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Biomedical subjects

P ROUS

Publications and source records attributed to P ROUS.

16 recordsLinked to original sources
PubMed1964

FURTHER EXPERIMENTS ON THE CAUSE OF SEQUENTIAL NEOPLASTIC CHANGES. THE EFFECTS OF 20-METHYLCHOLANTHRENE ON TRANSPLANTED EPIDERMAL MOUSE PAPILLOMAS AND THE DERIVATIVE CARCINOMAS.

When crystalline 20-methylcholanthrene (MC) and the cells of tar-induced mouse papillomas (paps.) are injected together into the thigh muscles of mice the carcinogen exerts a marked promoting and chemotactic influence upon the cells while it is dissolving in the tissue fluid. Under such circumstances it strongly stimulates and attracts them, with result they surround and include the scattered crystals in small cysts that later coalesce to form a larger one from which the MC only very gradually escapes. Because of these findings intramuscular tests were made to learn whether MC would hasten the occurrence or increase the number of cancers that now and again derive from paps.; but the tests were repeatedly marred by the extraordinary behavior of such cancerous cells as happened to be already present in the implanted material. They responded far more actively to MC than did the pap. cells and soon took over the growths. Some carcinomas which failed to grow when transplanted alone, or only gradually formed small, regressing nodules, gave rise rapidly to huge growths of similar sort when exposed to MC. To exclude cancerous cells so far as possible from the later tests small grafts of pap. tissue with MC crystals adhering to them were implanted subcutaneously. The pap. cells promptly lined the graft pockets, encysting the crystals incidentally, and formed tumors that enlarged progressively by keratinizing inwards. While they did this their living layer of pap. tissue was continually bathed in dissolved MC throughout many weeks. Despite these apparently favorable conditions the carcinogen neither hastened the occurrence nor increased the number of visible epidermal cancers deriving from the paps. It also failed to bring about sequential malignant changes in the carcinomas. These negative results accord with those already obtained through long exposure of the benign pulmonary adenomas of mice to urethane or methylcholanthrene, agents which rapidly induce these benign tumors yet which were found to be incapable of furthering the cancerous changes to which such growths are prone. They accord also with another previous finding, namely that MC fails to bring on the malignant changes of discontinuous, sequential sort that mammary mouse carcinomas often undergo "spontaneously." Taken together these facts indicate that the change or changes whereby normal cells are converted into benign tumor cells differ in nature from those taking place when they become cancer cells, as also from those occurring when cancer cells undergo further, step-like, malignant changes. A study has been begun to learn whether the widely various carcinomas deriving from benign papillomas differ from these latter and from one and other in their chromosomal content.

Animals↗
PubMed1962

The plating of tumor components on the subcutaneous expanses of young mice. Findings with benign and malignant epidermal growths and with mammary carcinomas.

A procedure analogous to the plating of bacteria is described whereby some complex tumors have been taken apart and their components separately propagated. It was the outcome of finding that the forcible injection of Locke's solution followed by air can be used to split the subcutaneous connective tissue of sucklings and weanlings horizontally over the entire expanse of their backs or bellies, without inducing any complicating inflammation. Tumor fragments suspended in Locke's were widely scattered on the surfaces thus exposed. Most of them remained where they had lodged on the body wall, and rapidly becoming fixed in place, formed growths protected by the overlying cutaneous layer-which, throughout many weeks, remained unattached either to the wall or to them. The procedure is more searching in its disclosure of tumor constituents than those currently employed, and it has the advantage that it preserves the neoplastic components that it reveals. It has been used thus far only to rescue for experimental purposes transplantable, benign, epidermal papillomas from the hidden carcinomas deriving from their cells, and to set free and maintain the neoplastic components of complex mammary tumors of milk factor type. Success was obtained with such of the latter as were chosen for separate propagation, though successive platings were sometimes required for their isolation. Incidentally the procedure revealed two components in the mammary growths which could not have been discerned by previous methods of search. Each formed tumors peculiar to itself.

Animals↗
PubMed1958

Fatal keratomas due to deep homografts of the benign papillomas of tarred mouse skin; normal proclivities and neoplastic disabilities as determinants of tumor course.

Six out of eight epidermal papillomas, induced with tar in mice of homogeneous strain, have grown after transfer to the subcutaneous tissue of sucklings and weanlings. Five of them have been thus maintained for nearly or quite a year and a half, and in seven to nine successive groups of mice. The tumor studied longest has been kept going in five parallel lines since its primary implantation. The papillomas have all grown progressively in most instances, and proved fatal. None has altered except through the occurrence of derivative cancers, but these have arisen so often as only to be excluded on transfer by a rigorous selection of grafts. Histologically the papillomas have been of a single, completely unaggressive kind, yet transfer has disclosed great differences in their abilities. The tumors they form are of unique sorts. The cells of some are able-bodied (Type A), capable of spreading along bare connective tissue and keratinizing like normal, reparative epidermis. They line graft pockets, differentiate into the free space these provide, and form cysts densely packed with keratin. The papilloma is thus turned outside in. The cysts become huge as keratin accumulates in them, and eventually they rupture with result either in subcutaneous dissecting cysts or keratinizing surface growths that are often prodigious in size and fantastic in shape, but sometimes are completely like the cutaneous papillomas ordinarily induced by carcinogens, and tend, when small, to regress or come away as these frequently do. One growth of Type A was placed in the peritoneal cavity or in the liver, spleen or lung, and at all these situations it formed introverted cysts resembling the subcutaneous. The cells of other papillomas are more or less crippled (Type C). In extreme instances they are unable to spread laterally, and produce relatively little keratin. They fail to line graft pockets, but their keratin inflames the exposed connective tissue, extravasation ensues, and a continually enlarging, fluid-filled cyst forms, with walls that are bare except where a stalked or cauliflower papilloma exists, projecting inwards. At last the cyst ruptures and a second dissecting cyst forms, also devoid of papilloma tissue; or else the overlying skin undergoes pressure necrosis, the cyst fluid escapes through a rent, and fatal infection ensues. All gradations exist between Type A and Type C. The cancers derivative from both exhibit a marked disability,-though invasive they are almost or quite unable to extend along bare connective tissue. The papillomas that are possessed of this faculty spread beyond them along the cyst wall, and kill the host through their unceasing activity. In collateral work a papilloma was transplanted that was found protruding from the external auditory canal of a mouse which had received an intramuscular injection of methylcholanthrene many months previously. The tumor is now in its 5th generation, after 15 months. The growths it forms are of Type A. All of the papillomas are functioning tumors, with their own cells as the functioning product. Their papilliferous shape, when on the skin, is due solely to inability of their cells to gain space in other ways. Intrinsically they are keratomas. The papillomas do well after transfer to deep situations because the growth of their cells is indirectly promoted, through favoring local conditions. No direct promotion takes place like that when the cells of prostatic and mammary tumors are stimulated to multiply by hormones. Doubtless many agents act in both ways, that is to say by dual promotion.

Allografts↗
PubMed1957

Comment.

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Humans↗
PubMed1955

Are carcinogens responsible for the superimposed neoplastic changes occurring in mouse tumor cells? The effect of methylcholanthrene and urethane on pulmonary adenomas and of methylcholanthrene on mammary carcinomas.

Three spontaneous pulmonary adenomas of C mice, morphologically resembling those induced by methylcholanthrene or urethane, were propagated in host after host under conditions such that the neoplastic cells were directly exposed, while proliferating, to one or the other of these agents. The successive periods of test lasted for more than a year in some instances, the total exposure to the carcinogens far exceeding that required to change normal pulmonary cells into adenoma cells. One of the adenomas remained unaltered, and the others underwent cancerous changes; but these took place with equal frequency in the control growths, and their occurrence was neither hastened nor delayed by the carcinogens. Two polymorphous mammary carcinomas of "milk-factor" type, with the characteristic tendency to form acini and tubules, were exposed to methylcholanthrene in the same way as the pulmonary adenomas and for periods quite as long. Their cells continued to differentiate, and in other respects underwent no significant change. Urethane had no influence on the rate of growth of the adenomas exposed to it; methylcholanthrene, on the other hand, markedly retarded the enlargement both of them and of the mammary tumors. Its inhibitory influence was not passed on from cell to cell however; when freed of the carcinogen by further transplantation, the retarded tumors grew as fast as the controls. Furthermore the retardation caused no evident delay in the occurrence of cancerous changes in the adenomas. One of the adenomas was maintained in twelve parallel lines while under test and new tumors arose in nine of them, the earliest appearing more than fifteen months after initial transfer of the growth. Always it was an adenoma solidum, this appearing almost concurrently in eight of the nine lines. In six of them it was soon followed by carcinomas, the sequence of events and the morphological findings both indicating that they had derived from it. Individually the cancers were widely various, but they were similar on the whole from line to line. Carcinomas of a wholly different aspect arose from the other adenoma undergoing cancerous change, and they were not preceded by adenoma solidum. In both instances the character of the superimposed neoplastic alterations seemed to have been determined by some inherent trait of the adenoma concerned.

Adenoma↗