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Proceedings of the 2014 6th International Advanced Research Workshop on In Silico Oncology and Cancer Investigation : the CHIC Project Workshop (IARWISOCI) : Athens, Greece, 3-4 November 2014. International Advanced Research Workshop on...最新文献

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Dendritic cell vaccination for glioblastoma multiforme: Clinical experience and future directions 树突状细胞疫苗治疗多形性胶质母细胞瘤:临床经验及未来发展方向
J. Dejaegher, L. Solie, S. Vleeschouwer, S. Gool
Dendritic cell vaccination is an experimental treatment for malignant gliomas, and has been subject of a translational program for more than ten years in our center. In vitro research, animal models and clinical trials for relapsed and newly diagnosed patients have been conducted. In this paper, we give an overview of the mechanism and rationale of this treatment for brain cancer. We also briefly discuss recently updated results of our clinical trials. Finally, we mention strategies to select patients for this therapy and additional immunotherapeutic strategies to further enhance the antitumor immune responses.
树突状细胞疫苗接种是恶性胶质瘤的一种实验性治疗方法,在我们中心已经进行了十多年的转化项目。对复发和新诊断患者进行了体外研究、动物模型和临床试验。在这篇文章中,我们对这种治疗脑癌的机制和原理进行了综述。我们还简要讨论了最近更新的临床试验结果。最后,我们提到了选择这种治疗的患者的策略和其他免疫治疗策略,以进一步增强抗肿瘤免疫反应。
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引用次数: 2
The importance of grid size and boundary conditions in discrete tumor growth modeling 网格大小和边界条件在离散肿瘤生长建模中的重要性
G. Tzedakis, Giorgos Grekas, E. Tzamali, K. Marias, V. Sakkalis
Modeling tumour growth has proven a very challenging problem, mainly due to the fact that cancer is a very complex process that spans multiple scales both in time and space. The desire to describe interactions in multiple scales has given rise to modeling approaches that use both continuous and discrete variables, called hybrid. The biochemical processes occurring in tumour environment are usually described by continuous variables. Cancer cells tend to be described as discrete agents interacting with their local neighborhood, which is comprised of their extracellular environment and nearby cancer cells. These interactions shape the microenvironment, which in turn acts as a selective force on clonal emergence and evolution. In this work, we study the effects of grid size and boundary conditions of the continuous processes on the discrete populations. We perform various tests on a simplified hybrid model with the aim of achieving faster execution runtimes. We conclude that we can reduce the grid size while maintaining the same dynamics of a larger domain by manipulating the boundary conditions.
模拟肿瘤生长已经被证明是一个非常具有挑战性的问题,主要是因为癌症是一个非常复杂的过程,在时间和空间上都跨越了多个尺度。在多个尺度上描述相互作用的愿望已经产生了使用连续和离散变量的建模方法,称为混合。肿瘤环境中发生的生化过程通常用连续变量来描述。癌细胞往往被描述为与它们的局部邻居相互作用的离散因子,这些邻居由它们的细胞外环境和附近的癌细胞组成。这些相互作用塑造了微环境,而微环境反过来又作为克隆出现和进化的选择性力量。在这项工作中,我们研究了连续过程的网格大小和边界条件对离散总体的影响。我们在一个简化的混合模型上执行各种测试,目的是实现更快的执行运行时。我们的结论是,我们可以通过操纵边界条件来减小网格尺寸,同时保持更大域的相同动态。
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引用次数: 1
Legal and ethical aspects of In Silico medicine 计算机医学的法律和伦理方面
Iheanyi Nwankwo, M. Stauch, Alan Dahi, N. Forgó
The following paper considers some of the novel ethical and legal issues that may arise in the context of in silico-based medicine, with particular reference to the development of hypermodels to optimize treatment decisions for specific diseases.
下面的论文考虑了在基于硅的医学背景下可能出现的一些新的伦理和法律问题,特别是涉及到为优化特定疾病的治疗决策而开发的超模型。
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引用次数: 0
A model of tumor growth coupling a cellular biomodel with biomechanical simulations 肿瘤生长模型与生物力学模拟的细胞生物模型耦合
Farhad Rikhtegar, E. Kolokotroni, G. Stamatakos, P. Büchler
The aim of this paper is to present the development of a multi-scale and multiphysics approach to tumor growth. An existing biomodel used for clinical tumor growth and response to treatment has been coupled with a biomechanical model. The macroscopic mechanical model is used to provide directions of least pressure in the tissue, which drives the geometrical evolution of the tumor predicted at the cellular level. The combined model has been applied to the case of brain and lung tumors. Results indicated that the coupled approach provides additional morphological information on the realistic tumor shape when the tumor is located in regions of tissue inhomogeneity. The approach might be used in oncosimulators for tumor types where the morphometry information plays a major role in the treatment and surgical planning.
本文的目的是介绍肿瘤生长的多尺度和多物理场方法的发展。现有的用于临床肿瘤生长和治疗反应的生物模型已与生物力学模型相结合。宏观力学模型用于提供组织中最小压力的方向,这驱动了在细胞水平上预测的肿瘤的几何演化。该组合模型已被应用于脑和肺肿瘤病例。结果表明,当肿瘤位于组织不均匀区域时,耦合方法提供了真实肿瘤形状的附加形态学信息。该方法可用于肿瘤类型的肿瘤模拟器,其中形态测量信息在治疗和手术计划中起主要作用。
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引用次数: 3
Modeling glioblastoma growth and inhomogeneous tumor invasion with explicitly numerically treated neumann boundary conditions 用明确数值处理的诺伊曼边界条件模拟胶质母细胞瘤生长和不均匀肿瘤侵袭
S. Giatili, G. Stamatakos
A couple of multiscale spatiotemporal simulation models of glioblastoma multiforme (GBM) growth and invasion into the surrounding normal brain tissue is presented. Both models are based on a continuous and subsequently finite mathematical approach centered around the non-linear partial differential equation of diffusion-reaction referring to glioma tumour cells. A novel explicit, strict and thorough numerical treatment of the three dimensional adiabatic Neumann boundary conditions imposed by the skull is also included in both models. The first model assumes a homogeneous representation of normal brain tissue whereas the second one, assuming an inhomogeneous representation of normal brain tissue, distinguishes between white matter, grey matter and cerebrospinal fluid. The predictions of the tumour doubling time by both models are compared for specific data sets. Clinical observational data regarding the range of the GBM doubling time values are utilized in order to ensure the realism of both models and their predictions. We assume that the inhomogeneous normal brain tissue representation is a virtual rendering of reality more credible than its homogeneous counterpart. The simulation results for the cases considered show that using the homogeneous normal brain based model may lead to an error of up to 10% for the first 25 simulated days in relation to the predictions of the inhomogeneous model. However, the error drops to less than 7% afterwards. This observation suggests that even by using a homogeneous brain based model and a realistic weighted average value of its diffusion coefficient, a rough but still informative estimate of the expected tumour doubling time can be achieved. Additional in silico experimentation aiming at statistically testing and eventually further supporting the validity of this hypothesis is in progress. It is noted that the values of the diffusion coefficients and the cell birth and death rates of the model are amenable to refinement and personalization by exploiting the histological and molecular profile of the patient. Work on this aspect is in progress.
本文介绍了多形性胶质母细胞瘤(GBM)生长和向周围正常脑组织浸润的多尺度时空模拟模型。这两个模型都是基于一个连续的,随后有限的数学方法为中心的非线性偏微分方程扩散-反应涉及胶质瘤肿瘤细胞。一个新的明确的,严格的和彻底的三维绝热诺伊曼边界条件施加颅骨的数值处理也包括在这两个模型。第一个模型假设正常脑组织的均匀表示,而第二个模型假设正常脑组织的非均匀表示,区分白质、灰质和脑脊液。针对特定的数据集,比较了两种模型对肿瘤加倍时间的预测。为了确保模型及其预测的真实性,利用了有关GBM加倍时间值范围的临床观察数据。我们假设非均匀的正常脑组织表示是现实的虚拟呈现,比其均匀对应更可信。所考虑的案例的模拟结果表明,与非均匀模型的预测相比,使用均匀的正常大脑模型在前25个模拟天中可能导致高达10%的误差。然而,之后误差下降到不到7%。这一观察结果表明,即使使用基于大脑的均匀模型和其扩散系数的真实加权平均值,也可以实现对预期肿瘤加倍时间的粗略但仍有信息的估计。其他旨在统计测试并最终进一步支持该假设有效性的计算机实验正在进行中。值得注意的是,扩散系数的值以及模型的细胞出生和死亡率可以通过利用患者的组织学和分子特征来改进和个性化。这方面的工作正在进行中。
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引用次数: 2
A collaborative central reviewing platform for cancer detection in digital microscopy images 数字显微镜图像中癌症检测的协同中央审查平台
Ioannis Karatzanis, A. Iliopoulos, M. Tsiknakis, V. Sakkalis, K. Marias
Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. Today, almost 3 decades later, virtual slide telepathology has become a promising tool for providing re-review of surgical pathology cases as part of a quality assurance program but also for educational purposes. In this paper we present the Central Review for Pathology images platform (CRP), developed by the Computational Medicine Laboratory at FORTH-ICS. The CRP is a secure cloud platform, which tries to address current issues that hamper the wider use of virtual pathology. The system offers an easy upgradable multi-format support for virtual slide files from different slide scanner vendors, enhanced collaboration capabilities and scheduling tools, a sophisticated mechanism for defining custom templates for reporting forms which adapts to all user needs and a virtual microscope viewer for the digital slides.
自1986年以来,远程病理实践不断发展。近30年后的今天,虚拟病理切片已经成为一种很有前途的工具,作为质量保证计划的一部分,它可以提供外科病理病例的重新审查,也可以用于教育目的。在本文中,我们介绍了由FORTH-ICS计算医学实验室开发的病理图像平台中央综述(CRP)。CRP是一个安全的云平台,它试图解决当前阻碍虚拟病理更广泛使用的问题。该系统为来自不同幻灯片扫描仪供应商的虚拟幻灯片文件提供了一个易于升级的多格式支持,增强的协作能力和调度工具,一个复杂的机制,用于定义自定义模板的报表,以适应所有用户的需求和虚拟显微镜查看数字幻灯片。
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引用次数: 4
Incorporating data protection in In Silico research: A case of the CHIC project 将数据保护纳入计算机研究:以CHIC项目为例
Elias Neri, Wouter Dhaeze
This is a case study of the solution provided by the CHIC project (http://chic-vph.eu) for the processing of sensitive retrospective and prospective patient data in a research environment. The case study focuses on the de-identification aspects of the CHIC data protection solution.
这是CHIC项目(http://chic-vph.eu)提供的解决方案的一个案例研究,用于在研究环境中处理敏感的回顾性和前瞻性患者数据。案例研究侧重于CHIC数据保护解决方案的去识别方面。
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引用次数: 0
Machine Learning Predictions of Cancer Driver Mutations. 癌症驱动突变的机器学习预测。
E Joseph Jordan, Ravi Radhakrishnan

A method to predict the activation status of kinase domain mutations in cancer is presented. This method, which makes use of the machine learning technique support vector machines (SVM), has applications to cancer treatment, as well as numerous other diseases that involve kinase misregulation.

提出了一种预测癌症激酶结构域突变激活状态的方法。该方法利用机器学习技术支持向量机(SVM),应用于癌症治疗以及许多其他涉及激酶失调的疾病。
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引用次数: 4
Intellectual property rights issues in multiscale cancer modeling 多尺度癌症建模中的知识产权问题
I. Lishchuk, M. Stauch, N. Forgó
In silico hyper-modeling is a complex process which requires interdisciplinary effort. Scientists from biology, medicine, bio-informatics, mathematics, engineering and other fields collaborate and contribute their knowledge and expertise. Researchers deserve recognition, intellectual input deserves protection and investments deserve reward. This paper investigates several IP regimes which may apply to cancer models and seeks to find solutions which would guarantee protection and reward.
在硅超建模是一个复杂的过程,需要跨学科的努力。来自生物学、医学、生物信息学、数学、工程和其他领域的科学家合作并贡献他们的知识和专业知识。研究人员应该得到认可,智力投入应该得到保护,投资应该得到回报。本文研究了几种可能适用于癌症模型的知识产权制度,并寻求能够保证保护和奖励的解决方案。
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引用次数: 0
A modular semantic infrastructure layout for the management of hypermodel-pertinent metadata in the context of In Silico oncology 一个模块化的语义基础结构布局,用于在计算机肿瘤学的上下文中管理与超模型相关的元数据
N. Christodoulou, G. Stamatakos
Over the previous years, semantic metadata have largely contributed to the management, exchange and querying of health-related data, including mathematical and computational disease simulation model descriptions, implementations and output results. In this paper, we present a proposal for an abstract semantic metadata infrastructure layout, indicating its modularity, and thus its capability to operate with different combinations of software tools. Its potential contribution for the purposes of the CHIC project is also reported.
在过去几年中,语义元数据在很大程度上有助于健康相关数据的管理、交换和查询,包括数学和计算疾病模拟模型的描述、实现和输出结果。在本文中,我们提出了一个抽象语义元数据基础设施布局的建议,表明了它的模块化,从而能够与不同的软件工具组合一起操作。还报告了它对CHIC项目的潜在贡献。
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引用次数: 1
期刊
Proceedings of the 2014 6th International Advanced Research Workshop on In Silico Oncology and Cancer Investigation : the CHIC Project Workshop (IARWISOCI) : Athens, Greece, 3-4 November 2014. International Advanced Research Workshop on...
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