Endocan serum concentration in uninfected newborn infants

Introduction: Endocan is a specific endothelial mediator involved in the inflammatory response. Its role in the diagnosis of sepsis has been studied in adult patients and late onset neonatal sepsis. The clinical signs of early onset sepsis (EOS) are nonspecific and routinely used biomarkers, such as C-reactive protein and procalcitonin, have low sensitivity, specificity and positive predictive value. Endocan could be useful as a biomarker for diagnosis of EOS, but at present normal range values for this molecule have not been reported. The aim of this study is to establish the normal values range for serum endocan in term and preterm newborns without risk factors for EOS and to characterize the variation pattern of its levels at different postnatal moments. Methodology: Mean endocan serum concentration (ESC) was measured in term and preterm newborns without clinical suspicion of EOS at different moments from birth. Results: ESC (ng/mL) in term newborns was 1.74+/-0.13 on day 1 and 2.02+/-0.41 on day 3 respectively, (p=0.09). In preterm newborns ESC (ng/mL) was 2.02+/-0.11 and 1.97+/-0.18, (p=0.8) for day 1 and 3 respectively. ESC was not significantly influenced by sex, mode of delivery, evidence of fetal distress or presence of minor birth trauma. Conclusions: ESC (ng/mL) between the first and third day of life in either term or preterm infants don’t appear to be significantly influenced by factors that are associated with elevation of inflammatory markers, thus using this biomarker for the diagnosis of EOS might reduce the false positive results

Loss of Endocan tumorigenic properties after alternative splicing of exon 2

<p>Abstract</p> <p>Background</p> <p>Endocan was originally described as a dermatan sulfate proteoglycan found freely circulating in the blood. Endocan expression confers tumorigenic properties to epithelial cell lines or accelerate the growth of already tumorigenic cells. This molecule is the product of a single gene composed of 3 exons. Previous data showed that endocan mRNA is subject to alternative splicing with possible generation of two protein products. In the present study we identified, and functionally characterized, the alternative spliced product of the endocan gene: the exon 2-deleted endocan, called endocanΔ2.</p> <p>Methods</p> <p>Stable, endocanΔ2-overexpressing cell lines were generated to investigate the biological activities of this new alternatively spliced product of endocan gene. Tumorigenesis was studied by inoculating endocan and endocanΔ2 expressing cell lines subcutaneously in SCID mice. Biochemical properties of endocan and endocanΔ2 were studied after production of recombinant proteins in various cell lines of human and murine origin.</p> <p>Results</p> <p>Our results showed that the exon 2 deletion impairs synthesis of the glycan chain, known to be involved in the pro-tumoral effect of endocan. EndocanΔ2 did not promote tumor formation by 293 cells implanted in the skin of severe combined immunodeficient (SCID) mice.</p> <p>Conclusion</p> <p>Our results emphasize the key role of the polypeptide sequence encoded by the exon 2 of endocan gene in tumorigenesis, and suggest that this sequence could be a target for future therapies against cancer.</p

Migration von /sw vom AFS ins DCE/DFS

/sw ist eine verteilte Softwarebereitstellung mit dem Ziel, jedem Benutzer Software zentral zur Verfügung zu stellen, ohne daß er sich darum kümmern muß, woher er seine Software bekommt. Für eine Außenstehenden ergibt sich somit das Bild eines großen Softwarepools, aus dem er sich fertig installierte Software für seine Plattform herunterladen kann. Voraussetzung dafür ist, daß ein Benuzter an seiner Workstation über AFS (Andrew File System), DFS (Distributed File System) oder ftp verfügt. Zur Zeit werden vom /sw für 18 verschiedenen Unix-Plattformen 594 Programme in 1024 verschiedenen Installationen angeboten. Die meisten Architekturen vom /sw liegen im AFS, bis auf die Architekturen DEC ALPHA, IRIX 4.0 und Linux, die im NFS liegen. In Zukunft wird es für die gesamte /sw Software nur noch eine Quelle geben, das DFS. Mit der Migration von /sw aus dem AFS ins DFS entfällt dann die Trennung von /sw in einen AFS-Teil und einem NFS-Teil und damit auch der AFS/NFS-Translators, der recht unstabil läuft. Die gesamte Software von /sw wurde aus dem AFS bzw. NFS ins DFS migriert, so daß für alle vom /sw unterstützten Architekturen nur noch eine Quelle zur Verfügung steht, die Stuttgarter DCE-Zelle. Jeder AFS-Klient hat über den AFS/DFS-Translator Zugriff auf /sw und für die NFS-Klienten wird das /sw-Fi-lesystem exportiert, so daß jeder NFS-Klient die Möglichkeit hat das DFS-Filesystem /sw zu mounten. Eine Workstation kann sowohl AFS- als auch DCE/DFS-Klient sein

Endocan serum concentration in uninfected newborn infants

Introduction: Endocan is a specific endothelial mediator involved in the inflammatory response. Its role in the diagnosis of sepsis has been studied in adult patients and late onset neonatal sepsis. The clinical signs of early onset sepsis (EOS) are nonspecific and routinely used biomarkers, such as C-reactive protein and procalcitonin, have low sensitivity, specificity and positive predictive value. Endocan could be useful as a biomarker for diagnosis of EOS, but at present normal range values for this molecule have not been reported. The aim of this study is to establish the normal values range for serum endocan in term and preterm newborns without risk factors for EOS and to characterize the variation pattern of its levels at different postnatal moments.&#x0D; Methodology: Mean endocan serum concentration (ESC) was measured in term and preterm newborns without clinical suspicion of EOS at different moments from birth.&#x0D; Results: ESC (ng/mL) in term newborns was 1.74+/-0.13 on day 1 and 2.02+/-0.41 on day 3 respectively, (p=0.09). In preterm newborns ESC (ng/mL) was 2.02+/-0.11 and 1.97+/-0.18, (p=0.8) for day 1 and 3 respectively. ESC was not significantly influenced by sex, mode of delivery, evidence of fetal distress or presence of minor birth trauma.&#x0D; Conclusions: ESC (ng/mL) between the first and third day of life in either term or preterm infants don’t appear to be significantly influenced by factors that are associated with elevation of inflammatory markers, thus using this biomarker for the diagnosis of EOS might reduce the false positive results.</jats:p

Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial)

Purpose: We aimed to identify gene expression signatures associated with angiogenesis and hypoxia pathways with predictive value for treatment response to bevacizumab/erlotinib (BE) of nonsquamous advanced non–small cell lung cancer (NSCLC) patients. Experimental Design: Whole-genome gene expression profiling was performed on 42 biopsy samples (from SAKK 19/05 trial) using Affymetrix exon arrays, and associations with the following endpoints: time-to-progression (TTP) under therapy, tumor-shrinkage (TS), and overall survival (OS) were investigated. Next, we performed gene set enrichment analyses using genes associated with the angiogenic process and hypoxia response to evaluate their predictive value for patients' outcome. Results: Our analysis revealed that both the angiogenic and hypoxia response signatures were enriched within the genes predictive of BE response, TS, and OS. Higher gene expression levels (GEL) of the 10-gene angiogenesis-associated signature and lower levels of the 10-gene hypoxia response signature predicted improved TTP under BE, 7.1 months versus 2.1 months for low versus high-risk patients (P = 0.005), and median TTP 6.9 months versus 2.9 months (P = 0.016), respectively. The hypoxia response signature associated with higher TS at 12 weeks and improved OS (17.8 months vs. 9.9 months for low vs. high-risk patients, P = 0.001). Conclusions: We were able to identify gene expression signatures derived from the angiogenesis and hypoxia response pathways with predictive value for clinical outcome in advanced nonsquamous NSCLC patients. This could lead to the identification of clinically relevant biomarkers, which will allow for selecting the subset of patients who benefit from the treatment and predict drug response. Clin Cancer Res; 21(23); 5253–63

Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial)

Purpose: We aimed to identify gene expression signatures associated with angiogenesis and hypoxia pathways with predictive value for treatment response to bevacizumab/erlotinib (BE) of nonsquamous advanced non–small cell lung cancer (NSCLC) patients. Experimental Design: Whole-genome gene expression profiling was performed on 42 biopsy samples (from SAKK 19/05 trial) using Affymetrix exon arrays, and associations with the following endpoints: time-to-progression (TTP) under therapy, tumor-shrinkage (TS), and overall survival (OS) were investigated. Next, we performed gene set enrichment analyses using genes associated with the angiogenic process and hypoxia response to evaluate their predictive value for patients' outcome. Results: Our analysis revealed that both the angiogenic and hypoxia response signatures were enriched within the genes predictive of BE response, TS, and OS. Higher gene expression levels (GEL) of the 10-gene angiogenesis-associated signature and lower levels of the 10-gene hypoxia response signature predicted improved TTP under BE, 7.1 months versus 2.1 months for low versus high-risk patients (P = 0.005), and median TTP 6.9 months versus 2.9 months (P = 0.016), respectively. The hypoxia response signature associated with higher TS at 12 weeks and improved OS (17.8 months vs. 9.9 months for low vs. high-risk patients, P = 0.001). Conclusions: We were able to identify gene expression signatures derived from the angiogenesis and hypoxia response pathways with predictive value for clinical outcome in advanced nonsquamous NSCLC patients. This could lead to the identification of clinically relevant biomarkers, which will allow for selecting the subset of patients who benefit from the treatment and predict drug response. Clin Cancer Res; 21(23); 5253–63

Supplementary Tables 1-3, Figures 1-6 from Gene Expression Signatures Predictive of Bevacizumab/Erlotinib Therapeutic Benefit in Advanced Nonsquamous Non–Small Cell Lung Cancer Patients (SAKK 19/05 trial)

Supplementary Tables 1-3, Figures 1-6. Supplementary Table 1: Statistical analysis of differences between the study group and the remaining group of patients for several variables. Supplementary Table 2: Primers used for the RT-qPCR assays. Supplementary Table 3: Leave-one-out cross-validation of the angiogenesis-associated and hypoxia gene signatures. Supplementary Figure 1: Average gene expression levels for the top 10-ranked angiogenesis signature calculated based on the microarray data (N = 42 patients) for low (Cluster A1), high (Cluster A2) and medium (Cluster A3) risk patients. Supplementary Figure 2: Average gene expression levels for the top 10-ranked hypoxia response signature calculated based on the microarray data (N = 42 patients). Supplementary Figure 3: Hierarchical clustering of top 10-ranked hypoxia-response genes significantly associated with TS, showing gene expression variation among patients. The heat map represents relative intensity values of gene expression levels. Supplementary Figure 4: Hierarchical clustering of top 10-ranked hypoxia-response genes significantly associated with OS, showing gene expression variation among patients. The heat map represents relative intensity values of gene expression levels. Supplementary Figure 5: Optimized between-group classification (OBC) sensitivity analysis for angiogenesis-associated signature (A) and hypoxia-response signature predictive of TTP under BE. Supplementary Figure 6: Association between the expression of 10-gene hypoxia-response signature predictive of TTP under BE in our study, and PFS of second line sorafenib-treated patients enrolled in the BATTLE-1 trial,1 GEO accession number: GSE33072;2 P = 0.0186, calculated by log-tank test.</p

Serum mesothelin for diagnosing malignant pleural mesothelioma : an individual patient data meta-analysis

PURPOSE: Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. METHODS: The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. RESULTS: At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). CONCLUSION: In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research