SPARC--A DIAGNOSTIC MARKER FOR INVASIVE MENINGIOMA

描述：(改编自调查人员的摘要) 相当大比例的良性脑膜瘤进展为不典型 以及无法通过手术治愈的恶性肿瘤。 没有任何标记物可以预测哪些良性肿瘤 进步。此外，没有标记来区分 组织形态上良性的，复发的肿瘤 组织形态良性，但生物侵袭性，侵袭性 肿瘤。此外，没有侵袭性的特异性标记物。这 如果肿瘤/脑界面不存在，则可能会错过表型 用于诊断的样本。这些并发症可能会导致 肿瘤的误诊和分级错误。因此，脑膜瘤 患者可能治疗过度，也可能治疗不足。他们已经确定了SPARC (富含半胱氨酸的酸性分泌蛋白)作为一种基因过度表达 并观察到其在异常细胞中的表达 在原发肿瘤的肿瘤/脑界面的浸润缘 标本。此外，利用异种移植模型，SPARC的表达 在侵袭邻近大鼠脑的人类肿瘤细胞中观察到， 提示SPARC是侵袭性肿瘤细胞的标志物。为了进一步 在其他侵袭性脑瘤中解决这种相关性，他们有 检测SPARC在复发组和非复发组的表达 所有级别的脑膜瘤。他们的初步数据表明，SPARC 脑膜瘤的表达与侵袭性表型有关， 不考虑肿瘤的级别。该提案旨在确定SPARC是否 过度表达是脑膜瘤侵袭性的指标(在 体内和体外)，从而提供了一种客观的诊断标志物 鉴别那些组织学上良性但生物学上为良性的患者 侵袭性、侵袭性肿瘤，从而识别出 需要辅助治疗和密切随访的个体。特定的 目的1：确定SPARC过度表达是否可作为诊断 脑膜瘤侵袭性标记物的免疫组织形态学和免疫组织化学研究 原发肿瘤标本的组织病理学分析。具体目标2： 确定SPARC在体内的过表达水平 用密度计法研究肿瘤细胞在体外的迁移情况 Northern印迹分析、Western印迹分析和细胞迁移分析 相应的原代肿瘤细胞系。

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.