Journal of neuro-oncology
-
Journal of neuro-oncology · Aug 2006
ReviewNew concepts in surgery of WHO grade II gliomas: functional brain mapping, connectionism and plasticity--a review.
Despite a recent literature supporting the impact of surgery on the natural history of low-grade glioma (LGG), the indications of resection still remain a matter of debate, especially because of the frequent location of these tumors within eloquent brain areas - thus with a risk to induce a permanent postoperative deficit. Therefore, since the antagonist nature of this surgery is to perform the most extensive glioma removal possible, while preserving the function and the quality of life, new concepts were recently applied to LGG resection in order to optimize the benefit/risk ratio of the surgery. First, due to the development of functional mapping methods, namely perioperative neurofunctional imaging and intrasurgical direct electrical stimulation, the study of cortical functional organization is currently possible for each patient - in addition to an extensive neuropsychological assessment. ⋯ Third, the better understanding of brain plasticity mechanisms, induced both by the slow-growing LGG and by the surgery itself, were equally studied in each patient and applied to the surgical strategy by incorporating individual dynamic potential of reorganization into the operative planning. The integration of these new concepts of individual functional mapping, connectivity and plastic potential to the surgery of LGG has allowed an extent of surgical indications, an optimization of the quality of resection (neuro-oncological benefit), and a minimization of the risk of sequelae (benefit on the quality of life). In addition, such a strategy has also fundamental applications, since it represents a new door to the connectionism and cerebral plasticity.
-
A prospective Phase II study of irinotecan (CPT-11) in adult patients with recurrent surgery and radiotherapy-refractory WHO Grade I meningioma. ⋯ The primary objective was to estimate the 6-month progression-free survival (PFS) after study entry. As no patient demonstrated PFS at 6-months, the study was stopped prematurely as specified by study design. Using CPT-11 in this moderately toxic dose schedule failed to demonstrate efficacy in this cohort of adult patients with recurrent surgery and radiotherapy-refractory meningioma.
-
Journal of neuro-oncology · Jul 2006
Comparative StudyInhibition of hypoxia inducible factor-1alpha (HIF-1alpha) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas.
Hypoxia inducible factor-1alpha (HIF-1alpha) regulates vascular endothelial growth factor (VEGF), the presumed principal mediator of angiogenesis in malignant gliomas, under normal physiologic conditions. We examined the effect of HIF-1alpha on VEGF secretion, tumor growth, and angiogenesis in malignant gliomas. ⋯ VEGF and HIF-1alpha are elevated in malignant gliomas. HIF-1alpha inhibition results in VEGF secretion inhibition. HIF-1alpha expression affects glioma tumor growth, suggesting clinical applications for malignant glioma treatment.
-
Journal of neuro-oncology · May 2006
Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers.
Lactacystin, a proteasome-inhibitor, has been shown to induce apoptosis of experimental gliomas in vitro. However, its systemic toxicity prevents further clinical use. To circumvent this problem, lactacystin can be delivered intratumorally. ⋯ Polymers released lactacystin for 21 days and intracranial implantation in rats neither generate local nor systemic toxicity at doses lower than 2%. Treatment with lactacystin/pCPP : SA polymers with loading concentrations of 1.0, 1.3, and 1.5% prolonged survival of animals intracranially challenged with 9L when polymers where inserted in the day of tumor implantation. In conclusion, lactacystin exhibits potent cytotoxic-activity against 9L and F98 in vitro, it can be efficiently incorporated and delivered using controlled-release polymers, and at the proposed concentrations lactacystin polymers are safe for CNS delivery and prolong survival in the 9L model.
-
Journal of neuro-oncology · May 2006
Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients.
Seizures are a common complication of primary (PBT) and metastatic (MBT) brain tumors, affecting approximately 50% of all patients during the course of their illness. Anti-convulsant therapy of these tumor-induced seizures is often inadequate with conventional anti-epileptic drugs (AEDs), due to a variety of factors, including activation of glutaminergic NMDA receptors, immune-mediated neuronal damage, and anatomic alterations of neuronal input pathways. Levetiracetam (LEV) is a new AED with a novel mechanism of action, which includes reducing the Ca++ current through neuron-specific, high voltage activated Ca++ channels (n-type). ⋯ Overall, the seizure frequency was reduced in 90% of patients (P<0.0001; Sign test). The most common toxicity was somnolence, noted in 37% of patients. LEV was very effective and well tolerated in brain tumor patients with seizures, and should be considered for add-on therapy to current AEDs, or as a substitute anti-convulsant for monotherapy.