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Nuclear β-Catenin Induces an Early Liver Progenitor Phenotype in Hepatocellular Carcinoma and Promotes Tumor Recurrence

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AMERICAN JOURNAL OF PATHOLOGY 2010年第1期176卷 472-481页

作者： Zulehner, Gudrun Mikula, Mario Schneller, Doris van Zijl, Franziska Huber, Heidemarie Sieghart, Wolfgang Grasl-Kraupp, Bettina Waldhoer, Thomas Peck-Radosavljevic, Markus Beug, Hartmut Mikulits, Wolfgang Med Univ Vienna Div Inst Canc Res Dept Internal Med 1 A-1090 Vienna Austria Med Univ Vienna Div Gastroenterol & Hepatol Dept Internal Med 3 A-1090 Vienna Austria Med Univ Vienna Ctr Publ Hlth Dept Epidemiol A-1090 Vienna Austria Res Inst Mol Pathol A-1030 Vienna Austria

Transforming growth factor-beta cooperates with oncogenic Ras to activate nuclear beta-catenin during the epithelial to mesenchymal transition of hepatocytes, a process relevant in the progression of hepatocellular carcinoma (HCC). In this study we investigated the role of beta-catenin in the differentiation of murine, oncogene-targeted hepatocytes and in 133 human HCC patients scheduled for orthotopic liver transplantation. Transforming growth factor-beta caused dissociation of plasma membrane E-cadherin/beta-catenin complexes and accumulation of nuclear beta-catenin in Ras-transformed, but otherwise normal hepatocytes in p19(ARF)-/- mice. Both processes were inhibited by Smad7-mediated disruption of transforming growth factor-beta signaling. Overexpression of constitutively active beta-catenin resulted in high levels of CK19 and M2-PK, whereas ablation of beta-catenin by axin overexpression caused strong expression of CK8 and CK18. Therefore, nuclear beta-catenin resulted in dedifferentiation of neoplastic hepatocytes to immature progenitor cells, whereas loss of nuclear beta-catenin led to a differentiated HCC phenotype. Poorly differentiated human HCC showed cytoplasmic redistribution or even loss of E-cadherin, suggesting epithelial to mesenchymal transition. Analysis of 133 HCC patient samples revealed that 58.6% of human HCC exhibited strong nuclear beta-catenin accumulation, which correlated with clinical features such as vascular invasion and recurrence of disease after orthotopic liver transplantation. These data suggest that activation of beta-catenin signaling causes dedifferentiation to malignant, immature hepatocyte progenitors and facilitates recurrence of human HCC after orthotopic liver transplantation. (Am J Pathol 2010, 176:472-481;DOI: 10.2353/ajpath.2010.090300)

关键词： Stem Cells beta Catenin Recurrent Neoplasm Hepatocellular Cancer Epithelial-Mesenchymal Transition Relapse KRT8 gene human-centered computing Hepatocytes Liver Transplantation Anaplasia

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NF-κB, JNK, and TLR Signaling Pathways in Hepatocarcinogenesis

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GASTROENTEROLOGY RESEARCH AND PRACTICE 2010年第Toll/Like...期2010卷 367694-367694页

作者： Maeda, Shin Yokohama City Univ Dept Gastroenterol Kanazawa Ku Yokohama Kanagawa 2360004 Japan

Hepatocellular carcinoma (HCC) is the third largest cause of cancer deaths worldwide. The role of molecular changes in HCC have been used to identify prognostic markers and chemopreventive or therapeutic targets. It seems that toll-like receptors (TLRs) as well as the nuclear factor (NF)-kappa B, and JNK pathways are critical regulators for the production of the cytokines associated with tumor promotion. The cross-talk between an inflammatory cell and a neoplastic cell, which is instigated by the activation of NF-kappa B and JNKs, is critical for tumor organization. JNKs also regulate cell proliferation and act as oncogenes, making them the main tumor-promoting protein kinases. TLRs play roles in cytokine and hepatomitogen expression mainly in myeloid cells and may promote liver tumorigenesis. A better understanding of these signaling pathways in the liver will help us understand the mechanism of hepatocarcinogenesis and provide a new therapeutic target for HCC.

关键词： JNK Pathway Tumor Promotion NF-kappa B Cytokines Inflammatory cell Hepatocarcinogenesis Chemopreventive Agent Oncogenes Liver Neoplastic Cell human-centered computing Bone Marrow Cells

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Rosuvastatin Counteracts Vessel Arterialisation and Sinusoid Capillarisation, Reduces Tumour Growth, and Prolongs Survival in Murine Hepatocellular Carcinoma

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GASTROENTEROLOGY RESEARCH AND PRACTICE 2010年第unknown期2010卷 640797-640797页

作者： Tijeras-Raballand, Annemilai Hainaud-Hakim, Patricia Contreres, Jean-Olivier Gest, Caroline Le Henaff, Carole Levy, Bernard I. Pocard, Marc Soria, Claudine Dupuy, Evelyne Hop Lariboisiere Inst Vaisseaux & Sang F-75010 Paris France Hop Lariboisiere Angiogenese & Rech Translat INSERM Equipe Labelli F-75010 Paris France Univ Paris 07 F-75010 Paris France Univ Rouen Lab MERCI F-76183 Rouen France Hop Europeen Georges Pompidou INSERM U970 Paris Cardiovasc Res Ctr F-75015 Paris France Univ Paris 05 F-75006 Paris France

Background and Aims. An arterial blood supply and phenotypic changes of the sinusoids characterise the liver vasculature in human hepatocellular carcinoma (HCC). We investigated the effects of rosuvastatin on liver vessel anomalies, tumour growth and survival in HCC. Methods. We treated transgenic mice developing HCC, characterized by vessel anomalies similar to those of human HCC, with rosuvastatin. Results. In the rosuvastatin group, the survival time was longer (P < .001), and liver weight (P < .01) and nodule surface (P < .01) were reduced. Rosuvastatin decreased the number of smooth muscle actin-positive arteries (P < .05) and prevented the sinusoid anomalies, with decreased laminin expression (P < .001), activated hepatic stellate cells (P < .001), and active Notch4 expression. Furthermore, rosuvastatin inhibited endothelial cell but not tumour hepatocyte functions. Conclusions. Rosuvastatin reduced the vessel anomalies and tumour growth and prolonged survival in HCC. These results represent new mechanisms of the effects of statin on tumour angiogenesis and a potential target therapy in HCC.

关键词： Molecular Targeted Therapy ZD4522 pressure vessels Tumours human-centered computing Anomalies

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Coagulation parameters and portal vein thrombosis in cirrhosis

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HEPATOLOGY RESEARCH 2010年第5期40卷 555-555页

作者： Filik, Levent Ankara Educ & Res Hosp Dept Gastroenterol Ankara Turkey

I READ WITH great interest the article by Weber A et al. The article reports important outcomes for cirrhotic patients and portal vein thrombosis (PVT). The authors retrospectively evaluated 236 patients. They excluded 148 patients and the data of 88 patients were analysed. They stated the significant difference of international normalized ratio (INR) and activated partial thrombo-plastin time (aPTT) in Child scores A, B and C cirrhosis. As we already know, the risk of PVT increases with severity of cirrhosis, and, hepatocellular carcinoma (HCC) is the most common risk factor. That is why, I think, the exclusion of HCC patients in the study group may have resulted in misleading conclusions being drawn.

关键词： Risk Factors Liver Cirrhosis Portal Vein Thrombosis human-centered computing exclusion

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Ubiquitous Mining with Interactive Data Mining Agents

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Journal of Computer Science & Technology 2009年第6期24卷 1018-1027页

作者：吴信东朱兴全陈琪君王飞跃 School of Computer Science and Information Engineering Hefei University of Technology Department of Computer Science University of Vermont Faculty of Engineering and Information Technology University of Technology Institute of Automation Chinese Academy of Sciences

Due to the increasing availability and sophistication of data recording techniques, multiple information sources and distributed computing are becoming the important trends of modern information systems. Many applications such as security informatics and social computing require a ubiquitous data analysis platform so that decisions can be made rapidly under distributed and dynamic system environments. Although data mining has now been popularly used to achieve such goals, building a data mining system is, however, a nontrivial task, which may require a complete understanding on numerous data mining techniques as well as solid programming skills. Employing agent techniques for data analysis thus becomes increasingly important, especially for users not familiar with engineering and computational sciences, to implement an effective ubiquitous mining platform. Such data mining agents should, in practice, be intelligent, complete, and compact. In this paper, we present an interactive data mining agent - OIDM （online interactive data mining）, which provides three categories （classification, association analysis, and clustering） of data mining tools, and interacts with the user to facilitate the mining process. The interactive mining is accomplished through interviewing the user about the data mining task to gain efficient and intelligent data mining control. OIDM can help users find appropriate mining algorithms, refine and compare the mining process, and finally achieve the best mining results. Such interactive data mining agent techniques provide alternative solutions to rapidly deploy data mining techniques to broader areas of data intelligence and knowledge informaties.

关键词： information systems human-centered computing data mining intelligent agents

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A Survey of Affect Recognition Methods: Audio, Visual, and Spontaneous Expressions

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IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE 2009年第1期31卷 39-58页

作者： Zeng, Zhihong Pantic, Maja Roisman, Glenn I. Huang, Thomas S. Univ Illinois Beckman Inst Urbana IL 61801 USA Univ London Imperial Coll Sci Technol & Med Dept Comp London SW7 2AZ England Univ Twente Fac Elect Engn Math & Comp Sci Enschede Netherlands Univ Illinois Dept Psychol Champaign IL 61820 USA

Automated analysis of human affective behavior has attracted increasing attention from researchers in psychology, computer science, linguistics, neuroscience, and related disciplines. However, the existing methods typically handle only deliberately displayed and exaggerated expressions of prototypical emotions, despite the fact that deliberate behavior differs in visual appearance, audio profile, and timing from spontaneously occurring behavior. To address this problem, efforts to develop algorithms that can process naturally occurring human affective behavior have recently emerged. Moreover, an increasing number of efforts are reported toward multimodal fusion for human affect analysis, including audiovisual fusion, linguistic and paralinguistic fusion, and multicue visual fusion based on facial expressions, head movements, and body gestures. This paper introduces and surveys these recent advances. We first discuss human emotion perception from a psychological perspective. Next, we examine available approaches for solving the problem of machine understanding of human affective behavior and discuss important issues like the collection and availability of training and test data. We finally outline some of the scientific and engineering challenges to advancing human affect sensing technology.

关键词： Evaluation/methodology human-centered computing affective computing introductory survey

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Shake Well Before Use: Intuitive and Secure Pairing of Mobile Devices

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IEEE TRANSACTIONS ON MOBILE computing 2009年第6期8卷 792-806页

作者： Mayrhofer, Rene Gellersen, Hans Univ Vienna A-1010 Vienna Austria Univ Lancaster Dept Comp Lancaster LA1 4WA England

A challenge in facilitating spontaneous mobile interactions is to provide pairing methods that are both intuitive and secure. Simultaneous shaking is proposed as a novel and easy-to-use mechanism for pairing of small mobile devices. The underlying principle is to use common movement as a secret that the involved devices share for mutual authentication. We present two concrete methods, ShaVe and ShaCK, in which sensing and analysis of shaking movement is combined with cryptographic protocols for secure authentication. ShaVe is based on initial key exchange followed by exchange and comparison of sensor data for verification of key authenticity. ShaCK, in contrast, is based on matching features extracted from the sensor data to construct a cryptographic key. The classification algorithms used in our approach are shown to robustly separate simultaneous shaking of two devices from other concurrent movement of a pair of devices, with a false negative rate of under 12 percent. A user study confirms that the method is intuitive and easy to use, as users can shake devices in an arbitrary pattern.

关键词： Algorithm/protocol design and analysis ubiquitous computing mobile environments authentication human-centered computing mobile applications

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Learning Situation Models in a Smart Home

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IEEE TRANSACTIONS ON SYSTEMS MAN AND CYBERNETICS PART B-CYBERNETICS 2009年第1期39卷 56-63页

作者： Brdiczka, Oliver Crowley, James L. Reignier, Patrick Xerox Corp Palo Alto Res Ctr Palo Alto CA 94304 USA Inst Natl Resch Informat & Automat INRIA Rhone Al PRIMA Res Grp F-38334 Saint Ismier France Inst Natl Polytech Grenoble F-38031 Grenoble 1 France Univ Grenoble 1 F-38041 Grenoble 9 France

This paper addresses the problem of learning situation models for providing context-aware services. Context for modeling human behavior in a smart environment is represented by a situation model describing environment, users, and their activities. A framework for acquiring and evolving different layers of a situation model in a smart environment is proposed. Different learning methods are presented as part of this framework: role detection per entity, unsupervised extraction of situations from multimodal data, supervised learning of situation representations, and evolution of a predefined situation model with feedback. The situation model serves as frame and support for the different methods, permitting to stay in an intuitive declarative framework. The proposed methods have been integrated into a whole system for smart home environment. The implementation is detailed, and two evaluations are conducted in the smart home environment. The obtained results validate the proposed approach.

关键词： Context awareness human-centered computing machine learning situation modeling situation split

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Mixed Reality humans: Evaluating Behavior, Usability, and Acceptability

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IEEE TRANSACTIONS ON VISUALIZATION AND COMPUTER GRAPHICS 2009年第3期15卷 369-382页

作者： Kotranza, Aaron Lok, Benjamin Deladisma, Adeline Pugh, Carla M. Lind, D. Scott Univ Florida Dept Comp & Informat Sci & Engn Gainesville FL 32611 USA Med Coll Georgia Dept Surg Augusta GA 30912 USA Northwestern Univ Feinberg Sch Med Chicago IL 60611 USA

This paper presents mixed reality humans (MRHs), a new type of embodied agent enabling touch-driven communication. Affording touch between human and agent allows MRHs to simulate interpersonal scenarios in which touch plays a crucial role. Two studies provide an initial evaluation of user behavior with an MRH patient and the usability and acceptability of an MRH patient for practice and evaluation of medical students' clinical skills. In Study I (n = 8), it was observed that students treated MRHs as social actors more than students in prior interactions with virtual human patients (n = 27), and used interpersonal touch to comfort and reassure the MRH patient similarly to prior interactions with human patients (n = 76). In the within-subjects Study II (n = 11), medical students performed a clinical breast exam on each of the MRH and human patient. Participants performed equivalent exams with the MRH and human patients, demonstrating the usability of MRHs to evaluate students' physical exam skills. The acceptability of the MRH patient for practicing exam skills was high as students rated the experience as believable and educationally beneficial. Acceptability was improved from Study I to Study II due to an increase in the MRH's visual realism, demonstrating that visual realism is critical for simulation of specific interpersonal scenarios.

关键词： Intelligent agents virtual reality human-centered computing user interfaces evaluation/methodology medicine

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Mood Recognition during Online Self-Assessment Tests

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IEEE TRANSACTIONS ON LEARNING TECHNOLOGIES 2009年第1期2卷 50-61页

作者： Moridis, Christos N. Economides, Anastasios A. Univ Macedonia Dept Informat Syst Thessaloniki 54006 Greece Univ Macedonia Dept Informat Syst Thessaloniki 54006 Greece

Individual emotions play a crucial role during any learning interaction. Identifying a student's emotional state and providing personalized feedback, based on integrated pedagogical models, has been considered to be one of the main limits of traditional tools of e-learning. This paper presents an empirical study that illustrates how learner mood may be predicted during online self-assessment tests. Here, a previous method of determining student mood has been refined based on the assumption that the influence on learner mood of questions already answered declines in relation to their distance from the current question. Moreover, this paper sets out to indicate that "exponential logic" may help produce more efficient models if integrated adequately with affective modeling. The results show that these assumptions may prove useful to future research.

关键词： Computer uses in education education human-centered computing human information processing personalization self-assessment Web-based interaction

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