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81.
A new Monte Carlo approach for the computation of the electron spectra of electron-capture nuclides is applied to obtain efficiencies in liquid scintillation counting for CIEMAT/NIST applications. The new method is applied to the radionuclides 109Cd and 125I by using a stochastic atomic rearrangement model, taking into account rearrangement processes including L-, M-, and N-subshells. The counting efficiencies were computed with the new code MICELLE which also comprises an approach for calculating the counting efficiency of a radionuclide in a gel phase sample. The calculated counting efficiencies are compared with experimental results. 相似文献
82.
《Expert opinion on investigational drugs》2013,22(7):917-920
More than one-third of the world is infected with tuberculosis (TB) and 5000 people die of TB everyday. Of the many diarylquinolones shown to be effective at inhibiting the multiple-cycle growth of Mycobacterium tuberculosis, R-207910 was the most active and was chosen as the lead compound. In the non-established infection mouse TB model, a single dose of R-207910 50 mg/kg had a bacteriostatic effect, and a bactericidal effect was observed at 100 mg/kg. In the established infection mouse model, treatment was started 12 – 14 days after infection, and when added to the triple therapy of isoniazid, rifampin and pyrazinamide or substituted for any component of the triple therapy, R-207910 increased the effectiveness. As ethambutol is chemically simple, and only has modest potency in treating TB, it was considered to be amenable to optimisation by combinatorial chemistry, and from the analogues synthesised that inhibited the growth of M. tuberculosis, SQ-109 was eventually selected as the lead compound for further testing. In female mice infected with M. tuberculosis H37Rv by tail-vein injection, treatment with SQ-109 25 mg p.o. initiated 20 days later for 5 days/week for 4 weeks reduced the counts by 1.87 log units, which was slightly more than with ethambutol 100 mg (1.67 log units). These results indicate that exciting new drugs are under development for the treatment of TB. 相似文献
83.
84.
Purpose. To investigate the blood-brain barrier (BBB) passage of theM1 muscarine agonist Lu 25-109(5-(2-Ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-methylpyridine) and potential metabolites using in vivomicrodialysis.
Methods. Anesthetized rats were administered an intravenous infusionof one of seven analogs with a Log D7.4 ranging from 0.35 to –2.4.Microdialysis probes were implanted in the brain and the jugular vein.The integrity of the BBB was evaluated using2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA), a compound notexpected to penetrate the BBB. The data was corrected for in vitrorecovery.
Results. Lu 25-109, Lu 24-165 (demethylated Lu 25-109) and Lu25-077 (N-demethylated Lu 25-109) entered the brain in a 1:1 ratio withthe blood. Although Lu 29-081 (hydroxylated Lu 25-109) presented asimilar Log D7.4 to Lu 25-109 and Lu 24-164, it entered the brain witha lower brain:blood ratio of 0.5. Lu 32-181 (Lu 25-109 N-oxide), Lu35-026 (deethylated and oxidized Lu 25-109) and Lu 31-126(deethylated Lu 25-109) were not detected in the brain samples, indicating nopenetration. Infusion of Lu 25-109 resulted in a time perspective ofthe formation and distribution of the two metabolites Lu 25-077 andLu 32-181. Although the hydroxylated compound (Lu 29-081) had aLog D7.4 of –0.6, within the range 0.35 to –0.83 of the compoundspenetrating the BBB, it showed a brain: blood ratio of 0.5. Lu 35-026showed an unusual infusion profile with a tmax of 100–150 min and asubsequent decrease in blood concentration.
Conclusions. Compounds with Log D7.4 above –0.83 penetrated theBBB, whereas compounds below –1.5 did not. Knowledge of LogD7.4 values is not sufficient to evaluate BBB passage because the valuedoes not predict the influence of active transport processes. 相似文献
85.
新疆天然植物黑加仑对食管癌细胞增殖、凋亡的影响 总被引:2,自引:0,他引:2
目的:观察新疆天然植物黑加仑水提物对食管癌细胞的影响及其作用机制。方法:采用四甲基偶氮唑蓝(MTT)法测定不同浓度(10-1、10-2、10-3g/ml)黑加仑水提物作用不同时间(12、24、36h)对人食管癌细胞株Eca109的细胞存活量的影响,以大鼠正常肝细胞(BRL)为正常对照细胞株;用Bradford法测定肿瘤细胞蛋白质合成的变化;采用流式细胞技术(FCM)观察黑加仑作用后肿瘤细胞周期变化及凋亡情况;通过倒置显微镜观察细胞的形态变化。结果:黑加仑水提物10-1g/ml组对人食管癌细胞株Eca109作用24h后,癌细胞的生长和蛋白合成均有明显抑制作用(P<0.05),对正常肝细胞的存活量及蛋白合成均无影响;流式细胞仪检测二倍体峰前出现凋亡峰,细胞凋亡率为49.6%;并且癌细胞呈现典型的凋亡细胞形态。结论:黑加仑水提物可通过诱导细胞凋亡而抑制人食管癌细胞株Eca109细胞的生长。 相似文献
86.
槲寄生碱抗肿瘤作用的研究 总被引:13,自引:0,他引:13
目的通过体内、体外实验研究槲寄生碱的抗肿瘤作用。方法体外实验采用MTT法测定槲寄生碱对食管癌细胞株(Eca109)生长的抑制作用。取对数生长期的肿瘤细胞培养24h后加入含不同浓度槲寄生碱培养液;作用24h后倾去上清液,加入MTT;4h后吸去上清液,加入二甲亚砜(DMSO);30min后测吸光度(A)并计算抑制率;体内实验将制备的肿瘤细胞悬液,以0.2mL/只的量接种于小鼠右前肢腋部皮下,24h后将已接种的小鼠随机分组。各组均连续给药7d,停药后1~3d将小鼠拉颈处死,剥取瘤块称重,计算抑瘤率。结果体外实验证实槲寄生碱对肿瘤细胞生长有显著的抑制作用;体内实验证实槲寄生碱可抑制肿瘤生长、延长荷瘤动物的生存期。结论槲寄生碱具有抗肿瘤作用。 相似文献
87.
Tetsuro Taki Yukihiro Shiraki Atsushi Enomoto Liang Weng Chen Chen Naoya Asai Yoshiki Murakumo Kohei Yokoi Masahide Takahashi Shinji Mii 《Cancer science》2020,111(12):4616
Stromal invasion is considered an important prognostic factor in patients with lung adenocarcinoma. The mechanisms underlying the formation of tumor stroma and stromal invasion have been studied in the lung; however, they are still unclear. CD109 is a glycosylphosphatidylinositol‐anchored glycoprotein highly expressed in several types of human malignant tumors including lung cancers. In this study, we investigated the in vivo functions of CD109 protein in malignant lung tumors. Initially, we identified an association between higher expression of CD109 protein in human lung adenocarcinoma and a significantly worse prognosis, according to immunohistochemical analysis. We also showed that CD109 deficiency significantly reduced the area of stromal invasive lesions in a genetically engineered CD109‐deficient lung adenocarcinoma mouse model, which correlated with the results observed in human lung adenocarcinoma. Furthermore, we identified latent TGF‐β binding protein‐1 (LTBP1) as a CD109‐interacting protein using mass spectrometry and confirmed their interaction by co‐immunoprecipitation. Importantly, increased CD109 expression enhanced stromal TGF‐β activation in the presence of LTBP1. Therefore, these data suggest the significance of the regulation of TGF‐β signaling through CD109 and LTBP1 interaction in tumor stroma and also reveal the importance of CD109 expression levels in promoting lung cancer cell proliferation, migration, and invasion, and thus predicting the outcome of patients suffering from lung adenocarcinoma. Therefore, CD109 protein could be a potential therapeutic target for this disease. 相似文献
88.
目的探讨Bufalin对食管鳞状细胞癌ECA109细胞中FAK活化和上皮-间质转化(epithelial-mesenehymal transition,EMT)的影响。方法采用RT-PCR法检测不同浓度Bufalin对食管鳞状细胞癌ECA109细胞中FAK、E-cadherin、vimentin mRNA表达的影响。Western blot法检测不同浓度Bufalin对ECA109细胞中FAK活化水平及FAK、E-cadherin、vimentin蛋白表达的影响。采用Transwell小室实验检测不同浓度Bufalin对ECA109细胞迁移与侵袭能力的影响。结果 RT-PCR结果表明Bufalin抑制FAK、E-cadherin、vimentin的mRNA表达。Western blot结果表明Bufalin抑制E-cadherin、vimentin的表达和FAK的活化。Transwell实验结果表明Bufalin可以抑制ECA109细胞的迁移及侵袭。药物干预组(20、40、60、80、100 nmol/L Bufalin及PF562271组)与阳性对照组相比,Transwell迁移实验结果显示穿过基膜的细胞个数由107.00±8.19下降至78.67±3.06、61.67±3.06、42.67±3.512、24.33±2.517、10.33±3.215、9.00±2.65;Transwell侵袭实验结果显示穿过基膜的细胞个数由127.67±8.02下降至102.33±4.51、87.33±7.10、73.00±4.58、57.33±2.52、39.00±3.61、37.33±2.52,差异均有统计学意义(P0.05)。结论 Bufalin可以抑制食管鳞状细胞癌中FAK的活化,提示Bufalin可能是通过下调FAK来抑制食管鳞状细胞癌EMT过程及食管癌的迁移及侵袭。 相似文献
89.
环氧化酶-2选择性抑制剂抑制人食管癌细胞的生长及其诱导凋亡 总被引:2,自引:0,他引:2
目的:探讨NS-398对食管癌细胞的生物学效应及可能的作用机制.方法:常规方法培养食管癌Eca-109和TE-13细胞,以不同浓度NS-398(5,10,20,40,80 μmol/L)处理24,48,72 h.采用四甲基唑蓝法(MTT)检测NS-398对Eca-109和TE-13细胞生长的抑制作用;流式细胞仪(FCM)检测细胞凋亡及COX-2,Bcl-2,Bax蛋白的表达;TUNEL法检测2种细胞凋亡情况;用放射免疫分析(RIA)检测培养液上清中前列腺素E2(PGE2)含量.结果:NS-398可抑制2种细胞的生长,并随药物浓度的增高及作用时间的延长抑制率逐渐增高,并使2种细胞产生的PGE2明显降低.NS-398使2种细胞G0/G1期细胞显著增多,S期细胞显著减少(Eca-109:F=22.39,P<0.01;TE-13:F=46.99,P<0.01),并引起了明显的细胞凋亡.NS-398使2种细胞COX-2和Bcl-2表达显著减少,而Bax表达显著增高.COX-2和Bcl-2的表达呈显著正相关(Eca-109:r=0.925,P<0.01;TE-13:r=0.925,P<0.01),COX-2和Bax表达呈显著负相关(Eca-109:r=-0.937,P<0.01;TE-13:r=-0.703,P<0.01)、Bax和bcl-2表达呈显著负相关(Eca-109:r=-0.926,P<0.01;TE-13:r=-0.753,P<0.01).结论:NS-398可抑制食管癌细胞的增殖并可诱导其凋亡,应用COX-2选择性抑制剂对食管癌进行化学预防或辅助治疗具有可能性. 相似文献
90.
仙鹤草水提液对食管癌Eca109细胞生长的抑制作用 总被引:10,自引:0,他引:10
目的:研究仙鹤草水提液对人食管癌Eca109细胞生长的抑制作用及其可能机制.方法:MTT法测定0g/L、2 g/L、4 g/L、8 g/L、16 g/L的仙鹤草水提液分别作用于Eca109细胞24 h、48 h、72 h,观察对Eca109细胞生长的抑制作用;采用免疫组织化学染色技术检测16 g/L仙鹤草水提液作用72 h对Eca109细胞Bcl-2、P53蛋白表达的影响.结果:MTT结果显示16 g/L仙鹤草水提液作用48 h和72 h后Eca109细胞生长明显受抑;免疫组化结果显示16 g/L仙鹤草水提液作用72 h后Eca109细胞内Bcl-2蛋白表达下调,P53蛋白表达上调.结论:仙鹤草水提液体外能诱导Eca109细胞凋亡,其机制可能与下调Bcl-2蛋白表达及上调P53蛋白表达有关. 相似文献