Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Transl Oncol. 2010 Jun 1;3(3):153-9. doi: 10.1593/tlo.09184.
Adenocarcinoma of the pancreas is a lethal malignancy, and better models to study tumor behavior in vivo are needed for the development ofmore effective therapeutics. Ionizing radiation is a treatment modality that is commonly used in the clinical setting, in particular, for locally confined disease; however, good model systems to study the effect of ionizing radiation in orthotopic tumors have not been established. In an attempt to create clinically relevant models for studying treatments directed against pancreatic cancer, we have defined a methodology to measure the effect of varying doses of radiation in established human pancreatic cancer orthotopic xenografts using two different pancreatic cancer cell lines (Panc-1 and BXPC3) infected with a lentiviral vector expressing CMV promoter-driven luciferase to allow bioluminescence imaging of live animals in real time. Quantifiable photon emission from luciferase signaling in vivo correlated well with actual tumor growth. Bioluminescence imaging of the established pancreatic xenografts was used to direct delivery of radiation to the orthotopic tumors and minimize off-target adverse effects. Growth delay was observed with schedules in the range of 7.5 Gy in five fractions to 10 Gy in four fractions, whereas doses 3 Gy or higher produced toxic adverse effects. In conclusion, we describe a model in which the effects of ionizing radiation, alone or in combination with other therapeutics, in orthotopic xenografts, can be studied.
胰腺腺癌是一种致命的恶性肿瘤，需要更好的体内肿瘤行为模型来开发更有效的治疗方法。电离辐射是一种在临床上常用的治疗方式，特别是对于局部局限性疾病；然而，尚未建立用于研究电离辐射对原位肿瘤影响的良好模型系统。为了创建用于研究针对胰腺癌的治疗方法的临床相关模型，我们定义了一种方法，使用两种不同的胰腺癌细胞系（Panc-1 和 BXPC3）感染表达 CMV 启动子驱动的荧光素酶的慢病毒载体，来测量不同剂量的辐射对已建立的人胰腺腺癌原位异种移植物的影响，从而实时对活体动物进行生物发光成像。来自活体荧光素酶信号的可量化光子发射与实际肿瘤生长很好地相关。已建立的胰腺异种移植的生物发光成像用于引导对原位肿瘤的放射治疗，并最大限度地减少脱靶不良反应。观察到与 7.5 Gy 分 5 次和 10 Gy 分 4 次的方案范围相关的生长延迟，而 3 Gy 或更高的剂量则会产生毒性不良反应。总之，我们描述了一种模型，其中可以研究单独或与其他治疗方法联合使用电离辐射对原位异种移植物的影响。
