Namatame Hiroaki, Akimoto Jiro, Matsumura Hiroyuki, Haraoka Jo, Aizawa Katsuo
Department of Neurosurgery, Tokyo Medical University, Japan.
Photodiagnosis Photodyn Ther. 2008 Sep;5(3):198-209. doi: 10.1016/j.pdpdt.2008.08.001. Epub 2008 Oct 22.
The usefulness of photodynamic therapy (PDT) as a local therapy for malignant glioma was evaluated by investigating histological changes in a rat C6 glioma model treated with a combination of talaporfin sodium, a water-soluble photosensitizer derived from chlorophyll and exposure to a diode laser.
Glioma cells (C6) at the confluence stage were transplanted stereotactically into the right frontal lobe of SD rats. Five days later, the rats underwent right frontal craniotomy and intravenous administration of talaporfin sodium. One hour after talaporfin sodium administration, each rat was irradiated by a 664 nm diode laser beam. The brain was removed 1, 3 or 6h after laser irradiation for histological examination of tumor-affected brain tissue and surrounding normal brain tissue.
In addition to the tumor mass, tumor cells invading surrounding edematous brain tissue were seen in untreated rats, ranging from the brain surface to a depth of 2mm. One hour after PDT, coagulation necrosis as well as disappearance of indication of cell viability such as disappearance of tumor cell processes and foamy changes of cytoplasm were noted in the tumor tissue at a depth of 0.5mm, accompanied by reduction of cytoplasmic glial fibrillary acidic protein (GFAP) expression and appearance of granular M30 cytodeath positivity. Three hours later, the cytoplasm of the residual tumor cells showed disappearance of GFAP expression and increased expression of M30 cytodeath. Six hours later, the foamy cytoplasm of swollen tumor cells demonstrated strong positivity for M30 cytodeath.
PDT using talaporfin sodium induced coagulation necrosis and apoptosis in rats with C6 glioma.
通过研究用叶绿素衍生的水溶性光敏剂替莫泊芬钠与二极管激光联合治疗的大鼠C6胶质瘤模型的组织学变化,评估光动力疗法(PDT)作为恶性胶质瘤局部治疗方法的有效性。
将汇合期的胶质瘤细胞(C6)立体定向移植到SD大鼠的右额叶。五天后,大鼠接受右额开颅手术并静脉注射替莫泊芬钠。在注射替莫泊芬钠一小时后,每只大鼠接受664nm二极管激光束照射。在激光照射后1、3或6小时取出大脑,对肿瘤累及的脑组织和周围正常脑组织进行组织学检查。
在未治疗的大鼠中,除了肿瘤块外,还可见肿瘤细胞侵入周围水肿的脑组织,范围从脑表面至2mm深度。光动力疗法后1小时,在0.5mm深度的肿瘤组织中观察到凝固性坏死以及细胞活力指标的消失,如肿瘤细胞突起消失和细胞质泡沫样改变,同时伴有细胞质胶质纤维酸性蛋白(GFAP)表达降低和颗粒状M30细胞死亡阳性出现。三小时后,残留肿瘤细胞的细胞质显示GFAP表达消失,M30细胞死亡表达增加。六小时后,肿胀肿瘤细胞的泡沫样细胞质显示M30细胞死亡强阳性。
使用替莫泊芬钠的光动力疗法在C6胶质瘤大鼠中诱导了凝固性坏死和凋亡。