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Advanced gastric cancer:Is there enough evidence to call second-line therapy standard?

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World Journal of Gastroenterology 2012年第44期18卷 6376-6378页

作者： hendrik-tobias arkenau Matilde Saggese Charlotte Lemech Drug Development Unit Sarah Cannon Research UKUniversity College LondonLondon W1G 6ADUnited Kingdom

Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence *** treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and *** the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical *** patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of *** these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been *** that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall *** two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall *** this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.

关键词： Gastric cancer Cancer of the gastro-esoph-ageal junction Second-line chemotherapy Best sup-portive care Survival

Signal pathways and precision therapy of small-cell lung cancer

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2293-2310页

作者： Min Yuan Yu Zhao hendrik-tobias arkenau Tongnei Lao Li Chu Qing Xu Department of Oncology Shanghai Tenth People’s HospitalTongji University200072 ShanghaiChina Drug Development Unit Sarah Cannon Research InstituteLondonUK Department of Oncology Centro Medico BO CHIMacaoSARChina Department of Radiation Oncology Fudan University Shanghai Cancer Center200032 ShanghaiChina Present address:Department of Oncology Shanghai Medical CollegeFudan University200032 ShanghaiChina

Small-cell lung cancer(SCLC)encounters up 15%of all lung cancers,and is characterized by a high rate of proliferation,a tendency for early metastasis and generally poor *** of the patients present with distant metastatic disease at the time of clinical diagnosis,and only one-third are eligible for potentially curative ***,investigations into the genomic make-up of SCLC show extensive chromosomal rearrangements,high mutational burden and loss-of-function mutations of several tumor suppressor *** the clinical development of new treatments for SCLC has been limited in recent years,a better understanding of oncogenic driver alterations has found potential novel targets that might be suitable for therapeutic ***,there are six types of potential treatable signaling pathways in SCLC,including signaling pathways targeting the cell cycle and DNA repair,tumor development,cell metabolism,epigenetic regulation,tumor immunity and *** this point,however,there is still a lack of understanding of their role in SCLC tumor biology and the promotion of cancer *** optimizing drug targets,improving drug pharmacology,and identifying potential biomarkers are the main focus and further efforts are required to recognize patients who benefit most from novel therapies in *** review will focus on the current learning on the signaling pathways,the status of immunotherapy,and targeted therapy in SCLC.

关键词： metabolism immunity alterations

基于循环游离DNA的染色体不稳定检测与转移性胃癌患者化疗应答相关性研究

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中华转移性肿瘤杂志 2023年第2期6卷 178-182页

作者：罗欣佩朱心怡郭献灵朱忠政钱红王辉茅伟刘卫星吴建国 hendrik-tobias arkenau 袁敏许青同济大学附属第十人民医院肿瘤科上海200072 英国莎卡隆癌症研究中心伦敦KF12261

目的通过对转移性胃癌患者进行低覆盖度全基因组测序,探索胃癌化疗耐药的发生发展和基因组学变化。方法收集2019年7—12月就诊于同济大学附属第十人民医院的9例转移性胃癌患者。在化疗前后收集外周血标本,提取血浆循环游离DNA(cfDNA)进... 详细信息

目的通过对转移性胃癌患者进行低覆盖度全基因组测序,探索胃癌化疗耐药的发生发展和基因组学变化。方法收集2019年7—12月就诊于同济大学附属第十人民医院的9例转移性胃癌患者。在化疗前后收集外周血标本,提取血浆循环游离DNA(cfDNA)进行低覆盖率的全基因组测序,并通过超灵敏染色体不稳定性检测(UCAD)进行染色体不稳定分析。结果根据化疗后的疗效评估将患者分为化疗有效组和化疗无效组。化疗有效组治疗后染色体不稳定水平低于治疗前[(1.186±1.642)%∶(5.639±7.666)%,P=0.017],化疗无效组治疗后染色体不稳定水平似乎高于治疗前(0.11%∶0.08%)。UCAD检测提示频繁的染色体拷贝数变化包括7p、8q、10q、11q、12q、17q增加,8p、17p缺失等。比较化疗前后的染色体拷贝数变化,2例(22.2%)患者在化疗后出现额外的拷贝数增加,包括11q、5p拷贝数增多,进一步疗效分析表明化疗耐药。结论基于血浆cfDNA的染色体不稳定动态检测有望作为转移性胃癌疗效评估和化疗耐药性产生的生物标志物。

关键词：循环游离DNA 染色体不稳定转移性胃癌化疗

Numerical and experimental investigation of sloshing under large amplitude roll excitation

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Journal of Hydrodynamics 2021年第4期33卷 787-803页

作者： Ronja Hoch Frank-hendrik Wurm Institute of Turbomachinery University of RostockRostockGermany

To enable a virtual design and optimization process of partially filled coolant tanks a reliable numerical approach is needed to predict the liquid and gas two phase flow inside the *** this study numerical results are validated by experimental data to examine the suitability of the method for the tank design *** liquid motion inside the tanks can be described as sloshing with high amplitude,off-resonant roll excitation and was examined using a homogeneous multiphase model and VOF interface capturing approach as well as an experimental setup including piezoelectric pressure sensors and qualitative observation of the free *** effect of two vertical baffles on the maximum pressure and the position of phase interface was *** comparison between the computational and experimental results reveals that the numerical model tends to under predict the experimental peak pressures but resolves the liquid surface in close agreement with the experiments.

关键词： Multiphase flows sloshing unsteady Reynolds averaged Navier-Stokes(URANS)

Role of mucosal dendritic cells in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第33期14卷 5138-5148页

作者： Jan hendrik Niess Department of Internal Medicine I Ulm UniversityUlm 89031 Germany

The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.

关键词： Dendritic cells Commensal Inflammatory bowel disease Mucosal immunity Host defence

Genomic landscape of pancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2014年第46期20卷 17498-17506页

作者： Niklas Gebauer Christian Schmidt-Werthern Veronica Bernard Alfred C Feller tobias Keck Nehara Begum Dirk Rades hendrik Lehnert Georg Brabant Christoph Thorns Department of Pathology University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Surgery University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Radiation Oncology University Hospital of Schleswig-Holstein 23538 LuebeckGermany Department of Internal Medicine I University Hospital of Schleswig-Holstein23538 LuebeckGermany

AIM: To investigate the prognostic role of genomic stability and copy number alterations (CNAs) pancreatic neuroendocrine tumors (PanNETs).

关键词： Array comparative genomic hybridization Copy number alterations Chromosomal aberrations Pancreatic neuroendocrine tumors Prognosis

Realising Data-Centric Scientific Workflows with Provenance-Capturing on Data Lakes

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Data Intelligence 2022年第2期4卷 426-438页

作者： hendrik Noltet Philipp Wieder Gesellschaft fur wissenschaftliche Datenverarbeitung mbH Gottingen Gottingen Gottingen 37077Germany

Since their introduction by James Dixon in 2010,data lakes get more and more attention,driven by the promise of high reusability of the stored data due to the schema-on-read *** on this idea,several additional requirements were discussed in literature to improve the general usability of the concept,like a central metadata catalog including all provenance information,an overarching data governance,or the integration with(high-performance)processing *** the necessity for a logical and a physical organisation of data lakes in order to meet those requirements is widely recognized,no concrete guidelines are yet *** most common architecture implementing this conceptual organisation is the zone architecture,where data is assigned to a certain zone depending on the degree of *** paper discusses how FAIR Digital Objects can be used in a novel approach to organize a data lake based on data types instead of zones,how they can be used to abstract the physical implementation,and how they empower generic and portable processing capabilities based on a provenance-based approach.

关键词： Data lake Provenance Workflows FAIRDigital Objects CWFR

Accurate simulation of surfaces and interfaces of ten FCC metals and steel using Lennard–Jones potentials

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npj Computational Materials 2021年第1期7卷 205-219页

作者： Krishan Kanhaiya Seonghan Kim Wonpil Im hendrik Heinz Department of Chemical and Biological Engineering University of Colorado at BoulderBoulderCO 80301USA Departments of Biological Sciences Chemistryand BioengineeringLehigh UniversityBethlehemPA 18015USA

The earlier integration of validated Lennard–Jones(LJ)potentials for 8 fcc metals into materials and biomolecular force fields has advanced multiple research fields,for example,metal–electrolyte interfaces,recognition of biomolecules,colloidal assembly of metal nanostructures,alloys,and *** we introduce 12-6 and 9-6 LJ parameters for classical all-atom simulations of 10 further fcc metals(Ac,Ca(α),Ce(γ),Es(β),Fe(γ),Ir,Rh,Sr(α),Th(α),Yb(β))and stainless *** parameters reproduce lattice constants,surface energies,water interfacial energies,and interactions with(bio)organic molecules in 0.1 to 5%agreement with experiment,as well as qualitative mechanical properties under standard *** are reduced up to a factor of one hundred in comparison to earlier Lennard–Jones parameters,embedded atom models,and density functional *** also explain a quantitative correlation between atomization energies from experiments and surface energies that supports parameter *** models are computationally very efficient and applicable to an exponential space of *** with a wide range of force fields such as the Interface force field(IFF),AMBER,CHARMM,COMPASS,CVFF,DREIDING,OPLS-AA,and PCFF enables reliable simulations of nanostructures up to millions of atoms and microsecond time ***-friendly model building and input generation are available in the CHARMM-GUI Nanomaterial *** a limitation,deviations in mechanical properties vary and are comparable to DFT *** discuss the incorporation of reactivity and features of the electronic structure to expand the range of applications and further increase the accuracy.

关键词： steel metals qualitative

Correlation of Lopingian to Middle Triassic Palynozones

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Journal of Earth Science 2018年第4期29卷 755-777页

作者： hendrik Nowak Elke Schneebeli-Hermann Evelyn Kustatscher Museum of Nature South Tyrol Bindergasse/Via Bottai 1 Bozen/Bolzano 39100 Italy Palaiontologisehes Institut und Museum Karl-Schmid-Strasse 4 Zurich 8006 Switzerland Department for Geo- und Umweltwissenschafien Pala'ontologie und Geobiologie Ludwig-Maximilians-Universitait and Bayerische Staatssammlung Jur P alaiontologie und Geob iologie Richard-Wagner-Strafle 10 Munchen 80333 Germany

Terrestrial floras underwent important changes during the Lopingian （Late Permian）, Early Triassic, and Middle Triassic, i.e., before, during, and after the end-Permian mass extinction. An accurate account of these developments requires reliable correlation. Macrofossils of land plants can only provide a low-resolution biostratigraphy, while detailed zonation schemes based on palynomorphs are available for many regions. Their applicability is still limited due to several factors, such as （micro-）floral provincialism, a lack of suitable marker taxa commonly occurring at important boundaries, and in many cases a lack of independent age control. Nevertheless, these palynostratigraphic schemes are regularly used for dating and correlation of successions between different regions. To support such efforts, the biozonation schemes based on palynomorphs from the Lopingian up to and including the Middle Triassic from across the world are summarized and revised. Thus, a consistent correlation of palynozones with the currently recognized international stages is established.

关键词： Permian Triassic land plants palynomorpbs biostratigraphy.