T Seufferlein

Philipps University of Marburg, Marburg, Hesse, Germany

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Publications (331)1398.2 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To identify genomic variants in the EGFR pathway and in cytokines predisposing to skin toxicity from EGFR inhibitors. Patients & methods: In 126 patients with cancer and EGFR inhibitor therapy skin toxicity was quantified and EGFR and inflammatory pathway genes were analyzed by deep sequencing. Results: We found 1437 SNPs in the 382-kb target region. Three SNPs in EGFR intron 1 were found exclusively in patients without skin rash. Another EGFR intron 23 SNP was associated with skin rash, overall survival and IL8 plasma concentrations. Moreover, carriers of the PIK3R1 326I variant were predisposed to skin rash and better survival. Conclusion: Comprehensive pathway-based resequencing revealed some new but only moderately strong genomic predictors of skin toxicity.
    Pharmacogenomics 09/2015; DOI:10.2217/pgs.15.97 · 3.22 Impact Factor
  • Annals of Oncology 09/2015; 26(suppl 5):v56-v68. DOI:10.1093/annonc/mdv295 · 7.04 Impact Factor
  • E Zizer · J Bartz · U Möhnle · M Güthle · T Seufferlein · M Wagner
    Zeitschrift für Gastroenterologie 08/2015; 53(08). DOI:10.1055/s-0035-1559083 · 1.05 Impact Factor
  • M Güthle · C Friesen · R Hofheinz · R Muche · T Ettrich · L Perkhofer · A Berger · T Seufferlein
    Zeitschrift für Gastroenterologie 08/2015; 53(08). DOI:10.1055/s-0035-1559240 · 1.05 Impact Factor
  • T Seufferlein · M Beil · A Micoulet · G von Wichert · S Paschke · J Spatz · G Adler
    Zeitschrift für Gastroenterologie 08/2015; 41(08). DOI:10.1055/s-0035-1555333 · 1.05 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):1435-1435. DOI:10.1158/1538-7445.AM2015-1435 · 9.33 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGFβ-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men.
    Nature Communications 07/2015; 6:7677. DOI:10.1038/ncomms8677 · 11.47 Impact Factor
  • T J Ettrich · L Perkhofer · T Seufferlein
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    ABSTRACT: Personalized tumor therapy or more precisely tumor-specific therapy has now become established in routine clinical oncology. Particularly for solid tumors, the emerging knowledge about pathways and signaling networks allows the establishment of new targeted therapies and hopefully a continuous improvement in patient care. Targeted therapies are now established as the standard of care as single agents or in combination with chemotherapy. Using targeted therapies, substantial improvements regarding tumor response, median progression-free survival and median overall survival can be achieved for selected gastrointestinal tumors. However, these strategies also have novel side effects that need to be addressed. Importantly, valid (positive) predictive biomarkers are needed for a rational use of these novel compounds. This review article presents the current state of targeted tumor therapy for the diagnostics and therapy of gastrointestinal tumors and provides assistance in integrating the current knowledge into the routine clinical context.
    Der Internist 07/2015; 56(9). DOI:10.1007/s00108-015-3752-6 · 0.31 Impact Factor
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    ABSTRACT: The protein kinase D isoenzymes PKD1/2/3 are prominent downstream targets of PKCs (Protein Kinase Cs) and phospholipase D in various biological systems. Recently, we identified PKD isoforms as novel mediators of tumour cell-endothelial cell communication, tumour cell motility and metastasis. Although PKD isoforms have been implicated in physiological/tumour angiogenesis, a role of PKDs during embryonic development, vasculogenesis and angiogenesis still remains elusive. We investigated the role of PKDs in germ layer segregation and subsequent vasculogenesis and angiogenesis using mouse embryonic stem cells (ESCs). We show that mouse ESCs predominantly express PKD2 followed by PKD3 while PKD1 displays negligible levels. Furthermore, we demonstrate that PKD2 is specifically phosphorylated/activated at the time of germ layer segregation. Time-restricted PKD2-activation limits mesendoderm formation and subsequent cardiovasculogenesis during early differentiation while leading to branching angiogenesis during late differentiation. In line, PKD2 loss-of-function analyses showed induction of mesendodermal differentiation in expense of the neuroectodermal germ layer. Our in vivo findings demonstrate that embryoid bodies transplanted on chicken chorioallantoic membrane induced an angiogenic response indicating that timed overexpression of PKD2 from day 4 onwards leads to augmented angiogenesis in differentiating ESCs. Taken together, our results describe novel and time-dependent facets of PKD2 during early cell fate determination.
    Scientific Reports 07/2015; 5:11742. DOI:10.1038/srep11742 · 5.58 Impact Factor
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    ABSTRACT: Despite a pronounced reduction of lethality rates due to upper gastrointestinal bleeding, esophageal variceal bleeding remains a challenge for the endoscopist and still accounts for a mortality rate of up to 40% within the first 6 weeks. A relevant proportion of patients with esophageal variceal bleeding remains refractory to standard therapy, thus making a call for additional tools to achieve hemostasis. Self-expandable metal stents (SEMS) incorporate such a tool. We evaluated a total number of 582 patients admitted to our endoscopy unit with the diagnosis "gastrointestinal bleeding" according to our documentation software between 2011 and 2014. 82 patients suffered from esophageal variceal bleeding, out of which 11 cases were refractory to standard therapy leading to SEMS application. Patients with esophageal malignancy, fistula, or stricture and a non-esophageal variceal bleeding source were excluded from the analysis. A retrospective analysis reporting a series of clinically relevant parameters in combination with bleeding control rates and adverse events was performed. The initial bleeding control rate after SEMS application was 100%. Despite this success, we observed a 27% mortality rate within the first 42 days. All of these patients died due to non-directly hemorrhage-associated reasons. The majority of patients exhibited an extensive demand of medical care with prolonged hospital stay. Common complications were hepatic decompensation, pulmonary infection and decline of renal function. Interestingly, we found in 7 out of 11 patients (63.6%) stent dislocation at time of control endoscopy 24 h after hemostasis or at time of stent removal. The presence of hiatal hernia did not affect obviously stent dislocation rates. Refractory patients had significantly longer hospitalization times compared to non-refractory patients. Self-expandable metal stents for esophageal variceal bleeding seem to be safe and efficient after failed standard therapy. Stent migration appeared to be a common incident that did not lead to reactivation of bleeding in any of our patients. SEMS should be considered a reasonable treatment option for refractory esophageal variceal bleeding after treatment failure of ligature and sclerotherapy and non-availability of or contraindication for other measures (e.g. TIPS).
    PLoS ONE 06/2015; 10(6):e0126525. DOI:10.1371/journal.pone.0126525 · 3.23 Impact Factor
  • J Walldorf · M Hermann · M Porzner · S Pohl · H Metz · K Mäder · A Zipprich · B Christ · T Seufferlein
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    ABSTRACT: The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. • Improved in vivo monitoring might balance interindividual differences in murine colitis. • In monitoring murine colitis, btMRI and hrUS are safe and technically feasible. • Very short examination times underline the usefulness especially of hrUS. • Results of btMRI and hrUS correlate with endoscopic and post-mortem findings.
    European Radiology 05/2015; 25(10). DOI:10.1007/s00330-015-3714-3 · 4.01 Impact Factor
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    ABSTRACT: T-Box transcription factors are expressed throughout the gestational period and coordinate a variety of embryonic events to allow for proper development, from the first differentiation of embryonic and extraembryonic tissues until final organogenesis. While the T-Box gene family comprises essential roles in early cellular differentiation, in adult tissues it has been also associated with cancer development. In spite of their common T-Box regulatory binding domain, T-Box family members utilize different cofactors and different spatiotemporal expression patterns to confer their specificity in diverse developmental processes. The earliest expression note of T-Box factors can be observed even before fertilization in primordial germ cells and just after zygotic gene activation (around the eight-cell blastomere stage). Thus, particularly the early stages of development are highly influenced by these key regulators in line with the notion that T-Box mutations lead to developmental disorders and even lethality. In this review, we summarize recently acquired findings on T-Box factors to provide a comprehensive overview on their role during early embryogenesis.
    Stem cells and development 05/2015; 24(16). DOI:10.1089/scd.2015.0102 · 3.73 Impact Factor
  • Lukas Perkhofer · Thomas J. Ettrich · Thomas Seufferlein
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    ABSTRACT: Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths in the Western world. Due to lack of specific symptoms and no accessible precursor lesions, primary diagnosis is commonly delayed, resulting in the identification of only 15-20% of patients with potentially curable disease. The major limiting factor is an already locally advanced or metastatic disease at the time of diagnosis. Consequently, systemic therapy forms the backbone of treatment strategy for the majority of patients. Summary: A deeper understanding of the molecular characteristics of pancreatic cancer has led to the identification of several potential therapeutic targets. A variety of targeted therapies are currently under clinical evaluation as single agents or in combination with chemotherapy for PDAC. This review highlights the current state of chemotherapy in pancreatic cancer and provides an outlook on its future perspectives. Key Message: This review focuses on the current chemotherapy regimens for the systemic treatment of PDAC. Practical Implications: Various neoadjuvant approaches have been explored, including chemoradiation, chemotherapy followed by chemoradiation or intensified chemotherapy without defining a standard of care so far. The standard of care is gemcitabine or 5-fluorouracil. The oral fluoropyrimidine S-1 may be a promising new agent in this setting. For first-line treatment of metastatic pancreatic cancer, no targeted therapy has yet demonstrated clinical benefit apart from the combination of the tyrosine kinase inhibitor erlotinib plus gemcitabine. Recently, novel chemotherapeutic regimens such as FOLFIRINOX and gemcitabine plus nanoparticle albumin-bound paclitaxel have been introduced. Both combinations have proved to be superior to the standard gemcitabine regimen. For second-line treatment the combination of 5-fluorouracil/leucovorin and oxaliplatin yields improved results compared to best supportive care.
    05/2015; 1(4):167-179. DOI:10.1159/000380785
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    ABSTRACT: To determine the long-term hepatobiliary complications of alveolar echinococcosis (AE) and treatment options using interventional methods. Included in the study were 35 patients with AE enrolled in the Echinococcus Multilocularis Data Bank of the University Hospital of Ulm. Patients underwent endoscopic intervention for treatment of hepatobiliary complications between 1979 and 2012. Patients' epidemiologic data, clinical symptoms, and indications for the intervention, the type of intervention and any additional procedures, hepatic laboratory parameters (pre- and post-intervention), medication and surgical treatment (pre- and post-intervention), as well as complications associated with the intervention and patients' subsequent clinical courses were analyzed. In order to compare patients with AE with and without history of intervention, data from an additional 322 patients with AE who had not experienced hepatobiliary complications and had not undergone endoscopic intervention were retrieved and analyzed. Included in the study were 22 male and 13 female patients whose average age at first diagnosis was 48.1 years and 52.7 years at the time of intervention. The average time elapsed between first diagnosis and onset of hepatobiliary complications was 3.7 years. The most common symptoms were jaundice, abdominal pains, and weight loss. The number of interventions per patient ranged from one to ten. Endoscopic retrograde cholangiopancreatography (ERCP) was most frequently performed in combination with stent placement (82.9%), followed by percutaneous transhepatic cholangiodrainage (31.4%) and ERCP without stent placement (22.9%). In 14.3% of cases, magnetic resonance cholangiopancreatography was performed. A total of eight patients received a biliary stent. A comparison of biochemical hepatic function parameters at first diagnosis between patients who had or had not undergone intervention revealed that these were significantly elevated in six patients who had undergone intervention. Complications (cholangitis, pancreatitis) occurred in six patients during and in 12 patients following the intervention. The average survival following onset of hepatobiliary complications was 8.8 years. Hepatobiliary complications occur in about 10% of patients. A significant increase in hepatic transaminase concentrations facilitates the diagnosis. Interventional methods represent viable management options.
    04/2015; 21(16):4925-32. DOI:10.3748/wjg.v21.i16.4925
  • M. Svinarenko · S.-F. Katz · T. Seufferlein · P. Schirmacher · A. Lechel
    Journal of Hepatology 04/2015; 62:S409-S410. DOI:10.1016/S0168-8278(15)30490-6 · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S415. DOI:10.1016/S0168-8278(15)30503-1 · 11.34 Impact Factor
  • Thomas J Ettrich · Lukas Perkhofer · Thomas Seufferlein
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    ABSTRACT: According to predictions pancreatic ductal adenocarcinoma will be the third most common cancer-related cause of death in 2030 due to its growing incidence and advances in prevention and treatment of other tumor entities. Pancreatic cancer is usually a (too) late diagnosed disease. Already at time of primary diagnosis nearly 80 % of patients have palliative disease due to local irresectability or distant metastases. Even after R0 resection of the primary tumor followed by adjuvant chemotherapy the 5-year overall survival rate does not exceed 20 %. Recently the treatment landscape has significanty changed in metastatic pancreatic cancer. For the first time, we have the opportunity to personalize our therapies in the field of pancreatic cancer. In addition, the range of therapeutic options after failure of first-line treatment expands more and more. After years of stagnation and negative results in clinical trials these advances inspire and dynamize the landscape of new clinical trials in this entity. © Georg Thieme Verlag KG Stuttgart · New York.
    DMW - Deutsche Medizinische Wochenschrift 04/2015; 140(7):508-511. DOI:10.1055/s-0041-101154 · 0.54 Impact Factor
  • A Meining · E Zizer · T Seufferlein
    Endoskopie heute 03/2015; 28(01). DOI:10.1055/s-0035-1545053 · 0.05 Impact Factor
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    ABSTRACT: Background: IgG4-associated autoimmune diseases are systemic diseases affecting multiple organs of the body. Autoimmune pancreatitis, with a prevalence of 2.2 per 100 000 people, is one such disease. Because these multi-organ diseases present in highly variable ways, they were long thought just to affect individual organ systems. This only underscores the importance of familiarity with these diseases for routine clinical practice. Methods: This review is based on pertinent articles retrieved by a selective search in PubMed, and on the published conclusions of international consensus conferences. Results: The current scientific understanding of this group of diseases is based largely on case reports and small case series; there have not been any randomized controlled trials (RCTs) to date. Any organ system can be affected, including (for example) the biliary pathways, salivary glands, kidneys, lymph nodes, thyroid gland, and blood vessels. Macroscopically, these diseases cause diffuse organ swelling and the formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with IgG4-positive plasma cells, which leads via an autoimmune mechanism to the typical histologic findings-storiform fibrosis ("storiform" = whorled, like a straw mat) and obliterative, i.e., vessel-occluding, phlebitis. A mixed Th1 and Th2 immune response seems to play an important role in pathogenesis, while the role of IgG4 antibodies, which are not pathogenic in themselves, is still unclear. Glucocorticoid treatment leads to remission in 98% of cases and is usually continued for 12 months as maintenance therapy. Most patients undergo remission even if untreated. Steroid-resistant disease can be treated with immune modulators. Conclusion: IgG4-associated autoimmune diseases are becoming more common, but adequate, systematically obtained data are now available only from certain Asian countries. Interdisciplinary collaboration is a prerequisite to proper diagnosis and treatment. Treatment algorithms and RCTs are needed to point the way to organ-specific treatment in the future.
    Deutsches Ärzteblatt International 02/2015; 112(8):128-+. DOI:10.3238/arztebl.2015.0128 · 3.52 Impact Factor
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    ABSTRACT: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis
    Nature 02/2015; 518(7538). DOI:10.1038/nature14177 · 41.46 Impact Factor

Publication Stats

5k Citations
1,398.20 Total Impact Points


  • 2015
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 2001–2015
    • Universität Ulm
      • • Institute of Orthopaedic Research and Biomechanics
      • • Clinic of Internal Medicine I
      • • Department of Internal Medicine
      Ulm, Baden-Württemberg, Germany
  • 2006–2014
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2013
    • Deutsche Krebsgesellschaft e.V.
      Berlín, Berlin, Germany
  • 2008–2013
    • Martin Luther University Halle-Wittenberg
      • Clinic for Internal Medicine I
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2009–2012
    • Universitätsklinikum Halle (Saale)
      Halle-on-the-Saale, Saxony-Anhalt, Germany
    • University Hospital Frankfurt
      Frankfurt, Hesse, Germany
  • 2011
    • Azienda Ospedaliero-Universitaria Pisana
      Pisa, Tuscany, Italy
  • 2007
    • Otto-von-Guericke-Universität Magdeburg
      • Clinic for Gastroenterology, Hepatology and Infectiology
      Magdeburg, Saxony-Anhalt, Germany
  • 2005
    • Prosper-Hospital Recklinghausen
      Recklinghausen, North Rhine-Westphalia, Germany
  • 2003
    • Klinikum Augsburg
      • II. Department of Internal Medicine
      Augsberg, Bavaria, Germany
  • 1994
    • Deutsche Forschungsgemeinschaft
      Bonn, North Rhine-Westphalia, Germany