Technology for efficient simulation of cancer cell transport

高效模拟癌细胞运输的技术

• 批准号: 10059089
• 负责人: Amanda E Randles
• 金额: $ 37.07万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059089
• 关键词: Address; Algorithms; Automobile Driving; Behavior; Biomedical Research; Biophysics; Blood Vessels; Blood flow; Cancer Biology; Cause of Death; Cell Communication; Cell model; Cells; Cellular biology; Cessation of life; Code; Collaborations; Communities; Complement; Complex; Computer Models; Computers; Data; Development; Devices; Diagnostic; Disease Progression; Disseminated Malignant Neoplasm; Exhibits; Extravasation; Fostering; Future; Geometry; Goals; In Vitro; Individual; Infrastructure; Intuition; Knowledge; Lead; Link; Liquid substance; Location; Malignant Neoplasms; Methods; Microfluidic Microchips; Modeling; Morphology; Movement; Neoplasm Circulating Cells; Neoplasm Metastasis; Outcomes Research; Patients; Pattern; Penetration; Plant Roots; Process; Property; Research; Research Personnel; Resolution; Role; Scientist; Site; Software Framework; Software Tools; Structure; Technology; Testing; Therapeutic; Tumor Cell Migration; United States; Vascular System; Work; anticancer research; base; biomechanical model; biophysical properties; bioprinting; cancer cell; cell behavior; cell motility; cell type; computer infrastructure; computing resources; experience; experimental study; hydrodynamic model; in silico; insight; interest; man; mathematical model; mechanical properties; novel diagnostics; novel therapeutics; open source; predictive modeling; simulation; tool; tumor

Cancer is the attributed cause of death in one in four cases in the United States and metastasis, a complex multistep process leading to the spread of tumors, is responsible for more than 90% of these deaths. However, predicting the location of these secondary tumor sites is still an elusive goal. One of the fundamental hurdles is to understand the trajectory of cell movement through the vascular system and the likelihood of penetration of the vessel wall. Studies have demonstrated that more than 50% of cancer metastatic sites could be explained by the blood flow pattern between the primary and secondary; however, the development of predictive models is still needed. Insight into the underlying mechanisms of cancer metastasis will provide insight into disease progression and lead to the development of new diagnostic or therapeutic methods targeting regions of the vasculature likely to incur secondary tumor sites. Tools that can be easily tuned to allow not only patient-specific but cell-specific modeling would complement ongoing in vitro experiments and provide this critical insight. Such computational models would allow researchers to probe the influence of different biophysical properties on cancer-specific cell behavior without the need for either expensive experimental trials for each cell-type or extrapolate from findings for one cancer to apply to another. An expected outcome of this research to create a usable, scalable, and extensible software framework for use by the wider biomedical research community to study the role of biophysical properties on a cell's transport and potential arrest. On such a platform, users will be able to introduce models of their cells-of-interest and perform simulations on them with models we (or others in the community) have developed. The ability to seamlessly introduce new cell-types with minimal effort will foster entirely new collaborations between researchers and provide biologists who would not traditionally leverage computational resources to study cell-specific properties in the context of realistic vascular geometries. This work will set the stage for future studies expanding the capabilities of this open source model.

在美国，癌症是四分之一病例的死因，而且转移是癌症的主要原因 导致肿瘤扩散的复杂多步骤过程，是 90% 以上的原因 这些死亡。然而，预测这些继发性肿瘤部位的位置仍然是一个难题 难以捉摸的目标。基本障碍之一是了解细胞运动的轨迹 通过血管系统和穿透血管壁的可能性。研究有 证明超过 50% 的癌症转移部位可以通过血液来解释 初级和次级之间的流动模式；然而，预测技术的发展 仍然需要模型。深入了解癌症转移的潜在机制将提供 洞察疾病进展并导致新诊断或治疗方法的开发 针对可能产生继发性肿瘤部位的脉管系统区域的方法。 可以轻松调整的工具不仅可以进行患者特异性建模，还可以进行细胞特异性建模 补充正在进行的体外实验并提供这一重要的见解。这样的计算 模型将使研究人员能够探究不同生物物理特性对 癌症特异性细胞行为，无需对每种细胞进行昂贵的实验试验 细胞类型或从一种癌症的发现推断适用于另一种癌症。预期结果 这项研究的目的是创建一个可用的、可扩展的、可扩展的软件框架，供 更广泛的生物医学研究界研究生物物理特性对细胞的作用 运输和可能的逮捕。在这样的平台上，用户将能够介绍模型 他们感兴趣的细胞，并用我们（或业内其他人）的模型对它们进行模拟 社区）已经发展起来。能够以最少的成本无缝引入新的细胞类型 这一努力将促进研究人员之间全新的合作，并为生物学家提供 传统上不会利用计算资源来研究细胞特定的特性 现实血管几何形状的背景。这项工作将为未来的研究扩展奠定基础 这个开源模型的功能。