ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of adenovirus-mediated endostatin gene transfer on transplanted lung cancer in mice and its mechanism of action.</p><p><b>METHODS</b>Transplant tumor model was induced by subcutaneous inoculation of 2 x 10(6) Lewis lung cancer (LLC) cells into the back of C57BL/6 mice. The mice were treated by intratumoral injection of 2 x 10(9) pfu Ad-mEndostatin. The expression of endostatin in situ and its maintaining time were detected by immunohistochemistry and Western Blot, respectively. The endostatin level in serum was determined by ELISA . The inhibition of tumor growth and changes of survival were recorded and the microvessel density (MVD) was determined by histochemical stainingwith CD31 and CD105 antibodies. The tumor apoptosis was observed by electron microscopy.</p><p><b>RESULTS</b>In comparison with controls, intratumoral injection of Ad-mEndostatin significantly inhibited the tumor growth and metastasis, and prolonged the survival rate of mice (P < 0.05). Strong positive expression of mEndostatin was seen in the tumor tissue after injection of Ad-mEndostatin, immunhistochemically ostained by mouse endostatin monoclonal antibody, while the control groups showed only very low expression or absence. Serum endostatin concentration was 1540 +/- 560 ng/ml at the second week of administration, the expression of endostatin diminished a month later. The microvessel density (MVD)) decreased from 42.4 +/- 4.8 to 10.5 +/- 3.2 per x 200 magnificetion microscopic field by CD10 staining and from 68.5 +/- 4.5 to 37.5 +/- 4.6 by CD31 staining, respectively (P < 0.05). More apoptotic tumor cells were seen under the transmission electron microscope.</p><p><b>CONCLUSION</b>Endostatin gene therapy mediated by adenoviral vector efficiently induces expression of endostatin in vivo, and inhibits the growth and metastasis of tumor. It is concluded that its action is targeted to tumor neovasculature and the mechanism is inhibition of tumor angiogenesis.</p>
Subject(s)
Animals , Male , Mice , Adenoviridae , Genetics , Angiogenesis Inhibitors , Genetics , Metabolism , Therapeutic Uses , Carcinoma, Lewis Lung , Metabolism , Pathology , Therapeutics , Cell Line, Tumor , Endostatins , Genetics , Metabolism , Therapeutic Uses , Genetic Therapy , Genetic Vectors , Mice, Inbred C57BL , Microvessels , Pathology , Neoplasm Transplantation , Neovascularization, Pathologic , Pathology , Random Allocation , Transfection , Tumor BurdenABSTRACT
Objective: To replace esophageal defects with artificially composed biodegradable materials and non-biodegradable materials. Met hods: A two-layered tube consisting of a collagen-chitosan sponge and an inner polyurethane stent was used to replace 5 cm esophageal segmental defect s in 15 dogs. The inner polyurethane stent was removed endoscopically at weekly intervals from 2 or 4 weeks. Results: Partial regeneration of es ophageal epithelia was observed in 5 dogs at week 2, and progressing constricti on occurred and the dogs became unable to swallow within 1 month. In the 10 dog s that the polyurethane stent was removed at week 4, regenerated esophageal tiss ue successfully replaced the defects, and complete epithelization was observed 1 month after surgery. Complete regeneration of esophageal mucosa structures, inc luding mucosal smooth muscle and mucosal glands were observed 3 months after surgery, and partial regeneration of esophageal muscle tissue was also observed 6 months after surgery. Conclusion: Our artificial prosthesis i n reconstruction of the cervical esophagus segment in dogs is feasible. Through temporary polyurethane tube, collagen-chitosan sponge provides a three-dimensi onal structure suitable for the regeneration and sufficient degradation time for the complete regeneration of esophagus.
ABSTRACT
Objective: To replace esophageal defects with artificially composed biodegradable materials and non-biodegradable materials. Met hods: A two-layered tube consisting of a collagen-chitosan sponge and an inner polyurethane stent was used to replace 5 cm esophageal segmental defect s in 15 dogs. The inner polyurethane stent was removed endoscopically at weekly intervals from 2 or 4 weeks. Results: Partial regeneration of es ophageal epithelia was observed in 5 dogs at week 2, and progressing constricti on occurred and the dogs became unable to swallow within 1 month. In the 10 dog s that the polyurethane stent was removed at week 4, regenerated esophageal tiss ue successfully replaced the defects, and complete epithelization was observed 1 month after surgery. Complete regeneration of esophageal mucosa structures, inc luding mucosal smooth muscle and mucosal glands were observed 3 months after surgery, and partial regeneration of esophageal muscle tissue was also observed 6 months after surgery. Conclusion: Our artificial prosthesis i n reconstruction of the cervical esophagus segment in dogs is feasible. Through temporary polyurethane tube, collagen-chitosan sponge provides a three-dimensi onal structure suitable for the regeneration and sufficient degradation time for the complete regeneration of esophagus.