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1.
Transforming growth factor-β (TGF-β) superfamily signaling via their cognate receptors is frequently modified by TGF-β superfamily co-receptors. Signaling through SMAD-mediated pathways may be enhanced or depressed depending on the specific co-receptor and cell context. This dynamic effect on signaling is further modified by the release of many of the co-receptors from the membrane to generate soluble forms that are often antagonistic to the membrane-bound receptors. The co-receptors discussed here include TβRIII (betaglycan), endoglin, BAMBI, CD109, SCUBE proteins, neuropilins, Cripto-1, MuSK, and RGMs. Dysregulation of these co-receptors can lead to altered TGF-β superfamily signaling that contributes to the pathophysiology of many cancers through regulation of growth, metastatic potential, and the tumor microenvironment. Here we describe the role of several TGF-β superfamily co-receptors on TGF-β superfamily signaling and the impact on cellular and physiological functions with a particular focus on cancer, including a discussion on recent pharmacological advances and potential clinical applications targeting these co-receptors.  相似文献   
2.
目的:观察黄芪多糖诱导的树突状细胞(dendritic cells,DC)和细胞因子诱导的杀伤细胞(cytokine-induced killer cells,CIK)对人食管癌Eca-109细胞作用的影响。方法:取健康人外周血单个核细胞在体外培养DC和CIK细胞,观察经APS(astragalus polysaccharide,APS)诱导DC细胞和常规培养的DC细胞形态和数量的区别,并分为APS诱导组:APS-DCCIK组,即经黄芪多糖诱导的DC与同源CIK共培养组;对照组:DC-CIK+APS组,即常规方法培养的DC与同源CIK共培养加用等量黄芪多糖组(100 mg·L~(-1));空白组:DC-CIK组,即常规方法培养的DC与同源CIK共培养组。(各组DC∶CIK=1∶5)。检测三组靶效比分别为2.5∶1、5∶1、10∶1时对Eca-109细胞的毒性。结果:APS诱导的DC细胞较空白组细胞集落多而且大;APS诱导DC细胞数量显著高于空白组,差异有统计学意义(P0.05);当DC∶CIK=1∶5时,APS诱导DC-CIK细胞数量明显高于空白组(P0.05);DC∶CIK=1∶5,效靶比分别为2.5∶1、5∶1、10∶1时,APSDC-CIK组的细胞毒活性明显高于DC-CIK组和DC-CIK+APS组,差异有统计学意义(P0.05)。结论:APS不仅可增加DC和DC-CIK细胞的增殖能力,还可增强DC-CIK细胞对食管癌Eca-109细胞的杀伤效应。  相似文献   
3.
目的:研究中药莪术醇联合顺铂对食管癌109细胞系的增殖凋亡、核因子(NF)-κB表达的影响,探讨莪术醇抗肿瘤的分子机制。方法将不同浓度莪术醇、顺铂、莪术醇和顺铂联合作用于食管癌109细胞,用噻唑蓝比色法(MTT 法)检测细胞增殖,流式细胞仪检测细胞凋亡, Western blot 法检测作用48小时后细胞 NF-κB 蛋白的表达情况。结果不同浓度莪术醇、顺铂均对食管癌细胞均有抑制增殖、促进凋亡作用,抑制率、凋亡率呈明显浓度依耐性;联合用药后抑制率、凋亡率显著提高,差异有统计学意义(P <0.05);4个浓度的莪术醇与顺铂(2.5 mg/L)作用食管癌48小时后 NF-κB 的表达量随浓度增加而下降,与对照组比较差异有统计学意义(P <0.05)。结论中药莪术醇对人食管癌109细胞株有明显抑制增殖,诱导凋亡的作用,其机制可能与下调NF-κB 蛋白的表达有关。  相似文献   
4.
目的 探讨神经生长因子(NGF)与食管鳞癌细胞分化的相关性。方法 采用有限稀释法分选出圆形和梭形单细胞克隆,采用无血清悬浮培养获得细胞球细胞, 贴壁的Eca109细胞分别在含血清和不含血清培养基中培养48h;分别采用反转录-聚合酶链式反应(RT-PCR)技术和免疫印迹法,检测NGF在食管鳞癌细胞中mRNA水平和蛋白水平的表达;免疫荧光技术检测NGF在食管鳞癌细胞中的表达定位;免疫组织化学法检测食管鳞癌组织中NGF的表达定位;用酶联免疫吸附法(ELISA)检测NGF在Eca109细胞培养基中的分泌情况。结果 在Eca109细胞中能检测到NGF的mRNA水平和蛋白水平的表达,其中NGF在细胞球细胞中的mRNA水平和蛋白水平的表达量最高。食管癌组织中检测到NGF表达于细胞质。Eca109细胞在无血清培养条件下能够分泌NGF,且明显高于含血清培养基中的含量。结论 食管癌细胞系Eca109表达并分泌NGF,并且食管癌组织中表达NGF,NGF可能在维持食管鳞状细胞癌的干细胞特性发挥了重要作用。  相似文献   
5.
目的 利用RNAi (RNA interference, RNAi) 技术抑制食管癌Eca-109细胞survivin基因表达,观察survivin基因沉默后对Eca-109细胞化疗敏感性的影响。方法 构建靶向survivin基因特定序列的小干扰RNA(small interference RNA, siRNA)真核表达载体并转染Eca-109细胞,筛选得到稳定转染的survivin干扰组细胞Eca-109 /si-survivin,同时设转染无关干扰质粒的Eca-109细胞为阴性对照组,未转染的Eca-109细胞为空白对照组;通过Western Blot法检测干扰前后survivin基因沉默抑制效果;随后将各组细胞与不同浓度的氟尿嘧啶(5-Fu)作用,MTT法检测各组细胞对5-Fu的半数抑制浓度(IC50),流式细胞仪分析各组细胞的凋亡率。结果 干扰组Eca-109 /si-survivin细胞survivin蛋白表达水平(18.75±3.12)较阴性对照组Eca-109 /si-control(44.17±3.15)及空白对照组Eca-109 (46.20±2.62)明显下调(P<0.05);联合应用5-Fu的Eca-109 /si-survivin干扰组细胞IC50为(18.75±1.53)mg·L-1,显著低于空白对照组(39.65±1.75)mg·L-1和阴性对照组(38.95±1.34)mg·L-1,差异具有统计学意义(P<0.05);联合应用5-Fu的Eca-109 /si-survivin干扰组细胞凋亡率为(37.35±1.52)%,明显高于空白对照组(11.26±1.21)%和阴性对照组(12.34±1.32)%,差异具有显著性(P<0. 05)。 结论 靶向survivin的siRNA能特异性沉默survivin基因表达,抑制细胞增殖,诱导细胞凋亡,并增强人食管癌Eca-109细胞对5-Fu的化疗敏感性。  相似文献   
6.
目的:探讨全反式维甲酸(ATRA)、5-氟尿嘧啶(5-FU)单独或联合作用对Eca109细胞增殖、迁移和血管内皮生长因子(VEGF)表达的影响。方法:将常规传代的Eca109细胞分为4组:ATRA组、5-FU组、ATRA+5-FU组和对照组,采用MTT法检测各组细胞的增殖情况,通过划痕实验测定各组细胞的迁移能力,采用RT-PCR和免疫细胞化学法分别检测各组细胞VEGF mRNA和蛋白的表达情况。结果:作用24、48和72 h后,ATRA+5-FU组的细胞生长抑制率均高于其他2组(F=23.432、13.605、73.369,P均<0.05);作用24 h后,ATRA+5-FU组的迁移率均低于其他3组(P均<0.001);作用48 h后,ATRA+5-FU组细胞VEGF mRNA和蛋白的相对表达量均低于其他3组(P均<0.05)。结论:ATRA、5-FU均能抑制食管癌细胞的增殖,且联合用药效果更为显著,可能与其抑制肿瘤血管生成有关。  相似文献   
7.
The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug-resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four-drug treatment regimen was introduced 40 years ago but the emergence of multidrug-resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti-TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug-target interactions, and their structure-activity relationship.  相似文献   
8.
9.
Colorectal cancer arises via a multistep carcinogenic process and the deregulation of multiple pathways. Thus, the simultaneous targeting of multiple pathways may be a promising therapeutic approach for colorectal treatment. CRM1 is an attractive cancer drug target, because it can regulate multiple pathways and tumor suppressor proteins. In this study, we investigated the anti-tumor activity of a novel reversible CRM1 inhibitor S109 in colorectal cancer. Our data demonstrate that S109 inhibits proliferation and induces cell cycle arrest in colorectal cancer cells. Mechanistically, we demonstrate that the activity of S109 is associated with the nuclear retention of major tumor suppress proteins. Furthermore, the Cys528 mutation of CRM1 prevented the ability of S109 to block nuclear export and inhibit the proliferation of colorectal cancer cells. Interestingly, S109 decreased the CRM1 protein level via proteasomal pathway. We argue that reversible CRM1 inhibitors but not irreversible inhibitors can induce the degradation of CRM1, because the dissociation of reversible inhibitors of CRM1 changes the conformation of CRM1. Taken together, these findings demonstrate that CRM1 is a valid target for the treatment of colorectal cancer and provide a basis for the development of S109 therapies for colorectal cancer.  相似文献   
10.
Study ObjectiveTo assess the efficacy of Tissucol Duo (Baxter AG, Vienna, Austria) fibrin sealant in decreasing the incidence of lymphocele (LC) after pelvic laparoscopic lymph node dissection using harmonic shears.DesignRandomized controlled trial (Canadian Task Force classification level I).SettingTertiary referral and educational center.PatientsSeventy-four patients randomized to the use of sealant per hemipelvis.InterventionFibrin sealant.Measurements and Main ResultsAfter bilateral pelvic lymphadenectomy a fibrin sealant was used in 1 hemipelvis but not the other, applied in 41 patients (55.4%) to the left and 33 patients (44.6%) to the right hemipelvis. The primary outcome was the incidence of LC after surgery in symptomatic and asymptomatic patients. Imaging (ultrasound, computed tomography, and magnetic resonance) was performed to detect LC at 3, 6, and 12 months after surgery. Overall, 26 patients (35.1%) developed LC, and 4 were symptomatic (5.4%). Allowing patients to serve as their own treatment group and control, the hemipelvis treated with Tissucol Duo corresponding to the treatment group and that not treated to the control group, LCs were found in 17 (23%) and 14 (19%) cases, respectively, but the difference was not significant. The mean initial LC maximum diameter was 27.1 mm (standard deviaiotn, 35.2), and LCs tended to decrease in size during the first year to a mean of 8.7 mm.ConclusionApplication of Tissucol Duo fibrin sealant after laparoscopic pelvic lymphadenectomy using ultrasonic shears does not decrease the occurrence of symptomatic or asymptomatic LC.  相似文献   
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