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

GM-CSF抑制乳腺癌生长和转移的机制

• 批准号: 8131794
• 负责人: Timothy D Eubank
• 金额: $ 24.15万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8131794
• 关键词: Address; Angiogenic Switch; Award; Cancer Patient; Cells; Collaborations; Data; Dose; Endothelium; Evaluation; Excision; Gene Expression Profile; Granulocyte-Macrophage Colony-Stimulating Factor; Growth; Human; Immune; Immunodeficient Mouse; Instruction; Investigation; Leukocytes; Liposomes; Mammary Neoplasms; Metastatic Neoplasm to the Lung; Methods; Modification; Mononuclear; Neoplasm Metastasis; Nude Mice; Outcome; Oxygen; Patients; Phagocytes; Phase; Phenotype; Physiological; Primary Neoplasm; Production; Proteomics; Recovery; Tumor Angiogenesis; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factors; Woman; angiogenesis; base; cell type; chemotherapy; fighting; killings; macrophage; malignant breast neoplasm; meetings; monocyte; neoplastic cell; outcome forecast; parent grant; programs; receptor; response; success; tumor; tumor growth

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.

奖项即将到来的ROO阶段的计划包括使用特定目标2的最终确定 克隆的脂质体作为单核吞噬细胞去除的替代方法（如在 “对施舍的变化”，完成特定目标3对GM-CSF对增长的影响的完成， 血管生成和免疫缺陷小鼠人类乳腺癌的转移，并进一步研究 响应GM-CSF治疗而产生的单核细胞和巨噬细胞亚群。 因此，具体目的将解决以下问题： 中央假设（原始修改）：GM-CSF处理诱导肿瘤的表型转换 浸润单核吞噬细胞和触发抗血管生成计划。 特定目标2（来自父授予）：确定负责SVEGFR-1产生的单元 对GM-CSF的响应。 特定目标3（来自父授予）：GM-CSF是否抑制肿瘤生长，血管生成和转移 裸鼠的人类肿瘤？ 基于父母赠款和/或协作产生的初步数据的新目标： 特定目的4：确定GM-CSF是否使用单核吞噬细胞表型改变 基因表达特征和蛋白质组学评估。