Lymph node status as a prognostic indicator after preoperative neoadjuvant chemoradiotherapy of rectal cancer.

AIM: The primary aim of this study was to examine lymph node status after neoadjuvant chemoradiotherapy (CRT) using a novel scoring system describing the pathological lymph node regression grade. The proposed scoring system was based on the percentage of fibrosis and the presence of residual tumour amount. The secondary aim of the study was to assess the oncological impact of this scoring system. METHOD: The project was a retrospective cohort study over a 10-year period. Two hundred and two patients with rectal cancer who had received CRT followed by curative surgery were included. A histopathologist prospectively scored each specimen and the impact of the scoring system on survival and recurrence was analysed. RESULTS: One hundred and ninety patients completed long-course preoperative CRT and formed the basis of the study. Overall, 40 recurrences (local and distant) were observed over a median follow-up of 36 months. The lymph node regression score was a significant predictor of tumour recurrence (hazard ratio 1.273, 95% CI 1.048-1.548; P = 0.015). The overall mortality rate was 21%, and a lower lymph node regression score was correlated with an improved survival curve (P = 0.01). CONCLUSION: The results demonstrate that lymph node response to neoadjuvant CRT based on a nodal regression scoring system is related to recurrence.

Angiopoietin-2 inhibition prevents transplant ischemia-reperfusion injury and chronic rejection in rat cardiac allografts.

Transplant ischemia-reperfusion injury (Tx-IRI) and allograft dysfunction remain as two of the major clinical challenges after heart transplantation. We investigated the role of angiopoietin-2 (Ang2) in Tx-IRI and rejection using fully MHC-mismatched rat cardiac allografts. We report that plasma levels of Ang2 were significantly enhanced in the human and rat recipients of cardiac allografts, but not in the rat recipients of syngrafts, during IRI. Ex vivo intracoronary treatment of rat cardiac allografts with anti-Ang2 antibody before 4-h cold preservation prevented microvascular dysfunction, endothelial cell (EC) adhesion molecule expression and leukocyte infiltration, myocardial injury and the development of cardiac fibrosis and allograft vasculopathy. Recipient preoperative and postoperative treatment with anti-Ang2 antibody produced otherwise similar effects without effecting microvascular dysfunction, and in additional experiments prolonged allograft survival. Recipient preoperative treatment alone failed to produce these effects. Moreover, ex vivo intracoronary treatment of allografts with recombinant Ang2 enhanced Tx-IRI and, in an add-back experiment, abolished the beneficial effect of the antibody. We demonstrate that neutralization of Ang2 prevents EC activation, leukocyte infiltration, Tx-IRI and the development of chronic rejection in rat cardiac allografts. Our results suggest that blocking Ang2 pathway is a novel, clinically feasible, T cell-independent strategy to protect cardiac allografts.

Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila.

In both vertebrate and invertebrate development, cells are often programmed to adopt fates distinct from their neighbors. Genetic analyses in Drosophila melanogaster have highlighted the importance of cell surface and secreted proteins in these cell fate decisions. Homologues of these proteins have been identified and shown to play similar roles in vertebrate development. Fringe, a novel signalling protein, has been shown to induce wing margin formation in Drosophila. Fringe shares significant sequence homology and predicted secondary structure similarity with bacterial glycosyltransferases. Thus fringe may control wing development by altering glycosylation of cell surface and/or secreted molecules. Recently, two fringe genes were isolated from Xenopus laevis. We report here the cloning and characterization of three murine fringe genes (lunatic fringe, manic fringe and radical fringe). We find in several tissues that fringe expression boundaries coincide with Notch-dependent patterning centres and with Notch-ligand expression boundaries. Ectopic expression of murine manic fringe or radical fringe in Drosophila results in phenotypes that resemble those seen in Notch mutants.