Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non-small cell lung cancer—in correlation with the tumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase

The efficacy of pemetrexed as a third- or fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer

“…Furthermore, the heterogeneity of TS staining within the tumors and lack of a standardized scoring system in NSCLC may have contributed to our results. Several studies have reported various percentages of patients with NSCLC -ranging from 29.6% to 72.5% -presenting TS positivity [10,11,[19][20][21][22]. In our study, TS positivity (20%) was lower than in other studies.…”

“…In our study, TS positivity (20%) was lower than in other studies. Third, there may be a discrepancy between TS enzymatic activity and protein expression by immunohistochemistry, as previously reported [22]. Thus, RT-PCR should be considered as an alternative method to determine the level of TS expression instead of protein expression [23,24].…”

Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues

“…Many reports showed that intratumoral DPD activity affects resistance to 5-FU [9][10][11]. Especially, nonsmall-cell lung cancers (NSCLCs) may be considered to be a tumor type that commonly displays a high level of DPD expression, which in turn is associated with decreased 5-FU activity [12,13].…”

Histone deacetylase inhibitor enhances sensitivity of non‐small‐cell lung cancer cells to 5‐FU/S‐1 via down‐regulation of thymidylate synthase expression and up‐regulation of p21waf1/cip1 expression

“…( 19 ) S‐1 mediates its antitumor effect via the blockage of DPD by CDHP. ( 15,17 ) Tegafur is a prodrug that generates 5‐FU in the blood largely as a result of metabolism by cytochrome p450 enzymes in the liver. The active metabolite of 5‐FU, FdUMP, forms a covalent complex with 5,10‐methylenetrahydrofolate and thymidylate synthase (TS), resulting in inhibition of DNA synthesis.…”