MABS TO MYOD FAMILY PROTEINS I MYOGENIC TUMOR DIAGNOSIS

MABS 至 MYOD 家族蛋白 I 肌源性肿瘤诊断

• 批准号: 2800099
• 负责人: PETER B DIAS
• 金额: $ 30.26万
• 依托单位: IMGENEX CORPORATION
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2800099
• 关键词: affinity chromatography; cell differentiation; diagnosis design /evaluation; human tissue; monoclonal antibody; myosins; neoplasm /cancer diagnosis; neoplastic cell; prognosis; protein purification; rhabdomyosarcoma; transcription factor

It is difficult to diagnose poorly differentiated rhabdomyosarcomas from other small round cell tumors and to identify subtypes of rhabdomyosarcomas that confer poor prognosis. Through SBIR Phase-I funding we developed and characterized monoclonal antibodies that are highly specific to MyoD, for distinguishing rhabdomyosarcomas from other malignancies. Our preliminary data using a monoclonal antibody to myogenin shows that there is a highly significant difference (p=0.0001) in staining between embryonal and alveolar rhabdomyosarcomas. We have also developed monoclonal antibodies specific to myf5 and myf6. We propose that spatio-temporal patterns of expression of members of the MyoD family (myf5, MyoD, myogenin and myf6) observed during development are reflected in rhabdomyosarcoma and may be responsible for the histologically and clinically distinct subtypes. for the Phase II study we will (1) test the diagnostic utility of monoclonal antibodies to MyoD on a large number of small round, spindle and anaplastic cell, pediatric and adult malignancies. Using the same tumor material we will also test (2) the diagnostic utility of monoclonal antibodies specific to myogenin, myf5 and myf6 for diagnosing rhabdomyosarcomas from other malignancies, (3) for distinguishing between the clinically distinct subtypes of rhabdomyosarcomas and (4) for predicting prognosis. PROPOSED COMMERCIAL APPLICATION: The use of monoclonal antibodies made to a family of tissue specific transcription factors to diagnose and subclassify tumors into clinically distinct prognostic groups is novel. This concept can be applies to various other malignancies. It offers the much needed and simple solution to the surgical pathologists and oncologists to promptly and accurately diagnose tumors and identify aggressive from non-aggressive tumors and will thus be of high commercial value.

诊断低分化横纹肌肉瘤很困难， 其他小圆细胞肿瘤，并确定亚型 预后差的横纹肌肉瘤 通过SBIR第一阶段 资助我们开发和表征单克隆抗体， 高度特异于MyoD，用于区分横纹肌肉瘤和 其他恶性肿瘤。 我们使用单克隆抗体的初步数据 结果显示， （p=0.0001）胚胎和肺泡之间的染色 横纹肌肉瘤 我们还开发了单克隆抗体 Myf 5和Myf 6的特性。 我们提出，时空模式的 MyoD家族成员（myf 5、MyoD、肌细胞生成素和MyoD）的表达 myf 6）在横纹肌肉瘤中得到反映 并可能导致组织学和临床上不同的 亚型 对于II期研究，我们将（1）测试诊断效用 MyoD的单克隆抗体上有大量的小圆， 梭形和间变性细胞，儿童和成人恶性肿瘤。 使用 同样的肿瘤材料，我们也将测试（2）的诊断效用 特异于肌细胞生成素、myf 5和myf 6的单克隆抗体， 诊断横纹肌肉瘤与其他恶性肿瘤，（3） 区分临床上不同的亚型 横纹肌肉瘤;（4）预测预后。 建议的商业应用：单克隆抗体的使用 组织特异性转录因子家族来诊断 并将肿瘤细分为临床上不同的预后组， 小说这一概念也适用于其他各种恶性肿瘤。它 为外科病理学家提供了急需的简单解决方案， 和肿瘤学家及时准确地诊断肿瘤， 从非侵袭性肿瘤中识别侵袭性肿瘤，因此将是 商业价值高。