Establishment and characterization of a novel xenograft model of human gastrointestinal stromal tumor in mice.

Abstract

BACKGROUND:

The clinical outcome of gastrointestinal stromal tumor (GIST) has been improved by the introduction of molecular-targeting drugs. However, resistance to these drugs appears during the course of treatment. The aim of this study was to establish and characterize a human xenograft model of GIST.

MATERIALS AND METHODS:

GIST tissue from a patient with esophageal GIST was implanted under the skin of a NOD-SCID mouse. The tumor became successfully engrafted and we investigated the effects of imatinib and sunitinib on this model. KIT mutation was investigated by complementary DNA analysis, and c-KIT (CD117) expression was evaluated by immunohistological staining.

RESULTS:

cDNA analysis of the tumor revealed a KIT mutation in exon 11. c-KIT expression was observed in each passaged tumor. Both imatinib and sunitinib significantly reduced the size of the xenograft tumor.

CONCLUSION:

We established a novel xenograft model of human GIST in mice. This xenograft model may be useful for studying GIST.

• Authors: Makoto Moriyama, Yutaka Shimada, Takuya Nagata, Tetsuya Omura, Shinichi Sekine, Koshi Matsui, Isaku Yoshioka, Tomoyuki Okumura, Shigeaki Sawada, Toru Yoshida, Kazuhiro Tsukada
• Journal: Anticancer research (Anticancer Res) Vol. 33 Issue 1 Pg. 175-81 (Jan 2013) ISSN: 1791-7530 [Electronic] Greece
• PMID: 23267143 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Indoles
• Piperazines
• Pyrimidines
• Pyrroles
• Imatinib Mesylate
• Proto-Oncogene Proteins c-kit
• Sunitinib

Topics

• Aged
• Animals
• Benzamides (therapeutic use)
• Disease Models, Animal
• Esophageal Neoplasms (drug therapy, genetics, pathology)
• Exons (genetics)
• Gastrointestinal Stromal Tumors (drug therapy, genetics, pathology, surgery)
• Gene Expression Regulation, Neoplastic
• Humans
• Imatinib Mesylate
• Indoles (therapeutic use)
• Male
• Mice
• Molecular Targeted Therapy
• Mutation
• Piperazines (therapeutic use)
• Proto-Oncogene Proteins c-kit (genetics, metabolism)
• Pyrimidines (therapeutic use)
• Pyrroles (therapeutic use)
• Sunitinib
• Transplantation, Heterologous