抗恶性肿瘤药2018-10张纬萍卢韵碧.PPT

* VP16主要抑制topoisomerase II * It does this by binding DNA at the transcription initiation complex and preventing elongation by RNA polymerase. As it can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis. 能嵌入到DNA双螺旋中相邻的鸟嘌呤和胞嘧啶碱基之间，与DNA结合形成复合物 * They are very toxic to a lot of cells. They have high cardiotoxicity. Always used for the resistant cancer. * They are very toxic to a lot of cells. They have high cardiotoxicity. Always used for the resistant cancer. * * Microtubules is an important part of the cytoskeleton and the mitotic spindle. Two GTP binding site, the site on beta tubublin and hydrolyze GTP to GDP, which named exchangeable GTP binding site. Another called nonexchangeable GTP binding site. * Both Vinblastine and Vincristine are very commonly used for cancer chemotherapy. Both of them come from the periwinkle plant vinca rosea They bind to the beta-tublin, close to the exchangeable GTP binding site. And disrupt assembly of microtubules. Vincristine is very specifc act as a mitotic spindle poison leading to arrest of cells in the M phase of the cell cycle. Vinblastine used for Hodgkin’s disease, non Hodgkin’s lymphomas, breast cancer and germ cell cancer. Vincristine effective when combined with prednisone for acute lymphoblastic leukemia in children and various hematologic malignancies. Main toxicity of Vincristine is neurotoxicity. Less myelosuppression than vinblastine. 还可干扰蛋白质合成、RNA多聚酶，对G1期也有作用 * Used on broad range of solid tumors (ovarian, advanced breast, hon-small cell and small cell lung, head and neck, esophageal, prostate and bladder cancer and AIDS-related Kaposi’s sarcoma) Abraxane is not associated with hypersensitivity reactions and premedication to prevent such reactions is not required. 我国的红豆杉和短叶紫杉的树皮中叶可以提取到 * * Nuclear receptors and membrane receptors * women at high risk for breast cancer 绝经后妇女 LH：间质细胞刺