SPARC--A DIAGNOSTIC MARKER FOR INVASIVE MENINGIOMA

描述：（改编自研究者摘要） 相当一部分良性脑膜瘤进展为非典型脑膜瘤， 以及外科手术难以治愈的恶性肿瘤。 没有标记物可以预测哪些良性肿瘤会 中求进工作总此外，没有标记来区分 组织形态学良性，复发性肿瘤， 组织形态学上良性，但生物学上具有侵袭性， 肿瘤的此外，没有侵袭性特异性标志物。这 如果肿瘤/脑界面不存在，则可能会错过表型。 用于诊断的标本。这些并发症可能导致 肿瘤的误诊和错误分级。因此，脑膜瘤 患者可能被过度治疗或治疗不足。他们已经确定了 （分泌的蛋白质呈酸性且富含半胱氨酸）作为过表达的基因 在星形细胞肿瘤中的表达，并观察到其在异常细胞中的表达 在原发性肿瘤的肿瘤/脑界面的浸润边缘 标本此外，使用异种移植模型， 在侵入邻近大鼠脑的人肿瘤细胞中观察到， 这表明，p53是侵袭性肿瘤细胞的标志物。进一步 为了解决其他侵袭性脑肿瘤中的这种相关性， 在复发性和非复发性的一个子集中检查了表达 所有级别的脑膜瘤。他们的初步数据表明， 表达与脑膜瘤的侵袭性表型相关， 不管肿瘤的等级如何。该提案旨在确定 过表达作为脑膜瘤侵袭性的指标（在 体内和体外），从而提供了用于诊断的客观诊断标志物。 识别那些组织学上良性但生物学上 侵袭性肿瘤，从而识别出那些 需要辅助治疗和密切随访的个体。具体 目的1：确定过度表达是否可作为诊断 脑膜瘤侵袭的标志物，使用免疫组织形态学和 原发性肿瘤标本的组织病理学分析。具体目标二： 为了确定在体内是否存在过表达的HSP70的水平， 与体外肿瘤细胞迁移相关，使用密度计 北方印迹分析、蛋白质印迹分析和细胞迁移测定 相应的原发肿瘤细胞系。

DESCRIPTION: (adapted from the investigator's abstract) A significant proportion of benign meningiomas progress into atypical and malignant tumors that are surgically intractable and incurable. There are no markers that will predict which benign tumors will progress. In addition, there are no markers to distinguish the histomorphologically benign, recurrent tumors from the histomorphologically benign, but biologically aggressive, invasive tumors. Furthermore, there are no invasive-specific markers. This phenotype may be missed if the tumor/brain interface is not present on the specimen used for diagnosis. These complications may lead to misdiagnosis and misgrading of the tumor. Consequently, menigioma patients may be either over-or under treated. They have identified SPARC (secreted protein acidic and rich in cysteine) as a gene over-expressed in astrocytic tumors and have observed its expression in abnormal cells at the infiltrating edge of the tumor/brain interface in primary tumor specimens. In addition, using a xenograft model, the expression of SPARC was observed in human tumor cells invading adjacent rat brain, suggesting that SPARC is a marker of invasive tumor cells. To further address this correlation in other invasive brain tumors, they have examined SPARC expression in a subset of recurrent and non-recurrent meningiomas of all grades. Their preliminary data suggest that SPARC expression is associated with the invasive phenotype in meningioma, regardless of tumor grade. This proposal aims to determine whether SPARC over expression serves as an indicator of meningioma invasiveness (in vivo and in vitro), thereby providing an objective diagnostic marker for identifying those patients with histologically benign but biologically aggressive, invasive tumors and consequently identifying those individuals in need of adjuvant therapy and close follow-up. Specific Aim 1: To determine whether SPARC over expression serves as a diagnostic marker for invasion in meningiomas, using immunohistomorphological and histopathological analyses of primary tumor specimens. Specific Aim 2: To determine whether the level of SPARC overexpression in vivo correlates with tumor cell migration in vitro, using demsitometric northern blot analyses, western blot analyses, and cell migration assays of the corresponding primary tumor cell lines.