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Journal of life sciences (Westlake Village, Calif.)最新文献

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Differences in Therapeutic Efficacy in Pancreatic Cancer Between Interstitial and Superficial Light Delivery Strategies in Targeted Photo Therapy 靶向光疗法中间质和浅表光传递策略对胰腺癌治疗效果的差异
Pub Date : 2018-09-04 DOI: 10.1101/408021
Nzola De Magalhães
The purpose of this study was to determine if therapeutic efficacy of a Cetuximab based near-infrared (NIR) targeted photo therapy (TPT) was dependent on light delivery strategies. We examined the cytotoxic effects of TPT in a pancreatic cancer mouse model, when administered to tumors interstitially and superficially. A subcutaneous mouse model of pancreatic cancer using BXPC-3 -GFP cells was established in male athymic (nu/nu) mice. The mice received intravenous (IV) injection of Cetuximab-IR700DX, 24 hours prior to near-infrared light irradiation. Interstitial illumination was administered at a 400mW/cm fixed power output, at a light dose of 100 J/cm to half the mice and at 300 J/cm to the remaining mice. Superficial illumination was administered at a 150mw/cm2 fixed power density at a dose of 50 J/cm2 to half the mice, and at 250 J/cm2 to the other half. Cellular damage and decrease in cell viability was determined by the decrease in GFP fluorescence intensity levels in whole animal images and in relative intensity measurements. Interstitially administered TPT resulted in greater long-term permanent damage (72 hours post treatment) to tumor cells (0% recovery at low dose, and 11% recovery at high dose) compared to superficially administered TPT (1% recovery at low dose, and 44% recovery at high dose). While these results demonstrated that near-infrared targeted photo therapy efficacy was dependent on the type of light delivery strategy, overall, both superficial and interstitial Cet-IR700DX based near-infrared targeted photo therapy can effect significant long-term damage (less signal recovery) to pancreatic cancer cells in vivo at lower doses regimens, compared to higher dose regimens (higher signal recovery).
本研究的目的是确定基于西妥昔单抗的近红外(NIR)靶向光疗(TPT)的治疗效果是否依赖于光传递策略。我们在胰腺癌小鼠模型中检测了TPT在肿瘤间质和表面给药时的细胞毒性作用。用BXPC-3 -GFP细胞在雄性胸腺(nu/nu)小鼠皮下建立小鼠胰腺癌模型。小鼠在近红外光照射前24小时静脉注射西妥昔单抗- ir700dx。以400mW/cm的固定功率输出进行间隙照明,一半小鼠的光剂量为100 J/cm,其余小鼠的光剂量为300 J/cm。对一半小鼠进行150mw/cm2固定功率密度的照射,剂量为50 J/cm2,对另一半小鼠进行250 J/cm2的照射。细胞损伤和细胞活力的降低是通过全动物图像和相对强度测量中GFP荧光强度水平的降低来确定的。与表面给药TPT(低剂量1%,高剂量44%)相比,间质给药TPT对肿瘤细胞的长期永久性损伤(治疗后72小时)更大(低剂量0%,高剂量11%)。虽然这些结果表明,近红外靶向光疗的效果取决于光传递策略的类型,但总体而言,与高剂量方案(更高的信号恢复)相比,低剂量方案对体内胰腺癌细胞具有显著的长期损伤(较少的信号恢复)。
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Journal of life sciences (Westlake Village, Calif.)
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