Clinical and Experimental Studies on Growth and Metastasis of Human Osteosarcomas

主要研究成果如下：1.目的1.建立一个评价地塞米松、细胞外基质蛋白和TGF-β对成骨细胞分化调控作用的体外实验体系。利用新开发的单克隆抗体检测骨源性恶性肿瘤中的骨唾液酸蛋白.在大鼠原位移植模型中联合化疗剂、MTX和B7转染的肿瘤疫苗对骨肉瘤的实验性治疗.证明hsp 90在调节人骨肉瘤细胞系BOS生长中的抑制作用。5.通过转染eta癌基因家族成员ElAF在人和小鼠恶性肿瘤细胞系中诱导MMP-9和高转移表型.在骨肉瘤的大鼠原位肿瘤植入模型中，证明存在伴随的肿瘤抗性，即原发病灶对转移性肿瘤生长的抑制作用。证实erbB 2表达缺失与骨肉瘤患者预后不良相关.用N-乙酰半胱氨酸预处理淋巴因子激活的杀伤细胞，通过抑制AICD、激活诱导的细胞死亡来增强抗肿瘤免疫。

Research results are summarized as follows.1. Establishment of an in vitro experimental system for evaluation of role of dexamethasone, extracellular matrix proteins, and TGF-beta in regulation of osteoblastic differentiation, using anewly developed human osteoblastic cell line, SV-HFO.2. Detection of bone sialoprotein in bone-derived malignancies using newly developed monoclonal antibodies.3. Experimental therapy of osteosarcoma with a combination of a chemotherapeutic reagent, MTX, and B7-transfected tumor vaccine in a rat orthotopic implantation model.4. Demonstration of an inhibitory role of hsp9O in regulation of growth of a human osteosarcoma cell line, BOS.5. Induction of MMP-9 and high metastatic phenotype in lines of human and mouse malignant tumor cells by transfection of ElAF, a member of eta oncogene fanily.6. Demonstration of presence of concomitant tumor resistance, an inhibitory effect of the primary lesion on metastatic tumor growth, in a rat orthotopic tumor implantation model of osteosarcoma.7. Demonstration of correlation between lack of erbB2 expression and poor prognosis in osteosarcoma patients.8. Augmentation of anti-tumor immunity by inhibition of AICD, activation-induced cell death, of lymphokine-activated killer cells by pretreatmen with N-acetyl cysteine.