Human tumour xenografts growing in immunodeficient mice: a useful model for assessing chemotherapeutic agents in bronchial carcinoma.

Abstract

Xenografts from eight human bronchial carcinomas have been established in CBA/Lac mice rendered immunodeficient by neonatal thymectomy followed three weeks later by whole body irradiation (7.35 Gy (735 rads)) after a priming dose of cytosine arabinoside. Growth rates of individual tumour lines remain constant and the histological and chromosomal characteristics of the original tumour are maintained through multiple serial passages over many months. With specific growth delay as the principal end point this system may be used to assess the response of histologically different lung tumours to chemotherapeutic agents.Chemotherapy is now widely used for palliation in most patients with small cell lung tumours' and in minority of those with inoperable non-small cell malignancies.2 The great variation in the response of individuals to the currently used drugs and the need to develop more effective agents, particularly for non-small cell tumours, has led to much interest in methods of assessing the efficiency of anticancer treatments in the laboratory.3 The success of in vitro testing of bacterial sensitivities to antibiotics led early workers to attempt to evaluate the effects of anticancer drugs on malignant cells growing in tissue culture and to correlate the results with the clinical response seen in the patient.4 " The results were disappointing,3 although the development of newer clonogenic assays appeared more encouraging.67Various animal models have been used in the development and testing of new anticancer agents. Transplantable rodent tumours, such as the Lewis lung carcinoma, have proved of little value as appreciable differences in sensitivity between these and human tumours were found. In an attempt to overcome this problem many workers have grown human tumours either in congenitally athymic "nude" mice89 or in rodents rendered immunodeficient by various techniques.'°" We have used such a system and find it a useful animal model for assessing the activity of anticancer agents in bronchial carcinoma.

12-O-Tetradecanoylphorbol 13-acetate induced differentiation in human lung squamous carcinoma cells

“…The three xenografts from which the cell lines were derived were obtained from untreated patients in 1983 and brief details of these xenografts have previously been reported (Fergusson et al, 1986). The pathology of both the NX002 and CX140 xenografts is consistent with that of poorly differentiated lung squamous carcinoma and has remained constant over the last 7 years.…”

Pre-clinical research in small animals using radiotherapy technology – a bidirectional translational approach

“…Furthermore, these systems are suitable for whole body irradiation of small animals which is of great importance to assure sufficient immunosuppression for tumour or bone marrow transplantations. As the technical demands are typically low, such simple devices as well as X-ray systems (industrial or clinical) or even clinical linear accelerators may be utilised [32][33][34][35][36][37][38][39][40][41][42][43].…”

Studying lung cancer in the laboratory: 1--Development of model systems.

“…29 At present the most commonly used in vivo model for growing lung cancers in the laboratory is the athymic or "nude" mouse. Immunological studies of these hairless mutants show absence of T lymphocytes in thymus dependent areas of the spleen, a normal complement of B cells, high levels of natural killer (NK) cells, and increased macrophage activity.…”