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Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

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World Journal of Gastroenterology 2009年第4期15卷 449-456页

作者： Markus Moehler Martin F Sprinzl Murad Abdelfattah Carl C Schimanski Bernd Adami Werner Godderz Klaus Majer Dimitri Flieger Andreas Teufel juergen siebler Thomas Hoehler Peter R Galle Stephan Kanzler 1st Medical Department Johannes Gutenberg-University Outpatient Clinic Outpatient Clinic of City Hospital Outpatient Clinic of 1st Medical Department Outpatient Clinic of 2nd Medical Department Leopoldina Krankenhaus

AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient *** received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 *** treatment choice of bevacizumab was at the discretion of the *** endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,*** complete responses were *** median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,*** median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically *** the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient *** gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.

关键词： First-line therapy Metastatic colorectalcancer Bevacizumab Capecitabine Irinotecan Tumorresponse

Advances in hepatitis C therapy: What is the current state-what come's next?

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World Journal of Hepatology 2016年第3期8卷 139-147页

作者： Steffen Zopf Andreas E Kremer Markus F Neurath juergen siebler Medical Department 1 University of Erlangen Nuremberg

Chronic hepatitis C virus(HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver *** is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ***,treatment of HCV has undergone a revolutionary change in recent *** admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents(DAA).Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal *** rates of sustained virological response(SVR) rates can be achieved with these novel *** in difficult to treat populations such as patients with liver cirrhosis,HCV-human immunodeficiency virus co-infections,after liver transplantion,or with chronic kidney disease comparable high rates of SVR can be *** anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or posttransplant *** 2nd generations DAAs will have higher resistance barriers,higher antiviral effects and a pan-genotypic *** review highlights the current state of the art of antiviral treatment in hepatitis Cand gives an outlook for upcoming therapies.

关键词： hepatitis C virus direct antiviral agents sustained virological response liver transplantation renal impairment cirrhosis

Classical bovine spongiform encephalopathy and chronic wasting disease:two sides of the prion coin

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Animal Diseases 2024年第1期4卷 1-18页

作者： Nicholas J.Haley juergen A.Richt Department of Microbiology and Immunology College of Graduate StudiesMidwestern UniversityGlendaleAZUSA Department of Diagnostic Medicine/Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKSUSA

Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion *** diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of *** they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic *** the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in *** importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to *** underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion *** the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.

关键词： Prion Bovine Spongiform Encephalopathy Chronic Wasting Disease Transmission Pathogenesis Zoonosis

Comparison of Hemospray~? and Endoclot? for the treatment of gastrointestinal bleeding

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World Journal of Gastroenterology 2019年第13期25卷 1592-1602页

作者： Francesco Vitali Andreas Naegel Raja Atreya Steffen Zopf Clemens Neufert juergen siebler Markus F Neurath Timo Rath Ludwig Demling Endoscopy Center of Excellence Division of Gastroenterology Friedrich-Alexander-University

BACKGROUND Gastrointestinal(GI) bleeding is a common indication for endoscopy. For refractory cases, hemostatic powders(HP) represent "touch-free" *** To analyze short term(ST-within 72 h-) and long-term(LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray(HS) and Endoclot(EC).METHODS HP was applied in 154 consecutive patients(mean age 67 years) with GI *** were followed up for 1 mo(mean follow-up: 3.2 mo).RESULTS Majority of applications were in upper GI tract(89%) with following bleeding sources: peptic ulcer disease(35%), esophageal varices(7%), tumor bleeding(11.7%), reflux esophagitis(8.7%), diffuse bleeding and erosions(15.3%). Overall ST success was achieved in 125 patients(81%) and LT success in 81 patients(67%). Re-bleeding occurred in 27% of all patients. In 72 patients(47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding(P = 0.04)CONCLUSION Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding.

关键词： Hemostatic powder Gastrointestinal bleeding Hemospray Endoclot Haemostasis

Combining thermal scanning probe lithography and dry etching for grayscale nanopattern amplification

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Microsystems & Nanoengineering 2024年第1期10卷 335-344页

作者： Berke Erbas Ana Conde-Rubio Xia Liu Joffrey Pernollet Zhenyu Wang Arnaud Bertsch Marcos Penedo Georg Fantner Mitali Banerjee Andras Kis Giovanni Boero juergen Brugger Microsystems Laboratory École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Center of MicroNanoTechnology(CMi) EPFLLausanne 1015Switzerland Laboratory of Nanoscale Electronics and Structures École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory for Bio-and Nano-Instrumentation École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory of Quantum Physics Topology and CorrelationsÉcole Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Present address:Institute of Materials Science of Barcelona ICMAB-CSIC Campus UABBellaterra 08193Spain Present address:School of Integrated Circuits and Electronics MIIT Key Laboratory for Low-Dimensional Quantum Structure and DevicesBeijing Institute of TechnologyBeijing 100081China

Grayscale structured surfaces with nanometer-scale features are used in a growing number of applications in optics and *** scanning probe lithography achieves a lateral resolution below 10 nm and a vertical resolution below 1 nm,but its maximum depth in polymers is ***,we present an innovative combination of nanowriting in thermal resist and plasma dry etching with substrate cooling,which achieves up to 10-fold amplification of polymer nanopatterns into SiO_(2) without proportionally increasing surface *** nanopatterns in SiO_(2) with 400 nm pitch and 150 nm depth are fabricated free of shape distortion after dry *** exemplify the possible applications of the proposed method,grayscale dielectric nanostructures are used for scalable manufacturing through nanoimprint lithography and for strain nanoengineering of 2D *** a method for aspect ratio amplification and smooth grayscale nanopatterning has the potential to find application in the fabrication of photonic and nanoelectronic devices.

关键词： lithography thermal pattern

Improvement on straightness of metal bar based on straightening stroke-deflection model

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Science China(Technological Sciences) 2009年第7期52卷 1866-1873页

作者： LEOPOLD juergen Fraunhofer Institute for Machine Tools and Forming Technology Chemnitz Germany

The straightening technics is one of important means to improve the straightness of metal bar. A novel way of predicting the straightening stroke is proposed based on mathematical methods and bending experimental and numerical simulation. The experimental and numerical simulation is conducted by following the mathematical load-stroke model of press straightening process under the elastic-plastic theory. For the linear guide rails, as an example, the stroke-deflection model focusing on the straightening stroke prediction can be achieved by contrasting and integrating the bending experimental results and finite element methods (FEM) simulation data. And then the formula for predicting the straightening stroke is presented based on the precise straightening stroke-deflection model. The stroke prediction formula with high precision can be applied to the straightening stroke prediction in the high straightness metal bar manufacturing process and automatic straightening machine conveniently.

关键词： straightness straightening stroke deflection stroke prediction metal bar

Mapping of liver-enriched transcription factors in the human intestine

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World Journal of Gastroenterology 2010年第31期16卷 3919-3927页

作者： Frank Lehner Ulf Kulik juergen Klempnauer juergen Borlak Department of General Visceral and Transplantation SurgeryHanover Medical School Molecular Medicine and Medical Biotechnol-ogy Fraunhofer Institute of Toxicology and Experimental Medi-cine Center of Pharmacology and Toxicology Hanover Medical School

AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at

关键词： Liver-enriched transcription factors Human intestine Caco-2 Gene expression

Effective treatment of gastrointestinal bleeding with thalidomide- Chances and limitations

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World Journal of Gastroenterology 2016年第11期22卷 3158-3164页

作者： juergen Bauditz Department of Internal Medicine Helios Klinik Anhalt/Zerbst Department of Gastroenterology Hepatology and InfectiologyCharité Campus MitteCharité University Hospital

For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960 s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibi t angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely.

关键词： Thalidomide Angiodysplasia Vascular malformation Gastrointestine Bleeding Therapy Angiogenesis Vascular endothelial growth factor

The future of geospatial intelligence

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Geo-Spatial Information Science 2017年第2期20卷 151-162页

作者： juergen Dold Jessica Groopman Hexagon Geosystems HeerbruggSwitzerland Independent Industry Analyst and IoT Advisor BerkeleyCAUSA

For centuries,humans’capacity to capture and depict physical space has played a central role in industrial and societal ***,the digital revolution and the emergence of networked devices and services accelerate geospatial capture,coordination,and intelligence in unprecedented *** the digital transformation of industry and society is the fusion of the physical and digital worlds-‘perceptality’-where geospatial perception and reality *** paper analyzes the myriad forces that are driving perceptality and the future of geospatial intelligence and presents real-world implications and examples of its industrial *** of sensors,robotics,cameras,machine learning,encryption,cloud computing and other software,and hardware intelligence are converging,enabling new ways for organizations and their equipment to perceive and capture ***,demands for performance,reliability,and security are pushing compute‘to the edge’where real-time processing and coordination are *** data place new restraints on economics,as pressures abound to actually use these data,both in real-time and for longer term strategic analysis and *** challenges require orchestration between information technology(IT)and operational technology(OT)and synchronization of diverse systems,data-sets,devices,environments,workflows,and people.

关键词： Big data virtual reality digital reality cloud computing edge computing geospatial data