MABS TO MYOD FAMILY PROTEINS I MYOGENIC TUMOR DIAGNOSIS

低分化横纹肌肉瘤的诊断比较困难。 其他小圆形细胞肿瘤，并鉴定其亚型 具有不良预后的横纹肌肉瘤。通过SBIR-I期 资助我们开发并鉴定了单抗 对MyoD高度特异，用于区分横纹肌肉瘤和 其他恶性肿瘤。我们用一种单抗获得的初步数据 对肌生成素的检测结果显示有非常显著的差异 胚胎与肺泡间染色(P=0.0001) 横纹肌肉瘤。我们还研制出了单抗 特定于myf5和myf6。我们提出了时空模式的概念 MyoD家族成员(myf5、myoD、mygenin和 在发育过程中观察到的Myf6)反映在横纹肌肉瘤中 可能是组织学上和临床上明显不同的 子类型。对于第二阶段研究，我们将(1)测试诊断实用程序 抗MyoD的单抗上有大量的小圆形， 梭形细胞和间变性细胞，儿童和成人恶性肿瘤。使用 我们还将测试相同的肿瘤材料(2)的诊断效用 抗肌生成素、myf5和myf6的单抗 横纹肌肉瘤与其他恶性肿瘤的诊断，(3) 区分临床上不同的亚型 横纹肌肉瘤；(4)预后预测。 拟议的商业应用：使用单抗 制作了一组组织特异性转录因子来诊断 并将肿瘤细分为临床上不同的预后组 小说。这一概念也适用于各种其他恶性肿瘤。它 为外科病理学家提供了急需且简单的解决方案 和肿瘤学家迅速准确地诊断肿瘤和 识别侵袭性和非侵袭性肿瘤，因此将是 很高的商业价值。

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.