Tomohiro Takenoue

Relation between thymidylate synthase expression and survival in colon carcinoma, and determination of appropriate application of 5-fluorouracil by immunohistochemical method

BackgroundThymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU) chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high expression of TS. But the relation between TS expression and overall survival of curatively resected colorectal cancer patients has been less studied.MethodsSpecimens of curatively resected colon carcinoma from 148 patients were included in this study. TS expression in the tumor was assessed by immunohistochemical staining technique, and the patients were categorized into TS-(+) and TS-(−) groups. First, the relation between TS expression and survival of patients was examined. Next, for each group, we compared survival between the chemotherapy-(+) and the chemotherapy-(−) subgroup.ResultsOverall survival was significantly better in the TS-(−) group (n=107) than in the TS-(+) group (n=41) (P=.0003). In the TS-(−) group, there was little difference between the chemotherapy-(+) and the chemotherapy-(−) subgroup. In the TS-(+) group, the survival of the chemotherapy-(+) subgroup was significantly better than the chemotherapy-(−) subgroup (P=.0439).ConclusionsTS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant chemotherapy may be appropriate for colon carcinoma with high expression of TS.

Bcl‐XL Antisense Sensitizes Human Colon Cancer Cell Line to 5‐Fluorouracil

Resistance to 5‐fluorouracil (5‐FU) has been frequently found in the treatment of digestive tract cancer patients. Our previous study suggested that high expression of endogenous Bcl‐XL, might be associated with resistance to 5‐FU in colorectal cancer. The aim of this study is to analyze the role of Bcl‐XL in 5‐FU resistance and to explore a new therapeutic strategy using Bcl‐XL antisense. First, western blot analysis shows that Bcl‐XL rather than Bcl‐2 is overexpressed in primary adenocarcinoma of colon. Second, when Colo320 cells, with undetectable endogenous Bcl‐XL expression, were transfected with Bcl‐XL gene, they acquired high resistance to 5‐FU. Finally, antisense oligodeoxynucleotides (ODNs) that targeted the start codon of Bcl‐XL mRNA (ASI) prove to be the most effective in DLD1 cells with high endogenous Bcl‐XL expression. Bcl‐XL protein expression was decreased in a dose‐dependent manner when the cells were treated with AS1 ODNs, while non‐sense and sense controls and 5‐FU had no effect on Bcl‐XL protein. 5‐FU treatment induced a level of apoptosis 10‐fold higher in DLD1 cells than in untreated control cells, while the same dose of 5‐FU induced a 55‐fold higher level of apoptosis in DLD1 cells treated with Bcl‐XL antisense oligodeoxynucleotides (P=0.0003). Moreover, AS1 ODNs coupled with 5‐FU decreased viable colon cancer cells 40% more than did 5‐FU alone (P < 0.05). These results suggest that Bcl‐XL is an important factor for 5‐FU resistance and the suppression of Bcl‐XL expression by the specific antisense ODNs can increase the sensitivity of colon cancer cells to 5‐FU.

GIANT SOLID CYSTIC TUMOR OF THE PANCREAS WITH A FIBROUS SEPTUM CAUSED BY EXTRACAPSULAR GROWTH IN MIDDLE-AGED WOMAN : REPORT OF A CASE

We report herein the case of a 57-year-old female who was admitted to our hospital for treatment of rectal carcinoma and incidentally found to have a giant cystic tumor, 20 cm in diameter, in the body and tail of the pancreas. Several imaging procedures, including ultrasonography, computed tomography, and magnetic resonance imaging, showed that this tumor was round and hypovascular, and had a septum with protuberant lesions. The capsule was 3–4 mm thick with partial calcification. A preoperative diagnosis of a solid cystic tumor (SCT) of the pancreas was made, even though these tumors are rarely found in females in their fifties. Moreover, few reports of SCT with a septum have been described. Distal pancreatectomy and splenectomy were performed, and the tumor was found to be filled with massive necrotic tissue. Microscopically, the tumor was confirmed to be a SCT with a fibrous septum. We present this case due to the atypical findings, including the age of the patient and the existence of a septum caused by extracapsular growth.