Ris H B, Li Q, Krueger T, Lim C K, Reynolds B, Althaus U, Altermatt H J
Department of Thoracic and Cardiovascular Surgery, University of Bern, Switzerland.
Int J Cancer. 1998 Jun 10;76(6):872-4. doi: 10.1002/(sici)1097-0215(19980610)76:6<872::aid-ijc17>3.0.co;2-4.
The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts grown in nude mice and were correlated with mTHPC uptake, histology and doubling time of the tumors. Non-thermal laser light was delivered to the tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and 0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was measured by histomorphometry. The mTHPC concentration in non-irradiated tumors was assessed by high-performance liquid chromatography (HPLC). The tumors were graded according to their doubling time and their vascular architecture as assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake for all 3 tumor types but revealed a larger extent of photosensitized necrosis for adenocarcinoma, which displayed a delicate tumor stroma with numerous small capillary vessels, than for mesothelioma and squamous cell carcinoma, which were both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts, compared with the lower drug dose. Our results demonstrate that different tumor xenografts respond differently to mTHPC-PDT for a given drug-light condition. In this setting, the photosensitizing effect was more closely related to the vascular architecture of the tumors than to the sensitizer uptake and doubling time of the different tumors
研究评估了间四羟基苯基氯卟啉（mTHPC）对裸鼠体内生长的人恶性间皮瘤、鳞状细胞癌和腺癌异种移植瘤的光动力效应，并将其与mTHPC摄取、组织学及肿瘤倍增时间相关联。分别在腹腔注射0.1和0.3 mg mTHPC/kg体重后4天，以表面照射的方式将非热激光照射至肿瘤。通过组织形态计量学测量肿瘤坏死程度。采用高效液相色谱法（HPLC）评估未照射肿瘤中的mTHPC浓度。根据组织学评估的肿瘤倍增时间及其血管结构对肿瘤进行分级。0.1 mg/kg剂量的mTHPC在所有3种肿瘤类型中摄取量相同，但与间皮瘤和鳞状细胞癌相比，腺癌显示出更大程度的光致敏坏死，腺癌具有精细的肿瘤基质和众多小毛细血管，而后两者的基质和血管均较少。与较低药物剂量相比，0.3 mg/kg剂量的mTHPC使所有3种肿瘤类型的肿瘤摄取量提高了2倍，间皮瘤和鳞状细胞癌的坏死程度更大，但腺癌异种移植瘤并非如此。我们的结果表明，在给定的药物-光照条件下，不同的肿瘤异种移植瘤对mTHPC光动力疗法的反应不同。在此情况下，光致敏效应与肿瘤的血管结构比与不同肿瘤的敏化剂摄取及倍增时间的关系更为密切。
