EWING'S SARCOMA--DIFFERENTIATION IN VITRO

尤因氏肉瘤--体外分化

• 批准号: 3916378
• 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/3916378
• 关键词: Ewing's tumor; antineoplastics; cell differentiation; cellular oncology; chromosome translocation; cyclic AMP; electron microscopy; histochemistry /cytochemistry; human tissue; immunochemistry; immunocytochemistry; monoclonal antibody; neoplasm /cancer immunology; neoplasm /cancer pharmacology; neurotrophic factors; pediatric neoplasm /cancer; phosphopyruvate hydratase; retinoate; tissue /cell culture

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 con- junction 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.

尤文氏肉瘤的组织发生仍然是个谜，尽管有很多 努力阐明它的起源。 我们假设尤因 肉瘤，在其通常的分化状态，缺乏任何特定的， 已知的儿童肿瘤的特征。 某些证据来自 其他的研究，如互惠的存在（11：22） 尤文肉瘤和外周血淋巴细胞染色体易位 神经上皮瘤，以及与面板相似的反应模式 单克隆抗体的研究表明， 这些不同肿瘤的组织发生。 由于神经 通常已知肿瘤对分化剂有反应 如二丁酰环AMP、神经生长因子和视黄酸 酸通过发展分化的神经组织的特征， 随着神经突和致密核心颗粒数量的增加， 在体外用以下物质处理一系列尤文肉瘤肿瘤细胞系 这些代理人在各种条件下，单独和在CON- 彼此的结合。 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， 在神经组织中发现的抗原在治疗前是阴性的， 之后在所有四条线上都是阳性的。 这些初步结果是 通过其他技术证实，包括儿茶酚胺 荧光，神经递质酶谱，细胞外 基质合成研究和单克隆抗体的模式 反应性