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 bone density of two groups of patients with osteosarcoma treated with high and low doses of MTX is compared with that of a group of healthy subjects of the same age. Bone density was measured in the radius at the mid point and at the trabecular distal point. In the patients treated with low doses there were differences in bone density as compared with the controls. In those treated with high doses the bone mineral content values were significantly lower than those for the controls (p greater than 0.01) at the trabecular distal point but not at the mid point. The significant reduction in BMC in patients treated with high doses indicated that the osteopaenic effect is dose-dependent. The decrease in density only at the site at which trabecular bone is prevalent shows that MTX acts mainly at the level of this type of bone in accordance with the proven greater sensitivity of trabecular bone to the action of other osteopaenic agents.
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PMID:The effects of methotrexate (MTX) on bone. A densitometric study conducted on 59 patients with MTX administered at different doses. 322 Jul 28

From 1977 to 1982, 62 patients with various advanced malignant solid tumors were treated by HD-MTX-CFR therapy and totally 129 courses were given. Majority of the patients suffered from malignant lymphoma (10), osteogenic sarcoma (11), lung cancer (16), esophageal cancer (3), breast cancer (3) and malignant melanoma (4). All were confirmed by cytology or pathology except one primary liver cancer. There were clinically measurable lesions in 59 patients for evaluation of the treatment, and 3 osteogenic sarcoma patients without metastasis were given a postoperative adjuvant chemotherapy. 33 out of 62 had received chemotherapy and/or radiotherapy before. Dose of MTX ranged from 2 to 3 gm per course in most patients and dose of CF, from 9 to 12 mg every 6 hours for 3 days. 2 (3.4%) patients achieved complete remission (1 osteogenic sarcoma and 1 malignant lymphoma) and 8 (13.6%), partial remission (1 osteogenic sarcoma, 5 malignant lymphoma, 1 esophageal cancer and 1 breast cancer) with a total response rate of 15.9%. No response was observed in all 16 lung cancers. The main side effects of HD-MTX-CFR therapy were leukopenia, thrombocytopenia, elevation of SGPT, nausea, vomiting, mucositis, skin rash, fever and fatigue. All patients were followed more than 3 years. 4 patients are still alive (9, 9, 4 and 7 years, respectively), including 3 osteogenic sarcoma patients who received postoperative adjuvant chemotherapy and 1 mycosis fungoides.
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PMID:[High-dose methotrexate with citrovorum factor rescue (HD-MTX-CFR) in the treatment of malignant solid tumors--clinical analysis of 62 patients]. 326 85

There are still some controversy on the role of adjuvant chemotherapy in the treatment of osteogenic sarcoma, and no relevant report has been published in Chinese medical literature. In this paper 15 patients with osteogenic sarcoma treated from March 1982 to March 1986 by high dose MTX with citrovorum factor rescue after surgery are reported. Another 15 patients treated by surgical amputation alone during the same period served for comparison. The sex, age and site of the tumor in the two groups were comparable. In the treated group, MTX 0.7-1.4 g/m2, averaged 0.92 g/m2 were given intravenously, followed by citrovorum factor rescue, once a month for 2-12 injections. 12 patients (80%) in this group were given more than 4 injections. All patients tolerated the treatment well and no death was ascribed to the treatment. The patients were followed for 7-48 months, in the HD-MTX treated group, 1 patient was lost in the follow up, 9 died and 5 were still alive (35.7%). In the comparison group, 2 were lost, 11 died and only 2 were still alive (15.4%). The 2 year survival rate for the treated group was 57.1% and 30.8% for the comparison group (P greater than 0.05). The authors suggest that the dose of MTX be increased and combined with other cytostatic drugs like doxorubicin and cisplatin when necessary for better results. Adjuvant chemotherapy has definite value in the treatment of osteogenic sarcoma if adequate dose and protocols are used. However, the best adjuvant chemotherapy program for Chinese patients still remains to be studied.
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PMID:[Postoperative adjuvant chemotherapy of high dose MTX for osteogenic sarcoma]. 326 74

Methotrexate (MTX) has demonstrated significant activity against relapsed and metastatic osteosarcoma. However, there is little published data to indicate the appropriate dose for MTX when given as a component of a multidrug regimen for the treatment of osteosarcoma. Therefore, the investigators at the Childrens Cancer Study Group undertook a randomized clinical trial that compared Adriamycin and vincristine given with either high-dose methotrexate or moderate-dose methotrexate as postoperation chemotherapy in the treatment of childhood osteosarcoma. We report here the results for 166 patients with completely resected nonmetastatic disease of an extremity. The two therapies demonstrated equivalent disease-free survival (DFS). Further, no therapy prejudices survival after relapse. Approximately 38% of patients remain disease free 4 years after diagnosis. Two relapses occurred in patients free of disease at least 36 months after initiation of treatment. Some factors found by other investigators to be prognostic of poorer DFS, namely, male sex, primary tumor in the humerus or femur, and larger primary tumors, demonstrated similar though not statistically significant trends. The presence of spontaneous necrosis in the tumor sample from the definitive surgery was associated with poor prognosis for DFS. We postulate that this feature represents rapidly growing tumors with increased potential for metastases.
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PMID:A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. 329 1

High-dose methotrexate (HDMTX) with leucovorin (LV) rescue has been used as a therapeutic strategy in oncology for more than a decade. Administration of HDMTX results in tumoricidal plasma concentrations of the drug without significant host toxicity, provided that plasma MTX levels are monitored and LV rescue is properly administered. The original premise of LV rescue was that the provision of reduced folate to normal cells would circumvent the metabolic block produced by MTX and allow resumption of DNA synthesis, although the presumed therapeutic selectivity of leucovorin has not yet been adequately explained. Despite a strong pharmacologic rationale and a vast clinical experience, HDMTX with leucovorin rescue has not been shown to be unequivocally superior to conventional doses of MTX in any clinical situation except, perhaps, for treatment of osteogenic sarcoma and childhood acute leukemia. While HDMTX is an important component of effective treatment regimens for these diseases, its precise contribution to the success of these regimens remains undefined. Although HDMTX can theoretically overcome all known mechanisms of MTX resistance, no data exist to suggest that this can be accomplished in the clinic. Thus, this well-known but poorly understood treatment regimen must remain a subject of clinical investigation rather than a part of routine clinical practice.
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PMID:High-dose methotrexate: a critical reappraisal. 331 19

Immediately after intravenous infusion of a high dose (concentration in serum greater than 1000 mumol/L) of methotrexate, the apparent conjugated bilirubin (Bc) concentrations in serum of two osteosarcoma patients, as measured by the Kodak Ektachem 400 analyzer, were greater than the corresponding total bilirubin concentrations, but decreased as the concentrations of methotrexate in serum decreased. In an interference study we found that methotrexate added to sera containing a wide range of basal Bc concentrations increased the measured Bc concentration in a linear and dose-related fashion. Methotrexate also interfered negatively with measurements of unconjugated bilirubin (Bu). The source of the interference appears to be an overlap in the absorption spectrum of methotrexate with Bc and Bu at 400 nm.
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PMID:Methotrexate interferes with determinations of conjugated bilirubin with the Kodak Ektachem 400. 345 54

Thirty-two patients with osteosarcoma of the femur and the tibia were treated with systemic chemotherapy and radical surgery between 1976 and 1984. Adriamycin (ADR) alone, ADR plus high-dose methotrexate with citrovorum factor (HD-MTX-CF) (protocol A) and ADR plus HD-MTX-CF plus cis-platinum plus bleomycin, cyclophosphamide and actinomycin-D (BCD) (protocol B) were given as chemotherapeutic regimens. Twenty-nine out of 32 patients received chemotherapy both preoperatively and postoperatively, and eleven of 29 patients had a good response. Amputation was performed on 19 patients and en bloc resection on 13 patients. No local recurrence was detected in any of the 32 patients. The disease-free survival rate was 35%. Disease-free survival rate of patients treated with protocol A and protocol B was 25% and 91% respectively. Fourteen out of 17 patients who developed pulmonary metastasis underwent thoracotomy. Survival rate after thoracotomy was 50%. The overall survival rate of 32 patients with osteosarcoma was 56%.
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PMID:Treatment for osteosarcoma--a study of thirty-two patients treated with systemic chemotherapy and radical surgery. 345 79

The primary site of metastasis of osteosarcoma is the lung. In the past, even if the primary lesion was completely removed by radical surgery, more than 90% of patients of died pulmonary metastasis with in one to two years. Control of osteosarcoma therefore depends upon the prevention and treatment of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin and high-dose methotrexate with Leucovorin rescue, dramatically improved the prognosis of osteosarcoma. In the past where systemic chemotherapy was not available, the five-year survival rate was around 19%. The majority of patients developed bilateral pulmonary metastasis within one year after onset, and died. These patients exhibited numerous micro-metastases as well. In patients receiving surgical adjuvant chemotherapy with 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, a single metastasis appearing after the termination of treatment, or early and multiple, appearing resistant to treatment. Surgery is indicated in the former situation while some therapeutic system must be devised for the latter. Recently, preoperative chemotherapy for limb-saving is given to patients with osteosarcoma of the extremities (NSH-3, 4, 5). The adjuvant of chemotherapy proved to be of great significance for improving the survival rate of osteosarcoma and for achieving limb salvage.
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PMID:[Surgery and adjuvant chemotherapy of osteosarcoma]. 346 May 27

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

Cerebral cortical sclerosis is an acquired condition that has rarely been described in cancer patients. We reviewed necropsy findings in all children with cancer who died at the Children's Hospital of Philadelphia during the 20 year period 1963-1982 and found cerebellar sclerosis in 14 children with cancer (12 with acute lymphoblastic leukemia, 1 each with neuroblastoma and osteogenic sarcoma). The lesions were focal (3), multifocal (9) or diffuse (2). They occurred more frequently in children with acute lymphoblastic leukemia who had received intravenous methotrexate therapy. Ten of these 12 children had also received whole brain irradiation. The pathogenesis of the cerebellar sclerosis is unknown, but it is possible that extrinsic cerebellar compression by tumor or chronically increased intracranial pressure may have played a role in 6, ischemia/hypoxia in 3, and methotrexate toxicity in 2. No clear associations could be ascertained in 3. Methotrexate may be a previously unrecognized cause of cerebellar cortical injury. In addition, oncologic treatment regimens that include other central nervous system-penetrating drugs and irradiation may sensitize cerebellar cortex and make it more susceptible to other cerebellar sclerosis-causative factors.
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PMID:Cerebellar sclerosis in pediatric cancer patients. 347 68


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