EWING'S SARCOMA--DIFFERENTIATION IN VITRO

尤文氏肉瘤--体外分化

• 批准号: 4691907
• 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/4691907
• 关键词: Ewing's tumor; cell differentiation; cellular oncology; chromosomes; cyclic AMP; human tissue; immunochemistry; monoclonal antibody; neoplasm /cancer immunology; neurotrophic factors

This histogenesis of Ewing's sarcoma remains enigmatic, despite much work to elucidate it 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.

尽管做了很多工作，但尤因肉瘤的组织发生仍然是个谜 来阐明它的起源。 我们假设尤因氏肉瘤 通常的分化状态，缺乏已知的任何特定特征 儿童肿瘤。 来自其他研究的某些证据，例如 尤文氏症中存在相互 (11:22) 染色体易位 肉瘤和周围神经上皮瘤，以及类似的反应模式 与单克隆抗体组，提出了一个可能的共同点 这些不同肿瘤的组织发生。 由于神经肿瘤 众所周知，一般都会对二丁酰等分化剂做出反应 环磷酸腺苷、神经生长因子和视黄酸通过开发功能 分化的神经组织，如神经突和数量增加 致密核心颗粒，我们治疗了一系列尤文氏肉瘤肿瘤细胞 在各种条件下，单独使用这些药物和 彼此结合。 迄今为止，初步结果强烈表明至少那些肿瘤 在体外成功生长的细胞本质上具有神经功能 对这些药物治疗的反应发生分化。 四之四 如此研究的线（并且之前报道缺乏任何自发证据） 神经分化的反应，即使在体外生长一年后） 在文化中产生细长的过程。 超微结构检查 这些过程揭示了致密的核心颗粒。 免疫细胞化学 神经元特异性烯醇化酶（神经组织中发现的一种抗原）的抗血清 所有四个系在治疗前均为阴性，但治疗后均为阳性。 这些初步结果正在通过其他技术得到证实，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反应性模式。