Growth inhibition of human cancer metastases by camptothecins in newly developed xenograft models

• Published in: Cancer research (Chicago, Ill.) Vol. 55; no. 23; pp. 5637 - 5641
• Main Authors: POTMESIL, M, VARDEMAN, D, KOZIELSKI, A. J, MENDOZA, J, STEHLIN, J. S, GIOVANELLA, B. C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-12-1995
• Subjects: Adenocarcinoma - prevention & control; Adenocarcinoma - secondary; Adrenal Gland Neoplasms - prevention & control; Adrenal Gland Neoplasms - secondary; Animals; Antineoplastic agents; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Brain Neoplasms - prevention & control; Brain Neoplasms - secondary; Burkitt Lymphoma - prevention & control; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Carcinoma, Squamous Cell - prevention & control; Carcinoma, Squamous Cell - secondary; Chemotherapy; Drug Screening Assays, Antitumor; Humans; Liver Neoplasms - prevention & control; Liver Neoplasms - secondary; Male; Medical sciences; Melanoma - prevention & control; Melanoma - secondary; Mice; Mice, Inbred Strains; Mice, Nude; Pharmacology. Drug treatments; Reproducibility of Results; Tumor Cells, Cultured; Antineoplastic agent; Animal model; Methodology; Liver; Central nervous system; Hepatic disease; Metastasis; Heterotransplantation; Alkaloid; Isomerases; Human; Intracranial; Nervous system diseases; Enzyme; Rodentia; DNA topoisomerase; Enzyme inhibitor; Antimetastatic agent; Malignant tumor; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Central nervous system disease; Digestive diseases
• ISSN: 0008-5472; 1538-7445

Several metastatic models have been developed using clonal selection of human malignant cells metastasizing into a specific organ in NIH-I Swiss immunodeficient mice. The organs of choice were the central nervous system (CNS), targeted by metastases of malignant melanoma, and the liver, with metastases of colon adenocarcinoma. Additional models of adrenal metastases by malignant melanoma, and CNS involvement by implanted human lung squamous carcinoma or lymphoblastoid cells, are also available. Organ metastases, as well as the effects of treatment, were confirmed by autopsies and histological examination of the tissues or by a surgical inspection of the liver. The treatment end points were established as the increases in survival times of treated mice relative to placebo-treated controls. Camptothecins injected i.m. or delivered via gastrointestinal tract inhibit the growth of CNS metastases and increase the survival of treated animals. 9-Amino-20(S)-camptothecin was effective in the CNS model and in the model of liver metastases. The drug increased 3.3- and 5.7-fold the survival rates relative to untreated controls with metastases of colon adenocarcinoma to the liver, and all camptothecins were significantly more effective than 5-fluorouracil, currently a drug of choice in treatment of this disease. The xenograft models of metastases are available for studies of drug passage through the blood-brain barrier optimization of drug delivery to the liver, and for the development of new camptothecin-based treatment strategies.