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An orthotopic nude mouse model for preclinical research of gastric cardia cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

A clinically relevant animal model for cancer of the esophagogastric junction does not exist. This study aimed to establish an orthotopic mouse model for human gastric cancer of the distal stomach and the gastric cardia.

Materials and methods

Human gastric cancer cell lines AGS, MKN-45, and NCI-N87 were injected subcutaneously into nude mice. These donor tumors were harvested after 4 weeks and minced into small tumor fragments. One donor tumor fragment was orthotopically implanted into the submucosa of either gastric cardia or distal stomach in other mice. The animals were killed 4, 8, and 12 weeks after tumor implantation. Volume of the primary tumor and local and systemic tumor spread were determined.

Results

The implantation technique resulted in a tumor take rate of 100%. An artificial dissemination of tumor cells into the abdominal cavity due to the procedure was not observed.

Conclusions

We report for the first time the development of a clinically relevant mouse model for human gastric cancer of the gastric cardia and the distal stomach. Primary tumor growth and local and systemic spread progressed continuously during the observation period and mimic the human situation of this disease. This model may be suitable to evaluate novel treatment strategies for this malignancy.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66

    Article  PubMed  Google Scholar 

  2. Forman D, Burley VJ (2006) Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Pract Res Clin Gastroenterol 20:633–649

    Article  PubMed  CAS  Google Scholar 

  3. Li H, Yao SC (1997) Surgical treatment for carcinomas of the oesophagus in Chinese language publications. Br J Surg 84:855–857

    Article  PubMed  CAS  Google Scholar 

  4. Stein HJ, von Rahden BH, Hofler H, Siewert JR (2003) Karzinom des osophagogastralen Ubergangs und Barrett-Osophagus. Ein nahezu klares onkologisches Modell? Chirurg 74:703–708

    Article  PubMed  CAS  Google Scholar 

  5. Freedman ND, Abnet CC, Leitzmann MF, Mouw T, Subar AF, Hollenbeck AR, Schatzkin A (2007) A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol 165:1424–1433

    Article  PubMed  Google Scholar 

  6. Pera M (2003) Trends in incidence and prevalence of specialized intestinal metaplasia, Barrett’s esophagus, and adenocarcinoma of the gastroesophageal junction. World J Surg 27:999–1008

    Article  PubMed  Google Scholar 

  7. Tajima Y, Yamazaki K, Makino R, Nishino N, Masuda Y, Aoki S, Kato M, Morohara K, Kusano M (2007) Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach. Br J Cancer 96:631–638

    Article  PubMed  CAS  Google Scholar 

  8. Böttcher KEM, Stein HJ, Roder JD, Siewert JR (1999) Chirurgische Therapie bei Karzinomen des proximalen Magendrittels und des ösophagogastralen Übergangs. Chir Gastroenterol 15:237–243

    Article  Google Scholar 

  9. Siewert JRHAH, Becker K, Gössner W (1987) Cardia cancer: attempt at a therapeutically relevant classification. Chirurg 58:25–32

    PubMed  CAS  Google Scholar 

  10. von Rahden BH, Feith M, Stein HJ (2005) Carcinoma of the cardia: classification as esophageal or gastric cancer? Int J Colorectal Dis 20:89–93

    Article  Google Scholar 

  11. Ichikura T, Chochi K, Sugasawa H, Mochizuki H (2007) Proposal for a new definition of true cardia carcinoma. J Surg Oncol 95:561–566

    Article  PubMed  Google Scholar 

  12. Verdecchia ACI, Gatta G, Lisi D, Faivre J, Forman D, EUROCARE Working Group (2004) Explaining gastric cancer survival differences among European countries. Int J Cancer 109:737–741

    Article  PubMed  CAS  Google Scholar 

  13. Kim DY, Joo JK, Ryu SY, Park YK, Kim YJ, Kim SK (2006) Clinicopathological characteristics and prognosis of carcinoma of the gastric cardia. Dig Surg 23:313–318

    Article  PubMed  Google Scholar 

  14. Saito H, Fukumoto Y, Osaki T, Fukuda K, Tatebe S, Tsujitani S, Ikeguchi M (2006) Distinct recurrence pattern and outcome of adenocarcinoma of the gastric cardia in comparison with carcinoma of other regions of the stomach. World J Surg 30:1864–1869

    Article  PubMed  Google Scholar 

  15. Sutter AP, Zeitz M, Scherubl H (2004) Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer. Onkologie 27:17–21 (see comment)

    Article  PubMed  CAS  Google Scholar 

  16. Kretzschmar A, Schlag PM (2006) Efficacy of current adjuvant and neoadjuvant therapeutic concepts in gastric cancer? Zentralbl Chir 131:121–125

    Article  PubMed  CAS  Google Scholar 

  17. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJH, Nicolson M, carffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20

    Article  PubMed  CAS  Google Scholar 

  18. Furukawa T, Fu X, Kubota T, Watanabe M, Kitajima M, Hoffman RM (1993) Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue. Cancer Res 53:1204–1208

    PubMed  CAS  Google Scholar 

  19. Hotz HG, Reber HA, Hotz B, Yu T, Foitzik T, Buhr HJ, Cortina G, Hines OJ (2003) An orthotopic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer. Pancreas 26:e89–e98

    Article  PubMed  Google Scholar 

  20. McColl KE (2006) Cancer of the gastric cardia. Best Pract Res Clin Gastroenterol 20:687–696

    Article  PubMed  CAS  Google Scholar 

  21. Cronin-Fenton DP, Sharp L, Carsin AE, Comber H (2007) Patterns of care and effects on mortality for cancers of the oesophagus and gastric cardia: a population-based study. Eur J Cancer 43:565–575

    Article  PubMed  CAS  Google Scholar 

  22. Valverde CM, Macarulla T, Casado E, Ramos FJ, Martinelli E, Tabernero J (2006) Novel targets in gastric and esophageal cancer. Crit Rev Oncol /hematol 59:128–138

    Article  Google Scholar 

  23. Tabernero J, Macarulla T, Ramos FJ, Baselga J (2005) Novel targeted therapies in the treatment of gastric and esophageal cancer. Ann Oncol 16:1740–1748

    Article  PubMed  CAS  Google Scholar 

  24. Saikawa Y, Kubota T, Kuo TH, Tanino H, Kase S, Furukawa T, Watanabe M, Ishibiki K, Kitajima M, Hoffman RM (1994) Combined effect of 5-fluorouracil and carboplatin against human gastric cancer cell lines in vitro and in vivo. Anticancer Res 14:461–464

    PubMed  CAS  Google Scholar 

  25. Recchia F, Saggio G, Candeloro G, Cesta A, Amiconi G, Blasio AD, Necozione S, Rea S (2007) Chemoimmunotherapy in the treatment of metastatic gastric cancer. Anti-Cancer Drugs 18:597–604

    Article  PubMed  CAS  Google Scholar 

  26. Liang DM, Chen JY, Zhang Y, Gan P, Lin J, Chen AB (2006) Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice. World J Gastroenterol 12:3810–3813

    PubMed  CAS  Google Scholar 

  27. Fujimoto-Ouchi K, Sekiguchi F, Yasuno H, Moriya Y, Mori K, Tanaka Y (2007) Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models. Cancer Chemother Pharmacol 59:795–805

    Article  PubMed  CAS  Google Scholar 

  28. Koyama TTA, Nariai K, Mitsunaga M, Yanaga K, Takahashi H (2007) Novel biomedical imaging approach for detection of sentinel nodes in an experimental model of gastric cancer. Br J Surg 94:996–1001

    Article  PubMed  CAS  Google Scholar 

  29. Kerbel RS (2003) Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol Ther 2:S134–S139

    PubMed  CAS  Google Scholar 

  30. Onn A, Isobe T, Itasaka S, Wu W, O’Reilly MS, Ki Hong W, Fidler IJ, Herbst RS (2003) Development of an orthotopic model to study the biology and therapy of primary human lung cancer in nude mice. Clin Cancer Res 9:5532–5539

    PubMed  CAS  Google Scholar 

  31. Takahashi T, Morotomi M, Nomoto K (2004) A novel mouse model of rectal cancer established by orthotopic implantation of colon cancer cells. Cancer Sci 95:514–519

    Article  PubMed  CAS  Google Scholar 

  32. Hotz HG, Reber HA, Hotz B, Foitzik T, Buhr HJ, Cortina G, Hines OJ (2001) An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats. Pancreas 22:113–121

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Sonja Dullat, Marco Arndt, and Petra Schwartz for their technical support.

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Authors and Affiliations

  1. Department of Surgery, Charité School of Medicine Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany

    Sarah Bhargava, Birgit Hotz, Heinz J. Buhr & Hubert G. Hotz

Authors
  1. Sarah Bhargava
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  2. Birgit Hotz
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  3. Heinz J. Buhr
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  4. Hubert G. Hotz
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Corresponding author

Correspondence to Hubert G. Hotz.

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Bhargava, S., Hotz, B., Buhr, H.J. et al. An orthotopic nude mouse model for preclinical research of gastric cardia cancer. Int J Colorectal Dis 24, 31–39 (2009). https://doi.org/10.1007/s00384-008-0584-z

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  • DOI: https://doi.org/10.1007/s00384-008-0584-z

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