the growth of Ehrlich's ascites cancer cells and to increase their mitotic rate.

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We have examined the influences of some radioactive substances, e. g., Ca⁴⁵, Sr⁹⁰, Fe⁵⁵⁵⁹, Ce¹³⁷ and Fission product (P) upon the development, either culturing the amphibian eggs in the medium annexed with the radioisotopes or injecting these substances into the pregnant mouse. The development of the amphibian egg is most seriously affected when operated soon after the fertilization, but even in the case operated after the gastrulation situs inversus cordis et viscerum and other anomalies have been observed. On the development of the fetus of the mouse, it is most effectual when the injection to the mother has been done at 8-10 days after the fertilization, resulting pseudencephaly, hydrocephaly, hydromyelia, microphthalmus, polydactyly, hemorrhage in the body wall and other anomalies.
On the other hand, we have also tested the effect of radioactive rainwater which has been brought about as a result of the explosion of atomic bombs since 1954. Dissolving the ashes of the rainwater into the distilled water, it has been injected into the pregnant mouse or used as a medium culturing the eggs of amphibia or Zebra Danio (a sort of tropical fish). The similar anomalies as induced by the radioisotopes are obtained in each case, that is, pseudencephaly, hydrocephaly etc. in the mouse fetus, microcephaly, anophthalmia, spin bifida, inversion of heart and visceral organs in Bufo vulgaris eggs, and cyclopia, vertebral flexure and other anomalies in Zebra Danio eggs. Remarkable is the fact that the effect of the radioactive rainwater is surprisingly serious, even when its radioactivity is considerably low.

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Cytopathological evaluations on HeLa cells in test tube cultures induced by anti-tumor drugs (Nitromin, 8-Azaguanine, Sarkomycin, Carzinophilin, Thio-TEPA and Mitomycin C), X-ray and Co⁶⁰ in sequence of dosage and time were described.
1. Range of effect measured by serial dilution and the time needed to induce maximal cell damage were determined as follows:
Complete cell desquamation from cover slip Minimalmitotic inhibition Hours after exposure
γ/c.c. γ/c.c.
Mitomycin C 50-25 0.005-0.002 96h
Carzinophilin 25-12.5 0.001-0.005 96h
Sarkomycin 500-250 62-31 24-48h
8-Azaguanine 2000-1000 125-62.5 24-48h
Nitromin 60-30 2.0-1.0 48-72h
2. Cell degeneration such as numerous cytoplasmic vacuolization induced by Azan and signet-ring like feature of cells in case of Sarkomycin respectively at both large dose were characteristically observed.
3. Regularly delayed giant cell induction at smaller dose in both cases of Mitomycin C and Thio-TEPA was prominent pattern of effect and this phenomenon was assumed to be analogous to the irradiation effect that we obtained by X-ray and Co⁶⁰ in this paper.
4. Both mitotic arrest and giant cell induction according to the same rate increase of irradiation dose were much more enhanced by Co⁶⁰ than X-ray.
5. The influence of Mitomycin C on HeLa cells has been throughly studied by means of morphological differential count of affected cells and plotting growth inhibitory curve by cell nuclei count.

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Vital observation on the cells in human ascites due to malignant tumor was performed by hanging-drop culture and cell suspension cultures of ascitic cells of celothelioma and Yoshida sarcoma were carried out by roller tube technic. The cytology of the cells was studied especially with the phase contrast microscope.
Results:
1) The cytological features of ascites due to malignant tumors in man are consist of two types of findings namely direct and indirect signs: the presence of malignant tumor cells, and characteristic cell composition and the cytological changes of the ascitic cells other than the tumor cells.
2) Cytological findings of malignant tumor cells in vital observation are more helpful for making diagnosis than those in the smear in which the cells are already dead.
3) The signet-ring cell derived from a malignant tumor cell is readily distinguishable from that of a phagocytic cell.
4) Cells of different type of malignant tumors, such as various types of stomach cancer, liver cancer, celothelioma and sarcoma show distinctly different cytological features in vital observation.
5) A medium for cell suspension culture of ascitic malignant tumor cells by roller tube technic was chosen after careful analyses of the components. Using this medium, the cytological changes of Yoshida sarcoma and celothelioma were studied on each culture day for 12 days and 21 days respectively.
6) Various drugs effective to malignant tumors were added to the above-mentioned cell suspension culture and the cytological mechanism of their efficacy was studied.

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After applying various tissue culture methods on Bashford's cancer in mice and the cancer in human, the authors at last succeeded in successive tissue culture of cancer for a long period of time with the roller-tube method. During this series of experiment we studied the morphology, motility, mitosis, phagocytosis, and viatl staining of cancer cells in culture, and obtaind the following results.
First of all in the case of Bashford's cancer, there appear three kinds of cells, i.e. cancer cells, fibroblasts and histiocytes, in the growth area. And the growth area itself can be divided into three zones of the peripheral, middle and central. They can be divided into the peripheral zone sparsely populated by cancer cells, fibroblasts and histiocytes; the middle zone occupied by cancer cells arranged in a thin laminar form; and the central zone with cells forming a thick layer of several laminae. The growth patterns of tissue are classified into six types of I to VI, starting from the type showing the least cancer-cell growth to the greatest growth. As for the culture fluid the combination of inactivated chicken serum, Hank's solution and chick embryo juice in the proportion of 50 per cent, 45 per cent and 5 per cent respectively is the most suitable medium for the observation of cancer cells, offering a better condition for the growth in the middle zone. In the phase-contrast microscopic observation, the morphological characteristics specific to cancer cells are maintained. In the 16 mm film of motion pictures taken of the culture, nuclei of cancer cells are rotating, and mitochondria show active transformation and also cells themselves are seen slowly moving. The average wandering velocity of cells is 0.6 to 0.7 μ per minutes. Showing an active mitosis, it took about 30 minutes in prophase, 30 minutes in metaphase, 10 minutes in anaphase, and 40 minutes in telophase. And sometimes multipolar mitosis can be observed. The carbon-particle phagocytosis of cells proves to be negative and the characteristics of cancer cells are distinctly revealed by the viatl staining of neutral red or Janus green. As for the culture medium mentioned above, when the medium is changed anew every four days, numbers of cancer cells increase gradually. Of those cancer cells cultured for three months but transferred to other test tubes once evry 15 or 20 days most cancer cells are entangled with on another by their tentacle-like projections, showing the thickening of nuclear membrane, a decreased number of mitochondria, and the enlargement of the Golgi apparatus. In the subcutaneous injections of cultured cancer cells to mice at the intervals of 20, 30, and 50 days after the initiation of the culture the tumors were successfully reproduced. These tumors were exactly identical with the original tumors.
With 10 case of human cervical carcinoma, successive culture was successfully carried out for as long as 3 months in one and for 4 months in another.

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Lately we experienced another case of “acute basophilocytic leukemia”, who was a 12 year-old boy complaining of anemia and hemorrhagic diathesis on admission and died of intracranial hemorrhage 2 months after the onset of the disease. On the simple method of bone marrow tissue culture devised by us, the predominant cells belonged to the basophils, showing their characteristic movement, and growth area revealed increased cell density and sharply defined outline that were typical of acute leukemia. Observating with fluorescence microscope, the growth area were more reddish than the other types of acute leukemia (myelogenous, lymphocytic and monocytic type) and each leukemic cell had reddish orange granules and a green nucleus somewhat tinged with yellow hue. The fluid culture of the bone marrow demonstrated an increase in number of mature basophils with a decrease of the blasts i.e. the maturation of the blasts into the mature basophils.

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This report deals with a rare case of bronchial carcinoma which arose from an tracheal bronchus in a 57-year-old male who succumbed to gangren of the right upper lung.
Clinically, his initial complaint was persistent pain of the right chest in June 1956. Cough and bloody sputum were increased, and he was diagnosed as primary carcinoma of the right lung. He died of general cachexia due to gangren of the lung in May 13, 1958.
At autopsy, the most remarkable findings was the existence of a goose-egg-size gangrenous cavity in the right upper lung. This cavity was communicated with an abnormal tracheal bronchus which arose from the right wall of the trachea, This abnormal trachea measured 0.5 cm in diameter and 1.0 cm in length, and its periphery was gangrenous. The communicated portion of the abnormal bronchus with pulmonal cavity revealed greysh white and hard, and tumorous. This portion was seemed to be a primary focus of pulmonal carcinoma. The metastasized foci were seen in the left lung, pericardium, pancreas, right adrenal gland and the regional lymph nodes.
Histologically, the finding of primary focus was solid carcinoma (carcinoma simplex) including many adenocarcinomatous nests, while majority of the metastatic nests was adenocarcinoma.

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For the purpose of early diagnosis of uterin cancer, in our Department of Obstetrics and Gynecology, Okayama University Hospital, we use three methods of diagnosis such as Papanicolaou's Method, T. P. T. Staining and Colposcopic Examination along with histological diagnosis by punch biopsy.
During the period of one year from September 1, 1957 to August 31, 1958, we examined all the patients visiting our outpatient clinic for the first time by Papanicolaou's Method and T. P. T. Staining as the screening test, and all suspicious cases were examined by Colposcopy and then we performed punch biopsy.
On the 230 cases suspected of early carcinoma after macroscopic examination and on whom three supplementary diagnostics as well as histological examination were carried out, we studied the relationship between the result of each supplementary diagnosis and that of the histological diagnosis.
As to the results, in each supplementary diagnosis performed on 35 cases with either the invasive carcinoma at early stage or carcinoma in situ, correct positive rate was 77.1 per cent by Papanicolaou's Method, 60.0 per cent by T. P. T. Staining and 77.1 per cent by Colposcopy.
On the other hand, correct negative rate was found to be 95.4 per cent by Papanicolaou's Method, 85.1 per cent by T. P. T. Staining and 95.4 per cent by Colposcopy. In the conbination of these three methods, correct positive rate was 91.4 per cent.
Besides in the comparative study of the histological classification, we found more positive cases in atypical epithelium and carcinoma in situ by the supplementary diagnostics.
From these results Papanicolaou's Method and T. P. T. Staining are quite suitable for the screening test, but T. P. T. Staining is a little inferior to Papanicolaou's Method. From the fact that the combination of these three supplementary diagnostics increases correct positive rate, it is desirous to use as many diagnostic methods in combination as possible for the carcinoma of the uterus.

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Study on exfoliative cytology was made in about one thousand cases of various kinds of oral lesion, of which particularly 237 cases of malignant neoplasms and 34 cases of precancerous lesions, such as leukoplakia and decubital ulcer, were summarized. The results of the study were classified in 5 classes according to Papanicolaou.
Biopsy revealed malignancy in 147 cases (91 per cent) of 161 cytology-positive cases, while cytology showed false negative in 49 cases (20.6 per cent) of 237 biopsy-positive malignancies.
Significant differences were noticed in the percentage of keratinized cells among leukoplakia (18 cases), decubital ulcer (16 cases) and normal mucosa and in that of parabasal cells between two lesions, but no malignant cytology could be found in all of these cases.

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With a view to ascertain the common specific characteristics of the respiratory enzyme system of cancer cells and changes in the enzyme activities in consonant with their origin and grade of differentiation the authors carried out a series of histochemical and biochemical investigations by studying the succinoxidase system, cytochrome oxidase system, DPNH-dehydrogenase system, and endogenous dehydrogenase system in various tumorous tissues, homologous non-tumorous tissues, and precancerous tissues, all from human or animals, by using cell suspensions, tissue slices, tissue homogenates, and mitochondria fractions with tetrazolium salts (NT, Nitro-NT, and Nitro-BT); and arrived at the following conclusions:
1. As for the activity of the succinoxidase system in normal glandular epithelial cells it is stronger in those matured and differentiated cells possessing vigorous metabolic function than in immature cells. However, in the cancer tissues, such as hepatoma and adenocarcinoma, the activity is generally lower than in the homologous normal tissues. In the cancer tissue the more highly differentiated cancer cells show stronger activity; and it is lowest in undifferentiated cancer cells.
2. Normal squamous epithelial cells show generally a lower activity, and of them young basal cells present a higher activity. However, in the case of squamous cell cancer the activity is still stronger, and in contrast it is higher in poorly differentiated cancer cells.
3. In normal non-epithelial cells, with a few exceptions (e. g. muscle cells), the activity of young cells is rather stronger than that of mature cells, and in the case of sarcomas (including leukemic cells) their activity is stronger than that of homologous tissue cells.
4. The endogenous dehydrogenase system activity of both cancer cells and sarcoma cells (including leukemic cells) is stronger than that of homologous non-tumorous cells.
5. The succinoxidase system activity of the rat liver tissue is elevated gradually at the precancerous stage by the DAB administration, and the activity is markedly diminished when the tissue became cancerous. On the other hand, the endogenous dehydrogenase system activity, rising gradually from the precancerous stage, does not fall even when cancerized.
6. In cancer cells the shape and structures of the mitochondria and their respiratory enzyme activities are on the whole irregular.
7. Cancer cells are apt to be easily destroyed in the course of the enzyme reaction, and moreover, it is liable to bring about the demolition and the decreased respiratory enzyme activity of mitochondria due to the destructive procedures as homogenization and or other treatments.

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Through the experimental research on cancer induction many factors which are responsible for cancer cell formation have been found but each of them is entirely different from others in its chemical or physical properties and no definitive cancer inducing moment has been drawn from the studies on the cancer inducing, when they have a common biological caracteristics, the cancer inducing ability. But it seems that there is still a way to approach the genesis of cancer cell formation from the observations on cancer cells by trying to find some characteristics or substance common and specific to cancer cells. The biochemical and morphological studies done by our collaborators suggested that the cancer cells should be born by the mutation.
Many morphologist reached to the same opinon from the observation on type and number of chromosomes. Resently some authors proved that the DNA contents in the nucleus is closely correlated the chromosome number. By using the apparatus of microspectrophotometry which is improved by Dr. Naora and Dr. Seno the authors tried to estimat the DNA contents in each cell stained by Feulgen reaction. The observation on ascitic hepatoma cells of rat (AH-130), Ehrlich ascites tumor cells and H-cell (derived from human ammunion cell and acquired the property as cancer cell in rat) proved that quantity of DNA in each cell is mainly of 2 and 4 times as that of lymphocytes from the same animal. Considering the rapid mitosis occuring in the growing tumor cells, they are mainly of tetraploidy because there is a possibility that the cell in some stage of mitosis has a large quantity of DNA as twice as that of the resting cell. This will mean the cancer cell will be born spontaneously by the mutation from normal cell but not by the gradual change through a stage like a pre-canceous cell.

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It is well known that in malignant tumors, their glycolysis are marked both under aerobic and anaerobic conditions, and this is the most important biochemical property common to all malignant tumors.
Using the New Yoshida Tumor, the authors investigated the quantitative relation in its glycolysis and the effect of thionin on its respiration in order to observe some apsects of its terminal respiration system and besides, the effect of some inhibitors on its glycolysis was studied.
The results were as follows:
1) It was found that as reported up to this time, both under aerobic and anaerobic conditions, the glycolysis by this tumor was as by other sorts of tumors and lactic acid was formed in a great quantity.
2) When glucose was added as the substrate, its endogenous respiration was inhibited and the higher the concentration of glucose was, the more marked the inhibitory effect was and yet, in any low concentration of glucose, its endogenous respiration was not accelerated.
3) The respiration inhibited by addition of glucose was recovered by addition of thion in: In this case, however, lactic acid formation was decreased.
4) When T. C. A. cycle intermediates were added as substrates, its respiration was little accelerated, but by addition of thionin at the same time as the intermediates, its respiration was accelerated to some degree.
Further, the respiration accelerted by addition of thionin was reduced after a long time reaction and conversely inhibited slightly.
5) KCN inhibited its respiration, but had no effect on glycolysis itself at all, whereas monoiodoacetic acid, 2-4 dinitrophenol, aureomycin and NaF inhibited not only its respiration but its glycolysis at the same time.

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For the purpose to revealing the mechanism of tumor cell formation some biochemical and morphological analysis have been carried out on the DAB rat hepatoma cells, especially in the changes of enzymatic activities and the morphology of mitochondria. The three dimentional observations of the morphological structure of the hepatoma tissue revealed that the hepatoma cells can grow apart from the capillaries in where the oxygen tension is supposed to be extremely low. Biochemical and cytochemical tests proved the low activities of succinic dehydrogenase, cytochrome C-cytochrome oxidase and catalase in tumor cells, whereas the marked higher activities in the adjacent non-tumorized liver cells. The ferritin, which is supposed to be the iron source of these enzymes, showed not so remarkable change, though a marked increase in the liver cells neighbouring to tumor cells. Observations in the course of tumor induction revealed that DAB uptake makes increase gradually the activities of the just describe enzymes and the quantity of ferritin.
These results will show that there is not gradual changes between the cells affected with DAB and the cancer cells, as far as concerning the enzymes belonging to respiratory system, differently from the expectation deduced from the morphological researches The cells affected with DAB are rich in mitochondria having normal structure but hepatoma cells have the mitochondria irregular both in number and shape having the ambiguous cristae. These resutls suport strongly the view that the cancer cell will be born spontaneously by the mutation but not the gradual change from the normal cells.

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In previous papers the author observed the permeability of Nile blue with the supravital staining method derived by Seno and Oguchi on several cells including tumor cells, and it has been proved that no differences on permeability can be seen between normal and tumor cells. By using the microscope alone for the observation of stained cells it is not sufficient to grasp the difference between normal and tumor cells. Then the author devised the method for quantitative estimation of dye penetrating into the cell by supravital staining by microspectrophotometry. With this method the ascites hepatoma cells show a great increase of permeability for Nile blue but that of Yoshida ascites tumor cells is decreased when compared with the normal liver cells and monocytes. L-cells (cultured cell) show the greatest permeability of all examined (monocytes, bone marrow cells, Yoshida tumor cells and ascites hepatoma cells). This will imply the rapid growing cell enhances the permeability as revealed in other experiments but in some of them a decreased permeability is found. Of course the different results on the permeability may be expected by chainging the permeable substances.
The author discussed that besides the molecular structure of the membrane itself, the changes in electric potential at membrane and intercellular molar concentration of the substances are also responsible factors for affecting the permeability.

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HST virus is one of filtrable agents successfully isolated from Yoshida tumor in 1950 by Hamazaki passing through the different species of animals, and it has already been verified that immunoserologically it is specific to this tumor and that it is also an indispensable factor for the growth and transplantation of the tumor. This time we carried out immunological and morphological studies on this virus adapted to embryonated eggs.
The HST virus successively inoculated into the yolk sack and chorioallantoic membrane of embryonated eggs in the microbiological department of our school can well become adaptation to embryonated eggs, and consequently the chick embryos usually die 4-6 days after the HST virus inoculation. In the liver of chick embryos dissociation, fatty degeneration, and necrobiosis of parenchymal cells, and the infiltration of monocytes and lymphoid cells can patho-anatomically be recognized.
It has been found that this virus adapted to the embryonated eggs maintains the properties essentially the same as the original HST virus in that when it is inoculated successively back to its host animals, guinea pigs, inflammatory tissue reaction occur successively, though slightly milder than in the case of original virus.
Next, in order to determined whether the virus successfully replaced from the embryonated eggs back to guinea pigs to be the same as the original HST virus, the cross-neutralization of two viruses by antisera were performed and it was proven that the tests were positive. Therefore the former was serologically quite identified with the latter, original HST virus.
On the other hand, after purifying the agent in the allantoic fluid and examining it under an electron-microscope, round particles of 30-60mμ in size were obtained.

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Transplantability of successively cultivated human amnion cell to conditioned rats was demonstrated.
1) Fifty passaged human amniotic cell (Strain H) which derived from normal person had produced the tumor in the X-radiated and cortisone-treated rats, just as HeLa cell.
2) Transfer of the first generation of H rat tumor to the second generation of conditioned rats was successfuly done.
3) Regrown of H-rat and HeLa-rat tumor cell in tissue culture was carried out and subcultivation of these regrown cell line was now in progress. (H-R cell and HL-R cell).
4) Immunocytotoxicity of anti-H and HeLa-rabbit sera on the H-R cell and HL-R cell in vitro was demonstrated.
5) Malignancy of H cell was discussed.

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In this experiment, effects of extripation of some endocrine organes on the heterotransplantability of Ehrlich ascites tumors to rats were examined.
Ehrlich mouse ascites tumor cells are inoculated intraabdominally.
In the cases of adrenalectomy, ovariectomy, hypophysectomy and splenectomy, tumor growth is not observed.
On the contrary, in the testectomized rats, marked abdominal tumor formation and growth of ascites tumor cells are seen. Metastasis are detected in the liver, spleen, pancreas, lung and lymphnodes. The 50% mortality time is 14 days in average and the pattern of the growth curve of ascites tumor cells resembles to that of the original host.
Marked anemia and emaciation are observed in the testectomized rats which are inoculated with tumor cells.
The activity of liver catalase is decreased markedly.
In conclusion, Ehrlich ascites tumor cells are successfully heterotransplanted to testectomized rats.

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In the experiment, hormonal effects on the heterotransplantability of Ehrlich ascites tumor cells to rats are examined.
Recently, in heteransplantation, many experiments on the accelation effect of cortisone are reported.
Ehrlich ascites tumor has started from breast cancer. So there is a possibility of having close connections to the hormones.
The rats are divided into 14 groups.
1st group is normal rats and these rats are treated with cortisone after inoculation of tumor.
2nd group is testectomized rats and treated with cortisone after inoculation of tumor.
3rd group is normal rats and these rats are treated with cortisone before inoculation of tumor cells.
4th group is testectomized rats and these rats are treated with cortisone acetate before inoculation of tumor cells.
5th group is normal rats and progesterone is injected to these rats.
6th group is testectomized rats and progesterone is injected to these rats.
7th group is normal rats and teststeron is injected to these rats.
8th group is testectomized rats and teststeron is injected to these rats.
9th group is normal rats and estrogen is injected to these rats.
10th group is testectomized rats and estrogen is injected to these rats.
11th group is normal rats and prehormone is injected to these rats.
12th group is testectomized rats and prehormon is inejcted to these rats.
13th group is normal rats and hyaluronidase is inoculated intraabdominally to these rats.
14th group is testectomized rats and hyaluronidase is inoculated intraabdominally to these rats.
Cortisone treatment before inoculation of tumor cells does not accelarate the tumor formation and growth of free ascites tumor cells.
On the contrary, cortisone treatment after inoculation of tumor cells is markedly increased the tumor growth.
Generally, estrogen accelarates the heterotransplantability of Ehrlich ascites tumor cells, but audrogen has not such an action. progesteron has a tendencey to promote the heterotransplantability. Prehormon promotes the heterotransplantability in normal rats, but has not such an action in testectomized rats.
Hyaluronidase accelarates the tumor growth, especially in normal rats.
In conclusion, cortisone concentration in the body plays an important roll in the heterotransplantation.

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Naturally, serial heterotransplantation of the transplantable tumors has been very difficult. AHLSTRÖM et al. and HORAVA et al. attempted the heterotransplantation of Ehrlich Ascites Tumor to rats and either of them failed in it. Recently, STROUD did serial transplantation of Ehrlich Ascites Tumor to rats, but this experiment is only a successive culture in the blody of rats.
Now, from the endocrinological point of view, a series of experiment of heterotransplantation of Ehrlich Ascites Tumors to rats was tested.
The effect of hormonal unbalance induced from testectomy was observed and interesting results were as follows: the serial heterotransplantation of Ehrlich Ascites Tumors to rats is possible as we experienced in the original host. The serial transplantation now has reached the 25th generation and in every generation Ascites inoculated back successfully. The intraperitoneal incula into rats never exceeded a total of 2ml of Ascites. Transfers of the tumor cells from donor to recipent rats were made after 7 or 8 days.
On the contrary, in the experiment of STROUD, he reported that transfers were made 3 or 4 days after inoculation and rats did not die of tumor. In testectomized rats, as well as in original host, bell-shaped curve of Growth of a population of free ascites tumor cells was seen. Initially, the cells increased exponentially, and the growth rate leveled off 7-8 days after an inoculum of tnmor cells.
In every generation, formation of great abdominal tumors, metastases and infiltrations were recognized. There were metastases and infiltrations in liver, pancreas, spleen, mesentery, intestine, lungs, diaphragm and lymphnodes. Remarked anemia, decreasing of the activity of liver catalase, emaciation and diarrhea are observed.
Finally, testectomized rats in every generations died of tumor. Within 10 days the mortality time was 50% in this case.
In conclusion, serial heterotransplantation of Ehrlich Ascites Tumors was succeeded in testectomized rats.

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In Report 1, effects of cortisone and X-radiation on the heterotransplantation of Ehrlich ascites tumor to rats are examined.
1st group of rats was given a total of 400r in two doses of 200r each on consecutive days and was treated with cortisone acetate. Cortisone given on the day of implantation (6mg) and second similar injection 1 week later.
In this group of rats. tumor growth is marked.
2nd group of rats is given a total of 400r in two doses of 200r each on consecutive days and treated with 6mg of cortisone acetate. These treatments were done 10 days after 1st inoculation. No tumor growth was seen in these rats.
3rd group of rats was treated with 12mg of cortisone acetate in total 10 days after 1st inoculation. Tumor growth was not observed.
In Report 2, effects of blocking the reticuloendothelial system on the heterotransplantation of Ehrlich ascites tumor were tested.
In conclusion, blocking the reticuloendothelial system by Indian ink is not so effective to the heterotransplantation of Ehrlich ascites tumor to rats.

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The author had an attempt to study the influence of splenectomy on the growth of Brown-Pearce Tumor by implanting its homogenate into the testicles of splenectomized rabbits. Not only transplantability, regression, days of survival and the mode of intraabdimonal metastasis but also the fluctuation in serum protein level, serum albumin globulin ratio, serum α₁, α₂ globulin fraction level and serum mucoprotein level in every 5 day after transplantation were examined.
1) Splenectomy has little influence on the transplantability and the regression of tumor in taken.
2) Mean days of survival were 16.2 in group transplanted with tumor within 3 weeks after splenectomy and 21.8 in nonsplenectomized group. But almost no differences in surviving time between the group transplanted with tumor 4 weeks or more after splenectomy and nosplenectomized group were seen.
3) On the mode of intraabdominal metastasis, the disseminated type with haemorrhagic ascites became to appear more frequently than the nodulated type without ascites in splenectomized group.
4) The decrease in serum protein level and serum albumin·globulin ratio after transplantation occurred early and intensively in splenectomized group.
5) In splenectomized group, it was very significant that the increase in serum α₁ globulin fraction level, determined paper electrophoretically, which continued to increase until the tumor growth reached to its peak, was more intensive and that the fluctuation of its level preceded about 5 days.
6) The fluctuation of serum α₂ globulin fraction level, also determined paper electrophoretically, was not so constant as that of α₁, but about 5 days' precedence of it in splenectomized group was more or less observed, too.
7) Serum mucoprotein level was determined by Weimer-Moshin's method, and was found that it became higher gradully according as tumor grows. In splenectomied group, the maximal increase in the level appeared about 5 days earlier than in the level of control group.
From the results described above, the author presumed that the growth of Brown-Pearce Tumor would be accelerated by the splenectomy.

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A gastric cancer has more malignant histopathological feature on the side of the lesser curvature than on that of the greater. This fact is also proved experimentally, i.e. the inoculated cancer in the greater curvature shows very slow growth of the tumor and far stronger proliferation of the connective tissue surrounding the tumor, compared with that in the lesser curvature. The authors have experimentally proved that the local blood supply plays an important role as the factor of these facts.
In the cancer tissue, decrease of the tissue respiration and increase of glycolysis are observed, compared with the normal tissue. This characteristic is also seen even in the normal stomach, in which the lesser curvature shows decreased tissue respiration and increased glycolysis, compared with the greater.
Consumption and production of pentose in the cancer tissue are greater on the side of the lesser curvature than of the greater, and this fact corresponds with the histopathological characteristic of the cancer tissue.
The cancer tissue has more ribonucleic acid on the side of the lesser curvature than of the greater. From these results, it would appear that the acceleraed pentose metabolism on the side of the lesser curvature has very close relation to the growth and infiltration of the cancer.

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