Telomerase activity of the Lugol-stained and -unstained squamous epithelia in the process of oesophageal carcinogenesis

Up-regulation of telomerase has been reported in many cancers. Our aim was to characterize telomerase activity in various states of the oesophagus to facilitate better understanding of carcinogenesis of oesophageal squamous cell carcinoma. During endoscopic examinations, we obtained 45 Lugol-stained normal epithelia, 31 Lugol-unstained epithelia (14 oesophagitis, 7 mild dysplasia, 5 severe dysplasia and 5 intramucosal cancer) and 9 advanced cancer. Telomerase activity was semi-quantified by a telomeric repeat amplification protocol using enzyme-linked immunosorbent assay, and expression of human telomerase reverse transcriptase mRNA was examined by in situ hybridization. In the Lugol-stained normal epithelia, telomerase activity increased in proportion to the increase of severity of the accompanying lesions, with a rank order of advanced cancer, intramucosal cancer, mild dysplasia and oesophagitis. In the Lugol-unstained lesions and advanced cancer, telomerase activity was highest in advanced cancer. Up-regulation of telomerase in normal squamous epithelium may be a marker of progression of oesophageal squamous cell carcinoma. Copyright 2001 Cancer Research Campaign © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Retargeting of a T cell line by anti Mage-3/HLA-A2 alpha beta TCR gene transfer

Background: The T cell receptor (TCR) is art heterodimeric protein on the cell membrane of cytotoxic T cells (CTLs). In CTLs TCRs mediate the recognition of target cells through interaction with specific, MHC class I presented peptides. Materials and Methods: As a model system to show proof of principle we chose the Jurkat/MA cell line and the HLA-A2.1 binding MAGE-3 derived peptide 271-279, as target specificity. Results: We show that this cell line can be successfully transduced with the dicistronic retroviral vector (LZRS) containing cDNAs encoding for the complete alpha and beta chains of the selected TCR. Following retroviral transduction, Jurkat/MA cells do express the anti-MAGE-3 TCR on their membrane. The transduced TCR is functional as travoductants are successfully triggered, upon stimulation with T2 cells or MAGE-3+ melanoma cells loaded with the MAGE-3 peptide. Conclusion: We conclude that TCR gene transfer is possible and it represents a powerful therapeutic tool for the genetical modification of T calls of patients sullering from cancer