peplomycin and Fibrosarcoma

We have previously reported that bleomycin and its derivative peplomycin enhance the release of cytokines by rat spleen cells during mitogen-stimulated cell culture in vitro, but liblomycin, another derivative of bleomycin, decreases cytokine release to below untreated control levels. Cytokine release correlated well with the inhibition of subcutaneous tumour growth after treatment with equivalent doses of the three analogues. In contrast, ascites tumour growth is completely inhibited by liblomycin and appears to be at least partly macrophage-mediated because the antitumour effect can be significantly inhibited by carageenan. This study shows that bleomycin and its analogues activate rat peritoneal macrophages and increase interleukin-6 release, O2- production, cell spreading, phagocytosis and random migration of macrophages, but only bleomycin enhances peritoneal macrophage invasion into a monolayer of rat lung endothelial cells in vitro. This study also shows that although liblomycin decreases spleen cell cytokine production and is less effective than bleomycin against subcutaneous tumour, as we have previously reported, the antitumour drug activates peritoneal macrophages and, compared to bleomycin, has a remarkable therapeutic effect on rat ascites tumour.

Topics: Animals; Bleomycin; Carrageenan; Cell Adhesion; Cell Migration Inhibition; Endothelium; Female; Fibrosarcoma; Flow Cytometry; Interleukin-6; Lipopolysaccharides; Lung; Macrophage Activation; Macrophages; Microspheres; Peplomycin; Phagocytosis; Rats; Rats, Inbred Strains; Superoxides; Tumor Cells, Cultured

We have studied the immunological effects that accompany a change in the chemical structure of a group of antineoplastic antibiotics by comparing the immunoregulatory cytokine release during mitogen-stimulated spleen cell culture after in vivo drug treatment. Whereas bleomycin and peplomycin increased cytokine levels in culture supernatants when compared with supernatants from untreated control rat spleen cell cultures, liblomycin generally reduced cytokine levels under the same culture conditions. We then compared these results with the antitumor effects of equivalent doses of the three drugs against a highly antigenic rat fibrosarcoma, KMT-17, both in vivo and in vitro. The results suggest that the immunoaugmenting effects of these antitumor antibiotics are essential for an optimal antitumor effect in vivo, and that these effects can be drastically altered by modification of the chemical structure of the drugs employed.

Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Cytokines; Drug Screening Assays, Antitumor; Female; Fibrosarcoma; Flow Cytometry; Interferons; Interleukin-2; Peplomycin; Rats; Spleen; Structure-Activity Relationship; T-Lymphocyte Subsets; Tumor Necrosis Factor-alpha

The blood lymphocyte population was monitored in 6 patients with advanced malignant tumors who were treated with large doses of a new cytotoxic drug termed pepleomycin. It was observed that the size of the cell population, its cellular composition, mitogen stimulations and natural killer activity did not change in any consistent ways during or after treatment. It is concluded that pepleomycin does not directly affect the lymphocytic population.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Bleomycin; Female; Fibrosarcoma; Humans; Kidney Neoplasms; Killer Cells, Natural; Leiomyosarcoma; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neoplasms; Peplomycin; Testicular Neoplasms; Thyroid Neoplasms