A possible role of thymidine phosphorylase expression and5-fluorouracil increased sensitivity in oropharyngeal cancer patients

G. Ranieri, L. Grammatica, R. Patruno, A. F. Zito, P. Valerio, S. Iacobellis, C. Gadaleta, G. Gasparini, D. Ribatti

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Thymidine Pi deoxyribosyltransferase (TP) is an enzyme involved in DNA synthesis up-regulated in tumours and it is also a pro-angiogenic factor. TP cannot activate capecitabine, because capecitabine first needs conversion by carboxylesterase and cytidine deaminase into 5-deoxy-fluorouridine. This compound can be activated by TP to 5-fluorouracil (5-FU). Although TP is not necessary for 5-FU toxicity, experimental data suggest that high levels of TP correlate with an enhanced response to 5-FU therapy. In this study, we have analysed by immunohistochemistry CD34, CD68 and TP positive cells in bioptic samples from 53 patients with T1-3 N0-1 M0 oropharyngeal squamous cell carcinoma (OSC) and from 24 patients with non-dysplastic oropharyngeal leukoplakia (NDOLP). Results showed that the mean of TP-positive cells, CD68 positive macrophages and CD34 positive endothelial cells eval-uated as microvessel density (MVD) was significantly higher in OSC than in NDOLP. Moreover, at a median follow-up of 19 months, patients with TP expression and higher MVD showed a better survival rate as compared to those with low MVD, probably as a consequence of 5-FU-based therapy.We hypothesized a role for TP in oropharyngeal tumourigenesis and 5-FU activation in the adjuvant setting of OSC patients.

Original languageEnglish
Pages (from-to)362-368
Number of pages7
JournalJournal of Cellular and Molecular Medicine
Volume11
Issue number2
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Thymidine Phosphorylase
Oropharyngeal Neoplasms
Fluorouracil
Thymidine
Microvessels
Leukoplakia
Squamous Cell Carcinoma
Cells
Cytidine Deaminase
Carboxylesterase
Macrophages
Angiogenesis Inducing Agents
Endothelial cells
Toxicity
Tumors
Survival Rate
Endothelial Cells
Chemical activation
Immunohistochemistry

Keywords

  • 5-fluorouracil
  • Capecitabine
  • Leukoplakia
  • Oropharyngeal squamous carcinoma
  • Platelet derived-endothelial cell growth factor
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

A possible role of thymidine phosphorylase expression and5-fluorouracil increased sensitivity in oropharyngeal cancer patients. / Ranieri, G.; Grammatica, L.; Patruno, R.; Zito, A. F.; Valerio, P.; Iacobellis, S.; Gadaleta, C.; Gasparini, G.; Ribatti, D.

In: Journal of Cellular and Molecular Medicine, Vol. 11, No. 2, 03.2007, p. 362-368.

Research output: Contribution to journalArticle

Ranieri, G. ; Grammatica, L. ; Patruno, R. ; Zito, A. F. ; Valerio, P. ; Iacobellis, S. ; Gadaleta, C. ; Gasparini, G. ; Ribatti, D. / A possible role of thymidine phosphorylase expression and5-fluorouracil increased sensitivity in oropharyngeal cancer patients. In: Journal of Cellular and Molecular Medicine. 2007 ; Vol. 11, No. 2. pp. 362-368.
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AU - Valerio, P.

AU - Iacobellis, S.

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