Comparison of Acoustic Structure Quantification (ASQ), shearwave elastography and histology in patients with diffuse hepatopathies.

Background: Objective of the study was to evaluate the diagnostic value of novel ultrasonographic modalities in comparison with simultaneously performed liver biopsy.

Methods: The results of simultaneously performed examinations using Acoustic Structure Quantification (ASQ), Virtual Touch Imaging and Quantification (VTIQ) and Virtual Touch Tissue Quantification (VTTQ) were compared with the findings of liver biopsy in patients with a wide variety of diffuse hepatopathies (n = 51). The histologically determined fibrosis stage according to Desmet and Scheuer was compared with quantitative measurements returned by the ultrasonographic imaging modalities.

Gene regulatory biomarker identification for skin toxicities induced by EGFR inhibitor treatment.

1 Federal Institute for Drugs and Medical Devices (BfArM), Research Division, Bonn, 2 Institute of Pharmacology of Natural Products and Clinical Pharmacology, 3 Department of Internal Medicine II, University of Ulm, Ulm, 4 Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care Medicine, Clinics Kempten-Oberallgäu, Kempten, and 5 Department of Internal Medicine I, University of Ulm, Ulm, and 4 Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, Germany.

Protein Kinase D2 Assembles a Multiprotein Complex at the Trans-Golgi Network to Regulate Matrix Metalloproteinase Secretion.

Vesicle formation and fission are tightly regulated at the trans-Golgi network (TGN) during constitutive secretion. Two major protein families regulate these processes: members of the adenosyl-ribosylation factor family of small G-proteins (ARFs) and the protein kinase D (PKD) family of serine/threonine kinases. The functional relationship between these two key regulators of protein transport from the TGN so far is elusive.

Caliber of the common bile duct: effect of cholecystectomy and other factors in a ultrasonographic study of 8534 patients.

Objective: The objective of the present study was to analyze the effects of different factors impacting the caliber of the common bile duct (CBD) and a comparison of maximum extrahepatic bile duct caliber in patients with and without a history of cholecystectomy.

Material And Methods: A retrospective data analysis was undertaken of 8534 patients (4480 females; 4054 males; average age: 59.2±18.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.

High-throughput screening identified inherited genetic variations in the EGFR pathway contributing to skin toxicity of EGFR inhibitors.

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.

Reprint of: Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria.

We investigate connections between single-cell mechanical properties and subcellular structural reorganization from biochemical factors in the context of two distinctly different human diseases: gastrointestinal tumor and malaria. Although the cell lineages and the biochemical links to pathogenesis are vastly different in these two cases, we compare and contrast chemomechanical pathways whereby intracellular structural rearrangements lead to global changes in mechanical deformability of the cell. This single-cell biomechanical response, in turn, seems to mediate cell mobility and thereby facilitates disease progression in situations where the elastic modulus increases or decreases due to membrane or cytoskeleton reorganization.

Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal transition.

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.

[Personalized tumor therapy for gastrointestinal tumors].

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.

A time frame permissive for Protein Kinase D2 activity to direct angiogenesis in mouse embryonic stem cells.

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.

Self-Expandable Metal Stents for Persisting Esophageal Variceal Bleeding after Band Ligation or Injection-Therapy: A Retrospective Study.

Background And Study Aims: 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.

In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice.

Objective: 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.

Materials And Methods: 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).

Results: 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.

A Fresh Look on T-Box Factor Action in Early Embryogenesis (T-Box Factors in Early Development).

T-Box transcription factors are expressed throughout the gestational period and coordinate a variety of embryonic events that enable proper development, from the first differentiation of embryonic and extraembryonic tissues until final organogenesis. Although the T-Box gene family comprises essential roles in early cellular differentiation, in adult tissues it has also been 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.

Hepatobiliary complications of alveolar echinococcosis: A long-term follow-up study.

Aim: To determine the long-term hepatobiliary complications of alveolar echinococcosis (AE) and treatment options using interventional methods.

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.

PRKD2: A two-pronged kinase crucial for the tumor-supporting activity of HSP90.

PRKD2 plays an important role in tumor cell survival, proliferation, migration, and angiogenesis. We recently reported that cell death and impaired blood vessel formation evoked by inhibition of the HSP90 chaperone in human cancer cells of various tissue origins is mediated by destabilization of PRKD2.

[Therapy in pancreatic cancer - and still it moves along!].

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.

IgG4-related autoimmune diseases: Polymorphous presentation complicates diagnosis and treatment.

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.

IGF-1 drives chromogranin A secretion via activation of Arf1 in human neuroendocrine tumour cells.

Hypersecretion is the major symptom of functional neuroendocrine tumours. The mechanisms that contribute to this excessive secretion of hormones are still elusive. A key event in secretion is the exit of secretory products from the Golgi apparatus.

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)).

Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial.

Context: Carcinoid syndrome (CS) is associated with elevated serotonin, diarrhea, flushing, and increased risk of valvular heart disease. Many patients respond to somatostatin analogs initially, but response diminishes in most patients. Additional options are needed.