Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network

Oesophageal adenocarcinoma, which arises from an acquired columnar lesion, Barrett's metaplasia, is rising in incidence more rapidly than any other cancer in the Western world. Elevated expression of c-MYC has been demonstrated in oesophageal adenocarcinoma; however, the expression of other members of the MYC/MAX/MAD network has not been addressed. The aims of this work were to characterise the expression of c-MYC, MAX and the MAD family in adenocarcinoma development and assess the effects of overexpression on cellular behaviour. mRNA expression in samples of Barrett's metaplasia and oesophageal adenocarcinoma were examined by qRT–PCR. Semi-quantitative immunohistochemistry and western blotting were used to examine cellular localisation and protein levels. Cellular proliferation and mRNA expression were determined in SEG1 cells overexpressing c-MYCER or MAD1 using a bromodeoxyuridine assay and qRT–PCR, respectively. Consistent with previous work expression of c-MYC was deregulated in oesophageal adenocarcinoma. Paradoxically, increased expression of putative c-MYC antagonists MAD1 and MXI1 was observed in tumour specimens. Overexpression of c-MYC and MAD proteins in SEG1 cells resulted in differential expression of MYC/MAX/MAD network members and reciprocal changes in proliferation. In conclusion, the expression patterns of c-MYC, MAX and the MAD family were shown to be deregulated in the oesophageal cancer model

Synovial Inflammation Induced By a Local Allergic Reaction

A rat model has been developed to examine the possible role of homocytotropic antibodies in initiating or exacerbating synovial inflammation. The technique, passive synovial anaphylaxis, involves passively sensitizing rat knee joints with specific IgE, then challenging intravenously with the corresponding antigen while monitoring for signs of inflammation. Swelling of the sensitized joints reached maximum 2 h after the challenge, then gradually decreased to prechallenge levels by 24 h. Radioisotopic joint scans detected a passive synovial anaphylaxis induced increase in local blood flow and exudation within the joints. The degree of swelling correlated directly with the amount of antigen specific IgE in the sensitizing serum, and individual joints remained sensitized for up to 36 days after the IgE injection