The growth of human tumours in immunosuppressed mice and their response to chemotherapy.
One hundred and sixteen human tumours were transplanted to thymectomized, irradiated, antilymphocyte serum-treated mice. In 12 cases the recipient mice died rapidly, presumably from infection. With the remaining 104 tumours, three-quarters grew to a varying extent, retaining the characteristic histological features of the primary tumours. Implant nodules varied widely in composition, from solid tumour and stroma to dense fibrous tissue without recognizable tumour cells. There was no relation between degree of malignancy and ability to grow, and also some benign tumours grew.In 44 cases, mice were treated with the drug or drugs most likely to be used in the patients and the effects on the implants were assessed histologically. Two tumours were largely destroyed and one showed marked metaphase arrest. Three other tumours showed lesser changes that were attributable to the drug but were of equivocal significance.There appeared to be differences in drug sensitivity between structurally different clones of the same tumour, and some tumours treated with two alkylating agents were damaged by one and not the other, suggesting that this model may have substantial discriminatory power. Assays such as this should not be used to guide treatment of the patient without prior validation. The practical and ethical difficulties of validation by clinical trial may be insurmountable, and an alternative approach to validation is proposed which does not raise these difficulties.
D000818:Animals; D002699:Chlorambucil / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D003609:Dactinomycin / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D008808:Mice, Inbred CBA; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010051:Ovarian Neoplasms; D013852:Thiotepa / Q000627:therapeutic use; D013934:Thymectomy; D014183:Transplantation, Heterologous; D014228:Triaziquone / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms; D014747:Vinblastine / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
D002699:Chlorambucil; D003609:Dactinomycin; D014750:Vincristine; D014747:Vinblastine; D003520:Cyclophosphamide; D013852:Thiotepa; D014228:Triaziquone; D008558:Melphalan; D005472:Fluorouracil; D008727:Methotrexate