Purpose: Malignant gliomas are the most aggressive human brain tumors without any curative treatment. The antitumor effect of tumor necrosis factor^related apoptosis-inducing ligand (TRAIL) in gliomas has thus far only been thoroughly established in tumor cell lines. In the present study, we investigated the therapeutic potential of TRAIL in primary human glioma cells. Experimental Design: We isolated primary tumor cells from 13 astrocytoma and oligoastrocytoma patients of all four WHO grades of malignancy and compared the levels of TRAIL-induced apoptosis induction, long-term tumor cell survival, caspase, and caspase target cleavage. Results: We established a stable culture model for isolated primary human glioma cells. In contrast to cell lines, isolated primary tumor cells from all investigated glioma patients were highly TRAIL resistant. Regardless of the tumor heterogeneity, cotreatment with the proteasome inhibitor bortezomib efficiently sensitized all primary glioma samples forTRAIL-induced apoptosis and tremendously reduced their clonogenic survival. Due to the pleiotropic effect of bortezomib enhanced TRAIL DISC formation upon TRAIL triggering, down-regulation of cFLIP L and activation of the intrinsic apoptosis pathway seem to cooperatively contribute to the antitumor effect of bortezomib/TRAIL cotreatment. Conclusion: TRAIL sensitivity of tumor cell lines is not a reliable predictor for the behavior of primary tumor cells. The widespread TRAIL resistance in primary glioma cells described here questions the therapeutic clinical benefit of TRAIL as a monotherapeutic agent. Overcoming TRAIL resistance by bortezomib cotreatment might, however, provide a powerful therapeutic option for glioma patients.

The general principles of memory apply and have implications in states of emotional arousal. Whereas education and age, unlike in previous reports, did not appear to influence recall, thus indicating that we had succeeded in tailoring IC to the individual, recall rate was low in most cases. Physicians should highlight the discrepancy and conflict between the requirements for the defence of medical practice in the law courts and the actual interests of patients. They should promote research to establish what really is 'appropriately informed consent'.

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Comprehensive evaluation after meningioma surgery is required to prevent poor long-term results after apparently successful surgery. In our study, tests and structured interviews revealed different aspects, especially concerning patient age. Because demographic variables clearly influenced satisfaction with life, evaluation of quality of life must account for these factors to improve comparison of different studies. However, prospective studies with larger cohorts and control groups are required to prove our hypotheses.