双膦酸盐对骨巨细胞瘤细胞超微结构的影响及细胞组织学变化

目的:探讨双膦酸盐对骨巨细胞瘤细胞超微结构的影响及细胞组织学变化。方法:取我院收治的7例双膦酸盐(唑来膦酸)治疗前后的患者肿瘤组织切片进行了透视电镜观察和TUNEL凋亡染色及图像分析。结果:双膦酸盐(唑来膦酸)治疗后的肿瘤组织切片中透视电镜下多核巨细胞和基质细胞出现了明显的凋亡表现,细胞质变化的特点是大量扩张紊乱的粗面内质网及分散于细胞质中包含于囊泡中央的高电子密度核。线粒体水肿或空泡化。巨细胞核变化的特点是形成致密的染色质材料分散于细胞核中,核膜增厚或分离,部分核碎裂和形成凋亡小体;双膦酸盐(唑来膦酸)治疗后的肿瘤组织切片中TUNEL染色强烈阳性,基质细胞凋亡率从治疗前的1.31%至治疗后的33.42%,差异有显著性意义(P=0.018),多核巨细胞凋亡率从治疗前的8.41%至治疗后的56.83%,差异有显著性意义(P=0.018)。结论:双膦酸盐可以诱导骨巨细胞瘤基质细胞和多核巨细胞的凋亡。从细胞和分子生物学水平证实双膦酸盐作为骨巨细胞瘤辅助治疗方法的可行性。

Cytochemical and ultrastructural changes in giant cell tumor of bone (GCT) stromal cell and multinucleated giant cells following bisphosphonate (BPs) administration.

Objective:To investigate the cytochemical and ultrastructural changes in GCT(Giant cell tumor of bone) stromal cell and multinucleated giant cells following Bisphosphonate administration.Methods:The feasibility of bisphosphonate inducing apoptosis of GCT stromal cell and multinucleated giant cells of GCT was explored with microscopy,electron microscopy and TUNEL apoptosis staining and image analysis.GCT specimens were collected at the time of biopsy and during definitive surgery.TUNEL assay was used to evaluate apoptotic DNA fragmentation in cells.Results:BPs(zoledronic acid) significantly induced apoptosis in both osetoclast-like giant cells and stromal tumor cells.Significant changes were observed in tumor samples under the transmission electron microscopy(TEM).In the cytoplasm these changes were characterized by abundant large tubular vesicles containing a central electrodense core scattered through the cytoplasm.In addition,mitochondria appeared to be edematous.Nuclear changes in the giant cells were characterized by the formation of dense chromatin material scattered through out the nucleus;the strong positive TUNEL-apoptosis staining were observed in the tumor samples after BPs administration.The apoptosis rate of stromal tumor cells increased significantly from 1.31% to 33.42% after BPs administration when the apoptosis rate of osetoclast-like giant cells increased significantly from 8.41% to 56.83% after BPs administration.Conclusion:BPs induces apoptosis of GCT stromal cell and multinucleated giant cells in dose-dependant manner.BPs may be considered as potential adjuvants in the treatment of GCT.