The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform
Tohru Ishikawa - One of the best experts on this subject based on the ideXlab platform.
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2013Co-Authors: Human Cancer Xenografts, Tohru Ishikawa, Fumiko Sekiguchi, Yu Fukase, Contact The Aacr Publications, Noriaki SawadaAbstract:Capecitabine (/V4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5'deoxy-5-fluorouridine (5'-dFUrd, doxifluridine). 5'-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to Dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of capecitabine and its intermediate metabolite 5'-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5'-dH rii were highly effective and inhibited tumor growth by mor
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positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts
Cancer Research, 1998Co-Authors: Tohru Ishikawa, Fumiko Sekiguchi, Yu Fukase, Noriaki Sawada, Hideo IshitsukaAbstract:Abstract Capecitabine (N4-pentyloxycarbonyl-5′-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5′-deoxy-5-fluorouridine (5′-dFUrd, doxifluridine). 5′-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to Dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of cape-citabine and its intermediate metabolite 5′-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5′-dFUrd were highly effective and inhibited tumor growth by more than 50% in 18 of 24 xenograft lines (75%) and 15 of 24 xenograft lines (63%), respectively, whereas 5-FUra and a mixture of tegafur and uracil were effective only in 1 of 24 (4.2%) and 5 of 24 (21%), respectively. The efficacy of capecitabine correlated with dThdPase activity. However, capecitabine was effective even in tumors with lower levels of dThdPase if DPD levels were also lower. In contrast, it was not as effective even in tumors with sufficient levels of dThdPase if DPD levels were very high. The efficacy of capecitabine consequently correlated very well with and depended on the ratio of these two enzymes in tumors. These results indicate that capecitabine might exert its efficacy through 5-FUra generated in tumor tissues but not through that generated in normal organs. On the other hand, there was no correlation between the efficacy of a mixture of tegafur and uracil and these enzyme activities in tumors. The efficacy of capecitabine would be optimized by selecting patients who have tumors with a high ratio of dThdPase to DPD activities.
Hideo Ishitsuka - One of the best experts on this subject based on the ideXlab platform.
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positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts
Cancer Research, 1998Co-Authors: Tohru Ishikawa, Fumiko Sekiguchi, Yu Fukase, Noriaki Sawada, Hideo IshitsukaAbstract:Abstract Capecitabine (N4-pentyloxycarbonyl-5′-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5′-deoxy-5-fluorouridine (5′-dFUrd, doxifluridine). 5′-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to Dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of cape-citabine and its intermediate metabolite 5′-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5′-dFUrd were highly effective and inhibited tumor growth by more than 50% in 18 of 24 xenograft lines (75%) and 15 of 24 xenograft lines (63%), respectively, whereas 5-FUra and a mixture of tegafur and uracil were effective only in 1 of 24 (4.2%) and 5 of 24 (21%), respectively. The efficacy of capecitabine correlated with dThdPase activity. However, capecitabine was effective even in tumors with lower levels of dThdPase if DPD levels were also lower. In contrast, it was not as effective even in tumors with sufficient levels of dThdPase if DPD levels were very high. The efficacy of capecitabine consequently correlated very well with and depended on the ratio of these two enzymes in tumors. These results indicate that capecitabine might exert its efficacy through 5-FUra generated in tumor tissues but not through that generated in normal organs. On the other hand, there was no correlation between the efficacy of a mixture of tegafur and uracil and these enzyme activities in tumors. The efficacy of capecitabine would be optimized by selecting patients who have tumors with a high ratio of dThdPase to DPD activities.
Noriaki Sawada - One of the best experts on this subject based on the ideXlab platform.
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2013Co-Authors: Human Cancer Xenografts, Tohru Ishikawa, Fumiko Sekiguchi, Yu Fukase, Contact The Aacr Publications, Noriaki SawadaAbstract:Capecitabine (/V4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5'deoxy-5-fluorouridine (5'-dFUrd, doxifluridine). 5'-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to Dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of capecitabine and its intermediate metabolite 5'-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5'-dH rii were highly effective and inhibited tumor growth by mor
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positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts
Cancer Research, 1998Co-Authors: Tohru Ishikawa, Fumiko Sekiguchi, Yu Fukase, Noriaki Sawada, Hideo IshitsukaAbstract:Abstract Capecitabine (N4-pentyloxycarbonyl-5′-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5′-deoxy-5-fluorouridine (5′-dFUrd, doxifluridine). 5′-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to Dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of cape-citabine and its intermediate metabolite 5′-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5′-dFUrd were highly effective and inhibited tumor growth by more than 50% in 18 of 24 xenograft lines (75%) and 15 of 24 xenograft lines (63%), respectively, whereas 5-FUra and a mixture of tegafur and uracil were effective only in 1 of 24 (4.2%) and 5 of 24 (21%), respectively. The efficacy of capecitabine correlated with dThdPase activity. However, capecitabine was effective even in tumors with lower levels of dThdPase if DPD levels were also lower. In contrast, it was not as effective even in tumors with sufficient levels of dThdPase if DPD levels were very high. The efficacy of capecitabine consequently correlated very well with and depended on the ratio of these two enzymes in tumors. These results indicate that capecitabine might exert its efficacy through 5-FUra generated in tumor tissues but not through that generated in normal organs. On the other hand, there was no correlation between the efficacy of a mixture of tegafur and uracil and these enzyme activities in tumors. The efficacy of capecitabine would be optimized by selecting patients who have tumors with a high ratio of dThdPase to DPD activities.
Renzo Hirayama - One of the best experts on this subject based on the ideXlab platform.
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both gene expression for orotate phosphoribosyltransferase and its ratio to dihydropyrimidine dehydrogenase influence outcome following fluoropyrimidine based chemotherapy for metastatic colorectal cancer
British Journal of Cancer, 2003Co-Authors: Wataru Ichikawa, Hiroyuki Uetake, Yoshinori Shirota, Hiroyuki Yamada, Takao Takahashi, Zenro Nihei, Kenichi Sugihara, Yasutsuna Sasaki, Renzo HirayamaAbstract:An important anticancer agent widely used in the treatment of colorectal cancers, 5-fluorouracil (5-FU), is catabolised rapidly to the inactive metabolite Dihydrofluorouracil (FUH2) by the first and rate-limiting enzyme-dihydropyrimidine dehydrogenase (DPD) (Heggie et al, 1987). The main mode of action of 5-FU is thought to be through its active metabolite: 5-fluoro-uridine-5′-triphosphate (FUTP) or 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP) (Danenberg, 1977). Metabolites such as FUTP can be incorporated into RNA, while FdUMP suppresses thymidylate synthase (TS), an essential DNA de novo synthetic enzyme that catalyses the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) (Danenberg, 1977; Pinedo and Peters, 1988).
Yu Fukase - One of the best experts on this subject based on the ideXlab platform.
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2013Co-Authors: Human Cancer Xenografts, Tohru Ishikawa, Fumiko Sekiguchi, Yu Fukase, Contact The Aacr Publications, Noriaki SawadaAbstract:Capecitabine (/V4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5'deoxy-5-fluorouridine (5'-dFUrd, doxifluridine). 5'-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to Dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of capecitabine and its intermediate metabolite 5'-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5'-dH rii were highly effective and inhibited tumor growth by mor
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positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts
Cancer Research, 1998Co-Authors: Tohru Ishikawa, Fumiko Sekiguchi, Yu Fukase, Noriaki Sawada, Hideo IshitsukaAbstract:Abstract Capecitabine (N4-pentyloxycarbonyl-5′-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5′-deoxy-5-fluorouridine (5′-dFUrd, doxifluridine). 5′-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to Dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of cape-citabine and its intermediate metabolite 5′-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5′-dFUrd were highly effective and inhibited tumor growth by more than 50% in 18 of 24 xenograft lines (75%) and 15 of 24 xenograft lines (63%), respectively, whereas 5-FUra and a mixture of tegafur and uracil were effective only in 1 of 24 (4.2%) and 5 of 24 (21%), respectively. The efficacy of capecitabine correlated with dThdPase activity. However, capecitabine was effective even in tumors with lower levels of dThdPase if DPD levels were also lower. In contrast, it was not as effective even in tumors with sufficient levels of dThdPase if DPD levels were very high. The efficacy of capecitabine consequently correlated very well with and depended on the ratio of these two enzymes in tumors. These results indicate that capecitabine might exert its efficacy through 5-FUra generated in tumor tissues but not through that generated in normal organs. On the other hand, there was no correlation between the efficacy of a mixture of tegafur and uracil and these enzyme activities in tumors. The efficacy of capecitabine would be optimized by selecting patients who have tumors with a high ratio of dThdPase to DPD activities.