DIAGNOSTIC ELECTRON MICROSCOPY AND PEDIATRIC PATHOLOGY

诊断电子显微镜和儿科病理学

• 批准号: 2464536
• 负责人: M TSOKOS
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2464536
• 关键词: Ewing's tumor; cell growth regulation; child (0-11); clinical research; clinical trial phase I; colony stimulating factor; colorectal neoplasms; dendritic cells; diagnosis design /evaluation; diagnosis quality /standard; diagnosis service; electron microscopy; health care referral /consultation; human subject; human therapy evaluation; human tissue; immunomodulators; leukocyte activation /transformation; meeting /conference /symposium; melanoma; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer pharmacology; neoplasm /cancer remission /regression; pediatric neoplasm /cancer; prognosis; tumor necrosis factor alpha

The purpose of this protocol is to examine the toxicity and immuno- modulatory activity of GM-CSF and TNF in pts. with advanced cancer. The combination of GM-CSF and TNF stimulates the maturation of dendritic cells from CD34+ bone marrow progenitor cells in vitro. TNF has a two-fold function in the maturation of dendritic cells, it up-regulates the expression of the GM-CSF receptor on bone marrow progenitors and prevents their maturation into granulocytes. Dendritic cells are the most potent antigen presenting cells of the immune system. They function as initiators in organ transplant rejection, major histocompatibility restricted T cell responses and in the formation of antibodies dependent on T cells. Dendritic cells are found in small numbers in many tissues and in peripheral blood. This study will examine the activity of TNF and GM-CSF to stimulate the maturation and function of dendritic cells. Epidermal Langerhans cells were quantitated by S100 staining and peripheral blood mononuclear dendritic cell precursors by dendritic CFU assay in methy- cellulose. S100+ cells in the epidermis doubled after treatment (2.55 before treatment to 5.98 after treatment, p=0.029). Dendritic colony forming units in peripheral blood were increased after treatment in 3 patients with colorectal cancer but were not increased in pts. with melanoma. The major goal of this protocol is to determine whether the combination of GM-CSF and TNF causes maturation of dendritic cells and increases their number in the blood, bone marrow and skin and to determine if this increase produces tumor regressions.

该方案的目的是检查毒性和免疫力 PTS中GM-CSF和TNF的调节活性。患有晚期癌症。 这 GM-CSF和TNF的组合刺激树突状细胞的成熟 来自CD34+骨髓祖细胞的体外。 TNF有两个倍 在树突状细胞的成熟中起作用，它上调了 GM-CSF受体在骨髓祖细胞上的表达并防止 它们成熟成粒细胞。 树突状细胞是最有效的 免疫系统的抗原呈现细胞。它们是发起人 在器官移植排斥反应中，主要的组织兼容性限制了T细胞 反应和抗体的形成取决于T细胞。 树突状细胞在许多组织中发现少量 外周血。 这项研究将检查TNF和GM-CSF的活性 刺激树突状细胞的成熟和功能。 表皮 通过S100染色和外周血对兰格汉斯细胞进行定量 通过树突状CFU测定在甲基甲基甲基的单核树突状细胞前体 纤维素。 表皮中的S100+细胞在处理后加倍（2.55 治疗后治疗前，P = 0.029）。 树突状殖民地 治疗后，外周血中的形成单位增加了3 结直肠癌的患者，但PT中没有增加。和 黑色素瘤。 该协议的主要目的是确定是否是否 GM-CSF和TNF的组合导致树突状细胞的成熟和 增加血液，骨髓和皮肤的数量，并确定 如果这种增加会产生肿瘤回归。