乳腺癌外科的治疗的新理念与进展.ppt

期望： 与肿瘤内科医师的积极交流和联合操作 化疗药物与放疗技术的更大进步 生物医学材料的进步，宜于器官移植和再造 基础医学研究的深入发展（个体化治疗） 难点:体内肿瘤负荷1cm3≈109~10 THANK YOU ! THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS THANKS * 当配体（生长因子）与细胞表面的异二聚体受体复合物（包括HER2蛋白）结合后，导致细胞内酪氨酸激酶的蛋白活化，发生酪氨酸自身的磷酸化，进而引发瀑布式的连锁反应，信号传导经细胞膜和细胞间质至细胞核，激活基因，促进有丝分裂。因此HER2蛋白在控制正常细胞生长和分裂中起了关键性作用。 * 生长因子受体在细胞周期调节和DNA损伤修复中起重要作用，赫赛汀?能阻断生长因子信号传导，从而干扰生长因子对肿瘤细胞的调节作用。。 加快过度表达HER2受体的降解和吸收。 抗血管生成作用涉及血管内皮生长因子，和其他血管生成因子的下调，赫赛汀?的作用机制于抗血管生成亦有关。 Reference: Petit AM, Rak J, Hung MC, et al. Neutralizing antibodies against epidermal growth factor and erbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997;151:1523-30. Sarup JC, Johnson RM, King KL, et al. Characterization of an anti-p185HER-2 monoclonal antibody that stimulates receptor function and inhibits tumor cell growth. Growth Regul 1991;1:72-82. Pietras RJ, Arboleda J, Reese DM, et al. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth human breast cancer cells. Oncogene 1995;10:2435-46. * 增强机体免疫系统对肿瘤细胞的识别和杀伤作用，通过抗体－依赖性细胞－介导的细胞毒作用（ADCC），聚集免疫细胞攻击并杀死肿瘤细胞。 增加肿瘤细胞对化疗的敏感性。 Reference: Carter P et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992;89:4285-9. Hancock MC et al. A monoclonal antibody against the c-erbB-2 expression in breast cancer. J Clin Oncol 1991;51:4575-80. Hotaling TE et al. The humanized anti-HER2 antibody rhuMAb HEr2 mediates antibody dependent cell-mediated cytotoxicity via FcgRIII [abstract]. Proc Am Assoc Cancer Res 1996;37:471. Kasprzyk PG et al. Therapy of an ani