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High yield reproducible rat model recapitulating human Barrett's carcinogenesis.

Publication ,  Journal Article
Matsui, D; Omstead, AN; Kosovec, JE; Komatsu, Y; Lloyd, EJ; Raphael, H; Kelly, RJ; Zaidi, AH; Jobe, BA
Published in: World journal of gastroenterology
September 2017

To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma (EAC) using the modified Levrat model of end-to-side esophagojejunostomy.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.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.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.

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Published In

World journal of gastroenterology

DOI

EISSN

2219-2840

ISSN

1007-9327

Publication Date

September 2017

Volume

23

Issue

33

Start / End Page

6077 / 6087

Related Subject Headings

  • Real-Time Polymerase Chain Reaction
  • Rats, Sprague-Dawley
  • Rats
  • Mucin-2
  • Male
  • Keratins
  • Keratin-19
  • Jejunum
  • Humans
  • Gastroesophageal Reflux
 

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Matsui, D., Omstead, A. N., Kosovec, J. E., Komatsu, Y., Lloyd, E. J., Raphael, H., … Jobe, B. A. (2017). High yield reproducible rat model recapitulating human Barrett's carcinogenesis. World Journal of Gastroenterology, 23(33), 6077–6087. https://doi.org/10.3748/wjg.v23.i33.6077
Matsui, Daisuke, Ashten N. Omstead, Juliann E. Kosovec, Yoshihiro Komatsu, Emily J. Lloyd, Hailey Raphael, Ronan J. Kelly, Ali H. Zaidi, and Blair A. Jobe. “High yield reproducible rat model recapitulating human Barrett's carcinogenesis.World Journal of Gastroenterology 23, no. 33 (September 2017): 6077–87. https://doi.org/10.3748/wjg.v23.i33.6077.
Matsui D, Omstead AN, Kosovec JE, Komatsu Y, Lloyd EJ, Raphael H, et al. High yield reproducible rat model recapitulating human Barrett's carcinogenesis. World journal of gastroenterology. 2017 Sep;23(33):6077–87.
Matsui, Daisuke, et al. “High yield reproducible rat model recapitulating human Barrett's carcinogenesis.World Journal of Gastroenterology, vol. 23, no. 33, Sept. 2017, pp. 6077–87. Epmc, doi:10.3748/wjg.v23.i33.6077.
Matsui D, Omstead AN, Kosovec JE, Komatsu Y, Lloyd EJ, Raphael H, Kelly RJ, Zaidi AH, Jobe BA. High yield reproducible rat model recapitulating human Barrett's carcinogenesis. World journal of gastroenterology. 2017 Sep;23(33):6077–6087.

Published In

World journal of gastroenterology

DOI

EISSN

2219-2840

ISSN

1007-9327

Publication Date

September 2017

Volume

23

Issue

33

Start / End Page

6077 / 6087

Related Subject Headings

  • Real-Time Polymerase Chain Reaction
  • Rats, Sprague-Dawley
  • Rats
  • Mucin-2
  • Male
  • Keratins
  • Keratin-19
  • Jejunum
  • Humans
  • Gastroesophageal Reflux