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Cited by 326

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Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme

Open access
Giannini, Caterina, Sarkaria, Jann N., Saito, Atsushi, Uhm, Joon H., Galanis, Evanthia, Carlson, Brett L., Schroeder, Mark A., James, C. David·2005·Neuro-Oncology

Abstract

We have previously described a panel of serially transplantable glioblastoma multiforme xenograft lines established by direct subcutaneous injection of patient tumor tissue in the flanks of nude mice. Here we report the characterization of four of these lines with respect to their histopathologic, genetic, and growth properties following heterotopic-to-orthotopic (flank-to-intracranial) transfer. Cells from short-term cultures, established from excised flank xenografts, were harvested and injected into the brains of nude mice (10(6) cells per injection). The intracranial tumors generated from these injections were all highly mitotic as well as highly invasive, but they lacked necrotic features in most instances and failed to show endothelial cell proliferation in all instances. For mice receiving injections from a common explant culture, tumor intracranial growth rate was consistent, as indicated by relatively narrow ranges in survival time. In contrast to the loss of epidermal growth factor receptor gene (EGFR) amplification in cell culture, high-level amplification and overexpression of EGFR were retained in intracranial tumors established from two EGFR-amplified flank tumors. A third intracranial tumor retained patient tumor amplification and high-level expression of platelet-derived growth factor receptor alpha gene. Because the heterotopic-to-orthotopic transfer and propagation of glioblastoma multiforme preserves the receptor tyrosine kinase (RTK) gene amplification of patient tumors, this approach should facilitate investigations for determining the extent to which RTK amplification status influences tumor response to RTK-directed therapies. The fact that such studies were carried out by using an invasive tumor model in an anatomically appropriate context should ensure a rigorous preclinical assessment of agent efficacy.

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Metadata

Authors
Giannini, C., Sarkaria, J. N., Saito, A., Uhm, J. H., Galanis, E., Carlson, B. L., Schroeder, M. A., & James, C. D.
Venue
Neuro-Oncology
Published
2005-04-01
Volume
7
Issue
2
Pages
164-176
ISSN
  • 1522-8517 (ISSN-L)
  • 1523-5866
OpenAlex
W2048043668
Cited by
326
References
25
FWCI
6.40
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. https://app.cochat.ai/papers/10.1215/s1152851704000821
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Giannini, C., Sarkaria, J. N., Saito, A., Uhm, J. H., Galanis, E., Carlson, B. L., Schroeder, M. A., & James, C. D. (2005). Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro-Oncology. https://doi.org/10.1215/s1152851704000821

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