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)

We used indicine N-oxide to treat 46 children with malignant solid tumors: 17 with osteosarcoma, 12 with neuroblastoma, 13 with a brain tumor, and 4 with other miscellaneous tumors. The efficacy and toxicity of the drug was assessed at the dose of 2000 mg/m2/day for five consecutive days. None of the 39 patients evaluable for response achieved a complete or partial response. Hepatotoxicity was experienced by 13 patients: 11 patients developed asymptomatic elevations of transaminases, 1 patient developed hyperbilirubinemia, and 1 developed ascites. Indicine N-oxide appears to be ineffective in the treatment of osteosarcoma, neuroblastoma, and pediatric brain tumors at this dose and schedule. Because higher doses are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity, we do not recommend further study of this agent in pediatric solid tumors.
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PMID:Phase II trial of indicine N-oxide in relapsed pediatric solid tumors. A report from the Childrens Cancer Study Group. 180 9

Diaziquone (AZQ), a new lipid-soluble antitumor agent, was given by 15-30-minute infusion on a daily X 5 schedule to 47 children with refractory solid tumors and leukemia. The starting daily dose of 6 mg/m2 was escalated to 10 and 35 mg/m2 in patients with solid tumors and leukemia, respectively. In patients with solid tumors, myelosuppression was dose-limiting at a daily dose of 10 mg/m2. In patients with leukemia, prolonged pancytopenia and bone marrow hypoplasia were observed at daily doses greater than or equal to 25 mg/m2. At these higher doses, significant hyperbilirubinemia associated with sepsis was also seen. Corresponding increases of transaminases or alkaline phosphatase and significant hemolysis were not noted. The maximum tolerated dose for this daily dose schedule was 9 mg/m2 in children with solid tumors and 25 mg/m2 in children with relapsed leukemia. Responses to AZQ included stabilization of disease in osteosarcoma, neurofibrosarcoma, pinealoma, and ependymoma. A patient with juvenile chronic myelocytic leukemia in blast crisis converted back to the chronic phase. A patient with acute lymphoblastic leukemia had a substantial decrease in cerebrospinal fluid blast count. Bone marrow aplasia was achieved in children with acute lymphoblastic leukemia and acute nonlymphoblastic leukemia; however, remissions were not achieved. A phase II study of AZQ in children with refractory malignancies is now being performed by the Childrens Cancer Study Group.
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PMID:Phase I clinical evaluation of diaziquone in childhood cancer. 385 80

Gunn rats, deficient in the enzyme uridine diphosphate glucuronyl transferase, were used to investigate the effects of unconjugated hyperbilirubinemia in cisplatin nephrotoxicity. The effect of bilirubin on the antineoplastic activity of cisplatin in osteosarcoma cell lines was also determined. The in vivo model involved three groups of rats (n=6 rats/group): homozygous Gunn rats (j/j), heterozygous Gunn rats (j/+), and congenic Wistar rats. On day 0, all rats were given 4 mg/kg cisplatin intraperitoneally. Blood was sampled on days 0, 3, and 5 for bilirubin, BUN, and creatinine and kidneys were taken on day 5. Cell culture was performed in four canine osteosarcoma cell lines using the average concentrations of bilirubin for homozygous Gunn rats at day 0 and 3. Bilirubin was added to cell lines alone and with cisplatin. Cell viability was assessed using the CellTiter Blue assay. Serum bilirubin levels were highly elevated in Gunn j/j, moderately elevated in Gunn j/+, and undetectable in Wistar rats at day 0. Bilirubin provided a nephroprotective effect, with significantly lower BUN and creatinine in Gunn j/j when compared with Wistar rats at day 5. Histological grading demonstrated preservation of the S3 segment in Gunn j/j when compared with Wistar rats (P<0.05). Bilirubin had no significant effect on the antineoplastic effect of cisplatin at either concentration in the four cell lines (P<0.001). Hyperbilirubinemia in the Gunn rat provided marked preservation of renal function and histology in a cisplatin nephrotoxicity model. Exogenous bilirubin did not interfere with the antineoplastic activity of cisplatin in vitro.
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PMID:Hyperbilirubinemia's protective effect against cisplatin nephrotoxicity in the Gunn rat. 1841 16