From the Department of Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Pancreas. 2013 Nov;42(8):1275-82. doi: 10.1097/MPA.0b013e318296f866.
Experimental data based on cell line-derived xenograft models (cell xenograft) seldom reproduce the clinical situation, and therefore we demonstrated here the superiority of a murine model involving transplantation of human pancreatic cancer tissue fragments (tumor graft), focusing on the histological features and drug delivery characteristics.
Tumor pieces from 10 pancreatic cancer patients were transplanted into SCID (severe combined immunodeficient) mice. Histological characteristics of tumor grafts, including morphology, desmoplastic reaction, and vascularization, were compared with those of cell xenografts. Drug delivery was evaluated by quantifying the concentrations of injected drug, and the results were compared with its histological features.
Eight of the 10 transplanted tumors successfully engrafted. Histological comparisons between tumor grafts and cell xenografts revealed the following: the amount of stroma was more (22.9% ± 11.8% vs 10.8% ± 5.4%; P < 0.05), vessel-cancer cell distance was longer (35.3 ± 39.0 vs 3.9 ± 3.1 μm; P < 0.001), and microvessel density was lower (6.8 ± 1.9 vs 10.8 ± 2.1 vessels/0.4 mm(2); P < 0.05) in tumor grafts. Drug concentrations in tumor grafts were lower than those in cell xenografts (3.3 ± 1.2 vs 6.0±0.2 μg/mL; P = 0.003), and the differences were correlated with the histological differences.
Pancreatic tumor grafts better reproduce the histological nature of clinical cancer and thus provide a more realistic model that is applicable for pharmacokinetic studies.
基于细胞系衍生的异种移植模型（细胞异种移植）的实验数据很少能重现临床情况，因此我们在这里展示了涉及移植人胰腺癌细胞组织片段（肿瘤移植）的小鼠模型的优越性，重点关注组织学特征和药物传递特征。
将来自 10 名胰腺癌患者的肿瘤组织块移植到 SCID（严重联合免疫缺陷）小鼠中。将肿瘤移植的组织学特征，包括形态、纤维母细胞反应和血管生成，与细胞异种移植进行比较。通过定量注射药物的浓度来评估药物传递，并将结果与其组织学特征进行比较。
10 个移植肿瘤中有 8 个成功植入。肿瘤移植与细胞异种移植的组织学比较显示：基质量更多（22.9%±11.8%比 10.8%±5.4%；P<0.05），血管-癌细胞距离更长（35.3±39.0 比 3.9±3.1μm；P<0.001），微血管密度更低（6.8±1.9 比 10.8±2.1 个/0.4mm²；P<0.05）。肿瘤移植中的药物浓度低于细胞异种移植（3.3±1.2 比 6.0±0.2μg/mL；P=0.003），差异与组织学差异相关。
胰腺肿瘤移植更好地重现了临床癌症的组织学性质，因此提供了更真实的模型，适用于药代动力学研究。
