Dr jing gao de salas9/13/2023 So, the overexpression of TP in tumor tissues can increase the concentration of 5-FU and thus enhance the anticancer effect. At the last enzymatic step, the metabolite 5'-deoxy-5-fluorouridine (5'-DFUR) is converted to 5-FU by Thymidine Phosphorylase (TP) which is more active in tumor tissues than in normal tissues. It is a prodrug which is converted to 5-FU in the tumors through a pathway with three enzymatic steps and two intermediary metabolites involved in. Ĭapecitabine is an orally-administered chemotherapeutic agent which was designed to generate 5-Fluorouracil (5-FU) preferentially in tumors. For advanced gastric cancer patients (AGC), combination chemotherapy with two or three drugs is most common with superiority compared to best supportive care in first-line or second-line therapy. But fluoropyrimidines are fundamental in gastric cancer. Several agents are now available for the systemic chemotherapy of patients with gastric cancer, including fluoropyrimidines, platinum, taxanes and so on. For these patients, chemotherapy is still the main method general accepted in the world. Although the improvement of diagnostic methods enables some patients to receive radical cure at early disease, about 40% patients still miss the opportunity of radical cure at the time of diagnosis, furthermore, about 50% patients occur relapse and metastasis after operation. Gastric cancer remains one of the most common causes of cancer death worldwide, especially in China. Further prospective evaluation in large samples should be performed to confirm these preliminary findings. In Chinese advanced gastric cancer, Thymidine Phosphorylase positive & β-tubulin III negative might predict response and prognosis to capecitabine plus paclitaxel chemotherapy. There was no correlation between β-tubulin III expression and response or survival among cohort 2 (n = 18). Among cohort 1, the response rate, median progression-free survival and overall survival in β-tubulin III positive (n = 22) and negative patients (n = 11) were 36.4%/72.7% (positive vs negative, P = 0.049), 86d/237d ( P = 0.046) and 201d/388d ( P = 0.029), respectively the response rate (87.5% vs 14.3%, P = 0.01) and median progression-free survival (251d vs 84d, P = 0.003) in Thymidine Phosphorylase positive & β-tubulin III negative patients (n = 8) were also significantly higher than those in Thymidine Phosphorylase negative & β-tubulin III positive patients (n = 7). The median age of 51 patients was 57 years (range, 27-75) with male 34 and female 17, and the response rate, median progression-free survival and overall survival were 43.1%, 120d and 265d. ![]() The relationships between expressions of biomarkers and response or survival were determined by statistical analysis. The clinical data and tumor biopsies prior treatment from 33 advanced gastric cancer patients receiving capecitabine plus paclitaxel (cohort 1, experimental group) and 18 patients receiving capecitabine plus cisplatin (cohort 2, control group) in Beijing Cancer Hospital from July 2003 to December 2008 were retrospectively collected and analyzed for Thymidine Phosphorylase and β-tubulin III expressions by immunohistochemistry. To assess the role of Thymidine Phosphorylase and β-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.
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