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Background and Objectives: Esophageal cancer has one of the worst prognoses of all cancers, mainly due to its aggressive growth pattern and late presentation. Using radiotherapy, chemotherapy, or even surgery it is only possible to cure a small minority and so alternative strategies need to be evaluated. In this study we aim to investigate the feasibility of using liposomes to transfect genes into human esophageal biopsies at high enough levels to achieve a biological effect.Methods: Human esophageal biopsies were transfected with constructs encoding Green Fluorescent Protein or human wild type p53. Expression of Green Fluorescent Protein within these samples was determined by FACScan analysis and confocal microscopy, whereas p53 expression was assessed by Western blotting and Reverse Transcriptase Polymerase Chain Reaction, probing for p53 and a downstream effector WAF1/p21.Results: Confocal microscopy verified the expression of Green Fluorescent Protein in human esophageal biopsies in cells 7 to 10 layers deep. Green Fluorescent Protein expression has also been demonstrated by FACScan analysis. The successful introduction and expression of wild type p53 has been shown in normal esophageal biopsies by Western blotting and RT-PCR and in Barrett's esophageal biopsies by Western blotting alone. In addition, we have demonstrated an increase in the expression of WAF1/p21 in 50% of biopsies transfected with p53.Conclusion: Liposome-mediated transfer of genes into human esophageal cells is feasible and can be performed at a sufficient dose to achieve expression of downstream genes. [ABSTRACT FROM AUTHOR]

Haemopoietic tissues exposed to ionizing radiation are shown to exhibit increased macrophage activation, defined by ultrastructural characteristics and increased lysosomal and nitric oxide synthase enzyme activities. Macrophage activation post-irradiation was also associated with enhanced respiratory burst activities and an unexpected neutrophil infiltration. Examination of p53-null mice demonstrated that macrophage activation and neutrophil infiltration were not direct effects of irradiation, but were a consequence of the recognition and clearance of radiation-induced apoptotic cells. Increased phagocytic cell activity was maintained after apoptotic bodies had been removed. These findings demonstrate that, contrary to expectation, recognition and clearance of apoptotic cells after exposure to radiation produces both a persistent macrophage activation and an inflammatory-type response. We also demonstrate a complexity of macrophage activation following radiation that is genotype dependent, indicating that the in vivo macrophage responses to radiation damage are genetically modified processes. These short-term responses of macrophages to radiation-induced apoptosis and their genetic modification are likely to be important determinants of the longer-term consequences of radiation exposure. Furthermore, in addition to any effects attributable to immediate radiation-induced damage, our findings provide a mechanism for the production of damage via a 'bystander' effect which may contribute to radiation-induced genomic instability and leukaemogenesis.