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Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer

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World Journal of Gastroenterology 2008年第1期14卷 1-14页

作者： Michael Hpfner Detlef schuppan hans scherübl Institute of Physiology Charité-Universittsmedizin Berlin Campus Benjamin Franklin Berlin 12200 Germany Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 United States Klinik für Innere Medizin Gastroenterologie und Gastrointestinale Onkologie Klinikum am Urban Vivantes Netzwerk für Gesundheit Berlin 10967 Germany

Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors （＂small molecule inhibitors＂） and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin （mTOr） upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, roTOr inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFr system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.

关键词： Growth factor receptor Hepatocellular cancer Small molecule inhibitor Monoclonal antibody Innovative cancer treatment Sorafenib Bevacizumab Erlotinib

Treatment of gastrointestinal neuroendocrine tumors with inhibitors of growth factor receptors and their signaling pathways: recent advances and future perspectives

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World Journal of Gastroenterology 2008年第16期14卷 2461-2473页

作者： Michael Hpfner Detlef schuppan hans scherübl Institute of Physiology Charité-Universitts-medizin Berlin Campus Benjamin Franklin Beth Israel Deaconess Medical Center and Harvard Medical school Klinik für Innere Medizin Gastroenterologie und Gastrointestinale Onkologie Klinikum am Urban Vivantes Netzwerk für Gesundheit

The limited efficacy of conventional cytotoxic treatment regimes for advanced gastrointestinal neuroendocrine cancers emphasizes the need for novel and more effective medical treatment options. recent findings on the specific biological features of this family of neoplasms has led to the development of new targeted therapies, which take into account the high vascularization and abundant expression of specific growth factors and cognate tyrosine kinase receptors. This review will briefly summarize the status and future perspectives of antiangiogenic, mTOr- or growth factor receptor-based pharmacological approaches for the innovative treatment of gastrointestinal neuroendocrine tumors. In view of the multitude of novel targeted approaches, the rationale for innovative combination therapies, i.e. combining growth factor (receptor)-targeting agents with chemo- or biotherapeutics or with other novel anticancer drugs such as HDAC or proteasome inhibitors will be taken into account.

关键词： Growth factor receptor Neuroendocrinegastrointestinal tumor Small molecule inhibitor lonoclonal antibody Multi kinase inhibition

UNIFOrM SUPErCONVErGENCE OF A FINITE ELEMENT METHOD WITH EDGE STABILIZATION FOr CONVECTION-DIFFUSION PrOBLEMS

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Journal of Computational Mathematics 2010年第1期28卷 32-44页

作者： Sebastian Franz Torsten Linβ hans-Grg roos Sebastian schiller Department of Mathematics and Statistics University of Limerick Institut für Numerische Mathematik Technische Universitt Dresden

In the present paper the edge stabilization technique is applied to a convection-diffusion problem with exponential boundary layers on the unit square, using a Shishkin mesh with bilinear finite elements in the layer regions and linear elements on the coarse part of the mesh. An error bound is proved for ‖πu-u^h‖Е, where πu is some interpolant of the solution u and uh the discrete solution. This supercloseness result implies an optimal error estimate with respect to the L2 norm and opens the door to the application of postprocessing for improving the discrete solution.

关键词： Convection-diffusion problems Edge stabilization FEM Uniform convergence Shishkin mesh.

The Top of the Biomimetic Triangle

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Journal of Bionic Engineering 2008年第2期5卷 91-94页

作者： Andrei P. Sommer Dan Zhu Matthias Wiora hans-Joerg Fecht Institute of Micro and Nanomaterials University of Ulm Ulm 89081 Germany Institute for Nanotechnology Forschungszentrum Karlsruhe Karlsruhe 76021 Germany

There is increasing observational evidence indicating that crystalline interfacial water layers play a central role in evolution and biology. For instance in cellular recognition processes, in particular during first contact events, where cells decide upon survival or entering apoptosis. Understanding water layers is thus crucial in biomedical engineering, specifically in the design of biomaterials inspired by biomimetic principles. Whereas there is ample experimental evidence for crystalline interfacial water layers on surfaces in air, their subaquatic presence could not be verified directly, so far. Analysing a polarity dependent asym- metry in the surface conductivity on hydrogenated nanocrystalline diamond, we show that crystalline interfacial water layers persist subaquatically. Nanoscopic interfacial water layers with an order different from that of bulk water have been identified at room temperature on both hydrophilic and hydrophobic model surfaces - in air and subaquatically. Their generalization and systematic inclusion into the catalogue of physical and chemical determinants of biocompatibility complete the biomimetic triangle.

关键词： biomimetic triangle crystalline interfacial water layers nanobionics diamond

Adaptive nanopores:A bioinspired label-free approach for protein sequencing and identification

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Nano research 2021年第1期14卷 328-333页

作者： Andrea Spitaleri Denis Garoli Moritz schutte hans Lehrach Walter rocchia Francesco De Angelis CONCEPT Lab Istituto Italiano di TecnologiaVia Morego 30Genova1-16163Italy Center for Omics Sciences IRCCS San Raffaele Scientific InstituteMilanVia Olgettina 58Milano1-20132Italy Plasmon Nanotechnology Unit Istituto Italiano di TecnologiaVia Morego 30Genova1-16163Italy AB ANALITICA s.r.l Via Svizzera 161-35127 PadovaItaly Alacris Theranostics GmbH Max-Planck-Strasse 3D-12489 BerlinGermany Max Planck Institute for Molecular Genetics Ihnestrasse 63-73D-14195 BerlinGermany

Single molecule protein sequencing would tremendously impact in proteomics and human biology and it would promote the development of novel diagnostic and therapeutic ***,its technological realization can only be envisioned,and huge challenges need to be *** difficulties are inherent to the structure of proteins,which are composed by several different *** long standing efforts,only few complex techniques,such as Edman degradation,liquid chromatography and mass spectroscopy,make protein sequencing ***,these techniques present significant limitations in terms of amount of sample required and dynamic range of *** is known that proteins can distinguish closely similar ***,several proteins can work as biological nanopores in order to perform single molecule detection and ***,while DNA sequencing by means of nanopores is demonstrated,very few examples of nanopores able to perform reliable protein-sequencing have been reported ***,we investigate,by means of molecular dynamics simulations,how a re-engineered protein,acting as biological nanopore,can be used to recognize the sequence of a translocating peptide by sensing the MshapeH of individual *** our simulations we demonstrate that it is possible to discriminate with high fidelity,9 different amino-acids in a short peptide translocating through the engineered *** method,here shown for fluorescence-based sequencing,does not require any labelling of the peptidic *** results can pave the way for a new and highly sensitive method of sequencing.

关键词： nanopores single molecule sequencing protein sequencing luorescence resonance energy transfer(FrET) amino-acids fluorescence

Voltage rise mitigation for solar PV integration at LV grids Studies from ***

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Journal of Modern Power Systems and Clean Energy 2015年第3期3卷 411-421页

作者： Guangya YANG Francesco MArrA Miguel JUAMPErEZ Søren Bækhøj KJÆr Seyedmostafa HASHEMI JacobØSTErGAArD hans Henrik IPSEN Kenn H.B.FrEDErIKSEN Centre for Electric Power and Energy Department of Electrical EngineeringTechnical University of Denmark2800 Kgs.LyngbyDenmark Danfoss Solar Inverter A/S 6430 NordborgDenmark Østkraft 3700 RønneDenmark FrEDErIKSEN Energimidt8600 SilkeborgDenmark

Solar energy from photovoltaic(PV)is among the fastest developing renewable energy systems *** by governmental subsidies and technological development,Europe has seen a fast expansion of solar PV in the last few *** the installed PV plants,most of them are situated at the distribution systems and bring various operational challenges such as power quality and power flow *** paper discusses the modelling requirements for PV system integration studies,as well as the possible techniques for voltage rise mitigation at low voltage(LV)grids for increasing PV *** solutions are listed and preliminary results are presented.

关键词： Solar photovoltaic(PV) Voltage rise Virtual power plants Ancillary services

BrICS to BrICSCESS——A perspective for practical action in the promotion of healthy lifestyles to improve public health in five countries

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Journal of Sport and Health Science 2019年第6期8卷 520-523页

作者： Ming-Kai Chin Elizabeth Anderson J.hans de ridder r.icardo rUvinha J.Larry Durstine BrICS Council of Exercise and Sport Science(BrICSCESS) Hong KongChina Department of Exercise Science University of South CarolinaColumbiaSC 29208USA school of Human Movement Sciences North-West University Potchefstroom CampusPotchefstroom 2520South Africa school of Arts Sciences and HumanitiesGraduate Program in Physical Activity SciencesUniversity of Sao PauloSao Paulo 03828-000Brazil

In 2006,during a United Nations General Assembly session in New York City,russia presented a concept for developing multilateral international ***,foreign ministers from other countries unanimously expressed interest ... 详细信息

关键词： promotion union initially

A SIMPLE PrOOF OF THE INEQUALITY r_M(MF(κ))≤1.2+(1/2~κ) IN MULTIPrOCESSOr schEDULING

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Acta Mathematicae Applicatae Sinica 1992年第3期8卷 245-251页

作者：越民义 hans KELlerEr 俞忠良 Institute of Applied Mathematics Academia Sinica Beijing 100080 China Institut fur Mathematik Technische Universitat GrazA-8010 GrazAustria. Mathematics Section Nanjing Forestry UniversityNanjing 200028China Institut fur MathematikTechnische Universitat GrazA-8010 GrazAustria.e consider the well-known problem of scheduling n independent tasks nonpreemptivelyon m identical processors with the objective of minimizing the makespan. Coffman Garey andJohnson described an algorithm MULTIFIT based on bin-packing with a worst case performancebetter than the LPT-algorithm. The bound 1.22 obtained by them was claimed by Friesen in1984 that it can be improved to 1.2. In this paper we give a simp1e proof for this bound.

We consider the well-known problem of scheduling n independent tasks nonpreemptivelyon m identical processors with the objective of minimizing the makespan. Coffman, Garey andJohnson described an algorithm MULTIFIT, based on bin-packing, with a worst case performancebetter than the LPT-algorithm. The bound 1.22 obtained by them was claimed by Friesen in1984 that it can be improved to 1.2. In this paper we give a simp1e proof for this bound.

关键词： FFD IN MULTIPrOCESSOr schEDULING A SIMPLE PrOOF OF THE INEQUALITY r_M MF

Kinematic Analysis of Leaf Growth in Grasses:A Comment on Spatial and Temporal Quantitative Analysis of Cell Division and Elongation rate in Growing Wheat Leaves under Saline Conditions

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Journal of Integrative Plant Biology 2009年第5期51卷 433-436页

作者： hans schnyder Monika Kavanova C.Jerry Nelson Lehrstuhl für Grünlandlehre Technische Universitt München85350 Freising-WeihenstephanGermany Department of Cell & Developmental Biology John Innes Centre Division of Plant Sciences University of Missouri

Hu and schmidhalter （2008） conducted a study with wheat seedlings growing in saline and non-stressed （control） conditions with the aim of identifying and quantifying the cellular basis for the reduction in leaf growth. We applaud their goals as salinity is an important issue for plant ecology and food production; however, we have concerns about the methodology used and the subsequent conclusJons that are drawn.

关键词： Kinematic Analysis of Leaf Growth in Grasses cell length