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)

Methotrexate reduces intracellular pools of 5-methyltetrahydrofolate and could result in reduced conversion of homocysteine to methionine by methionine synthetase. This study was designed to investigate the effects of moderate dose to very high dose methotrexate on methionine and total homocysteine as reflections of methotrexate induced intracellular events. Methionine and total homocysteine were measured prior to, during, and following twenty-six 24-h i.v. infusions of 33.6 g/m2 methotrexate (very high dose methotrexate) in 16 children with acute lymphocytic leukemia and seven 4-h i.v. infusions of 8 g/m2 methotrexate (high dose methotrexate) in 5 children with osteogenic sarcoma. Amino acids were measured by gas chromatography/mass spectrophotometry. Mean methionine levels decreased by 70.0 +/- 3.1% (SE) with very high dose methotrexate and 72.6 +/- 5.9% with high dose methotrexate at 24 and 4.5 h, respectively, after beginning methotrexate infusions. Mean total homocysteine levels increased by 61.7 +/- 3.1% with very high dose methotrexate and 55.6 +/- 17.5% with high dose methotrexate at 36 and 24 h, respectively, after beginning methotrexate infusions. No consistent or significant changes were noted in levels of total cysteine, leucine, isoleucine, or valine. Similar changes did not occur in patients receiving prednisone, vincristine, daunomycin, and intrathecal methotrexate as therapy for acute lymphocytic leukemia. These changes in homocysteine and methionine may reflect biological effects of methotrexate that may predict cytotoxicity of methotrexate.
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PMID:Changes in plasma methionine and total homocysteine levels in patients receiving methotrexate infusions. 279 Aug 1

Food-derived bioactive peptides are reported to express a variety of functions in vivo. We studied the in vitro effect of three bioactive tripeptides, isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-lysine-proline (LKP), on osteoblast proliferation and gene expression. We used UMR-106 osteosarcoma cells, human marrow-derived mesenchymal stem cells (hMSC) and osteoblasts differentiated from hMSC. Treatment with 50 mum-IPP increased UMR-106 cell and hMSC proliferation. The gene expression of hMSC-differentiated osteoblasts was analysed by the microarray method. Microarray analysis revealed that IPP up-regulated 270 genes and down-regulated 100 genes. VPP and LKP, by contrast, had a very modest influence on osteoblast gene expression. Real-time PCR confirmed that IPP up-regulated PTHrP, BMP-5 and CREB-5 and down-regulated VDR and caspase-8. IPP possesses potential to increase osteoblast proliferation, differentiation and signalling. Agents that increase the number and function of osteoblasts could improve bone mass and structure, and decrease fracture risk.
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PMID:Effects of bioactive peptides isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-lysine-proline (LKP) on gene expression of osteoblasts differentiated from human mesenchymal stem cells. 1746 96