Growth of human lung tumor in the brain of the nude rat as a model to evaluate antitumor agent delivery across the blood-brain barrier.
Growth of human lung tumor in the brain of the nude rat as a model to evaluate antitumor agent delivery across the blood-brain barrier.
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发表时间：
1985-06
期刊：
影响因子：
11.2
通讯作者：
E. Neuwelt;E. Frenkel;A. D'Agostino;D. Carney;J. Minna;P. Barnett;C. I. McCormick
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文献类型：
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作者：
E. Neuwelt;E. Frenkel;A. D'Agostino;D. Carney;J. Minna;P. Barnett;C. I. McCormick
我们利用NCI-N417D人肺小细胞癌在脑内和s.c内生长的裸鼠建立了脑肿瘤模型。从接种脑内肿瘤到出现神经系统症状的中位潜伏期为13天，脑内肿瘤发生率为91%（29 / 32）。中位生存期为13天，所有动物在第26天死亡。肿瘤是离散性的，边界清楚，偶有脑膜轻扩散，周围脑水肿的证据很少。在脑内，这种肿瘤通常不渗透Evan蓝白蛋白（Mr . 68,500），但不渗透荧光素（Mr . 376）。尽管存在差异，但与同一动物体内生长的相同肿瘤相比，脑内肿瘤对甲氨蝶呤的渗透性更低（P < 0.005）。在血脑屏障开放和不开放的情况下，动脉和静脉给药甲氨蝶呤的途径进行评估。甲氨蝶呤动脉内给药显著（P < 0.025）增加脑肿瘤内及同侧脑的给药量，打开渗透血脑屏障后给药显著（P < 0.0025）增加。打开屏障后，肿瘤内甲氨蝶呤浓度提高3 ~ 4倍，肿瘤周围脑内甲氨蝶呤浓度提高10 ~ 20倍。因此，裸鼠提供了一个模型来研究脑内生长的人肺小细胞癌的生物学和治疗反应性，在那里它形成了类似于人类的血肿瘤屏障。该模型进一步提供了独特的机会来研究渗透血脑屏障打开在肿瘤治疗中的作用，肿瘤对化疗药物敏感，肿瘤特异性单克隆抗体可用。
We have developed a brain tumor model in the nude rat utilizing NCI-N417D human small cell carcinoma of the lung grown both intracerebrally and s.c. The median latency period from the time of intracerebral tumor inoculation to the onset of neurological symptoms is 13 days with an intracerebral tumor take rate of 91% (29 of 32). The median survival is 13 days, and all animals were dead by Day 26. The tumor is discrete, well circumscribed, with occasional leptomeningeal spread and with minimal evidence of surrounding cerebral edema. Intracerebrally, this tumor is usually impermeable to Evan's blue:albumin (Mr 68,500) but not fluorescein (Mr 376). Although variable, the intracerebral tumor is less permeable to methotrexate than is the same tumor grown s.c. in the same animal (P less than 0.005). The intraarterial and i.v. routes of methotrexate administration in the presence and absence of blood-brain barrier opening were evaluated. Drug delivery to the intracerebral tumor and ipsilateral brain was significantly (P less than 0.025) greater when the methotrexate was given intraarterially and was significantly (P less than 0.0025) increased after osmotic blood-brain barrier opening. After barrier opening, methotrexate concentration was enhanced 3- to 4-fold in tumor and 10- to 20-fold in brain around tumor. Thus, the nude rat provides a model to investigate the biology and therapeutic responsiveness of human small cell carcinoma of the lung grown intracerebrally where it develops a blood-tumor barrier similar to that seen in humans. This model further provides the unique opportunity to investigate the role of osmotic blood-brain barrier opening in the treatment of a tumor which is sensitive to chemotherapeutic agents and for which tumor-specific monoclonal antibodies are available.