Inter-alpha Inhibitors in Detecting CNS Cancer

描述（由申请人提供） 总体目标是开发一种基于脑脊液（CSF）中α间抑制蛋白（laIp）的可销售的新型预测标记物，可用于CNS癌症的管理。原发性和转移性中枢神经系统癌症以及软脑膜受累患者的成本效益护理、症状的成功缓解和新的治疗见解在很大程度上取决于可靠的诊断测试和结局指标。现代神经影像学对中枢神经系统肿瘤的早期诊断和后续监测是有用的。然而，这些研究是昂贵的，并受到假阴性和假阳性结果的限制。脑脊液细胞学检查是诊断软脑膜癌病的“金标准”。不幸的是，假阴性结果非常常见。目前，没有生物化学标记物可以检测原发性和转移性CNS癌症的存在或活性。在我们的初步研究中，当用特异性抗人IaIp的单克隆抗体通过蛋白质印迹分析CNS癌症患者的CSF时，IaIp的水平相对于来自非癌症对照患者或来自没有可证实的CNS疾病的系统性癌症的那些大大升高。 IaIp的水平表明与肿瘤负荷和疾病进展以及对治疗的反应相关，提高了IaIp作为敏感指标的潜力。与常规CSF细胞学相比，CSF中laIp的检测似乎是CSF中肿瘤细胞存在的更准确的预测因子。 在本提案中，我们将专注于开发一种灵敏的定量测定和一种快速的半定量免疫测定形式，可以在没有仪器的情况下使用。 我们将确定CSF中IaIp水平的测量是否允许早期检测和随后监测原发性和转移性CNS恶性肿瘤，以及CSF IaIp水平是否有助于准确预测治疗反应和生存。

DESCRIPTION (provided by applicant) The overall goal is to develop a marketable novel predictive marker based on inter-alpha inhibitor proteins (laIp) in cerebrospinal fluid (CSF) that can be utilized in the management of CNS cancer. Cost effective care, successful palliation of symptoms and new therapeutic insights for patients with primary and metastatic CNS cancer as well as with the involvement of leptomeninges depend largely on reliable diagnostic tests and outcome measures. Modem neuroimaging is useful in early diagnosis and subsequent monitoring of patients with CNS cancer. However, these studies are expensive and are limited by false negative and false positive findings. CSF cytology is the "gold standard' diagnosis for leptomeningeal carcinomatosis. Unfortunately, false-negative results are very common. Currently, there are no biochemical markers that can detect the presence or activity of primary and metastatic CNS cancer. In our preliminary studies, when the CSF of CNS cancer patients were analyzed by Westernblot with a monoclonal antibody specific against human laIp, the levels of lalp were greatly elevated relative to those from non-cancer control patients or from systemic cancers without demonstrable CNS disease. The levels of IaIp suggest correlation with tumor burden and disease progression as well as response to therapy, raising the potential of lalp as a sensitive indicator. The detection of laIp in CSF seems to be a more accurate predictor of the presence of tumor cells in the CSF than conventional CSF cytology. In this proposal, we will focus on the development of a sensitive quantitative assay and a rapid semi quantitative immunoassay format that can be used without instrumentation. We will determine whether measurement of lalp levels in CSF allows for early detection and subsequent monitoring of primary and metastatic CNS malignancies and whether CSF IaIp levels facilitate an accurate prediction of treatment response and survival.