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)

High-dose chemotherapy with autologous peripheral blood stem cell transplantation was administered to 10 patients with refractory bone and soft tissue sarcoma (2 patients with primitive neuroectodermal tumor, 4 patients with Ewing's sarcoma, 3 patients with synovial sarcoma and one patient with osteosarcoma). Busulfan 4 mg/kg x 4, melphalan 140 mg/m2 and thiotepa 200 mg/m2 x 3 were used in the high-dose chemotherapy. Complications related to the treatment were limited to one patient who developed hepatic veno-occlusive disease, no serious complications were seen in the other patients. Four patients died of their disease, one patient was alive with the disease and 5 patients were alive with no evidence of disease. The prognosis for non-resectable primitive neuroectodermal tumor and Ewing's sarcoma is said to be very poor. However, there are some patients in whom the disease is kept in remission by high-dose chemotherapy with autologous peripheral blood stem cell transplantation, so this therapy may be a possible substitute for radical operation. With spindle cell sarcomas, the efficacy of this treatment was temporary, so it will be necessary to investigate frequent high-dose chemotherapy and to change the high-dose chemotherapy regimen.
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PMID:[High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for refractory bone and soft tissue sarcomas]. 1050 May 30

High-dose chemotherapy of solid tumors aims at eliminating residual or metastatic tumor cells, which remained after conventional treatment. Thus, anticancer drugs used for high-dose chemotherapy should display significant cytotoxicity against the respective tumors. As little data are available about the in-vitro toxicity of busulfan and treosulfan especially on pediatric tumor cell lines, we compared the cytotoxicity of treosulfan and busulfan on four Ewing tumor, four neuroblastoma, two osteosarcoma and two leukemia cell lines in vitro. Growth inhibition of tumor cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide test after 24, 48, 72 and 96 h. Treosulfan and busulfan reduced the growth of all tumor cell lines in a time-dependent and dose-dependent manner. In vitro treosulfan was consistently more cytotoxic than busulfan. Fifty percent growth inhibitions of 608-0.73 micromol/l were determined for treosulfan and of above 5,000-2.81 micromol/l for busulfan. Both drugs exhibited similar cytotoxicity profiles. Busulfan-sensitive/resistant cell lines were also sensitive/resistant to treosulfan. Overall, the leukemia cell lines were most sensitive to busulfan and treosulfan. The Ewing tumor cell lines were the second most sensitive followed by the neuroblastoma cell lines. The osteosarcoma cell lines were the most resistant cell lines. Although the in-vitro stability of both drugs makes direct comparison of their in-vitro toxicity difficult and does not allow any estimation of dosages needed clinically, the in-vitro results indicate substantial cytotoxicity of both drugs on leukemias, Ewing tumors and neuroblastomas. These data suggest further evaluation of treosulfan for high-dose chemotherapy of advanced Ewing tumors, neuroblastomas and high-risk leukemias.
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PMID:Cytotoxicity of treosulfan and busulfan on pediatric tumor cell lines. 1691 11

Osteosarcoma typically arises in tissues of mesenchymal origin, and is the most malignant bone tumor characterized by high local aggressiveness, with poor therapeutic outcome. Busulfan has been widely used to treat CML. So far, there are no reports on the therapeutic effect of busulfan on osteosarcoma. Here, we showed that busulfan dose-dependently reduced the cell viability and proliferation, and induced cell apoptosis, senescence, and reactive oxygen species levels in two osteosarcoma cell lines. Moreover, a series of loss-of-function and gain-of-function experiments further indicated that busulfan may have its anti-osteosarcoma effect by upregulating the microRNA-200 (miR-200) family which subsequently downregulated its target genes ZEB1 and ZEB2. Furthermore, treatment with busulfan potentially inhibited the growth of implanted osteosarcoma in nude mice. Taken together, our data suggest that busulfan may have an anti-osteosarcoma effect through downregulating ZEB1 and ZEB2 through activating the miR-200 family, highlighting a possibility of using busulfan as a novel therapy for osteosarcoma.
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PMID:Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo. 2481 2