Transforming growth factor-beta2 (TGF-beta2) is known to suppress the immune response to cancer cells and plays a pivotal role in tumor progression by regulating key mechanisms including proliferation, metastasis, and angiogenesis. For targeted protein suppression the TGF-beta2-specific antisense oligodeoxynucleotide AP 12009 was developed. In vitro experiments have been performed to prove specificity and efficacy of the TGF-beta2 inhibitor AP 12009 employing patient-derived malignant glioma cells as well as peripheral blood mononuclear cells (PBMCs) from patients. Clinically, the antisense compound AP 12009 was assessed in three Phase I/II-studies for the treatment of patients with recurrent or refractory malignant (high-grade) glioma WHO grade III or IV. Although the study was not primarily designed as an efficacy evaluation, prolonged survival compared to literature data and response data were observed, which are very rarely seen in this tumor indication. Two patients experienced long-lasting complete tumor remissions. These results implicate targeted TGF-beta2-suppression using AP 12009 as a promising novel approach for malignant gliomas and other highly aggressive, TGF-beta-2-overexpressing tumors.

Stereolithographic (SL) biomodeling is a new technology that allows three-dimensional (3D) imaging data to be used in the manufacture of accurate solid plastic replicas of anatomical structures. The authors describe their experience with a patient series in which this relatively new visualization method was used in surgery for cerebral aneurysms. Using the rapid prototyping technology of stereolithography, 13 solid anatomical biomodels of cerebral aneurysms with parent and surrounding vessels were manufactured based on 3D computerized tomography scans (three cases) or 3D rotational angiography (10 cases). The biomodels were used for diagnosis, operative planning, surgical simulation, instruction for less experienced neurosurgeons, and patient education. The correspondence between the biomodel and the intraoperative findings was verified in every case by comparison with the intraoperative video. The utility of the biomodels was judged by three experienced and two less experienced neurosurgeons specializing in microsurgery. A prospective comparison of SL biomodels with intraoperative findings proved that the biomodels replicated the anatomical structures precisely. Even the first models, which were rather rough, corresponded to the intraoperative findings. Advances in imaging resolution and postprocessing methods helped overcome the initial limitations of the image threshold. The major advantage of this technology is that the surgeon can closely study complex cerebrovascular anatomy from any perspective by using a haptic, "real reality" biomodel, which can be held, allowing simulation of intraoperative situations and anticipation of surgical challenges. One drawback of SL biomodeling is the time it takes for the model to be manufactured and delivered. Another is that the synthetic resin of the biomodel is too rigid to use in dissecting exercises. Further development and refinement of the method is necessary before the model can demonstrate a mural thrombus or calcification or the relationship of the aneurysm to nonvascular structures. This series of 3D SL biomodels demonstrates the feasibility and clinical utility of this new visualization medium for cerebrovascular surgery. This medium, which elicits the intuitive imagination of the surgeon, can be effectively added to conventional imaging techniques. Overcoming the present limitations posed by material properties, visualization of intramural particularities, and representation of the relationship of the lesion to parenchymal and skeletal structures are the focus in an ongoing trial.

Our results indicate a high sensitivity of FET PET for detecting high-grade glioma in patients with neurological symptoms and recently observed brain lesions by MRI. In the setting of evaluating new brain lesions of unknown significance via FET PET a negative image can encourage a wait and see strategy-of course in accordance with the clinical picture and morphological imaging.

Telomerase activation is not an independent prognostic parameter in GBM but predicts aggressive tumor behavior solely in a younger patient cohort.

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