130 results on '"Uwe A. Wittel"'
Search Results
102. Perioperative Ergebnisse der Pankreaskopfresektion: konsekutive Erfahrung eines Chirurgen an einer Universitätsklinik und an einem kommunalen Klinikum
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Uwe A. Wittel, Ulrich Adam, Ulrich F. Wellner, Tobias Keck, Ulrich T. Hopt, Hartwig Riediger, and Frank Makowiec
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Gastroenterology - Published
- 2013
103. Anti-Tumor-Autoantikörper bei Patienten mit Pankreaskarzinom und Chronischer Pankreatitis
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Uwe A. Wittel, B. Vogt, M Menzel, Guido Wolff-Vorbeck, and Ulrich T. Hopt
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Gastroenterology - Published
- 2013
104. Stereotactic body radiotherapy (SBRT) in recurrent or oligometastatic pancreatic cancer: Simultaneus intergrated protection (SIP) versus conventional SBRT A toxicity review of two different treatment approaches
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Uwe A. Wittel, Katja Zirlik, Thomas Brunner, Tanja Schimek-Jasch, Anca L. Grosu, Ursula Nestle, R. Wiehle, Eleni Gkika, and Sonja Adebahr
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Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Pancreatic cancer ,Toxicity ,medicine ,food and beverages ,Radiology ,medicine.disease ,business ,Upper abdomen ,Stereotactic body radiotherapy - Abstract
e15692Background: SBRT in pancreatic cancer can be limited by its proximity to critical organs at risk (OAR) of the upper abdomen. In this study we evaluate the toxicity and efficacy of two differe...
- Published
- 2016
105. EP-1272: Stereotactic radiotherapy in pancreatic cancer. Review of two different treatment approaches
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Sonja Adebahr, Tanja Schimek-Jasch, Ursula Nestle, Simon Kirste, Uwe A. Wittel, Eleni Gkika, R. Wiehle, A.L. Grosu, Thomas B. Brunner, and K. Zirlik
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Oncology ,Stereotactic radiotherapy ,medicine.medical_specialty ,Radiology Nuclear Medicine and imaging ,business.industry ,Internal medicine ,Pancreatic cancer ,Medicine ,Radiology, Nuclear Medicine and imaging ,Hematology ,business ,medicine.disease - Published
- 2016
106. 712 Postoperative Pancreatitis After Pancreaticoduodenectomy Predicts Clinically Relevant Postoperative Pancreatic Fistulas
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Christian M Kühlbrey, Frank Makowiec, Ulrich T. Hopt, Niki Samiei, and Uwe A. Wittel
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medicine.medical_specialty ,Hepatology ,business.industry ,medicine.medical_treatment ,General surgery ,Gastroenterology ,medicine ,Pancreatitis ,Pancreaticoduodenectomy ,business ,medicine.disease ,Surgery - Published
- 2016
107. Reconstruction of complex abdominal wall defects with enteric fistulae with strattice reconstructive tissue matrix
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Tobias Keck, D. Tittelbach-Helmrich, Uwe A. Wittel, and Ulrich T. Hopt
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Abdominal wall ,Matrix (mathematics) ,medicine.anatomical_structure ,Materials science ,Gastroenterology ,medicine ,Biomedical engineering - Published
- 2012
108. Interplay between Smoking-induced Genotoxicity and Altered Signaling in Pancreatic Carcinogenesis
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Navneet Momi, Moorthy P. Ponnusamy, Sukhwinder Kaur, Uwe A. Wittel, Sushil Kumar, and Surinder K. Batra
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Cancer Research ,Nitrosamines ,DNA repair ,Angiogenesis ,Pyridines ,Review ,Biology ,Receptors, Nicotinic ,Metastasis ,Nicotine ,Proto-Oncogene Proteins p21(ras) ,Pancreatic cancer ,Proto-Oncogene Proteins ,medicine ,Humans ,Epigenetics ,Inflammation ,Polymorphism, Genetic ,Smoking ,Cancer ,General Medicine ,medicine.disease ,Pancreatic Neoplasms ,Immunology ,Mutation ,Cancer research ,ras Proteins ,Signal transduction ,medicine.drug ,Signal Transduction - Abstract
Despite continuous research efforts directed at early diagnosis and treatment of pancreatic cancer (PC), the status of patients affected by this deadly malignancy remains dismal. Its notoriety with regard to lack of early diagnosis and resistance to the current chemotherapeutics is due to accumulating signaling abnormalities. Hoarding experimental and epidemiological evidences have established a direct correlation between cigarette smoking and PC risk. The cancer initiating/promoting nature of cigarette smoke can be attributed to its various constituents including nicotine, which is the major psychoactive component, and several other toxic constituents, such as nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and polycyclic aromatic hydrocarbons. These predominant smoke-constituents initiate a series of oncogenic events facilitating epigenetic alterations, self-sufficiency in growth signals, evasion of apoptosis, sustained angiogenesis, and metastasis. A better understanding of the molecular mechanisms underpinning these events is crucial for the prevention and therapeutic intervention against PC. This review presents various interconnected signal transduction cascades, the smoking-mediated genotoxicity, and genetic polymorphisms influencing the susceptibility for smoking-mediated PC development by modulating pivotal biological aspects such as cell defense/tumor suppression, inflammation, DNA repair, as well as tobacco-carcinogen metabolization. Additionally, it provides a large perspective toward tumor biology and the therapeutic approaches against PC by targeting one or several steps of smoking-mediated signaling cascades.
- Published
- 2012
109. The pathobiological impact of cigarette smoke on pancreatic cancer development (Review)
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Uwe A. Wittel, Thorsten Wiech, Gabriel Seifert, Ulrich T. Hopt, Navneet Momi, and Surinder K. Batra
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Oncology ,Nicotine ,Cancer Research ,medicine.medical_specialty ,Acinar Cells ,medicine.disease_cause ,Article ,Tobacco smoke ,Risk Factors ,Smoke ,Internal medicine ,Pancreatic cancer ,Tobacco ,medicine ,Acinar cell ,Animals ,Humans ,Pancreas ,business.industry ,Cancer ,medicine.disease ,Pancreatic Neoplasms ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Carcinogens ,Cancer research ,Pancreatitis ,Carcinogenesis ,business ,Carcinoma, Pancreatic Ductal ,medicine.drug - Abstract
Despite extensive efforts, pancreatic cancer remains incurable. Most risk factors, such as genetic disposition, metabolic diseases or chronic pancreatitis cannot be influenced. By contrast, cigarette smoking, an important risk factor for pancreatic cancer, can be controlled. Despite the epidemiological evidence of the detrimental effects of cigarette smoking with regard to pancreatic cancer development and its unique property of being influenceable, our understanding of cigarette smoke-induced pancreatic carcinogenesis is limited. Current data on cigarette smoke-induced pancreatic carcinogenesis indicate multifactorial events that are triggered by nicotine, which is the major pharmacologically active constituent of tobacco smoke. In addition to nicotine, a vast number of carcinogens have the potential to reach the pancreatic gland, where they are metabolized, in some instances to even more toxic compounds. These metabolic events are not restricted to pancreatic ductal cells. Several studies show that acinar cells are also greatly affected. Furthermore, pancreatic cancer progenitor cells do not only derive from the ductal epithelial lineage, but also from acinar cells. This sheds new light on cigarette smoke-induced acinar cell damage. On this background, our objective is to outline a multifactorial model of tobacco smoke-induced pancreatic carcinogenesis.
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- 2012
110. Taurocholate-induced pancreatitis: a model of severe necrotizing pancreatitis in mice
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Robert Lauch, Thorsten Wiech, Subhankar Chakraborty, Surinder K. Batra, Babette Boss, Ulrich T. Hopt, and Uwe A. Wittel
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Lung Diseases ,Male ,Taurocholic Acid ,medicine.medical_specialty ,Necrosis ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Severity of Illness Index ,Injections ,Mice ,Endocrinology ,Internal medicine ,Albumins ,Internal Medicine ,medicine ,Animals ,Interleukin 6 ,Pancreas ,Inflammation ,Mice, Inbred BALB C ,Hepatology ,medicine.diagnostic_test ,biology ,Common bile duct ,Dose-Response Relationship, Drug ,business.industry ,Interleukin-6 ,Pancreatitis, Acute Necrotizing ,Albumin ,Reproducibility of Results ,Lipase ,medicine.disease ,Dose–response relationship ,Disease Models, Animal ,Bronchoalveolar lavage ,medicine.anatomical_structure ,Amylases ,biology.protein ,Acute pancreatitis ,Pancreatitis ,Feasibility Studies ,medicine.symptom ,business ,Bronchoalveolar Lavage Fluid ,Ceruletide - Abstract
OBJECTIVES The outcome from acute pancreatitis depends on the severity of systemic complications. To be able to investigate mechanisms underlying the development of these systemic complications in acute pancreatitis in both wild-type and genetically engineered animal models, a mouse model of severe necrotizing pancreatitis was developed and characterized. METHODS Pancreatitis was induced by retrograde infusion of sodium taurocholate into the common bile duct in mice. After determining the optimum volume and concentration of taurocholate, the pancreatic damage and systemic inflammatory response were compared with those in cerulein-induced pancreatitis. RESULTS Pancreatic damage was higher in taurocholate pancreatitis than hyperstimulation-induced pancreatitis (24 hours: cerulein, 5.8 +/- 0.2 points; taurocholate, 14.8 +/- 0.8 points; P < 0.001) and mortality reached up to 60% within the first 24 hours after taurocholate administration. Pulmonary damage was detected, as measured by an increase in albumin in bronchoalveolar lavage fluid only in taurocholate-induced pancreatitis (12 hours: cerulein, 97.1 +/- 22.83 mg/g of protein; taurocholate, 234.0 +/- 32.7 mg/g of protein; P < 0.001). Furthermore, plasma interleukin 6 concentration was significantly elevated in mice with taurocholate-induced pancreatitis (12 hours: cerulein, 2.6 +/- 6.1 pg/mL; taurocholate, 2168.8 +/- 941.7 microg/mL; P < 0.001) as compared with all other groups. CONCLUSIONS Taurocholate pancreatitis is a reliable model for severe necrotizing pancreatitis in mice with significantly greater pancreatic damage and systemic inflammatory response in comparison with cerulein-induced pancreatitis.
- Published
- 2008
111. Cigarette smoke-induced differential expression of the genes involved in exocrine function of the rat pancreas
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Uwe A, Wittel, Ajay P, Singh, Brandon J, Henley, Mahefatiana, Andrianifahanana, Mohammed P, Akhter, Diane M, Cullen, and Surinder K, Batra
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Mucins ,Pancreatic Ducts ,Cystic Fibrosis Transmembrane Conductance Regulator ,Pancreas, Exocrine ,Rats ,Receptor, Cholecystokinin A ,Rats, Sprague-Dawley ,Gene Expression Regulation ,Pancreatitis ,Trypsin Inhibitor, Kazal Pancreatic ,Trypsinogen ,Animals ,Female ,Tobacco Smoke Pollution ,RNA, Messenger ,Carbonic Anhydrases - Abstract
Little is known about the molecular and biological aspects of the epidemiological association between smoking and pancreatic pathology, such as chronic pancreatitis and pancreatic cancer. Recently, we reported that tobacco smoke exposure induced morphological alterations in the rat pancreas. Here, we have investigated the alterations in the expression of genes associated with exocrine pancreatic function and cellular differentiation upon exposure to cigarette smoke.Female rats were exposed to environmental smoke inhalation for 2 d/wk (70 min/d) for 12 weeks. The expression profiles of trypsinogen, pancreas-specific trypsin inhibitor, cholecystokinin A receptor, cystic fibrosis transmembrane conductance regulator (CFTR), carbonic anhydrase, and Muc1 and Muc4 mucins transcripts were analyzed by RNA slot blot analysis. Muc4 expression was also examined by immunohistochemistry.Our data revealed that the ratio of trypsinogen to that of the protective pancreas-specific trypsin inhibitor was elevated upon cigarette smoke exposure. The expression of carbonic anhydrase and CFTR remained unaltered when inflammatory signs were not detected in histological examinations. On the other hand, when pancreatic inflammation was present, the levels of CFTR and carbonic anhydrase were increased, indicating ductal and/or centroacinar cell involvement. No changes in the expression of Muc1 and Muc4 mucins were observed.Our data show that cigarette smoke exposure leads to an increased vulnerability to pancreatic self-digestion. Moreover, the concomitant involvement of pancreatic ducts occurs only when focal pancreatic inflammation is present.
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- 2006
112. Delayed response toward activation stimuli in pancreatic stellate cells
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Diane M. Cullen, Uwe A. Wittel, Mohammed P. Akhter, Surinder K. Batra, Mahefatiana Andrianifahanana, Brandon J. Henley, and Ajay P. Singh
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medicine.medical_specialty ,Pathology ,Endocrinology, Diabetes and Metabolism ,Cell Culture Techniques ,Inflammation ,Biology ,Endocrinology ,Pancreatic cancer ,Internal medicine ,Gene expression ,Internal Medicine ,medicine ,Animals ,Receptor ,Pancreas ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Hepatology ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,medicine.disease ,Rats ,Gene expression profiling ,medicine.anatomical_structure ,Rats, Inbred Lew ,Pancreatitis ,medicine.symptom ,Cell Division - Abstract
Pancreatic stellate cells (PSCs) are known to be crucially involved in the development of pancreatic fibrosis, a characteristic feature of chronic pancreatitis and pancreatic cancer. The key event in the pathogenesis of fibrosis represents a transition process of quiescent PSCs into a myofibroblastlike phenotype associated with cell activation in terms of proliferation and synthesis of profibrogenic substances. There is little information available regarding the dynamics of the complex processes initiated by an activating stimulus in quiescent stellate cells.Using microarray analysis, we characterized the expression profiles during PSC activation caused by in vitro cultivation on days 2, 4, 7, and 14 after cell isolation. Activation status has been identified by the expression of the activation marker alpha-smooth muscle actin. Genes of interest were subjected to reverse transcription-polymerase chain reaction. To test biologic functions, the responsiveness of stellate cells toward the activators activin A and transforming growth factor-beta1 was investigated in dependence on the cell transition status.Our results revealed that freshly isolated (=quiescent) PSCs were refractory to stimuli for several days, a phenomenon that we referred to as delay phase.The retarded response could be considered a protection mechanism to prevent inappropriate stellate cell activation.
- Published
- 2006
113. Chronic pancreatic inflammation induced by environmental tobacco smoke inhalation in rats
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Mahefatiana Andrianifahanana, Krishan K. Pandey, Bogdain Prokopczyk, Surinder K. Batra, Uwe A. Wittel, Diane M. Cullen, Sonny L. Johansson, Mohammed P. Akhter, and Randall E. Brand
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medicine.medical_specialty ,Nicotine ,Trypsinogen ,Pancreatitis-Associated Proteins ,Sensitivity and Specificity ,Severity of Illness Index ,Tobacco smoke ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Random Allocation ,Reference Values ,Risk Factors ,Internal medicine ,Pancreatic cancer ,Pancreatitis, Chronic ,Acinar cell ,Medicine ,Animals ,Cotinine ,Probability ,Hepatology ,Inhalation ,business.industry ,Biopsy, Needle ,Gastroenterology ,medicine.disease ,Immunohistochemistry ,Rats ,Disease Models, Animal ,Pancreatic Function Tests ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Pancreatitis ,Female ,Tobacco Smoke Pollution ,business ,Pancreas - Abstract
OBJECTIVE Despite a strong epidemiological association between cigarette smoking and pancreatic diseases, such as pancreatic cancer and chronic pancreatitis, the effects of long-term cigarette smoke inhalation on the pancreas have not been clearly determined. In the present study, we investigated the effect of cigarette smoke inhalation on the pancreas. METHODS Thirty-six female Sprague Dawley rats were exposed to two different doses of environmental tobacco smoke averaging 100 mg or 160 mg/m3 total suspended particulate matter (TSP) per m3 for 70 min twice a day for 12 wk. The animals were sacrificed and examined for the effects of tobacco smoke exposure on pancreatic morphology and function. RESULTS In 58% (7/12) of the animals, exposure to 160 mg/m3 TSP cigarette smoke induced a chronic pancreatic inflammatory process with fibrosis and scarring of pancreatic acinar structures. Animals with fibrotic alterations showed an induction of pancreatic pro-collagen 1 gene expression, and the infiltration of immune cells was accompanied by the expression of the inflammatory mediators MIP-1alpha, IL-1beta, and TGF-beta in 33% (4/12) of the animals. Acinar cell stress was manifested by a significant up-regulation of pancreatitis-associated protein expression (PAP) in smoke-exposed animals (smoke-exposed 6,932 +/- 1,236 vs control 3,608 +/- 305, p < 0.05). Possibly contributing to the morphological damage to the exocrine pancreas, the inhalation of cigarette smoke induced trypsinogen and chymotrypsinogen gene expression and, furthermore, reduced pancreatic enzyme content. CONCLUSIONS This study provides experimental evidence of morphological pancreatic damage induced by the inhalation of cigarette smoke, which is likely to be mediated by alterations of acinar cell function.
- Published
- 2006
114. Engineering and characterization of a divalent single-chain Fv angiotensin II fusion construct of the monoclonal antibody CC49
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Devendra K. Agrawal, Apollina Goel, David Colcher, Uwe A. Wittel, Janina Baranowska-Kortylewicz, Takashi Kurizaki, Subhash C. Chauhan, Surinder K. Batra, and Maneesh Jain
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Angiotensin receptor ,Time Factors ,Intrinsic activity ,Antibodies, Neoplasm ,medicine.medical_treatment ,Recombinant Fusion Proteins ,Genetic Vectors ,Biophysics ,Immunoglobulin Variable Region ,Enzyme-Linked Immunosorbent Assay ,Biochemistry ,Divalent ,Mice ,Monoclonal antibody CC49 ,Antigen ,Antigens, Neoplasm ,Neoplasms ,medicine ,Animals ,Humans ,Molecular Biology ,Immunoglobulin Fragments ,Chromatography, High Pressure Liquid ,DNA Primers ,Glycoproteins ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Angiotensin II ,Antibodies, Monoclonal ,Cell Biology ,Surface Plasmon Resonance ,Fusion protein ,Molecular biology ,Protein Structure, Tertiary ,Kinetics ,chemistry ,Radioimmunotherapy ,Electrophoresis, Polyacrylamide Gel ,Dimerization ,hormones, hormone substitutes, and hormone antagonists ,Protein Binding - Abstract
For the therapy of solid tumors, co-administration of angiotensin II (AngII) results in an increased uptake of drugs into the tumor interstitium. We have engineered a dimeric sc(Fv) 2 -AngII fusion construct that combines the superior kinetics of covalent dimeric scFvs [sc(Fv) 2 ], recognizing the pancarcinoma tumor-associated antigen 72 (TAG-72), with the advantageous intrinsic activity of AngII. The binding characteristics of the fusion construct were unaltered by the addition of the AngII sequence [affinity constant K A 1.18 × 10 7 and 8.42 × 10 6 M −1 for sc(Fv) 2 and sc(Fv) 2 -AngII, respectively]. The binding of the fusion construct to the angiotensin receptor (AT 1 ) was similar to AngII, and the arterial contraction was 16 ± 1% of the response observed with norepinephrine. In animal studies, the radiolabeled sc(Fv) 2 -AngII construct exhibited similar uptake and a more homogeneous distribution within the tumor as compared to sc(Fv) 2 .
- Published
- 2005
115. Xenografting pancreatic cancer: Impact on histology and RNA expression profiles
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Vincent Vuaroqueaux, Peter Bronsert, Simon Kuesters, Uwe A. Wittel, Ilona Kohler, Ulrich T. Hopt, Frederic Foucault, and Heiner Fiebig
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Pathology ,medicine.medical_specialty ,Rna expression ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Pancreatic cancer ,Gastroenterology ,medicine ,Histology ,medicine.disease ,business - Published
- 2013
116. Anti-tumor autoantibodies in patients with pancreatic carcinoma and chronic pancreatitis
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Uwe A. Wittel, B. Vogt, Guido Wolff-Vorbeck, and Ulrich T. Hopt
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Antitumor activity ,medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Autoantibody ,medicine.disease ,Internal medicine ,medicine ,Pancreatitis ,In patient ,CA19-9 ,Pancreatic carcinoma ,business - Published
- 2013
117. Pharmacokinetics and biodistribution of 177Lu-labeled multivalent single-chain Fv construct of the pancarcinoma monoclonal antibody CC49
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Erik D. Moore, Peter R. Gwilt, Jing Li, Subhash C. Chauhan, David Colcher, Maneesh Jain, Surinder K. Batra, and Uwe A. Wittel
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Biodistribution ,medicine.drug_class ,Antibodies, Neoplasm ,Metabolic Clearance Rate ,medicine.medical_treatment ,Mice, Nude ,chemical and pharmacologic phenomena ,Lutetium ,Monoclonal antibody ,Mice ,Monoclonal antibody CC49 ,Pharmacokinetics ,In vivo ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Tissue Distribution ,Radionuclide Imaging ,Immunoglobulin Fragments ,Radioisotopes ,biology ,Chemistry ,Carcinoma ,Antibodies, Monoclonal ,General Medicine ,respiratory system ,Radioimmunotherapy ,Virology ,Organ Specificity ,Cancer research ,biology.protein ,Female ,Antibody ,Radiopharmaceuticals ,Single-Chain Antibodies - Abstract
Lutetium-177 (177Lu) is a radionuclide of interest for radioimmunoimaging (RII) and radioimmunotherapy (RIT) on account of its short half-life (161 h) and the ability to emit both beta and gamma radiation. Single-chain Fv (scFv) constructs have shown advancement in cancer diagnosis and therapy due to the pharmacokinetics advantage and seem to be intriguing tools in oncology. The objective of this study was to evaluate the pharmacokinetics and biodistribution characteristics of the 177Lu-labeled tetravalent scFv of CC49 MAb and intact CC49 IgG in vivo.Conjugation and labeling conditions of multivalent scFv with 177Lu were optimized without affecting integrity and immunoreactivity. For this purpose, multivalent scFv constructs {dimer, sc(Fv)2; tetramer, [sc(Fv)2]2} of the MAb CC49 were expressed as secretory proteins in Pichia pastoris. The purified scFv constructs and IgG form of CC49 were conjugated with a bifunctional chelating agent, ITCB-DTPA, and labeled with 177Lu. The comparative biodistribution, blood clearance, and tumor-targeting characteristics of 177Lu-labeled tetravalent [sc(Fv)2]2 construct of CC49 MAb and intact CC49 IgG were investigated in the athymic mice bearing LS-174T xenografts.Approximately, 90% of 177Lu incorporation was achieved using ITCB-DTPA chelator, and the labeled immunoconjugates maintained integrity and immunoreactivity. Blood clearance studies demonstrated an alpha half-life (t1/2alpha) of 177Lu-labeled [sc(Fv)2]2 and IgG of CC49 at 4.40 and 9.50 min and a beta half-life (t1/2beta) at 375 and 2,193 min, respectively. At 8 h post administration, the percent of the injected dose accumulated/gram (%ID/g) of the LS-174T tumor was 6.4+/-1.3 and 8.9+/-0.6 for 177Lu-labeled [sc(Fv)2]2 and IgG of CC49, respectively, in the absence of L-lysine. The corresponding values were 8.0+/-0.6 and 8.4+/-1.2 in the presence of L-lysine. Renal accumulation of [sc(Fv)2]2 was significantly (p0.005) reduced in the presence of L-lysine.The results of this study demonstrate that the ITCB-DTPA conjugation and 177Lu-labeling of scFvs are feasible without influencing the antibody characteristics. 177Lu-labeled [sc(Fv)2]2 showed faster clearance and equivalent tumor uptake at 8 h compared with its IgG form, with a markedly reduced renal uptake in the presence of L-lysine. Therefore, 177Lu-labeled [sc(Fv)2]2 may be a potential radiopharmaceutical for the treatment of cancer.
- Published
- 2004
118. Does the genetic strain influence severity of acute necrotizing pancreatitis and SIRS in a murine model?
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Ulrich T. Hopt, S. Richter, Uwe A. Wittel, Gabriel Seifert, and Karoline C. Sander
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Acute necrotizing pancreatitis ,medicine.medical_specialty ,Hepatology ,ORAI1 ,Toxin ,business.industry ,Endocrinology, Diabetes and Metabolism ,Genetic strain ,Gastroenterology ,macromolecular substances ,Pharmacology ,medicine.disease_cause ,medicine.anatomical_structure ,TRPC3 ,Murine model ,medicine ,Histopathology ,Pancreas ,business - Abstract
s / Pancreatology 14 (2014) S1eS129 S101 profiles measured. EAP severity was assessed by standard biochemical parameters and blinded histopathology. Results: GSK-7975A inhibited calcium influx and necrotic pathway activation inmurine (at 3, 10 or 30 mM, p
- Published
- 2014
119. Portal venous resection in cancer of the pancreatic head: What are the relevant predictors of survival?
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B Kulemann, Frank Makowiec, Uwe A. Wittel, Peter Bronsert, Jens Hoeppner, Tobias Keck, Ulrich T. Hopt, Dirk Bausch, Hryhoriy Lapshyn, and Ulrich F. Wellner
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medicine.medical_specialty ,Hepatology ,Proportional hazards model ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Retrospective cohort study ,medicine.disease ,eye diseases ,medicine.anatomical_structure ,Lymphatic system ,Pancreatic cancer ,Statistical significance ,medicine ,sense organs ,Radiology ,business ,Lymph node ,Microvessel ,Grading (tumors) - Abstract
Introduction: When tumors are found to be adherent to the superior mesenteric or portal vein during pancreatoduodenectomy, en bloc portal venous resection (PVR) is an option to achieve complete tumor resection. It has also been reported that PVR without confirmed histopathologic portal venous infiltration (PVI) is associated with significantly better survival. The aim of this study was to evaluate oncologic outcome and prognostic factors in patients receiving PVR for pancreatic cancer. Methods: A unicenter retrospective study was performed on the basis of a prospectively maintained database. IBM SPSS Version 21 was used for all calculations with the significance level set to p=0.05. Results: From 2001 to 2013, 103 patients received pancreatoduodenectomy with PVR for pancreatic head cancer. Median survival in patients with PVR without PVI was 25 months, whereas confirmed PVI was associated with poor median survival of 14 months (p
- Published
- 2014
120. Chemokine ligand CXCL16 is an indicator of infected necrosis in necrotizing pancreatitis
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Andrea I. Schmidt, Pauli Puolakkainen, Ulrich T. Hopt, Leena Kylänpää, and Uwe A. Wittel
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Chemokine ,Pathology ,medicine.medical_specialty ,Hepatology ,biology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Ligand (biochemistry) ,Immunology ,biology.protein ,Medicine ,Infected necrosis ,business ,Necrotizing pancreatitis ,CXCL16 - Published
- 2014
121. Su1831 Perioperative and Long Term Outcome After Extended (Portal Vein, Multivisceral) Resection for Cancer of the Pancreatic Head
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Frank Makowiec, Birte Kulemann, Tobias Keck, Ulrich F. Wellner, Uwe A. Wittel, Hryhoriy Lapshyn, Ulrich T. Hopt, Jens Hoeppner, and Peter Bronsert
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medicine.medical_specialty ,Hepatology ,business.industry ,Multivisceral resection ,Gastroenterology ,Portal vein ,Cancer ,Perioperative ,medicine.disease ,Pancreatic head ,Surgery ,Medicine ,Radiology ,business - Published
- 2014
122. Tu1622 Portal Venous Resection in Cancer of the Pancreatic Head: What Are the Relevant Predictors of Survival?
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Hryhoriy Lapshyn, Dirk Bausch, Birte Kulemann, Ulrich F. Wellner, Ulrich T. Hopt, Tobias Keck, Uwe A. Wittel, Peter Bronsert, Jens Hoeppner, and Frank Makowiec
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,medicine ,Cancer ,Radiology ,medicine.disease ,business ,Pancreatic head ,Venous resection ,Surgery - Published
- 2014
123. Mucin antibodies - new tools in diagnosis and therapy of cancer
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Grish C. Varshney, Apollina Goel, Surinder K. Batra, and Uwe A. Wittel
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medicine.drug_class ,medicine.medical_treatment ,Cell ,Monoclonal antibody ,Epitope ,law.invention ,law ,Neoplasms ,medicine ,Animals ,Humans ,Protein Isoforms ,Immunoglobulin Fragments ,biology ,Mucin ,Mucin-1 ,Mucins ,Cancer ,Antibodies, Monoclonal ,Radioimmunotherapy ,medicine.disease ,Molecular biology ,medicine.anatomical_structure ,biology.protein ,Recombinant DNA ,Antibody - Abstract
Many cancer and diseased cells are distinguished from their normal counterparts by an altered expression of cell-surface epitopes. One family of molecules that show altered expression on tumor cells is mucins (MUC). Unlike normal tissue where MUC exists as heavily glycosylated form, the disease- or tumor-associated MUC molecules are underglycosylated. Such underglycosylation of the core protein in cancer tissues exposes new epitopes on the cell surface that are unique to cancer tissues. Several monoclonal antibodies (Mabs) have been generated against these normal and tumor-associated mucins. Enzymatic fragments of Mabs like F(ab')2 and Fab have shown improved clinical utility for diagnosis, imaging, and therapy of cancer. Genetic-engineering methods have been used to design antibody fragments exhibiting high functional affinity, good tumor localization, and rapid clearance from the blood stream thus minimizing radiation exposure to the normal tissues. Such recombinant fragments have shown encouraging results in preclinical studies using xenografted tumor bearing mice and present a whole new avenue for radioimmunotherapy and diagnosis of cancer.
- Published
- 2001
124. Expression of nerve growth factors in pancreatic neural tissue and pancreatic cancer
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Jens Standop, Parviz M. Pour, Uwe A. Wittel, Alexis Ulrich, Matthias B. Schneider, Åke Andrén-Sandberg, and Helmut Friess
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Histology ,Tropomyosin receptor kinase B ,Receptors, Nerve Growth Factor ,Tropomyosin receptor kinase A ,03 medical and health sciences ,Pancreatic cancer ,medicine ,Humans ,Nerve Growth Factors ,Nerve Tissue ,Pancreas ,030102 biochemistry & molecular biology ,biology ,medicine.disease ,Immunohistochemistry ,Pancreatic Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Nerve growth factor ,nervous system ,Cancer cell ,biology.protein ,CA19-9 ,Anatomy ,Neurotrophin - Abstract
One of the characteristics of pancreatic cancer is its tendency to invade neural tissue. We hypothesized that the affinity of cancer cells for nerve tissue is related to the presence of growth factors in neural tissue and their receptors in cancer cells. Sections of pancreatic cancer and normal pancreatic tissue were examined by immunohistochemistry for the expression of the neurotrophins NGF, BDNF, NT-3, NT-4, and their receptors TrkA, TrkB, and TrkC, as well as the low-affinity receptor, p75NTR. TrkA expression was found in duct, islet, and cancer cells; TrkB was found in the α-cells of the islet only. The anti-pan-Trk antibody (TrkB3), which is presumed to recognize all three receptors, immunoreacted with duct and acinar cells in normal tissue and with cancer cells. The staining with TrkC was similar to that of TrkA. The low-affinity receptor p75NTR was expressed in the neural tissue and in scattered duct cells of the normal tissue only. Duct and acinar cells, as well as neural tissue and cancer cells, showed weak to strong immunoreactivity with NGF. NT-3 expression was noted in capillary endothelia and erythrocytes. NT-4 showed specific staining for ductule cells. The expression and distribution of neurotrophins and their receptors suggest their role in the potential of pancreatic cancer cells for neural invasion.
- Published
- 2001
125. Su1653 Trends in Pancreatic Surgery: Indications, Operative Techniques and Postoperative Outcome of 1120 Pancreatic Resections
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Frank Makowiec, Hartwig Riediger, Tobias Keck, Uwe A. Wittel, Ulrich F. Wellner, Ulrich T. Hopt, and Ulrich Adam
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medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,medicine ,Postoperative outcome ,business ,Surgery ,Pancreatic surgery - Published
- 2013
126. Potentials of Plasma NGAL and MIC-1 as Biomarker(s) in the Diagnosis of Lethal Pancreatic Cancer
- Author
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Aaron R. Sasson, Sushovan Guha, Shailender Singh, Michael J. Baine, Uwe A. Wittel, Randall E. Brand, Sukwinder Kaur, Kavita Mallya, Lynette M. Smith, Maneesh Jain, Surinder K. Batra, and Subhankar Chakraborty
- Subjects
Pathology ,lcsh:Medicine ,Lipocalin ,Gastroenterology ,Body Mass Index ,0302 clinical medicine ,Basic Cancer Research ,Blood plasma ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,Acute-phase protein ,Lipocalins ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Biomarker (medicine) ,Research Article ,medicine.medical_specialty ,Growth Differentiation Factor 15 ,CA-19-9 Antigen ,Radioimmunoassay ,Sensitivity and Specificity ,Diagnosis, Differential ,Pancreatic Cancer ,03 medical and health sciences ,Lipocalin-2 ,Diagnostic Medicine ,Pancreatitis, Chronic ,Proto-Oncogene Proteins ,Internal medicine ,Pancreatic cancer ,Gastrointestinal Tumors ,medicine ,Humans ,Biology ,Retrospective Studies ,030304 developmental biology ,Tumor marker ,Analysis of Variance ,business.industry ,lcsh:R ,Cancers and Neoplasms ,medicine.disease ,Pancreatic Neoplasms ,Logistic Models ,Pancreatitis ,lcsh:Q ,GDF15 ,business ,Biomarkers ,Acute-Phase Proteins ,General Pathology - Abstract
Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91) and compared it with those in healthy control (HC) individuals (n = 24) and patients with chronic pancreatitis (CP, n = 23). The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD) plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2), 219.2 U/mL (7.8) and 4.5 ng/mL (4.1), respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81%) but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively). For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively). CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2) pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml). Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029). Overall, MIC-1 in combination with CA19-9 improved the diagnostic accuracy of differentiating PC from CP and HCs.
- Published
- 2013
127. Pathobiological Implications of MUC16 Expression in Pancreatic Cancer
- Author
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Uwe A. Wittel, Moorthy P. Ponnusamy, Eric Cruz, Surinder K. Batra, Srustidhar Das, Subodh M. Lele, Imayavaramban Lakshmanan, Subhankar Chakraborty, Dhanya Haridas, Judy M. Anderson, Sushil Kumar, Satyanarayana Rachagani, and Michael A. Hollingsworth
- Subjects
Pathology ,Microarrays ,Tumor Physiology ,Gene Expression ,lcsh:Medicine ,Biochemistry ,Metastasis ,0302 clinical medicine ,Pancreatic tumor ,Molecular Cell Biology ,Basic Cancer Research ,Neoplasm Metastasis ,lcsh:Science ,0303 health sciences ,Microscopy, Confocal ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,Immunohistochemistry ,Primary tumor ,3. Good health ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Adenocarcinoma ,Pancreas ,Research Article ,medicine.medical_specialty ,Blotting, Western ,Biology ,Pancreatic Cancer ,03 medical and health sciences ,Cell Line, Tumor ,Pancreatic cancer ,Gastrointestinal Tumors ,Cancer Detection and Diagnosis ,medicine ,Humans ,030304 developmental biology ,lcsh:R ,Pancreatic Ducts ,Membrane Proteins ,Computational Biology ,Cancers and Neoplasms ,Cancer ,medicine.disease ,Pancreatic Neoplasms ,CA-125 Antigen ,lcsh:Q ,Ovarian cancer - Abstract
MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.
- Published
- 2011
128. SEVERE NECROTIZING PANCREATITIS IN MICE INDUCED BY RETROGRADE TAUROCHOLATE INFUSION INTO THE COMMON BILE DUCT
- Author
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Ulrich T. Hopt, Robert Lauch, B. Boss, and Uwe A. Wittel
- Subjects
medicine.medical_specialty ,Hepatology ,Common bile duct ,business.industry ,Endocrinology, Diabetes and Metabolism ,General surgery ,Gastroenterology ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Internal Medicine ,medicine ,Necrotizing pancreatitis ,business - Published
- 2006
129. Oxygen Radical Production Precedes Alcohol-Induced Acute Pancreatitis in Rats.
- Author
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Uwe A. Wittel
- Published
- 2003
- Full Text
- View/download PDF
130. Pathobiological implications of MUC16 expression in pancreatic cancer.
- Author
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Dhanya Haridas, Subhankar Chakraborty, Moorthy P Ponnusamy, Imayavaramban Lakshmanan, Satyanarayana Rachagani, Eric Cruz, Sushil Kumar, Srustidhar Das, Subodh M Lele, Judy M Anderson, Uwe A Wittel, Michael A Hollingsworth, and Surinder K Batra
- Subjects
Medicine ,Science - Abstract
MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.
- Published
- 2011
- Full Text
- View/download PDF
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