权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterizing Prostate Cancer By ex vivo MRS Signatures

通过离体 MRS 特征表征前列腺癌

基本信息

批准号：
9248210
负责人：
Leo L Cheng
金额：
$ 55.64万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-27 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9248210
关键词：
Address Adjuvant Therapy African American Age Benign Biochemical Biological Biopsy Blood Screening Cancer Detection Cancer Diagnostics Cancer Patient Cancerous Clinic Clinical Clinical Management Diagnosis Diagnostic Errors Dimensions Disease Early Diagnosis Enzymes Evaluation Exploratory/Developmental Grant for Diagnostic Cancer Imaging Fresh Tissue Funding Gland Gleason Grade for Prostate Cancer Growth Histologic Histology Human Incidence Indolent Institution Location Magic Magnetic Resonance Spectroscopy Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate Maps Measures Messenger RNA Metabolic Metabolic Marker Operative Surgical Procedures Outcome PSA Velocity Pathologic Pathology Patient Recruitments Patient-Focused Outcomes Patients Process Prospective Studies Prostate Prostate-Specific Antigen Prostatectomy Prostatic Neoplasms Protocols documentation Protons Quality of life Recurrence Resolution Sampling Sampling Errors Sensitivity and Specificity Serum Site Spatial Distribution Structure of base of prostate Survival Rate Techniques Testing Time Tissue Sample Tissues Translations Work androgen deprivation therapy cancer recurrence cancer risk cancer statistics cancer therapy clinically significant follow-up genetic profiling histological specimens human study improved individual patient laser capture microdissection metabolomics neoplastic novel diagnostics pre-clinical prognostic public health relevance response sample collection success treatment response treatment strategy tumor tumor growth

项目摘要

DESCRIPTION (provided by applicant): Serum prostate specific antigen testing improved early detection of prostate tumors, increased diagnosed prostate cancer (PCa) incidence, and shifted newly detected PCa treatment to earlier stages. These successes also generated controversies for effective management of earlier-stage PCa, chiefly: (1) the all-too-common false-negative biopsy finding through tissue sampling errors in asymptomatic patients who harbor small, heterogeneously distributed PCa; and (2) the uncertain malignant potential of most newly detected tumors, with PCa pathologies similar at biopsy but which PCa statistics indicate will trace drastically different disease paths. Greater sensitivity/specificity for PCa diagnostic and prognostic approaches would address both these urgent needs. Our original R01 studies used high resolution magic-angle-spinning proton magnetic resonance spectroscopy (HRMAS 1HMRS), which we developed to permit intact tissue analysis and correlation with pathology, in order to produce proof-of-concept PCa metabolic markers. We then developed PCa metabolomics and demonstrated that PCa metabolomic profiles improve accuracy in PCa detection, diagnosis, and characterization. Profile analyses of histologically-defined benign prostate tissue from PCa patients allowed us to identify PCa pathological stage and predict PCa recurrence by showing the existence of delocalized PCa metabolomic field-effects, or metabolomic fields. These PCa metabolomic fields: 1) yield measures of PCa signatures in histo-benign tissue and thus are likely to reduce histological sampling errors by indicating PCa presence for patients with false-negatives biopsies, and 2) have the capacity to predict PCa malignant potential for patients with positive biopsies. Thus PCa metabolomic fields are likely to contribute most significantly to the PCa clinic by distinguishing aggressive from indolent disease and informing treatment strategies through markers that support active surveillance for indolent tumors or suggest that the patient harbors an aggressive PCa and needs timely institution of adjuvant therapies. These significant outcomes from our original R01 studies comprise the basis for our renewal application, in which we propose: (1) to systematically investigate spatial distributions of PCa metabolites and metabolomic profiles localized at and delocalized beyond their pathological origins in PCa glands to precisely define PCa metabolomic field markers; (2) to use banked PCa tissue samples with known clinical outcomes to test PCa metabolomic profile predictions of PCa growth rate and biochemical recurrence and therapy response, as well as to analyze different pathological components associated with genetic profiles from these same samples via laser capture microdissection and real-time quantitative PCR; and (3) to establish, through longitudinal patient follow-up, the prognostic ability of PCa metabolites, metabolomic profiles, and metabolomic fields as metabolomic criteria that answer the ultimate challenges of the current PCa clinic by predicting PCa risk for biopsy-negative patients and the suitability of entering active surveillance for biopsy-positive patients.

描述（由申请人提供）：血清前列腺特异性抗原检测改善了前列腺肿瘤的早期检测，增加了诊断的前列腺癌（PCa）发生率，并将新检测到的PCa治疗转移到早期阶段。这些成功也对早期PCa的有效管理产生了争议，主要是：（1）在具有小的、不均匀分布的PCa的无症状患者中，由于组织采样错误而导致的非常常见的假阴性活检结果;以及（2）大多数新检测到的肿瘤的不确定恶性潜力，PCa病理学在活检时相似，但PCa统计学表明将追踪截然不同的疾病路径。PCa诊断和预后方法的更高灵敏度/特异性将解决这两个迫切的需求。我们最初的R 01研究使用高分辨率魔角旋转质子磁共振波谱（HRMAS 1HMRS），我们开发该技术以允许完整组织分析和与病理学的相关性，以产生概念验证的PCa代谢标志物。然后，我们开发了PCa代谢组学，并证明了PCa代谢组学谱提高了PCa检测，诊断和表征的准确性。PCa患者的组织学定义的良性前列腺组织的轮廓分析允许我们通过显示离域PCa代谢组学场效应或代谢组学场的存在来识别PCa病理阶段并预测PCa复发。这些PCa代谢组学字段：1）产生组织良性组织中PCa特征的测量，因此可能通过指示具有假阴性活检的患者的PCa存在来减少组织学采样误差，以及2）具有预测具有阳性活检的患者的PCa恶性潜力的能力。因此，前列腺癌代谢组学领域可能有助于最显着的前列腺癌临床区分侵略性惰性疾病和通知治疗策略，通过标记物，支持积极监测惰性肿瘤或建议患者窝藏侵略性前列腺癌，需要及时的辅助治疗。我们最初的R 01研究的这些重要结果构成了我们更新申请的基础，其中我们提出：（1）系统地研究PCa代谢物的空间分布和在PCa腺体中定位于和离域于其病理起源之外的代谢组学谱，以精确地定义PCa代谢组学场标记;（2）使用具有已知临床结果的库存PCa组织样品来测试PCa代谢组学谱预测PCa生长速率和生化复发和治疗反应，以及通过激光捕获显微切割和实时定量PCR分析来自这些相同样品的与遗传谱相关的不同病理组分;和（3）通过纵向患者随访建立PCa代谢物的预后能力，代谢组学特征，和代谢组学领域作为代谢组学标准，通过预测活检的PCa风险来应对当前PCa临床的最终挑战-阴性患者以及对活检阳性患者进行主动监测的适宜性。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Applications of high-resolution magic angle spinning MRS in biomedical studies II-Human diseases.

高分辨率魔角旋转MRS在生物医学研究中的应用II-人类疾病

DOI：
10.1002/nbm.3784
发表时间：
2017-11
期刊：
NMR in biomedicine
影响因子：
2.9
作者：
Dietz C;Ehret F;Palmas F;Vandergrift LA;Jiang Y;Schmitt V;Dufner V;Habbel P;Nowak J;Cheng LL
通讯作者：
Cheng LL

Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and mass spectrometry.

DOI：
10.1007/s00259-013-2379-x
发表时间：
2013-07
期刊：
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
影响因子：
9.1
作者：
Spur, Eva-Margarete;Decelle, Emily A.;Cheng, Leo L.
通讯作者：
Cheng, Leo L.

Metabolomic Prediction of Human Prostate Cancer Aggressiveness: Magnetic Resonance Spectroscopy of Histologically Benign Tissue.

DOI：
10.1038/s41598-018-23177-w
发表时间：
2018-03-26
期刊：
Scientific reports
影响因子：
4.6
作者：
Vandergrift LA;Decelle EA;Kurth J;Wu S;Fuss TL;DeFeo EM;Halpern EF;Taupitz M;McDougal WS;Olumi AF;Wu CL;Cheng LL
通讯作者：
Cheng LL

Magnetic resonance spectroscopy: A promising tool for the diagnostics of human prostate cancer?