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目的:采用~(125) Ⅰ籽源薄层片在荷瘤鼠体内模拟临床植入治疗肿瘤残基,观察对肿瘤的抑制效果、可行性和安全性。方法:小鼠皮 下接种艾氏腹水瘤细胞后24 h,治疗组在接种部位分别植入1粒表观活度为23. 3 MBq(O.63 mCi)和29. 6 MBq(0. 8 mCi)二种剂量 的~(125) Ⅰ籽源薄层片,对照组植入无放射活性的空籽源薄层片。治疗15 d,测量肿瘤体积并绘制肿瘤生长曲线。处死小鼠后称取瘤重并 计算肿瘤抑制率。流式细胞仪检测和电镜观察肿瘤细胞的凋亡情况,常规病理切片观察对肿瘤组织的破坏程度、载体支架周围的组 织反应等。结果:治疗15 d,动态观察~(125) Ⅰ籽源薄层片的抑瘤效果显示,2个治疗组随治疗时间的延长,照射累积剂量增加,抑瘤效果 显著增加,成瘤率分别是63. 6%和63. 6%(对照组100%),肿瘤倍增时间从1. 6 d 延长为2. 74 d 和2. 84 d,抑瘤率分别为63. 0%和75. 8%,凋亡率较对照组显著增加约2倍(P<0. 001) 。电镜超微结构观察显示肿瘤细胞出现核固缩、染色质边集和凋亡小体,但2个治 疗组间无显著差异。病理切片显示,~(125) Ⅰ籽源薄层片周围从内向外有少量炎症细胞浸润,纤维组织增生包裹了载体支架阻止了籽源的 移位;邻近籽源的肿瘤细胞由凝固性坏死向外逐渐减弱为变性坏死;其它周围组织无明显变化。结论:~(125) Ⅰ籽源薄层片能明显抑制小 鼠艾氏腹水瘤生长,促进肿瘤细胞凋亡,是植入治疗肿瘤残基切实可行又安全的方法。
OBJECTIVE: To study the inhibitory effect, feasibility and safety of 125I Ⅰ seeds slice on clinical tumor implantation in tumor bearing mice. Methods: The mice were subcutaneously inoculated with Ehrlich ascites tumor cells 24 h after treatment, the treatment group were implanted in the site of an apparent activity of 23. 3 MBq (O.63 mCi) and 29. Two doses of ~ (125) Ⅰ seeds were used in the 6 MBq (0.8 mCi) seed layer, and the control group was implanted with radioactive empty seed sheets. After 15 days of treatment, the tumor volume was measured and the tumor growth curve was drawn. The mice were sacrificed and weighed tumor weight and calculate the tumor inhibition rate. Flow cytometry and electron microscopy were used to observe the apoptosis of tumor cells. The histopathology was used to observe the extent of tumor tissue destruction and the tissue reaction around the scaffold. Results: After 15 days of treatment, the dynamic observation of the tumor-inhibiting effect of ~ (125) Ⅰ seeds showed that the tumor-bearing effects of the two treatment groups were significantly increased with the increase of treatment time and the cumulative dose of irradiation, 63. 6% and 63. 6% (control group 100%), tumor doubling time from 1. 6 d to 2. 74 d and 2. 84 d, tumor inhibition rates were 63. 0% and 75. 8%, the apoptosis rate was significantly increased by about 2 times (P <0.001) compared with the control group. Electron microscopy showed nuclear pyknosis, chromatin margination, and apoptotic bodies in the tumor cells, but there was no significant difference between the two treatment groups. Pathological sections showed that there was a small amount of inflammatory cells infiltrating from the inside of the seed layer of ~ (125) Ⅰ seeds, and the fibrous scaffolds surrounded the carrier and prevented the displacement of the seed source. The tumor cells adjacent to the seed source changed from coagulation necrosis Outside gradually weakened to degeneration and necrosis; other surrounding tissue no significant change. CONCLUSION: The seed layer slice of ~ (125) Ⅰ can significantly inhibit the growth of Ehrlich ascites tumor and promote the apoptosis of tumor cells. It is a feasible and safe method for implantation of tumor residues.