Abstract
Background
Pyrimidine nucleoside phosphorylase (PyNPase) is the enzyme that converts 5’-deoxy-5-fluorouracil (5’DFUR) to 5-fluorouracil (5FU). Its activity in cancer tissue may correlate with the selective antitumor activity of 5’DFUR in breast cancer.
Methods
Two hundred and sixteen T2 breast cancer patients were treated consecutively with surgery followed by 5’DFUR (600 mg/body/day)+tamoxifen (20 mg/body/day) for 2 years. PyNPase activity in breast cancer tissue, determined by high-performance liquid chromatography, ranged from 4.2-626.0 μg FU/mg protein/hr (mean±SD, 203.5±122.4), and the examined patients were divided into two groups: group A (high PyNPase group), cases with the PyNPase activity equal to or more than the mean value of 203.5 μg FU/mg protein/hr, and group B (low PyNPase group), cases with activity less than the mean value.
Results
Although there was no difference in relapse-free survival (RFS) between groups A and B, among node-positive patients (n=83) those in group A tended to have a longer RFS. When divided into subgroups according to estrogen receptor (ER) status, among node-positive and ER-positive tumors (n = 49), the RFS was significantly better in group A than in group B (p<0.05).
Conclusion
Intratumoral PyNPase activity might be of use as a predictor of the effect of adjuvant 5’DFUR on breast cancer.
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Abbreviations
- PyNPase:
-
Pyrimidine nucleoside phosphorylase
- 5’DFUR:
-
5’-Deoxy-5-fluorouracil
- 5FU:
-
5-Fluorouracil
- PD-ECGF:
-
Platelet-derived endothelial cell growth factor
- ER:
-
Estrogen receptor
- PR:
-
Progesterone receptor
- RFS:
-
Relapse-free survival
References
Ishitsuka H, Miwa M, Takemoto K,et al: Role of uridine phosphorylase for antitumor activity of 5’-deoxy-5-fluorouridine.Jpn J Cancer Res 71:112–123, 1980.
Suzuki S, Hongu Y, Fukazawa H,et al: Tissue distribution of 5’-deoxy-5-fluorouridine and derivated 5-furuorouracil in tumor.Jpn J Cancer Res 71:238–245, 1980.
Furukawa K, Yoshimura A, Sumizawa T,et al: Angiogenic factor.Nature 356:668, 1992.
Usuki K, Saras J, Waltenberger J,et al: Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity.Biochem Biophys Res Commun 184:1311–1316, 1992.
Takahashi H, Uchino J, Ogita M,et al: Pyrimidine nucleoside phosphorylase activity and biological characteristics of breast cancer.Int J Oncol 7:1139–1144, 1995.
Peters GJ, Wets M, Keepers YPAM,et al: Transformation of mouse fibroblasts with the oncogenes H-ras or trk is associated with pronounced changes in drug sensitivity and metabolism.Int J Cancer 54:250–455, 1993.
Haraguchi M, Furukawa T, Sumizawa T,et al: Sensitivity of human KB cells expressing platelet-derived endothelial cell growth factor to pyrimidine antimetabolites.Cancer Res 53:5680–5682, 1993.
Eda H, Fujimoto K, Watanabe S,et al: Cytokines induced uridine phosphorylase in mouse colon 26 carcinoma cells and make the cells more susceptible to 5’-deoxy-5-fluorouridine.Jpn J Cancer Res 84:341–347, 1993.
Iida Y, Tokuda Y, Arai K,et al: Measurement of cytosol estrogen receptor in human breast cancer using 16a -125-estradiol.Nucl Med 24:327–333, 1987.
Kobayashi S, Iwase H, Karamatsu S,et al: Fundamental and clinical studies on the monoclonal EIA kit for the measurement of progesterone recepteor (PgR) in human breast cancer tissues.Morm Clinic 36:277–281, 1988.
Uchino J, Samejima N, Tanabe T,et al: Positive effect of tamoxifen as part of adjuvant chemo-endocrine therapy for breast cancer.Br J Cancer 69:767–771, 1994.
Toi M, Hoshina S, Taniguchi T,et al: Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast cancer.Int J Cancer 64:79–82, 1995.
Yamamoto Y, Toi M, Tominaga T: Prediction of the effect of 5’-deoxy-5-fluorouridine by the status of angiogenic enzyme thymidine phosphorylase expression in recurrent breast cancer patients.Oncol Report 3:863–865, 1996.
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Hata, Y., Takahashi, H., Sasaki, F. et al. Intratumoral pyrimidine nucleoside phosphorylase (pynpase) activity predicts a selective effect of adjuvant 5’-deoxy-5-fluorouridine (5’ dfur) on breast cancer. Breast Cancer 7, 37–41 (2000). https://doi.org/10.1007/BF02967186
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DOI: https://doi.org/10.1007/BF02967186