Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma

  • Authors:
    • Nobutaka Nagai
    • Yuko Shiroyama
    • Takafumi Oshita
    • Keiji Mukai
    • Kazushi Shigemasa
    • Tsuneo Fujii
    • Yasuhiro Katsube
    • Shigeru Matsubayashi
    • Takahiro Murakami
    • Koso Ohama
  • View Affiliations

  • Published online on: September 1, 2002     https://doi.org/10.3892/or.9.5.1033
  • Pages: 1033-1040
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Patients with advanced cervical carcinoma were treated with oral fluoropyrimidine (UFT) as neoadjuvant chemotherapy and its antitumor effect was examined. The relationship between thymidylate synthase (TS) or dihydropyrimidine dehydrogenase (DPD) activity in tumor tissue and apoptosis was also investigated. The subjects were 56 patients with advanced cervical carcinoma. The patients received two courses of therapy consisting of UFT at a dose of 600 mg/day for 5 days and 2 days off treatment. The TS and DPD activity in tumor tissue was measured before and after UFT administration by the FdUMP binding assay and a catalytic assay in 38 patients, respectively. Apoptosis was detected by the TUNEL method, and the apoptotic index (AI) was calculated. Tumor tissue activity of TS or DPD was unrelated to clinicopathologic factors or to the activity of the other enzyme. The mean tumor TS and DPD activity before UFT administration was 5.42±3.92 pmol/g tissue and 206.54±128.58 pmol/mg/min, respectively, and the levels of these enzymes in two patients showing an antitumor effect were below the mean values. The AI increased from 1.10±0.57% before UFT to 1.27±0.81% afterwards, and the DPD activity before UFT showed an inverse relationship with the AI after UFT (r=-0.6938). In patients with DPD activity below the median value (186.92 pmol/mg/min), UFT administration significantly caused an increase of the AI (p=0.0002). These results indicate that the DPD activity of advanced cervical carcinoma is a determinant of sensitivity to UFT, suggesting an association between UFT therapy and the induction of apoptosis.

Related Articles

Journal Cover

September-October 2002
Volume 9 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Nagai N, Shiroyama Y, Oshita T, Mukai K, Shigemasa K, Fujii T, Katsube Y, Matsubayashi S, Murakami T, Ohama K, Ohama K, et al: Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma. Oncol Rep 9: 1033-1040, 2002
APA
Nagai, N., Shiroyama, Y., Oshita, T., Mukai, K., Shigemasa, K., Fujii, T. ... Ohama, K. (2002). Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma. Oncology Reports, 9, 1033-1040. https://doi.org/10.3892/or.9.5.1033
MLA
Nagai, N., Shiroyama, Y., Oshita, T., Mukai, K., Shigemasa, K., Fujii, T., Katsube, Y., Matsubayashi, S., Murakami, T., Ohama, K."Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma". Oncology Reports 9.5 (2002): 1033-1040.
Chicago
Nagai, N., Shiroyama, Y., Oshita, T., Mukai, K., Shigemasa, K., Fujii, T., Katsube, Y., Matsubayashi, S., Murakami, T., Ohama, K."Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma". Oncology Reports 9, no. 5 (2002): 1033-1040. https://doi.org/10.3892/or.9.5.1033