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1.
Joanna Szkandera Michael Stotz Florian Eisner Gudrun Absenger Tatjana Stojakovic Hellmut Samonigg Peter Kornprat Renate Schaberl-Moser Wael AlZoughbi Anna Lena Ress Friederike Sophia Seggewies Armin Gerger Gerald Hoefler Martin Pichler 《PloS one》2013,8(11)
Background
With growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients.Methods
Data from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.Results
We calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients’ survival in the whole cohort. Kaplan-Meier curve reveals a dNLR≥2.3 as a factor for decreased CSS in PC patients (p<0.001, log-rank test). An independent significant association between high dNLR≥2.3 and poor clinical outcome in multivariate analysis (HR = 1.24, CI95% = 1.01–1.51, p = 0.041) was identified.Conclusion
In the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability. 相似文献2.
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4.
Spatiotemporally resolved functional MRI (fMRI) in animals can reveal how wide-spread neural networks are organized and accompanying electrophysiological recordings can show how small neural assemblies contribute to this organization. Here we present a novel technique that yields high-resolution structural and functional images of the monkey brain with small, tissue-compatible, intraosteally implantable radiofrequency coils. Voxel sizes as small as 0.0113 microl with high signal-to-noise and contrast-to-noise ratios were obtained, revealing both structural and functional cortical architecture in great detail. Up to a certain point, contrast sensitivity increased with decreasing voxel size, probably because of the decreased partial volume effects. Spatial specificity was demonstrated by the lamina-specific activation in experiments comparing responses to moving and flickering stimuli. The implications of this technique for combined fMRI/electrophysiology experiments and its limitations in terms of spatial coverage are discussed. 相似文献
5.
Hellmut Becher 《Development genes and evolution》1929,119(1):143-170
Ohne Zusammenfassung 相似文献
6.
Fiedler U Krissl T Koidl S Weiss C Koblizek T Deutsch U Martiny-Baron G Marmé D Augustin HG 《The Journal of biological chemistry》2003,278(3):1721-1727
Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have been identified as ligands with different effector functions of the vascular assembly and maturation-mediating receptor tyrosine kinase Tie-2. To understand the molecular interactions of the angiopoietins with their receptor, we have studied the binding of Ang-1 and Ang-2 to the Tie-2 receptor. Enzyme-linked immunosorbent assay-based competition assays and co-immunoprecipitation experiments analyzing the binding of Ang-1 and Ang-2 to truncation mutants of the extracellular domain of Tie-2 showed that the first Ig-like loop of Tie-2 in combination with the epidermal growth factor (EGF)-like repeats (amino acids 1-360) is required for angiopoietin binding. The first Ig-like domain or the EGF-like repeats alone are not capable of binding Ang-1 and Ang-2. Concomitantly, we made the surprising finding that Tie-2 exon-2 knockout mice do express a mutated Tie-2 protein that lacks 104 amino acids of the first Ig-like domain. This mutant Tie-2 receptor is functionally inactive as shown by the lack of ligand binding and receptor phosphorylation. Collectively, the data show that the first 104 amino acids of the Tie-2 receptor are essential but not sufficient for angiopoietin binding. Conversely, the first 360 amino acids (Ig-like domain plus EGF-like repeats) of the Tie-2 receptor are necessary and sufficient to bind both Ang-1 and Ang-2, which suggests that differential receptor binding is not likely to be responsible for the different functions of Ang-1 and Ang-2. 相似文献
7.
Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation 总被引:19,自引:0,他引:19
Fiedler U Reiss Y Scharpfenecker M Grunow V Koidl S Thurston G Gale NW Witzenrath M Rosseau S Suttorp N Sobke A Herrmann M Preissner KT Vajkoczy P Augustin HG 《Nature medicine》2006,12(2):235-239
The angiopoietins Ang-1 and Ang-2 have been identified as ligands of the receptor tyrosine kinase Tie-2 (refs. 1,2). Paracrine Ang-1-mediated activation of Tie-2 acts as a regulator of vessel maturation and vascular quiescence. In turn, the antagonistic ligand Ang-2 acts by an autocrine mechanism and is stored in endothelial Weibel-Palade bodies from where it can be rapidly released upon stimulation. The rapid release of Ang-2 implies functions of the angiopoietin-Tie system beyond its established role during vascular morphogenesis as a regulator of rapid vascular responses. Here we show that mice deficient in Ang-2 (encoded by the gene Angpt2) cannot elicit an inflammatory response in thioglycollate-induced or Staphylococcus aureus-induced peritonitis, or in the dorsal skinfold chamber model. Recombinant Ang-2 restores the inflammation defect in Angpt2(-/-) mice. Intravital microscopy showed normal TNF-alpha-induced leukocyte rolling in the vasculature of Angpt2(-/-)mice, but rolling cells did not firmly adhere to activated endothelium. Cellular experiments showed that Ang-2 promotes adhesion by sensitizing endothelial cells toward TNF-alpha and modulating TNF-alpha-induced expression of endothelial cell adhesion molecules. Together, these findings identify Ang-2 as an autocrine regulator of endothelial cell inflammatory responses. Ang-2 thereby acts as a switch of vascular responsiveness exerting a permissive role for the activities of proinflammatory cytokines. 相似文献
8.
J Szkandera G Absenger N Dandachi P Regitnig S Lax M Stotz H Samonigg W Renner A Gerger 《Molecular genetics and genomics : MGG》2012,287(9):755-764
To elucidate the role of predictive factors on individual's drug response, based on genetic variation, we examined the association between eight germline polymorphisms in genes involved in protection against oxidative stress, apoptosis, oncogenic transformation, proliferation, immune response and DNA repair (TP53, NQO1, IL6, TLR4 and XRCC1) and the pathological response to anthracycline-based neoadjuvant chemotherapy in 70 patients with breast cancer. The DNA was genotyped for eight polymorphisms in five genes (TP53, NQO1, IL6, TLR4 and XRCC1) by 5'-exonuclease (TaqMan?) technology. Fisher's exact test was used to evaluate the association between genotype, clinicopathological parameters and pathological response. A good pathological response, defined as a pathological complete response or residual isolated invasive tumor cells, was found significantly more frequently for estrogen (ER) and progesterone receptor (PR) negative breast carcinomas compared to ER and PR positive and ER or PR positive carcinomas, respectively (43.5 vs. 37.5 and 10.3?%, p?=?0.006), and was significantly associated with high tumor grade (G3) (p?=?0.002). A non-significant trend towards a good pathological response was shown in patients carrying the Arg/Arg or Arg/Pro TP53 codon 72 gene variant compared to those harboring the Pro/Pro variant (17.6 or 37.9?% vs. 0; p?=?0.071). No association was found between NQO1 Pro187Ser, IL6 -174G>C, TLR4 Asp299Gly and Thr399Ile, and XRCC1 Arg194Trp, Arg399Gln and Arg280His and pathological response. The present study shows hormone receptor status and tumor grade as predictors for pathological response to neoadjuvant anthracycline-based chemotherapy. Among various functional germline polymorphisms, a potential predictive value was only found for the TP53 Arg72Pro gene variant. 相似文献
9.
10.
Flow-dependent regulation of angiopoietin-2 总被引:1,自引:0,他引:1