SummaryResearchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. © 2001 Cancer Research Campaign http://www.bjcancer.comIt is widely accepted that mutations in the Kirsten ras (Ki-ras) gene in patients with colorectal cancer develop early in the progression from adenoma to carcinoma. Our first collaborative study including 2721 patients, clarified that Ki-ras mutations are not only 692

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Justicia procumbens is a traditional Taiwanese herbal remedy used to treat fever, pain, and cancer. Justicidin A, isolated from Justicia procumbens, has been reported to suppress in vitro growth of several tumor cell lines as well as hepatoma cells. In this study, justicidin A activated caspase-8 to increase tBid, disrupted mitochondrial membrane potential (Dw m ), and caused the release of cytochrome c and Smac/DIABLO in Hep 3B and Hep G2 cells. Justicidin A also reduced Bcl-x L and increased Bax and Bak in mitochondria. Caspase-8 inhibitor (Z-IETD) attenuated the justicidin A-induced disruption of Dw m . Growth of Hep 3B implanted in NOD-SCID mice was suppressed significantly by oral justicidin A (20 mg/kg/day). These results indicate that justicidin A-induced apoptosis in these cells proceeds via caspase-8 and is followed by mitochondrial disruption. Supplementary materials are available at http://myweb. ncku.edu.tw/~a725/.

The objective of this retrospective comparative study was to improve the outcome of patients with suspected occult Candida infection after gastrointestinal surgery by early presumptive therapy. It was conducted in the National Cheng Kung University Hospital in Taiwan. A total of 36 patients with prolonged ileus with fever after gastrointestinal tract surgery between January 1995 and December 2002 were examined for two time periods: those treated before and those treated after January 1999. One set of patients did not receive early presumptive therapy (EPT) until Candida infection was confirmed, and they were designated EPT(-). Another group of patients with suspected occult Candida infection received EPT and were designated EPT(+). Fluconazole, 400 mg/day, was given as EPT. Urine, wound, intraperitoneal drainage, and blood specimens were obtained from patients for fungus culture before starting treatment and weekly until symptoms subsided. The primary endpoints were the frequency of candidiasis and the persistence of candidemia; the secondary endpoint was the efficiency of EPT in the clinical outcome. There was no difference in Candida peritonitis, wound colonization, or urine colonization in the two treatment groups. Candida albicans accounted for 87.5%% of the isolated Candida species: 84.6%% in the EPT(+) group and 89.5%% in the EPT(-) group. In the EPT(+) group, the positive blood culture rate was 66.7%%. The fever subsided rapidly in 17 patients (94%%), the hospital stay and intensive care unit stay were shorter, and the mortality decreased significantly: 11%% vs. 78%%, P < 0.001. Persistent gastrointestinal ileus was the main cause of breakthrough candidemia. We concluded that EPT with fluconazole improves the prognosis of patients with occult Candida infection after gastrointestinal surgery. Surgical intervention was required in patients with breakthrough candidemia.