Purpose: The receptor tyrosine kinase Axl has recently been identified as a critical element in the invasive properties of glioma cell lines. However, the effect of Axl and its ligand growth arrestŝ pecific gene 6 (Gas6) in human gliomas is still unknown. Experimental Design: Axl and Gas6 expression was studied in 42 fresh-frozen and 79 paraffinembedded glioma specimens by means of reverse transcription-PCR and immunohistochemistry. The prognostic value of Axl and Gas6 expression was evaluated using a population-based tissue microarray derived from a cohort of 55 glioblastoma multiforme (GBM) patients.Results: Axl and Gas6 were detectable in gliomas of malignancy gradesWHO 2 to 4. Moderate to high Axl mRNA expression was found in 61%, Axl protein in 55%, Gas6 mRNA in 81%, and Gas6 proteinin 74% of GBMsamples, respectively. GBM patients withhigh Axl expression and Axl/Gas6 coexpression showed a significantly shorter time to tumor progression and an association with poorer overall survival. Comparative immunohistochemical studies showed that Axl staining was most pronounced in glioma cells of pseudopalisades and reactive astrocytes. Additionally, Axl/ Gas6 coexpression was observed in glioma cells and tumor vessels. In contrast, Axl staining was not detectable in nonneoplastic brain tissue and Gas6 was strongly expressed in neurons.Conclusions: In human gliomas, Axl and Gas6 are frequently overexpressed in both glioma and vascular cells and predict poor prognosis in GBM patients. Our results indicate that specific targeting of the Axl/Gas6 signaling pathway may represent a potential new approach for glioma treatment.
The objective of this study was to compare MRI response assessment with metabolic O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG). Methods: Eleven patients with rHGG were treated biweekly with bevacizumab-irinotecan. MR images and 18 F-FET PET scans were obtained at baseline and at follow-up 8-12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For 18 F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and 18 F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS). Results: At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, 18 F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and 18 F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P 5 0.025, and 7.9 vs. 2.3 mo, P 5 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and 18 F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI. Conclusion: In rHGG patients undergoing antiangiogenic treatment, 18 F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.
The software-generated graphic QOL profiles were found to be an important tool for screening patients for clinically relevant problems. Thus, computer-based QOL monitoring can contribute to an optimization of treatment (e.g., symptom management, psychosocial interventions) and facilitate data collection for research purposes.
In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.
There is neuropathologic evidence that, in early stages of the Parkinson variant of multiple system atrophy (MSA-P), the putamen shows a distinct topographical pathology affecting predominantly the dorsolateral and caudal regions while leaving the rostral to midparts almost intact. We investigated the topographic profile of putaminal degeneration in MSA-P patients in vivo by means of diffusion-weighted imaging (DWI), which has been shown to reveal abnormalities in the basal ganglia of patients with MSA-P compared to patients with PD and healthy controls. For this purpose, regional trace of the diffusion tensor (rTrace(D)) values were determined in the entire, anterior, and posterior putamen in 15 patients with probable MSA-P, in 20 patients with PD, and in 11 healthy volunteers matched for age and disease duration. MSA-P patients had significantly higher rTrace(D) values in entire, anterior, and posterior putamen compared to both controls and PD patients. Trace(D) values were significantly higher in the posterior compared to the anterior putamen in the MSA-P group. There were no significant differences between posterior and anterior putamen in both the control and PD group. Our study demonstrates prominent involvement of the posterior putamen in early disease stages of MSA-P in vivo by assessing putaminal diffusivity with the help of DWI.
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