title: A distinct phenotypic change in gliomas at the time of magnetic resonance imaging detection.
abstract: OBJECTIVE
  Although gliomas remain refractory to treatment, it is not clear whether this characteristic is fixed at the time of its origin or develops later. The authors have been using a model of neurocarcinogenesis to determine whether a time exists during a glioma's evolution during which it is detectable but still curable, thus providing a justification for exploring the clinical merits of an early detection and treatment strategy. The authors recently reported the presence of 2 distinct cellular subsets, 1 expressing nestin and the other both glial fibrillary acidic protein (GFAP) and osteopontin (OPN), within all examined gliomas that developed after in utero exposure to ethylnitrosourea.
  
  
  METHODS
  In this study, the authors used magnetic resonance (MR) imaging to assess when these 2 subpopulations appeared during glioma evolution.
  
  
  RESULTS
  Using T2-weighted and diffusion-weighted MR imaging, the authors observed that gliomas grew exponentially once detected at rates that were location-dependent. Despite large differences in growth rates, however, they determined by correlating histochemistry with imaging in a second series of animals, that all lesions initially detected on T2-weighted images contained both subsets of cells. In contrast, lesions containing only nestin-positive cells, which appeared on average 40 days before detection on MR images, were not detected.
  
  
  CONCLUSIONS
  The sequential appearance of first the nestin-positive cells followed several weeks later by those expressing GFAP/OPN suggests that all gliomas arise through common early steps in this model. Furthermore, the authors hypothesize that the expression of OPN, a molecule associated with cancer aggressiveness, at the time of T2-weighted detection signals a time during glioma development when the lesion becomes refractory to treatment.
authors: Department of Neurology, Stanford University Medical School, Stanford, California 94305, USA.
authors: Taichang
authors: T
authors: Jang
authors: Binulal
authors: B
authors: Sathy
authors: Yi-Hua
authors: YH
authors: Hsu
authors: Milton
authors: M
authors: Merchant
authors: Benjamin
authors: B
authors: Recht
authors: Chen
authors: C
authors: Chang
authors: Lawrence
authors: L
authors: Recht
mesh_terms: D000477:Alkylating Agents; D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005038:Ethylnitrosourea; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D053495:Osteopontin / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000477:Alkylating Agents; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C506897:Spp1 protein, rat; D053495:Osteopontin; D005038:Ethylnitrosourea