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Optic nerve glioblastoma is a rare entity that usually presents with rapidly progressive vision loss, which eventually results in blindness and, ultimately, death. As with malignant gliomas in other anatomical locations, local recurrence is common. Isolated rapid changes in vision, atypical neuroimaging findings, and the rarity of optic nerve glioblastoma may render diagnosis challenging and, thus, delay treatment. The authors present a case of optic nerve glioblastoma that was treated with subtotal resection followed by adjuvant radiation therapy and temozolomide. One year following the initial diagnosis, the patient developed a right cerebellar lesion, which was histopathologically consistent with glioblastoma. This case represents the first report of transtentorial dissemination of an optic nerve glioblastoma. In addition, the authors reviewed the literature regarding optic nerve glioblastomas. Of the 73 previously reported cases of malignant optic nerve gliomas, 32 were histologically confirmed glioblastomas. The mean age at diagnosis was 62 years, and 56% were male; the median survival was 7 months. A malignant glioma of the optic nerve should be considered in the differential diagnosis of a patient with rapidly progressive visual loss. However, the incidence of optic nerve glioblastoma is exceedingly low.

In spite of increasing attention on targeted therapeutics in the treatment of glioblastoma multiforme, radiation therapy remains the most clinically effective treatment modality. However, radiotherapy only offers palliation, with hypoxia representing a major mechanism of tumor resistance. Traditional strategies to overcome the therapeutic barrier to irradiation imposed by tumor tissue hypoxia consist of improving tumor oxygenation and administering agents that increase the tumor cell sensitivity to irradiation (radiosensitizers). There is also increasing evidence that tumor tissue is composed of diverse populations of cells with heterogeneous sensitivities to irradiation. The radioresistant tumor-initiating CD133-positive glioblastoma cancer stem cells are preferentially expanded in hypoxic conditions. Therefore, identifying therapies that can specifically target the glioblastoma cancer stem cells will lead to more durable responses to radiation therapy.

Background: Interleukin-13 (IL-13) receptors are overexpressed in glioblastoma multiforme (GBM). The presence of IL-13 binding sites in GBM and their absence in normal brain tissue validates IL-13 receptor as an important target in human GBM., Objective: This review discusses the bench-to-bedside experience with a recombinant cytotoxin composed of human IL-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR), delivered via convection-enhanced delivery (CED), in GBM treatment., Methods: The authors review publications regarding the laboratory research and clinical development of IL-13-directed therapies and summarize the future of IL-13-targeted cytotoxin., Conclusion: The IL-13 receptor remains an important potential target in GBM, and preliminary experience with the IL-13-PE38QQR cytotoxin (also called cintredekin besudotox) has helped to pave the way for study of CED as an important means of drug delivery to malignant gliomas. Ongoing analysis of recently completed clinical trials will determine the future of this agent and its potential therapeutic targets.

Glioblastoma multiforme (GBM) is a heterogeneous group of tumors, and neuroimaging characteristics have not been well-defined in molecular subgroups. Eighty-five patients with GBM were analyzed regarding imaging characteristics and correlation to p53 expression. The p53 positivity was graded according to percentage of positive cells (Grade 0, for < 10%; Grade 1, for <25%; Grade 2, for 26-50%; Grade 3, for >50% labeled cells). Imaging characteristics evaluated in the preoperative MRI were location and number of lesions, dimensions of enhancing lesion and of surrounding edema, mass effect, tumor borders, enhancement pattern after intravenous contrast administration, and tumor necrosis. Eighteen tumors had p53 expression >50% in immunohistochemical staining. Preoperative MRI of patients harboring those tumors with high p53 positivity revealed typical lesions with ring enhancement pattern and well-defined borders in T1-weighted images with contrast, and they were significantly different from other groups of p53 expression. There was no difference in terms of location and number of the lesions, dimensions of enhancing lesion and surrounding edema, mass effect, and the tumor necrosis between four different groups of p53 expression. A special subgroup of GBMs with p53 overexpression has ring enhancement pattern and well-defined border on MRI that may be influential in preoperative planning and postoperative management of adjunct therapy.

Object: The goal of this study was to investigate survival and functional outcomes in patients with high-grade intracranial astrocytomas as a function of the location of the lesion in the dominant or nondominant hemisphere (DH and NDH, respectively), and to suggest management strategies for such patients based on these data., Methods: Data were collected from the Glioma Outcomes Project database, a longitudinal database of demographic, clinical, and outcome data for patients with high-grade intracranial gliomas. From the entire database of 788 patients, a subset of all 280 right-handed patients with newly diagnosed, unilateral gliomas involving potentially eloquent cortex was selected as the sample population. Two cohorts were defined based on the location of the tumor in the right or left cerebral hemisphere. All other relevant demographic and clinical data were nearly identical between the cohorts. A Kaplan-Meier analysis was conducted to assess survival, and Karnofsky Performance Scale scores assigned at 6 and 12 months postoperatively were compared as a measure of functional outcome. The analysis demonstrated no difference in survival between patients with lesions in the DH and those with tumors in the NDH. Additionally, no statistically significant difference in functional outcomes was observed between the two groups., Conclusions: Laterality of high-grade gliomas is not an independent prognostic factor for predicting survival or functional outcome. The findings in this study demonstrate that fears of increased postoperative morbidity or mortality in otherwise resectable tumors of the DH are unfounded, and the authors therefore advocate that the surgeon's decision to operate be guided by validated outcome predictors and not biased by tumor lateralization.

Background: Angiogenesis is a critical determinant of tumor growth and metastasis. We hypothesized that contrast-enhanced ultrasound (CEU) with microbubbles targeted to alpha(v)-integrins expressed on the neovascular endothelium could be used to image angiogenesis., Methods and Results: Malignant gliomas were produced in 14 athymic rats by intracerebral implantation of U87MG human glioma cells. On day 14 or day 28 after implantation, CEU was performed with microbubbles targeted to alpha(v)beta3 by surface conjugation of echistatin. CEU perfusion imaging with nontargeted microbubbles was used to derive tumor microvascular blood volume and blood velocity. Vascular alpha(v)-integrin expression was assessed by immunohistochemistry, and microbubble adhesion was characterized by confocal microscopy. Mean tumor size increased markedly from 14 to 28 days (2+/-1 versus 35+/-14 mm2, P<0.001). Tumor blood volume increased by approximately 35% from day 14 to day 28, whereas microvascular blood velocity decreased, especially at the central portions of the tumors. On confocal microscopy, alpha(v)beta3-targeted but not control microbubbles were retained preferentially within the tumor microcirculation. CEU signal from alpha(v)beta3-targeted microbubbles in tumors increased significantly from 14 to 28 days (1.7+/-0.4 versus 3.3+/-1.0 relative units, P<0.05). CEU signal from alpha(v)beta3-targeted microbubbles was greatest at the periphery of tumors, where alpha(v)-integrin expression was most prominent, and correlated well with tumor microvascular blood volume (r=0.86)., Conclusions: CEU with microbubbles targeted to alpha(v)beta3 can noninvasively detect early tumor angiogenesis. This technique, when coupled with changes in blood volume and velocity, may provide insights into the biology of tumor angiogenesis and be used for diagnostic applications.

Both increased cell proliferation and apoptosis play important roles in the malignant growth of glioblastomas. We have demonstrated recently that the differential expression of protein kinase C (PKC)-eta increases the proliferative capacity of glioblastoma cells in culture; however, specific functions for this novel PKC isozyme in the regulation of apoptosis in these tumors has not been defined. In the present study of several glioblastoma cell lines, we investigated the role of PKC-eta in preventing UV- and gamma-irradiation-induced apoptosis and in caspase-dependent signaling pathways that mediate cell death. Exposure to UV or gamma irradiation killed 80% to 100% of PKC-eta-deficient nonneoplastic human astrocytes and U-1242 MG cells, but had little effect on the PKC-eta-expressing U-251 MG and U-373 MG cells. PKC-eta appears to mediate resistance to irradiation specifically such that when PKC-eta was stably expressed in U-1242 MG cells, more than 80% of these cells developed resistance to irradiation-induced apoptosis. Reducing PKC-eta expression by transient and stable expression of antisense PKC-eta in wild-type U-251 MG cells results in increased sensitivity to UV irradiation in a fashion similar to U-1242 MG cells and nonneoplastic astrocytes. Irradiation of PKC-eta-deficient glioblastoma cells resulted in the activation of caspase-9 and caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and a substantial increase in subdiploid DNA content that did not occur in PKC-eta-expressing tumor cells. A specific inhibitor (Ac-DEVD-CHO) of caspase-3 blocked apoptosis in PKC-eta-deficient U-1242 MG cells. The data demonstrate that resistance to UV and gamma irradiation in glioblastoma cell lines is modified significantly by PKC-eta expression and that PKC-eta appears to block the apoptotic cascade at caspase-9 activation.