RGD Reference Report - Inhibition of SUR1 decreases the vascular permeability of cerebral metastases. - Rat Genome Database

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Inhibition of SUR1 decreases the vascular permeability of cerebral metastases.

Authors: Thompson, Eric M  Pishko, Gregory L  Muldoon, Leslie L  Neuwelt, Edward A 
Citation: Thompson EM, etal., Neoplasia. 2013 May;15(5):535-43.
RGD ID: 12791991
Pubmed: PMID:23633925   (View Abstract at PubMed)
PMCID: PMC3638356   (View Article at PubMed Central)

Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. We investigated if inhibiting SUR1 reduces cerebral edema due to metastases, the most common brain tumor, and explored the putative association of SUR1 and the endothelial tight junction protein, zona occludens-1 (ZO-1). Nude rats were intracerebrally implanted with small cell lung carcinoma (SCLC) LX1 or A2058 melanoma cells (n = 36). Rats were administered vehicle, glyburide (4.8 µg twice, orally), or dexamethasone (0.35 mg, intravenous). Blood-tumor barrier (BTB) permeability (K (trans)) was evaluated before and after treatment using dynamic contrast-enhanced magnetic resonance imaging. SUR1 and ZO-1 expression was evaluated using immunofluorescence and Western blots. In both models, SUR1 expression was significantly increased (P < .05) in tumors. In animals with SCLC, control mean K (trans) (percent change ± standard error) was 101.8 ± 36.6%, and both glyburide (-21.4 ± 14.2%, P < .01) and dexamethasone (-14.2 ± 13.1%, P < .01) decreased BTB permeability. In animals with melanoma, compared to controls (117.1 ± 43.4%), glyburide lowered BTB permeability increase (3.2 ± 15.4%, P < .05), while dexamethasone modestly lowered BTB permeability increase (63.1 ± 22.1%, P > .05). Both glyburide (P < .001) and dexamethasone (P < .01) decreased ZO-1 gap formation. By decreasing ZO-1 gaps, glyburide was at least as effective as dexamethasone at halting increased BTB permeability caused by SCLC and melanoma. Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain edema treatmentISOAbcc8 (Rattus norvegicus)12791991; 12791991associated with Neoplasms and ExperimentalRGD 
brain edema treatmentIMP 12791991associated with Neoplasms and ExperimentalRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of tight junction disassembly  IMP 12791991 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc8  (ATP binding cassette subfamily C member 8)

Genes (Mus musculus)
Abcc8  (ATP-binding cassette, sub-family C member 8)

Genes (Homo sapiens)
ABCC8  (ATP binding cassette subfamily C member 8)


Additional Information