Liver Cancer: pre-Malignant Stiffening, Membrane Transduction, & Nuclear Rheology

肝癌：癌前硬化、膜转导、

• 批准号: 8866921
• 负责人: Dennis E. Discher
• 金额: $ 197.87万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-16 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8866921
• 关键词: Advisory Committees; Alcohol consumption; American; Animal Model; Area; Back; Biomedical Engineering; Breast; Cancer Center; Cancer Etiology; Cancer cell line; Cause of Death; Cells; Cessation of life; Chemistry; Cirrhosis; Clinic; Clinical; Colon; Communities; Correlative Study; Country; DNA Maintenance; Devices; Diagnosis; Doctor of Philosophy; Education and Outreach; Engineering; Europe; European; Exhibits; Faculty; Fibrosis; Frequencies; Goals; Hepatology; Hospitals; Human; In Situ; Individual; Knowledge; Laboratories; Lead; Leadership; Liver; Liver Fibrosis; Liver diseases; Lung; Malignant Neoplasms; Malignant neoplasm of liver; Mastectomy; Measurement; Measures; Mechanics; Medical center; Medicine; Membrane; Methods; Modeling; Molecular; Nature; Neoplasm Metastasis; Nuclear; Organ; Palliative Care; Pathology; Patients; Pennsylvania; Philadelphia; Physics; Physiology; Pilot Projects; Premalignant; Primary carcinoma of the liver cells; Public Health; Publications; Relative Risks; Reporting; Research Project Grants; Resources; Rheology; Role; Sampling; Scientist; Signal Transduction; Site; Staging; Students; Tissue Model; Tissues; Training; Translating; Uncertainty; Universities; Vision; Work; Xenograft Model; base; cancer cell; cancer risk; elastography; human disease; insight; interdisciplinary approach; interest; liver transplantation; member; mouse model; multi-scale modeling; next generation; physical property; professor; programs; public health relevance; research study; rib bone structure; symposium; theories; tumor; tumor growth

 DESCRIPTION (provided by applicant): PSOC Penn Liver Cancer: pre-Malignant Stiffening, Membrane Transduction, & Nuclear Rheology, The Transdisciplinary nature of Cancer Physics requires efficient and effective interactions across multiple boundaries. We have chosen to focus on primary liver cancer, predominantly hepatocellular carcinoma (HCC), which are highly morbid tumors that represent the third most common cause of cancer death worldwide. HCC almost always arises in the setting of end-stage liver fibrosis, termed cirrhosis, and new in situ methods of measuring liver stiffness are emerging as effective predictors of the relative risk of HCC. Patients with stiffer livers demonstrate dramatically increased rates of HCC, but clinical acceptance will no doubt be helped by - or even require - studies proposed here. We seek to determine the nature of the relationships between human HCC with fresh primary samples and the mechanics of liver tissues, the signals to cells, and the roles of nuclear mechanics in DNA stability and tumor growth. Five clinicians at Penn who regularly see patients or samples with liver disease and liver cancer are involved in the proposed PSOC Penn, and so the opportunities to impact the Clinic are tangible. In formulating this cross-cutting proposal with 3 Research Projects and 2 Cores, we propose a Multi-PI Leadership Plan to best represent the diverse areas of expertise and responsibility: Dennis Discher PhD (Prof. Eng'g Appl Sci, Grad Groups Physics, Cell & Molec Biol) Contact PI, Admin Core Lead, PI of Project-3 Nuclear Rheology: Cancer Cell line Expertise. Paul Janmey PhD (Prof. Physiology, Physics, and Bioengineering) PI of Project-1 Liver Mechanics: Cancer Cell line Expertise. Rebecca Wells MD (Assoc. Prof. Medicine, Pathology, and Laboratory Medicine) PI of Core-1 Liver Cancer Tissue and Models: Expertise in Mechanisms of Liver Disease. David E. Kaplan MD (Asst. Professor of Medicine, and Director of Hepatology) Co-PI of Core-1 Liver Cancer Tissue and Models: Clinical Expertise in Liver Cancer. Andrea Liu PhD (Prof. Physics and Chemistry) PI of Core-2 Theory: Expertise in Statistical Physics Modeling. Penn is a single, integrated Campus, with all of the labs involved in the Center walkable within 5-10 minutes, and Penn's Medical Center Hospital serves the greater Philadelphia area with one of the larger liver disease centers in the country. To integrate the proposed PSOC Penn within the University's broad and deep efforts in Cancer, all leaders and faculty members of the PSOC will become members of Penn's Abramson Cancer Center (if they are not already). The Director of the Abramson Cancer Center, Prof. Chi Van Dang, will be PI of Pilot Project-1 and will be a key member of the Center Advisory Committee. More broadly, the PSOC Penn will support through Education & Outreach a wide variety of programs that aim to build a vibrant community of students and fellows who embody the multidisciplinary approach to understanding the physics of cancer with an aim of transforming the next generation of scientists, engineers and clinicians.

 描述（由适用提供）：PSOC PENN肝癌：前化疗法，膜转导和核流变性，癌症物理学的跨学科性质需要跨多个边界的有效相互作用。我们选择专注于原发性肝癌，主要是肝细胞癌（HCC），它们是高度病态的肿瘤，代表了全球癌症死亡的第三大原因。 HCC几乎总是在终阶段肝纤维化，称为肝硬化的情况下出现，而新的原位测量肝脏僵硬方法正在成为有效的HCC相对风险的预测指标。僵硬的生命患者表现出大幅提高HCC的速度，但毫无疑问，临床接受率会得到（甚至需要）在此提出的研究。我们试图确定人类HCC与新的主要样品与肝组织力学，信号对细胞的机械以及核力学在DNA稳定性和肿瘤生长中的作用的性质。宾夕法尼亚州的五名临床医生经常看到患者或肝病和肝癌样本参与拟议的PSOC PENN，因此影响诊所的机会是有形的。用3 研究项目和2个核心，我们提出了一个多PI领导计划，以最好地代表专业知识和责任的潜水领域：Dennis Discher PhD（Eng'g Appl SCI教授，Grad Appl SCI，Grad Groups Physics，Cell＆Molec Biol）联系PI，Project-3核局部PI，PROPACH PI LEAD，PROCE-3核真菌学：癌细胞系专业知识。 Project-1肝脏力学的Paul Janmey PhD（生理学，物理学和生物工程教授）PI：癌细胞系专业知识。 Core-1肝癌组织和模型的Rebecca Wells医学博士（医学，病理学和实验室医学副教授）PI：肝病机理方面的专业知识。 Core-1肝癌组织和模型的David E. Kaplan MD（助理医学教授和肝病学主任）Co-PI：肝癌的临床专业知识。 Core-2理论的Andrea Liu PhD（物理和化学教授）PI：统计物理建模方面的专业知识。宾夕法尼亚州是一个单一的综合校园，所有实验室在5-10分钟内都参与中心步行，而宾夕法尼亚州医疗中心医院为大费城地区提供服务，该地区是该国较大的肝病中心之一。为了将拟议的PSOC Penn纳入大学在癌症方面的广泛而深刻的努力中，PSOC的所有领导者和教职员工都将成为Penn的艾布拉姆森癌症中心（如果还没有）。艾布拉姆森癌症中心的主任奇·范·丹（Chi Van Dang）教授将成为Pilot Project-1的PI，并将是中心咨询委员会的主要成员。更广泛地说，PSOC Penn将通过教育和宣传各种计划来支持，旨在建立一个充满活力的学生和研究员社区，这些学生体现了多学科方法，以理解癌症的物理学，以改变下一代科学家，工程师和临床医生。