Although 5-fluorouracil (5-FU) is an important drug for colorectal cancer (CRC) treatment, no useful biomarker is currently available to predict treatment response. Since 5-FU is converted into active or inactive forms by orotate phosphoribosyltransferase (OPRT) or dihydropyrimidine dehydrogenase (DPD), a correlation between these enzymes and response to 5-FU has been suggested. However, such a correlation has not been investigated prospectively. Therefore, in the present study, we aimed to prospectively evaluate whether OPRT and DPD were predictive factors of the response to 5-FU treatment in patients with resectable CRC. The present investigation was designed as a multicenter prospective cohort study. OPRT and DPD activities were assessed in biopsy samples, obtained surgically from patients with resectable CRC. The OPRT/DPD ratio was calculated and the cut-off values for this ratio were determined for 5-year disease-free survival (DFS) and overall survival (OS). Patients were treated with 5-FU/leucovorin (LV) regimens and oral 5-FU. The endpoint of this study was the correlation between the OPRT/DPD ratio and 5-year DFS and OS. The cut-off value for the OPRT/DPD ratio was determined by using the maximum χ2 statistic method against 5-year DFS and OS. Sixty-eight patients were enrolled from July 2003 to May 2005. The median follow-up period was 1925 days. The OPRT/DPD ratio cut-off values for 5-year DFS and OS were 0.015 and 0.013, respectively. During the 5-year DFS and OS periods, patients with higher cut-off values had a better prognosis than those with lower ratios (P=0.03 and 0.02, respectively). In conclusion, our results suggest that the OPRT/DPD ratio could be a predictive factor for response to 5-FU/LV adjuvant chemotherapy.
Lymphocyte subpopulations of the spleen were assayed in 26 patients with gastric cancer and 5 patients with benign disease using two-color flow cytometric analysis. The ratio of Leu 2a+.Leu 15+ cells, or suppressor T cells, in the gastric cancer patients was about 6 per cent, being higher than that in the patients with benign disease (p less than 0.05). There were fewer Leu 7+.Leu 11- cells, or natural killer-NK-cells, in the gastric cancer patients in stage III or IV than in those with stages I or II (p less than 0.05). The ratio of Leu 3a+.Leu 8- cells, or helper T cells, in the stage IV patients accounted for about 15 per cent of the splenic lymphocytes, which was less than that seen in the patients in stages I or II (p less than 0.05). The ratio of Leu 2a+.Leu 15- cells, or cytotoxic T cells, was approximately twice that of suppressor T cells. The pre-operative administration of lentinan plus OK-432 increased the ratio of Leu 4+.HLA-DR+ cells, or activated T cells, and cytotoxic T cells (p less than 0.05 and p less than 0.01, respectively). The above results suggest that lymphocyte subpopulations in the spleen may have more immunosuppressive potential in proportion with the stage of gastric cancer, but that this reduced immune state may be altered when lentinan and OK-432 are given to these patients.
We herein report the case of a 69-year old woman presenting with an abdominal mass, who was found to have a mixed mesodermal tumor (MMT) of the cecum. Imaging studies and endoscopic investigations were consistent with the diagnosis of a nonepithelial malignant tumor of the cecum. On laparotomy, a knuckle-sized firm mass involving the cecum was noticed. As a result, a right hemicolectomy was performed. Pathological examinations, including immunohistochemical staining, resulted in the diagnosis of mesodermal mixed tumor, homologous type. The patient was advised to undergo postoperative chemotherapy but she did not comply. She has been followed up as an outpatient and is still alive 1.5 years after the operation.
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