Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Norway.
BMC Cancer. 2012 Sep 4;12:388. doi: 10.1186/1471-2407-12-388.
Antiangiogenic agents that disrupt the vascular endothelial growth factor pathway have been demonstrated to normalize tumor vasculature and improve tumor oxygenation in some studies and to induce hypoxia in others. The aim of this preclinical study was to investigate the effect of sunitinib treatment on the morphology and function of tumor vasculature and on tumor oxygenation.
A-07-GFP and R-18-GFP human melanoma xenografts grown in dorsal window chambers were used as preclinical tumor models. Morphologic parameters of tumor vascular networks were assessed from high-resolution transillumination images, and tumor blood supply time was assessed from first-pass imaging movies recorded after a bolus of 155 kDa tetramethylrhodamine isothiocyanate-labeled dextran had been administered intravenously. Tumor hypoxia was assessed from immunohistochemical preparations of the imaged tissue by use of pimonidazole as a hypoxia marker.
Sunitinib treatment reduced vessel densities, increased vessel segment lengths, did not affect blood supply times, and increased hypoxic area fractions.
Sunitinib treatment did not improve vascular function but induced hypoxia in A-07-GFP and R-18-GFP tumors.
已有研究表明，抗血管生成药物可破坏血管内皮生长因子通路，使肿瘤血管正常化并改善肿瘤氧合，但也有研究表明其可诱导肿瘤缺氧。本临床前研究旨在探讨舒尼替尼治疗对肿瘤血管形态和功能以及肿瘤氧合的影响。
采用 A-07-GFP 和 R-18-GFP 人黑色素瘤异种移植瘤在背部窗室中生长作为临床前肿瘤模型。从高分辨率透射图像评估肿瘤血管网络的形态学参数，并在静脉内注射 155 kDa 四甲基罗丹明异硫氰酸酯标记的右旋糖酐后，从记录的首过成像电影中评估肿瘤血供时间。通过使用 pimonidazole 作为缺氧标志物对成像组织的免疫组化制剂评估肿瘤缺氧。
舒尼替尼治疗降低了血管密度，增加了血管节段长度，不影响血液供应时间，并增加了缺氧区域分数。
舒尼替尼治疗并未改善血管功能，反而诱导了 A-07-GFP 和 R-18-GFP 肿瘤的缺氧。
