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 short-term metabolic fate of labeled nitrogen derived from [13N]ammonia or from L-[amide-13N]glutamine was determined in murine tumors known to be resistant (Ridgeway Osteogenic Sarcoma (ROS] or sensitive (Sarcoma-180 (S-180)) to glutaminase therapy. At 5 min after intraperitoneal injection of [13N]ammonia or of L-[amide-13N]glutamine, only about 0.7% of the label recovered in both tumors was in protein and nucleic acid. After [13N]ammonia administration, most of the label (over 80%) was in a metabolized form; a large portion of this metabolized label (50-57%) was in the urea fraction with a smaller amount in glutamine (37-42%). The major short-term fate of label derived from L-[amide-13N]glutamine was incorporation into components of the urea cycle with smaller amounts in the acidic metabolites and in acidic amino acids. No labeled urea was found during in vitro studies in which S-180 tumor slices were incubated with [13N]ammonia, suggesting that the [13N]urea formed in the tumor in the in vivo experiments was not due to de novo synthesis through carbamyl phosphate in the tumor. Both tumors exhibited very low glutamine synthetase activity. Following glutaminase treatment, glutamine synthetase and gamma-glutamyltransferase activities, while remaining low, increased in the resistant tumor but not in the sensitive tumor; this increase may be related to the insensitivity of the ROS tumor toward glutaminase treatment.
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PMID:[13N]Ammonia and L-[amide-13N]glutamine metabolism in glutaminase-sensitive and glutaminase-resistant murine tumors. 286 80

Amine-carboxyboranes have been shown to prevent osteoporosis and loss of bone mass in rodents. In vitro studies using CF1 mouse pup calvaria and rat UMR-106 osteosarcoma cells showed that amine-carboxyborane derivatives reduced significantly the loss of intracellular calcium into the growth medium from 10(-4) to 10(-8) M over 48 hours. Amine-carboxyborane derivatives were more effective than calcitonin or simple boron salts. Calcium incorporation into these cells and proline incorporation into collagen was accelerated in the presence of amine carboxyboranes. The amine-carboxyborane derivatives effectively inhibited lysosomal and proteolytic enzymes as well as activities of serine elastase, prostaglandin cyclooxygenase, and 5'-lipoxygenase in mouse macrophages, human PMNs, leukocytes and Be Sal cells. IC50 values were in the range of 10(-6) M. In lactating ovariectomized female rats after administered amine-carboxyboranes for 14 days at 8 mg/kg/day orally, the femur and humerus showed increased volume, weight, density and ash weight. Serum calcium levels were elevated significantly with minimum reductions on serum inorganic phosphate levels. Femur calcium levels were elevated after treatment with amine-carboxyborane derivatives, but not with etidronate. Humerus total lipids after 14 days were slightly elevated probably due to increased levels of triglycerides and phospholipids.
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PMID:The anti-osteoporotic activity of amine-carboxyboranes in rodents. 764 84

beta-Cystathionase (EC 4.4.1.8) from Bordetella avium is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the hydrolysis of L-cystine to yield pyruvic acid, NH3, and thiocysteine. The latter compound is highly toxic toward MC3T3-E1 osteogenic cells, rat osteosarcoma cells, and other cell lines maintained in tissue culture (Gentry-Weeks, C. R., Keith, J. M., and Thompson, J. (1993) J. Biol. Chem. 268, 7298-7314). Site-directed mutagenesis has established that lysine 214 of the sequence TKYVGGHSD, is primarily responsible for internal aldimine binding of PLP in the holoenzyme. Translation of the DNA sequence of the beta-cystathionase gene (metC) from B. avium, reveals 4 cysteine residues/enzyme subunit (M(r) = 42,600), and spectrophotometric analysis with 4,4'-dithiodipyridine showed that there were no disulfide linkages in the native protein. beta-Cystathionase is inhibited by sulfhydryl-reactive agents, including N-ethylmaleimide (NEM). To elucidate the mechanism of NEM inhibition, each of the 4 cysteine residues at positions 88, 117, 279, and 309 was individually replaced by alanine or glycine. The mutant proteins C88A, C117G, C279G, and C309A were purified to homogeneity, and each was assayed for enzyme activity, PLP-binding, NEM sensitivity, and susceptibility to chymotrypsin digestion. The activities of mutant proteins C88A and C279G were comparable with that of the native enzyme, and since both forms were inhibited by NEM, neither cysteine 88 nor 279 are prerequisite for enzyme activity. By elimination, cysteine residues 117 and 309 must be the targets for alkylation, and resultant inactivation of beta-cystathionase, by the -SH reactive agent. Substitution of cysteine 117 and 309 with glycine and alanine, respectively, yielded the inactive proteins C117G and C309A. PLP was not detectable in these proteins, and their absorption spectra lacked the peak (at 420 nm) that is characteristic of internal PLP-Schiff base formation. Edman degradation revealed that C117G (M(r) approximately 36,000) also lacked the first 63 amino acids comprising the N terminus of the native protein. The beta-cystathionase mutants C117G and C309A showed enhanced susceptibility to chymotrypsin digestion. Cysteine residues 117 and 309 may reside in conformationally sensitive environments, and in the native enzyme these amino acids most probably serve a structural function. Toxicity assays performed with the various mutant proteins obtained by site-directed mutagenesis established that only catalytically active forms of beta-cystathionase were were cytotoxic for tissue culture cells.
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PMID:beta-Cystathionase from Bordetella avium. Role(s) of lysine 214 and cysteine residues in activity and cytotoxicity. 770 18

Glucocorticoids have marked effects on bone metabolism, and continued exposure of skeletal tissue to excessive amounts of these steroids results in osteoporosis. Therefore, in the present proteomic study, we characterized the potential effects of glucocorticoids on protein expression in human osteoblastic cells. Using two-dimensional gel electrophoresis and mass spectrometry, we identified an increased expression of glutamine synthetase (GS) in dexamethasone (Dex)-treated human MG-63 osteosarcoma cells. GS is an enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Intracellular and extracellular glutamate levels may be important in cell signalling mediated by glutamate transporters and receptors which have recently been found in bone cells. The induction of GS protein by Dex was accompanied by an increase in mRNA level and enzyme activity. Dex induction of GS was also mediated by glucocorticoid receptors (GRs) because it was blocked by the GR antagonist RU-38486. In addition, Dex induction of GS expression was partially blocked by cyclohexamide indicating that it at least partly required new protein synthesis. GS induction by Dex was not associated with apoptosis as determined by Bax/Bcl-2 ratio and DNA staining. In addition to MG-63 cells, Dex induction of GS was also observed in human G-292 osteosarcoma cells as well as conditionally immortalized human preosteoblastic (HOB-03-C5) and mature osteoblastic (HOB-03-CE6) cells. However, in two other human osteosarcoma cell lines, SaOS-2 and U2-OS, GS expression was not affected by Dex. This observation may be explained by the lower levels of GR protein in these cells. In summary, this is the first report of the regulation of GS expression by glucocorticoids in bone cells. The role of GS in bone cell metabolism and glucocorticoid action on the skeleton is not yet known, but as a modulator of intracellular glutamate and glutamine levels, it may have an important role in these processes.
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PMID:Glucocorticoids induce glutamine synthetase expression in human osteoblastic cells: a novel observation in bone. 1496 10

The current positive computed tomography (CT) contrast agents (PCTCAs) including clinical iodides, present high CT density value (CT-DV). However, they are incapable for the accurate diagnosis of some diseases with high CT-DV, such as osteosarcoma. Because bones and PCTCAs around osteosarcoma generate similar X-ray attenuations. Here, an innovative strategy of negative CT contrast agents (NCTCAs) to reduce the CT-DV of osteosarcoma is proposed, contributing to accurate detection of osteosarcoma. Hollow mesoporous silica nanoparticles, loading ammonia borane molecules and further modified by polyethylene glycol, are synthesized as NCTCAs for the diagnosis of osteosarcoma. The nanocomposites can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, resulting in nearly 20 times reduction of CT density in osteosarcoma. This helps form large CT density contrast between bones and osteosarcoma, and successfully achieves accurate diagnosis of osteosarcoma. Meanwhile, The NCTCAs strategy greatly expands the scope of CT application, and provides profound implications for the precise clinical diagnosis, treatment, and prognosis of diseases.
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PMID:Negative CT Contrast Agents for the Diagnosis of Malignant Osteosarcoma. 3183 12