Neurosurg Focus
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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.
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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.
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Adenovirus transduction in gene therapy is dependent on the expression of the coxsackie virus-adenovirus receptor (CAR) for initial binding and on the integrin receptors (avb3, avb5) for viral internalization. Low and variable expression of CAR may be responsible for the low transduction rates seen with native adenoviral vectors. The goal of this study was to demonstrate increased transduction efficiency by retargeting the adenovirus with a fibroblast growth factor (FGF) ligand, FGF-2. ⋯ Fibroblast growth factor-2-retargeted adenoviral vectors may be used to increase the transduction of GBM-derived endothelial cells, enabling a new and efficient antiangiogenesis strategy for the treatment of malignant gliomas.
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Because the prognosis for patients with glioblastoma multiforme (GBM) remains poor, investigators have focused on developing new and more effective treatment modalities. Targeted toxins represent a new class of compounds composed of a potent protein toxin and a carrier ligand that will recognize cell surface antigens located on target tissue. A recombinant fusion protein was created that contains the translocation and catalytic portions of diphtheria toxin that are responsible for cell entry and killing, respectively, fused to the noninternalizing aminoterminal fragment portion of human plasminogen activator. This diptheria toxin-uPA fusion protein (DTAT) has the advantage over other fusion proteins of targeting malignant glioma cells and the endothelial cells of the neovasculature that express the urokinase-type plasminogen activator receptor (uPAR). Another protein, DTAT13, was synthesized to target uPAR on the neovasculature and the uPAR and interleukin-13 receptor-expressing GBM cells. The authors describe the in vitro and in vivo efficacy of DTAT and DTAT13 against GBM. ⋯ Both DTAT and DTAT13 might have potential for clinical application against GBM because of their ability to target both the tumor cells and neovasculature simultaneously with an absence of serious systemic side effects. The discovery that DTAT13 was less toxic than DTAT indicated that the bispecific fusion protein might target a broader subset of antigenetically diverse patients with tumors while reducing the systemic exposure to toxin that would be necessary if two agents were administered separately.