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Although authors are usually considered to be the main perpetrators of research and publication misconduct, any person involved in the process has the potential to offend. Editors may breach ethical standards particularly with respect to conflicts of interest. In the same way that authors are now required to declare competing interests, notably commercial affiliations, financial interests and personal connections, so must editors. Editors can influence the chances of acceptance or rejection of a paper by reviewer selection. Reviewers should also be ready to disclose conflicts of interest. They must ensure that their reviews are evidence based and free from destructive criticism driven by self interest. It seems likely that ultimately we will progressively move towards 'open' peer review in which both the authors and the reviewers are known to each other. There is an urgent need for increased transparency of the relationship between editors and owners. The events of the last few years indicate that unless this interface is fully understood by all parties, conflicts may arise. There is also a need for a radical overhaul in the relationship between journals, journal editors and the biomedical industry. It is now increasingly accepted that all clinical trials should be registered in a centrally held database and that protocols should include the primary and secondary outcome measures and the intended approach to data analysis thereby avoiding opportunistic post hoc analyses. However, the even more radical proposal that journals should cease to publish clinical trials sponsored by industry deserves wider debate. [ABSTRACT FROM AUTHOR]

Purpose: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility. The prognostic role of the polymorphism was assessed in 102 patients with advanced gastric adenocarcinoma., Experimental Design: We followed up 102 consecutive Caucasian patients with advanced gastric adenocarcinoma for >5 years and determined the status of the TP53 codon 72 polymorphism in DNA samples extracted from archived gastric tissues., Results: The frequency of the arginine homozygous allele was positively correlated to patient age at baseline (P = 0.002). However, the age-related increase in the percentage of codon 72 arginine p53 was not correlated to the prognosis for gastric cancer patients. Multivariable analysis in patients who had surgery showed that baseline age may be inversely associated with patient survival (odds ratio, 1.1; 95% confidence interval, 1.0-1.2; P = 0.02). Furthermore, alcohol consumption may be associated with reduced survival (P = 0.06)., Conclusions: These findings indicate that codon 72 arginine p53 may not be associated with a prolonged survival in patients with advanced gastric adenocarcinoma, but further study is needed to assess whether this polymorphism is associated with a late onset or slow progress of early gastric adenocarcinoma.

Purpose: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility and prognosis. To examine the role of the polymorphism in the gastric adenocarcinoma, we examined 397 patients with or without the cancer., Experimental Design: DNA samples were extracted from archived gastric tumor tissues and/or normal tissues of gastric adenocarcinoma and noncancer patients. The TP53 codon 72 genotypes were determined by PCR-RFLP., Results: The overall genotype frequencies for Pro/Pro, Arg/Pro, and Arg/Arg were 7.3, 45.1, and 47.6%, respectively. A significant stepwise increased frequency of codon 72 Arg p53 with age was observed in patients with gastric cancer, but not in noncancer patients (P = 0.01). Patients with gastric cardia cancer had a significantly higher frequency of homozygous Arg allele than those with non-cardia tumors (P = 0.03) or than noncancer patients. After adjustment for age and gender, a logistic regression analysis suggested that the risk for a p53 Arg homozygous patient to develop cardia cancer is 3.1 95% confidence interval, 1.4-7.3) times greater than for p53 Pro homozygous and p53 Arg/Pro heterozygous patients. No close relationship was observed among patient gender, tumor histological type, p53 protein expression, and codon 72 genotype distribution., Conclusions: These findings indicate that codon 72 Arg p53 may be associated with a prolonged survival for patients who have had gastric adenocarcinoma, especially non-cardia adenocarcinoma. It may confer, however, a different role on patients who suffer cardia gastric adenocarcinoma.

Small intestinal mucosal T cell activation results in villous atrophy and crypt hyperplasia. There is conflicting evidence as to whether a Th1 IFN-gamma response may be involved. Using a murine intestinal transplant model of T cell-mediated enteropathy we aimed to study the role of IFN-gamma on the development of villous atrophy and crypt hyperplasia. Isografts or allografts of foetal small intestine from 129SV-/- IFN-gamma receptor knockout mice or wild type mice were implanted under the kidney capsule of Balb/c recipient mice. Grafts were examined histologically at intervals from 2 to 9 days post implantation for signs of rejection. Quantitative rtPCR for IFN-gamma, TNFalpha and IL-4 was conducted on grafts at 5 and 9 days post implantation. In allografts, rejection accompanied by the development of villous atrophy and crypt hyperplasia, occurred in a time-dependent manner. However this process was markedly slower in the IFN-gamma receptor knockout grafts compared to the wild type grafts at 5 days (chi2 = 10.08, P = 0.007) and 9 days post implantation (chi2 = 13.25, P = 0.004). There were also significantly fewer TNFalpha transcripts in allografts of IFN-gamma-/- intestine than in wild type allografts (P = 0.02). IFN-gamma has a partial, but not obligatory, role in the development of villous atrophy and crypt hyperplasia during T cell mediated rejection of intestinal allografts.

In epithelial tissue, cell-matrix and cell-cell adhesive interactions have important roles in the normal organization and stabilization of the cell layer. The malignant conversion of epithelial cells involves alterations in the expression and function of these adhesion systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Fascin is an actin-crosslinking protein that is found in the core actin bundles of cell-surface spikes and projections that are implicated in cell motility. We demonstrate that fascin is not detectable in normal colonic epithelium, but is dramatically up-regulated in colorectal adenocarcinoma. To test the hypothesis that fascin could participate in tumor invasive behavior, we developed a cell culture model to examine the effect of fascin expression on the adhesive interactions, invasiveness, and differentiation of colonic epithelial cells. We report marked effects on the organization of cell-surface protrusions, actin cytoskeleton, and focal adhesions in the absence of alterations in the protein levels of the major components of these structures. These effects correlate with alterations in cell movements on two-dimensional matrix, and increased invasiveness in three-dimensional matrix. The cells also show increased proliferation and decreased capacity for normal glandular differentiation in collagen gels. We propose that up-regulation of fascin, by promoting the formation of protrusive, actin-based, cell-motility structures, could be a significant component in the acquisition of invasive phenotype in colonic carcinoma.