Repression of multiple myeloma growth and preservation of bone with combined radiotherapy and anti-angiogenic agent.
Repression of multiple myeloma growth and preservation of bone with combined radiotherapy and anti-angiogenic agent.
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联合放疗和抗血管生成剂抑制多发性骨髓瘤生长并保存骨骼。
DOI：
10.1667/rr1734.1
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发表时间：
2010-06
影响因子：
3.4
通讯作者：
Griffin RJ
中科院分区：
文献类型：
--
作者：
Jia D;Koonce NA;Halakatti R;Li X;Yaccoby S;Swain FL;Suva LJ;Hennings L;Berridge MS;Apana SM;Mayo K;Corry PM;Griffin RJ
在SCID-rab小鼠模型中测试了电离辐射（含或不含抗血管生成剂anginex (Ax)）对多发性骨髓瘤生长的影响。携带含有人类多发性骨髓瘤细胞的预植入骨移植物的小鼠每周接受不同方案的治疗，持续8周。通过生物发光强度（IVIS）、血清中人λ Ig轻链水平（ELISA）和骨移植物体积（caliper）评估，在未治疗的小鼠中观察到多发性骨髓瘤的快速生长。接受联合治疗的小鼠的肿瘤负荷在治疗8周后减少到基线值的59%（卡尺法）、43% （ELISA法）和2% （IVIS法）。单纯的Ax或放疗减缓了肿瘤的生长，但不能阻止肿瘤的生长。停止治疗四周后，给予Ax +放疗的小鼠的肿瘤负荷仍然很小，但其他三组的肿瘤负荷明显增加。经组织学评估，Ax +辐射抑制多发性骨髓瘤伴随着骨移植物中破骨细胞数量和活性的显著下降。通过显微ct成像和x线摄影评估，Ax +辐射保留了骨移植的完整性，而其他三组则失去了骨移植的完整性。这些结果表明，当抗血管生成药物启动放射治疗时，可能是局灶性多发性骨髓瘤的有效治疗方法。
The effects of ionizing radiation, with or without the antiangiogenic agent anginex (Ax), on multiple myeloma growth were tested in a SCID-rab mouse model. Mice carrying human multiple myeloma cell-containing pre-implanted bone grafts were treated weekly with various regimens for 8 weeks. Rapid multiple myeloma growth, assessed by bioluminescence intensity (IVIS), human lambda Ig light chain level in serum (ELISA), and the volume of bone grafts (caliper), was observed in untreated mice. Tumor burden in mice receiving combined therapy was reduced to 59% (by caliper), 43% (by ELISA), and 2% (by IVIS) of baseline values after 8 weeks of treatment. Ax or radiation alone slowed but did not stop tumor growth. Four weeks after the withdrawal of the treatments, tumor burden remained minimal in mice given Ax + radiation but increased noticeably in the other three groups. Multiple myeloma suppression by Ax + radiation was accompanied by a marked decrease in the number and activity of osteoclasts in bone grafts assessed by histology. Bone graft integrity was preserved by Ax + radiation but was lost in the other three groups, as assessed by microCT imaging and radiography. These results suggest that radiotherapy, when primed by anti-angiogenic agents, may be a potent therapy for focal multiple myeloma.