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  • PMID: 24343111 was deleted because it is a duplicate of PMID: 24366975
Neuro Oncol. 2014 Jan;16(1):72-80. doi: 10.1093/neuonc/not238.

Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies.

Abstract

BACKGROUND:

Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies.

METHODS:

In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor.

RESULTS:

All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and post treatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors.

CONCLUSIONS:

Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.

PMID:
24366975
PMCID:
PMC3870831
DOI:
10.1093/neuonc/not238
[Indexed for MEDLINE]

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