Development of an Assay for the Early Detection of Ovarian Cancer

描述（由申请人提供）：本提案解决了缺乏简单可靠的卵巢癌早期检测方法的问题。设计和创造相对便宜和坚固的材料用于常规LPA（溶血磷脂酸）筛选描述。所建议的方法是为训练最少的人员最终使用而设计的。该项目汇集了化学传感、材料制造、荧光光谱和妇科肿瘤学方面的专家。LPA目前是一种有争议的早期卵巢癌生物标志物。所提出的努力至少将促进LPA的进一步研究，并体现一个独特的视角，以帮助回答有关LPA在盆腔肿块分诊、卵巢癌诊断和疾病复发监测中的相关性的重要问题。此外，LPA相关酶活性筛选是药物开发的必要条件，LPA监测在动脉粥样硬化和相关血管疾病中也具有明显的临床应用价值。因此，提出的研究显然会产生对生物医学界有意义的发现。具体目标有三个：LPA选择性化学传感器的研究。LPA的独特结构将导致高选择性、仿生结合和传感试剂的设计。具体目标2。使用量身定制的固体支架，以提高生物介质中LPA的选择性和灵敏度。LPA选择性聚合材料将用于预先浓缩LPA，并在Aim 1中描述的选择性指示剂分析之前简化分析基质。具体目标3。方法采用人血、尿样进行验证。本特定目的的目的是验证(i)通过与现有技术的比较，提出的LPA检测方法，以及（ii） LPA作为诊断为盆腔肿块的女性的生物标志物。公共卫生相关性：卵巢癌是影响妇女的最致命的癌症之一。这是由于无法检测到它，而它仍然局限于卵巢。早期发现会导致90%的存活率。LPA是目前有争议的卵巢癌诊断生物标志物，是该应用的主题。一种简单的检测LPA的新方法和一种验证LPA作为准确生物标志物可靠性的新方法将从拟议的研究中产生。

DESCRIPTION (provided by applicant): This proposal addresses the lack of simple and reliable methods for the early detection of ovarian cancer. The design and creation of relatively inexpensive and robust materials for the routine LPA (lysophosphatidic acid) screening are described. The proposed methods are designed for eventual use by minimally-trained personnel. The project brings together experts in chemosensing, materials fabrication, fluorescence spectroscopy and gynecological oncology. LPA is currently a controversial biomarker for early stage ovarian cancer. The proposed efforts will, at the very least, enable further LPA research and also embody a unique perspective to help answer significant questions concerning LPA's relevance in pelvic mass triaging, ovarian cancer diagnosis, and monitoring for disease recurrence. In addition, LPA-associated enzyme activity screening is needed for pharmaceutical development, and LPA monitoring is also of apparent clinical utility in atherosclerosis and related vascular disorders. Thus, the study proposed would clearly produce findings of significance to the biomedical community. There are three Specific Aims: Specific Aim 1. The investigation of selective chemosensors for LPA. The unique structure of LPA will lead to the design of highly selective, biomimetic binding and sensing reagents. Specific Aim 2. The use of tailored solid supports to enhance selectivity and sensitivity for LPA in biological media. LPA-selective polymeric materials will be used to pre-concentrate LPA and simplify the analytical matrix prior to analysis by the selective indicator reagents described in Aim 1. Specific Aim 3. Methods validation using human blood and urine samples. The goals of this Specific Aim are to validate (i) the proposed assay for LPA via comparison to established techniques, and (ii) LPA as a biomarker for triaging women diagnosed with a pelvic mass. PUBLIC HEALTH RELEVANCE: Ovarian cancer is one of the most lethal cancers affecting women. This is due to the inability to detect it while still localized to the ovaries. Early detection would result in a 90 % survival rate. LPA, a currently controversial biomarker for ovarian cancer diagnosis, is the subject of this application. A simple new method for detecting LPA and a fresh approach to validating LPA's reliability as an accurate biomarker would emanate from the proposed studies.