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 biologic activity in terms of survival of normal hematopoietic stem, osteosarcoma, and L1210 leukemia cells was determined for the following compounds:cyclophosphamide, its derivatives isophosphamide and trophosphamide, its possible metabolites nor-nitrogen mustard, hydroxylamine mustard, 4-ketocyclophosphamide, and and acrolein, and two substitutes for its primary active metabolite 4-hydroxycyclosphamide anhydro-dimer (4-hydroxy-CP-anhydro-dimer) and 4-hydroperoxycyclophosphamide (4-hydroperoxy-CP). On a molar basis none of the compounds shows a better therapeutic ratio between osteosarcoma and bone marrow stem cells than the parent compound. The therapeutic ratio between L1210 leukemia and normal cells is slightly better for 4-hydroperoxy-CP only. It may be concluded that the conversion of 4-hydroxy-CP-anhydro-dimer and 4-hydroperoxy-CP to the primary active metabolite 4-hydroxycyclophosphamide differs quantitatively. Moreover, it appears that by the use of these precursors a better therapeutic ratio might be obtained for some malignancies but not for others.
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PMID:Biologic activity of two derivatives and six possible metabolites of cyclophosphamide (NSC-26271). 106 68

Cytosolic calcium and its parathyroid hormone induced increase was evaluated in rat osteosarcoma cells by quin 2 fluorometry. Electron microscopic calcium detection in depot organelles (i.e. the recently defined calciosomes) is improved by a new precipitation method with hydroxylamine naphthoic acid and fluoride combined with X-ray microanalysis. As shown in submandibulary gland and pancreatic B cells, a new combination of GBHA staining with laser microprobe mass analysis (LAMMA) for the first time enables direct kinetical studies of calcium at the microscopical level using stable calcium isotopes (i.e. Ca44) as tracers.
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PMID:[Morphological demonstration of function-dependent cellular calcium redistributions in secretory cells by x-ray microanalysis, LAMMA and fluorescence cytometry]. 170 2

CD9 is a signal-initiating glycoprotein of uncertain membrane insertion which contains more than one locus of acylation and is distinguished by being the major acylatable platelet protein. The N-terminus of CD9 is blocked to Edman degradation. We investigated whether [3H]myristic acid could be incorporated into CD9, whether that incorporation occurred via an amide linkage, and whether myristate and palmitate were differentially incorporated into the two domains. Pulse-labeling studies, performed on the human osteogenic sarcoma cell line SKOSC which expresses 22 and 24 kDa variants of CD9 demonstrated that the respective precursors of 20.5 and 23 kDa were not radiolabeled by either [3H]myristic acid or [3H]palmitic acid, but that both fatty acids could be ligated to CD9 during the later stages of protein maturation. The failure to incorporate myristic acid cotranslationally suggest that CD9 does not contain amino-terminal amide-bonded myristic acid. Incorporation of radiolabel from both fatty acids proceeded very rapidly and could be visualized after a 10 s pulse. Although myristic acid was partially metabolized into palmitic acid, incorporation of authentic [3H]myristate into CD9 could be demonstrated. The myristic acid bonds were shown to be as sensitive to hydroxylamine treatment as those linking palmitate. Both fatty acids were also incorporated into CD9 in hydroxylamine-sensitive bonds in the presence of cycloheximide, reaching 30-40% of the levels in untreated controls. The sensitivity of myristate ligands to hydroxylamine demonstrates that this fatty acid is not linked via amide, but rather via ester bonds. The sensitivity of [3H]myristate and [3H]palmitate bonds to 2-mercaptoethanol further suggests that either fatty acid is linked via thioester rather than hydroxyester bonds to each domain on CD9. Limited proteolysis analysis with Staphylococcus aureus V8 proteinase of CD9, labeled in the absence or presence of cycloheximide, showed that [3H]myristic acid and [3H]palmitic acid labeled identical peptides, and to the same extent, suggesting that myristate is an alternative substrate for the transacylase(s) involved.
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PMID:Myristic acid is incorporated into the two acylatable domains of the functional glycoprotein CD9 in ester, but not in amide bonds. 219 73