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1.
The chirality of the title heterocycles is discussed considering their genesis by desymmetrization of the corresponding adamantanes. Some rules for the specification of the absolute configurations of the enantiomers (R or S) for this type of compounds are proposed. © 1996 Wiley-Liss, Inc. 相似文献
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V.O. Oria P. Bronsert A.R. Thomsen M.C. Föll C. Zamboglou L. Hannibal S. Behringer M.L. Biniossek C. Schreiber A.L. Grosu L. Bolm D. Rades T. Keck M. Werner U.F. Wellner O. Schilling 《Translational oncology》2018,11(6):1307-1322
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with frequent post-surgical local recurrence. The combination of adjuvant chemotherapy with radiotherapy is under consideration to achieve a prolonged progression-free survival (PFS). To date, few studies have determined the proteome profiles associated with response to adjuvant chemoradiation. We herein analyzed the proteomes of primary PDAC tumors subjected to additive chemoradiation after surgical resection and achieving short PFS (median 6 months) versus prolonged PFS (median 28 months). Proteomic analysis revealed the overexpression of Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) and Monoamine Oxidase A (MAOA) in the short PFS cohort, which were corroborated by immunohistochemistry. In vitro, specific inhibition of ALDH1A1 by A37 in combination with gemcitabine, radiation, and chemoradiation lowered cell viability and augmented cell death in MiaPaCa-2 and Panc 05.04 cells. ALDH1A1 silencing in both cell lines dampened cell proliferation, cell metabolism, and colony formation. In MiaPaCa-2 cells, ALDH1A1 silencing sensitized cells towards treatment with gemcitabine, radiation or chemoradiation. In Panc 05.04, increased cell death was observed upon gemcitabine treatment only. These findings are in line with previous studies that have suggested a role of ALDH1A1 chemoradiation resistance, e.g., in esophageal cancer. In summary, we present one of the first proteome studies to investigate the responsiveness of PDAC to chemoradiation and provide further evidence for a role of ALDH1A1 in therapy resistance. 相似文献
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F W Sum A Gilbert A M Venkatesan K Lim V Wong M O'Dell G Francisco Z Chen G Grosu J Baker J Ellingboe M Malamas I Gunawan J Primeau E Largis K Steiner 《Bioorganic & medicinal chemistry letters》1999,9(14):1921-1926
CL316243 is a highly selective and potent beta3-adrenergic receptor agonist, and has been shown in rodent models to be an effective agent for treating obesity and Type II diabetes. To improve the oral absorption and pharmacokinetic profiles of CL316243, a number of prodrugs have been synthesized and evaluated. Several ester-type prodrugs show significant improvements in oral bioavailability in both rodent and primate models. 相似文献
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Tsurumi C Esser N Firat E Gaedicke S Follo M Behe M Elsässer-Beile U Grosu AL Graeser R Niedermann G 《PloS one》2010,5(12):e15605
Background
Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of great importance.Methodology/Principal Findings
Here, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry.Conclusions/Significance
Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics. 相似文献5.
Christiane Berghof Ioana Georgeta Grosu Peter Lönnecke Luminita Silaghi-Dumitrescu 《Inorganica chimica acta》2011,374(1):127-133
Starting from the heterotopic multidentate ligand 1,2-phenylenebis(thio)diacetic acid (1), cis-rac-[PdCl2{1,2-(HOOCCH2S)2C6H4-κ2S,S′}] (2), cis-rac-[Rh{1,2-(HOOCCH2S)2C6H4-κ2S,S′}(cod)]BF4 (3) and cis-rac-[Ni{1,2-(OOCCH2S)2C6H4-κ4O,O′S,S′}{cis-(C3H4N2)}2] (4) were prepared and characterised by X-ray diffraction and conventional spectroscopic techniques. Compounds 1-4 show extensive hydrogen-bonded networks (XH?O, X = O, N) in the solid state. 相似文献
6.
Hwei-Ru Tsou Gloria MacEwan Gary Birnberg George Grosu Matthew G. Bursavich Joel Bard Natasja Brooijmans Lourdes Toral-Barza Irwin Hollander Tarek S. Mansour Semiramis Ayral-Kaloustian Ker Yu 《Bioorganic & medicinal chemistry letters》2010,20(7):2321-2325
We discovered 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity over PI3Kα. An X-ray co-crystal structure of one inhibitor with the mTOR-related PI3Kγ revealed the key hydrogen bonding interactions. 相似文献
7.
Crina Cismaş Nicolas Vanthuyne Hélène Rispaud Richard Attila Varga Elena Bogdan Christian Roussel Ion Grosu 《Chirality》2011,23(2):167-171
The first geometric enantiomers in the cyclic compounds series are reported. The investigated compounds are 2,2‐disubstituted‐5‐methyl‐1,3‐dioxane derivatives in which the substituents at position 2 bear chiral centers with identical substituents but with opposite configurations. The structure of the unlike isomers was determined from the solid state molecular structure of the compounds obtained by single crystal X‐ray diffractometry and the enantiomers of these diastereoisomers were observed by chiral column HPLC base‐line separation. The investigated compounds were obtained by a diastereoselective bromination reaction of the corresponding 2,2‐dialkyl and 2,2‐dibenzyl‐5‐methyl‐1,3‐dioxanes. Chirality, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
8.
V Aranapakam J D Albright G T Grosu P S Chan J Coupet T Saunders X Ru H Mazandarani 《Bioorganic & medicinal chemistry letters》1999,9(13):1733-1736
Synthesis and structure-activity relationships (SAR) of arginine vasopressin receptor (AVP) antagonists are described. Potent and orally active compounds are prepared when tricyclic 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine moiety in VPA-985 1 is replaced with a compound 7 or 12. 相似文献
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Erica Hlavin Bell Simon Kirste Jessica L. Fleming Petra Stegmaier Vanessa Drendel Xiaokui Mo Stella Ling Denise Fabian Isabel Manring Cordula A. Jilg Wolfgang Schultze-Seemann Maureen McNulty Debra L. Zynger Douglas Martin Julia White Martin Werner Anca L. Grosu Arnab Chakravarti 《PloS one》2015,10(3)