Erickson Kristian, Braun Rod D, Yu Daohai, Lanzen Jennifer, Wilson David, Brizel David M, Secomb Timothy W, Biaglow John E, Dewhirst Mark W
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cancer Res. 2003 Aug 1;63(15):4705-12.
The purpose of this study was to test the hypothesis that longitudinal O(2) gradients in tumor affect response to manipulation of oxygenation. Previously we showed that pO(2) is higher on the fascial than the tumor surface of the R3230Ac rat mammary carcinoma when growing in a dorsal skin-fold window chamber, reflecting a longitudinal oxygen gradient. Magnetic resonance angiography verified prior results: the fascial surface has arterioles and higher vascular density than tumor; and the tumor surface has no arterioles. Phosphorescence lifetime imaging was used to measure each surface hypoxic percentage (HP; percentage of pixels < 10 mm Hg) before and after administration of mannitol or glucose (1 g/kg, i.v.) followed by O(2) breathing. The fascial surface had a smaller HP (median = 2.72%) than tumor (median = 27.94%; P = 0.0002) at baseline. HP on the fascial surface was positively correlated with HP on the tumor surface (P = 0.0067). HP decreased on the fascial surface after either sugar + O(2) (mannitol P = 0.03; glucose P = 0.06; combined P = 0.002), but HP did not change on the tumor surface. Therefore, the tumor surface is refractory to improvement in pO(2) with this method. Additional refinements may be needed to improve pO(2) of analogous regions in larger tumors; mechanism-driven suggestions are provided.
本研究的目的是验证肿瘤内纵向氧梯度影响氧合调控反应这一假说。此前我们发现，R3230Ac大鼠乳腺癌在背部皮褶窗小室内生长时，筋膜表面的pO₂高于肿瘤表面，这反映了纵向氧梯度。磁共振血管造影证实了先前的结果：筋膜表面有小动脉且血管密度高于肿瘤；而肿瘤表面没有小动脉。在静脉注射甘露醇或葡萄糖（1 g/kg）后进行吸氧，利用磷光寿命成像测量给药前后每个表面的低氧百分比（HP；像素<10 mmHg的百分比）。基线时，筋膜表面的HP（中位数=2.72%）低于肿瘤表面（中位数=27.94%；P=0.0002）。筋膜表面的HP与肿瘤表面的HP呈正相关（P=0.0067）。糖+氧处理后，筋膜表面的HP降低（甘露醇P=0.03；葡萄糖P=0.06；联合处理P=0.002），但肿瘤表面的HP没有变化。因此，用这种方法肿瘤表面的pO₂难以改善。可能需要进一步改进以提高较大肿瘤类似区域的pO₂；本文提供了基于机制的建议。
