Cancer cells suppress p53 in adjacent fibroblasts.

The p53 tumor suppressor serves as a crucial barrier against cancer development. In tumor cells and their progenitors, p53 suppresses cancer in a cell-autonomous manner. However, p53 also possesses non-cell-autonomous activities. For example, p53 of stromal fibroblasts can modulate the spectrum of proteins secreted by these cells, rendering their microenvironment less supportive of the survival and spread of adjacent tumor cells. We now report that epithelial tumor cells can suppress p53 induction in neighboring fibroblasts, an effect reproducible by tumor cell-conditioned medium. The ability to suppress fibroblast p53 activation is acquired by epithelial cells in the course of neoplastic transformation. Specifically, stable transduction of immortalized epithelial cells by mutant H-Ras and p53-specific short inhibitory RNA endows them with the ability to quench fibroblast p53 induction. Importantly, human cancer-associated fibroblasts are more susceptible to this suppression than normal fibroblasts. These findings underscore a mechanism whereby epithelial cancer cells may overcome the non-cell-autonomous tumor suppressor function of p53 in stromal fibroblasts.

Appendectomy in familial Mediterranean fever: clinical, genetic and pathological findings.

BACKGROUND: Abdominal attacks of familial Mediterranean fever (FMF) may simulate acute appendicitis and bring about considerable uncertainty. The similar presentation of the two clinical entities often leads to an unnecessary appendectomy. METHODS: 182 consecutive FMF patients were retrospectively reviewed for this study. Clinical and genetic data was compared between those who had undergone an appendectomy (n=71) and those who had not (n=111). RESULTS: The frequency of appendectomy found in FMF was far above the reported rate in the general population (40% vs. 12-25%). The rate of non-inflamed appendectomies was extremely high (80% vs. 20%) and remained constant over time. Tertiary hospitals and improved therapeutic and diagnostic measures that have evolved over the years did not reduce misdiagnosis of acute appendicitis in FMF. Severe phenotype and homozygosity for M694V were identified as risk factors for appendectomy in FMF. A change from the regular diffuse involvement to right lower quadrant abdominal pain was found to be the best predictor of inflamed appendix in FMF patients undergoing appendectomy for suspected acute appendicitis. CONCLUSION: Reliance on clinical parameters should improve diagnostic accuracy of acute appendicitis in the FMF patient population.

Monteggia and equivalent lesions. A study of 41 cases.

Forty-one patients who suffered from a Monteggia fracture and were treated between 1984 and 1993 were reviewed retrospectively using a new motion score of the elbow joint. There were 14 children and 27 adults of whom 34 were available for review. The results in children were significantly better than those of the adults. Among the adults, the final results of the patients who had a Bado Type 1 equivalent injury were significantly worse than those of the other groups, especially when associated with a fracture of the radial head. The type of fracture, open or closed, the presence of a fracture of the olecranon, and the energy level of the trauma did not have any significant prognostic value. Good correlation was shown between the new motion score and the Figgie elbow score. The Bado Type 1 equivalent injuries should be considered as a special subgroup of the Monteggia lesion, necessitating extra attention in treatment and rehabilitation, and a close followup of the patient.