Grossman Craig E, Carter Shirron L, Czupryna Julie, Wang Le, Putt Mary E, Busch Theresa M
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Int J Mol Sci. 2016 Jan 14;17(1):101. doi: 10.3390/ijms17010101.
Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor(®))-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm.
胸腔光动力疗法（PDT）可与手术联合用于治疗肺癌及其胸膜癌。然而，对胸腔进行光照会使组织暴露于广泛的光通量率下。在胸腔内PDT的小鼠模型中，我们研究了2-(1-己氧基乙基)-2-去乙烯基焦脱镁叶绿酸-a（HPPH；光卟啉（®））介导的PDT在不同入射光通量率（75对150 mW/cm）下减轻非小细胞肺癌负担的疗效。为了更好地理解生长因子信号在胸腔内PDT后疾病进展中的作用，我们在治疗后增殖区域评估了表皮生长因子受体（EGFR）的表达和激活情况。75 mW/cm的低光通量率使肿瘤负担降低幅度最大。生物发光成像和细胞增殖（抗Ki-67）组织学染色确定了PDT后两种光通量率下的疾病进展区域。然而，仅在以150 mW/cm的较高光通量率治疗后，才检测到增殖区域EGFR激活增加。这些数据表明，光通量率可能影响生存因子如EGFR的激活，而较低光通量率下较弱的激活可能导致75 mW/cm的PDT后肿瘤负担较小。
