PLK (polo-like kinase), the human counterpart of polo in Drosophila melanogaster and of CDC5 in Saccharomyces cerevisiae, belongs to a family of serine/threonine kinases. It is intimately involved in spindle formation and chromosome segregation during mitosis. The purpose of this study was to determine whether PLK1 is overexpressed in primary colorectal cancer specimens as compared with normal colon mucosa and to assess its relation to other kinases as a potential new tumor marker. In the present study, immunohistochemical analyses were performed of PLK1 expression in 78 primary colorectal cancers as well as 15 normal colorectal specimens. Furthermore, we examined the relationship between other kinases, Aurora-A and Aurora-C, and PLK1 expression. In normal colon mucosa, some crypt cells showed weakly positive staining for PLK1 in 13 out of 15 cases, the remaining cases being negative. Elevated expression of PLK1 was observed in 57 (73.1%) of the colorectal cancers, statistically significant associations being evident with pT (primary tumor invasion) (P = = = =0.0006, Mann-Whitney U test), pN (regional lymph nodes) (P = = = =0.008, χ χ χ χ 2 test) and the Dukes' classification (P = = = =0.0005, MannWhitney U test). Mean proliferating cell nuclear antigen-labeling index was 52.3%, with a range of 24.1% to 77.3%. Values for lesions with high and low PLK1 expression were 54.7 ± ± ± ±10.3% (mean ± ± ± ±SD) and 45.9 ± ± ± ±11.9% (P = = = =0.002, Student's t test). PLK1 was significantly associated with Aurora-A, but PLK1 staining was more diffuse and extensive than for Aurora-A or Aurora-C. Interestingly, PLK1 overexpression was significantly associated with p53 accumulation in colorectal cancers. Our results suggest overexpression of PLK1 might be of pathogenic, prognostic and proliferative importance, so that this kinase might have potential as a new tumor marker for colorectal cancers. (Cancer Sci 2003; 94: 148-152)

ObjectiveThis exploratory trial was performed to determine whether Daikenchuto accelerates recovery of gastrointestinal function in patients undergoing open colectomy for colon cancer.MethodsA total of 386 patients undergoing colectomy at 1 of the 51 clinical trial sites in Japan from January 2009 to June 2011 were registered for the study (JFMC39-0902). Patients received either placebo or Daikenchuto (15.0 g/day, t.i.d) between post-operative day 2 and post-operative day 8. Primary end-points included time to first bowel movement, frequency of bowel movement and stool form. The incidence of intestinal obstruction was evaluated post-operatively. The safety profile of Daikenchuto until post-operative day 8 was also evaluated.ResultsThe results for 336 patients (Daikenchuto, n = 174; placebo, n = 162) were available for statistical analysis. The time to first bowel movement did not differ significantly between the two groups. All patients reported having diarrhea or soft stools immediately after surgery, and the time until stool normalization (50th percentile) in the Daikenchuto and placebo groups was 6 days and 7 days, respectively. The placebo group had a significantly greater number of hard stools at post-operative day 8 (P = 0.016), and bowel movement frequency continued to increase until post-operative day 8 as well. In contrast, bowel movement frequency in the Daikenchuto group increased until post-operative day 6, however decreased from post-operative day 7 and was significantly lower at post-operative day 8 compared with the placebo group (P = 0.024).ConclusionThe moderate effects of Daikenchuto were observed ∼1 week after the operation. Although Daikenchuto had an effect on gastrointestinal function after open surgery in patients with colon cancer, this study did not show its clinical benefits adequately.

These findings suggest that curative gastrectomy combined with HAI or systemic chemotherapy should be attempted for patients with primary tumors without serosal invasion or any other noncurative factors.

Background Up to 6-months oxaliplatin-containing regimen is now widely accepted as a standard adjuvant chemotherapy for stage III colorectal cancer (CRC). However, oral fluoropyrimidine monotherapy is used for some part of patients, especially in Asian countries including Japan, and its optimal duration is yet to be fully investigated. Methods A total of 1306 patients with curatively-resected stage III CRC were randomly assigned to receive capecitabine (2500 mg/m 2 /day) for 14 out of 21 days for 6 ( n = 654) or 12 ( n = 650) months. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were relapse-free survival (RFS), overall survival (OS), and adverse events. Results The 3- and 5-year DFS were 70.0% and 65.3% in the 6M group and 75.3% and 68.7% in the 12M group, respectively ( p = 0.0549, HR = 0.858, 90% CI: 0.732–1.004). The 5-year RFS was 69.3% and 74.1% in the 6M and 12M groups, respectively ( p = 0.0143, HR = 0.796, 90% CI: 0.670–0.945). The 5-year OS was 83.2% and 87.6%, respectively ( p = 0.0124, HR = 0.727, 90% CI: 0.575–0.919). The incidence of overall grade 3–4 adverse events was almost comparable in both groups. Conclusions Although 12-month adjuvant capecitabine did not demonstrate superior DFS to that of 6-month, the observed better RFS and OS in the 12-month treatment period could be of value in selected cases.

EAGLE was a randomized, multicenter phase III study which evaluated the superiority of bevacizumab 10 mg/kg plus FOLFIRI compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC previously treated with first-line bevacizumab plus an oxaliplatin-based regimen. The results suggest that the higher 10 mg/kg dose offers no clear clinical benefit compared with bevacizumab 5 mg/kg in this setting.