Article thumbnail

Characterization of a human tumorsphere glioma orthotopic model using magnetic resonance imaging

By Kelvin Wong, Geoffrey S. Young, Milan Makale, Xintao Hu, Nalan Yildirim, Kemi Cui, Stephen T. C. Wong and Santosh Kesari


Magnetic resonance imaging (MRI) is the imaging modality of choice by which to monitor patient gliomas and treatment effects, and has been applied to murine models of glioma. However, a major obstacle to the development of effective glioma therapeutics has been that widely used animal models of glioma have not accurately recapitulated the morphological heterogeneity and invasive nature of this very lethal human cancer. This deficiency is being alleviated somewhat as more representative models are being developed, but there is still a clear need for relevant yet practical models that are well-characterized in terms of their MRI features. Hence we sought to chronicle the MRI profile of a recently developed, comparatively straightforward human tumor stem cell (hTSC) derived glioma model in mice using conventional MRI methods. This model reproduces the salient features of gliomas in humans, including florid neoangiogenesis and aggressive invasion of normal brain. Accordingly, the variable, invasive morphology of hTSC gliomas visualized on MRI duplicated that seen in patients, and it differed considerably from the widely used U87 glioma model that does not invade normal brain. After several weeks of tumor growth the hTSC model exhibited an MRI contrast enhancing phenotype having variable intensity and an irregular shape, which mimicked the heterogeneous appearance observed with human glioma patients. The MRI findings reported here support the use of the hTSC glioma xenograft model combined with MRI, as a test platform for assessing candidate therapeutics for glioma, and for developing novel MR methods

Topics: Laboratory Investigation - Human/Animal Tissue
Publisher: Springer US
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1997). 104:473–481 123risk of anaplasia in magnetic resonance-nonenhancing supratentorial cerebral tumors.
  2. (2007). A
  3. (2009). Activation of tumor cell integrin alphavbeta3 controls angiogenesis and metastatic growth in the brain.
  4. (2005). Angiogenesis in gliomas: imaging and experimental therapeutics.
  5. (2001). Apparent diffusion coefficients in the evaluation of high-grade cerebral gliomas.
  6. (2008). Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence.
  7. (2007). Chakravarti A
  8. (2007). Choong PF
  9. (2008). Correlation of F-18-fluoro-ethyl-tyrosin uptake with vascular and cell density in non-contrastenhancing gliomas.
  10. (1998). Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas.
  11. (2005). Diagnostic imaging. Section 1B, Diagnosis. In: Berger MS, Prados MD (eds) Textbook of neuro-oncology.
  12. (2002). Dynamic contrast-enhanced magnetic resonance imaging as a surrogate marker of tumor response to antiangiogenic therapy in a xenograft model of glioblastoma multiforme.
  13. (2002). Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis.
  14. (2006). Genetically engineered models have advantages over xenografts for preclinical studies.
  15. (2008). Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas.
  16. (2008). Glioblastoma multiforme: an emerging paradigm of anti-VEGF therapy.
  17. (2003). Imaging glioblastoma multiforme.
  18. (2009). Imaging glioma cell invasion in vivo reveals mechanisms of dissemination and peritumoral angiogenesis.
  19. (2007). In vivo imaging in a murine model of glioblastoma.
  20. (2007). Magnetic resonance imaging determination of tumor grade, early response to temozolomide in a genetically engineered mouse model of glioma.
  21. (2000). Markoe A
  22. (1992). Measurement of blood–brain barrier permeability in a tumor model using magnetic resonance imaging with gadolinium-DTPA.
  23. (2002). MRI of mouse models for gliomas shows similarities to humans and can be used to identify mice for preclinical trials.
  24. (2006). Noninvasive bioluminescence imaging of luciferase expressing intracranial U87 xenografts: correlation with magnetic resonance imaging determined tumor volume and longitudinal use in assessing tumor growth and antiangiogenic treatment effect.
  25. (2007). Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma.
  26. (2008). Paradoxical imaging findings in cerebral gliomas.
  27. (2004). Perfusion MRI of U87 brain tumors in a mouse model.
  28. Peschke P et al (2007) Transcriptional network governing the angiogenic switch in human pancreatic cancer.
  29. (2000). Quantitative measurement of microvascular permeability in human brain tumors achieved using dynamic contrast-enhanced MR imaging: correlation with histologic grade.
  30. (2008). The role of regulatory T cells in malignant glioma.
  31. (1998). The significance of lack of MR contrast enhancement of supratentorial brain tumors in adults: histopathological evaluation of a series.
  32. (2006). Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.
  33. (2000). Vascular apoptosis and involution in gliomas precede neovascularization: a novel concept for glioma growth and angiogenesis.