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Deniz Caylioglu Rieke Johanna Meyer Dana Hellmold Carolin Kubelt Michael Synowitz Janka Held-Feindt 《International journal of molecular sciences》2021,22(7)
Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences. 相似文献
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Dr. Omer K. Rasheed Cassandra Buhl Dr. Jay T. Evans Dr. Kendal T. Ryter 《ChemMedChem》2021,16(8):1246-1251
Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha (TNF) and promote the development of a Th1/Th17 immune response that might be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6′-amide and sulfonamide α,α-d -trehalose compounds with various substituents on the aromatic ring was synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-type lectin receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure–activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human-Mincle-specific stimulation in a HEK reporter cell line. 相似文献
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《Planning》2015,(12):33-35
目的:探讨IL-27与LTB4在非小细胞肺癌组织中的表达情况及临床意义。方法:采用免疫组化S-P法分别检测60例非小细胞肺癌组织及正常肺组织中的IL-27与LTB4的表达水平。结果:IL-27与LTB4在肺癌组织中的总阳性表达率分别为41.67%、63.33%,各种检测指标的阳性率在肺癌组织与对照组之间均存在着差异性(P<0.05)。IL-27与LTB4的表达均与肿瘤的分化程度有关(P<0.05),IL-27的表达与肺癌的TNM分期相关(P<0.05),与病理类型无关(P>0.05)。LTB4的表达与组织学类型、临床分期无关(P>0.05),IL-27与LTB4之间存在密切相关性。结论:IL-27、LTB4与肺癌发生机制及发展有密切关系,联合进行检测两者表达水平对于肺癌临床诊断、评估恶性程度及判断预后有重要意义。 相似文献
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In this paper, any two of the three anticorrosion agents, that is emulsifier (OP-10), soluble glass (Na2O·nSiO2) and glycerin (C3H8O3), were treated simultaneously on the surface of amorphous (a-) MgNi+5% Ml2Mg17 (Ml denotes the lanthanum-rich mish metal) electrode and the electrolyte. Effect of the synergistic anticorrosion treatment on charging/discharging cycle stability of the electrode was investigated. Contrasted with single treatment method, the cycling stability of the electrodes was further improved. The desirable synergistic anticorrosion method was that the electrode was treated by the soluble glass, and that OP-10 was added into the electrolyte. The cyclic voltammogram (CV) results of the electrode show clearly that the anticorrosion agent can change the electrochemical activity and mechanism of the electrode. The concentration of the anticorrosion agent in the electrolyte treated by the synergistic anticorrosion method was also investigated. The appropriate concentration of the anticorrosion agents in the electrolyte is 0.143%. 相似文献
8.
M. K. Karthikeyan R. K. Gupta V. Rajesh B. R. Ghosh P. P. Sinha 《Journal of Failure Analysis and Prevention》2007,7(6):429-433
17-4 PH stainless steel is used as internal drive shaft material in liquid engine pumps. One of the drive shafts failed during
operation. The shaft pieces were in contact for short duration after failure, which has resulted in abrasion of fractured
surfaces. Samples from the location of failure were taken, and investigation of the failure was carried out using optical
and scanning electron microscopy. The microstructural analysis of the material and fractographic analysis of the fractured
surface show that the failure was caused by excessive torsion. 相似文献
9.
^17O系统的R矩阵分析 总被引:2,自引:1,他引:1
采用多道多能级R矩阵理论,全面系统地分析~(17)O系统中10.5 MeV激发能以下有关~(16)O(n,n)~(16)O·~(16)O(n,a)~(13)C和~(13)C(a,a)~(13)C的全部实验数据。有关~(16)O的中子反应截面计算值被收入中国评价数据库CENDL-2和美国的评价数据库ENDF/B-6。对在R矩阵分析中如何确定本底、道半径和边界条件等问题予以讨论。 相似文献
10.
通过分析影响磁体高温性能的因素,设计了新磁体的成分为:Cu含量高,Fe含量低,Zr适量,Sm含量高;采用粉末冶金工艺制备了高温Sm_2(CoFeCuZr)_(17)永磁体。制得的磁体室温磁性能为:B_r1.075 T,H_(ei)2 098.2 kA/m,H_(eb) 776.1 kA/m,H_k843.8 kA/m,(BH)_(max)210.0 kj/m~3;在200℃时的磁性能为:B_r0.991 T,H_(ci)1 175.7 kA/m,H_(cb)531.7 kA/m,H_k577.9 kA/m,(BH)_(max)172.5 kJ/m~3;矫顽力温度系数β(20~200℃)为-0.24%/℃。经理论分析和实验验证,磁体的使用温度均超过400℃,为高温环境(高于400℃)提供了一种实用性永磁材料。 相似文献