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

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122

Summary.-The transplantability of a xenografted human adenocarcinoma has been examined in mice that had been immune-suppressed by thymectomy and whole -body irradiation and the results have been compared with transplantation into athymic (nude) mice. Two alternative techniques were used to prevent marrow failure following whole-body irradiation: reconstituting the animals with a marrow graft, or protecting them by an injection of cytosine arabinoside (Ara-C) 2 days before the irradiation. The results show that the Ara-C-prepared mice were more receptive to transplantation than marrow-grafted or nude mice, and they were the only animals that developed regional metastases from implanted xenografts. Some recovery of immunity occurred in both types of immune-suppressed mice, which was evident more than 5 weeks after immune-suppression and which was more marked in females than in males. It was concluded that the immune-suppressed mice were superior to nude mice for short-term experiments but they may be less satisfactory for long-term experiments.DURING the past 5 years we have been engaged in a programme of research on the growth and response to treatment of human tumours grafted into immunesuppressed mice. The results that we have published so far (Pickard, Cobb and Steel, 1975;Kopper and Steel, 1975; Courtenay et al., 1976) were obtained with mice that had been immune-suppressed by a standard technique of thymectomy, wholebody irradiation, and marrow reconstitution. Within the past 18 months we have explored methods of improving the level of immune suppression, and this paper describes our results. MATERIAL AND METHODSOriginal method of immune suppression.-The original technique involved thymectomy at 3-4 weeks of age. Male and female mice of the Institute of Cancer Research colony of CBA/lac mice were used, and have continued to be employed throughout the work described here. The thymectomy was performed under ether anaesthesia. The mouse was laid out in a supine position, head towards the operator, and a 5-7 mm incision was made in the skin overlying the suprasternal notch. The neck muscles were pulled apart with 2 pairs of forceps and the sternum was split to a distance of 3 mm using sharppointed scissors. The 2 lobes of the thymus could then be easily seen and were quickly sucked out through a glass tube connected via a glass collecting-chamber to a rotary vacuum pump. Finally, the skin was closed with a single metal Michel clip, and the animal was immediately placed in a warm box while it recovered from the anaesthetic. A skilled operator could perform a thymectomy by this technique in about 1 min, with an operative mortality of less than 500.Two weeks after thymectomy the mice were given 900 rad whole-body irradiation from a 60Co source, and on the same day they received an i.v. injection of syngeneic marrow cells. The standard inoculum of nucleated marrow cells was in excess of 5 x 106. Marrow from non-thymectomized donors was used, on the basis of the work of Miller, Doak and Cross (1963). Tumour implant...

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 90%

Improved immune-suppression techniques for the xenografting of human tumours

Steel¹,

Courtenay²,

Rostom³

1978

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122

“…Tumour lines.-The histological, biochemical and growth-kinetic characteristics of these xenograft lines have been reported (Houghton and Taylor, 1978a, b (Pickard, Cobb and Steel, 1975;Houghton and Taylor, 1978b). The tumour growth-rate is at least partially dictated by the host, and may reflect heterogeneity in the immune capabilities of immunedeprived mice.…”

Section: Materials and Amethodsmentioning

confidence: 99%

Evaluation of single-agent therapy in human colorectal tumour xenografts

Houghton¹,

Houghton²

1978

Summary.-The responses of 6 human colorectal tumour xenografts to 7 cytotoxic agents have been established. Tumour responses have been quantified by growth inhibition, and the time taken for 3H-thymidine fractional incorporation (TFI) to recover to the control value after treatment. The chemosensitivity of each tumour line to a spectrum of agents was individual, and no pattern of response which would allow prediction of individual agent efficacy was apparent. Cyclophosphamide, methyl-CCNU and 5-fluorouracil produced marked growth inhibition in individual tumour lines, whereas actinomycin-D, cis-dichlorodiammine platinum, doxorubicin and pentamethylmelamine showed little activity. Data presented agree with clinical evaluation for single-agent therapy. The uptake and incorporation of radiolabelled 5-fluorouracil into 4 tumour lines is reported. No marked differences between 3 FUinsensitive lines and 1 sensitive line have been observed.

“…THERE have been many reports in the literature on the successful growth and maintenance of human colorectal tumours in immune-deprived mice (Houghton and Taylor, 1976;Cobb, 1973; Pickard, Cobb and Steel, 1975) and in nude mice (Povlsen and Rygaard, 1971). Some data regarding the chemosensitivity of human colorectal tumour xenografts are now available (Houghton, Houghton and Taylor, 1977;Kopper and Steel, 1975;Cobb and Mitchley, 1974).…”

mentioning

confidence: 99%

Maintenance of biological and biochemical characteristics of human colorectal tumours during serial passage in immune-deprived mice

Houghton¹,

Taylor²

1978

The effect of serial passage in immune-deprived mice on certain biological and biochemical parameters has been studied in a series of 6 human colorectal tumour xenografts. Histological integrity is maintained for up to 10 serial passages, together with production of epithelial mucins and carcinoembryonic antigen. Passaged tumours retain human lactate dehydrogenase and glucose-6-phosphate dehydrogenase isoenzyme patterns and a human chromosome constitution. The induction of a murine tumour has been identified in this system, and the importance of routine checks for the presence of human tissue during serial passage is stressed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4