Subject(s)
Gastrointestinal Stromal Tumors/diagnosis , Thoracic Neoplasms/diagnosis , Antineoplastic Agents/therapeutic use , Benzamides , Chemotherapy, Adjuvant , DNA Mutational Analysis , Female , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/surgery , Humans , Imatinib Mesylate , Immunohistochemistry , Middle Aged , Neoplasm Recurrence, Local , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Reoperation , Thoracic Neoplasms/genetics , Thoracic Neoplasms/surgery , Thoracotomy , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
BACKGROUND: Lung ischemia-reperfusion injury remains a significant problem after lung transplantation. Caspase-mediated apoptotic pathways play an important role in lung ischemia-reperfusion injury, and caspase-3 is presumed to be the "effector" protease in the apoptotic cascade. Silencing gene expression of caspase-3 by short hairpin RNA (shRNA) can downregulate the caspase cascade. Therefore, we evaluated the therapeutic efficacy of caspase-3 shRNA in a rat model of lung ischemia-reperfusion injury. METHODS: Lung ischemia-reperfusion injury was induced in rats by clamping the hilum of the left lung for 1 hour. In vivo delivery of caspase-3 shRNA was performed by intratracheal administration 48 hours before ischemia. As controls, animals received either scrambled shRNA or RNase-free 5% dextrose in water solution. Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to assess the gene silencing efficacy. The therapeutic effects of shRNA were evaluated by lung function analysis and the ratio of wet/dry weight. RESULTS: In this study, we have shown that ischemia-reperfusion injury is associated with an increased level of lung caspase-3 messenger RNA. Animals treated with caspase-3 shRNA showed a significant downregulation in lung expression of caspase-3 at transcripts and protein levels. Lung function was protected by caspase-3 shRNA therapy, inasmuch as levels of partial pressure of oxygen and carbon dioxide were significantly increased and reduced, respectively. CONCLUSIONS: In summary, we have demonstrated the therapeutic potential of shRNA to knock down the expression of caspase-3 and prevent lung apoptotic injury. Our findings may have some potential therapeutic relevance for treating lung ischemia-reperfusion injury after transplantation.
Subject(s)
Caspase 3/genetics , Gene Silencing , Inverted Repeat Sequences , Lung/blood supply , RNA , Reperfusion Injury/genetics , Reperfusion Injury/prevention & control , Animals , Male , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To summarize the experience of diagnosis and treatment of esophageal leiomyoma. METHODS: Clinical data of 52 patients with esophageal leiomyoma were analyzed from 1993 to 2002. RESULTS: About 54% patients in this group had difficulty of food intake. The diagnostic accuracy of gastrointestinal barium meal series, computed tomography, gastric endoscope and endoscopic ultrasonography (EUS) for esophageal leiomyoma was 64% 44% 27% and 90% respectively. All patients received operation, resection of esophageal leiomyoma by videothoracoscopy (VAS) and endoscope were performed in 6, 9 patients respectively. The remaining 37 patients received regular open operation,in whom 32 cases received enucleation of esophageal leiomyoma, 5 cases received partial esophageal resection and esophageal-gastric anastomosis. No serious complications occurred except only one case needed operation again because of bleeding. CONCLUSION: EUS is an effective method for diagnosing esophageal leiomyoma. VAS and endoscopic treatment should be considered for suitable cases in order to reduce the trauma.
