肿瘤药物张博详细分析.ppt

腹泻的处理 饮食调节 清淡饮食 避免辛辣和乳制品 药物治疗 阿片类制剂：盐酸洛哌丁胺或苯以哌啶 粘膜保护剂：思密达 严重者药物减量或停药 高血压的处理 轻者不需要处理 ≥160/100mmHg和/或出现相应症状需要治疗 严重者药物减量或暂停 * 多吉美是一种2-芳基尿素，它不仅可以抑制与细胞生长密切相关的丝氨酸/苏氨酸激酶Raf-1，而且可以抑制多种与血管生成密切相关的酪氨酸激酶，例如VEGFR2-3、PDGFR、C-kit等。 * 下面具体解释一下多吉美靶向作用于肿瘤细胞增殖和血管生成的作用机理： 一些生长因子如表皮生长因子EGF、血管内皮生长因子VEGF及血小板衍生生长因子PDGF与细胞表面受体结合后从而向细胞核传递信号，导致细胞的增殖存活及血管的生成。EGF、 VEGF及PDGF与其受体结合后可激活RAS-RAF-MEK-ERK信号通路，将信号传至细胞核，促进其他生长因子的表达、细胞的增殖及肿瘤血管的生成。多吉美的作用靶点是抑制RAF，KIT,FLT-3及 RET，VEGFR-2, PDGF-β等激酶的活性而阻止生长因子及血管生成因子的促生长及生成信号向细胞核传递，从而起到抑制肿瘤细胞增殖和血管生成的作用。 * 这是酪氨酸激酶受体模式图，当外源信号与受体结合后，引起临近受体的偶联，进而受体的胞内部分发生磷酸化，其结果是细胞内信号的活化，最终将活化信号传入细胞核，引起细胞生物学改变。 * * * Sunitinib malate 顯示能強力抑制所有已知的 PDGF 和 VEGF 受體、KIT、FLT3 和 RET 所介入的多 RTKs。 Sunitinib malate 在低濃度（nanomolar）也能抑制這些受體，顯示其活性強度相當高 Sunitinib malate 能直接和間接地抑制多種腫瘤類型的成長，因為它有抗腫瘤和抗血管增生的活性作用。 * The human epidermal growth factor family of receptors consists of 4 transmembrane proteins with different properties (HER1-4), all involved in regulation of cell proliferation and survival.1-5 The prototype HER member HER1/EGFR (Erb-B1) binds a variety of growth factors, with ligand binding activating tyrosine kinase activity within the cytoplasmic domain and through various signal transduction intermediates.1 HER2 has no known ligand-binding activity, but its tyrosine-kinase activity is transactivated through HER2 interaction with other HER members (heterodimerization), usually following ligand binding to those receptors.3 The HER2 extracellular domains are fixed in an open conformation (exposed domain II loop) that resembles a ligand-activated state, and thus HER2 can constitutively interact functionally with other HER members.6 HER3 lacks inherent tyrosine kinase activity, but ligand binding promotes HER heterodimerization, resulting in complexes (eg, HER2/HER3) with highly proliferative signaling activity.2,4 The HER signaling network, mediated by these receptor interactions, stimulates and regulates not only cell proliferation, but also mobility, adhesion and