Moses B L, Chan D W, Hruban R H, Forastiere A, Richtsmeier W J
Department of Otolaryngology--Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Md.
Arch Otolaryngol Head Neck Surg. 1993 Jun;119(6):612-7. doi: 10.1001/archotol.1993.01880180026004.
To study intra-arterial infusion of chemotherapeutic agents, human squamous carcinoma cells were obtained from the FaDu cell line and were implanted in athymic rats (rnu/rnu). The xenografts were grown and then were reimplanted on a vascular pedicle and were completely isolated from the surrounding tissue. The vascular isolation of these pedicles was confirmed radiographically and histologically. After 26 days of growth, an osmotic pump was implanted to deliver either saline, intra-arterial cisplatin, or intravenous cisplatin to the vascular pedicle. Platinum levels were identified in the tumors following intra-arterial and intravenous infusions, demonstrating the usefulness of this model for delivery of antineoplastic agents. We were unable to detect differences between tumor groups for final tumor volume, tumor platinum levels, and tumor histology with the one-dose schedule used. We were able to show a remarkable uniformity of the tumor platinum levels with varying serum platinum levels with intra-arterial and intravenous infusion of cisplatin. The toxicity of each drug administration method was assessed by levels of renal platinum and rat serum creatinine and blood urea nitrogen. No differences in toxicity with the dose administrated. We believe the immunodeficient rat with a xenografted isolated vascular pedicle is an excellent model to study the effect of intra-arterial therapeutic modalities on head and neck squamous cell carcinoma.
为研究动脉内灌注化疗药物,从FaDu细胞系获取人鳞状癌细胞并植入无胸腺大鼠(rnu/rnu)体内。异种移植瘤生长后,再移植到血管蒂上,并与周围组织完全隔离。通过影像学和组织学方法确认这些蒂的血管隔离情况。生长26天后,植入渗透泵,向血管蒂输送生理盐水、动脉内顺铂或静脉内顺铂。在动脉内和静脉内输注后,在肿瘤中鉴定出铂水平,证明该模型在递送抗肿瘤药物方面的有效性。使用单剂量方案时,我们未能检测到肿瘤组在最终肿瘤体积、肿瘤铂水平和肿瘤组织学方面的差异。通过动脉内和静脉内输注顺铂,我们能够显示出肿瘤铂水平在血清铂水平变化时具有显著的一致性。通过肾铂水平、大鼠血清肌酐和血尿素氮水平评估每种给药方法的毒性。给药剂量的毒性无差异。我们认为,带有异种移植孤立血管蒂的免疫缺陷大鼠是研究动脉内治疗方式对头颈部鳞状细胞癌影响的优秀模型。