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  • 1985-1989  (2)
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  • 1
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cytostatic and antimetastatic activities of 1,2-di(3,5-dioxopiperazin-1-yl) propane (ICRF-159, razoxane) were studied in a transplantable, slowly growing osteosarcoma in Sprague-Dawley rats. This tumor model is characterized by osteoid formation and spontaneous metastasization to lungs, kidneys and lymph nodes. Razoxane given intraperitoneally (i.p.) from 2 days before to 14 days after tumor transplantation (30 mg/kg or 10 mg/kg per day) resulted in a dose-dependent prolongation of median survival time (83 or 48 days respectively, versus 38 days for the control group), but showed no influence on the growth of the primary tumor. Early treatment with razoxane (30 mg/kg i.p. from day −2 to + 14) showed a greater inhibition of pulmonary metastases than later treatment (30 mg/kg i.p. from day +14 to +28 after transplantation). Whereas 59·9 per cent of the total sectional area of the lungs in the control animals was covered by osteosarcoma metastases, only 3·4 per cent and 26·1 per cent respectively was affected in the early and late razoxane treatment groups. Toxic side-effects of these treatment schedules were reversible diffuse alopecia, but no retardation of body weight gain.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Bisphosphonate-linked cytostatic N-Lost derivative ; Bone-seeking agent ; Bone tumor ; Osteosarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to investigate whether the newly synthesized bisphosphonic acidlinked N-Lost derivative BAD retains bone-seeking and cytostatic properties. The paper describes experiments on mutagenicity in vitro and on toxicity in vivo. BAD is characterized by very low mutagenic activity toward histidine auxotrophic Salmonella typhimurium strains. Cytotoxic effects were tested in rat osteosarcoma and in Walker carcinosarcoma 256B. The LD50 of i.v. injected BAD was 146 mg/kg. Acute toxicity is probably caused by calcium complexing of the bisphosphonate part of the molecule. Labeling experiments showed moderate accumulation in bone and osteosarcoma, as well as in lung metastases. BAD effected high tumor growth inhibition in osteosarcoma and Walker carcinosarcoma-bearing rats and marked prolongation of survival; histologic and radiographic examination revealed rapid calcification of osteosarcoma and lung metastases. BAD-pretreatment produced protective effects against osteolysis induced by intratibially implanted Walker carcinosarcoma ascites cells. The cytostatic efficacy of equitoxic doses of BAD in rat osteosarcoma is comparable to that of dacarbazine and in Walker carcinosarcoma to that of melphalan.
    Type of Medium: Electronic Resource
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