Growth characteristics of human colorectal tumours during serial passage in immune-deprived mice

Summary.-Mice immunologically deprived by thymectomy, cytosine arabinoside treatment and whole-body irradiation were used to study the growth of human tumours as xenografts. 10/16 melanoma biopsies, 4/13 ovarian carcinoma biopsies and 3/6 uterine cancer biopsies grew as serially transplantable xenograft lines.The tumour lines were studied through serial passages by histology, histochemistry, electron microscopy, chromosome analysis, immune fluorescence, growth rate measurement and mitotic counts. They retained the characteristics of the tumours of origin, with the exception of loss of pigmentation in two melanomas, histological dedifferentiation in the uterine carcinomas, and increased mitotic frequency and growth rate in some melanomas.It was concluded that this type of animal preparation is as useful as alternative methods of immunological deprivation, or as athymic nude mice, for the growth of human tumour xenografts, at least for some experimental purposes.

Section: Discussionsupporting

confidence: 52%

Human tumour xenografts established and serially transplanted in mice immunologically deprived by thymectomy, cytosine arabinoside and whole-body irradiation

Selby¹,

Thomas²,

Monaghan³

et al. 1980

“…Human solid tumours have now been heterotransplanted to the nude mouse (Fogh et al, 1980;Rofstad et al, 1982) or immune-deprived animals (Houghton & Taylor, 1978;Steel et al, 1983) in many laboratories. Our overall success rate of 44% with lung tumours agrees well with the experience of other workers (Sharkey et al, 1978;Shorthouse et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

Growth of human bronchial carcinomas in nude mice

Mattern¹,

Jager²,

Sonka³

et al. 1985

Summary Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large cell and small cell carcinoma had a lower success rate (38% for both). The average volume doubling times in the first passage in nude mice ranged from 8.2 in large cell carcinomas to 18.9 days in adenocarcinomas. In subsequent passages an increase in growth rate was found, the overall average doubling time falling from 14.5 days in the first passage to 7.1 days in the second passage. In a study with 171 non-small cell lung carcinomas (NSCLC), the growth data in nude mice were correlated with the clinical data of the corresponding patients. A relationship between the growth parameters in nude mice and prognosis of patients could not be found.During the past 3 years we have transplanted in the course of cooperative clinical studies 255 human lung tumours into nude mice. In this report we describe the incidence and rate of growth of these tumours in the nude mouse, as primary transplants and passaged tumours, and further we examined whether the growth characteristics of these tumours might be of clinical prognostic value. Comparison of a part of the presented data with other measurements and the clinical course will be published elsewhere. Materials and methodsNude mice Athymic nude NMRI-mice (own breeding or Zentralinstitut fur Versuchstierzucht, Hannover), female, 6-9 weeks old, were kept under standardized conventional conditions (Makrolon cages, 270C room temperature, 50% relative humidity, autoclaved bedding) in a separated room especially controlled against infections. An autoclaved special diet (altromin 1410, Altromin Spezialfutterwerke, D-4937 Lage) and acidified water (pH 2-3) were given ad libitum. Patients and tumoursTwo hundred and fifty five histologically verified lung tumours and their lymph node metastases from 213 patients were xenografted into nude mice.

“…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

Self Cite

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.