The Schedule Dependency for Induction of Thymidine Phosphorylase Activity and the Enhancement of Capecitabine Efficacy by Docetaxel on the SNU-484 Gastric Cancer Cell Line That was Injected into Xenografted Nude Mice

PURPOSE: Docetaxel (Taxotere(R)) and capecitabine are used in combination to treat advanced gastric cancer. Thymidine phosphorylase (TP) is an essential enzyme for the activation of capecitabine in tumors. This study sought to identify the best combination therapy with capecitabine and using two different schedules for docetaxel, a TP up-regulator, to enhance capecitabine's efficacy. METHODS: The human gastric cancer cell line SNU-484 was cultured and docetaxel (2 microgram/ml) was added to the 24-well plates that contained 5 x 10(5) cells/well. The total RNA was isolated and RT-PCR was done to identify the TP expression. Four- or five-week-old BALB/c-nu/nu mice were subcutaneously inoculated with the SNU-484 cells. The nude mice were divided into two groups and they were given capecitabine 539 mg/m2 p.o. from days 1 to 14: Group 1 was given docetaxel 15 mg/m2 i.v. on day 1; Group 2 was given docetaxel 7.5mg/m2 on days 1 and 8. Tumor tissues were excised on days 1, 8 and 15 to measure the TP and bcl-2 levels. RESULTS: TP was expressed 2 hours after docetaxel administration. Group 2 had a higher TP concentration in the tumor tissues and a better antitumor effect than did Group 1. There was no difference in the bcl-2 concentration in the two groups. CONCLUSION: These results suggest that docetaxel stimulates the TP expression in tumor tissues and it enhances the antitumor activity of capecitabine. A weekly docetaxel injection with capecitabine administration can be used to treat gastric cancer more effectively than when docetaxel is injected once per cycle. Capecitabine had no bcl-2 suppressive effect in this study.

Giant Gastrointestinal Stromal Tumor Accompanying Stomach Cancer

We report a case of giant malignant gastrointestinal stromal tumor (GIST) accompanying an advanced gastric adenocarcinoma. A 73-year-old male patient was admitted to our hospital due to epigastric discomfort. In gastrofiberscopic examination, a localized Borrmann III gastric cancer at the lower body and antrum was noted. In endoscopic ultrasonographic examination, T3 hyperechoic advanced gastric cancer lesion and a relatively well-marginated heterogenous hypoechoic huge mass with a size of 10 cm were noted. In abdomen CT findings, localized wall thickening in the gastric antrum and the anterior wall, and a 11-cm-sized large heterogeneously enhancing mass in gastric body, posterior wall were noted. We did a radical subtotal gastrectomy, including a huge mass, with D2 lymph node dissection. Pathologic findings revealed double primary gastric neoplasms (synchronous occurrence of an adenocarcinoma and a huge GIST). Although closely juxtaposed, these two tumors had not merged and were separated by the thin rim of the muscularis propria.