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951.
Ulrike Schoetz Diana Klein Julia Hess Seyd Shnayien Steffen Spoerl Michael Orth Samet Mutlu Roman Hennel Anja Sieber Ute Ganswindt Benedikt Luka Andreas R. Thomsen Kristian Unger Verena Jendrossek Horst Zitzelsberger Nils Blüthgen Claus Belka Steffen Unkel Bertram Klinger Kirsten Lauber 《Cell death & disease》2021,12(12)
Resistance against radio(chemo)therapy-induced cell death is a major determinant of oncological treatment failure and remains a perpetual clinical challenge. The underlying mechanisms are manifold and demand for comprehensive, cancer entity- and subtype-specific examination. In the present study, resistance against radiotherapy was systematically assessed in a panel of human head-and-neck squamous cell carcinoma (HNSCC) cell lines and xenotransplants derived thereof with the overarching aim to extract master regulators and potential candidates for mechanism-based pharmacological targeting. Clonogenic survival data were integrated with molecular and functional data on DNA damage repair and different cell fate decisions. A positive correlation between radioresistance and early induction of HNSCC cell senescence accompanied by NF-κB-dependent production of distinct senescence-associated cytokines, particularly ligands of the CXCR2 chemokine receptor, was identified. Time-lapse microscopy and medium transfer experiments disclosed the non-cell autonomous, paracrine nature of these mechanisms, and pharmacological interference with senescence-associated cytokine production by the NF-κB inhibitor metformin significantly improved radiotherapeutic performance in vitro and in vivo. With regard to clinical relevance, retrospective analyses of TCGA HNSCC data and an in-house HNSCC cohort revealed that elevated expression of CXCR2 and/or its ligands are associated with impaired treatment outcome. Collectively, our study identifies radiation-induced tumor cell senescence and the NF-κB-dependent production of distinct senescence-associated cytokines as critical drivers of radioresistance in HNSCC whose therapeutic targeting in the context of multi-modality treatment approaches should be further examined and may be of particular interest for the subgroup of patients with elevated expression of the CXCR2/ligand axis.Subject terms: Radiotherapy, Head and neck cancer, Senescence, Tumour heterogeneity 相似文献
952.
Nuno Vale Ana Correia-Branco Bárbara Patrício Diana Duarte Fátima Martel 《Bioorganic & medicinal chemistry letters》2017,27(15):3507-3510
The investment in cancer research is critical to find more and better treatments, but essentially to save lives. Here, we describe the synthesis and characterization on new bromothiazole derivatives with amino acids and with core of nitazoxanide, an FDA-approved antiprotozoal drug. Using a human adenocarcinoma-derived cell line (the Caco-2 cell line), we then investigated the antiproliferative (3H-thymidine incorporation) and cytotoxic (extracellular lactate dehydrogenase activity) effect of these derivatives. All the derivatives caused a concentration–dependent decrease in cell proliferation and viability. At their highest concentration, all compounds were able to reduce 3H-thymidine incorporation by more than 80%, corresponding to a more marked antiproliferative effect than butyrate. As to their cytotoxic effect, it was comparable to that of butyrate. The ability of bromo substituent in thiazole ring with new sequences of amino acids in inducing cell death and apoptosis in Caco-2 cells (and other cell lines) is now being studied. 相似文献
953.
Gary C. Kemp Arnaud C. Tiberghien Neki V. Patel Francois DHooge Sanjay M. Nilapwar Lauren R. Adams Simon Corbett David G. Williams John A. Hartley Philip W. Howard 《Bioorganic & medicinal chemistry letters》2017,27(5):1154-1158
A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro. 相似文献
954.
Linking molecular evolution to biological function is a long‐standing challenge in evolutionary biology. Some of the best examples of this involve opsins, the genes that encode the molecular basis of light reception. In this issue of Molecular Ecology, three studies examine opsin gene sequence, expression and repertoire to determine how natural selection has shaped the visual system. First, Escobar‐Camacho et al. ( 2017 ) use opsin repertoire and expression in three Amazonian cichlid species to show that a shift in sensitivity towards longer wavelengths is coincident with the long‐wavelength‐dominated Amazon basin. Second, Stieb et al. ( 2017 ) explore opsin sequence and expression in reef‐dwelling damselfish and find that UV‐ and long‐wavelength vision are both important, but likely for different ecological functions. Lastly, Suvorov et al. ( 2017 ) study an expansive opsin repertoire in the insect order Odonata and find evidence that copy number expansion is consistent with the permanent heterozygote model of gene duplication. Together these studies emphasize the utility of opsin genes for studying both the local adaptation of sensory systems and, more generally, gene family evolution. 相似文献
955.
956.
The spider tree of life: phylogeny of Araneae based on target‐gene analyses from an extensive taxon sampling 下载免费PDF全文
Ward C. Wheeler Jonathan A. Coddington Louise M. Crowley Dimitar Dimitrov Pablo A. Goloboff Charles E. Griswold Gustavo Hormiga Lorenzo Prendini Martín J. Ramírez Petra Sierwald Lina Almeida‐Silva Fernando Alvarez‐Padilla Miquel A. Arnedo Ligia R. Benavides Silva Suresh P. Benjamin Jason E. Bond Cristian J. Grismado Emile Hasan Marshal Hedin Matías A. Izquierdo Facundo M. Labarque Joel Ledford Lara Lopardo Wayne P. Maddison Jeremy A. Miller Luis N. Piacentini Norman I. Platnick Daniele Polotow Diana Silva‐Dávila Nikolaj Scharff Tamás Szűts Darrell Ubick Cor J. Vink Hannah M. Wood Junxia Zhang 《Cladistics : the international journal of the Willi Hennig Society》2017,33(6):574-616
957.
Patrícia?Branco Diana?Francisco Margarida?Monteiro Maria?Gabriela?Almeida Jorge?Caldeira Nils?Arneborg Catarina?Prista Helena?AlbergariaEmail authorView authors OrcID profile 《Applied microbiology and biotechnology》2017,101(1):159-171
We recently found that Saccharomyces cerevisiae (strain CCMI 885) secretes antimicrobial peptides (AMPs) derived from the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) that are active against various wine-related yeast and bacteria. Here, we show that several other S. cerevisiae strains also secrete natural biocide fractions during alcoholic fermentation, although at different levels, which correlates with the antagonistic effect exerted against non-Saccharomyces yeasts. We, therefore, term this biocide saccharomycin. The native AMPs were purified by gel-filtration chromatography and its antimicrobial activity was compared to that exhibited by chemically synthesized analogues (AMP1 and AMP2/3). Results show that the antimicrobial activity of the native AMPs is significantly higher than that of the synthetic analogues (AMP1 and AMP2/3), but a conjugated action of the two synthetic peptides is observed. Moreover, while the natural AMPs are active at pH 3.5, the synthetic peptides are not, since they are anionic and cannot dissolve at this acidic pH. These findings suggest that the molecular structure of the native biocide probably involves the formation of aggregates of several peptides that render them soluble under acidic conditions. The death mechanisms induced by the AMPs were also evaluated by means of epifluorescence microscopy-based methods. Sensitive yeast cells treated with the synthetic AMPs show cell membrane disruption, apoptotic molecular markers, and internalization of the AMPs. In conclusion, our work shows that saccharomycin is a natural biocide secreted by S. cerevisiae whose activity depends on the conjugated action of GAPDH-derived peptides. This study also reveals that S. cerevisiae secretes GAPDH-derived peptides as a strategy to combat other microbial species during alcoholic fermentations. 相似文献
958.
Wittgens Andreas Kovacic Filip Müller Markus Michael Gerlitzki Melanie Santiago-Schübel Beatrix Hofmann Diana Tiso Till Blank Lars Mathias Henkel Marius Hausmann Rudolf Syldatk Christoph Wilhelm Susanne Rosenau Frank 《Applied microbiology and biotechnology》2017,101(7):2865-2878
Applied Microbiology and Biotechnology - The human pathogenic bacterium Pseudomonas aeruginosa produces rhamnolipids, glycolipids with functions for bacterial motility, biofilm formation, and... 相似文献
959.