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Extracellular proteases are crucial regulators of cell function. The family of matrix metalloproteinases (MMPs) has classically been described in the context of extracel-lular matrix (ECM) remodelling, which occurs throughout life in diverse processes that range from tissue mor-phogenesis to wound healing. Recent evidence has implicated MMPs in the(More)
PURPOSE To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT(More)
Many nonlinear option pricing problems can be formulated as optimal control problems, leading to Hamilton-Jacobi-Bellman (HJB) or Hamilton-Jacobi-Bellman-Isaacs (HJBI) equations. We show that such formulations are very convenient for developing monotone discretization methods which ensure convergence to the financially relevant solution, which in this case(More)
Matrix metalloproteinases (MMPs) are increasingly being implicated in the pathogenesis of several CNS diseases. In multiple sclerosis, MMPs could be responsible for the influx of inflammatory mononuclear cells into the CNS, contribute to myelin destruction and disrupt the integrity of the blood-brain barrier; in Alzheimer's disease, MMPs might mediate the(More)
The convergence of a penalty method for solving the discrete regularized American option valuation problem is studied. Sufficient conditions are derived which both guarantee convergence of the nonlinear penalty iteration and ensure that the iterates converge monotonically to the solution. These conditions also ensure that the solution of the penalty problem(More)
Fifty-one patients with intracranial chordomas who were surgically treated between 1960 and 1984 were studied. Median patient age was 46 years, and 73% presented with diplopia or headache. Nineteen tumors were classified as the "chondroid" type. The extent of surgical removal was a biopsy in 11 patients and subtotal removal or greater in 40. Thirty-nine(More)
We studied AG3340, a potent metalloproteinase (MMP) inhibitor with pM affinities for inhibiting gelatinases (MMP-2 and -9), MT-MMP-1 (MMP-14), and collagenase-3 (MMP-13) in many tumor models. AG3340 produced dose-dependent pharmacokinetics and was well tolerated after intraperitoneal (i.p.) and oral dosing in mice. Across human tumor models, AG3340 produced(More)
PURPOSE Concomitant temozolomide (TMZ)/radiotherapy followed by adjuvant TMZ has increased survival in patients with glioblastoma multiforme (GBM). However, few options are effective for patients who experience treatment failure. We conducted a multicenter, phase II study to assess the efficacy and safety of continuous dose-intense TMZ for recurrent GBM.(More)
Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by(More)
Introduction Elderly patients have glioblastomas (GBM) that are aggressive and poorly responsive to treatment. They are also prone to the side effects of treatment of GBM. Methods To shed light on the treatment of elderly patients with GBM, we reviewed the treatment toxicities and survival of patients 65 years of age or older who were treated with(More)