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01-05-2007 | Research Paper

Establishment of a novel orthotopic xenograft model of human gallbladder carcinoma

Authors: Jan-Hendrik Egberts, Bodo Schniewind, Clemens Schafmayer, Marie-Luise Kruse, Bence Sipos, Fred Fändrich, Holger Kalthoff, Jürgen Tepel

Published in: Clinical & Experimental Metastasis | Issue 3/2007

Abstract

Objective

Gallbladder cancer is characterized by high morbidity and mortality. An appropriate human xenograft animal model could serve as a research tool to investigate new therapeutic strategies.

Summary background data

To date, the few reports describing a xenograft animal model showed significant limitations. We improved a murine orthotopic human xenotransplantation model by implanting human gallbladder carcinoma cells directly into the lumen of the gallbladder.

Methods

Mz-ChA-1 cells were orthotopically injected into the gallbladder of Severe Combined Immune Deficiency (SCID) beige mice inducing the growth of solid tumors. The natural course of the disease, tumor growth, and metastases were analyzed. The cytotoxic drug gemcitabine was tested in vitro and in vitro.

Results

All animals revealed solid tumors in the inoculated area with liver infiltration. The median tumor volume in the untreated group was significantly higher than in the gemcitabine-treated group. Immunohistochemical staining revealed expression of human cytokeratin 7 and cytokeratin 8. To analyze tumor cell proliferation, the tumors were stained for the antigen Ki-67, and labeling indices were calculated for both groups. Animals receiving gemcitabine treatment showed significantly lower mean labeling indices. In vitro investigation revealed a significant reduction of DNA synthesis. DNA fragmentation, as a measure of apoptosis, was elevated by roughly 20% within 24 h of treatment. With this, we successfully established an orthotopic xenotransplant animal model and investigated the in vitro and in vivo effects of gemcitabine in human xenografted Mz-ChA-1 gallbladder adenocarcinoma.

Conclusion

This model resembles the clinical situation as closely as possible and offers a relevant option for the preclinical testing of new therapeutic strategies.

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Title: Establishment of a novel orthotopic xenograft model of human gallbladder carcinoma
Authors: Jan-Hendrik Egberts
Bodo Schniewind
Clemens Schafmayer
Marie-Luise Kruse
Bence Sipos
Fred Fändrich
Holger Kalthoff
Jürgen Tepel
Publication date: 01-05-2007
Publisher: Kluwer Academic Publishers
Published in: Clinical & Experimental Metastasis / Issue 3/2007
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-007-9058-x

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Abstract

Objective

Summary background data

Methods

Results

Conclusion

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