Molecular Imaging of Cachexia in Pancreatic Cancer

胰腺癌恶病质的分子影像

• 批准号: 9026680
• 负责人: Zaver M. Bhujwalla
• 金额: $ 37.06万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9026680
• 关键词: Body Weight decreased; Brain; C-reactive protein; Cachexia; Cells; Cessation of life; Characteristics; Critical Pathways; Databases; Dietary Intervention; Early Diagnosis; Event; Evolution; Exhibits; Fatigue; Fingerprint; Frequencies; Functional Imaging; Future; Heart; Human; Human body; Image; Imaging Techniques; Implant; Inflammation; Kidney; Lead; Liver; Lung; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Malignant neoplasm of pancreas; Metabolic; Metabolism; Modality; Molecular; Mus; Muscle; Muscular Atrophy; Myoblasts; Nature; Normal tissue morphology; Optical reporter; Organ; Pancreas; Pancreatic Ductal Adenocarcinoma; Patients; Pilot Projects; Pre-Clinical Model; Prospective Studies; Quality of life; Refractory; Reporter; Reporting; Research Design; Resected; Resolution; Sampling; Serum; Severities; Skeletal Muscle; Solid Neoplasm; Spleen; Syndrome; System; Therapeutic; Translating; Transplantation; Treatment outcome; Weight; Xenograft Model; Xenograft procedure; base; cancer cachexia; cancer cell; design; effective therapy; human subject; indexing; insight; magnetic resonance spectroscopic imaging; molecular imaging; molecular marker; mortality; non-invasive imaging; novel; optical imaging; public health relevance; red fluorescent protein; reduced food intake; response; tumor; tumor xenograft; volunteer; wasting

 DESCRIPTION (provided by applicant): Cachexia is an underexplored and yet devastating consequence of cancer that is the cause of 20% of all cancer related deaths. Cachexia inducing tumors cause a `wasting away' of the body. Defined as a weight loss of 5% over 3 to 6 months, the condition is associated with poor treatment outcome, fatigue, and extremely poor quality of life. Because of the multi-factorial characteristics of this condition, it has been difficult to understand the impact of the tumor on body organs, and the sequence of events that leads to this lethal condition. To date there are no known cures for this condition. Current molecular and functional imaging approaches are ideally suited to understand critical metabolic changes in the body with the onset of cachexia. Since the syndrome occurs with the highest frequency and severity in pancreatic cancer, we intend to use molecular and functional imaging to understand cancer-induced cachexia and the cachexia cascade in human pancreatic cancer xenografts and human subjects. In Aim1 we will use a myoblast-based reporter system to detect the onset of cachexia in human xenograft models of pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer, and follow temporal changes in organ metabolites noninvasively with 1H MRSI, and in extracts of organs, muscle, and serum with high resolution 1H MRS. In Aim 2 we will validate the most easily translatable 1H MRS indices identified in Aim 1 in a pilot study of 20 normal volunteers, 38 non- cachectic PDAC patients, and 38 cachectic PDAC patients, and evaluate changes in serum in retrospective samples from a data bank, and in prospective studies from the PDAC patients. The studies will reveal new perspectives of this condition that may, in the future, lead to effective treatments. The ability to noninvasively detec this condition early on with noninvasive imaging, preferably before or with minimal weight loss, will provide the opportunity to treat the condition before it becomes refractory, design and optimize therapeutic strategies, and detect response to such treatments.

 描述（由申请人提供）：恶病质是一种未被充分研究但具有破坏性的癌症后果，是所有癌症相关死亡的20%的原因。恶病质诱导肿瘤导致身体的“消耗”。定义为在3至6个月内体重减轻5%，这种情况与治疗效果差，疲劳和生活质量极差有关。由于这种疾病的多因素特征，很难理解肿瘤对身体器官的影响，以及导致这种致命疾病的事件顺序。到目前为止，还没有已知的治愈这种疾病的方法。目前的分子和功能成像方法非常适合于了解恶病质发作时体内的关键代谢变化。由于该综合征在胰腺癌中发生的频率和严重程度最高，因此我们打算使用分子和功能成像来了解人类胰腺癌异种移植物和人类受试者中癌症诱导的恶病质和恶病质级联反应。在Aim 1中，我们将使用基于成肌细胞的报告系统来检测胰腺导管腺癌（PDAC）（最常见的胰腺癌）的人类异种移植模型中恶病质的发作，并使用1H MRSI非侵入性地跟踪器官代谢物的时间变化，以及器官，肌肉，在目标2中，我们将在20名正常志愿者的试点研究中验证目标1中确定的最容易翻译的1H MRS指数，38名非恶病质PDAC患者和38名恶病质PDAC患者，并在来自数据库的回顾性样品和来自PDAC患者的前瞻性研究中评价血清的变化。这些研究将揭示这种疾病的新观点，在未来可能会导致有效的治疗。早期使用非侵入性成像非侵入性地检测这种状况的能力，优选地在体重减轻之前或以最小的体重减轻，将提供在其变得难治之前治疗该状况的机会，设计和优化治疗策略，并检测对这种治疗的反应。