Su1153 - Extending Myotomy Both Downwards and Upwards for Manometric Pattern III Achalasia Patients Improves the Final Outcome
2018; Elsevier BV; Volume: 154; Issue: 6 Linguagem: Inglês
10.1016/s0016-5085(18)34265-3
ISSN1528-0012
AutoresGiovanni Capovilla, Renato Salvador, Luca Provenzano, Guerrino Voltarel, Anna Perazzolo, Dario Briscolini, Loredana Nicoletti, Andrea Costantini, Stefano Merigliano, Mario Costantini,
Tópico(s)Gastrointestinal Tumor Research and Treatment
ResumoBackground: Glycogen synthase kinase 3b (GSK3b), a serine/threonine protein kinase, has emerged as a therapeutic target for common chronic diseases including inflammation, immunity and neurodegenerative disorders.GSK3 b was recognized as a putative suppressor of cellular neoplastic transformation and tumor development, but emerging evidence suggests that GSK3b promotes various cancers including brain tumors, pancreatic cancer and colon cancer.We evaluated the effectiveness of a GSK3 b inhibitor as a chemoprevention agent in a surgical rat reflux model of esophageal cancer.Materials and Methods: The rat reflux model was created by performing an end-to-side esophagojejunostomy in Sprague Dawley rats.The surgery promoted the reflux of gastro-duodenal contents into the esophagus.GSK3b inhibitor (AR-A014418, Calbiochem, San Diego, CA, USA) was dissolved in 200uL of DMSO.Beginning four weeks post surgery, all animals were administered either 5mg/kg body weight injections of GSK3 b inhibitor or equivalent injections of DMSO 3 days per week into the subcutaneous tissue of the back.Animals were sacrificed 40 weeks after surgery and their esophagi were examined.Results: Twenty two rats survived 40 weeks post-surgery and were included in the study.Of these, 12 were included in the control group (Figure 1a), and the remaining 10 received GSK3 b inhibitor administration (Figure 1b).58% (7/12) of the controls developed esophageal cancer (Figure 1c), but animals that received the GSK3b inhibitor did not develop cancer.(0/10) (p=0.005,Chi-squared) (Table 1).Barrett's metaplasia was found in 83% (10/12) of the rats in the control group (Figure 1d).However, only 30% (3/10) of the rats in the GSK3 b inhibitor group displayed signs of Barrett's metaplasia, indicating a significant protection of GSK3 b inhibitor (p=0.03,Chisquared).All of the rats in the GSK3 b inhibitor and control groups developed proliferative hyperplasia.Conclusions: GSK3b inhibitor protected against the development of esophageal cancer in a clinically relevant surgical reflux model.Further investigation is required regarding the potential clinical use of GSK3 b inhibitor as a chemopreventive agent.Histological findings Su1152
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