Universitatsklinik Und Poliklinik For Innere Medizin I

Halle (Saale), Germany

Universitatsklinik Und Poliklinik For Innere Medizin I

Halle (Saale), Germany

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Schneider K.U.,University of Heidelberg | Dietrich D.,Epigenomics AG | Fleischhacker M.,Charité - Medical University of Berlin | Leschber G.,ELK Berlin Chest Hospital | And 11 more authors.
BMC Cancer | Year: 2011

Background: DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples.Methods: SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH.Results: A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference.Conclusions: Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples. © 2011 Schneider et al; licensee BioMed Central Ltd.


Schmidt B.,Universitatsklinik Und Poliklinik For Innere Medizin I | Liebenberg V.,Metanomics Health GmbH | Dietrich D.,Epigenomics AG | Schlegel T.,Epigenomics AG | And 15 more authors.
BMC Cancer | Year: 2010

Background: This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.Methods: Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.Results: Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).Conclusions: Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous. © 2010 Schmidt et al; licensee BioMed Central Ltd.


Fleischhacker M.,Universitatsklinik Und Poliklinik For Innere Medizin I | Dietrich D.,University of Bonn | Liebenberg V.,Epigenomics AG | Field J.K.,University of Liverpool | Schmidt B.,Universitatsklinik Und Poliklinik For Innere Medizin I
Expert Review of Respiratory Medicine | Year: 2013

It is now widely accepted that cancer is caused by complex interactions between genetic and epigenetic factors and the environment. Only in the last 20 years, DNA methylation has been recognized as an epigenetic mechanism, which plays a major role during the development and progression of cancers. Accordingly, DNA methylation profiling provides a useful source for biomarkers in distinct clinical questions; for example, risk stratification, diagnosis, staging, prognosis and therapy-response prediction. In the last 10 years, not only has an increase in the number of papers published on this subject been seen, but also an impressive technological advancement allowing for the highly sensitive and accurate quantification of DNA methylation biomarkers in challenging sample types. However, the development of a suitable biomarker with appropriate assay technology is not trivial. This is especially true for the choice of biomarkers used for the management of early diagnosis of lung cancer. © 2013 Informa UK Ltd.


PubMed | Institute For Pathologie, Universitatsklinik Und Poliklinik For Innere Medizin I and Martin Luther University of Halle Wittenberg
Type: Journal Article | Journal: Pneumologie (Stuttgart, Germany) | Year: 2016

A patient presented himself with pungent, breath-dependent right chest pain and dyspnea at rest in our emergency department. The physical examination and the ECG revealed no relevant findings. The laboratory results showed an increased CRP, leukocytosis, elevated D-dimers and a respiratory partial insufficiency. In the thoracic CT angiography unclear pulmonary nodules (PN) were seen. The bronchoscopy was macroscopically normal. In the BAL yeasts and a high proportion of immune senescence cells (CD57+) were identified. After a pulmonary wedge resection resulted histologically an epithelioid cell-granulomatous inflammation. Molecular pathological a mycelium genome, in particular Pichia guilliermondii (PC) was detected. The therapy with fluconazole was successful. PC rarely causes candidemia, increased in immunocompromised patients. In our judgement this is in Europe the first described case of PC-infection in a patient, which presented no predisposition to infection with opportunistic pathogens apart from type 2 diabetes.It should be thought of fungal infection by these pathogens group in case of unclear PN, especially in combination with possibly predisposing factors.


Rolli C.G.,Max Planck Institute for Intelligent Systems (Stuttgart) | Rolli C.G.,University of Heidelberg | Seufferlein T.,Universitatsklinik Und Poliklinik For Innere Medizin I | Kemkemer R.,Max Planck Institute for Intelligent Systems (Stuttgart) | And 2 more authors.
PLoS ONE | Year: 2010

Cell migration is a fundamental feature of the interaction of cells with their surrounding. The cell's stiffness and ability to deform itself are two major characteristics that rule migration behavior especially in three-dimensional tissue. We simulate this situation making use of a micro-fabricated migration chip to test the active invasive behavior of pancreatic cancer cells (Panc-1) into narrow channels. At a channel width of 7 mm cell migration through the channels was significantly impeded due to size exclusion. A striking increase in cell invasiveness was observed once the cells were treated with the bioactive lipid sphingosylphosphorylcholine (SPC) that leads to a reorganization of the cell's keratin network, an enhancement of the cell's deformability, and also an increase in the cell's migration speed on flat surfaces. The migration speed of the highly deformed cells inside the channels was three times higher than of cells on flat substrates but was not affected upon SPC treatment. Cells inside the channels migrated predominantly by smooth sliding while maintaining constant cell length. In contrast, cells on adhesion mediating narrow lines moved in a stepwise way, characterized by fluctuations in cell length. Taken together, with our migration chip we demonstrate that the dimensionality of the environment strongly affects the migration phenotype and we suggest that the spatial cytoskeletal keratin organization correlates with the tumor cell's invasive potential. © 2010 Rolli et al.


Fleischhacker M.,Charité - Medical University of Berlin | Schmidt B.,Universitatsklinik Und Poliklinik For Innere Medizin I | Weickmann S.,Charité - Medical University of Berlin | Fersching D.M.I.,Ludwig Maximilians University of Munich | And 6 more authors.
Clinica Chimica Acta | Year: 2011

Extracellular nucleic acids are present in plasma, serum, and other body fluids and their analysis has gained increasing attention during recent years. Because of the small quantity and highly fragmented nature of cell-free DNA in plasma and serum, a fast, efficient, and reliable isolation method is still a problem and so far there is no agreement on a standardized method. We used spin columns from commercial suppliers (QIAamp DNA Blood Midi Kit from Qiagen; NucleoSpin Kit from Macherey-Nagel; MagNA Pure isolation system from Roche Diagnostics) to isolate DNA from 44 plasma samples in parallel at laboratories in Berlin and Munich. DNA in all samples was quantified by real-time PCR on a LightCycler 480 using three different targets (GAPDH, ß-globin, ERV). The quantities of cell-free DNA for the different isolation methods and genes varied between medians of 1.6. ng/mL and 28.1. ng/mL. This considerable variation of absolute DNA values was mainly caused by the use of different isolation methods (P < 0.0001). Comparable results were achieved by the use of the genes GAPDH and ERV while higher values were obtained by use of ß-globin. The laboratory site had only minor influence on DNA yield when manual extraction methods were used. © 2011 Elsevier B.V.


Hautmann H.,TU Munich | Eberhardt R.,Thoraxklinik An der Universitatsklinik | Heine R.,Diakoniekrankenhaus Halle | Herth F.,Thoraxklinik An der Universitatsklinik | And 6 more authors.
Pneumologie | Year: 2011

Flexible bronchoscopy is a standard examination today and is conducted not only in nearly every hospital but also in privately owned practices. The vast majority of patients want sedation for this examination. Such a procedure is nearly always necessary in complex and interventional procedures, irrespective of the patients wish. The recommendation at hand to use sedation measures for flexible bronchoscopy is based on the results of numerous clinical studies and also takes account of individual experiences in this area. The structural and procedural requirements and the requirements for staff training are defined and should describe the minimum standard when it comes to conducting a bronchoscopy under sedation. Furthermore the drugs recommended for sedation are discussed and their methods of application shown. Finally the recommendations also include suggestions for patient clarification, monitoring and discharge. They should provide the examiner with concrete operating options and therefore above all increase patient safety. © Georg Thieme Verlag KG Stuttgart · New York.


Grabenhorst M.,Charité - Medical University of Berlin | Schmidt B.,Universitatsklinik Und Poliklinik For Innere Medizin I | Liebers U.,Charité - Medical University of Berlin | Oestmann J.-W.,Charité - Medical University of Berlin
American Journal of Roentgenology | Year: 2015

OBJECTIVE. Bronchoscopic lung volume reduction promises to become an effective treatment option in severe chronic obstructive pulmonary disease. Several techniques are currently being investigated, including implantation of devices into the lung and instillation of hot water vapor or polymer. This article reviews the spectrum of radiologic manifestations on chest radiography and CT that occur after the intervention. CONCLUSION. Familiarity with the intended effects and adverse events will aid the radiologist in supporting bronchoscopic lung volume reduction. © American Roentgen Ray Society.


Temme C.,Martin Luther University of Halle Wittenberg | Temme C.,Universitatsklinik Und Poliklinik For Innere Medizin I | Zhang L.,Martin Luther University of Halle Wittenberg | Zhang L.,Max Planck Institute of Microstructure Physics | And 6 more authors.
RNA | Year: 2010

The CCR4-NOT complex is the main enzyme catalyzing the deadenylation of mRNA. We have investigated the composition of this complex in Drosophila melanogaster by immunoprecipitation with a monoclonal antibody directed against NOT1. The CCR4, CAF1 (=POP2), NOT1, NOT2, NOT3, and CAF40 subunits were associated in a stable complex, but NOT4 was not. Factors known to be involved in mRNA regulation were prominent among the other proteins coprecipitated with the CCR4-NOT complex, as analyzed by mass spectrometry. The complex was localized mostly in the cytoplasm but did not appear to be a major component of P bodies. Of the known CCR4 paralogs, Nocturnin was found associated with the subunits of the CCR4-NOT complex, whereas Angel and 3635 were not. RNAi experiments in Schneider cells showed that CAF1, NOT1, NOT2, and NOT3 are required for bulk poly(A) shortening and hsp70 mRNA deadenylation, but knock-down of CCR4, CAF40, and NOT4 did not affect these processes. Overexpression of catalytically dead CAF1 had a dominant-negative effect on mRNA decay. In contrast, overexpression of inactive CCR4 had no effect. We conclude that CAF1 is the major catalytically important subunit of the CCR4-NOT complex in Drosophila Schneider cells. Nocturnin may also be involved in mRNA deadenylation, whereas there is no evidence for a similar role of Angel and 3635. Copyright © 2010 RNA Society.


PubMed | Universitatsklinik Und Poliklinik For Innere Medizin I
Type: | Journal: BMC cancer | Year: 2010

This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.

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