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1. 发明申请

US20140011274A1 ISOLATION AND USE OF SOLID TUMOR STEM CELLS 审中-公开
标题翻译：分离和使用固体肿瘤干细胞
公开(公告)号：US20140011274A1
公开(公告)日：2014-01-09
申请号：US13714921
申请日：2012-12-14
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： C12N5/09
CPC分类号： C12N5/0693 , C12N5/0695 , C12N2503/00 , 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 to both 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和产生新肿瘤的能力的细胞。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。

2. 发明授权

US08357491B2 Isolation and use of solid tumor stem cells 有权
标题翻译：实体肿瘤干细胞的分离和使用
公开(公告)号：US08357491B2
公开(公告)日：2013-01-22
申请号：US12979991
申请日：2010-12-28
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12N5/0693 , C12N5/0695 , C12N2503/00 , 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 to both 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和产生新肿瘤的能力的细胞。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。

3. 发明申请

US20080194022A1 Isolation and use of solid tumor stem cells 审中-公开
标题翻译：实体肿瘤干细胞的分离和使用
公开(公告)号：US20080194022A1
公开(公告)日：2008-08-14
申请号：US11788489
申请日：2007-04-20
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： C12N5/06
CPC分类号： C12N5/0693 , C12N5/0695 , C12N2503/00 , 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。

4. 发明授权

US07115360B2 Isolation and use of solid tumor stem cells 有权
标题翻译：实体肿瘤干细胞的分离和使用
公开(公告)号：US07115360B2
公开(公告)日：2006-10-03
申请号：US10343692
申请日：2001-08-02
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad al-Hajj
IPC分类号： C12Q1/00 , C12N5/00
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.
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。

5. 发明申请

US20110092378A1 ISOLATION AND USE OF SOLID TUMOR STEM CELLS 有权
标题翻译：分离和使用固体肿瘤干细胞
公开(公告)号：US20110092378A1
公开(公告)日：2011-04-21
申请号：US12979991
申请日：2010-12-28
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： C12Q1/68 , C12N5/09 , G01N33/566 , C40B30/00
CPC分类号： C12N5/0693 , C12N5/0695 , C12N2503/00 , 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 to both 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和产生新肿瘤的能力的细胞。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来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。

6. 发明授权

US07713710B2 Isolation and use of solid tumor stem cells 有权
标题翻译：实体肿瘤干细胞的分离和使用
公开(公告)号：US07713710B2
公开(公告)日：2010-05-11
申请号：US11753191
申请日：2007-05-24
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： G01N33/53
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 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. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.
摘要翻译：建立的肿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。实体肿瘤异质性反映了由实体肿瘤干细胞产生的肿瘤细胞后代的存在。该发现是实体肿瘤干细胞组合物的基础，区分功能不同的肿瘤细胞群体的方法，使用这些肿瘤细胞群体研究治疗剂对肿瘤生长的影响的方法，以及用于鉴定和测试新型抗癌剂的方法针对固体肿瘤干细胞的疗法。

7. 发明授权

US06984522B2 Isolation and use of solid tumor stem cells 有权
标题翻译：实体肿瘤干细胞的分离和使用
公开(公告)号：US06984522B2
公开(公告)日：2006-01-10
申请号：US09920517
申请日：2001-08-01
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： C12N5/00 , C12N5/08 , C12N15/63 , A01N65/00 , A61K48/00
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. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.
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。实体肿瘤异质性反映了由实体肿瘤干细胞产生的肿瘤细胞后代的存在。该发现是实体肿瘤干细胞组合物的基础，区分功能不同的肿瘤细胞群体的方法，使用这些肿瘤细胞群体研究治疗剂对肿瘤生长的影响的方法，以及用于鉴定和测试新型抗癌剂的方法针对固体肿瘤干细胞的疗法。

8. 发明授权

US09492538B2 Isolation and use of solid tumor stem cells 有权
公开(公告)号：US09492538B2
公开(公告)日：2016-11-15
申请号：US11150524
申请日：2005-06-10
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： A61K39/00 , A61K39/395 , A01K67/027 , C12N5/095 , G01N33/50 , G01N33/574 , C12Q1/68 , C07K14/705 , C07K14/71 , C07K16/28 , C07K16/30
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 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. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

9. 发明授权

US07850961B2 Methods for targeting solid tumor stem cells in a solid tumor using a notch4 receptor antagonist 有权
标题翻译：使用切口4受体拮抗剂在固体肿瘤中靶向实体瘤干细胞的方法
公开(公告)号：US07850961B2
公开(公告)日：2010-12-14
申请号：US11529869
申请日：2006-09-29
申请人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Sean J. Morrison , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： A61K39/395 , C07K16/28 , C07K16/30
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来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。

10. 发明申请

US20090004205A1 Prospective identification and characterization of breast cancer stem cells 审中-公开
标题翻译：乳腺癌干细胞的前瞻性鉴定和表征
公开(公告)号：US20090004205A1
公开(公告)日：2009-01-01
申请号：US11651214
申请日：2007-01-09
申请人： Michael F. Clarke , Max S. Wicha , Muhammad Al-Hajj
发明人： Michael F. Clarke , Max S. Wicha , Muhammad Al-Hajj
IPC分类号： A61K39/395 , A61P35/00
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. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.
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来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。该发现是实体肿瘤干细胞组合物的基础，区分功能不同的肿瘤细胞群体的方法，使用这些肿瘤细胞群体研究治疗剂对肿瘤生长的影响的方法，以及用于鉴定和测试新型抗癌剂的方法针对固体肿瘤干细胞的疗法。

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