【摘 要】
:
Decreased levels of cell cycle inhibitor p27Kip1 due to excessive degradation occur in a variety of aggressive human tumors.Since reduced p27Kip1 expression has been associated with a poor prognosis i
【机 构】
:
Department of Chemistry and Biochemistry University of Colorado-Boulder USA
【出 处】
:
BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
论文部分内容阅读
Decreased levels of cell cycle inhibitor p27Kip1 due to excessive degradation occur in a variety of aggressive human tumors.Since reduced p27Kip1 expression has been associated with a poor prognosis in many human cancers and resistance to certain anti-tumor therapies, it has been postulated that elevation of p27Kipl expression could improve prognosis and perhaps even provide a cure for malignant cancers.However, this concept has not been proven or rigorously tested largely due to the absence of specific small molecule inhibitors that perturb abnormal reduction in p27Kip1 levels.The abundance of p27Kip1 is primarily controlled by the ATP-dependent ubiquitin-proteasome pathway.Ubiquitination of p27Kip1 is primarily catalyzed by SCFskp2, a multi-protein E3 ligase complex and requires specific interaction between Skp2 and Cks 1.Mutations in Skp2 or Cks 1 that disrupt the Cks 1-Skp2 interaction perturb p27Kip1 degradation.We have developed a non-radioactive, robust, high throughput screening assay for the Skp2-Cks1 interaction based on the Amplified Luminescent Proximity Homogeneous Assay Technology (AlphaScreenTM).Using this assay we screened small molecule compound libraries for inhibitors that disrupt Skp2-Cks 1 binding.Several compounds were identified and shown to be able to inhibit p27 ubiquitination both in vitro and in cancer cells.Identifying specific small molecule inhibitors of p27Kip1 degradation is a first step towards evaluating whether inhibition of p27Kip1 degradation would be an effective anti-cancer therapy approach and translating what we have learned about the basic mechanisms of p27Kip1 degradation into potential new drug leads in cancer biology.
其他文献
本文首先分析了术前对患者的访视、术前对手术器械的消毒管理等手术前应注意的问题,其次介绍了患者体位的摆放、术中记录等手术过程中应注意的问题,然后分析了术后患者的交接问题、正确处理患者的隐私问题等手术后应注意的问题,介绍了保障完善、系统的规章制度;抓好落实手术人员规则,洗手规则等安全管理。
本文首先介绍了手术室护理严格执行各项查对制度;加强手术物品的清点等健全严格执行手术室各项规章制度,其次介绍了严格执行手术护理记录单书写规范,然后介绍了注重培养护士良好的言谈举止,手术室护士应该按照其工作职责做好自己的本职工作,不可超越职责干医疗及其他工作,强化法律意识,防范手术风险。
手术室病人安全管理是整个护理质量的组成部分,病人安全管理的目标是杜绝事故,减少差错,确保患者手术安全顺利进行.本文介绍了为了确保病人的安全管理,防止在执行护理操作技术过程中出现的缺陷、差错、事故等问题,结合本院手术室实际情况,建立健全和完善手术室各项规章制度,加强制定目标管理,近年来无护理差错事故发生.首先必须建立健全和完善手术室的各项规章制度,使护理工作有章可循、有据可依。其次是定期开展安全护理
本文首先介绍了备齐物品及抢救药物和器械、心理护理等外科手术麻醉前准备,其次介绍了体位、定位等麻醉操作过程中的护理配合,然后介绍了血压下降和心率缓慢、呼吸抑制等术中并发症的处理。
现代眼科手术技术的飞跃发展与先进的仪器设备的不断出现、更新息息相关,做好手术设备的使用管理是保证眼科显微手术顺利进行的必要条件,本文介绍了在医院没有专职设备维护人员的情况下,手术室通过严格规范的管理,并通过专科、专人的管理模式,严格的制度化管理,细致的各个环节控制监督,提高了护士对精密贵重仪器的管理意识,主动管理,科学管理,确保了仪器性能完好,使用安全,提高手术效率,延长了仪器和耗品的使用寿命,保
本文首先分析了机体防御功能下降、各种植入性操作不当等易感因素,其次介绍了空气、器械等传播途径,然后介绍了严格做好手术间的清洁和空气消毒,手术物品灭菌严格把关等切断传播途径、控制感染,介绍了认真检查病人术前准备情况,杜绝在手术室进行备皮工作;护士长每日带领值控组成员认真检查各班的消毒、查对制度等监督检查。
手术室是外科手术的重要场地,其护理质量直接关系手术质量,如何提高手术室护理质量,笔者认为只有不断地总结工作中的经验、教训,才能提高护理水平.在围手术期护理过程中有相当多潜在和明显的护理缺陷,防范、杜绝这些缺陷是提高手术期护理质量的先决条件,是减少差错事故的必然手段.笔者从事手术室护理20多年,认为手术室护理缺陷的发生与护士的工作责任心、专业技术水平、接受新业务、新技术的能力及个人文化修养有关.
Phloretin (Ph), which is obtained from apples, juice, and cider, is a known inhibitor of the type Ⅱ glucose transporter (GLUT2).In this study, elevated expression (> 5-fold) of GLUT2 mRNA was detected
The developmentally regulated PLAG1 proto-oncogene has been implicated in the development of various human tumor types, such as pleomorphic salivary gland adenomas, Iipoblastomas, hepatoblastomas and
Molecular or personalized medicine is the future of patient management and molecular imaging plays a key role towards this goal.Angiogenesis, the formation of new blood vessels, is a critical process