Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Serum copper level (SCL), serum zinc level (SZL), and SCL/SZL ratio were measured in 18 patients with biopsy-proven osteogenic sarcoma. Measurements were made on sequentially collected serum samples beginning prior to the institution of therapy and continuing periodically until documented relapse. All patients were treated by curative resection and adjuvant therapy consisting of high dose methotrexate (with leucovorin rescue) with or without BCG immunotherapy. The SCL, SZI, and SCL/SZL determinations were made using proton-induced x-ray fluorescence spectrometry. SCL was significantly elevated (p less than .0001) in the 18 patients with primary untreated osteogenic sarcoma )173 +/- 30 microgram/dl) compared with a sex and age-matched normal group (115 +/- 16 microgram/dl). A significantly different SZL was not found, however, so that an elevated SCL/SZL ratio in the osteogenic sarcoma patients was primarily due to the altered SCL. SCL and SCL/SZL did not change significantly following curative surgery or become more abnormal in those patients who developed recurrent disease. The SCL and SCL/SZL were noted to be markedly elevated in those patients receiving BCG therapy, raising concern regarding the specificity of these tests as markers of tumor activity. SCL, SZL, and SCL/SZL did not appear useful as markers of tumor activity in patients with osteogenic sarcoma.
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PMID:Serum copper and zinc measurement in patients with osteogenic sarcoma. 30 81

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in 19 patients with sarcomas, 12 of which were osteosarcomas at various stages. Patients with primary or metastatic osteosarcoma had elevated SCL, whereas amputated osteosarcoma patients who were clinically tumor-free had nearly normal SCL. Patients with primary osteosarcoma had elevated SZL, those with metastases had depressed zinc levels, and amputated patients who were clinically tumor-free and nearly normal SZL. Thus, the ratio of SCL:SZL in metastatic osteosarcoma patients is higher than in patients with primary osteosarcoma. SCL and SZL are compared to clinical histories for selected patients. Patients with the more advanced disease and poorest prognoses had the most elevated SCL and highest SCL:SZL ratios. It appears that the determination of SCL and SZL in osteosarcoma patients may be of value in prognosis and therapy evaluation; furthermore, the ratio of SCL:SZL may be useful in discriminating between patients with primary and metastatic osteosarcoma.
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PMID:Copper and zinc levels in serum from human patients with sarcomas. 76 64

Ceruloplasmin (Cp) levels in sera of osteosarcoma patients, women on chemical contraceptives, and normal individuals were determined by radial immuno-diffusion (RID) and rocket electroimmunophoresis (REP) techniques; serum copper levels (SCL) were determined by atomic absorption spectroscopy. Ratios of SCL/Cp were constant in all groups tested, indicating that the ratio of bound to unbound copper in the serum is maintained relative to normal levels both in osteosarcoma patients and in women receiving chemical contraceptives. There was a highly significant increase over normal levels in Cp concentration in sera from patients with osteosarcoma and from women on chemical contraceptives, in agreement with our previous data on SCL. Either RID or REP can be used to measure serum Cp. The latter method appears to be faster and more sensitive, whereas the former is easier to perform. It appears that the determination of serum Cp in osteosarcoma patients may be of value in differential diagnosis of the disease in selected patients, and in evaluation of the efficacy of therapy.
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PMID:Ceruloplasmin levels in sera from human patients with osteosarcoma. 106 68

In order to study the role of trace elements as potential osteoblastic toxins, we measured bone aluminum, copper, and iron in 106 ambulant patients with histologically proven liver disease. We used analytical and histochemical methods and we correlated our results with serum biochemistry, forearm and spinal bone density, and dynamic bone histomorphometry. Patients with chronic liver disease had higher iron-stained perimeters than control subjects (P less than 0.001). However, the mean iron-stained perimeter was no greater than 5% of the total mineralized bone perimeter and did not correlate significantly with either the osteoblast perimeters or bone formation rates. The mean concentration of bone iron were 2.5 times (P less than 0.01) greater in the patients than in the controls although 80% of the patients fell within the normal range. There was a weak negative correlation between bone iron and the osteoblast perimeters (R = 0.18, P = ns) and between bone iron and bone formation (R = -0.30, P less than 0.05). There were 57 patients (56% of the total) with diminished bone formation, but only 16 had elevated bone iron concentrations. In a regression analysis, age, hypogonadism, and serum albumin concentrations were the most important predictors of osteoblast perimeters and bone formation rates. In vitro experiments using rat osteoblast-like osteosarcoma cells showed that an iron concentration of 400 mumol/liter was required to diminish cellular proliferation and function. Iron concentrations are elevated in the bones of patients with chronic liver disease. However, there is at present insufficient evidence that this metal is responsible for the osteoblast dysfunction seen in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does iron affect osteoblast function? Studies in vitro and in patients with chronic liver disease. 207 Feb 71

The concentrations of calcium and magnesium, and of the trace elements iron, copper, manganese and zinc were determined in the amputation specimen of a 25-year-old patient with osteosarcoma and compared with the tumor-free, normal bone tissue. Not only the concentrations of calcium and magnesium, but also those of the trace elements were significantly higher in the osseous portion of the tumor. The periosseous concentrations of trace elements iron, copper and zinc were also significantly higher in the tumor than in the normal bone tissue.
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PMID:[Mineral and trace element determination in human osteosarcoma. Case report]. 659 3

Heterocyclic thiosemicarbazones, thioureas and 2-substituted pyridine N-oxides as well as representative nickel, cobalt and copper complexes were shown to be potent antineoplastic/cytotoxic agents. The cytotoxicity was demonstrated against single cell leukemia as well as cell lines derived from solid tissue (colon adenocarcinoma, HeLa, KB, skin, bronchogenic lung, bone osteosarcoma and glioma). In L1210 cells, DNA synthesis and subsequently RNA synthesis were particularly inhibited by the agents. IMP dehydrogenase activity and thus purine de novo synthesis was reduced significantly by the agents. Dihydrofolate reductase, ribonucleoside reductase, nucleoside kinase and DNA polymerase alpha activities were inhibited by the agents. d(NTP) pool levels were reduced by most of the agents. DNA strand scission was present with all of the derivatives; however, there was no evidence of intercalation, cross linking or alkylation/binding to bases of DNA. This new group of compounds may offer novel exploratory derivatives for future investigations in the treatment of cancer.
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PMID:The cytotoxicity of heterocyclic thiosemicarbazones and their metal complexes on human and murine tissue culture cells. 849 Feb 2

Limb salvage is widely used but has different disadvantages. Attempting to establish a new limb conservative procedure, we treate patients with malignant bone tumor by intraoperative microwave heating on tumor bearing bone in place and neoadjvant chemotherapy. The tumors were localized at distal femur in 16, proximal tibia in 5, femur shaft in 2, and illia in 2. Pathological diagnosis showed osteosarcoma in 16 patents, parosteoal osteosarcoma in 4, chondrosarcoma in 3, and leiomyosarcoma in 2. The stage of tumor was II b in 18 patients, II a in 6, and III b in 3. Operative technique was wide resection for tumor in soft tissue, protecting the surrounding tissue from heat injury by copper net, and cheating tumor bone at 50 C for 15 minutes. Follow-up varied from 4 to 180 months (mean 57 months). The 5-, 10-years surviral rates were 70.19% and 54.83% respectively. Functional results of 21 patients were > 15 points by Enneking system. The advantages of the method and keeping the shape and continuity of the tumor bearing bone without osteotomy and internal fixation, controlling the time and temperature of heating treatment easily, benefiting for bone remodeling of heated bone. The indications, complications, and surgical procedure of this method were discussed in detail.
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PMID:[Microwave heating and neoadjuvant chemotherapy for malignant bone tumor]. 1037 34

A number of thiosemicarbazones have been tested previously and herein are included three bis(thiosemicarbazones) for comparison to the previous derivatives. In general the uncomplexed thiosemicarbazones were more potent in the cytotoxic screens than the bis(thiosemicarbazone) except in the murine L1210 and the human colon SW480 screens. Mode of action studies have only demonstrated slight differences in the effects of the two types of compounds on nucleic acid metabolism. The symmetrical and unsymmetrical bis(thiosemicarbazones) complexes of copper, nickel, zinc, and cadmium have been examined to compare them to the heterocyclic N(4)-substituted thiosemicarbazones metal complexes. These new derivatives demonstrated excellent activity against the growth of suspended lymphomas and leukemias although it should be pointed out that generally they were not as active as the copper complexes of N(4)-substituted thiosemicarbazones. Nevertheless, selected bis(thiosemicarbazones) complexes were active against the growth of human lung MB9812, KB nasopharynx, epidermoid A431, glioma UM-86, colon SW480, ovary 1-A9, breast MCK-7, and osteosarcoma Saos-2. In human HL-60 promyelocytic leukemia cells the complexes preferentially inhibited DNA and purine syntheses over 60 min. The regulatory enzyme of the de novo purine pathway, IMP dehydrogenase, appeared to be a major target of the complexes. However, minor inhibition of the activities of DNA polymerase alpha, PRPP-amido transferase, ribonucleotide reductase, and nucleoside kinases occurred over the same time period. No doubt these effects of the complexes on nucleic acid metabolism were additive since the d[NTP] pool levels were reduced after 60 min as was DNA synthesis. The symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes did not cause as severe DNA fragmentation as the heterocyclic N(4)-substituted thiosemicarbazone metal complexes; furthermore, their metabolic effects in the tumor cell were more focused on a single synthetic pathway.
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PMID:The cytotoxicity of symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes in murine and human tumor cells. 1096 96

Copper(II) complexes of 6-(2-chlorobenzylamino)purine (HL1) and 6-(3-chlorobenzylamino)purine (HL2), respectively, were prepared. Depending on the pH of the medium and the molar ratio of reactants the following mononuclear (trigonal-bipyramidal) and dinuclear (octahedral, trigonal-bipyramidal or tetrahedral) complexes were isolated: [Cu2(mu-HL1)2(mu-Cl2)2(HL1)2Cl2] (1a,b), [Cu2(mu-Cl)2(mu-L1)2(H2O)2] (2a), [Cu2(mu-Cl)2(mu-L2)2(H2O)2] (2b), [Cu(H+L2)2Cl3]Cl.H2O (3a,b), [Cu2(mu-Cl)2(HL1)2Cl2] (4a), and [Cu2(mu-Cl)2(HL2)2Cl2] (4b). The compounds were characterized by elemental analyses, electronic, infrared and mass (FAB+, ES+) spectral data, magnetic susceptibility temperature dependence measurements and molar conductivity data. An X-ray single-crystal structural analysis of [Cu(H+L2)2Cl3]Cl.2H2O (3b) showed that the Cu2+ ion is penta-coordinated by three chloride ions and by two H+L2 ligands. Thus, the Cu2+ ion adopts a distorted trigonal bipyramidal coordination geometry with the protonated H+L2 ligands coordinated in trans apical positions, while the three chloride ions are situated in an equatorial plane. The cytotoxic activity of the complexes was determined by a calcein AM assay. Mouse melanoma cell line B16-FO, human malignant melanoma cell line G361, human osteogenic sarcoma cell line HOS and human breast adenocarcinoma cell line MCF7 were used. IC50 values, the drug concentrations lethal to 50% of the tumor cells, were estimated. One of the important mechanisms responsible for the cytotoxicity of cytokinin-derived compounds, the inhibition of cyclin-dependent kinases by the studied complexes, was also determined.
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PMID:Preparation, physicochemical properties and biological activity of copper(II) complexes with 6-(2-chlorobenzylamino)purine (HL1) or 6-(3-chlorobenzylamino)purine (HL2). The single-crystal X-ray structure of. 1133 Apr 78

We have identified a novel 14-exon human lysyl oxidase-like gene, LOXL4, on chromosome 10q24. The cDNA and derived amino acid sequence of LOXL4 demonstrates a conserved C-terminal region including the characteristic copper-binding site, lysyl and tyrosyl residues and a cytokine receptor-like domain. One of the four N-terminal SRCR domains contains a 13 amino acid insertion encoded by a short exon not present within the closely homologous LOXL2 and LOXL3 genes. The 3.5-kb LOXL4 mRNA is present in pancreas and testis and at lower levels in several other tissues. Fibroblasts, smooth muscle and osteosarcoma (HOS) cells express LOXL4. No expression was detected in HCT-116 and DLD-1 colon, MCF-7 breast and DU-145 prostate cancer cell lines.
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PMID:A novel human lysyl oxidase-like gene (LOXL4) on chromosome 10q24 has an altered scavenger receptor cysteine rich domain. 1169 88


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