High yield reproducible rat model recapitulating human Barrett’s carcinogenesis

Autor: Hailey Raphael, Ashten N. Omstead, Blair A. Jobe, Juliann E. Kosovec, Yoshihiro Komatsu, Emily J. Lloyd, Daisuke Matsui, Ali H. Zaidi, Ronan J. Kelly
Rok vydání: 2017
Předmět:
Male
Esophageal Neoplasms
Carcinogenesis
Gastroesophageal reflux disease
Gastroenterology
Rats
Sprague-Dawley
0302 clinical medicine
Medicine
Experimental rat model
Stomach
Anastomosis
Surgical
Respiratory infection
General Medicine
Basic Study
Jejunum
medicine.anatomical_structure
Mucin genes
030220 oncology & carcinogenesis
Disease Progression
Gastroesophageal Reflux
Keratins
030211 gastroenterology & hepatology
Esophageal adenocarcinoma
medicine.medical_specialty
Perforation (oil well)
Adenocarcinoma
Real-Time Polymerase Chain Reaction
Barrett Esophagus
03 medical and health sciences
Esophagus
Internal medicine
Biomarkers
Tumor
Animals
Humans
Levrat
Keratin-19
Mucin-2
business.industry
medicine.disease
Small intestine
Rats
Disease Models
Animal
Dysplasia
Cytokeratins
Histopathology
business
Esophagitis
Esophagojejunostomy
Zdroj: World Journal of Gastroenterology
ISSN: 1007-9327
DOI: 10.3748/wjg.v23.i33.6077
Popis: Aim To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma (EAC) using the modified Levrat model of end-to-side esophagojejunostomy. Methods End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10 (n = 6), 17 (n = 8), 24 (n = 9), 31 (n = 6), 38 (n = 6), and 40 (n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation was completed to determine respective rates of carcinogenic development. Quantitative reverse transcription-polymerase chain reaction was performed to determine gene expression levels of MUC2, CK19, and CK20, and results were compared to determine significant differences throughout disease progression stages. Results The overall study mortality was 15%. Causes of mortality included anastomotic leak, gastrointestinal hemorrhage, stomach ulcer perforation, respiratory infection secondary to aspiration, and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery, 100% of animals presented with esophagitis. Barrett's esophagus (BE) was first observed at 10 wk, and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk, and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition, two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine, respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. Conclusion Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden, which may facilitate broader adoption to study EAC development, progression, and therapeutics.
Databáze: OpenAIRE
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