A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil

Beck, Amy; Etienne, Marie‐Christine; Chéradame, S; Fischel, Jean‐Louis; Formento, Patricia; Renée, Nicole; Milano, Gérard

doi:10.1016/0959-8049(94)00216-r

Cited by 238 publications

(143 citation statements)

References 12 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…DPD and β-ureidopropionase) are usually low or not detectable in many tumors [36,37,38]. In our and other panels of colon cancer cell lines, DPD activity was low to not detectable [39,40], in contrast to pancreatic and breast cancer [40,41,42]. Therefore, it is unlikely that β-Amino-iso-butyric acid is involved in the angiogenic activity of TP.…”

Section: Discussionmentioning

confidence: 49%

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

Bijnsdorp

Azijli

Jansen

et al. 2010

Biochemical Pharmacology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 49%

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

Bijnsdorp

Azijli

Jansen

et al. 2010

Biochemical Pharmacology

View full text Add to dashboard Cite

“…In fact, prospective randomised clinical studies have found the administration of UFT to be an effective adjuvant chemotherapy for NSCLC patients (Wada et al, 1996;Kato et al, 2004). On the other hand, many experimental and clinical studies have also revealed the 5-FU sensitivity to be affected by several biomarkers, such as its target molecule TS (Rustum et al, 1997), several fluoropyrimidine metabolising enzymes (Peters et al, 1986;Peters et al, 1991), and DPD, an enzyme of 5-FU catabolism (Beck et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, a congenital deficiency of DPD can result in severe life-threatening toxicity when 5-FU is administered (Wei et al, 1996). In contrast, many experimental studies have demonstrated the intratumoural DPD activity to affect the resistance to 5-FU (Beck et al, 1994;Ishikawa et al, 1999). Previous clinical studies also found an overexpression of DPD in tumour cells to be associated with 5-FU resistance (Higashiyama et al, 2001) and a poor prognosis in many cancer patients treated with 5-FU, including NSCLCs (Huang et al, 2000;Nakagawa et al, 2002), colorectal cancers (Ichikawa et al, 2003b), and breast cancers (Horiguchi et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies have reported their sensitivity to be associated with the target molecule TS (Rustum et al, 1997), fluoropyrimidinemetabolising enzymes such as orotate phosphoribosyltransferase (OPRT) (Peters et al, 1986), and the 5-FU-catabolitic enzyme such as dihydropyrimidine dehydrogenase (DPD) (Beck et al, 1994). However, there were only a few clinical studies on the simultaneous evaluations of these biomarkers to evaluate 5-FU sensitivity (Isshi et al, 2002;Fujii et al, 2003;Ichikawa et al, 2003a).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

et al. 2006

View full text Add to dashboard Cite

The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eightytwo carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r ¼ 0.203), between the TS and DPD expression (r ¼ 0.098), or between the OPRT and DPD expression (r ¼ 0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P ¼ 0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P ¼ 0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P ¼ 0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P ¼ 0.0003), OPRT status (hazard ratio 2.543; P ¼ 0.0005), and DPD status (hazard ratio 2.840; Po0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.

show abstract

“…Our previous studies demonstrated four biological markers, including thymidylate synthase (TS) (Huang et al, 2000), vascular endothelial growth factor-A (VEGF-A), VEGF-C (Nakashima et al, 2004), and E (epithelial)-cadherin , to be significant prognostic factors for NSCLC patients. Thymidylate synthase is reported to be related to tumour cell proliferation and responsiveness to 5-FU-based chemotherapy (Navalgund et al, 1980;Beck et al, 1994). VEGF-A and VEGF-C are members of the VEGF family associated with angiogenesis or lymphangiogenesis (Dvorak et al, 1995;Skobe et al, 2001).…”

mentioning

confidence: 99%

Clinical application of biological markers for treatments of resectable non-small-cell lung cancers

et al. 2005

View full text Add to dashboard Cite

We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (Po0.01), VEGF-A status (P ¼ 0.03), VEGF-C status (P ¼ 0.03), and E-cadherin status (P ¼ 0.03) were significant prognostic factors in patients with stage I NSCLCs. The Ki-67 proliferation index (P ¼ 0.02) and TS status (Po0.01) were significant prognostic factors in patients with stage II -III NSCLCs. In patients with stage II -III NSCLCs, furthermore, the survival of UFT (a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients. Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs. Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast, tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs. Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours.

show abstract

A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil

Cited by 238 publications

References 12 publications

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

Clinical application of biological markers for treatments of resectable non-small-cell lung cancers

Contact Info

Product

Resources

About