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

项目总结（参见Inslfunclons）： 即将到来的ROO阶段的计划包括使用 氯膦酸化脂质体作为单核吞噬细胞去除的替代方法（如在 “对救济金的修改”），完成关于GM-CSF对生长的影响的具体目标3， 免疫缺陷小鼠中人乳腺癌的血管生成和转移，以及进一步的研究 转化为响应GM-CSF处理产生的单核细胞和巨噬细胞亚群。 因此，具体目标将解决以下问题： 中心假设（原始修改）：GM-CSF治疗诱导肿瘤表型转换 浸润单核吞噬细胞并触发抗血管生成程序。 具体目标2（fmm亲本gmnt）：确定在细胞中负责sVEGFR-1产生的细胞。 对GM-CSF的反应。 具体目标3（来自母基金）：GM-CSF是否抑制肿瘤生长、血管生成和转移 在裸鼠体内的肿瘤细胞 新目标基于从母基金和/或合作产生的初步数据： 具体目的4：使用以下方法确定GM-CSF是否改变单核吞噬细胞表型： 基因表达特征和蛋白质组学评估。

PROJECT SUMMARY (See Inslfucllons): 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 (fmm parent gmnt): 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.