Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7
Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7
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DOI：
10.1097/00006123-199607000-00025
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发表时间：
1996-07-01
期刊：
影响因子：
4.8
通讯作者：
Black, KL
中科院分区：
文献类型：
--
作者：
Matsukado, K;Inamura, T;Black, KL
目的：颈动脉内输注缓激肽类似物RMP-7可增加脑肿瘤毛细血管的通透性。本研究试图确定以下内容：1）静脉内或颈动脉内输注RMP-7时放射性标记的[C-14]卡铂进入脑肿瘤的单向转运Ki; 2）连续输注RMP-7期间肿瘤毛细血管通透性增加的持续时间和程度;以及3）卡铂联合RMP-7治疗对胶质瘤大鼠存活率的影响。使用患有RG 2胶质瘤的Wistar大鼠，并使用定量放射自显影术测定单向传递常数Ki。结果：与单纯灌注生理盐水相比，动脉灌注RMP-7 15 min可使[C-14]卡铂向肿瘤的转运增加2.7倍（P < 0.001）。与10分钟、30分钟或60分钟输注相比，颈动脉内输注RMP-7（0.1 μ g/kg/min）15分钟时，[C-14]葡聚糖和[C-14]卡铂向肿瘤中的转运显著增加（P < 0.01）。在肿瘤植入后第5天和第7天用单独的卡铂（10 mg/kg）治疗的大鼠在31天表现出存活率的适度增加（37%，与对照组相比）。
OBJECTIVE: Intracarotid infusion of the bradykinin analog, RMP-7, can increase permeability in brain tumor capillaries. This study sought to determine the following: 1) the unidirectional transport, K-i, of radiolabeled [C-14]carboplatin into brain tumors with either intravenous or intracarotid RMP-7 infusions; 2) the duration and extent of increased permeability in tumor capillaries during continuous RMP-7 infusions; and 3) the effect on survival of carboplatin combined with RMP-7 treatment in rats with gliomas.METHODS: Wistar rats with RG2 gliomas were used, and a unidirectional transfer constant, K-i, was determined using quantitative autoradiography. In the survival study, the rats were treated with intra-arterial carboplatin and RMP-7 at Days 5 and 7 after tumor implantation.RESULTS: Intracarotid infusion of RMP-7 for 15 minutes increased the transport of [C-14]carboplatin to tumors by 2.7-fold, as compared with saline infusion alone (P < 0.001). The transports of [C-14]dextran and [C-14]carboplatin into tumors were significantly higher with 15 minutes of intracarotid infusion of RMP-7 (0.1 mu g/kg/min), compared to those with 10-, 30-, or 60-minute infusions (P < 0.01). Rats treated at Days 5 and 7 after tumor implantation with carboplatin alone (10 mg/kg) exhibited a modest increase in survival at 31 days (37%, compared to