Application of BMP for reconstruction of bone defect after the removable of malignant bone tumor

BMP在恶性骨肿瘤摘除术后骨缺损重建中的应用

• 批准号: 10680792
• 负责人: SHIMIZU Tominaga
• 金额: $ 1.92万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680792/
• 关键词: malignant bone tumor; anti cancer drug; bone defect; reconstruction; bone morphogenetic protein; 手術

In a treatment of malignant bone tumor, huge loss of bone is caused by tumor wide resection. As a filling up the small defect such as small tumor of digital bone, bone transplant is a useful method. But huge bone defect caused by removal of the pelvic bone has not been successfully reconstructed by previous method. Furthermore, the patient suffering from malignant tumor has chemotherapy or radiation therapy, is in a disadvantage state because these treatment cause a negative affect for bone formation or repair. This study focused on the effect of the anti-cancer drug for bone forming reaction, and improvement of the ideal method for filling up the defect caused by tumor resection, especially pelvic bone tumor. First, we examined the influence of anti-cancer drug for bone-forming reaction by means of the implantation of pellet consisted of bone morphogenetic protein (BMP) and collagen carrier, which has an ability of forming subcutaneous bone. Anti cancer drug receiving group has less a … More bility of bone formation than control group; successful bone formation has been achieved in control group in 2 or 3 weeks by means of enchondral bone formation, on the other hand no mature bone formation but chondroid formation was seen in anti-cancer drug group. Next, we examined the influence of anti-cancer drug for fracture repair using rat femoral bone fracture model. Less ability for fracture repair was revealed in anti-cancer drug group. By an immunohistochemical study using anti-VEGF antibody, less positive staining around BMP pellet was seen in anti-cancer drug group, that indicates the drug had influenced a negative effect for new vascular formation which had been needed for new bone formation. Finally, we made the rabbit model bearing huge bone defect in pelvis. As a treatment of filling up the defect, we applied the triphosphate calcium cement paste. The paste alone did not cause the sufficient healing, but the combination of titanium wire and the paste caused successful and powerful replacement for the bone defect. Less

在恶性骨肿瘤的治疗中，大面积切除肿瘤会造成巨大的骨损失。骨移植是填补指骨小肿瘤等小缺损的一种有效方法。但由于骨盆骨的切除而造成的巨大骨缺损，以往的方法都未能成功重建。此外，恶性肿瘤患者接受化疗或放疗，处于不利状态，因为这些治疗对骨的形成或修复产生负面影响。本研究的重点是抗癌药物对骨形成反应的影响，以及对肿瘤切除，特别是骨盆骨肿瘤术后缺损的理想填充方法的改进。首先，我们通过植入具有皮下成骨能力的骨形态发生蛋白（BMP）和胶原载体组成的微球，研究了抗癌药物对成骨反应的影响。抗肿瘤药物治疗组骨形成能力明显低于对照组；对照组在2 ~ 3周内以内软骨成骨方式成功成骨，而抗癌药物组未见成熟骨形成，但见软骨样体形成。接下来，我们采用大鼠股骨骨折模型，检测抗癌药物对骨折修复的影响。抗肿瘤药物组骨折修复能力较弱。利用抗vegf抗体进行免疫组化研究，抗癌药物组BMP颗粒周围阳性染色较少，说明抗癌药物对新骨形成所必需的新血管形成产生了负面影响。最后，我们制作了骨盆巨大骨缺损兔模型。我们采用三磷酸钙水泥浆作为缺损的填充物。单纯使用膏体不能充分愈合，但钛丝与膏体的结合对骨缺损进行了成功有力的置换。少

项目成果

Shimizu T, et al.: "Sequential expression of bone morphogenetic protein, tumor necrosis factor, and their receptors in bone forming reaction after mouse marrow ablation"Bone. 23. 127-133 (1998)

Shimizu T 等人：“小鼠骨髓消融后骨形成反应中骨形态发生蛋白、肿瘤坏死因子及其受体的序列表达”Bone.

Mori S, Takaoka K, et al.: "Antiangiogenic agent(TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2"Bone. 22. 99-105 (1998)

Mori S、Takaoka K 等人：“抗血管生成剂 (TNP-470) 抑制骨形态发生蛋白 2 诱导的异位骨形成”骨。

Mehdi R, Shimizu T, Yoshimura Y, Gomyo H, Takaoka K.: "Expression of bone morphogenetic protein and its receptors in osteosarcoma and malignant fibrous histiocytoma."Japanese Journal of Clinical Oncology. 30. 272-275 (2000)

Mehdi R、Shimizu T、Yoshimura Y、Gomyo H、Takaoka K.：“骨形态发生蛋白及其受体在骨肉瘤和恶性纤维组织细胞瘤中的表达。”日本临床肿瘤学杂志。

Tominaga Shimizu, et al.: "Sequential expression of TNF, BMP and their receptors in bone forming reaction after mouse femoral narrow ablation"Bone. 23. 127-133 (1998)

Tominaga Shimizu 等人：“小鼠股骨狭窄消融后骨形成反应中 TNF、BMP 及其受体的顺序表达”Bone。

Tominaga Shimizu, et al.: "Malignant fibroushistiocytoma of iliac bone"Modern Surgical Challenges for Muschloskeletal Sarcoma. 7. 16-28 (1998)

Tominaga Shimizu 等人：“髂骨恶性纤维组织细胞瘤”肌肉骨骼肉瘤的现代外科挑战。