Reply: Thymidylate synthase polymorphism and survival of colorectal cancer patients treated with 5-fluorouracil

British Journal of Cancer (2002) 86, 1366. DOI: 10.1038/sj/bjc/6600230 www.bjcancer.co

The TP53 colorectal cancer international collaborative study on the prognostic and predictive significance of p53 mutation: influence of tumor site, type of mutation, and adjuvant treatment

PURPOSE: The aims of the TP53 Colorectal Cancer (CRC) International Collaborative Study were to evaluate the possible associations between specific TP53 mutations and tumor site, and to evaluate the prognostic and predictive significance of these mutations in different site, stage, and treatment subgroups. PATIENTS AND METHODS: A total of 3,583 CRC patients from 25 different research groups in 17 countries were recruited to the study. Patients were divided into three groups according to site of the primary tumor. TP53 mutational analyses spanned exons 4 to 8. RESULTS: TP53 mutations were found in 34% of the proximal colon tumors and in 45% of the distal colon and rectal tumors. They were associated with lymphatic invasion in proximal tumors. In distal colon tumors, deletions causing loss of amino acids were associated with worse survival. In proximal colon tumors, mutations in exon 5 showed a trend toward statistical significance (P < .05) when overall survival was considered. Dukes' C tumors with wild-type TP53 and those with mutated TP53 (proximal tumors) showed significantly better prognosis when treated with adjuvant chemotherapy. CONCLUSION: Analysis of TP53 mutations from a large cohort of CRC patients has identified tumor site, type of mutation, and adjuvant treatment as important factors in determining the prognostic significance of this genetic alteration

The expression of RUNX3 in colorectal cancer is associated with disease stage and patient outcome

RUNX3 is believed to have tumour suppressor properties in several cancer types. Inactivation of RUNX3 has been shown to occur by methylation-induced transcriptional silencing and by mislocalization of the protein to the cytoplasm. The aim of this study was to examine the clinical significance of RUNX3 expression in a large series of colorectal cancers using immunohistochemistry and tissue arrays. With advancing tumour stage, expression of RUNX3 in the nucleus decreased, whereas expression restricted to the cytoplasmic compartment increased. Nuclear RUNX3 expression was associated with significantly better patient survival compared to tumours in which the expression of RUNX3 was restricted to the cytoplasm (P=0.025). These results support a role for RUNX3 as a tumour suppressor in colorectal cancer

Agent-Based Modeling for Studying the Spontaneous Emergence of Money

International audienceA central question in economics is how a society accepts money, defined as a commodity used as a medium of exchange, as an unplanned outcome of the individual interactions. This question has been approached theoretically in the literature and investigated by means of agent-based modeling. While an important aspect of the theory is the individual's speculative behavior, that is, the acceptance of money despite a potential short-term loss, previous work has been unable to reproduce it with boundedly rational agents. We investigate the reasons for the failure of previous work to have boundedly rational agents learn speculative strategies. Starting with an agent-based model proposed in the literature, where the intelligence of the agents is guided by a learning classifier system that is shown to be capable of learning trade strategies (core strategies) that involve short sequences of trades, we test several modifications of the original model and we come up with a set of assumptions that enable the spontaneous emergence of speculative strategies, which explain the emergence of money even when the agents have bounded rationality