• World Neurosurg · May 2019

    Progesterone is more effective than dexamethasone in prolonging overall survival and preserving neurologic functions in experimental animals with orthotopic glioblastoma allografts.

    • Yin Cheng, Wan Lung Yeung, Zhang Ping De P Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong Special Administrative Re, Ning Li, Mei Yee Kiang, and Leung Gilberto K K GKK Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong Special Administra.
    • Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong Special Administrative Region, People's Republic of China.
    • World Neurosurg. 2019 May 1; 125: e497-e507.

    ObjectiveDexamethasone (DEXA) has been widely used in the management of peritumoral brain edema. DEXA, however, has many systemic side effects and can interact negatively with glioma therapy. Progesterone (PROG), however, is a well-tolerated and readily accessible anti-inflammatory and antiedema agent, with potent neuroprotective properties. We investigated whether PROG could serve as a viable alternative to DEXA in the management of peritumoral brain edema.MethodsWe used an orthotopic C6 glioblastoma model with male Sprague-Dawley rats. Tumor grafts were allowed to grow for 14 days before drug treatment with DEXA 1 mg/kg, PROG 10 mg/kg, or PROG 20 mg/kg for 5 consecutive days. The overall animal survival and neurologic function were evaluated. Mechanistic studies on blood-brain barrier permeability and angiogenic responses were performed on the ex vivo tumor grafts.ResultsWe found that all drug treatments prolonged overall survival to different extents. PROG 10 mg led to significantly longer survival and better preservation of neurologic function and body weight. The blood-brain barrier permeability was better preserved with PROG 10 mg than with DEXA, possibly through downregulation of matrix metalloproteinase-9 and aquaporin-4 expression. Antiangiogenic responses were also observed in the PROG group.ConclusionsThe present proof-of-concept pilot study has provided novel information on the use of PROG as a corticosteroid-sparing agent in brain tumor management. Further translational and clinical studies are warranted.Copyright © 2019 Elsevier Inc. All rights reserved.

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