TY  - JOUR
A1  - Donat, Ulrike
A1  - Rother, Juliane
A1  - Schäfer, Simon
A1  - Hess, Michael
A1  - Härtl, Barbara
A1  - Kober, Christina
A1  - Langbein-Laugwitz, Johanna
A1  - Stritzker, Jochen
A1  - Chen, Nanhai G.
A1  - Aguilar, Richard J.
A1  - Weibel, Stephanie
A1  - Szalay, Alandar A.
T1  - Characterization of Metastasis Formation and Virotherapy in the Human C33A Cervical Cancer Model
JF  - PLoS ONE
N2  - More than 90% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervical cancer cell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A-RFP cells. RFP positive cancer cells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervical cancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases.
KW  - metastasis
KW  - renal cancer
KW  - oncolytic viruses
KW  - lymph nodes
KW  - kidneys
KW  - lung and intrathoracic tumors
KW  - secondary lung tumors
KW  - cancer treatment
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119674
SN  - 1932-6203
VL  - 9
IS  - 6
ER  - 
TY  - JOUR
A1  - Enigk, Fabian
A1  - Wagner, Antje
A1  - Samapati, Rudi
A1  - Rittner, Heike
A1  - Brack, Alexander
A1  - Mousa, Shaaban A.
A1  - Schäfer, Michael
A1  - Habazettl, Helmut
A1  - Schäper, Jörn
T1  - Thoracic epidural anesthesia decreases endotoxin-induced endothelial injury
JF  - BMC Anesthesiology
N2  - Background: The sympathetic nervous system is considered to modulate the endotoxin-induced activation of immune cells. Here we investigate whether thoracic epidural anesthesia with its regional symapathetic blocking effect alters endotoxin-induced leukocyte-endothelium activation and interaction with subsequent endothelial injury. Methods: Sprague Dawley rats were anesthetized, cannulated and hemodynamically monitored. E. coli lipopolysaccharide (Serotype 0127: B8, 1.5 mg x kg(-1) x h(-1)) or isotonic saline (controls) was infused for 300 minutes. An epidural catheter was inserted for continuous application of lidocaine or normal saline in endotoxemic animals and saline in controls. After 300 minutes we measured catecholamine and cytokine plasma concentrations, adhesion molecule expression, leukocyte adhesion, and intestinal tissue edema. Results: In endotoxemic animals with epidural saline, LPS significantly increased the interleukin-1 beta plasma concentration (48%), the expression of endothelial adhesion molecules E-selectin (34%) and ICAM-1 (42%), and the number of adherent leukocytes (40%) with an increase in intestinal myeloperoxidase activity (26%) and tissue edema (75%) when compared to healthy controls. In endotoxemic animals with epidural infusion of lidocaine the values were similar to those in control animals, while epinephrine plasma concentration was 32% lower compared to endotoxemic animals with epidural saline. Conclusions: Thoracic epidural anesthesia attenuated the endotoxin-induced increase of IL-1 beta concentration, adhesion molecule expression and leukocyte-adhesion with subsequent endothelial injury. A potential mechanism is the reduction in the plasma concentration of epinephrine.
KW  - endotoxemia
KW  - myeloperoxidase
KW  - endothelial injury
KW  - adhesion molecules
KW  - inflammatory response
KW  - intestinal microvascular perfusion
KW  - cell-adhesion
KW  - induced impairment
KW  - reperfusion injury
KW  - sepsis
KW  - neutrophil
KW  - lidocaine
KW  - lung injury
KW  - cytokines
KW  - epidural anesthesia
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116787
VL  - 14
IS  - 23
ER  - 
TY  - THES
A1  - Schäfer, Michael
T1  - Das Würzburger Landgericht in der ersten Hälfte des 14. Jahrhunderts und seine ältesten Protokolle : Edition und Auswertung
T1  - The "Iudicium Provinciale" of Würzburg in the first half of the 14th century and its Minutes. Edition and Evaluation
N2  - Diese mediävistische Promotion beinhaltet drei große Themenbereiche. Der erste besteht aus einer Edition der frühesten maßgeblichen Quellen zum Landgericht (Iudicium provinciale) des Hochstifts Würzburg: die abschriftlich vorhandenen Gemeinurteile aus der Frühzeit, das anschließende erste Originalprotokoll und der folgende, zweite Band der Gerichtsmitschriften. Insgesamt werden so ca. die ersten vierzig Jahre des 14. Jh. abgedeckt. Die zu den frühesten ihrer Art gehörenden Notizen liefern aufschlussreiche Informationen nicht nur über Rechtsorganisation und Prozessrecht des Spätmittelalters, sondern vertiefen auch die Möglichkeiten zur sozial- und landesgeschichtlichen Analyse. Dies wird im begleitenden Interpretationsteil angegangen und ein systematischer Querschnitt durch die wichtigsten Aspekte des Landgerichts geboten. Dabei können etliche der bisherigen Fehldeutungen durch die materialgestütze Auswertung korrigiert werden. Hinzu kommt ein methodischer Teil, der die Möglichkeiten statistischer Methoden und Analysen für die Geschichtswissenschaft überprüft. Zur besseren Bearbeitung immensen Materialfülle dieser Protokolle wurde der älteste Band zudem als Datenbank konzipiert.
N2  - This mediaevistic graduation constists of three parts. First there is an edition of the earliest and most relevant sources to the regional court (Landgericht, Iudicium provinciale) of the Würzburg diocese: the as a copy existing common judgements (Gemeinurteile) from the earliest times, furthermore the first original minutes and the following, second volume of the court with its remarks. Altogether these texts cover approx. the first forty years of the fourteenth century. The notes are among the earliest of their kind and the given informations show not only the organization of right and justice, or details of the procedural law in the late middle ages, but also the shows considerable ways to answer questions of social history and details of territorial history. This is concerned in the accompanying interpretation part and the systematic investigation of the most important aspects of the regional court. Some of past misinterpretations are to be corrected by the evaluation according to the edited sources. In addition comes a methodical part, which examines the chances of statistic methods and analyses for the science of history. For better treatment of these minutes the earliest volumes are summarized in a database solution.
KW  - Würzburg <Hochstift>
KW  - Landgericht
KW  - Gerichtsbuch
KW  - Geschichte 1317-1334
KW  - Würzburg <Hochstift>
KW  - Landgericht
KW  - Recht
KW  - Geschichte
KW  - Quelle
KW  - Würzburg <Hochstift>
KW  - court
KW  - iurisdiction
KW  - history
KW  - sources
Y1  - 2002
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-7443
ER  - 
TY  - JOUR
A1  - Burns, Alan J.
A1  - Goldstein, Allan M.
A1  - Newgreen, Donald F.
A1  - Stamp, Lincon
A1  - Schäfer, Karl-Herbert
A1  - Metzger, Marco
A1  - Hotta, Ryo
A1  - Young, Heather M.
A1  - Andrews, Peter W.
A1  - Thapar, Nikhil
A1  - Belkind-Gerson, Jaime
A1  - Bondurand, Nadege
A1  - Bornstein, Joel C.
A1  - Chan, Wood Yee
A1  - Cheah, Kathryn
A1  - Gershon, Michael D.
A1  - Heuckeroth, Robert O.
A1  - Hofstra, Robert M.W.
A1  - Just, Lothar
A1  - Kapur, Raj P.
A1  - King, Sebastian K.
A1  - McCann, Conor J.
A1  - Nagy, Nandor
A1  - Ngan, Elly
A1  - Obermayr, Florian
A1  - Pachnis, Vassilis
A1  - Pasricha, Pankaj J.
A1  - Sham, Mai Har
A1  - Tam, Paul
A1  - Vanden Berghe, Pieter
T1  - White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies
JF  - Developmental Biology
N2  - Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.
KW  - Neural crest cells
KW  - Rat mynteric plexus
KW  - Intestinal pseudoobstruction
KW  - Hypertrophic pyloric-stenosis
KW  - Hirschsprung disease liability
KW  - Slow-transit constipation
KW  - Oxide synthase gene
KW  - Term follow-up
KW  - Nitric-oxide
KW  - In-vivo
KW  - Enteric nervous system
KW  - Enteric neuropathies
KW  - Stem cells
KW  - Cell replacement therapy
KW  - Hirschsprung disease
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187415
VL  - 417
IS  - 2
ER  - 
TY  - JOUR
A1  - Eckardt, Jan-Niklas
A1  - Stasik, Sebastian
A1  - Kramer, Michael
A1  - Röllig, Christoph
A1  - Krämer, Alwin
A1  - Scholl, Sebastian
A1  - Hochhaus, Andreas
A1  - Crysandt, Martina
A1  - Brümmendorf, Tim H.
A1  - Naumann, Ralph
A1  - Steffen, Björn
A1  - Kunzmann, Volker
A1  - Einsele, Hermann
A1  - Schaich, Markus
A1  - Burchert, Andreas
A1  - Neubauer, Andreas
A1  - Schäfer-Eckart, Kerstin
A1  - Schliemann, Christoph
A1  - Krause, Stefan W.
A1  - Herbst, Regina
A1  - Hänel, Mathias
A1  - Frickhofen, Norbert
A1  - Noppeney, Richard
A1  - Kaiser, Ulrich
A1  - Baldus, Claudia D.
A1  - Kaufmann, Martin
A1  - Rácil, Zdenek
A1  - Platzbecker, Uwe
A1  - Berdel, Wolfgang E.
A1  - Mayer, Jiří
A1  - Serve, Hubert
A1  - Müller-Tidow, Carsten
A1  - Ehninger, Gerhard
A1  - Stölzel, Friedrich
A1  - Kroschinsky, Frank
A1  - Schetelig, Johannes
A1  - Bornhäuser, Martin
A1  - Thiede, Christian
A1  - Middeke, Jan Moritz
T1  - Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia
JF  - Cancers
N2  - Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
KW  - acute myeloid leukemia
KW  - BCOR
KW  - BCORL1
KW  - loss-of-function
KW  - risk stratification
KW  - survival
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236735
SN  - 2072-6694
VL  - 13
IS  - 9
ER  - 
TY  - JOUR
A1  - Schäfer, Natalie
A1  - Bühler, Michael
A1  - Heyer, Lisa
A1  - Röhr, Merle I. S.
A1  - Beuerle, Florian
T1  - Endohedral Hydrogen Bonding Templates the Formation of a Highly Strained Covalent Organic Cage Compound
JF  - Chemistry—A European Journal
N2  - A highly strained covalent organic cage compound was synthesized from hexahydroxy tribenzotriquinacene (TBTQ) and a meta-terphenyl-based diboronic acid with an additional benzoic acid substituent in 2’-position. Usually, a 120° bite angle in the unsubstituted ditopic linker favors the formation of a [4+6] cage assembly. Here, the introduction of the benzoic acid group is shown to lead to a perfectly preorganized circular hydrogen-bonding array in the cavity of a trigonal-bipyramidal [2+3] cage, which energetically overcompensates the additional strain energy caused by the larger mismatch in bite angles for the smaller assembly. The strained cage compound was analyzed by mass spectrometry and \(^{1}\)H, \(^{13}\)C and DOSY NMR spectroscopy. DFT calculations revealed the energetic contribution of the hydrogen-bonding template to the cage stability. Furthermore, molecular dynamics simulations on early intermediates indicate an additional kinetic effect, as hydrogen bonding also preorganizes and rigidifies small oligomers to facilitate the exclusive formation of smaller and more strained macrocycles and cages.
KW  - boronate esters
KW  - hydrogen bonding
KW  - dynamic covalent chemistry
KW  - density functional calculations
KW  - cage compounds
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256762
VL  - 27
IS  - 19
ER  -