ISSN:
1573-7373
Keywords:
blood-brain barrier
;
bradykinin
;
brain tumor
;
carboplatin
;
glucocorticoid
;
RG2 glioma
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract A blood-tumor barrier (BTB) limits delivery of antitumoragents to brain tumors. This study sought todetermine whether dexamethasone (DXN) treatment of rats withintracranial gliomas would 1) further impair delivery ofcarboplatin to brain tumors, and 2) whether intracarotidinfusion of the bradykinin analog, RMP-7, would improvedelivery during concurrent DXN treatment. Wistar rats withRG2 gliomas were utilized and a unidirectional transport,Ki, of radiolabeled [14C] carboplatin was determined usingquantitative autoradiography. In DXN pretreatment animals, 3 mg/kg/dayof DXN was administered intraperitoneally for 3 daysprior to Ki determinations. At 10 days aftertumor implantation, Ki of [14C] carboplatin into DXN-treatedtumors and brain surrounding tumor (BST) was significantlylower compared to non-DXN treated tumors and BST(3.30 ± 0.91 vs. 4.47 ± 1.80, p〈 0.05, and 0.94 ± 0.84 vs. 2.18± 0.79, p 〈 0.05, respectively). Intracarotid infusionof RMP-7 (0.1 mg/kg/min) significantly increased the Kifor carboplatin in DXN-treated tumors (6.35 ± 3.10vs. 3.30 ± 0.91, p 〈 0.01), however, RMP-7increased Ki to a greater extent in tumorsnot pretreated with DXN (12.07 ± 3.60 vs.4.47 ± 1.80, p 〈 0.0001). Our studiesshow that dexamethasone decreases transport of carboplatin intobrain tumors. Intracarotid infusion of RMP-7 selectively increasescarboplatin transport to tumors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1005706329630
