公开(公告)号：US20070190647A1

公开(公告)日：2007-08-16

申请号：US11529869

申请日：2006-09-29

申请人： Michael Clarke ,  Sean Morrison ,  Max Wicha ,  Muhammad Al-Haaj

发明人： Michael Clarke ,  Sean Morrison ,  Max Wicha ,  Muhammad Al-Haaj

IPC分类号： C12N5/06 ,  C12N5/08

CPC分类号： C12N5/0695 ,  A01K67/0271 ,  A61K39/39558 ,  A61K2039/505 ,  A61K2039/5152 ,  A61K2039/5158 ,  C07K14/705 ,  C07K14/70585 ,  C07K14/71 ,  C07K16/28 ,  C07K16/2863 ,  C07K16/30 ,  C12N2501/42 ,  C12N2503/00 ,  C12N2503/02 ,  C12Q1/6886 ,  G01N33/5011 ,  G01N33/57492

摘要： A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

摘要翻译： 建立的实体瘤内的一小部分细胞具有干细胞的特性。 这些实体肿瘤干细胞产生更多的肿瘤干细胞和肿瘤中大部分已经失去广泛增殖能力的细胞和产生新肿瘤的能力。 因此，实体肿瘤异质性反映了由固体肿瘤干细胞产生的肿瘤细胞后代的存在。 我们已经开发了异种移植模型，其中我们已经能够通过在严重免疫缺陷小鼠的乳腺中注射肿瘤从原发肿瘤中建立肿瘤。 这些异种移植物测定使我们能够进行生物学和分子测定来表征克隆型实体瘤干细胞。 我们还发现证据强烈地暗示Notch途径，特别是Notch 4，作为致癌过程的中心途径。