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)

Osteocalcin is initially synthesized as an 11 kD molecule consisting of a 23-residue translocation signal peptide that is cleaved during translation, a 26-residue propeptide that targets the protein for gamma-carboxylation, and the 49-residue mature protein. Although the majority of newly synthesized osteocalcin is deposited into bone matrix, a small amount can be detected in blood, and it is this characteristic that has led to its current clinical use as a specific index of osteoblastic activity. Nothing is known, however, about the fate of the propeptide. If osteocalcin and the propeptide are cosecreted, then the concentration of the propeptide could also be useful as a marker of osteoblastic function and, further, may be superior to osteocalcin because it would be unaffected by binding to bone. To test this hypothesis, we synthesized a peptide corresponding to 21 residues of the osteocalcin propeptide from humans and produced a polyclonal antibody to this peptide. Human sera were screened for the presence of the propeptide, and the human osteosarcoma cell line MG-63 was tested for secretion of the propeptide. We could not detect any osteocalcin propeptide in sera from normal adults or individuals with renal failure or primary hyperparathyroidism or those on long-term coumadin therapy. Likewise there was no propeptide present in media from cells grown in the presence of vitamin K, 1,25-(OH)2D3, warfarin, or warfarin plus 1,25-(OH)2D3. In contrast, the cell extract, characterized by high-performance liquid chromatography, contained mature osteocalcin, free propeptide, and the proosteocalcin precursor when cells were grown in the presence of 1,25-(OH)2D3 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The osteocalcin propeptide is not secreted in vivo or in vitro. 154 60

36 patients with advanced malignancy were studied in a phase I trial of continuous 24-h infusion of floxuridine (FUdR) plus etoposide plus cisplatin (FEP) administered for 5 consecutive days at 4-week intervals. Study design fixed the dose rate of etoposide and cisplatin with escalation of FUdR only. Dose rate-limiting toxicity related to the FUdR component was stomatitis and diarrhoea and was invariably associated with leukopenia and thrombocytopenia when grade 3 or 4 level gastrointestinal toxicity was observed. Only 3 of 64 courses were associated with transient renal failure related to cisplatin. Drug-related deaths occurred (leukopenia-associated sepsis) in 4 patients with poor performance status (ECOG 3 and 4). Responses occurred in 15 of 26 evaluable patients (all previously treated minimally or untreated) including 5/11 non-small cell lung cancer; 3/3 oesophageal; 2/2 breast; 4/5 gastric; 1 osteogenic sarcoma; and 1 unknown primary (probably ovary). The recommended dose rates for a 5-day infusion of the three agents for good risk patients is 20 mg/m2 per day of each drug. For poor risk patients including age greater than 65 years; performance status 2 or greater; or extensive bone metastases or prior radiation; the recommended starting dose rates are: FUdR 15 mg/m2 per day; etoposide 15 mg/m2 per day; and cisplatin 20 mg/m2 per day. Dose escalation of FUdR to a maximum of 25 mg/m2 daily is feasible in selected patients demonstrating optimal tolerance.
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PMID:Infusion of floxuridine plus etoposide plus cisplatin in human malignancies. 183 61

An 18-year-old female patient receiving adjuvant chemotherapy for osteogenic sarcoma developed a pruritic erythematous rash during infusion of the eighth dose of methotrexate (8 g/m2) in the series. In other respects, the infusion proceeded normally but the 24-hour serum concentration of methotrexate was unexpectedly and extremely high, 574 mumols/L. Dosing error was excluded, as was the hypothesis that the high concentrations were due to the presence of methotrexate-specific antibodies. Acute oliguria and renal failure were the primary manifestations of the drug-induced toxicity and the high concentrations can be attributed to decreased renal elimination of the drug over the first 24 hours. Treatment consisted of folinic acid rescue, forced diuresis, sequential charcoal haemoperfusion and haemodialysis, and repeated oral doses of activated charcoal. After examination of the contribution of the extracorporeal procedures and the charcoal to the elimination of the drug, the relative lack of morbidity was attributed primarily to the folinic acid rescue and the intensive supportive care.
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PMID:Survival after unexpected high serum methotrexate concentrations in a patient with osteogenic sarcoma. 228 98

From August 1990 to June 1993, 30 patients with osteosarcoma of lower extremities were treated with chemotherapy by hyperthermic regional isolated perfusion. There were 19 male and 11 female with a mean age of 21 (15-28) years. All of the tumors were located in the lower limbs: 20 on the femora, 9 on the tibiae and 1 on the fibula. Chemotherapy was going on for 60 minutes during hyperthermic regional isolated perfusion. Temperature was kept at 42 degrees C in deep soft tissue around the tumor during perfusion. The results showed that local edema of the limbs were reduced observably, tumors were shrunken and hardened after perfusion. Perimeter of the limbs were decreased and mobility of the limbs increased. Pathological examination indicated that all of the tumors responded well to the chemotherapy by perfusion and 90%-95% of the osteosarcoma cells were destroyed. Two cases were complicated with compression syndrome, and 1 with renal failure. The authors would suggest that hyperthermic regional isolated perfusion is an effective chemotherapeutic method in management of malignant tumors of limbs.
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PMID:[On the method of hyperthermic chemotherapy by regional isolated perfusion for tumors of lower extremities]. 780 65

A case report of toxicity following concurrent administration of high-dose methotrexate and amoxycillin is presented. A 16-year-old male patient was administered 10 high-dose methotrexate cycles for treatment of a fully malignant osteogenic sarcoma. Methotrexate was administered at a dosage of 8 g/m2 and infused intravenously over a 6-h period. The patient received pre- and posttreatment hydration and sodium bicarbonate for alkalinization of urine. Calcium folinate rescue was performed when appropriate. During the 10th cycle, coadministration of amoxycillin (1 g/6 h, p.o.) resulted in prolonged and marked enhancement of methotrexate serum levels. Pharmacokinetic parameters obtained in cycle 10 indicate significant differences for total plasma clearance, mean residence time, and distribution half-life when compared to those in cycles 1-9. Amoxycillin decreased the renal clearance of methotrexate, probably by competition at the common tubular secretion system and by secondary methotrexate-induced renal impairment. The patient experienced acute and subacute toxicity with renal failure, myelosuppression, mucositis, nausea, vomiting, fever, and dermatologic abnormalities. Patients receiving amoxycillin during methotrexate therapy should be closely monitored to avoid severe toxicity.
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PMID:Pharmacokinetic interaction between high-dose methotrexate and amoxycillin. 824 43

We report on an 18.5-year-old woman with osteosarcoma and delayed methotrexate (MTX) elimination due to renal failure after high-dose MTX, in whom rescue with high doses of folinic acid caused intolerable side effects. In this life-threatening clinical situation, the patients was rescued by the administration of recombinant carboxypeptidase G2, a bacterial enzyme that rapidly hydrolyzes MTX into inactive metabolites. This is the first report on the successful clinical use of this alternative catabolic route for the elimination of MTX.
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PMID:Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure. 851 32

This prospective study was designed to test the activity of an ifosfamide-etoposide (VP-16) regimen on poor-risk, nonmetastatic, osteogenic sarcoma. A total of 13 patients with nonmetastatic osteogenic sarcoma with a poor histologic response to primary high-dose methotrexate-doxorubicin (Adriamycin)-cisplatinum chemotherapy received a total of six 5-day courses of ifosfamide (1,800 mg/m2) and etoposide (100 mg/m2) at three weekly intervals. The protocol was well tolerated, with only one case of transient renal failure. At present, eight patients (62%) have been in sustained complete remission with no evidence of recurrent disease for a mean follow-up of 3.4 years (range, 1.5-7.0 years). One patient is alive with lung metastases, and four have died of progressive disease. This prospective, albeit small, study confirms the efficacy of an ifosfamide-VP-16-based regimen in poor-risk, extremity, nonmetastatic osteogenic sarcoma. The demonstrated activity should spark large trials of ifosfamide-containing regimens in osteogenic sarcoma.
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PMID:Postsurgical etoposide-ifosfamide regimen in poor-risk nonmetastatic osteogenic sarcoma. 949 63

Isolated perfusion of the extremities with high-dose tumour necrosis factor alpha (TNF-alpha) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated kidney perfusion. We studied the feasibility of a perfusion with TNF-alpha and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 microg TNF-alpha. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-alpha and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated kidney perfusion, with TNF-alpha alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the kidney to perfusion with TNF-alpha, the minimal threshold concentration of TNF-alpha to exert its anti-tumour effects was not reached. The applicability of TNF-alpha in isolated kidney perfusion for human tumours seems, therefore, questionable.
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PMID:In vivo isolated kidney perfusion with tumour necrosis factor alpha (TNF-alpha) in tumour-bearing rats. 1002 9

An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate.
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PMID:Pharmacokinetic interaction between high-dose methotrexate and oxacillin. 1214 45

Immunological evaluation by panel reactive antibody (PRA) and determination of anti-HLA specificity is an important phase in the assessment of patients awaiting kidney transplant. The main causes of immunization are previous solid organ transplants, blood transfusions, and pregnancy; immunogenicity can also be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone allografts is not yet fully understood. We report the case of a 19-year-old patient with osteosarcoma who underwent resection of the left proximal tibia with reconstruction using human bone in 1997 (donor typing: A3, A29 (19) - B44 (12), Bw4 - DR13 (6), DR7, DR52, DR53). The patient was subsequently placed on the waiting list for a cadaver donor kidney transplant because of chronic kidney failure caused by cisplatin toxicity. Pretransplant immunological screening using the CDC (complement dependent cytotoxicity) technique revealed a PRA of 63% and anti-A3 and anti-A68 antibodies. The presence of IgG antibody specificity against class I and class II donor antigens (specifically anti-A3, B44, DR7 antibodies) was highlighted using flow cytometry (Tepnel-Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I - II - Tepnel-Luminex) detected direct antibodies against all donor antigen specificities. This is the first reported case of immune induction after a bone graft in a kidney transplant candidate. It underlines the importance of the availability of HLA typing data of all human allograft donors.
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PMID:[Anti-HLA antibodies after bone graft and their impact on kidney transplant programs]. 1938 96


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