Neurosurg Focus
-
Glioblastomas multiforme (GBMs) are highly vascular brain tumors characterized by abnormal vessel structures in vivo. This finding supports the theory that glioma-associated endothelial cells (ECs) have intrinsically different properties from ECs in normal human brain. Therefore, identification of the functional and phenotypic characteristics of tumor-associated ECs is essential for designing a rational antiangiogenic therapy. ⋯ The GBM-associated ECs are resistant to cytotoxic drugs, and they undergo less apoptosis than control cells. Also, GBM-associated ECs migrate faster than controls and constitutively produce high levels of growth factors such as endothelin-1, interleukin-8, and vascular endothelial growth factor. An understanding of these unique characteristics of glioma-associated ECs is important for the development of novel antiangiogenic agents that specifically target tumor-associated ECs in gliomas.
-
Review
Standard treatment and experimental targeted drug therapy for recurrent glioblastoma multiforme.
Glioblastoma multiforme (GBM) tumors almost invariably recur despite initial treatments. Correct diagnosis using a variety of imaging techniques and the involvement of a multidisciplinary tumor board are critical for evaluating each stage of a patient's progression and determining optimal management. Standard therapies for recurrence generally include repeated resection, radiation therapy, chemotherapy, and supportive care; however, salvage therapy must be highly individualized, and not all patients are eligible for every type of standard therapy. ⋯ Experimental targeted drug therapies have been developed to inhibit aberrant cell-signaling pathways involved in tumorigenesis, and enrolling patients in clinical trials using these therapies is another option for treatment of recurrent GBM. The use of these novel therapies is often confined to large research institutions, but the severe limitations of standard treatment options make it important to highlight the potential of experimental therapies. In this paper the authors outline standard therapies and review the emerging role of targeted drug therapy in the treatment of recurrent GBM.
-
Adenoviruses historically have been one of the main vectors used in human gene therapy. To date, the majority of brain tumor trials of these vectors have used replication-defective viruses. ⋯ These adenoviruses, once they are rendered conditionally replicative by transductional and transcriptional modifications, offer significant promise for patients with malignant glioma. In this review, the authors discuss the genetic approaches to adenoviral modification and their applications in the field of neurooncology.
-
Celecoxib (Celebrex) appears to be unique among the class of selective COX-2 inhibitors (coxibs), because this particular compound exerts a second function that is independent of its celebrated ability to inhibit COX-2. This second function is the potential to inhibit cell proliferation and stimulate apoptotic cell death at much lower concentrations than any other coxibs. Intriguingly, these two functions are mediated by different moieties of the celecoxib molecule and can be separated. ⋯ In view of the controversy that has recently arisen regarding the life-threatening side effects of this class of coxibs, it may be worthwhile to pursue further the potential benefits of drugs such as DMC for anticancer therapy. Because DMC is not a coxib yet potently maintains celecoxib's antitumor potential, one may be inclined to speculate that this novel compound could potentially be advantageous in the management of COX-2-independent cancers. In this summary, the implications of recent findings with DMC will be presented and discussed.
-
Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. ⋯ Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.