The tumorigenesis of GISTs is driven by gain-of-function mutations in KIT or plateletderived growth factor receptor α(PDGFRA),resultingin constitutive activation of the tyrosine kinase and its downstream signaling pathways. Oncogenic KIT or PDGFRA mutations are compelling therapeutic targets for the treatment of GISTs,and the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GISTs. However,most GIST patients develop clinical

resistance to imatinib selleck and other tyrosine kinase inhibitors. Five mechanisms of resistance have been characterized:(1) acquisition of a secondary point mutation in KIT or PDGFRA;(2) genomic amplification of KIT;(3) activation of an alternative receptor

tyrosine kinase;(4) loss of KIT oncoprotein expression; and(5) wild-type GIST. Currently,sunitinib is used as a secondline treatment for patients after imatinib failure,and regorafenib has been approved for patients whose disease is progressing on both imatinib and sunitinib. Phase Ⅱ/Ⅲ trials are currently in progress to evaluate novel inhibitors and immunotherapies 点击此处 targeting KIT,its downstream 哪里 effectors such as phosphatidylinositol 3-kinase,protein kinase B and mammalian target of rapamycin,heat shock protein 90,and histone deacetylase inhibitor. Other candidate targets have been identified,including ETV1,AXL,insulin-like growth factor 1 receptor,KRAS,FAS receptor,protein kinase c theta,ANO1(DOG1),CDC37,and aurora kinase A. These candidates warrant clinical evaluation as novel therapeutic

targets in GIST.
通过分析雷贝拉唑、血清胃泌素与十二指肠球部溃疡的关系,阐述雷贝拉唑治疗十二指肠球部溃疡的效果及雷贝拉唑在治疗十二指肠球部溃疡的过程中对胃泌素的影响,探讨雷贝拉唑、血清胃泌素对DU发展及愈合的作用。
乳腺癌的发生与发展与患者体内信号通路的异常及癌基因的表达产物关系十分密切,而近年来针对这些方面的异常的治疗成为乳腺癌治疗研究的热点,一系列的靶向治疗的药物成功上市,这些药物的应用明显提高了乳腺癌患者的生存质量及生存率,曲妥珠单抗即为其中经典的药物之一。本文将从作用机制、临床应用、耐药、不良反应四个方面对其在乳腺癌中的研究进展进行简要综述。
由美国德克萨斯大学健康科学中心癌症治疗研究中心、美国癌症研究协会和贝勒(Baylor)医学院共同主办的第37届圣安东尼奥乳腺癌研讨会,于2014年12月9~13日在美国圣安东尼奥市顺利召开。作为全球乳腺癌领域的年度盛会,此次会议同样公布了一批令人瞩目的研究结果,其范围涵盖基础、转化和临床领域。在此,笔者选取一些热点的临床研究进行较详尽的回顾,以飨读者。1激素受体阳性乳腺癌治疗进展
应用5,6,7,8-四氢苯并噻吩膦亚胺(2)与烷基异氰酸酯的氮杂Wittig反应生成碳二亚胺2,在不同的条件下,2分别与不同的亲核试剂反应,有效地合成了不同取代的新型稠合噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物.所得化合物的结构由1H NMR,IR,MS和元素分析所确证.初步的体外抗肿瘤活性测试,结果显示目标化合物具有抑制肿瘤细胞的生长,其中5d对口腔肿瘤细胞KB2IC50值为19.