Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new compounds, 4-[4-[bis-(2-chloroethyl)-amino-]phenyl]-1- hydroxybutane-1,1-bisphosphonic acid (BAD) and aminotris-(methylenephosphonato)-diamminoplatinum(II) (ADP) that both have cytostatic and osteotropic properties, have shown good therapeutic efficacy against an osteosarcoma which metastasizes and kills by lung metastases. We therefore combined each of these drugs with the antimetastic agent razoxane. Razoxane (20 mg/kg i.p., 5 days/week for 6 weeks) was administered in combination with either BAD (30 mg/kg i.p.) or ADP (37.5 mg/kg i.v.) twice weekly for 3 weeks. Tumour volumes, body weight, survival time and occurrence of metastases were recorded, in addition to the measurement of the metastasis area compared to the total lung area in serial histological lung samples. In both experiments, razoxane effected a significant increase in life span while being ineffective in tumour inhibition. Razoxane in combination with BAD displayed an enhanced anticancer activity which was not significant. ADP had a good antineoplastic activity and a large increase in survival time (144 per cent ILS). Razoxane used in combination with ADP did not influence antitumour efficacy. Median survivals of both ADP-treated groups were significantly longer than the razoxane-treated group. Analysis of the lung metastasis area showed a maximum of 57 per cent for the controls while all treated groups occupied a lesser area. The lowest metastases area was found with the combination treatment BAD + RAZ (18 per cent). This was considered an antimetastatic effect, while ADP treatment effected a time delay only. No change in metastatic pattern was observed in any of the treatment groups. Histological examination showed no effect on the capillaries in the proliferating region of the tumours that could account for the lower occurrence of metastases.
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PMID:Therapeutic efficacy of two different cytostatic-linked phosphonates in combination with razoxane in the transplantable osteosarcoma of the rat. 235 Sep 20

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.
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PMID:Antimetastatic effects of razoxane in a rat osteosarcoma model. 347 Jan 64