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Article: Progesterone is more effective than dexamethasone in prolonging overall survival and preserving neurologic function in experimental animals with orthotopic glioblastoma allografts

TitleProgesterone is more effective than dexamethasone in prolonging overall survival and preserving neurologic function in experimental animals with orthotopic glioblastoma allografts
Authors
KeywordsDexamethasone
Functional outcome
Glioblastoma
Peritumoral edema
Progesterone
Survival
Issue Date2019
PublisherElsevier Inc. The Journal's web site is located at http://www.worldneurosurgery.org/
Citation
World Neurosurgery, 2019, v. 125, p. e497-e507 How to Cite?
AbstractObjective: Dexamethasone (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. Methods: We 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. Results: We 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. Conclusions: The 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.
Persistent Identifierhttp://hdl.handle.net/10722/268226
ISSN
2019 Impact Factor: 1.829
2015 SCImago Journal Rankings: 0.526

 

DC FieldValueLanguage
dc.contributor.authorCheng, Y-
dc.contributor.authorYeung, WL-
dc.contributor.authorZhang, P-
dc.contributor.authorLi, N-
dc.contributor.authorKiang, MY-
dc.contributor.authorLeung, GKK-
dc.date.accessioned2019-03-18T04:21:15Z-
dc.date.available2019-03-18T04:21:15Z-
dc.date.issued2019-
dc.identifier.citationWorld Neurosurgery, 2019, v. 125, p. e497-e507-
dc.identifier.issn1878-8750-
dc.identifier.urihttp://hdl.handle.net/10722/268226-
dc.description.abstractObjective: Dexamethasone (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. Methods: We 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. Results: We 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. Conclusions: The 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.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.worldneurosurgery.org/-
dc.relation.ispartofWorld Neurosurgery-
dc.subjectDexamethasone-
dc.subjectFunctional outcome-
dc.subjectGlioblastoma-
dc.subjectPeritumoral edema-
dc.subjectProgesterone-
dc.subjectSurvival-
dc.titleProgesterone is more effective than dexamethasone in prolonging overall survival and preserving neurologic function in experimental animals with orthotopic glioblastoma allografts-
dc.typeArticle-
dc.identifier.emailZhang, P: pingder@hku.hk-
dc.identifier.emailLeung, GKK: gkkleung@hku.hk-
dc.identifier.authorityLeung, GKK=rp00522-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.wneu.2019.01.113-
dc.identifier.pmid30710720-
dc.identifier.scopuseid_2-s2.0-85061775529-
dc.identifier.hkuros297079-
dc.identifier.volume125-
dc.identifier.spagee497-
dc.identifier.epagee507-
dc.publisher.placeUnited States-

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