In vivo
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Treosulfan (L-threitol-1,4-bismethanesulfonate, Ovastat) was tested on human renal tumor cells growing as xenografts in athymic nude mice and as monolayers in vitro, in comparison with clinically used cytostatic drugs (in vivo, cyclophosphamide, vinblastine, and 5-fluorouracil; in vitro, vinblastine and 5-fluoro-2'-deoxyuridine) which were administered at equitoxic or equivalent dose levels, respectively. Four human renal tumor xenografts (N-U 2, N-U 26, MRI-H 121, KTCTL-1M) were investigated in vivo, and seven renal tumor cell lines (KTCTL-1M, KTCTL-2, KTCTL-26A, KTCTL-30, KTCTL-84, MRI-H 121, N-U 2) under in vitro conditions. The investigations of the four human renal tumor xenografts revealed that treosulfan is capable of inducing pronounced growth inhibitions ranging from 60-100% in comparison with untreated control tumors. ⋯ These results reveal the remarkable antitumor efficacy of treosulfan towards human renal-cell carcinomas, especially under in vivo conditions. This activity was similarly high or even better than in cyclophosphamide and vinblastine. The in vitro data obtained in monolayer cultures also confirmed the remarkable antiproliferative activity of treosulfan in renal tumor cells, but did not mirror very well the pattern of antitumor activity observed in vivo.
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Hypoxic tumors are frequently resistant to radiation therapy. Polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) was tested for its ability to increase oxygen tension in the hypoxic rat osteogenic sarcoma UMR-106, murine Lewis lung carcinoma LL2 and rat gliosarcoma 9L. In addition, PEG-Hb was tested as an adjunct for radiotherapy in UMR-106 and human prostate carcinoma PC-3 solid tumors. ⋯ PEG-Hb increased tumor oxygen content and improved the effectiveness of radiotherapy in these rodent models.
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Growth factors play an important role in tissue repair. While the effectiveness of growth factor therapy in animal wound healing models and limited human clinical trials has been demonstrated, the ideal method for their administration to the wound remains unclear. Experimental data suggest that the continuous presence in the early stages of wound repair is beneficial. ⋯ A single application of irradiated EGF genetransfected fibroblasts to wounds can thus continuously deliver the transgene in vivo and could be used to administer drugs to the wound bed during the crucial first seven days of wound-healing.
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Hydrocortisone-acetate (HA)-treatment of BALB/c-mice induced a profound suppression of the lymphatic immune system with statistically significant decreases of thymocyte proliferation and maturation rates as well as peripheral blood lymphocyte (PBL) counts. To check its putative immunoprotective/immunorestoring activity, the optimal immunomodulating dosage of commercially available mistletoe extract standardized for the galactoside-specific mistletoe lectin (ML-1) was regularly administered (1 ng ML-1 per kg body weight; subcutaneously). ⋯ Counts of BALB/c-mouse peripheral blood mononuclear cells also revealed statistically significant increases after ML-1 co-administration, as compared to HA-treated animals. Accordingly, ML-1 treatment may be supposed to restore the lymphatic system after immunosuppressive corticoid treatment and thus this treatment may be of great benefit to patients.
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Comparative Study
Enhancement of immune responses to suramin correlates with antineoplastic activity in BALB/c-mice.
The antiparasitic naphthylurea suramin (SUR) could be shown to exert immunomodulating and antimetastatic activity in BALB/c-mice. Regular intraperitoneal administration of SUR yielded significant weight gain of spleen and significant enhancement of peritoneal macrophage activity in chemiluminescence assays. The number of thymocytes per mg organ weight did not show evident differences in control and SUR treated groups; however, determinations of lymphocyte subsets revealed up-regulation of mature cells expressing helper/inducer (L3T4) or cytotoxic/suppressor (Lyt-2) phenotypes but down-regulation of immature cells presenting both L3T4/Lyt-2 antigens. ⋯ To evaluate the antimetastatic activity of SUR, sarcoma L-1 cells were intravenously inoculated into BALB/c-mice. In this model system the number of experimental lung metastases significantly decreased, as compared to control mice which received injections of saline solution. Accordingly, SUR can be regarded as an immunomodulating and antimetastatic substance which seems to be promising for clinical trials in oncology.