Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxanthine:guanine phosphoribosyltransferase (HPRT) activity was measured in 14 human osteosarcomas to test whether a subset of these tumors was deficient in the purine salvage pathway enzyme and thus provide a rationale for therapy with methotrexate-thymidine rescue. All tumors contained HPRT activity within the range previously reported for xenografts of human osteosarcoma. Three patients received methotrexate (3.375 g/m2/24 hours) as a 72-hour continuous infusion with thymidine rescue (2.0 g/m2/24 hours) beginning 24 hours after the start of the methotrexate infusion. The methotrexate-thymidine infusion was well tolerated by all patients with no significant toxicity; however, there were no responses. We conclude that osteosarcomas are not deficient in HPRT activity. Therefore, the previously reported rationale for therapy of osteosarcoma with methotrexate-thymidine based on lack of activity of this enzyme is not valid. This combination, although well tolerated, is inconvenient and requires prolonged hospitalization. Therefore, without a valid rationale it cannot be recommended for therapy of patients with osteosarcoma.
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PMID:Hypoxanthine:guanine phosphoribosyltransferase activity in primary human osteosarcomas. A rationale for therapy with methotrexate-thymidine rescue? 310 47

It has recently been reported that human osteosarcomas may lack the purine salvage pathway enzyme, hypoxanthine:guanine phosphoribosyltransferase (EC 2.4.2.8). We have established a quantitative assay for measurement of this enzyme in human osteosarcoma xenografts with analysis of products by thin-layer chromatography. Nucleotidase or phosphatase activity was readily detected and could be abolished by preheating cytosol at 60 degrees C for 10 min and performing the assay at pH 10. Alternatively, the use of 25 mM NaF at pH 7.4 also inhibited this activity. The pH optimum for this enzyme in red blood cell sonicates and tumor cytosols was pH 10. All six human osteosarcoma xenografts contained hypoxanthine:guanine phosphoribosyltransferase activity ranging from 0.97 to 4.06 nmol/min/mg of protein at pH 7.4. Control human red blood cell sonicates demonstrated activity of 0.83 nmol/min/mg of protein. These data demonstrate that human osteosarcoma xenografts contain substantial activities of this purine salvage pathway enzyme.
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PMID:Hypoxanthine:guanine phosphoribosyltransferase activity in xenografts of human osteosarcoma. 346 7

The transplantable murine Dunn osteosarcoma has no detectable hypoxanthine:guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This was established from the tumors directly and from tissue culture cell lines derived from the tumor using a variety of assays: e.g., no [3H]hypoxanthine uptake into tumor or tissue culture cells, no conversion of [3H]hypoxanthine to [3H]IMP by cell extracts from tumors or tissue culture cells, no growth of tissue culture cells in hypoxanthine:aminopterin:thymidine medium, and normal growth of these cells in 10 microM 6-mercaptopurine. Ten human osteosarcomas have been assayed, and two have no apparent hypoxanthine:guanine phosphoribosyltransferase enzyme activity. After high-dose methotrexate treatment in vivo, murine tumors could be selectively killed and normal tissues could be spared by using a rescue regimen of hypoxanthine-thymidine-allopurinol.
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PMID:Absence of hypoxanthine:guanine phosphoribosyltransferase activity in murine Dunn osteosarcoma. 657 63