The Mechanisms of GM-CSF Inhibition of Breast Cancer Growth and Metastasis

该奖项即将到来的Roo阶段的计划包括使用 克隆化脂质体作为去除单核巨噬细胞的替代方法 “对救济的改变”)，完成关于GM-CSF对生长的影响的具体目标3， 免疫缺陷小鼠人乳腺癌的血管生成和转移及其进一步研究 转化为GM-CSF治疗后产生的单核细胞和巨噬细胞亚群。 因此，具体目标将涉及以下问题： 中心假说(原始修改)：GM-CSF治疗诱导肿瘤表型转换 渗入单核巨噬细胞并触发抗血管生成程序。 具体目标2(来自父母赠款)：确定在 对GM-CSF的反应。 特定目标3(来自Parent Grant)：GM-CSF是否抑制肿瘤生长、血管生成和转移 在裸鼠身上发现人类肿瘤吗？ 基于母公司拨款和/或合作产生的初步数据的新目标： 特定目标4：确定GM-CSF是否改变单核巨噬细胞表型 基因表达特征和蛋白质组学评价。

The plan for the upcoming ROO phase of the award includes finalization of Specific Aim 2 using the clodronated liposomes as an alternate method for mononuclear phagocyte removal {as discussed In "Changes made to alms'), completion of Specific Aim 3 on the effects of GM-CSF on the growth, angiogenesis, and metastases in human breast cancer in immunodeficient mice, and further investigation into monocyte and macrophage subpopulations generated in response to GM-CSF treatment. Thus the Specific Aims will address the following questions: Central Hypothesis (modification from original): GM-CSF treatment induces a phenotype switch In tumor infiltrating mononuclear phagocytes and triggers an anti-angiogenic program. Specific Aim 2 (from parent grant): To determine the cells responsible for sVEGFR-1 production in response to GM-CSF. Specific Aim 3 (from parent grant): Does GM-CSF Inhibit tumor growth, angiogenesis, and metastases of human tumors in nude mice? New Aims based on preliminary data generated from the parent grant and/or collaboration: Specific Aim 4: To determine if GM-CSF changes mononuclear phagocyte cell phenotypes using gene expression signatures and proteomic evaluation.