We determined intratumoral thymidine phosphorylase (dThdPase) activity in 213 patients with T2N0M0 or T2N1M0 breast cancer. After surgery doxifluridine, an intermediate metabolite of capecitabine, and tamoxifen were given by mouth. According to dThdPase activity the examined patients were classified as: A, high activity group; tumors with the activity not less than the mean value and B, low activity group; tumors with activity less than the mean value. Group A had a better prognosis than group B in node-positive patients (disease-free survival, p=0.0446; overall survival, p=0.0788). Intratumoral dThdPase activity might be a useful marker for predicting responsiveness to doxifluridine treatment in the adjuvant setting.
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http://dx.doi.org/10.3892/ijo.17.6.1205 | DOI Listing |
Oncol Rep
October 2007
Product Research Department, Kamakura Research Center, Chugai Pharmaceutical Co., Ltd., Kanagawa 247-8530, Japan.
We have evaluated the antitumor activity of XELOX (a combination therapy of capecitabine (Xeloda) and oxaliplatin) in human colorectal and gastric cancer xenograft models. In human colorectal cancer model CXF280, antitumor activity of the combination at two-thirds of the maximum tolerated dose (MTD) was superior to that of each monotherapy at MTD. Furthermore, in human colorectal cancer model COL-05-JCK and human gastric cancer xenograft model GXF 97, the combination also showed at least additive antitumor activity.
View Article and Find Full Text PDFIn Vivo
October 2005
Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Background: The synergistic antitumor effect of a combination of docetaxel and capecitabine is reported to be attributable to docetaxel-mediated up-regulation of thymidine phosphorylase (dThdPase).
Materials And Methods: Intravenous docetaxel (15 mg/kg) was given to nude mice bearing xenografts of the gastric cancer cell lines MKN45 and MKN28. Mice were sacrificed on days 7, 10 and 22 and tumor samples were taken to measure the activities of thymidylate synthase, dihydropyrimidine dehydrogenase, dThdPase and orotate phosphoribosyltransferase.
Gynecol Oncol
September 2005
Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan.
Objective: Co-expression patterns of the genes implicated in angiogenesis and tumor invasion in cervical carcinoma cells were investigated together with invasive activity of tumor cells. Transcript levels of those genes were also compared between tumor cells and normal cervical tissues.
Methods: Real-time quantitative RT-PCR analysis was conducted on selected 11 genes (total VEGF-A, VEGF(121), VEGF(165), VEGF(189), VEGF-B, C and D, bFGF, dThdPase, MMP-2 and uPA) using 11 cervical carcinoma cell lines and 14 normal cervical tissues.
Oncol Rep
July 2005
Product Research Department, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
5'-deoxy-5-fluorouridine (5'-DFUR, Furtulon) is activated to 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase) highly expressed in many types of tumors. In previous studies, we demonstrated that taxanes (paclitaxel or docetaxel) up-regulated the tumor levels of dThdPase and enhanced the efficacy of 5'-DFUR in human colon and mammary xenograft models. In the present study, combination therapy of 5'-DFUR with taxanes in human gastric cancer xenograft models also showed, at the least, additive anti-tumor activity without significant augmentation of toxicity.
View Article and Find Full Text PDFBiochem Pharmacol
May 2005
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague, Czech Republic.
A series of thymine phosphonomethoxyalkyl derivatives were evaluated for their ability to inhibit thymidine phosphorylase (dThdPase) purified from rat spontaneous T-cell lymphoma. A kinetic study of thymidine phosphorolysis catalyzed by dThdPase was performed with thymidine and/or inorganic phosphate as substrates. Data show that the substantial inhibitory effect of these acyclic nucleotide analogues is decreasing in the order of (R)-FPMPT>(S)-FPMPT>or=(R)-HPMPT>(S)-PMPT>(S)-HPMPT>PMET>or=(R)-PMPT.
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