公开(公告)号：US20140017703A1

公开(公告)日：2014-01-16

申请号：US14010003

申请日：2013-08-26

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Johnathan Lancaster ,  Douglas Marchion ,  Dung-Tsa Chen

IPC分类号： G01N33/50

CPC分类号： G01N33/5044 ,  G01N33/57449 ,  G01N2440/14 ,  G01N2800/52

摘要： Despite initial sensitivity BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome, and as therapeutic targets. Induced in-vitro OVCA cisplatin-resistance was associated with BAD-pathway expression. Expression of the pathway was also associated with resistance of 7 different cancers cell-types to 8 chemotherapeutic agents. Phosphorylation of the BAD-protein was associated with platinum-resistance in OVCA cells and primary OVCA specimens, and also overall patient survival. Targeted modulation of BAD-phosphorylation levels influenced cisplatin-sensitivity. A 47-gene BAD-pathway signature was associated in-vitro phospho-BAD levels and with survival of 838 patients with ovarian, breast, colon, and brain cancer. The survival advantage associated with both BAD-phosphorylation and also the BAD-pathway signature was independent of surgical cytoreductive status. The BAD apoptosis pathway influences human cancer chemo-sensitivity and overall survival. The pathway is useful as a biomarker of therapeutic response, patient survival, and therapeutic target.

摘要翻译： 尽管初始敏感性在患者样品和细胞系中评估BAD蛋白磷酸化作为化学敏感性和/或临床结果的决定因素，并作为治疗靶点。 诱导的体外OVCA顺铂抗性与BAD通路表达相关。 该途径的表达也与7种不同癌细胞类型对8种化学治疗剂的抗性有关。 BAD蛋白的磷酸化与OVCA细胞和原发性OVCA标本中的铂抗性相关，以及总体患者存活。 BAD磷酸化水平的靶向调节影响顺铂敏感性。 47位基因BAD通路标记与体外磷酸化BAD水平相关，838例卵巢癌，乳腺癌，结肠癌和脑癌患者存活。 与BAD-磷酸化和BAD-通路特征相关的生存优势与手术细胞减少状态无关。 BAD凋亡途径影响人类癌症化学敏感性和总体生存。 该途径可用作治疗反应，患者存活和治疗靶标的生物标志物。

公开(公告)号：US10240208B2

公开(公告)日：2019-03-26

申请号：US15300808

申请日：2015-03-31

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Mokenge P. Malafa ,  Jennifer Permuth ,  Dung-Tsa Chen

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/6886

摘要： The current invention pertains to miRNAs that are differentially expressed in samples of an individual having pancreatic cancer, or having a high risk of developing pancreatic cancer, as compared to the corresponding sample of an individual not having pancreatic cancer, or having low risk of developing pancreatic cancer, respectively. In certain embodiments, the miRNAs are differentially expressed in a tissue sample or blood plasma sample of an individual having a pancreatic lesion and having a high risk of developing pancreatic cancer as compared to the corresponding tissue sample or blood sample of an individual having the pancreatic lesion and having no risk or low risk of developing pancreatic cancer. These differentially expressed miRNAs can be used as biomarkers for diagnosis, treatment, and/or prevention of pancreatic cancer, particularly, in a subject having a pancreatic lesion. Microarray containing miRNAs indicative of the presence of pancreatic cancer, or having a high risk of pancreatic cancer development, particularly, in a subject having a pancreatic lesion, and methods of use of the microarrays are also provided.

公开(公告)号：US10240206B2

公开(公告)日：2019-03-26

申请号：US14765156

申请日：2014-02-03

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： W. Douglas Cress ,  Dung-Tsa Chen

IPC分类号： C12Q1/6886 ,  G01N33/574 ,  A61N5/10 ,  G06F19/22

摘要： Biomarkers, methods, assays, and kits are provided for predicting the efficacy of adjuvant chemotherapy (ACT) in a subject with early-stage non-small cell lung cancer (NSCLC).

公开(公告)号：US20230046649A1

公开(公告)日：2023-02-16

申请号：US17816087

申请日：2022-07-29

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Mokenge P. Malafa ,  Jennifer Permuth ,  Dung-Tsa Chen

IPC分类号： C12Q1/6886

摘要： The current invention pertains to miRNAs that are differentially expressed in samples of an individual having pancreatic cancer, or having a high risk of developing pancreatic cancer, as compared to the corresponding sample of an individual not having pancreatic cancer, or having low risk of developing pancreatic cancer, respectively. In certain embodiments, the miRNAs are differentially expressed in a tissue sample or blood plasma sample of an individual having a pancreatic lesion and having a high risk of developing pancreatic cancer as compared to the corresponding tissue sample or blood sample of an individual having the pancreatic lesion and having no risk or low risk of developing pancreatic cancer. These differentially expressed miRNAs can be used as biomarkers for diagnosis, treatment, and/or prevention of pancreatic cancer, particularly, in a subject having a pancreatic lesion. Microarray containing miRNAs indicative of the presence of pancreatic cancer, or having a high risk of pancreatic cancer development, particularly, in a subject having a pancreatic lesion, and methods of use of the microarrays are also provided.

公开(公告)号：US09528982B2

公开(公告)日：2016-12-27

申请号：US14010003

申请日：2013-08-26

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Johnathan Lancaster ,  Douglas Marchion ,  Dung-Tsa Chen

IPC分类号： G01N33/574 ,  G01N33/50

CPC分类号： G01N33/5044 ,  G01N33/57449 ,  G01N2440/14 ,  G01N2800/52

摘要： Despite initial sensitivity BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome, and as therapeutic targets. Induced in-vitro OVCA cisplatin-resistance was associated with BAD-pathway expression. Expression of the pathway was also associated with resistance of 7 different cancers cell-types to 8 chemotherapeutic agents. Phosphorylation of the BAD-protein was associated with platinum-resistance in OVCA cells and primary OVCA specimens, and also overall patient survival. Targeted modulation of BAD-phosphorylation levels influenced cisplatin-sensitivity. A 47-gene BAD-pathway signature was associated in-vitro phospho-BAD levels and with survival of 838 patients with ovarian, breast, colon, and brain cancer. The survival advantage associated with both BAD-phosphorylation and also the BAD-pathway signature was independent of surgical cytoreductive status. The BAD apoptosis pathway influences human cancer chemo-sensitivity and overall survival. The pathway is useful as a biomarker of therapeutic response, patient survival, and therapeutic target.

摘要翻译： 尽管初始敏感性在患者样品和细胞系中评估BAD蛋白磷酸化作为化学敏感性和/或临床结果的决定因素，并作为治疗靶点。 诱导的体外OVCA顺铂抗性与BAD通路表达相关。 该途径的表达也与7种不同癌细胞类型对8种化学治疗剂的抗性有关。 BAD蛋白的磷酸化与OVCA细胞和原发性OVCA标本中的铂抗性相关，以及总体患者存活。 BAD磷酸化水平的靶向调节影响顺铂敏感性。 47位基因BAD通路标记与体外磷酸化BAD水平相关，838例卵巢癌，乳腺癌，结肠癌和脑癌患者存活。 与BAD-磷酸化和BAD-通路特征相关的生存优势与手术细胞减少状态无关。 BAD凋亡途径影响人类癌症化学敏感性和总体生存。 该途径可用作治疗反应，患者存活和治疗靶标的生物标志物。

公开(公告)号：US12129522B2

公开(公告)日：2024-10-29

申请号：US17816087

申请日：2022-07-29

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Mokenge P. Malafa ,  Jennifer Permuth ,  Dung-Tsa Chen

IPC分类号： C12Q1/6886

CPC分类号： C12Q1/6886 ,  C12Q2600/118 ,  C12Q2600/158 ,  C12Q2600/178

摘要： The current invention pertains to miRNAs that are differentially expressed in samples of an individual having pancreatic cancer, or having a high risk of developing pancreatic cancer, as compared to the corresponding sample of an individual not having pancreatic cancer, or having low risk of developing pancreatic cancer, respectively. In certain embodiments, the miRNAs are differentially expressed in a tissue sample or blood plasma sample of an individual having a pancreatic lesion and having a high risk of developing pancreatic cancer as compared to the corresponding tissue sample or blood sample of an individual having the pancreatic lesion and having no risk or low risk of developing pancreatic cancer. These differentially expressed miRNAs can be used as biomarkers for diagnosis, treatment, and/or prevention of pancreatic cancer, particularly, in a subject having a pancreatic lesion. Microarray containing miRNAs indicative of the presence of pancreatic cancer, or having a high risk of pancreatic cancer development, particularly, in a subject having a pancreatic lesion, and methods of use of the microarrays are also provided.

公开(公告)号：US20150376713A1

公开(公告)日：2015-12-31

申请号：US14765156

申请日：2014-02-03

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Douglas W. Cress ,  Dung-Tsa Chen

IPC分类号： C12Q1/68 ,  A61N5/10

CPC分类号： C12Q1/6886 ,  A61N5/10 ,  C12Q2600/106 ,  C12Q2600/158 ,  C12Q2600/16 ,  G06F19/22

摘要： Biomarkers, methods, assays, and kits are provided for predicting the efficacy of adjuvant chemotherapy (ACT) in a subject with early-stage non-small cell lung cancer (NSCLC).

摘要翻译： 提供生物标志物，方法，测定和试剂盒用于预测辅助化疗（ACT）在具有早期非小细胞肺癌（NSCLC）的受试者中的功效。

公开(公告)号：US09115388B2

公开(公告)日：2015-08-25

申请号：US14355385

申请日：2012-11-01

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Amer A. Beg ,  Steven A. Enkemann ,  Dung-Tsa Chen

IPC分类号： A61K31/436 ,  A61K31/05 ,  A61K31/353 ,  A61K31/4468 ,  A61K38/06 ,  A61K38/20 ,  A61K35/17 ,  A61K35/30 ,  A61K31/4965 ,  C12Q1/68

CPC分类号： C12Q1/6813 ,  A61K31/05 ,  A61K31/353 ,  A61K31/436 ,  A61K31/4468 ,  A61K31/4965 ,  A61K35/17 ,  A61K35/30 ,  A61K38/06 ,  A61K38/2013 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/118 ,  C12Q2600/158

摘要： Methods for predicting NF-kappaB (NF-kB) activity in a tumor, and more particularly to methods for predicting survival and therapeutic outcome, and selecting therapy in subjects with tumors, e.g., adenocarcinomas, e.g., lung adenocarcinomas and melanomas.

摘要翻译： 用于预测肿瘤中的NF-κB（NF-kB）活性的方法，更具体地，涉及用于预测存活和治疗结果的方法，以及在具有肿瘤的受试者例如腺癌例如肺腺癌和黑素瘤中选择治疗。

公开(公告)号：US20140302060A1

公开(公告)日：2014-10-09

申请号：US14355385

申请日：2012-11-01

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Amer A. Beg ,  Steven A. Enkemann ,  Dung-Tsa Chen

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6813 ,  A61K31/05 ,  A61K31/353 ,  A61K31/436 ,  A61K31/4468 ,  A61K31/4965 ,  A61K35/17 ,  A61K35/30 ,  A61K38/06 ,  A61K38/2013 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/118 ,  C12Q2600/158

摘要： Methods for predicting NF-kappaB (NF-kB) activity in a tumor, and more particularly to methods for predicting survival and therapeutic outcome, and selecting therapy in subjects with tumors, e.g., adenocarcinomas, e.g., lung adenocarcinomas and melanomas.

摘要翻译： 用于预测肿瘤中的NF-κB（NF-kB）活性的方法，更具体地，涉及用于预测存活和治疗结果的方法，以及在具有肿瘤的受试者例如腺癌例如肺腺癌和黑素瘤中选择治疗。

公开(公告)号：US20130252831A1

公开(公告)日：2013-09-26

申请号：US13891433

申请日：2013-05-10

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Dung-Tsa Chen

IPC分类号： C12N15/10

CPC分类号： C12N15/1089 ,  C12Q1/6809 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/118 ,  C12Q2600/158 ,  G01N33/57415 ,  G01N33/57423 ,  G01N2800/52 ,  C12Q2537/165

摘要： A “malignancy-risk” (MR) gene signature score was developed with abundant proliferative genes using principal component analysis. This MR gene signature was shown to be a predictive and prognostic factor of overall survival in early-stage NSCLC. The malignancy-risk signature showed a significant association with OS, with poor survival seen in patients having a higher MR score and better survival seen in patients having a low MR score. As a prognostic factor, the MR gene signature showed a positive correlation with TNM stage, histologic grade, and smoking status. Combination of the MR signature with each clinical parameter often showed the best survival in the low MR group with good clinical outcome. The MR gene profile, tested with a PCA scoring method, discriminated overall survival in lung cancer patients was a predictor independent of pathological staging and other clinical parameters.

摘要翻译： 使用主成分分析开发了具有丰富增殖基因的“恶性风险”（MR）基因标记评分。 该MR基因特征被证明是早期NSCLC的总生存期的预测因素和预后因素。 恶性肿瘤风险标志与OS显着相关，在MR评分较低的患者中MR评分较高，生存期较好的患者存活率差。 作为预后因素，MR基因特征与TNM分期，组织学分级和吸烟状态呈正相关。 结合MR检查与临床各项临床参数，经常显示出低MR组的最佳生存率，临床疗效良好。 用PCA评分法测定的MR基因谱，区分肺癌患者的总生存期是独立于病理分期和其他临床参数的预测因子。