85%;8μM6r处理PC3细胞,处于S期的细胞数比例显著增加至22.79%,证明6r可阻滞肿瘤细胞周期于S期。Western blotting结果显示,6r对SW620细胞及肿瘤组织中GSTπ的表达无明显影响,8μM6r可显著增加抑制PC3细胞中EGFR/PI3K/Akt及Cyclin D1的表达水平。 体内实验结果:裸鼠移植瘤实验中,与阴性对照组比较,以8mg/kg剂量尾静脉注射给药3周后,6r对结肠癌SW620皮下移植瘤生长抑制率为44.17%;给药3周后,6r对前列腺癌PC3皮下移植瘤的生长抑制率为63.3%;给药4周后,对原位前列腺癌PC-3M细胞移植瘤抑制率为60.5%,且无明显副作用。动物实验结果证明6r具有较强的体内抗肿瘤活性。Western
bolotting结果显示,6r对SW620肿瘤组织中GSTπ的表达无明显影响。6r可显著增加裸鼠肿瘤组织中cleaved-caspase-3的表达水平,促进线粒体内细胞色素C的释放,增加Bax的表达而下调bcl-2的表达,使两者比例降低,抑制EGFR/PI3K/Akt蛋白的表达。 结论 化合物6r具有较强的体内外抗肿瘤活性,其可能的作用机制是通过靶向EGFR,抑制EGFR的表达及PI3K/Akt信号通路,通过bcl-2/Bax-Cyt-C-caspase-3线粒体介导的凋亡通路诱导肿瘤细胞凋亡。同时,6r通过下调周期蛋白Cyclin D1的表达,阻滞肿瘤细胞周期于S期,抑制肿瘤细胞的增殖。因此,6r有潜力成为抗癌的候选药物之一。
介绍了2014年第1季度面市或获批以及分别进入Ⅲ、Ⅱ、Ⅰ期临床试验的最具前景的各5个代表性药物,旨在为新药研发工作者提供参考。
目的探讨非小细胞肺癌(NSCLC)中抗表皮生长因子受体(EGFR)融合基因和棘皮动物微管查关蛋白样-4与间变性淋巴激酶融合基因(EML4-ALK)基因临床病理特征的相关性。方法应用即时荧光定量聚合酶链反应(PCR)法检测NSCLC中EML4-ALK、EGFR,并对其临床病理特征进行相关性分析。结果 mTOR抑制剂 160例NSCLC中60例(37.5%)存在EGFR基因突变,腺癌高于非腺癌;不吸烟患者高于吸烟患者;女性患者高于男性患者;差异均有统计学意义(均0.05)。结论 NSCLC患者中,EGFR及EML4-ALK阳性患者在临床病理上有一些相同或相似的特征,即女性、非吸烟、腺癌患者中较为多见,但也有一些不同的特征:EML4-ALK阳性患者中,腺癌中多伴有黏液产生的腺泡样结构,不同时合并EGFR突变。
Cluster of differentiation 74(CD74) performs multiple roles in B cells,T
cells,and antigen-presenting cells within the immune system; it also participates in major histocompatibility complex class Ⅱ-restricted 因为 antigen presentation and inflammation. Recently,a role for CD74 in carcinogenesis has been described. CD74 promotes cell proliferation and motility and prevents cell death in a macrophage migration inhibitory
factordependent manner. Its roles as an accessory signal receptor on the cell surface and the ability to interact with other signaling molecules make CD74 an attractive therapeutic target for the treatment of cancer. This review focuses on the original role of CD74 in the immune system and its emerging tumor-related functions. First,the structure of CD74 will be summarized. Second,the current understandings about the expression,cellular localization,molecular mechanisms and signaling pathways of CD74 in immunity and cancerwill be reviewed. Third,the examples that suggest CD74 is a promising molecular therapeutic target are reviewed and discussed. Although the safety and efficacy of CD74-targeted strategies are under development,deeply understanding of the regulation of AZD2281体外 CD74 will hold promise for the use of CD74 as a therapeutic target and may develop the CD74-targeted therapeutic agents such as neutralized antibody and compounds.
脑是非小细胞肺癌常见的转移部位,手术和放疗是以往脑转移治疗的基石,但近年来随着对肿瘤发生发展机制的认识深化,靶向治疗在脑转移治疗中开始崭露头角。本文主要针对一些相关热点问题如脑转移治疗手段等(手术、放疗、化疗、靶向治疗)进行简要述评。
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Lung cancer, is the most common cause of cancer death in men and second only to breast cancer in women. Currently, the first line therapy of choice is platinumbased combination chemotherapy. A therapeutic plateau has been reached with the prognosis for patients with advanced non-small cell lung cancer(NSCLC) remaining poor.