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)

The energy metabolism of Dunn osteosarcoma subcutaneously implanted in C3H/He mice was studied in vivo by a 31P-NMR spectrometer with surface-coils. The spectra of Dunn osteosarcoma showed peaks of sugar phosphate, inorganic phosphate, phosphocreatine, phosphomonoester, and ATPs. In the early stage of the tumor growth phosphocreatine and ATP showed large signal intensities and the tissue pH was 7.23 +/- 0.08. Following the tumor growth phosphocreatine and ATP decreased and the tissue pH fell to 6.82 +/- 0.08. Immediately after a small dose of MTX (2 mg/kg) was administered, an increase of inorganic phosphate and a decrease of phosphocreatine were temporarily observed when MTX concentrations of the tumor tissues were maximum. High energy metabolites were apparently consumed with the active transport of MTX. After twelve hours of a high dose of MTX (500 mg/kg) was administered, disappearance of phosphocreatine and ATP with an increase of inorganic phosphate was observed previous to the histological change. In vivo 31P-NMR spectroscopy may be useful in the evaluation of chemotherapy.
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PMID:[In vivo 31P-NMR studies on energy metabolism and the effect of methotrexate in murine implanted osteosarcoma]. 346 60

"Neo-adjuvant therapy" with preoperative high-dose methotrexate (HD-MTX) and CF rescue therapy was investigated in four children with osteogenic sarcoma. Immediately after the diagnosis of osteogenic sarcoma from biopsy, the patients were treated with three to five courses of weekly HD-MTX (300 mg/kg) with CF rescue. Three patients had en bloc tumor resection and one patient underwent disarticulation of the hip joint after the pre-operative HD-MTX. The effect of HD-MTX was evaluated on the basis of pathological changes between the specimen of the primary tumor taken at biopsy and that during surgery. Two out of four patients showed marked tumor cell reduction (greater than 50%) of the specimen upon surgery. Two patients who responded to the preoperative HD-MTX were further treated with HD-MTX on a post-operative adjuvant therapy basis for 18 months. Both of these patients survived with no evidence of disease for 35.6+ and 20.9+ months. Two patients who responded poorly to HD-MTX were treated with a multi-drug postoperative adjuvant therapy including cis-platinum, adriamycin, cyclophosphamide, actinomycin D, and bleomycin. One patient had a solitary lung metastasis at 12.2 months after amputation. Wedge resection of the metastatic tumor was performed and adjuvant therapy with cis-platimum has been given for 20 months. He has remained with no evidence of disease for more than 30 months. Another patient has been receiving multi-drug neo-adjuvant therapy without any evidence of disease for 11.9 months after surgery. These data suggest that neo-adjuvant chemotherapy based on the response to preoperative HD-MTX is more useful for increasing the cure rate of childhood osteogenic sarcoma.
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PMID:[Neo-adjuvant therapy in childhood osteogenic sarcoma: a pilot study of selective postoperative chemotherapy based on response to preoperative high-dose methotrexate]. 348 34

During the use of a therapeutic regimen of high-dose methotrexate (HD-MTX) with leucovorin rescue in two cases of osteogenic sarcoma and malignant lymphoma without central nervous system (CNS) involvement, serial EEG monitoring before and after MTX infusion was performed with special reference to occipital basic activity. The EEGs were analyzed as to the power average spectrum using an ATAC-450 (NIHON KOHDEN). At 48 hours after the initiation of MTX, there was a transient but statistically significant slowing, such as a drop in the dominant frequency and a decrease in the alpha/theta ratio. Complete recovery of EEG changes occurred within one week. No clinical symptoms suggestive of CNS impairment were noted in either case. These data suggest that EEG alterations might be a reflection of subclinical CNS impairment. Therefore, serial EEGs might be a good early indicator for the detection of leukoencephalopathy in high-risk patients.
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PMID:[Spectral EEG analysis in children treated with high-dose methotrexate]. 349 31

The primary site of the metastasis of osteosarcoma is the lung. More than 90% of patients have died of pulmonary metastasis in one to two years. Control of osteosarcoma depend upon the prevention of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin, high-dose methotrexate with Leucovorin rescue and Cisplatinum, dramatically improved the prognosis of osteosarcoma. In the past, when systemic chemotherapy was not available, the five-year survival rate was around 19%. In patients who receive chemotherapy with the current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, with a single metastasis appearing after termination of treatment (late isolated type), or early and multiple, emerging in reaction to treatment (early multiple type). It is generally accepted that post-operative chemotherapy can inhibit pulmonary micro metastasis and prove to be of great significance in improving the survival rate of patients with osteosarcoma of extremities and achieve limb salvage operation. On the other hand, effective control of the side effects of drug administration such as nausea, vomiting, alopecia, cardio (ADM) and renal (CDDP) toxicity and bone marrow suppression, is a problem that must be solved as soon as possible.
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PMID:[Significance of surgical adjuvant chemotherapy in osteosarcoma]. 349 46

Chemotherapeutical treatment with high dose methotrexate (HD-MTX) of osteogenic sarcoma has been performed at the Orthopaedic University Clinic of Vienna since 1975. In accordance with the cooperative study for osteosarcoma (Coss) which has been in use in Germany and Austria since 1977, HD-MTX has been used in larger quantity beside other cytostatic drugs. The total of 4259 g MTX has been applied to 36 patients who were suffering from malignant bone tumors. We report about the toxicity and compatibility of MTX. Within 231 cycles of treatment in 8 cases a high toxicity (grade IV after modified WHO-Score) was found. One patient died in consequence of the chemotherapy by fungal infection.
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PMID:[Compatibility and toxicity of methotrexate in the treatment of bone tumors]. 349 91

7-Hydroxy-MTX production after consecutive high-dose MTX therapy (12 g/m2) was measured in 7 patients with osteosarcoma by HPLC. 7-Hydroxy-MTX serum values in the last cycle were found to be significantly lower compared with the first high-dose MTX treatment of the adjuvant chemotherapy protocol (COSS 80). Moreover, in another patient highly reduced 7-hydroxy-MTX production was correlated with severe clinical toxicity. As 7-hydroxy-MTX is a 200 fold less potent dihydrofolic acid reductase inhibitor compared with MTX decreased production of the metabolite may lead to enhanced clinical toxicity which may not be predictable monitoring MTX serum levels alone.
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PMID:7-Hydroxy-methotrexate and clinical toxicity following high-dose methotrexate therapy. 385 53

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.
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PMID:Control of primary osteosarcoma with chemotherapy. 387 85

A randomized two-arm study was undertaken to determine relative tumoricidal effects of intra-arterial cis-diamminedichloroplatinum II (I/A-CDP) and high-dose methotrexate with citrovorum factor rescue (MTX-CF) in the treatment of the primary tumor in patients with osteosarcoma. Responses were evaluated by clinical, radiographic, angiographic, and pathologic parameters. Fifteen patients were randomized to receive MTX-CF and 15 to I/A-CDP. In the MTX-CF arm there were four responses (three complete responses, one partial response) whereas in the I/A CDP arm there were nine responses (seven complete responses, two partial responses). Two patients who failed MTX-CF and requested alternative treatment with I/A-CDP also responded. The total I/A-CDP response was 11/17.
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PMID:Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma. 387 32

Temporary neurologic abnormalities were detected in 9 of 60 patients undergoing treatment with high-dose methotrexate and citrovorum factor rescue (MTX-CF) for osteosarcoma. The incidence of abnormalities and abnormalities themselves were more severe than previously reported. This was attributed to an increased dose and more frequent administration of MTX-CF. In view of the transient nature of the abnormalities, a biochemical cause is implicated, and the mechanisms by which it may occur are discussed.
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PMID:Transient neurologic disturbances induced by high-dose methotrexate treatment. 387 90

Severe toxicity associated with high-dose methotrexate (HD-MTX) combined with citrovorum factor rescue (CR-Rescue) was evaluated in the 365 courses in 54 patients with osteosarcoma. Anaphylactoid reaction developed in 8 patients (14.8%), 8 courses (2.2%). The mean age was 14 years old. The total dose given was 85770mg in mean and 1840 mg per body weight (kg). The occurrence was proportional to the dose and the number of the course. Plasma MTX concentration remained under 10(-7) mol/l during the episode. Delayed clearance of MTX from plasma was treated with massive CF-Rescue in 10 patients (19%) (the mean age of 13.6), in 12 courses (3.3%), which was observed on an average at the 7th course when the total dose reached to 59530 mg, or 1390 mg per body weight (kg). Neurotoxicity was observed in only one patient (1.9%), one course (0.3%). Severe toxicity associated with HD-MTX therapy tended to occur according to dose escalation and the number of administration. To overcome severe toxicity careful observation of clinical symptoms and signs as well as adequate treatment of side effects without delay are of importance.
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PMID:[Evaluation of severe side effects of high-dose methotrexate in osteosarcoma]. 658 5


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