BACKGROUND: Cancer of the oesophagus has so far eluded every attempt at pharmacological treatment. The recent advent of somatic gene therapy offers a new therapeutic approach to malignant tumours. AIM: To investigate whether and how gene transfer into the oesophagus can be achieved. METHODS: A LacZ reporter gene was used as marker and transferred into the oesophagus of rats using cationic liposomes. Gene transfer was achieved by either luminal instillation into a closed segment using a double balloon catheter, or by intramural injection through a needle. Expression of beta-galactosidase was monitored in the oesophagus and various control tissues by histochemistry, polymerase chain reaction (PCR), reverse transcriptase PCR, and Southern blotting. RESULTS: Up to 100 days after in vivo gene transfer beta-galactosidase activity could be demonstrated in the oesophagus. Following luminal application, the transgene was expressed in epithelial cells whereas intramural injection induced preferential expression in fibroblasts. CONCLUSION: In vivo gene transfer into the esophagus is feasible and safe, and the route of administration largely determines cell type specificity. This novel approach will enable in vivo studies of growth, differentiation, and malignant transformation in the oesophagus, and may open new avenues to the confinement of oesophageal malignancies.
BACKGROUND: Cancer of the oesophagus has so far eluded every attempt at pharmacological treatment. The recent advent of somatic gene therapy offers a new therapeutic approach to malignant tumours. AIM: To investigate whether and how gene transfer into the oesophagus can be achieved. METHODS: A LacZ reporter gene was used as marker and transferred into the oesophagus of rats using cationic liposomes. Gene transfer was achieved by either luminal instillation into a closed segment using a double balloon catheter, or by intramural injection through a needle. Expression of beta-galactosidase was monitored in the oesophagus and various control tissues by histochemistry, polymerase chain reaction (PCR), reverse transcriptase PCR, and Southern blotting. RESULTS: Up to 100 days after in vivo gene transfer beta-galactosidase activity could be demonstrated in the oesophagus. Following luminal application, the transgene was expressed in epithelial cells whereas intramural injection induced preferential expression in fibroblasts. CONCLUSION: In vivo gene transfer into the esophagus is feasible and safe, and the route of administration largely determines cell type specificity. This novel approach will enable in vivo studies of growth, differentiation, and malignant transformation in the oesophagus, and may open new avenues to the confinement of oesophageal malignancies.
Authors: P L Felgner; T R Gadek; M Holm; R Roman; H W Chan; M Wenz; J P Northrop; G M Ringold; M Danielsen Journal: Proc Natl Acad Sci U S A Date: 1987-11 Impact factor: 11.205
Authors: J M Wilson; D M Jefferson; J R Chowdhury; P M Novikoff; D E Johnston; R C Mulligan Journal: Proc Natl Acad Sci U S A Date: 1988-05 Impact factor: 11.205
Authors: Pouyan E Boukany; Andrew Morss; Wei-Ching Liao; Brian Henslee; Hyunchul Jung; Xulang Zhang; Bo Yu; Xinmei Wang; Yun Wu; Lei Li; Keliang Gao; Xin Hu; Xi Zhao; O Hemminger; Wu Lu; Gregory P Lafyatis; L James Lee Journal: Nat Nanotechnol Date: 2011-10-16 Impact factor: 39.213
Authors: Xiaoyun Ding; Martin Stewart; Armon Sharei; James C Weaver; Robert S Langer; Klavs F Jensen Journal: Nat Biomed Eng Date: 2017-03-09 Impact factor: 25.671