American Journal of Cancer

The problem of chronic suppurating foci is met frequently in the practice of surgery. Chronic osteomyelitis is one of the most common examples of such a condition. Every surgeon is cognizant of the difficulties of successful treatment and of the necessity for persistent cooperation on the part of the patient. Inadequate observation and therapy may result in eventual permanent disability or even loss of life. As the disease progresses, extensive local changes take place in the tissues owing to the constant irritative effects of the discharging suppurative material. Chronic irritation, both physical and chemical in nature, has long been accepted as a factor in the production of malignant growth. Carcinoma as an end result of a chronic suppurative process has been reported by Benedict (1), Blanco (2), Collins (4), Devars (5), Wakeley (9) and others. But that this condition is rare is shown by the fact that of 365 cases of osteomyelitis cared for at this hospital in twenty-two years, only one has been accompanied by malignant growth. The tendency for such a growth to remain localized for a long time is shown in the case herein described and in the others reported in the literature. The growth may progress, however, to such an extent as to undermine the vitality of the patient in a marked degree. Case Report A forty-seven-year-old woman, unmarried, was admitted to the Peter Bent Brigham Hospital complaining of weakness and inability to walk, owing to a sore leg. Eighteen years previously she had struck the left leg above the ankle against a table. Several weeks later she was taken to a hospital where incision and drainage were performed for what was apparently an acute osteomyelitis. During the ensuing year four additional operations were undertaken for drainage. Spontaneous drainage occurred intermittently after these procedures. Further professional aid was not sought because of the patient9s faith in Christian Science. She could walk with the help of a cane until one year prior to admission, when a fracture of the tibia occurred and she was compelled to use crutches. At that time the narrow opening of the sinus became larger, and ulceration slowly extended up the leg toward the knee. A sinus also developed in the upper third of the tibia. At the same time the patient became weaker and lost weight. Three weeks before admission to the hospital she fell and fractured the left tibia below the knee.

J. H. Harrison

The American Journal of Cancer

Epidermoid Carcinoma in Osteomyelitis: Case Report

骨髓炎中的表皮样癌：病例报告

In 1931 two male and two female albino rats of unknown heredity were mated. Their offspring were bred without any regard to age or blood relationship, the only rule being to select the larger and more healthy animals of the litter for breeding and use the rest in experiments. The present colony, numbering 750 members, consists entirely of the descendants of the four original rats. In 1934, three years after the establishment of the colony, an old rat developed a tumor of the uterus (Fig. 1), and this has since been transplanted through 55 generations into 600 animals without a single instance of spontaneous regression. If the inoculation is made in the axillary space, about one-third of those surviving three weeks have metastases in the lungs. The only agent which has halted the growth of the tumor is radiation. After eight days there is little or no difference between tumors which spring from 0.1 c.c. and 0.2 c.c. of inoculum. Even with 0.00001 c.c. tumors grew in 31 per cent of animals inoculated. With 0.1 c.c. the growth is so rapid that experiments have been terminated fourteen days after transplantation because of the fact that the animals begin to die. Fig. 2 shows tumors arising from 0.01 and 0.001 c.c. fourteen days after inoculation.

J. A. Pollia

A Transplantable Uterine Rat Sarcoma of 100 Per Cent Transmissibility

100%可移植性的移植性子宫大鼠肉瘤

Reference has been made in earlier papers (1, 2) to the development of sarcoma in a series of mice in which we were studying the carcinomatous changes in the mammary gland as well as in the vagina and cervix under the influence of estrogenic hormones. The formation of sarcoma following the injection of estrogenic hormones had previously been observed by Cori (3) in a mouse, in which it developed adjacent to an oil cyst. The development of sarcomas has been recorded also by Gardner, Smith, Allen and Strong (4), and by Burrows and other investigators, both in rats and mice injected with cancerigenic hydrocarbons (5–10). Recently Lacassagne (11) described the appearance of spindle-cell sarcomas in mice injected with four estrogenic hormones. Since our earlier reports we have found several additional sarcomas in mice, produced by the injection of hormones, and in particular one originating in striated muscle tissue. These observations will be described here and we shall include, also, in our report sarcomas in mice injected with lutein hormones and with liver extract prepared for the treatment of pernicious anemia.

E. L. Burns

V. Suntzeff

Leo Loeb

The Development of Sarcoma in Mice Injected with Hormones or Hormone-Like Substances

激素或类激素物质注射小鼠后肉瘤的发展

Of the sulphur compounds contained in the blood, glutathione has attracted the attention of most investigators. Our interest became focused on this compound and its relation to malignancy because of the many conflicting results reported in this field and, furthermore, because of the probable chemical importance of glutathione in cellular metabolism.

In 1888 de Rey Pailhade (20, 21) described a sulphur compound, philothion, which undoubtedly was identical with glutathione, and in 1908 Heffter pointed out its important reversible oxidation-reduction properties. Hopkins (11, 12) thought it to be a dipeptide of cysteine and glutamic acid, but since that time much work has been done to clarify both its chemical structure and physiologic properties. It has finally been shown that it is a tripeptide containing glutamic acid, cysteine and glycine (2). The active structural unit of glutathione is a sulphydryl group, and because of its occurrence in a reduced (GSH) and oxidized or disulphide (GSSG) form, the biologic importance of this reversible catalytic oxidation-reduction complex is evident.

The distribution of glutathione in nature is widespread and it has been recovered from all animal tissues. In human tissue, the highest concentrations have been observed in liver (250 mg. per cent) and spleen (300 mg. per cent). Variable concentrations have been found in malignant tissue; many investigators have reported abnormally high figures. Pickard and Marsden recovered large amounts in cases of carcinoma of the breast and embryonal carcinoma of the testis. Woodward, working with animals, was unable to find increased glutathione in carcinomatous and sarcomatous tissues, but recovered another reducing substance, an ascorbic acid-like compound in concentrations four to six times greater than glutathione. Interestingly, this substance was most evident in growing parts of the tumor, being practically absent in the necrotic portions. This same investigator found that irradiation of tumors resulted in a definite diminution in the glutathione content, but only when it was effective in retarding the growth of the lesion. Boyland made an important contribution to the knowledge of the distribution of glutathione in demonstrating that in the extraction of tumor tissues iodine is reduced also by ascorbic acid, thus giving erroneously high glutathione determinations. L. J. Harris subsequently showed that a large part of the reducing substance that interferes in iodometric determinations is actually not ascorbic acid, but an unknown compound.

A. E. Osterberg

R. J. Coffey

J. A. Bargen

C. F. Dixon

E. V. Maclay

A Comparative Study of the Reducing Substance (So-Called Glutathione) of the Blood in Normal, Malignant and Non-Malignant Conditions

正常、恶性及非恶性状态下血液中还原物质（所谓谷胱甘肽）的比较研究

It is known that many organs have the property of oxidizing the fatty acids. By means of perfusion experiments it has been demonstrated that the liver (Embden et al.) and the kidney (Snapper and Grunbaum) oxidize the fatty acids in the beta position: the liver forms large amounts of β-hydroxybutyric acid and of aceto-acetic acid, which are destroyed only to a small extent, while the kidney has a strong oxidizing effect also on the acetone (ketone) bodies. Organ extracts have likewise been found capable of oxidizing fats. Liver extracts contain enzymes capable of oxidizing β-hydroxybutyric acid to aceto-acetic acid or reducing the latter to β-hydroxybutyric acid (Wakeman and Dakin) and also, according to Kuhnau, of destroying β-hydroxybutyric acid and forming dicarboxylic acids by oxidation of aceto-acetic acid. Aceto-acetic acid is partially reduced by minced kidney to β-hydroxybutyric acid (Embden and Michaud). Dehydrogenases of the higher fatty acids have been found in the pancreas and the intestine (Tangl and Berend) and in the bile and the fatty tissue (Quagliarello), in the liver (Mazza and Stolfi), and in the kidney (Mazza).

One of the most satisfactory procedures for the study of biological oxidation of the fatty acids is the use of tissue slices, which allows the manometric determination of the gas exchange in the presence of a fatty acid and the simultaneous investigation of the breakdown products of the latter. With this technic the oxidation of various fatty acids by liver tissue has been studied (Wigglesworth, Mazza, Quastel and Wheatley, Jowett and Quastel, Califano, Ciaranfi, Cook and Edson, Bossa). Corresponding investigations have been carried out on kidney tissue (Jowett and Quastel, Quastel and Wheatley, Mazza, Bossa, Ciaranfi), and on spleen and testicle (Jowett and Quastel). These have demonstrated that tissues from various organs are able to oxidize the fatty acids, to produce acetone bodies, and to destroy the latter under certain conditions. According to Mazza and to Ciaranfi, the oxidation of fatty acids in the kidney takes place not only in the beta position, but also in the omega position.

E. Ciaranfi

On the Ability of Tumor Tissue to Oxidize the Fatty Acids in vitro

肿瘤组织体外氧化脂肪酸的能力研究

C. W. Hutchison

D. H. Kling

Malignant Synovioma

恶性滑膜瘤

The gross pathology of bone tumours occurring spontaneously in an inbred strain of mice has already been described (4). In general, these appear to represent almost every possible phase of proliferative activity of the osteoblast; they may occur in any bone, and several or even all the bones in an animal may be affected. It is no exaggeration to say that every type of histologic change may occasionally be illustrated from a single mouse. The tumours from the first 106 sarcoma mice observed have been reexamined in an attempt to classify them according to the predominating type of cell. A number of these animals had multiple lesions of different types. Mouse 1688, for example, had a spindle-celled tumour of the tibia and an ossifying tumour involving the spine and ribs. Bone and osteoid tissue were the main features of tumours of the spine, ilium, and right femur of mouse 2706, which also had almost pure spindle-celled tumours of the rib and left femur. Mouse 2810 had a giant-celled tumour of the tibia and an osteoma of the spine. A number of similar examples might be quoted from the records. Of the 118 tumours, 89 consisted principally of bone and osteoid tissue; 20 were predominantly spindle-celled growths; 5 were mainly giant-celled tumours; and in only one was cartilage the principal feature, although it was present in 5 tumours of other types. There were two tumours in which spindle cells and osteoid tissue were present in equal amounts, and these must be classed as mixed tumours (one of these also contained cartilage), while one tumour was mainly round-celled, with some osteoid tissue and cartilage in addition. Giant cells were seen in 22 tumours altogether, and in only 10 tumours were there no signs of osteogenesis. The accompanying illustrations show the main types of tissue encountered.

F. C. Pybus

E. W. Miller

The Histology of Spontaneous Bone Tumours in Mice

小鼠自发性骨肿瘤的组织学研究

The results described below are based upon the examination of the organs, and especially of the livers, of 1004 mice under treatment with, in all, 84 compounds, as follows: The primary object of the investigation was to seek for any evidence of the production of cancer of the bladder by pure chemical compounds, which might throw light upon the occupational incidence of this form of cancer in chemical workers and especially in those handling β-naphthylamine. No tumours of the bladder have been obtained, but some peculiar changes in that organ were produced by 1:29-azonaphthalene, and by no other of the compounds hitherto tested. This result has led to further experiments, now in progress, with other compounds related to 1:29-azonaphthalene. Systematic examination of the livers of animals receiving compounds under test has been carried out since the detection, by one of the authors of the present paper, of neoplastic changes in the livers of mice receiving 3:4:5:6-dibenzcarbazole (Boyland and Brues 1937). Hence a large amount of comparative histologic material has been collected which serves to demonstrate the specificity of action of the very few compounds, out of the 84 named in this paper, which produce any considerable change in the structure of the liver.

J. W. Cook

C. L. Hewett

E. L. Kennaway

N. M. Kennaway

Effects Produced in the Livers of Mice by Azonaphthalenes and Related Compounds

小鼠肝脏中由偶氮萘和相关化合物产生的影响

An account of the origin and development of an inbred strain of mice with a high incidence of bone tumours has already been given (1), and a preliminary description of some of the more important characteristics of the lesions has also appeared (2).

The object of the present communication is to illustrate in more detail the main features, such as the sites and types of lesions, and other points of interest and importance. The material has been obtained over a period of five years during the development of the high-incidence strain, and comes from the main Simpson stock, the earlier selected and inbred sarcoma lines, as well as from the later inbred strain which is now in its eighth generation. Bone lesions have been found in more than 300 mice, and the majority of these have been examined microscopically (see following paper).

The Gross Pathology of Spontaneous Bone Tumours in Mice

小鼠自发性骨肿瘤的大体病理学

Studies of induced Cysticercus sarcoma in rats have demonstrated (1) a direct relationship between the number of parasites in the host's liver and the duration of the latent period. An increase in the number of cysts decreased directly the average time interval before the onset of malignant disease and increased directly the probability of its occurrence, demonstrating that the extent of the surface area of the host's tissue exposed to the incitant is an important factor in the initiation of the malignant process. Previously demonstrated (2) genetic differences in the occurrence of Cysticercus sarcoma were defined (1) as differences in the host's susceptibility to Cysticercus infestation and in longevity or resistance to common laboratory diseases. Families with a low percentage of bearers of Cysticercus sarcoma among the infested rats were relatively short-lived and resistant to Cysticercus disease, while longevity or increased susceptibility to Cysticercus infestation contributed equally to a higher percentage of bearers of induced Cysticercus tumors. The occurrence of neoplastic disease in the walls of Cysticercus cysts was found (3) to be fortuitously distributed among the several lobes of the liver and the several types of cells which composed the cyst wall. Further, malignant disease in Cysticercus cysts was shown to be independent (4) of the age of the rat when infested, and among equally infested rats to be independent of the genetic susceptibility of the host to Cysticercus infestation.

Publication Information	Publisher: American Association for Cancer Research Inc.，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1931，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

American Journal of Cancer

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