Metastatic Spread of Human Tumour Implanted into Thymectomized, Antithymocyte Serum Treated Hamsters

Summary.-Five out of 18 primary explants of human carcinomata obtained at operation have been grown progressively for a minimum of one month in thymectomized, x-irradiated mice reconstituted with syngeneic bone marrow and subsequently treated also with anti-thymocyte serum. All the tumours which proliferated were of gastrointestinal origin, growing locally but not metastasizing although direct invasion of the ribs occurred in one case. No implanted breast carcinomata grew in this system. THE aim of the present experiments was to determine whether immunedeficient mice provided a suitable environment for the progressive growth of implanted human carcinomata.Numerous methods of heterotransplantation have been described and reviewed (Chesterman, 1959). It is generally accepted that cell mediated immunity is largely responsible for xenograft rejection and that anti-thymocyte serum (James, 1967) and x-irradiation (Toolan, 1955) are effective immunosuppressants in this context. Thymectomy appears to enhance the action of anti-thymocyte serum (ATS) on first generation tumour graft survival in mice (Jeejeebhoy, 1967;Phillips and Gazet, 1970). Thymectomy combined with irradiation and bone marrow reconstitution to produce immune deprived mice is now a well known immunosuppressive regimen. A relatively more permanent immune impairment is produced in deprived mice than with ATS treatment alone, which is specific for T lymphocyte depletion and dependent on serum potency and the period of its administration. In these bone marrow reconstituted mice, a lymphoid population of cells will eventually develop so that ATS administration would be an added precaution against the cell mediated response returning. In order to keep ATS toxicity to a minimum, low doses of serum were injected twice weekly until the graft seemed to have established. MATERIALS AND METHODSMale and female adult A2G mice, inbred for at least 45 generations, were used. The mice were weaned and separated according to sex at 3 weeks of age. Female New Zealand white rabbits weighing between 2-5 and 3-5 kg were employed for ATS preparation.Two ml of a thymocyte suspension prepared from the thymuses of 8 A2G mice were injected intravenously through the ear vein of each rabbit according to the method of Levey and Medawar (1966

Section: Resultscontrasting

confidence: 74%

Transplantation of Human Tumour to Immune Deprived Mice Treated with Anti-thymocyte Serum

Detre¹,

Gazet²

1973

“…Extensive studies were made of the transplantability of human tumours into immune deprived mice and hamsters and this series of xenografts was given a . P " designation (Cobb, 1972(Cobb, , 1974 sion. The exposure time was up to 6 weeks, after which the sections were stained with haematoxylin and eosin.…”

Section: Materials and Method)smentioning

confidence: 99%

“…IN RECENT years the successful graftinig of human tumouirs into immune deprived animals has been reported from a number of laboratories (Phillips and Gazet, 1970;Povlsen and Rygaard, 1971;Castro, 1972;Cobb, 1972Cobb, , 1974Arnstein et al, 1974;Giovanella, Stehlin and Williams, 1974). Xenografts of human tumoturs provide a further type of experimental tumour for research into the nature and the treatment of cancer.…”

mentioning

confidence: 99%

The growth kinetics of xenografts of human colorectal tumours in immune deprived mice

Pickard¹,

Cobb²,

Steel³

1975

Self Cite

The technique of labelled mitoses was used to examine cell proliferation within grafts of human colonic and rectal tumours in immune deprived mice. Most of the data were obtained on the first passage but in some cases up to the third passage was used. It was found to be difficult to obtain precise kinetic data on this type of tumour material, but the results did allow some estimates to be made, particularly of the duration of the G2 and S phases of the mitotic cycle. The average G2 duration was 6 h and the average S phase was 14 h. It is concluded that whilst xenografts may differ in a number of respects from the tumour in the patient, they nevertheless constitute a type of experimental tumour that is worthy of further study.

“…The tumour was a well differentiated, mucus producing, adenocarcinoma and had metastasized to the regional lymph node. Two years later (June, 1973) The viability of cells was assessed microscopically by their ability to resist staining with nigrosin (Kaltenbach, Kaltenbach and Lyons, 1958).…”

Section: Patient Rg (Tumour Number P116)-mentioning

confidence: 99%

“…CARCINOMA arising in the large bowel in man can be transplanted successfully subcutaneously in immune deprived animals (Povlsen and Rygaard, 1971;Castro, 1972;Cobb, 1972). If we wish to use this xenograft model to learn more about a tumour in man, we need to understand to what extent transplantation to a xenogeneic host alters the tumour cell population.…”

mentioning

confidence: 99%

The Behaviour of Carcinoma of the Large Bowel in Man Following Transplantation into Immune Deprived Mice

Lm¹

1973

Self Cite

Summary.-The growth of carcinoma of the human large bowel was studied in the first 2 passages in immune deprived mice. The tumours were obtained from large bowel resections on 3 people. There was a strong histological similarity between the patient's tumour and the tumour that grew subcutaneously in the mice 2-8 months after implantation. One dissimilarity observed was a higher mitotic index in some of the tumours growing in the immune deprived animals. In the second passage of the bowel tumours, cells were implanted into groups of 8-10 animals in the following sites: subcutaneous, intramuscular, intravenous, intrahepatic, intraperitoneal and intrathoracic. Growth of tumour was observed from all 3 tumours when they were implanted subcutaneously, intramuscularly, intraperitoneally and intrathoracically. Infiltration of muscle by tumour was a frequent finding. Lung metastases developed after intravenous injection of cells in 1 of the 3 tumours. In none of the 3 tumours did growth follow injection of cells directly into the substance of the liver. On no occasions were spontaneous metastases observed.