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

We previously observed that Pim-3 with serine/threonine kinase activity, was aberrantly expressed in malignant lesions of endodermderived organs, liver and pancreas. Because Pim-3 protein was not detected in normal colon mucosal tissues, we evaluated Pim-3 expression in malignant lesions of human colon, another endodermderived organ. Pim-3 was detected immunohistochemically in welldifferentiated (

An experimental study was carried out to evaluate heat production by an ultrasonically activated device (USAD) using an animal model. In an anesthetized living pig, the gastroepiploic and mesenteric vessels were coagulated and cut by an USAD at a power level of 70% (n = 8) or 100% (n = 8). During the division, the time-discrete temperature change on the surface of the animal tissue adjacent to the blade was measured by thermography. To compare the USAD with conventional electrocautery (EC), a full-thickness incision of the gastric wall was performed by each device, and the temperature change was measured. With the USAD, the temperature increased gradually and remained below 150 degrees C during the entire activating time at both power levels. By contrast, with EC at 30 W, the temperature increased rapidly and exceeded 350 degrees C within only a few seconds. The area above 60 degrees C reached a final width of 10 mm for the USAD, as compared with 22 mm for EC. Microscopically, thermal alterations such as carbonization and vaporization were much more severe and extensive in the adjacent tissue when using EC rather than the USAD. With the USAD, heat production is much slower and more limited than with conventional EC; thus, the USAD causes fewer thermal alterations in adjacent tissue. USAD should be preferred for tissue coagulation and cutting during endscopic surgery.

The thymidylate synthase (TS) gene has a polymorphic repeated sequence in its 5′ ′ ′ ′-untranslated region. The repeat length is associated with TS protein expression, which suggests that we may be able to predict the efficacy of 5-fluorouracil (5-FU)-based chemotherapy from a patient's TS Key words: Thymidylate synthase -Loss of heterozygosity -Gene polymorphism -Pharmacogenomics -Cancer chemotherapy Thymidylate synthase (TS) catalyzes the reductive methylation of dUMP by 5,10-methylenetetrahydrofolate to form dTMP and dihydrofolate. TS has been an important target for cancer chemotherapy because of its central, rate-limiting role in the de novo synthesis of dTTP. 1) 5-Fluorouracil (5-FU) inhibits TS by forming a stable ternary complex among 5,10-methylenetetrahydrofolate, TS and fluoro-dUMP, the metabolite of 5-FU. Based on this mechanism, the TS expression level in cancer tissue has been expected to be a predictor of response to 5-FU-based chemotherapy, and indeed, recent studies have shown that the sensitivity of various tumors to 5-FU-based chemotherapy is associated with the intratumoral level of TS. 2-5)The TS gene is known to have a unique tandemly repeated sequence in the 5′-untranslated region (5′-UTR) and is polymorphic in the numbers of this repeat.6) The double (2R) or the triple (3R) repeats are the most common, although higher numbers are also found less frequently. We previously reported that this polymorphism was associated with TS protein expression in human gastrointestinal cancers.7) The cancer tissue with 3R/3R genotype showed significantly higher TS protein expression than did that with 2R/3R genotype. This association between TS genotype and TS expression, together with the role of TS expression in 5-FU-based chemotherapy, suggest that the TS genotype might be a novel predictor of efficacy for 5-FU-based chemotherapy. Some clinical evidence has been reported to support this potential of the TS genotype, [8][9][10][11] although the studies had relatively small numbers of subjects, and validation by a larger-scale clinical study is needed.One of advantages of clinical use of TS genotype would be that the genotype can be determined through a blood test, and so the strategy would be applicable to patients with cancer that is not easily accessible. This expectation is based on the assumption that the genotype in normal tissue, i.e. peripheral blood cells, is identical with that in cancer tissue. However, this assumption has not yet been validated in the case of the TS genotype. Theoretically, the TS genotype in cancer tissue could be changed by genetic alterations, including instability of repeat length and allelic loss. To test this possibility, we analyzed the TS genotype

The objective of this study was to evaluate the effects of nutrition intervention on nutritional states and healing of pressure ulcers by standardizing or unified factors including nursing, care and treatment in a multicenter open randomized trial. Tube-fed patients with Stage III-IV pressure ulcers were selected. The control group (30 patients) received the same nutrition management as before participating in this trial, whereas the intervention group (30 patients) was given calories in the range of Basal Energy Expenditure (BEE) × 1.1 × 1.3 to 1.5. The intervention period was 12 weeks. The efficacy and safety were evaluated based on the nutritional states and the sizes of ulcers (length × width), and on the incidence of adverse events related to the study, respectively. The calories administered to the control and intervention groups were 29.1 ± 4.9 and 37.9 ± 6.5 kcal/kg/day, respectively. Significant interactions between the presence or absence of the intervention and the intervention period were noted for nutritional states (p<0.001 for body weight, p<0.05 for prealbumin). Similarly, the size of ulcers differed significantly between subjects in the intervention group and in the control group (p<0.001). The results suggest that nutrition intervention could directly enhance the healing process in pressure ulcer patients.