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{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/14716816","sourcedb":"PubMed","sourceid":"14716816","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/14716816","text":"Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2'-deoxyuridine.\nAIM: To determine the expression levels of three metabolic enzymes of fluoropyrimidines: thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in seven human gastrointestinal cancer cell lines, and to compare the enzyme levels with the sensitivity to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd).\nMETHODS: TS, TP and DPD mRNA levels were assessed by semi-quantitative RT-PCR, TP and DPD protein contents were measured by ELISA. Fifty percent inhibitory concentrations of growth (IC50), representing the sensitivity to drugs, were determined by MTT assay.\nRESULTS: IC50 values ranged from 1.28 to 12.26 microM for 5-FU, and from 5.02 to 24.21 microM for FdUrd, respectively. Cell lines with lower DPD mRNA and protein levels tended to be more sensitive to 5-FU (P\u003c0.05), but neither TS nor TP correlated with 5-FU IC50 (P\u003e0.05). Only TS mRNA level was sharply related with FdUrd sensitivity (P\u003c0.05), but TP and DPD were not (P\u003e0.05). A correlation was found between mRNA and protein levels of DPD (P\u003c0.05), but not TP (P\u003c0.05).\nCONCLUSION: DPD and TS enzyme levels may be useful indicators in predicting the antitumor activity of 5-FU or FdUrd, respectively.","tracks":[{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":200,"end":549},"obj":"OBJECTIVE"},{"id":"T2","span":{"begin":559,"end":807},"obj":"METHODS"},{"id":"T3","span":{"begin":817,"end":1280},"obj":"RESULTS"},{"id":"T4","span":{"begin":1293,"end":1411},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":414,"end":420},"obj":"HP_0002664"},{"id":"T2","span":{"begin":459,"end":486},"obj":"HP_0006901"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"14716816-0#65#96#gene1806","span":{"begin":65,"end":96},"obj":"gene1806"},{"id":"14716816-0#117#140#diseaseC0685938","span":{"begin":117,"end":140},"obj":"diseaseC0685938"},{"id":"14716816-1#111#134#gene1890","span":{"begin":311,"end":334},"obj":"gene1890"},{"id":"14716816-1#136#138#gene1890","span":{"begin":336,"end":338},"obj":"gene1890"},{"id":"14716816-1#197#220#diseaseC0685938","span":{"begin":397,"end":420},"obj":"diseaseC0685938"}],"relations":[{"id":"65#96#gene1806117#140#diseaseC0685938","pred":"associated_with","subj":"14716816-0#65#96#gene1806","obj":"14716816-0#117#140#diseaseC0685938"},{"id":"111#134#gene1890197#220#diseaseC0685938","pred":"associated_with","subj":"14716816-1#111#134#gene1890","obj":"14716816-1#197#220#diseaseC0685938"},{"id":"136#138#gene1890197#220#diseaseC0685938","pred":"associated_with","subj":"14716816-1#136#138#gene1890","obj":"14716816-1#197#220#diseaseC0685938"}],"attributes":[{"subj":"14716816-0#65#96#gene1806","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"14716816-0#117#140#diseaseC0685938","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"14716816-1#111#134#gene1890","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"14716816-1#136#138#gene1890","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"14716816-1#197#220#diseaseC0685938","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":65,"end":96},"obj":"gene:1806"},{"id":"T1","span":{"begin":117,"end":140},"obj":"disease:C0685938"},{"id":"T2","span":{"begin":344,"end":375},"obj":"gene:1806"},{"id":"T3","span":{"begin":397,"end":420},"obj":"disease:C0685938"},{"id":"T4","span":{"begin":336,"end":338},"obj":"gene:1890"},{"id":"T5","span":{"begin":397,"end":420},"obj":"disease:C0685938"},{"id":"T6","span":{"begin":311,"end":334},"obj":"gene:1890"},{"id":"T7","span":{"begin":397,"end":420},"obj":"disease:C0685938"},{"id":"T8","span":{"begin":377,"end":380},"obj":"gene:1806"},{"id":"T9","span":{"begin":397,"end":420},"obj":"disease:C0685938"},{"id":"T10","span":{"begin":306,"end":308},"obj":"gene:7298"},{"id":"T11","span":{"begin":397,"end":420},"obj":"disease:C0685938"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"},{"subj":"T8","pred":"source","obj":"DisGeNET"},{"subj":"T9","pred":"source","obj":"DisGeNET"},{"subj":"T10","pred":"source","obj":"DisGeNET"},{"subj":"T11","pred":"source","obj":"DisGeNET"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubMed_Structured_Abstracts","color":"#93bcec","default":true},{"id":"PubmedHPO","color":"#d6ec93"},{"id":"DisGeNET5_gene_disease","color":"#e893ec"},{"id":"DisGeNET","color":"#93ecce"}]}]}}