Salivary Biomarkers in the Diagnosis of BRONJ

唾液生物标志物在 BRONJ 诊断中的应用

• 批准号: 8286837
• 负责人: Tara L Aghaloo
• 金额: $ 11.58万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8286837
• 关键词: Advisory Committees; Alveolus; Animal Model; Appearance; Basic Science; Biochemical; Biological Markers; Biological Process; Biopsy; Body Fluids; Bone Diseases; Bone necrosis; Cancer Patient; Cancer Prognosis; Caring; Cell Proliferation; Clinical; Clinical Research; Clinical Sciences; Committee Members; Comorbidity; Complication; Confusion; Debridement; Defensins; Diagnosis; Diagnostic; Diagnostics Research; Dictionary; Diffuse; Disease; Excision; Exhibits; Exposure to; Fistula; Fracture; Functional disorder; Future; Gene Proteins; Genetic Transcription; Goals; Grant; HIV; Hepatitis; Histologic; Histopathology; Human; Hyperbaric Oxygen; Hypercalcemia of Malignancy; Immune response; Immunoglobulins; Impaired wound healing; In Vitro; Incidence; Independent Scientist Award; Individual; Infection; Intravenous; Irregular Bone; Jaw; Jaw Fractures; Knowledge; Laboratories; Liquid substance; Liver neoplasms; Lung Neoplasms; MALDI-TOF Mass Spectrometry; Malignant Neoplasms; Marker Discovery; Mass Spectrum Analysis; Medical; Metabolism; Metastatic Neoplasm to the Bone; Methodology; Modality; Modeling; Monitor; Mouth Diseases; Muramidase; Necrosis; Operative Surgical Procedures; Oral; Oral cavity; Oral health; Osteoclasts; Osteocytes; Pain; Pathogenesis; Patient observation; Patients; Peptides; Periodontal Diseases; Periodontitis; Peroxidases; Pharmaceutical Preparations; Plasma; Prevention; Prevention Protocols; Process; Prostate; Proteins; Proteome; Proteomics; Quality of life; Radiation therapy; Reaction; Recording of previous events; Reporting; Research; Research Infrastructure; Risk; Risk Assessment; Saliva; Salivary; Salivary Proteins; Serum; Severities; Shotguns; Signal Transduction; Sjogren' s Syndrome; Staging; Structure; Swelling; System; Testing; Tooth Diseases; Tooth structure; Training; Trauma; Treatment Protocols; Treatment outcome; Two-Dimensional Gel Electrophoresis; bisphosphonate; bone; cancer diagnosis; candidate marker; cell motility; chemotherapy; clinical Diagnosis; clinically relevant; cost; design; disease diagnosis; improved; in vivo; malignant mouth neoplasm; maxillofacial; oncology; outcome forecast; ovarian neoplasm; pancreatic neoplasm; patient oriented research; programs; proline-rich proteins; response; saliva diagnostic; sample collection

DESCRIPTION (provided by applicant): The overall goal of the K02 independent scientist award is to expand Dr. Aghaloo's current research program with (1) formal and informal training in patient-oriented research and statistical methodology, (2) to gain additional knowledge in the basic and clinical sciences of oncology, and (3) to obtain training in proteomics and biomarkers to perform an exploratory patient-oriented study to identify differentially expressed proteins in the saliva of BRONJ patients at different stages of severity. Her current R01 grant focuses on the pathophysiology of bisphosphonate related osteonecrosis of the jaws (BRONJ), by studying both in vitro mechanisms of osteoclast inhibition by bisphosphonates (BPs) and utilizing a clinically relevant in vivo BRONJ animal model. The research strategy in this K02 application will expand those studies with an exploratory study of salivary proteins and peptides to aid in diagnosis, monitoring, and management of BRONJ patients. Intravenous BPs are commonly used medications to treat primary and metastatic bone cancer. Though BPs reduce fracture risk and reduce hypercalcemia of malignancy, many patients develop ONJ. To date, diagnosis of BRONJ has been clinical, often combined with radiographic studies and biopsies to confirm necrotic bone. Therapy ranges from watchful waiting to medical therapy and conservative debridement to hyperbaric oxygen to extensive jaw resection. Outcomes of these treatment modalities are generally assessed by clinical examination, but confusion of continued exposed and necrotic bone vs. delayed wound healing from surgery are challenging to differentiate. In the era of biomarkers, utilizing serum or salivary body fluids is an attractive approach to aid in diagnosis, monitoring, and evaluating responses to treatment. Human plasma and serum is widely used in disease diagnosis, monitoring, and prognosis, and serum profiling has been well documented for various cancers with high sensitivity. More recently, human salivary proteome analysis has been shown to be important for understanding oral health and disease pathogenesis. Therefore, the objective of the research strategy is to identify and validate candidate salivary biomarkers for BRONJ diagnosis, testing the hypothesis that salivary biomarkers are associated with the clinical diagnosis of BRONJ. To achieve our research strategy objective and test our hypothesis, we propose two specific aims: (1) to identify saliva proteins and peptides from cancer patients with Stage I-III BRONJ and (2) to validate proteomics results and develop candidate markers for Stage I-III BRONJ diagnosis. In addition to identifying saliva biomarkers associated with BRONJ, this grant will result in training, hands-on expertise in clinical research, as well as the establishment of an oncology, biomarker, and proteomics infrastructure to allow Dr. Aghaloo to design future clinical studies, whether for ONJ or other oral diseases.

描述（由申请人提供）：K02独立科学家奖的总体目标是扩展Aghaloo博士目前的研究项目，包括：(1)以患者为导向的研究和统计方法的正式和非正式培训；(2)获得肿瘤学基础和临床科学的额外知识；(3)获得蛋白质组学和生物标志物方面的培训，开展面向患者的探索性研究，鉴定不同严重程度BRONJ患者唾液中的差异表达蛋白。她目前的R01资助重点是通过研究双膦酸盐（bp）抑制破骨细胞的体外机制和利用临床相关的体内BRONJ动物模型，研究双膦酸盐相关颌骨骨坏死（BRONJ）的病理生理学。本K02应用的研究策略将通过对唾液蛋白和肽的探索性研究来扩展这些研究，以帮助BRONJ患者的诊断、监测和管理。静脉注射bp是治疗原发性和转移性骨癌的常用药物。尽管bp可降低骨折风险和恶性肿瘤的高钙血症，但许多患者仍会发生ONJ。迄今为止，BRONJ的诊断一直是临床诊断，通常结合影像学检查和活检来确认坏死骨。治疗范围从观察等待到药物治疗，从保守清创到高压氧再到广泛的下颌切除术。这些治疗方式的结果通常通过临床检查来评估，但混淆持续暴露和坏死骨与手术后延迟伤口愈合是具有挑战性的。在生物标志物时代，利用血清或唾液体液是一种有吸引力的方法来帮助诊断、监测和评估治疗反应。人血浆和血清广泛用于疾病诊断、监测和预后，血清谱分析对各种癌症具有很高的敏感性。最近，人类唾液蛋白质组分析已被证明对了解口腔健康和疾病发病机制很重要。因此，本研究策略的目的是识别和验证BRONJ诊断的候选唾液生物标志物，验证唾液生物标志物与BRONJ临床诊断相关的假设。为了实现我们的研究策略目标并验证我们的假设，我们提出了两个具体目标：(1)鉴定I-III期BRONJ癌症患者的唾液蛋白和肽；(2)验证蛋白质组学结果并开发I-III期BRONJ诊断的候选标记物。除了确定与BRONJ相关的唾液生物标志物外，这笔资助还将导致临床研究方面的培训，实践专业知识，以及建立肿瘤学，生物标志物和蛋白质组学基础设施，以便Aghaloo博士设计未来的临床研究，无论是针对ONJ还是其他口腔疾病。