Blood-sampling collection prior to surgery may have a significant influence upon biomarker concentrations measured

Abstract Background Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and disease progression. The validation of biomarkers is a cumbersome process involving many steps. Serum samples from lung cancer patients were collected in the framework of a larger study for evaluation of biomarkers for early detection of lung cancer. The analysis of biomarker levels measured revealed a noticeable difference in certain biomarker values that exhibited a dependence of the time point and setting of the sampling. Biomarker concentrations differed significantly if taken before or after the induction of anesthesia and if sampled via venipuncture or arterial catheter. Methods To investigate this observation, blood samples from 13 patients were drawn 1–2 days prior to surgery (T1), on the same day by venipuncture (T2) and after induction of anesthesia via arterial catheter (T3). The biomarkers Squamous Cell Carcinoma antigen (CanAG SCC EIA, Fujirebio Diagnostics, Malvern, USA), Carcinoembrionic Antigen (CEA), and CYFRA 21-1 (Roche Diagnostics GmbH, Mannheim, Germany) were analyzed. Results SCC showed a very strong effect in relation to the sampling time and procedure. While the first two points in time (T1; T2) were highly comparable (median fold-change: 0.84; p = 0.7354; correlation ρ = 0.883), patients showed a significant increase (median fold-change: 4.96; p = 0.0017; correlation ρ = -0.036) in concentration when comparing T1 with the sample time subsequent to anesthesia induction (T3). A much weaker increase was found for CYFRA 21-1 at T3 (median fold-change: 1.40; p = 0.0479). The concentration of CEA showed a very small, but systematic decrease (median fold-change: 0.72; p = 0.0039). Conclusions In this study we show the unexpectedly marked influence of blood withdrawal timing (before vs. after anesthesia) and procedure (venous versus arterial vessel puncture) has on the concentration of the protein biomarker SCC and to a less extent upon CYFRA21-1. The potential causes for these effects remain to be elucidated in subsequent studies, however these findings highlight the importance of a standardized, controlled blood collection protocol for biomarker detection

Publisher Correction: Truncated FGFR2 is a clinically actionable oncogene in multiple cancers.

This paper was originally published under a standard Springer Nature license

Auxofuran, a Novel Metabolite That Stimulates the Growth of Fly Agaric, Is Produced by the Mycorrhiza Helper Bacterium Streptomyces Strain AcH 505

The mycorrhiza helper bacterium Streptomyces strain AcH 505 improves mycelial growth of ectomycorrhizal fungi and formation of ectomycorrhizas between Amanita muscaria and spruce but suppresses the growth of plant-pathogenic fungi, suggesting that it produces both fungal growth-stimulating and -suppressing compounds. The dominant fungal-growth-promoting substance produced by strain AcH 505, auxofuran, was isolated, and its effect on the levels of gene expression of A. muscaria was investigated. Auxofuran and its synthetic analogue 7-dehydroxy-auxofuran were most effective at a concentration of 15 μM, and application of these compounds led to increased lipid metabolism-related gene expression. Cocultivation of strain AcH 505 and A. muscaria stimulated auxofuran production by the streptomycete. The antifungal substances produced by strain AcH 505 were identified as the antibiotics WS-5995 B and C. WS-5995 B completely blocked mycelial growth at a concentration of 60 μM and caused a cell stress-related gene expression response in A. muscaria. Characterization of these compounds provides the foundation for molecular analysis of the fungus-bacterium interaction in the ectomycorrhizal symbiosis between fly agaric and spruce

Correction: Riedlinger, T. et al. The Direct and Indirect Roles of NF-κB in Cance: Lessons from Oncogenic Fusion Proteins and Knock-In Mice (vol 6, 36, 2018)

We would like to report an error in a previously published paper[...

The Direct and Indirect Roles of NF-kappa B in Cancer: Lessons from Oncogenic Fusion Proteins and Knock-in Mice

NF-kappa B signaling pathways play an important role in the regulation of cellular immune and stress responses. Aberrant NF-kappa B activity has been implicated in almost all the steps of cancer development and many of the direct and indirect contributions of this transcription factor system for oncogenesis were revealed in the recent years. The indirect contributions affect almost all hallmarks and enabling characteristics of cancer, but NF-kappa B can either promote or antagonize these tumor-supportive functions, thus prohibiting global NF-kappa B inhibition. The direct effects are due to mutations of members of the NF-kappa B system itself. These mutations typically occur in upstream components that lead to the activation of NF-kappa B together with further oncogenesis-promoting signaling pathways. In contrast, mutations of the downstream components, such as the DNA-binding subunits, contribute to oncogenic transformation by affecting NF-kappa B-driven transcriptional output programs. Here, we discuss the features of recently identified oncogenic RelA fusion proteins and the characterization of pathways that are regulating the transcriptional activity of NF-kappa B by regulatory phosphorylations. As NF-kappa B's central role in human physiology prohibits its global inhibition, these auxiliary or cell type-specific NF-kappa B regulating pathways are potential therapeutic targets

High-sensitivity cardiac troponin T for diagnosis of NSTEMI in the elderly emergency department patient: a clinical cohort study

<p><b>Purpose:</b> The aim of this study is to evaluate the impact of age on the diagnostic performance of high-sensitivity troponin T (hsTnT) under routine conditions.</p> <p><b>Materials and methods:</b> Data of 4118 consecutive emergency department (ED) patients who underwent a routine TnT measurement between 11 October 2012 and 30 November 2013 were analysed. Diagnostic accuracy of hsTnT was compared in four age categories (<50, 50–64, 65–74, ≥75 years of age) for different cut-off values. Primary endpoint was a main hospital diagnosis of NSTEMI.</p> <p><b>Results:</b> The median age of the study population (<i>n</i> = 4118) was 61 years (IQR: 45–75 years). NSTEMI was diagnosed in 3.3% (<i>n</i> = 136) of all patients. There were significant differences in hsTnT concentrations between age-groups (<i>p</i> < 0.001) in all patients, but not in NSTEMI patients (<i>p</i> = 0.297). 72.2% of all patients ≥75 years of age (583/808) without NSTEMI had hsTnT concentrations above the 99th percentile of a healthy reference population. Specificity at 14 ng/L was 93.6% (95% CI: 92.12–94.87) in patients below 50 years of age and 27.9% (95% CI: 24.78–31.08) in patients 75 years of age and older.</p> <p><b>Conclusions:</b> Patients’ age needs to be considered at least one influencing factor on hsTnT concentrations at admission and should be included in the clinical interpretation of hsTnT concentrations for further clinical workup beneath other influencing factors like comorbidities and symptom onset time. The implementation of age-specific cut-off values could be considered for single troponin testing at admission but is associated with an increased risk of underdiagnosis of NSTEMI.</p

Abyssomicins, inhibitors of the para-aminobenzoic acid pathway produced by the marine Verrucosispora strain AB-18-032

A screening method was established to detect inhibitors of the biosynthetic pathways of aromatic amino acids and para-aminobenzoic acid, the precursor of folic acid, using an agar plate diffusion assay modified as an antagonism test. By this screening method, a family of three novel polycyclic polyketides named as abyssomicins was isolated from a marine strain of Verrucosispora. The main component abyssomicin C inhibits the pathway between chorismate and para-aminobenzoic acid and is strongly active against gram-positive bacteria, including multi-resistant clinical isolates of Staphylococcus aureus