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971.
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite numerous efforts to target epidermal growth factor receptor (EGFR), commonly dysregulated in GBM, approaches directed against EGFR have not achieved the same degree of success as seen in other tumor types, particularly as compared to non-small cell lung cancer (NSCLC). EGFR alterations in glioblastoma lie primarily in the extracellular domain, unlike the kinase domain alterations seen in NSCLC. Small molecule inhibitors are difficult to develop for the extracellular domain. Monoclonal antibodies can be developed to target the extracellular domain but must contend with the blood brain barrier (BBB). We review the role of EGFR in GBM, the history of trialed treatments, and the potential paths forward to target the pathway that may have greater success. 相似文献
972.
Dr. Liam J. Stephens Dr. Aviva Levina Dr. Iman Trinh Dr. Victoria L. Blair Dr. Melissa V. Werrett Prof. Peter A. Lay Prof. Philip C. Andrews 《Chembiochem : a European journal of chemical biology》2020,21(8):1188-1200
RuII-arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new RuII-arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes ( 2 a , b and 5 ) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC50=39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity. 相似文献
973.
Veronika Stahl Yuan Shi Werner Kraft Tim Lanz Peter Vetter Raouf Jemmali Fiona Kessel Dietmar Koch 《International Journal of Applied Ceramic Technology》2020,17(5):2040-2050
Thanks to their high energy density and thermal conductivity, metallic Phase Change Materials (mPCM) have shown great potential to improve the performance of thermal energy storage systems. However, the commercial application of mPCM is still limited due to their corrosion behavior with conventional container materials. This work first addresses on a fundamental level, whether carbon-based composite-ceramics are suitable for corrosion critical components in a thermal storage system. The compatibility between the mPCM AlSi12 and the Liquid Silicon Infiltration (LSI)-based carbon fiber reinforced silicon carbide (C/C-SiC) composite is then investigated via contact angle measurements, microstructure analysis, and mechanical testing after exposure. The results reveal that the C/C-SiC composite maintains its mechanical properties and microstructure after exposure in the strongly corrosive mPCM. Based on these results, efforts were made to design and manufacture a container out of C/C-SiC for the housing of mPCM in vehicle application. The stability of the component filled with mPCM was proven nondestructively via computer tomography (CT). Successful thermal input- and output as well as thermal storage ability were demonstrated using a system calorimeter under conditions similar to the application. The investigated C/C-SiC composite has significant application potential as a structural material for thermal energy storage systems with mPCM. 相似文献
974.
Dr. Ivan A. Yaremenko Dr. Paolo Coghi Parichat Prommana Congling Qiu Peter S. Radulov Yuanqing Qu Yulia Yu. Belyakova Dr. Enrico Zanforlin Dr. Vladimir A. Kokorekin Yuki Yu Jun Wu Prof. Fabrice Fleury Dr. Chairat Uthaipibull Dr. Vincent Kam Wai Wong Prof. Alexander O. Terent'ev 《ChemMedChem》2020,15(13):1118-1127
This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC50=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma. 相似文献
975.
Wolfgang Habel Werner Haeusler Peter Sartori 《Advanced Synthesis \u0026amp; Catalysis》1995,337(1):589-592
Photochlorination and Metalorganic Following Reactions of a Cross-linked Poly(carbosilane) The synthesis of a perchlorinated cross-linked poly(carbosilane) of the general composition [(Cl2Si)1,5(SiCl) (CCl2)3]x ( II ) was achieved through the photochlorination of [(Cl2Si)1,5(SiCl)(CH2)3]x ( I ). The perchlorinated product was investigated by elemental analysis and spectroscopic methods. Furthermore the permethylated and perphenylated compounds [(Me2Si)1,5(SiMe)(CMe2)3]x ( III ) and [(Ph2Si)1,5(SiPh)(CPh2)3]x ( IV ) were synthesized by reactions with methyl- and phenyllithium. The products obtained were characterized by elemental analysis and 1H, 13C, 29Si NMR and IR spectroscopy. The number and weight averages Mn and Mw were determined by gel permeation chromatography. 相似文献
976.
977.
A new nanocomposite of Ge/carbon nanotubes (n-Ge/CNTs) was reported by a facile precursor method through a pyrolysis technique. Among it, germanium nanoparticles are encapsulated with a thin layer of amorphous carbon, which benefits to keep a good electronic contact with carbon nanotubes. Germanium nanoparticles are mainly supported inside the carbon nanotubes, which can effectively buffer the volume changes of Germanium. The composite was an effectively mixed (Li+ and e−) conducting network, which is vital to a quick Li insertion. The composite was shown to exhibit a reversible capacity of about 750 mAh g−1 (74.4 mA g−1) and an improved rate performance, compared with that of CNTs processed as the same condition. Our results demonstrated the composite to be a good active Li-storage material for Li batteries. 相似文献
978.
Long‐term testing of a high temperature polymer electrolyte membrane fuel cell: The effect of reactant gases 下载免费PDF全文
F. Javier Pinar Nadine Pilinski Peter Wagner 《American Institute of Chemical Engineers》2016,62(1):217-227
The investigations have been conducted with different oxidants and fuels with the aim of determining the state‐of‐the‐art of commercially available high temperature polymer electrolyte fuel cells based on polybenzimidazole for its application in combined heat and power generation systems. The fuel cell test performed with synthetic reformate (?63 μV/h) showed an increase of anode charge and mass transfer resistances. This behavior has suggested that CO may be generated from the CO2 included in the synthetic reformate via reverse water gas shift reaction. The fuel cell test performed with pure O2 developed the highest degradation rates (?70 μV/h) due to fast oxidative degradation of membrane electrode assembly materials such as cathode catalyst and membrane. Fuel cell operation with H2/air exhibited the lowest degradation rates (?57 μV/h) and it requires longer investigating times to identify the different degradation mechanisms. Moreover, fuel cell tests performed with air suggested longer break‐in procedures to complete catalyst activation and redistribution of electrolyte. © 2015 American Institute of Chemical Engineers AIChE J, 62: 217–227, 2016 相似文献
979.
980.
Incorporation of [14C] from acetoacetate, D(-)- and L(+)-3-hydroxybutyrate, glucose, glutamine, acetate and palmitate in cellular lipids were
studied in cultures in human diploid fibroblasts (HDF). The results showed that acetoacetate was 2–10 times more effective
as a lipogenic precursor than was either D- or L-3-hydroxybutyrate. Its extent of incorporation into lipids was 2- to 8-fold
more than the other precursors examined under conditions when the overall rates of nonsaponifiable and saponi-fiable lipogenesis
as measured by3H2O incorporation were essentially unchanged. Acetoacetate supported both saponifiable and nonsaponifiable lipid syntheses with
half-saturation values (Km app.) of 185 μM and 30 μM, respectively. Glucose stimulated acetoacetate incorporation into lipids whereas, conversely, acetoacetate
inhibited [14C] glucose incorporation into lipids. The presence of low density lipoproteins (LDL) cholesterol (@40 μg cholesterol/mL) inhibited
the incorporation of [14C] from acetoacetate 56% into nonsaponifiable lipids; the inhibition was consistently higher (75%) when [14C] glucose or glutamine were the precrusors. The loss of 3-hydroxy-3-methyl-glutaryl CoA (HMG CoA) reductase activity upon
addition of LDL-cholesterol was greater than the suppression of [14C] incorporation from acetoacetate or glucose into nonsaponifiable lipids. In the presence of glucose, [14C] acetoacetate was incorporated into 3-βOH sterols (digitonin precipitable). 7.7±1.1 times more effectively than was [14C] glucose. The results suggest that HDF would be a suitable model to investigate the effects of various precrusors of HMG
CoA on the rate of cholesterol biosynthesis. 相似文献