本研究基于乳腺癌组织的基因表达谱数据,采用系统生物学方法推测乳腺癌转移中Runx2对细胞外基质重塑的调节机制.采用相关性分析程序分析49例乳腺原发癌和15例淋巴结转移癌组织的基因表达谱数据,筛选与Runx2呈相关性表达的基因,结果得到与ECM重塑相关的候选基因52个,包括ECM成分11个,ECM降解酶及其抑制剂8个,细胞信号分子33个.利用转录调节因子结合序列数据库搜索候选基因启动子区的Runx2结合模序,筛选其中Runx2转录调控的ECM重塑相关基因,并判断可能调节Runx2的上游信号分子;文献检索实验证实的与Runx2有相互调节关系的基因,并基于Runx2上游调控信号分子和下游转录调节基因的分析,构建得到以Runx2为中心的ECM重塑的生物学调控网络.WNT和TGF/BMPs是启动Runx2表达的主要信号通路,Runx2通过转录调节ECM组分、ECM降解酶及其抑制剂和信号分子调节ECM重塑,促进癌细胞完成转移的生物学过程.
目的探讨TGF-β1受体阻滞剂SB-431542对树突状细胞(DC)融合疫苗制备的影响。方法①SB-431542(TGF-β1受体阻滞剂)与粒细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)、脂多糖(LPS)联合应用,刺激C57BL/6小鼠骨髓来源DC成熟,应用聚乙二醇(PEG)融合技术融合DC和小鼠胰腺癌细胞(Panc02),制备融合疫苗。②观察细胞形态、细胞表面表达、MTT法检测肿瘤细胞体外杀伤细胞毒活性。结果①在SB-431542参与下,成熟DC的细胞数目及形态无显著改变;②DC表面CD80、CD86、CD40的表达较未加SB-431542显著增高;MTT比色法,添加SB-431542的DC疫苗组对肿瘤细胞的杀伤抑制率显著提高。结论
www.selleckchem.cn/products/tg101209.html SB-431542组融合细胞的分子表达较非SB-431542组显著提高;体外MTT显示SB-431542组有更好的抗肿瘤效应,说明SB-431542对增强融合疫苗抗肿瘤效应有明显的增强作用。
Inflammation is a primary defense process against various extracellular stimuli,such as viruses,pathogens,foods,and
environmental BTK inhibitor pollutants.When cells respond to stimuli for short periods of time,it results in acute or physiological inflammation.However,if the stimulation is sustained for longer time or a pathological state occurs,it is known as chronic or pathological inflammation.Several studies have shown that tumorigenesis in the gastrointestinal (GI) tract is closely associated with chronic inflammation,for which abnormal cellular alterations that accompany chronic inflammation
such as oxidative stresses,gene mutations,epigenetic changes,and inflammatory cytokines,are shared with carcinogenic processes,which forms a critical cross-link between chronic inflammation and carcinogenesis.Transforming growth factor (TGF)-β is a multi-potent cytokine that plays an important role in regulation of cell growth,apoptosis and differentiation.Most importantly,TGF-β is a strong anti-inflammatory cytokine that regulates the development of 通常 effector cells.TGF-β has a suppressive effect on carcinogenesis under normal conditions by inhibiting abnormal cell growth,but on the other hand,many GI cancers originate from uncontrolled cell growth and differentiation by genetic loss of TGF-β signaling molecules or perturbation of TGF-β adaptors.Once a tumor has developed,TGF-β exerts a promoting effect on the tumor itself and stromal cells to enhance cell growth,alter the responsiveness of tumor cells to stimulate invasion and metastasis,and inhibited immune surveillance.Therefore,novel development of therapeutic agents to inhibit TGF-β-induced progression of tumor and to retain its growth inhibitory activities,in addition to anti-inflammatory actions,could be useful in oncology.In this review,we discuss the role of TGF-β in inflammation and carcinogenesis of the GI tract related to abnormal TGF-β signaling.