Department of Neurosurgery, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, CT, USA. The Cancer Journal
(Impact Factor: 4.24).
01/2012; 18(1):20-5. DOI: 10.1097/PPO.0b013e3183243f6e3
Glioblastoma multiforme is a highly infiltrative tumor that typically has a central region of necrosis surrounded by contrast-enhancing proliferative tumor cells surrounded by diffuse isolated tumor cells that migrate into the brain. The goal of surgery is often directed toward the central necrotic region and the imaging-defined enhancing margin. To limit morbidity from removing functional brain tissue, the infiltrative tumor cells found in surrounding brain are generally not considered part of the surgical target. This is also the site where tumors recur after treatment. It is well accepted by most surgeons and neuro-oncologists that, when possible, aggressive resection of malignant gliomas is the preferred initial step in management. Although there are limited randomized prospective studies that address extent of resection and survival, the benefit of aggressive surgical resection will not be debated in this report. Tumor resection to the maximum extent that is safely possible can decrease tumor burden and thereby enhance the effects of adjuvant therapies, improve symptoms from mass effect, reduce the frequency of seizures, and provide tissue for pathological and genomic studies to better identify and test novel therapy.Surgery for glioblastoma is highly dependent on imaging. Magnetic resonance imaging can provide an anatomic definition of the lesion and functional capacity of critical cortical regions and allow for precise localization within the brain. The common use of stereotactic guidance, intraoperative imaging, functional magnetic resonance imaging, and physiologic monitoring have enhanced the surgeon's ability to achieve aggressive tumor removal while protecting the patient from neurologic impairment. This review will address the use of these techniques as an important first step in managing patients with glioblastoma.
Available from: plosone.org
- "Astrocytoma and glioblastoma represent the majority of primary tumors of the central nervous system . Even well differentiated tumors bear a grim prognosis for the patients due to the diffuse infiltration of the surrounding brain that prevents complete resection of the glioma . Low grade diffuse astrocytomas show an almost complete propensity to progress to malignant anaplastic astrocytoma and subsequently to glioblastoma. "
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ABSTRACT: Astrocytomas and their most malignant variant glioblastoma multiforme (GBM) represent the vast majority of primary brain tumors. Despite the current progress in neurosurgery, radiation therapy and chemotherapy, most astrocytomas remain fatal disorders. Although brain tumor biology is a matter of intense research, the cell-of-origin and the complete astrocytoma-inducing signaling pathway remain unknown. To further identify the mechanisms leading to gliomagenesis, we transduced primary astrocytes on a p53(-/-) background with c-Myc, constitutively active myr-Akt or both, myr-Akt and c-Myc. Transduced astrocytes showed oncogene-specific alterations of morphology, proliferation and differentiation. Following prolonged periods of cultivation, oncogene-transduced astrocytes expressed several stem-cell markers. Furthermore, astrocytes coexpressing c-Myc and Akt were tumorigenic when implanted into the brain of immunocompetent C57BL/6 mice. Our results reveal that the loss of p53 combined with oncogene overexpression in mature astrocytes simulates pivotal features of glioma pathogenesis, providing a good model for assessing the development of secondary glioblastomas.
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ABSTRACT: High-grade gliomas (HGGs) account for the vast majority of all gliomas, including glioblastoma (World Health Organization (WHO) grade IV) and anaplasticgliomas (WHO grade III). Despite tremendous efforts in developing multimodal treatments, the overall prognosis remains poor; however, survival time varies considerably between patients. The nature of diffuse permeation into surrounding brain parenchyma poses dilemma for neurosurgeons between extensive surgical resection to eliminate as much as tumor cells as possible and adverse effects associated with brain function. Heterogeneity in both cytology and gene expression makes it difficult to coordinate an effective therapy which works for every patient. This article reviews recent advancements in the molecular mechanism, multimodal treatment and clinical management, and the updated view on the biomarkers in patients with HGG, both in primary and recurrent setting, with an emphasis on targeted therapies tailored to the patient.
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