EWING'S SARCOMA--DIFFERENTIATION IN VITRO

尤文氏肉瘤--体外分化

• 批准号: 3963074
• 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/3963074
• 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.

尤因肉瘤的组织起源仍然是个谜，尽管有很多工作要做 阐明它的起源。我们假设尤因的肉瘤，在它通常的情况下 分化状态，缺乏任何已知童年的特定特征 肿瘤。来自其他研究的某些证据，例如 尤文肉瘤中的相互(11：22)染色体易位 周围神经上皮瘤和与面板类似的反应性模式 提示了一种可能的共同的组织发生 这些原本不同的肿瘤。因为神经肿瘤一般都是 已知对诸如二丁酰环AMP之类的差异剂起反应， 神经生长因子和维甲酸的发展特点 分化的神经组织，如神经突起和数量增加的 致密核心颗粒，我们已经治疗了一系列尤文肉瘤细胞 在各种条件下与这些药物进行体外培养，单独和 彼此联合起来。 到目前为止，初步结果强烈表明，至少这些肿瘤 在体外成功培养的细胞具有天生的神经功能 对这些药物的治疗反应的差异性。四个中的四个 这样研究的线条(和之前报道的缺乏任何自发的证据 神经分化，即使在体外生长了一年之后)回应 在培养中产生细长的过程。超微结构检查 这些过程中有致密的核心颗粒。免疫细胞化学 神经元特异烯醇化酶抗血清是一种在神经组织中发现的抗原， 治疗前均为阴性，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，以及单抗反应性模式。