EWING'S SARCOMA--DIFFERENTIATION IN VITRO

尤因氏肉瘤--体外分化

• 批准号: 3939349
• 负责人: T J TRICHE
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3939349
• 关键词: Ewing's tumor; cell differentiation; cellular oncology; chromosome translocation; cyclic AMP; electron microscopy; histogenesis; human tissue; immunochemistry; monoclonal antibody; neoplasm /cancer immunology; neurotrophic factors; phosphopyruvate hydratase; retinoate

The histogenesis of Ewing's sarcoma remains enigmatic, despite much work to elucidate its origins. We have assumed that Ewing's sarcoma, in its usual state of differentiation, lacks any specific features of known childhood tumors. Certain lines of evidence from other studies, such as the presence of a reciprocal (11:22) chromosomal translocation in Ewing's sarcoma and peripheral neuroepithelioma, and similar patterns of reactivity with panels of monoclonal antibodies, have suggested a possible common histogenesis for these otherwise dissimilar tumors. Since neural tumors in general are known to respond to differentiating agents such as dibutyryl cyclic AMP, nerve growth factor, and retinoic acid by developing features of differentiated neural tissues such as neurites and increased numbers of dense core granules, we have treated a series of Ewing's sarcoma tumor cell lines in vitro with these agents under a variety of conditions, alone and in conjunction with one another. To date, the initial results strongly suggest that at least those tumors which are successfully grown in vitro are intrinsically capable of neural differentiation in response to treatment with these agents. Four of four lines so studied (and reported previously to lack any spontaneous evidence of neural differentiation, even after year of growth in vitro) responded by producing long, slender processes in culture. Ultrastructural examination of these processes revealed dense core granules. Immunocytochemistry with antisera to neuron-specific enolase, an antigen found in neural tissue, was negative prior to treatment but positive afterwards in all four lines. These initial results are being confirmed with other techniques, including catecholamine fluorescence, neurotransmitter enzyme profiles, extracellular matrix synthesis studies, and patterns of monoclonal antibody reactivity.

尤文肉瘤的组织发生仍然是个谜，尽管 许多工作来解释它的起源。 吾等已假设 尤文氏肉瘤在其通常的分化状态下， 已知儿童肿瘤的具体特征。 某些线条 来自其他研究的证据，例如存在互惠 (11：22）尤文肉瘤中的染色体易位， 周围神经上皮瘤和类似的反应模式 与单克隆抗体的面板，已经提出了一个可能的 共同的组织发生。 由于神经肿瘤一般都是对 分化剂如二丁酰环AMP、神经 生长因子和视黄酸， 分化的神经组织，如神经突， 许多致密的核心颗粒，我们已经处理了一系列的 尤文氏肉瘤肿瘤细胞系在体外与这些药物在 各种各样的条件，单独和结合一个 另 到目前为止，初步结果强烈表明，至少那些 在体外成功生长的肿瘤本质上 能够响应于用以下物质处理而神经分化： 这些代理人。 四条线中的四条进行了研究（并报告 以前缺乏任何自发的神经证据， 分化，即使在体外生长一年后）， 在培养中产生细长的突起。 超微结构 对这些过程的检查显示出致密的核心颗粒。 神经元特异性烯醇化酶抗血清免疫细胞化学， 一种在神经组织中发现的抗原， 治疗后，所有四条线均呈阳性。 这些初始 结果正在用其他技术证实，包括 儿茶酚胺荧光，神经递质酶谱， 细胞外基质合成的研究，以及 单克隆抗体反应性。