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Journal of Translational Medicine

, 6:77

First Online: 03 December 2008Received: 31 October 2008Accepted: 03 December 2008DOI: 10.1186-1479-5876-6-77

Cite this article as: Xie, Q., Thompson, R., Hardy, K. et al. J Transl Med 2008 6: 77. doi:10.1186-1479-5876-6-77

Abstract

Animal models greatly facilitate understanding of cancer and importantly, serve pre-clinically for evaluating potential anti-cancer therapies. We developed an invasive orthotopic human glioblastoma multiforme GBM mouse model that enables real-time tumor ultrasound imaging and pre-clinical evaluation of anti-neoplastic drugs such as 17-allylamino-17-demethoxy geldanamycin 17AAG. Clinically, GBM metastasis rarely happen, but unexpectedly most human GBM tumor cell lines intrinsically possess metastatic potential. We used an experimental lung metastasis assay ELM to enrich for metastatic cells and three of four commonly used GBM lines were highly metastatic after repeated ELM selection M2. These GBM-M2 lines grew more aggressively orthotopically and all showed dramatic multifold increases in IL6, IL8, MCP-1 and GM-CSF expression, cytokines and factors that are associated with GBM and poor prognosis. DBM2 cells, which were derived from the DBTRG-05MG cell line were used to test the efficacy of 17AAG for treatment of intracranial tumors. The DMB2 orthotopic xenografts form highly invasive tumors with areas of central necrosis, vascular hyperplasia and intracranial dissemination. In addition, the orthotopic tumors caused osteolysis and the skull opening correlated to the tumor size, permitting the use of real-time ultrasound imaging to evaluate antitumor drug activity. We show that 17AAG significantly inhibits DBM2 tumor growth with significant drug responses in subcutaneous, lung and orthotopic tumor locations. This model has multiple unique features for investigating the pathobiology of intracranial tumor growth and for monitoring systemic and intracranial responses to antitumor agents.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-6-77 contains supplementary material, which is available to authorized users.

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Autor: Qian Xie - Ryan Thompson - Kim Hardy - Lisa DeCamp - Bree Berghuis - Robert Sigler - Beatrice Knudsen - Sandra Cottingham

Fuente: https://link.springer.com/



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