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468 Publications visible to you, out of a total of 468
Portraying the expression landscapes of cancer subtypes. A case study of glioblastoma multiforme and prostate cancer
HNPCC-Sys - Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, GGN - German Glioma Network

Abstract (Expand)

Self-organizing maps (SOM) portray molecular phenotypes with individual resolution. We present an analysis pipeline based on SOM machine learning which allows the comprehensive study of large scale … clinical data. The potency of the method is demonstrated in selected applications studying the diversity of gene expression in Glioblastoma Multiforme (GBM) and prostate cancer progression. Our method characterizes relationships between the samples, disentangles the expression patterns into well separated groups of co-regulated genes, extracts their functional contexts using enrichment techniques, and enables the detection of contaminations and outliers in the samples. We found that the four GBM subtypes can be divided into two “localized” and two “intermediate” ones. The localized subtypes are characterized by the antagonistic activation of processes related to immune response and cell division, commonly observed also in other cancers. In contrast, each of the “intermediate” subtypes forms a heterogeneous continuum of expression states linking the “localized” subtypes. Both “intermediate” subtypes are characterized by distinct expression patterns related to translational activity and innate immunity as well as nervous tissue and cell function. We show that SOM portraits provide a comprehensive framework for the description of the diversity of expression landscapes using concepts of molecular function.

Authors: Lydia Hopp, Henry Löffler-Wirth, M. Fasold, Hans Binder

Date Published: 27th Jan 2014

Publication Type: Not specified

Human Diseases: brain glioma, prostate cancer

Significant dose Escalation of Idarubicin in the treatment of aggressive Non- Hodgkin Lymphoma leads to increased hematotoxicity without improvement in efficacy in comparison to standard CHOEP-14: 9-year follow up results of the CIVEP trial of the DSHNHL.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: Dose escalation and modification of CHOP has improved the prognosis of patients with aggressive lymphoma; even in the rituximab era, dose escalation for high-risk patients is exploited and … frequently limited by drug toxicity. Idarubicin (Id) is a 4-demethoxy anthracycline analogue of daunorubicin with activity against lymphoma and has been reported to cause less cardiotoxicity than other anthracylines. The aim of this study was to replace doxorubicine with idarubicin in the CHOEP regimen and to find the maximum tolerable dose (MTD) of idarubicin based on hematotoxicity. PATIENTS AND METHODS: Between 11/96 and 09/98, 64 patients (pts) aged 18-75 yrs (pts. 18-60, LDH not elevated, >60 years all risk groups) with newly diagnosed aggressive lymphoma received 6 cycles of CIVEP-14 with an escalating dose of idarubicin, consisting of idarubicin (11-16 mg/m(2) d1) and standard doses of cyclophosphamide, vincristine, etoposide, and prednisone with G-CSF support. RESULTS: 55 pts (median age 56 yrs) were evaluable for a final analysis with a median observation time of 9.3 years. The CR-rate was 77.4% ; the 5 and 8-year-EFS rates were 46.4% (95%CI 32.5-60.3%) and 43.5% (29.4-57.6%), respectively, and the 5- and 8 yr OS rates were 64.6% (51.7-77.5%) and 59.9% (46.4-73.4%). 14/55 patients have died due to lymphoma progression, and 2/55 patients (3.6%) due to treatment related toxicity, 4/55 due to other causes (3 infections, 1 acute heart failure). In a matched pair analysis comparing CHOEP-14 and CIVEP-14, CIVEP-14 had a higher hematotoxicity with no significant differences in the event free and overall survival for the two regimens. CONCLUSIONS: Thus, idarubicin cannot be used instead doxorubicin even if its dose is escalated to achieve similar hematotoxicity. Doxorubicin remains the standard anthracycline for the treatment of aggressive NHL.

Authors: K. Hohloch, C. Zwick, M. Ziepert, D. Hasenclever, U. Kaiser, A. Engert, H. G. Hoffkes, F. Kroschinsky, R. Mesters, A. C. Feller, M. Loffler, L. Trumper, M. Pfreundschuh

Date Published: 3rd Jan 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Methylation associated pathway activity deregulation in lung adenocarcinoma
CapSys - Systems Medicine of Community Acquired Pneumonia

Abstract (Expand)

Methylation impairments are tightly associated with gene expression and molecular pathway deregulation in cancer development. However, other regulatory mechanisms exist, making it important to distinguish … those from methylation driven changes. Here we specifically assessed molecular pathway states associated with gene methylation in lung adenocarcinoma. Paired gene expression and methylation data (id:GSE32867) were obtained from Gene Expression Omnibus. Self organizing maps (Wirth, H. et al.BMC Bioinformatics 2011;12:306 ) and in-house pathway signal flow algorithms were applied to describe expression (PSF) and methylation (mPSF) states in KEGG pathways. 35 and 24 KEGG pathways had at least one branch deregulated at significance levels p<0.05 and 0.05<p < 0.1, respectively. Because many pathways are multibranch, our analysis totalled in 54 up- (PSF>1) and 73 down-regulated (PSF<1) branches. From these branches, 19 were positively (mPSF<0) or negatively (mPSF>0) correlated with methylation states (see table).

Authors: L. Nersisyan, Henry Löffler-Wirth, A. Gevorgyan, Hans Binder, A. Arakelyan

Date Published: 2014

Publication Type: Not specified

Human Diseases: lung disease

Mining common pathway deregulation profiles in lung diseases
CapSys - Systems Medicine of Community Acquired Pneumonia

Abstract (Expand)

This study is aimed at investigating lung diseases described by common pathomechanisms based on evaluation of gene expression profiles in molecular pathways. 16 datasets containing 428 samples for 22 … health conditions were taken from Gene Expression Omnibus. Self organizing maps (Wirth, H. et al.BMC Bioinformatics 2011;12:306) and cluster analysis with dynamic tree cut were used for gene expression based disease clustering. In-house pathway signal flow algorithm and phylogenetic analysis were applied to find common pathway deregulation patterns in clusters. Analysis resulted in grouping the 22 conditions into 5 clusters (fig.1). PSF and phylogenetic analysis identified unique pathway deregulation patterns for each cluster (fig.2).

Authors: A. Arakelyan, L. Nersisyan, Henry Löffler-Wirth, Hans Binder

Date Published: 2014

Publication Type: Not specified

Human Diseases: lung disease

External ventricular drain infections: risk factors and outcome
SepNet - German Competence Network Sepsis

Abstract (Expand)

External ventricular drainage (EVD) is frequently used in neurosurgery to drain cerebrospinal fluid in patients with raised intracranial pressure. We performed a retrospective single center study in … order to evaluate the incidence of EVD-related infections and to identify underlying risk factors. 246 EVDs were placed in 218 patients over a 30-month period. EVD was continued in median for 7 days (range 1-44). The cumulative incidence of EVD-related infections was 8.3% (95% CI, 5.3-12.7) with a device-associated infection rate of 10.4 per 1000 drainage days (95% CI, 6.2-16.5). The pathogens most commonly identified were coagulase-negative Staphylococcus (62%) followed by Enterococcus spp. (19%). Patients with an EVD-related infection had a significantly longer ICU (11 versus 21 days, P \textless 0.01) and hospital stay (20 versus 28.5 days, P \textless 0.01) than patients without. Median total duration of external drainage was twice as long in patients with EVD-related infection (6 versus 12 days, P \textless 0.01). However, there was no significant difference in the duration between first EVD placement and the occurrence of EVD-related infection and EVD removal in patients without EVD-related infection (6 versus 7 days, P = 0.87), respectively. Interestingly no risk factor for EVD-related infection could be identified in our cohort of patients.

Authors: S. Hagel, T. Bruns, M. W. Pletz, C. Engel, R. Kalff, C. Ewald

Date Published: 2014

Publication Type: Journal article

Human Diseases: disease by infectious agent

Anforderungen an ein modernes und umfassendes Informationsmanagement für Krankenhäuser
Management of health information systems

Abstract

Not specified

Author: Alfred Winter

Date Published: 2014

Publication Type: InCollection

How to Assess Quality of Electronic Health Record Systems
Management of health information systems

Abstract

Not specified

Author: Alfred Winter

Date Published: 2014

Publication Type: InCollection

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