title: Reduction in γ-glutamyl hydrolase expression is associated with response to uracil and tegafur/leucovorin chemotherapy in patients with colorectal cancer.
abstract: To identify the genes and clinical parameters associated with efficacy of uracil and tegafur/leucovorin (UFT/LV) chemotherapy in colorectal cancer (CRC), we compared the levels of reduced folate in tumors between patients receiving LV and those not receiving LV (study I), and explored the changes in the expression levels of 14 genes after two weeks of UFT/LV chemotherapy in 73 patients with CRC (study II). In study I, the reduced folate levels after LV administration were approximately 3-fold higher than those without LV administration in patients with right-sided tumors or aged >75 years old (p=0.019). In study II, the reduction in γ-glutamyl hydrolase (GGH) expression in responders and in patients with right-sided tumors or aged >75 years old was significantly greater than that in non-responders (p<0.001) and in other patients, respectively (p=0.003). Increase of reduced folate and reduction in GGH expression were associated with response to UFT/LV chemotherapy in patients with right-sided tumors or aged >75 years old.
authors.affiliation: Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya Isehara, Kanagawa, 259-1193, Japan. sadahiro@is.icc.u-tokai.ac.jp
authors.forename: Sotaro
authors.initials: S
authors.lastname: Sadahiro
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kazutake
authors.initials: K
authors.lastname: Okada
authors.forename: Akemi
authors.initials: A
authors.lastname: Kamijo
authors.forename: Hideki
authors.initials: H
authors.lastname: Nagase
authors.forename: Junji
authors.initials: J
authors.lastname: Uchida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D005641:Tegafur / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000494:pharmacology / Q000627:therapeutic use*; D011623:gamma-Glutamyl Hydrolase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D005641:Tegafur; D014498:Uracil; D005492:Folic Acid; D011623:gamma-Glutamyl Hydrolase; D002955:Leucovorin
keywords: Colorectal cancer; folate; gene expression; leucovorin; tegafur-uracil; γ-glutamyl hydrolase (GGH)