Effect of biological response modifiers on growth and cell proliferation of human tumor xenografts in nude mice.
The effect of biological response modifiers on macroscopic tumor growth and on tumor cell proliferation of a human renal cell carcinoma and a squamous cell carcinoma (hypopharynx) in nude mice has been studied. Tumor necrosis factor alpha (TNF-alpha) and interferon alpha (IFN-alpha) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) were applied either alone or in combination, and TNF-alpha was also combined with etoposide (ETP). TNF-alpha and IFN-alpha alone or in combination did not substantially affect the course of tumor growth, however, they did influence the pattern of tumor growth. There was also only a marginal effect on tumor cell proliferation. However, IFN-alpha protects the animals from tumor growth associated weight loss. ETP and ETP plus TNF-alpha leads to a deceleration of tumor growth, a decrease of the labeling index and to a significant decrease of the animal weight which indicates that the first two effects may be partly due to the toxicity of the treatment. GM-CSF modifies cell proliferation in a dose-dependent manner, i.e. stimulation at low doses and tendency to inhibition at higher doses. Although there is no substantial direct antineoplastic effect of the agents studied, the results make clear that indirect effects of therapeutic agents due to therapy induced cachexia should always be regarded. It is interesting that IFN-alpha has a protective effect against cachexia.
Maurer-Schultze
B
B
Institute of Medical Radiation and Cell Research, University of Würzburg, Germany.
Bassukas
I D
ID
Hofmockel
G
G
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007012:Hypopharyngeal Neoplasms; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*
D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor