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 effect of purified human platelet factor 4, a platelet alpha-granule protein, on the growth of the human osteoblastic osteosarcoma cell lines Saos-2 and G-292 was investigated. Platelet factor 4 (20 ng/ml to 2 micrograms/ml) caused a significant, dose-dependent inhibition of human osteoblast-like osteosarcoma cell proliferation. Platelet factor 4 exerted its inhibitory effect under all growth conditions tested: serum-free, serum-stimulated and thrombin-stimulated. The platelet factor 4-induced cell inhibition was not associated with a cytotoxic effect on the cells (assessed by lactate dehydrogenase release). The inhibitory effect of platelet factor 4 was not affected by the presence of indomethacin in the cultures, indicating that the effect was prostaglandin-independent. These results suggest that platelet factor 4 has direct antitumor effects and that it may be important in pathological and physiological processes of bone.
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PMID:Human platelet factor 4 is a direct inhibitor of human osteoblast-like osteosarcoma cell growth. 152 Mar 9

The Multi-Institutional Osteosarcoma Study (MIOS) was designed to determine whether intensive multiagent adjuvant chemotherapy improves the outcome of patients with nonmetastatic high-grade osteosarcoma of the extremity as compared with concurrent controls. After definitive surgery of the primary tumor, patients were randomly assigned to immediate adjuvant chemotherapy or to observation without adjuvant treatment. Updated results of this trial indicate that the projected six-year event-free survival for the control group is 11% compared to 61% for the chemotherapy group (p less than 0.001). Similar results were observed in patients who declined randomization but who were followed according to the treatment arms of the protocol. When randomized and nonrandomized patients are pooled according to assigned treatment, a survival advantage favoring those patients treated with immediate adjuvant chemotherapy is apparent. An analysis of prognostic factors among patients receiving immediate adjuvant chemotherapy reveals that elevation of the serum lactic dehydrogenase at diagnosis is the factor most predictive of adverse outcome. Location of the primary site in the tibia confers a favorable prognosis. The authors conclude that the natural history of high-grade osteosarcoma of the extremity has not changed over the past two decades. The administration of immediate adjuvant chemotherapy has a significant favorable impact on event-free survival and should be recommended for all such patients.
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PMID:Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. 188 63

Alterations of blood analyses have been studied at relapse of patients with osteosarcoma and Ewing's sarcoma. The tests included erythrocyte sedimentation rate (ESR), haemoglobin (Hb), leukocyte and thrombocyte counts, gamma glutamyltransferase (GT), lactate dehydrogenase (LD) and alkaline phosphatase (ALP). Sixteen relapsing patients diagnosed from 1970 to 1987 were eligible in each sarcoma group. Median age was 16 years (range 9-30) at diagnosis. The blood tests seemed to be of no help in detecting relapse of osteosarcoma, while ESR, LD and GT rose significantly in relapsing patients with Ewing's sarcoma. ESR was best correlated to disease activity.
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PMID:Alterations of blood analyses at relapse of osteosarcoma and Ewing's sarcoma. 197 22

Of 33 surgical specimens of osteosarcoma obtained from 24 patients, eight were established as transplantable tumor lines in immune-deprived CBA/CaJ inbred mice. Each line retained the histological characteristics of the corresponding primary tumor and produced human lactate dehydrogenase isozymes. Volume doubling times, which ranged from a mean of 12.3 +/- 5.6 to 39.3 +/- 9.8 days, were stable for individual lines over multiple passages. Flow cytometric analysis indicated similar cellular DNA content values in the primary human tumors and established xenograft lines; the presence of two separate stem lines, as in the original tumors, was observed in the laboratory models. Comparison of two methods of immune deprivation indicated that thymectomy, whole-body irradiation, and bone marrow reconstitution was associated with a higher rate of successful engraftment than was thymectomy, 1-beta-D-arabinofuranosylcytosine treatment, and whole-body irradiation. Bone marrow-reconstituted mice also showed less variability in tumor volume doubling time. We conclude that osteosarcoma can be heterotransplanted into bone marrow-reconstituted mice with a relatively high success rate and that the xenografts retain features characteristic of the tumors of origin. The availability of these models should prove useful in the development of new therapeutic regimens and in understanding the biology of osteosarcoma.
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PMID:Development and characterization of pediatric osteosarcoma xenografts. 232 4

Six hundred and fifty-six patients with osteosarcoma of the extremities (107 metastatic and 549 with localized disease) were followed from 2.5 to 20 years (average: 10 years) to evaluate whether their pretreatment serum lactate dehydrogenase (LDH) enzyme levels had a clinical value in predicting the course of the disease. The percentage of patients who had an elevated serum LDH at the time of diagnosis was significantly higher in those patients with metastatic disease than those who had localized disease (64% versus 33%, p < 0.0001). For those who presented with localized disease and had an increased serum LDH level, far more ultimately developed a relapse of disease (60% versus 38%, p < 0.0001) than those patients with a normal pre-treatment value. The prognostic significance of the serum LDH was more pronounced for the 247 patients treated with adjuvant chemotherapy (relapse rate of 72% versus 48%; p < 0.0002) than the 271 patients treated with neoadjuvant chemotherapy (relapse rate: 46% versus 28%, p < 0.005). Following treatment, serum LDH levels almost uniformly returned to normal and no correlation between postoperative levels and relapse of disease could be identified. We have demonstrated that in patients with osteosarcoma of the extremities, pretreatment serum LDH levels have a definite prognostic value which should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.
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PMID:Prognostic significance of serum lactate dehydrogenase in patients with osteosarcoma of the extremities. 798 4

The mechanisms involved in the mitogenic actions of insulin-like growth factor-I (IGF-I) on skeletal cells are at present unclear. We have investigated the role of glucose-6-phosphate dehydrogenase (G6PD) in this mechanism and provide strong evidence that stimulation of G6PD activity is required for the growth promoting activities of IGF-I. IGF-I (10 ng/ml) significantly elevated G6PD activity in MG-63 human osteosarcoma cells within 30 min which preceded the IGF-I induced DNA synthesis in these cells. Inhibition of G6PD activity by epiandrosterone decreased DNA synthesis in IGF-I stimulated MG-63 cells but this was partly overcome by the addition of a combination of the four deoxyribonucleosides. IGF-I did not cause a general increase in cell metabolism as succinate dehydrogenase and iso-citrate dehydrogenase activity were not altered. Although IGF-I caused a significant increase in lactate dehydrogenase activity this was not inhibited by epiandrosterone. The culture of metatarsals of 4-week-old rats with IGF-I (10 ng/ml) also stimulated G6PD activity in osteoblasts lining the metaphyseal trabeculae.
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PMID:Mitogenic action of insulin-like growth factor-I on human osteosarcoma MG-63 cells and rat osteoblasts maintained in situ: the role of glucose-6-phosphate dehydrogenase. 825 63

Remarkable progress has been made in the treatment of osteosarcoma in the past two decades as a result of the development of effective adjuvant chemotherapy. However, the prognosis is poor in patients with early lung metastases. We review the lactate dehydrogenase release prognostic factor in the development of early lung metastases. This is a retrospective study. Eighteen patients with osteosarcoma were divided in two groups: Group A, patients with normal lactate dehydrogenase and Group B, patients with elevated lactate dehydrogenase. A univaried analysis was established. Ten patients (55%) had elevated levels of lactate dehydrogenase at diagnosis; nine of these patients developed lung metastases in the first twelve months. The difference in patients with normal levels of lactate dehydrogenase was significant (p: 0.02). The value of lactate dehydrogenase as an isolated single factor is limited. It is necessary to consider the tumoral volume, the patient's age and the histologic subtype in the prognosis of these patients, to predict the early development of pulmonary metastatic disease.
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PMID:[Lactic dehydrogenase as a prognostic factor in the development of pulmonary metastatic disease in patients with osteosarcoma]. 896 78

The authors investigated the influence of methotrexate (MTX) serum concentration on (histologically evaluated) tumor necrosis, induced by a primary multiagent chemotherapy, including MTX, for osteosarcoma. MTX serum peaks in 151 patients, preoperatively treated with MTX (8-12g/m2), cisplatin (120mg/m2) and Adriamycin (60mg/m2), were analyzed. Significantly (p < 0.01) higher serum MTX mean peaks were observed in patients with complete tumor necrosis (MTX 773.8 mumol/l) compared to patients with 90-99% tumor necrosis (639.8 mumol/l), 50-89% tumor necrosis (649.1 mumol/l) or less than 50% tumor necrosis (610 mumol/l). Complete tumor necrosis was observed in 9% of patients with MTX peaks of less than 600 mumol/l, in 27% of patients with serum MTX peaks between 600 and 699 mumol/l and in 37% of those with MTX peaks ranging from 700 to 799 mumol/l. Higher MTX peaks (800-899, 900-999, > 1000 mumol/l) were not associated with a further increase of cases with complete tumor necrosis. 40% of patients with an MTX peak greater than 700 mumol/l had complete tumor necrosis, compared to 15.5% of patients who did not reach this value (p < 0.002). At a multivariant analysis including age, sex, tumor site and volume, pretreatment serum alkaline phosphatase and lactic dehydrogenase levels, MTX peaks of 700 mumol/l and, less significantly, the histologic type (telangiectatic osteosarcoma), were independent factors influencing tumor necrosis. The authors conclude that MTX serum peaks significantly influence chemotherapy-induced tumor necrosis in osteosarcoma. In a primary treatment consisting of cisplatin, Adriamycin and MTX, complete tumor necrosis can be obtained in 40% of patients with MTX peak concentrations > or = 700 mumol/l.
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PMID:Methotrexate serum concentration and histological response to multiagent primary chemotherapy for osteosarcoma of the limbs. 898 Nov 89

Multidisciplinary treatment of osteosarcoma in the Faculty of Medicine Ramathibodi Hospital, Mahidol University, using preoperative intraarterial and postoperative chemotherapy, with or without local irradiation, combined with surgery and prophylactic lung irradiation provided an excellent 5 years' survival of 55 per cent, the same rate as the 9 years' survival. The survival was stable after 4.4 years. The patients with local irradiation had more tumor destruction apparent on the surgical specimen. The administration of prophylactic whole lung irradiation provided an outcome without any undesirable complication. Sixteen per cent of the cases with PLI developed lung metastasis compared to 48 per cent without PLI. The most important prognostic factor was low level of serum lactic acid dehydrogenase. The unanswered question is what is the optimal treatment for osteosarcoma?
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PMID:Osteosarcoma: a study of 130 cases. 917 82

One hundred thirty patients with high grade osteosarcoma were enrolled in a randomized prospective multidisciplinary treatment that included intraarterial chemotherapy, local irradiation, limb salvage surgery, and prophylactic whole lung irradiation. The patients were evaluated to stage the prognostic factors. In a multivariate analysis, a minimal level of serum lactic acid dehydrogenase less than 300 IU/L showed a significant prognostic value. The history of trauma before diagnosis of disease, local irradiation of the affected site, histologic response to preoperative multidisciplinary therapy, and prophylactic whole lung irradiation were associated with significantly better prognosis in the log rank test. Patient age, site of the primary tumor, presentation of fracture, pathologic subtype, signs and symptoms, serum alkaline phosphatase level, and erythrocyte sedimentation rate were not found to be prognostic factors. The 9-year survival rate of the whole group was 55%.
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PMID:Prognostic factors among 130 patients with osteosarcoma. 941 42


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