Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil.
Although the intratumoral expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are known to affect the antitumor activity of 5-fluorouracil (5-FU), the importance of orotate phosphoribosyltransferase (OPRT) has remained unclear. This study investigated the relatio...
| Asıl Yazarlar: | , , , , , |
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| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
2007
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| _version_ | 1826292991949537280 |
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| author | Sakamoto, E Nagase, H Kobunai, T Oie, S Oka, T Fukushima, M Oka, T |
| author_facet | Sakamoto, E Nagase, H Kobunai, T Oie, S Oka, T Fukushima, M Oka, T |
| author_sort | Sakamoto, E |
| collection | OXFORD |
| description | Although the intratumoral expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are known to affect the antitumor activity of 5-fluorouracil (5-FU), the importance of orotate phosphoribosyltransferase (OPRT) has remained unclear. This study investigated the relationship between intratumoral OPRT expression and the antitumor activity of 5-FU using human NCI60 cell lines with similar levels of TS and DPD messenger RNAs, as well as 31 tumor xenografts. The OPRT mRNA level was positively correlated with the 5-FU efficacy in these cell lines. In vitro, the 50% growth-inhibitory concentrations of 5-FU were closely correlated with the OPRT mRNA levels in cancer cell lines with similar levels of TS mRNAs when combined with a DPD inhibitor. Moreover, downregulation of OPRT with small-interfering RNA decreased the sensitivities of the cultured tumor cells to 5-FU. These results suggest that the OPRT expression level in tumors is an additional determinant of the efficacy of 5-FU. |
| first_indexed | 2024-03-07T03:23:13Z |
| format | Journal article |
| id | oxford-uuid:b82667e3-e48f-48d5-8f6f-a3bb4a35480f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:23:13Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:b82667e3-e48f-48d5-8f6f-a3bb4a35480f2022-03-27T04:53:54ZOrotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b82667e3-e48f-48d5-8f6f-a3bb4a35480fEnglishSymplectic Elements at Oxford2007Sakamoto, ENagase, HKobunai, TOie, SOka, TFukushima, MOka, TAlthough the intratumoral expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are known to affect the antitumor activity of 5-fluorouracil (5-FU), the importance of orotate phosphoribosyltransferase (OPRT) has remained unclear. This study investigated the relationship between intratumoral OPRT expression and the antitumor activity of 5-FU using human NCI60 cell lines with similar levels of TS and DPD messenger RNAs, as well as 31 tumor xenografts. The OPRT mRNA level was positively correlated with the 5-FU efficacy in these cell lines. In vitro, the 50% growth-inhibitory concentrations of 5-FU were closely correlated with the OPRT mRNA levels in cancer cell lines with similar levels of TS mRNAs when combined with a DPD inhibitor. Moreover, downregulation of OPRT with small-interfering RNA decreased the sensitivities of the cultured tumor cells to 5-FU. These results suggest that the OPRT expression level in tumors is an additional determinant of the efficacy of 5-FU. |
| spellingShingle | Sakamoto, E Nagase, H Kobunai, T Oie, S Oka, T Fukushima, M Oka, T Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. |
| title | Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. |
| title_full | Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. |
| title_fullStr | Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. |
| title_full_unstemmed | Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. |
| title_short | Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. |
| title_sort | orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5 fluorouracil |
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