Glioblastoma multiforme (GBM) is a highly lethal brain tumor for which little treatment is available. The epidermal growth factor receptor (EGFR) signaling pathway is thought to play a crucial role in GBM pathogenesis, initiating the early stages of tumor development, sustaining tumor growth, promoting infiltration, and mediating resistance to therapy. The importance of this pathway is highlighted in the fact that EGFR is mutationally activated in over 50% of GBM tumors. Consistent with this, we show here that concomitant activation of wild-type and/or mutant (vIII) EGFR and ablation of Ink4A/Arf and PTEN tumor suppressor gene function in the adult mouse central nervous system generates a fully penetrant, rapid-onset high-grade malignant glioma phenotype with prominent pathological and molecular resemblance to GBM in humans. Studies of the activation of signaling events in these GBM tumor cells revealed notable differences between wild-type and vIII EGFR-expressing cells. We show that wild-type EGF receptor signals through its canonical pathways, whereas tumors arising from expression of mutant EGFR vIII do not use these same pathways. Our findings provide critical insights into the role of mutant EGFR signaling function in GBM tumor biology and set the stage for testing of targeted therapeutic agents in the preclinical models described herein. glioblastoma ͉ mouse model ͉ receptor tyrosine kinase ͉ mTORC1/2 ͉ STAT3 G lioblastoma multiforme is the most common and lethal primary malignant cancer of the central nervous system (CNS). Despite multimodal therapies, the median survival of GBM patients is Ϸ1 year. The deadly nature of GBMs resides in their explosive growth characteristic, extreme invasive behavior, and intrinsic resistance to current therapies. Despite efforts to develop novel treatments, little improvement in overall survival or progression-free survival has been achieved in the past 5 decades, reflecting an unmet need in the treatment of this cancer (1). Personalized medicine based on targeting essential molecular mechanisms for GBM survival offers an alternative therapeutic strategy.Over the years, our knowledge of GBM biology has steadily improved. From a molecular standpoint, GBMs are a highly heterogeneous tumor with multiple signaling pathways differentially activated or silenced with converging and parallel complex interactions (2). It is these intricacies that are thought to confer GBM with its notorious plasticity in response to therapeutic interventions. Therefore, a major challenge in the clinic is to determine the appropriate events to target. The most common genetic abnormality in GBMs is the activation of receptor tyrosine kinases (RTKs), of which, aberrant expression of EGFR is the most frequent (2). Concomitant with EGFR gene amplification events is the occurrence of an intragenic in-frame deletion of exons 2Ϫ7 of the EGFR gene. This rearrangement product, known as EGFRvIII, codes for a ligandindependent receptor, which is constitutively activated and highly oncogenic (reviewed in ref....

"Endoscope-assisted microsurgery" is a major advance in the microsurgical treatment of intracranial aneurysms; the endoscope allows better observation of regional anatomic features because of its magnification, illumination, and ability to "look around corners."

Object Chordomas and chondrosarcomas are rare and difficult to treat tumors for which the optimum treatment modality remains controversial. The aim of this study was to evaluate the surgery-related results and complications in a series of patients in whom radical resection was the treatment of choice. Methods The authors conducted a retrospective analysis of the surgery-related results and complications associated with chordoma and chondrosarcoma in 64 patients of whom 33 (52%) had previously undergone some form of treatment. Total or near-total excision was achieved in 56% and this rate increased to 68% in patients without prior treatment. The main complications were postoperative cerebrospinal fluid leakage, intraoperative arterial injury, and new-onset cranial nerve deficits. Arterial injury occurred only and perioperative death occurred more often in patients who had undergone previous treatment. Conclusions Analysis of the results provides support for a policy of radical excision of chordomas and chondrosarcomas at the time of first presentation. A higher incidence of procedure-related complications is found in patients who have already undergone surgery and radiotherapy.

No abstract

No abstract