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BM Pützer M Hitt WJ Muller P Emtage J Gauldie FL Graham 《Canadian Metallurgical Quarterly》1997,94(20):10889-10894
Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host-tumor relationship involves immunomodulating cytokines and also the presence of costimulatory molecules. To examine the antitumor effect of direct in vivo gene transfer of murine interleukin 12 (IL-12) and B7-1 into tumors, we developed an adenovirus (Ad) vector, AdIL12-B7-1, that encodes the two IL-12 subunits in early region 1 (E1) and the B7-1 gene in E3 under control of the murine cytomegalovirus promoter. This vector expressed high levels of IL-12 and B7-1 in infected murine and human cell lines and in primary murine tumor cells. In mice bearing tumors derived from a transgenic mouse mammary adenocarcinoma, a single intratumoral injection with a low dose (2.5 x 10(7) pfu/mouse) of AdIL12-B7-1 mediated complete regression in 70% of treated animals. By contrast, administration of a similar dose of recombinant virus encoding IL-12 or B7-1 alone resulted in only a delay in tumor growth. Interestingly, coinjection of two different viruses expressing either IL-12 or B7-1 induced complete tumor regression in only 30% of animals treated at this dose. Significantly, cured animals remained tumor free after rechallenge with fresh tumor cells, suggesting that protective immunity had been induced by treatment with AdIL12-B7-1. These results support the use of Ad vectors as a highly efficient delivery system for synergistically acting molecules and show that the combination of IL-12 and B7-1 within a single Ad vector might be a promising approach for in vivo cancer therapy. 相似文献
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Seiz Marco Offenhäuser Philipp Andersson Stefan Hötzer Johannes Hierl Henrik Nestler Britta Resch Michael 《The Journal of supercomputing》2021,77(11):12508-12536
The Journal of Supercomputing - With ever-increasing computational power, larger computational domains are employed and thus the data output grows as well. Writing this data to disk can become a... 相似文献
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Two types of model catalysts are compared: thin film catalysts consisting of polyhedral noble metal nanocrystals (Rh and Pt) supported by reducible and non‐reducible oxides, and their inverted pendants, submonolayers of titania and vanadia deposited under UHV conditions on the respective metal surfaces (Pd and Rh(111) and Rh (polycrystalline)). The structure and composition of the inverse catalysts were examined in situ by LEED and AES and the nanoparticles were characterized by HRTEM. The activity of thin film and inverse catalysts was studied in a series of reactions, such as the ring opening of methylcyclopentane and methylcyclobutane, the dissociation of CO and the CO methanation. Reaction conditions comprise atmospheric pressure but also molecular beam experiments. The reaction rates are related to the oxidation state of the supporting oxide, to the free metal surface area and to the number of sites at the interface between metal and support. This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
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Felicitas Stoll Andrea Seidel-Gltzer Ina Burghaus Oliver Gring Max Sauter Peter Rose Volker Daniel Mathias Haag Matthias Schwab Johannes Riffel Florian Andr Lenka Taylor Johanna Weiss Jürgen Burhenne Volker Cleeves Walter E. Haefeli Antje Blank 《International journal of molecular sciences》2022,23(24)
Bile acids (BA) play an important role in cholesterol metabolism and possess further beneficial metabolic effects as signalling molecules. Blocking the hepatocellular uptake of BA via sodium-taurocholate co-transporting polypeptide (NTCP) with the first-in-class drug bulevirtide, we expected to observe a decrease in plasma LDL cholesterol. In this exploratory phase I clinical trial, volunteers with LDL cholesterol > 130 mg/dL but without overt atherosclerotic disease were included. Thirteen participants received bulevirtide 5 mg/d subcutaneously for 12 weeks. The primary aim was to estimate the change in LDL cholesterol after 12 weeks. Secondary endpoints included changes in total cholesterol, HDL cholesterol, lipoprotein(a), inflammatory biomarkers, and glucose after 12 weeks. In addition, cardiac magnetic resonance imaging (CMR) was performed at four time points. BA were measured as biomarkers of the inhibition of hepatocellular uptake. After 12 weeks, LDL cholesterol decreased not statistically significantly by 19.6 mg/dL [−41.8; 2.85] (Hodges–Lehmann estimator with 95% confidence interval). HDL cholesterol showed a significant increase by 5.5 mg/dL [1.00; 10.50]. Lipoprotein(a) decreased by 1.87 mg/dL [−7.65; 0]. Inflammatory biomarkers, glucose, and cardiac function were unchanged. Pre-dose total BA increased nearly five-fold (from 2026 nmol/L ± 2158 (mean ± SD) at baseline to 9922 nmol/L ± 7357 after 12 weeks of treatment). Bulevirtide was generally well tolerated, with most adverse events being administration site reactions. The exploratory nature of the trial with a limited number of participants allows the estimation of potential effects, which are crucial for future pharmacological research on bile acid metabolism in humans. 相似文献
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S. Alioli S. Badger J. Bellm B. Biedermann F. Boudjema G. Cullen A. Denner H. van Deurzen S. Dittmaier R. Frederix S. Frixione M.V. Garzelli S. Gieseke E.W.N. Glover N. Greiner G. Heinrich V. Hirschi S. Höche J. Huston H. Ita N. Kauer F. Krauss G. Luisoni D. Maître F. Maltoni P. Nason C. Oleari R. Pittau S. Plätzer S. Pozzorini L. Reina C. Reuschle T. Robens J. Schlenk M. Schönherr F. Siegert J.F. von Soden-Fraunhofen F. Tackmann F. Tramontano P. Uwer G. Salam P. Skands S. Weinzierl J. Winter V. Yundin G. Zanderighi M. Zaro 《Computer Physics Communications》2014
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本文通过高效液相色谱检测,研究了儿茶素在三种不同液相体系(对照系;吐温20-胶束体系;磷脂-脂质体乳化体系)中的自动氧化模式。结果表明:不管是在pH3.5还是pH4.5下,与对照相比,嵌和在吐温20-胶束体系和磷脂-脂质体乳化体系中的儿茶素自动氧化速度显著降低(即这两种双亲和结构对儿茶素免遭氧化有保护作用);而且,磷脂-脂质体乳化体系中的儿茶素自动氧化速度比吐温20-胶束体系中更低。 相似文献
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Transient CFD simulations are performed to investigate the flow behaviour inside an unshrouded pump using the SAS method. Two blade designs are compared at two different tip clearances and the results are validated by measurements. The detected vortex structure is visualized by the normalized helicity, further discussed regarding its development and behaviour and finally implicated to the efficiency of the two different blade designs. 相似文献