Geir Olav Hjortland, Solveig Suzanne Garman-Vik, Siri Juell, Øyvind Edon Olsen, Henry Hirschberg, Øystein Fodstad, and Olav Engebraaten
The aim of this study was to target immunotoxin treatment to the high-molecular-weight melanoma—associated antigen (HMW-MAA) and thereby examine any changes in the survival of immunodeficient rats with human glioblastoma multiforme (GBM).
To target treatment specifically to human glioma cells, Pseudomonas exotoxin A (PE) was conjugated to the 9.2.27 antibody, which recognizes the HMW-MAA. Treatment of the antigen-positive glioma cell line U87MG with the resulting 9.2.27—PE caused cytotoxicity with a median inhibitory concentration of 1 ng/ml. Intratumoral 9.2.27—PE treatment of intracranial U87MG tumors in nude rats prolonged the survival of these animals by 43% compared with controls. In additional studies on the use of this targeted treatment, the authors precultured freshly dissected glioblastoma multiforme (GBM) biopsy tissue for 1 to 2 weeks. Inoculation of this tissue into the rat brain resulted in diffuse infiltrative gliomas. The markers glial fibrillary acidic protein and S100 protein were found to be expressed in the original biopsy specimens, as well as in the glioma xenografts in nude rat brains. Intratumoral immunotoxin treatment of such established tumors with 9.2.27—PE was effective and prolonged survival time from 30% to as high as 90% in animals with tumors originating from four different GBM specimens.
Targeted treatment of highly invasive GBMs proved effective, and these results emphasize the clinical relevance of this antigen as a target molecule for immunotoxin treatment of human GBMs.
Hans Kristian Moe, Turid Follestad, Nada Andelic, Asta Kristine Håberg, Anne-Mari Holte Flusund, Kjell Arne Kvistad, Elin Hildrum Saksvoll, Øystein Olsen, Sebastian Abel-Grüner, Oddrun Sandrød, Toril Skandsen, Anne Vik, and Kent Gøran Moen
The aim in this study was to investigate if MRI findings of traumatic axonal injury (TAI) after traumatic brain injury (TBI) are related to the admission Glasgow Coma Scale (GCS) score and prolonged duration of posttraumatic amnesia (PTA).
A total of 490 patients with mild to severe TBI underwent brain MRI within 6 weeks of injury (mild TBI: median 2 days; moderate to severe TBI: median 8 days). The location of TAI lesions and measures of total TAI lesion burden (number and volume of lesions on FLAIR and diffusion-weighted imaging and number of lesions on T2*-weighted gradient echo or susceptibility-weighted imaging) were quantified in a blinded manner for clinical information. The volume of contusions on FLAIR was likewise recorded. Associations between GCS score and the location and burden of TAI lesions were examined with multiple linear regression, adjusted for age, Marshall CT score (which includes compression of basal cisterns, midline shift, and mass lesions), and alcohol intoxication. The predictive value of TAI lesion location and burden for duration of PTA > 28 days was analyzed with multiple logistic regression, adjusted for age and Marshall CT score. Complete-case analyses of patients with TAI were used for the regression analyses of GCS scores (n = 268) and PTA (n = 252).
TAI lesions were observed in 58% of patients: in 7% of mild, 69% of moderate, and 93% of severe TBI cases. The TAI lesion location associated with the lowest GCS scores were bilateral lesions in the brainstem (mean difference in GCS score −2.5), followed by lesions bilaterally in the thalamus, unilaterally in the brainstem, and lesions in the splenium. The volume of TAI on FLAIR was the measure of total lesion burden most strongly associated with the GCS score. Bilateral TAI lesions in the thalamus had the largest predictive value for PTA > 28 days (OR 16.2, 95% CI 3.9–87.4). Of the measures of total TAI lesion burden, the FLAIR volume of TAI predicted PTA > 28 days the best.
Bilateral TAI lesions in the brainstem and thalamus, as well as the total volume of TAI lesions on FLAIR, had the strongest association with the GCS score and prolonged PTA. The current study proposes a first step toward a modified classification of TAI, with grades ranked according to their relation to these two measures of clinical TBI severity.