Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA metabolism in bone marrow cells was measured under high-dose Methotrexate/Leucovorin adjuvant chemotherapy of a patient with primary amputation of his right leg because of osteogenic sarcoma. The biochemical data showed that there was no rescue effect of Leucovorin after 200 mg/kg Methotrexate. Corresponding to this "biochemical failure" of the rescue effect the patient died from the complications of a long and very severe bone marrow suppression. To improve the safety of this therapeutic regimen the intravenous injection and in some cases a higher dose of Leucovorin is recommended.
 ...
PMID:[High-dose methotrexate/leucovorin adjuvant chemotherapy of osteogenic sarcoma: biochemical effects in DNA-synthesis of bone marrow cells (author's transl)]. 30 51

Osteosarcoma is the one of the tumors that's prognosis have been improved dramatically by the introduction of chemotherapy consisting mainly of adriamycin, high-dose methotrexate with Leucovorin rescue and cisplatinum. Now, the purpose of the treatment for osteosarcoma are assurance of their life and functional and beautiful limb-sparing. Recently, preoperative chemotherapy for limb saving is given to patients with osteosarcoma of the extremities. The five year survival rate increased to 65% and limb sparing rate became above 50%. It is generally accepted that pre- and 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.
 ...
PMID:[Adjuvant chemotherapy of osteosarcoma]. 230 48

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.
 ...
PMID:[Surgery and adjuvant chemotherapy of osteosarcoma]. 346 May 27

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.
 ...
PMID:[Significance of surgical adjuvant chemotherapy in osteosarcoma]. 349 46

High-dose methotrexate/Leucovorin rescue therapy is based on the assumption of differences in the transport system for folate compounds between normal and malignant proliferating cells. Thus, under normal conditions, methotrexate (MTX) and Leucovorin (citrovorum factor, CF) in low doses can enter the cells by an active transport system, whereas in some malignancies - such as osteosarcoma - these substances only penetrate through the cell membrane by passive diffusion if they are given in very high doses. Therefore, after high-dose MTX treatment, the cytotoxic effect of the folate antagonist is compensated for by rescue with Leucovorin in low doses only in the normal cell system. The consequence of this kind of treatment is a selective antitumor effect. To avoid cytotoxic side effects, this therapeutic regimen must be monitored carefully. The decrease of the ratio of 3H-deoxyuridine (dUR) beta H-thymidine (dTR) incorporation into the DNA of the cells is a good biochemical parameter for estimating the MTX effect on rapidly proliferating cell systems. Using this indicator, it was shown that the usually administered dose of Leucovorin is not sufficient for an effective rescue of the bone marrow cells as long as the MTX serum concentration is equal or higher than 10(-6) M. If in critical cases the MTX elimination is retarded, a rescue can only be achieved by Leucovorin at doses tenfold higher than the actual amount of MTX in the whole body system. The Leucovorin rescue does under such circumstances can be calculated according to the formula Leucovorin (mg) = 10 x MTX (mg/l) x 0.76 x body weight (kg).
 ...
PMID:Biochemical control of high-dose methotrexate/Leucovorin rescue therapy. 696 15