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)

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

In 61 patients (pts.) with biopsy proven osteogenic sarcoma a disease free survival rate of > 80% was obtained using T-7 chemotherapy. This can be explained by successful eradication of pulmonary micrometastases with aggressive chemotherapy. The prognosis for pts. < 12 years was significantly improved since a higher dose off Methotrexate was used for this younger age group. The histologic effect of preoperative chemotherapy on the primary tumor is of prognostic value for the outcome of the disease. Pts. with good histologic effect on the primary tumor (grade III and IV effect) show a 100% disease free survival rate, whereas pts. with poor histologic effect (grade I and II effect) have a 50% chance to develop metastases. The role of cis platinum in future therapeutic trials is discussed based on the experience with cis platinum in phase II trials.
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PMID:[Combination chemotherapy in osteogenic sarcoma: the Memorial Sloan-Kettering cancer center experience (author's transl)]. 615 96

Methotrexate (MTX) polyglutamates were detected in osteogenic sarcoma tumor samples obtained from patients 24 or 48 h after receiving high-dose MTX/leucovorin rescue therapy. Tumor samples were assayed by high-performance liquid chromatography, and polyglutamyl metabolites, along with MTX, were quantitated using both direct u.v. absorption at 313 nm and an enzyme titration assay. Good agreement between these two methods was found although the more sensitive enzyme assay detected peaks in some samples not detected by u.v. absorbance. A wide variation in MTX:MTX polyglutamate levels (1:1 to 25:1) was found among the six clinical samples studied. Also, no correlation between the extent of polyglutamate formation and plasma levels (determined at the time of tumor sampling) was observed. High intracellular levels of a derivative which appears to be the 7-hydroxy metabolite of MTX were also detected in four of six samples. This material coeluted with authentic standard, showed spectral properties like standard 7-OH-MTX, and did not inhibit dihydrofolate reductase.
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PMID:Detection by high-performance liquid chromatography of methotrexate and its metabolites in tumor tissue from osteosarcoma patients treated with high-dose methotrexate/leucovorin rescue. 620 60

Methotrexate (MTX)-resistant sublines of malignant human cells were selected in vitro by stepwise increase in drug concentration in the medium. By this procedure a subline of Burkitt's lymphoma cells (RAJI) was made 290-fold resistant (RAJI/MTX-R), T-cell leukemia cells (CCRF-CEM) were obtained 210-fold resistant (CEM/MTX-R), and 3 MTX-resistant human osteosarcoma lines were selected: TE-85/MTX-R (19-fold resistant; relative to wild-type); MG-63/MTX-R (8-fold resistant); and SAOS-2/MTX-R (200-fold resistant). We also studied a B-cell lymphoblastoid line, WI-L2/m4, that was 13,000-fold resistant. Assay of cellular dihydrofolate reductase (DHFR) showed the following pattern of activity in resistant cell lines, relative to parental cell activity: RAJI/MTX-R, 550-fold increased; CEM/MTX-R, unchanged; TE-85/MTX-R, 4-fold increased; MG-63/MTX-R, 6-fold increased; SAOS-2/MTX-R, unchanged; and WI-L2/m4, 110-fold increased. Measurement of MTX membrane transport showed decreased uptake in CEM/MTX-R and SAOS-2/MTX-R, relative to parental cell lines. The other DHFR-overproducing cells all gave normal initial MTX uptake rates but increased total uptake. The DHFR-overproducing lines all had significant cross-resistance to both metoprine and trimetrexate; the two lines with defective MTX transport were not cross-resistant, and the CEM/MTX-R cells showed collateral sensitivity to these agents. Only minor cross-resistance to homofolic acid was found in all MTX-resistant lines. The highly MTX-resistant RAJI/MTX-R and WI-L2/m4 cells showed minor cross-resistance to the dual inhibitor of thymidylate synthetase and DHFR, CB3717 (5- and 15-fold, respectively). These studies demonstrated that, depending upon the mechanism of resistance, MTX-resistant human tumor cells may be effectively killed by antifolates with different routes of uptake into cells, or with a different enzyme target. Thus, there are at least three functionally distinct classes of folate antagonist with antitumor activity.
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PMID:Patterns of cross-resistance to the antifolate drugs trimetrexate, metoprine, homofolate, and CB3717 in human lymphoma and osteosarcoma cells resistant to methotrexate. 622 14

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

The relationship between total surface antigen expression per cell (means) - measured by fluorescence-labelled monoclonal antibodies (fluorescence-histograms) and the distribution of cells in the cell cycle (DNA-histograms) and size-scattergrams (cell sorter FACS-IV) were analysed in drug treated unsynchronized and synchronized osteogenic sarcoma cells (2OS) in vitro. Drugs with various sites of action in the cell cycle were used. Adriamycin, Vindesine, in concentrations applied accumulate cells in G2 + M phase. Methotrexate arrests cells in the boundary of G1/S phase. Size-scattergram and DNA-histogram analysis have shown that the entrance of cells to the cell cycle is usually accompanied by an increase in the cells size and amount of their DNA. The size of the cells influenced antigenic expression much more than the distribution of the cells in the various cell cycle phases: in the bigger cells the expression per cell was more pronounced. The increase of antigen expression was the highest for Adriamycin and for Methotrexate treated cells. However, this increase was limited and never exceeded plus 50% in relation to the control. This relatively low difference resulted from the fact, that a given phase of the cell cycle included cells markedly heterogenic in respect of size and antigenic content. It was also shown that lower concentration of serum in culture medium and confluent growth of older cultures decrease surface antigen expression per cell.
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PMID:Analysis of surface antigen expression per cell of human osteogenic sarcoma cells by fluorescence-labelled monoclonal antibodies. 659 41

9 patients with osteosarcoma were treated with a total of 122 infusions of high-dose methotrexate (MTX; 140-350 mg/kg) followed by leucovorin rescue. Plasma kinetics of MTX and 7-hydroxymethotrexate (7-OH-MTX) has been routinely monitored. Due to inadequate hydration and alkalinization, 1 of the 122 high-dose MTX infusions was followed by delayed disappearance of MTX and 7-OH-MTX from plasma with subsequent development of severe mucositis. Serious hepatotoxicity repeatedly developed in another patient with inconspicuous MTX kinetics. The benefit of monotherapy with high-dose MTX for adjuvant treatment of osteosarcoma remains questionable, since 6 of 8 patients with primary osteosarcoma developed pulmonary metastases within 4-12 months (median 5 months), 2 have been disease-free and alive for 25 and 53 months.
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PMID:High-dose methotrexate for osteosarcoma: toxicity and clinical results. 660 Aug 27

Two patients treated with high dose methotrexate otrexate with citrovorum rescue (HDMTX-CF) for osteogenic sarcoma developed the acute onset of neurologic deficits. Prior to the onset of symptoms, one child suffered brief episodes of altered consciousness. Both patients developed hemiparesis and then steadily improved over 72 hours. Laboratory evaluations disclosed normal coagulation parameters and nontoxic serum methotrexate levels at onset of symptoms. Computed tomography in one child disclosed a large low absorption abnormality. This patient represents the first reported case of positive radiologic findings associated with this syndrome. The two patients recovered completely and received further HDMTX-CF without sequelae. This condition may result from transient demyelination or embolic cerebrovascular disease.
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PMID:High dose systemic methotrexate-associated acute neurologic dysfunction. 660 69

Osteosarcoma patients free of CNS metastases are at risk for acquiring leukoencephalopathy after receiving multiple courses of high dose intravenous methotrexate followed by oral leucovorin rescue (MTX-LV). A prospective study of the adequacy of CNS rescue of MTX biochemical toxicity by oral leucovorin was undertaken in newly diagnosed neurologically normal osteosarcoma patients. Prior to surgical resection of the primary tumor, ten patients received 4 weekly courses of MTX-LV. During the fourth weekly MTX-LV treatment, 0 and 72 hr serum and CSF determinations of MTX, 5-methyl-tetrahydrofolate (5-MTHF) and LV were made. No CSF MTX was detectable at 0 hr in any patient, but a significant elevation in CSF MTX occurred in 9/9 patients at 72 hr (mean 47.2 +/- 31.8 ng/ml or 1.04 +/- 0.7 X 10(-7) M). There was no significant change in mean CSF 5-MTHF over 72 hr despite a rise in serum 5-MTHF. MTX exceeded 5-MTHF in 6/9 patients in CSF, whereas only 3/8 patients had higher MTX in the serum at 72 hr. No acute systemic or neurotoxicity was seen. The failure of oral leucovorin to consistently elevate CSF 5-MTHF levels at 72 hr in the context of significant levels of CSF MTX may result in intermittent CNS folate deficiency. The clinical and pathological syndrome of leukoencephalopathy may be related to this phenomenon and may evolve after repeated MTX-LV treatments.
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PMID:The inability of oral leucovorin to elevate CSF 5-methyl-tetrahydrofolate following high dose intravenous methotrexate therapy. 661 87


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