Prediction of 5'-deoxy-5-fluorouridine sensitivity in colorectal cancer cases by thymidine phosphorylase activity and preliminary identification of susceptibility related genes.
We confirmed that the enzyme activity of thymidine phosphorylase (TP) can substitute for 5'-deoxy-5-fluorouridine (5'-dFUR) sensitivity in clinical colorectal cancer (CRC) tissues. Moreover, the idenfication of susceptible genes other than TP will be desired for prediction or treatment of 5'-dFUR. We initially established conditions for the MTT assay system in vivo to compare the growth inhibition rate and TP activity in 18 cases of CRC. TP activity levels were concordant with 5'-dFUR sensitivity in the CRCs (p<0.05). In 18 CRC cases, 4 cases of high sensitivity and 3 cases of low sensitivity to 5'-dFUR were compared to analyze expression profiles of 9437 genes on cDNA microarray chips. As a result, a cluster of genes related to the sensitivity were identified and another cluster of genes related to the insensitivity of 5'-DFUR were also listed. We determined that TP expression can precisely predict 5'-dFUR sensitivity in CRCs and found susceptibility related genes.
Mimori
Koshi
K
Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan.
Ueo
Hiroaki
H
Kuroki
Tamotsu
T
Shiraishi
Takeshi
T
Creer
Shenoa
S
Taylor
Scott
S
Ishii
Hideshi
H
Mori
Masaki
M
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000235:genetics* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D005467:Floxuridine; D013939:Thymidine Phosphorylase; C025034:doxifluridine