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1. 发明申请

WO2006024026A3 MOLECULAR PROFILE OF STATIN RESPONSIVE CANCERS AND USES THEREOF 审中-公开
标题翻译：斯坦丁反应性癌症的分子概况及其用途
公开(公告)号：WO2006024026A3
公开(公告)日：2006-10-12
申请号：PCT/US2005030575
申请日：2005-08-25
申请人： UNIV LELAND STANFORD JUNIOR , SHACHAF CATHERINE , YOUSSEF SAWSAN , PEREZ OMAR , GOLDSTEIN MATTHEW J , NOLAN GARRY P , STEINMAN LAWRENCE , FELSHER DEAN W
发明人： SHACHAF CATHERINE , YOUSSEF SAWSAN , PEREZ OMAR , GOLDSTEIN MATTHEW J , NOLAN GARRY P , STEINMAN LAWRENCE , FELSHER DEAN W
IPC分类号： C07K2/00
CPC分类号： G01N33/5011 , A61K31/00 , A61K31/40 , G01N33/5748
摘要： Inhibitors of the mevalonate pathway are shown to affect the phosphorylation and activation of oncogenic signaling molecules, demonstrating a mechanism for the anti-proliferative activity of such agents. Methods are provided for predicting whether a tumor will be responsive to therapy. The ability to predict responsiveness to therapy allows patient selection, optimization of treatment, determination of whether on whether to proceed with a specific therapy, and how to optimize dose, and choice of treatment. An oncogenic profile is obtained from the subject cells, where the phosphorylation status of specific oncogenic signaling molecules associated by a responsive phenotype is determined. Tumors having an activated myc signaling pathway, as evidenced by the phosphorylation status of proteins in the pathway, are shown to be responsive to treatment with mevalonate pathway inhibitors, including statins.
摘要翻译：显示甲羟戊酸途径的抑制剂影响致癌信号传导分子的磷酸化和激活，证明了这些试剂的抗增殖活性的机制。提供了预测肿瘤是否对治疗有反应的方法。预测对疗法的响应能力允许患者选择，优化治疗，确定是否继续进行特定疗法，以及如何优化剂量以及治疗的选择。从受试细胞获得致癌概况，其中确定了与响应表型相关的特定致癌信号分子的磷酸化状态。显示具有激活的myc信号传导途径的肿瘤，如通路中蛋白质的磷酸化状态所证明的，显示出对甲羟戊酸途径抑制剂（包括他汀类药物）的治疗有响应。

2. 发明申请

WO2019165232A1 INHIBITORS OF PHOSPHOLIPID SYNTHESIS AND METHODS OF USE 审中-公开
公开(公告)号：WO2019165232A1
公开(公告)日：2019-08-29
申请号：PCT/US2019/019185
申请日：2019-02-22
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , GOUW, Arvin , FELSHER, Dean W. , JIN, Feng , ZARE, Richard N. , MARGULIS, Katherine , SCHOW, Steven R. , GREENHOUSE, Robert , LOUGHHEAD, David Garrett , RICHARDS, Steven
发明人： GOUW, Arvin , FELSHER, Dean W. , JIN, Feng , ZARE, Richard N. , MARGULIS, Katherine , SCHOW, Steven R. , GREENHOUSE, Robert , LOUGHHEAD, David Garrett , RICHARDS, Steven
IPC分类号： A61K31/18 , A61K31/196 , C07C311/21 , A61P3/00
摘要： Inhibitors of Glycerol 3-Phosphate Acyltransferase (GPAT) are provided; and methods of use in the treatment of cancer; and treatment of conditions relating to metabolic syndrome and hyperlipidemia.

3. 发明申请

WO2013009809A3 A METHOD OF DETERMINING THE PROGNOSIS OF HEPATOCELLULAR CARCINOMAS USING A MULTIGENE SIGNATURE ASSOCIATED WITH METASTASIS 审中-公开
公开(公告)号：WO2013009809A3
公开(公告)日：2013-01-17
申请号：PCT/US2012/046169
申请日：2012-07-11
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , FELSHER, Dean, W. , TRAN, Phuoc , ADAM, Stacey , BELLOVIN, David, I.
发明人： FELSHER, Dean, W. , TRAN, Phuoc , ADAM, Stacey , BELLOVIN, David, I.
IPC分类号： C12Q1/68 , C12N15/11
摘要： Expression of MYC alone, in a conditional transgenic mouse model of Twist1 - and MYC -induced hepatocellular carcinoma (HCC), resulted in tumors that failed to metastasize, whereas Twist1 co-expression with MYC resulted in tumors associated with extra-hepatic metastases to the lymph nodes, spleen, peritoneum, and lungs. Twist1 also caused a marked increase in circulating tumor cells. Combined inactivation of Twist1 and MYC resulted in sustained regression of both primary and metastatic tumors as shown by gross and microscopic pathology, X-ray computed tomography and bioluminescence imaging, as well as the suppression of circulating tumor cells. Through genomic analysis a 20-gene signature comprising 17 up-regulated genes and 3 down -regulated genes has been identified that is highly predictive of metastasis and overall survival in human patients with HCC. Another aspect of the disclosure methods of determining the metastatic status of an hepatocellular carcino ma of a patient, comprising obtaining a first differential gene expression profile from a carcinoma sample from a subject having an hepatocellular carcinoma and creating a report summarizing the normalized data obtained by the first gene expression analysis and including a determination of the metastatic status of the hepatic carcinoma.

4. 发明申请

WO2006033769A3 ASSAYS AND COMPOSITIONS FOR IDENTIFICATION OF CANCER ASSOCIATED LIVER STEM CELLS 审中-公开
公开(公告)号：WO2006033769A3
公开(公告)日：2006-03-30
申请号：PCT/US2005/030335
申请日：2005-08-25
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , SHACHAF, Catherine , FELSHER, Dean, W.
发明人： SHACHAF, Catherine , FELSHER, Dean, W.
IPC分类号： A01K67/00 , A01K67/033 , A01K67/027
摘要： A transgenic animal model for liver cancer and liver stem cells derived therefrom are provided. Animals are genetically modified to comprise an oncogene that is conditionally expressed in liver cells. After induction of expression, and tumor formation, expression of the oncogene can be inactivated, resulting in regression of the tumor, and generation of a population of liver stem cells with latent tumorigenic properties.

5. 发明申请

WO2006024026A2 MOLECULAR PROFILE OF STATIN RESPONSIVE CANCERS AND USES THEREOF 审中-公开
标题翻译： STATIN反应性癌症的分子特征及其用途
公开(公告)号：WO2006024026A2
公开(公告)日：2006-03-02
申请号：PCT/US2005/030575
申请日：2005-08-25
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , SHACHAF, Catherine , YOUSSEF, Sawsan , PEREZ, Omar , GOLDSTEIN, Matthew J. , NOLAN, Garry P. , STEINMAN, Lawrence , FELSHER, Dean W.
发明人： SHACHAF, Catherine , YOUSSEF, Sawsan , PEREZ, Omar , GOLDSTEIN, Matthew J. , NOLAN, Garry P. , STEINMAN, Lawrence , FELSHER, Dean W.
IPC分类号： C12Q1/68
CPC分类号： G01N33/5011 , A61K31/00 , A61K31/40 , G01N33/5748
摘要： Inhibitors of the mevalonate pathway are shown to affect the phosphorylation and activation of oncogenic signaling molecules, demonstrating a mechanism for the anti-proliferative activity of such agents. Methods are provided for predicting whether a tumor will be responsive to therapy. The ability to predict responsiveness to therapy allows patient selection, optimization of treatment, determination of whether on whether to proceed with a specific therapy, and how to optimize dose, and choice of treatment. An oncogenic profile is obtained from the subject cells, where the phosphorylation status of specific oncogenic signaling molecules associated by a responsive phenotype is determined. Tumors having an activated myc signaling pathway, as evidenced by the phosphorylation status of proteins in the pathway, are shown to be responsive to treatment with mevalonate pathway inhibitors, including statins.
摘要翻译：显示甲羟戊酸途径的抑制剂影响致癌信号分子的磷酸化和活化，证明了这种药剂的抗增殖活性的机制。提供了预测肿瘤是否对治疗有反应的方法。预测对治疗反应的能力允许患者选择，优化治疗，确定是否进行特定治疗，以及如何优化剂量以及治疗选择。从受试细胞获得致癌概况，其中确定由响应表型相关的特异性致癌信号分子的磷酸化状态。具有激活的myc信号通路的肿瘤，如通路中的蛋白质的磷酸化状态所证明的，对甲羟戊酸途径抑制剂（包括他汀）的治疗有反应。

6. 发明申请

WO2013009809A2 A METHOD OF DETERMINING THE PROGNOSIS OF HEPATOCELLULAR CARCINOMAS USING A MULTIGENE SIGNATURE ASSOCIATED WITH METASTASIS 审中-公开
标题翻译：一种用转移瘤相关多基因信号确定肝细胞癌预后的方法
公开(公告)号：WO2013009809A2
公开(公告)日：2013-01-17
申请号：PCT/US2012046169
申请日：2012-07-11
申请人： UNIV LELAND STANFORD JUNIOR , FELSHER DEAN W , TRAN PHUOC , ADAM STACEY , BELLOVIN DAVID I
发明人： FELSHER DEAN W , TRAN PHUOC , ADAM STACEY , BELLOVIN DAVID I
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6813 , C12Q1/6886 , C12Q2600/118 , C12Q2600/158
摘要： Expression of MYC alone, in a conditional transgenic mouse model of Twist1- and MYC-induced hepatocellular carcinoma (HCC), resulted in tumors that failed to metastasize, whereas Twist1 co-expression with MYC resulted in tumors associated with extra-hepatic metastases to the lymph nodes, spleen, peritoneum, and lungs. Twist1 also caused a marked increase in circulating tumor cells. Combined inactivation of Twist1 and MYC resulted in sustained regression of both primary and metastatic tumors as shown by gross and microscopic pathology, X-ray computed tomography and bioluminescence imaging, as well as the suppression of circulating tumor cells. Through genomic analysis a 20-gene signature comprising 17 up-regulated genes and 3 down -regulated genes has been identified that is highly predictive of metastasis and overall survival in human patients with HCC. Another aspect of the disclosure methods of determining the metastatic status of an hepatocellular carcino ma of a patient, comprising obtaining a first differential gene expression profile from a carcinoma sample from a subject having an hepatocellular carcinoma and creating a report summarizing the normalized data obtained by the first gene expression analysis and including a determination of the metastatic status of the hepatic carcinoma.
摘要翻译：在Twist1和MYC诱导的肝细胞癌（HCC）的条件转基因小鼠模型中单独表达MYC导致未转移的肿瘤，而Twist1与MYC共表达导致肿瘤与肝外转移相关淋巴结，脾脏，腹膜和肺。 Twist1也引起循环肿瘤细胞显着增加。 Twist1和MYC联合失活导致原发性和转移性肿瘤持续消退，如大体和微观病理学，X线计算机断层扫描和生物发光成像以及循环肿瘤细胞的抑制所示。通过基因组分析，已经鉴定了包含17个上调基因和3个下调基因的20个基因标签，其高度预测人类HCC患者的转移和总体存活。确定患者的肝细胞癌的转移状态的公开方法的另一个方面，包括获得来自患有肝细胞癌的受试者的癌样品的第一差异基因表达谱并创建总结了由该患者的肝细胞癌获得的标准化数据首先进行基因表达分析并包括确定肝癌的转移状态。

7. 发明申请

WO2006033769A2 ASSAYS AND COMPOSITIONS FOR IDENTIFICATION OF CANCER ASSOCIATED LIVER STEM CELLS 审中-公开
标题翻译：用于鉴定癌相关肝干细胞的测定和组合物
公开(公告)号：WO2006033769A2
公开(公告)日：2006-03-30
申请号：PCT/US2005030335
申请日：2005-08-25
申请人： UNIV THE BOARD OF TRUSTEES OF , SHACHAF CATHERINE , FELSHER DEAN W
发明人： SHACHAF CATHERINE , FELSHER DEAN W
IPC分类号： C12Q1/68
CPC分类号： G01N33/5011 , C12Q1/6897
摘要： A transgenic animal model for liver cancer and liver stem cells derived therefrom are provided. Animals are genetically modified to comprise an oncogene that is conditionally expressed in liver cells. After induction of expression, and tumor formation, expression of the oncogene can be inactivated, resulting in regression of the tumor, and generation of a population of liver stem cells with latent tumorigenic properties.
摘要翻译：提供了用于肝癌的转基因动物模型和由其衍生的肝干细胞。动物被遗传修饰以包含在肝细胞中有条件表达的癌基因。诱导表达和肿瘤形成后，可以使癌基因的表达失活，导致肿瘤消退，并产生具有潜伏致瘤特性的肝干细胞群。

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