Levels and expressions of orotate phosphoribosyltransferase in gastric carcinoma and normal gastric mucosa tissues

Sakurai, Yoshinori; Kamoshida, Shingo; Furuta, Shinpei; Sunagawa, Risaburo; Inaba, Kazuki; Isogaki, Jun; Komori, Yoshiyuki; Uyama, Ichiro; Tsutsumi, Yutaka

doi:10.1007/s10120-007-0440-9

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…OPRT has a higher expression in cancer than in normal tissue. This study did not show any association between histological characteristics and OPRT, but some reports have correlated OPRT expression with tumor grade or location, implying that part of OPRT regulation is posttranslational [26]. Another hypothesis is that individual variations in drug response are because of genetic polymorphisms that influence the drug-metabolizing enzymes that determine pharmacodynamics.…”

Section: Discussionmentioning

confidence: 71%

Predictive values of 5-fluorouracil pathway genes for S-1 treatment in patients with advanced gastric cancer

et al. 2011

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Determination of significant associations between gene expression and predefined endpoints might improve treatment tailoring for advanced gastric cancer. We investigated the mRNA expression of 5-fluorouracil (5-FU) pathway genes in prechemotherapeutic tumor samples of primary gastric cancer to try to predict the treatment outcome of S-1 monotherapy. 5-FU pathway genes, dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS), and thymidine phosphorylase (TP), were analyzed using quantitative real-time PCR of RNA extracted from archived formalin-fixed paraffin-embedded tissues. We selected the median value for each gene as a cutoff to separate patients into high and low gene expression groups. High OPRT gene expression was significantly associated with tumor response (P = 0.014). In a combined analysis including OPRT, patients with high OPRT and TP showed a higher overall response rate than did the remaining patients (40 vs. 10%, respectively; P = 0.002). For survival, patients with high OPRT and low TS levels showed prolonged survival in both progression-free survival (3.4 vs. 2.4 months, P = 0.024) and overall survival (11.0 vs. 8.2 months, P = 0.007). In a multivariate analysis, the combinations of OPRT and TP for response and OPRT and TS for both progression-free survival and overall survival were independent variables. To conclude, mRNA expression levels of molecular markers in formalin-fixed paraffin-embedded specimens of primary gastric tumors can be useful for identifying patients with advanced gastric cancer who would most likely benefit from S-1 treatment.

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Section: Discussionmentioning

confidence: 71%

Predictive values of 5-fluorouracil pathway genes for S-1 treatment in patients with advanced gastric cancer

et al. 2011

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“…Thus, theoretically, a high amount of TS and DPD and a low amount of TP and OPRT in the tumor tissue is expected to be associated with a low probability of response to 5-FU and a poor prognosis. In line with this theory, retrospective clinical studies have shown that expression levels of 5-FU metabolism-related enzymes are associated with a response to 5-FU in several cancers [4][5][6][7][8][9][10][11]. Ichikawa et al have reported that the response rate to a fluoropyrimidine-based protocol was 75% in colorectal tumors with low levels of DPD and TS mRNA, and the median survival time was longer in patients with these tumors than in patients with tumors with high DPD and TS mRNA levels [12].…”

Section: Introductionmentioning

confidence: 88%

“…FdUMP exerts its anticancer activity through the formation of a ternary complex with thymidylate synthase (TS) and 5, 10-methylenetetrahydrofolate (MTHF), resulting in the inhibition of TS and the blockade of the DNA synthetic process. 5-FU is also phosphorylated to 5-fluorouridine-monophosphate (FUMP) by OPRT [6,7] and to 5-fluorouridine (FUR), which 6 is subsequently converted to FUMP by UP [8,9]. FUMP is then phosphorylated to fluorouridine diphosphate, which can be either converted to FdUMP or phosphorylated to the active metabolite fluorouridine triphosphate, which is extensively incorporated into RNA (F-RNA), disrupting normal RNA processing and function.…”

Section: Introductionmentioning

confidence: 99%

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Combined evaluation of dihydropyrimidine dehydrogenase and thymidine phosphorylate mRNA levels in tumor predicts the histopathological effect of 5-fluorouracil-based chemoradiotherapy

Tateishi¹,

Tatemoto²,

Ohno³

et al. 2009

Cancer Letters

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S-1 (Teysuno®): A Review of Its Use in Advanced Gastric Cancer in Non-Asian Populations

Sanford¹

2013

Drugs

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S-1 (Teysuno(®)) is an oral anticancer agent comprising the 5-fluorouracil (5-FU) prodrug tegafur and targeted modulators, gimeracil and oteracil. S-1 in combination with cisplatin is a recommended first-line treatment for gastrointestinal cancers in Japan and has recently been approved in the EU for the treatment of advanced gastric cancer. This article reviews S-1 pharmacology from an EU perspective. In a randomized, open-label trial in 24 non-Asian countries in patients with advanced gastric cancer, there were no significant differences between S-1 plus cisplatin and 5-FU plus cisplatin groups in median overall survival (OS) [primary endpoint], progression-free survival or overall response rate. In a post hoc analysis of OS, S-1 plus cisplatin was noninferior to 5-FU plus cisplatin. There were no significant between-group differences in patient quality of life, according to the Functional Assessment of Cancer Therapy (Gastric) Trial Outcome Index, except that S-1 plus cisplatin recipients had a significantly longer time to worsening in physical well-being than 5-FU plus cisplatin recipients. Overall, S-1 plus cisplatin was better tolerated than 5-FU plus cisplatin, with significantly lower rates of haematological, some gastrointestinal tract and other adverse events, serious adverse events and deaths resulting from toxicity, along with significantly fewer haematological and renal function abnormalities. Compared with 5-FU, S-1 plus cisplatin recipients had significantly higher rates of hand-foot syndrome and hyperbilirubinaemia, although there were no between-group differences in the proportions of patients with increased liver enzymes. S-1 is a useful alternative to 5-FU for patients with advanced gastric cancer.

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Levels and expressions of orotate phosphoribosyltransferase in gastric carcinoma and normal gastric mucosa tissues

Cited by 4 publications

References 23 publications

Predictive values of 5-fluorouracil pathway genes for S-1 treatment in patients with advanced gastric cancer

Predictive values of 5-fluorouracil pathway genes for S-1 treatment in patients with advanced gastric cancer

Combined evaluation of dihydropyrimidine dehydrogenase and thymidine phosphorylate mRNA levels in tumor predicts the histopathological effect of 5-fluorouracil-based chemoradiotherapy

S-1 (Teysuno®): A Review of Its Use in Advanced Gastric Cancer in Non-Asian Populations

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