公开(公告)号：US07655408B2

公开(公告)日：2010-02-02

申请号：US12098577

申请日：2008-04-07

申请人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

发明人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  A01K2217/05 ,  C07H21/04 ,  C07K14/47 ,  C07K14/4748 ,  C07K16/3069 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/57434 ,  G01N2333/47 ,  G01N2800/56

摘要： This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.

摘要翻译： 本发明涉及两种不同PCA3 mRNA序列的发现。 这些序列中的一个对应于短的PCA3 mRNA分子，而另一个PCA3 RNA分子更长，因为它包含外显子3和外显子4a之间的另外的序列。 短RNA与前列腺癌相关，而长RNA序列与前列腺的非恶性状态相关。 基于这两种PCA3 RNA序列的差异表达水平，提供了诊断前列腺疾病的方案。 本发明还涉及前列腺癌的治疗方法。

公开(公告)号：US08241848B2

公开(公告)日：2012-08-14

申请号：US13080262

申请日：2011-04-05

申请人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

发明人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  A01K2217/05 ,  C07H21/04 ,  C07K14/47 ,  C07K14/4748 ,  C07K16/3069 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/57434 ,  G01N2333/47 ,  G01N2800/56

摘要： This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.

摘要翻译： 本发明涉及两种不同PCA3 mRNA序列的发现。 这些序列中的一个对应于短的PCA3 mRNA分子，而另一个PCA3 RNA分子更长，因为它包含外显子3和外显子4a之间的另外的序列。 短RNA与前列腺癌相关，而长RNA序列与前列腺的非恶性状态相关。 基于这两种PCA3 RNA序列的差异表达水平，提供了诊断前列腺疾病的方案。 本发明还涉及前列腺癌的治疗方法。

公开(公告)号：US20110306055A1

公开(公告)日：2011-12-15

申请号：US12935201

申请日：2010-02-24

申请人： Jean-Francois Haince ,  Guillaume Beaudry ,  Genevieve Garon ,  Michel Houde ,  Timothy J. Holzer ,  Martin Beaulieu ,  Nicolas Bertrand

发明人： Jean-Francois Haince ,  Guillaume Beaudry ,  Genevieve Garon ,  Michel Houde ,  Timothy J. Holzer ,  Martin Beaulieu ,  Nicolas Bertrand

IPC分类号： C12Q1/68

CPC分类号： G01N33/57419 ,  C12Q1/34 ,  C12Q1/527 ,  G01N33/573 ,  G01N2800/52

摘要： The present invention provides a novel method for diagnosing, monitoring, prognosing and staging Lymph Node (LN) status in colorectal cancer (CRC) that is more sensitive and accurate than conventional detection technologies such as histopathology. The Guanylyl Cyclase C (GCC) gene is specifically expressed in apical epithelial cells of the GI tract from the duodenum to the rectum and the detection of GCC mRNA in LNs is indicative of the presence of metastases. Quantitative RT-PCR (RT-qPCR) detection of GCC mRNA to identify the presence of colorectal cancer (CRC) cells in LNs has the potential to aid in CRC staging. When used in combination with glucuronidase B (GUSB), accurate quantification of GCC can be achieved with less than a 2-fold variation between intact and highly degraded RNA specimens. The invention also relates to a newly designed GCC/GUSB assay that uses relative quantification having improved prognostic value for time to recurrence and relapse-free survival in Stage I or II colon cancer patients. The GCC/GUSB assay also improves the statistical power of prognosis stratification for relative risk of recurrence and relapse-free survival.

摘要翻译： 本发明提供了一种用于诊断，监测，预后和分期结直肠癌（CRC）中的淋巴结（LN）状态的新方法，其比常规检测技术如组织病理学更灵敏和准确。 Guanylyl Cyclase C（GCC）基因在十二指肠至直肠胃肠道的顶端上皮细胞中特异性表达，LN检测GCC mRNA表示存在转移灶。 定量RT-PCR（RT-qPCR）检测GCC mRNA以鉴定LN中结肠直肠癌（CRC）细胞的存在有助于CRC分期。 当与葡糖醛酸糖苷酶B（GUSB）组合使用时，可以在完整和高度降解的RNA标本之间以小于2倍的变化实现GCC的准确定量。 本发明还涉及一种新设计的GCC / GUSB测定法，其使用相对定量，其具有改善I期或II期结肠癌患者的复发和无复发存活时间的预后价值。 GCC / GUSB测定还提高了复发和无复发生存相对风险的预后分层的统计学功能。

公开(公告)号：US08192931B2

公开(公告)日：2012-06-05

申请号：US12500749

申请日：2009-07-10

申请人： Yves Fradet ,  Camille Chypre ,  Lyson Piché ,  Geneviéve Garon

发明人： Yves Fradet ,  Camille Chypre ,  Lyson Piché ,  Geneviéve Garon

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/158 ,  C12Q2600/16

摘要： The present invention relates to prostate cancer. More specifically, the present invention relates to a method to detect prostate cancer in a patient sample by detecting the RNA encoded by the gene PCA3. More particularly the present invention relates to a method for determining a predisposition, or presence of prostate cancer in a patient comprising: (a) contacting a biological sample of a patient with at least one oligonucleotide that hybridizes to a PCA3 polynucleotide; (b) detecting in the biological sample an amount of PCA3 and second prostate specific polynucleotides; and (c) comparing the amount of PCA3 polynucleotide that hybridizes to the oligonucleotide to a predetermined cut off value, and therefrom determining the presence or absence of prostate cancer in the biological sample. The present invention further relates to diagnostic kits for the detection of prostate cancer or the risk of developing same in a patient comprising: (a) at least one container means having disposed therein at least one oligonucleotide probe or primer that hybridizes to one a PCA3 nucleic acid or complement thereof; (b) at least one oligonucleotide probe or primer that hybridizes with a second prostate specific nucleic acid or complement thereof; and (c) reagents enabling a detection of PCA3 and of the second prostate specific nucleic acid when PCA3 or second prostate-specific nucleic acid sequence is present.

摘要翻译： 本发明涉及前列腺癌。 更具体地，本发明涉及通过检测由基因PCA3编码的RNA来检测患者样品中前列腺癌的方法。 更具体地说，本发明涉及一种用于确定患者中前列腺癌的倾向或存在的方法，包括：（a）使患者的生物样品与至少一种与PCA3多核苷酸杂交的寡核苷酸接触; （b）在生物样品中检测PCA3和第二前列腺特异性多核苷酸的量; 和（c）将与寡核苷酸杂交的PCA3多核苷酸的量与预定的切断值进行比较，从而确定生物样品中前列腺癌的存在或不存在。 本发明还涉及用于检测前列腺癌的诊断试剂盒或在患者中发生相同危险的诊断试剂盒，其包含：（a）至少一个容器装置，其中设置有至少一种与PCA3核酸之一杂交的寡核苷酸探针或引物 酸或其互补物; （b）与第二前列腺特异性核酸或其互补体杂交的至少一种寡核苷酸探针或引物; 和（c）当存在PCA3或第二前列腺特异性核酸序列时能够检测PCA3和第二前列腺特异性核酸的试剂。

公开(公告)号：US07368545B1

公开(公告)日：2008-05-06

申请号：US09675650

申请日：2000-09-29

申请人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

发明人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

IPC分类号： C07H21/04

CPC分类号： C12Q1/6886 ,  A01K2217/05 ,  C07H21/04 ,  C07K14/47 ,  C07K14/4748 ,  C07K16/3069 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/57434 ,  G01N2333/47 ,  G01N2800/56

摘要： This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostrate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.

摘要翻译： 本发明涉及两种不同PCA3 mRNA序列的发现。 这些序列中的一个对应于短的PCA3 mRNA分子，而另一个PCA3 RNA分子更长，因为它包含外显子3和外显子4a之间的另外的序列。 短RNA与前列腺癌相关，而长RNA序列与前列腺的非恶性状态相关。 基于这两种PCA3 RNA序列的差异表达水平，提供了诊断前列腺疾病的方案。 本发明还涉及前列腺癌的治疗方法。

公开(公告)号：US20150218646A1

公开(公告)日：2015-08-06

申请号：US14416036

申请日：2013-06-14

申请人： DIAGNOCURE INC.

发明人： Jean-François Haince ,  Guillaume Beaudry ,  Yves Fradet ,  Éric Paquet

IPC分类号： C12Q1/68 ,  G06F19/00

CPC分类号： C12Q1/6886 ,  C12Q2600/118 ,  C12Q2600/158 ,  C12Q2600/16 ,  C12Q2600/166 ,  G01N33/57434 ,  G06K9/6269 ,  G06K9/6282 ,  G16B25/00 ,  G16B40/00 ,  G16H50/30 ,  Y02A90/26

摘要： The present invention relates to prostate cancer signatures which are useful for providing a clinical assessment of prostate cancer from a biological sample of a subject. By performing initial gene expression studies on urine samples from prostate cancer and non-prostate cancer subjects, and using the PCA3/PSA prostate cancer test as a performance benchmark, the present inventors have surprisingly discovered multiple signatures that are informative in urine-based prostate cancer tests, as well as in tissue-based tests. The signatures relate to combinations of at least two prostate cancer markers whose expression pattern in urine has been validated as being associated (either positively or negatively) with a clinical assessment of prostate cancer. The prostate cancer markers can be used in conjunction with bioinformatics approaches to generate a prostate cancer score, which correlates with a clinical assessment of prostate cancer. Methods, kits and compositions relating to the aforementioned signatures are also described.

摘要翻译： 本发明涉及可用于从受试者的生物样品提供前列腺癌的临床评估的前列腺癌特征。 通过对来自前列腺癌和非前列腺癌患者的尿液样本进行初步的基因表达研究，并且使用PCA3 / PSA前列腺癌试验作为性能基准，本发明人惊奇地发现在尿液前列腺癌中有信息的多个特征 测试，以及基于组织的测试。 该标记涉及至少两种前列腺癌标志物的组合，其在尿液中的表达模式已被验证为与前列腺癌的临床评估相关联（或正面或负面）。 前列腺癌标志物可与生物信息学方法结合使用以产生与前列腺癌的临床评估相关的前列腺癌评分。 还描述了与上述签名相关的方法，试剂盒和组合物。

公开(公告)号：US08618276B2

公开(公告)日：2013-12-31

申请号：US13565044

申请日：2012-08-02

申请人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

发明人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

IPC分类号： C07H21/04

CPC分类号： C12Q1/6886 ,  A01K2217/05 ,  C07H21/04 ,  C07K14/47 ,  C07K14/4748 ,  C07K16/3069 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/57434 ,  G01N2333/47 ,  G01N2800/56

摘要： This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.

摘要翻译： 本发明涉及两种不同的PCA3 mRNA序列的发现。 这些序列中的一个对应于短的PCA3 mRNA分子，而另一个PCA3 RNA分子更长，因为它包含外显子3和外显子4a之间的另外的序列。 短RNA与前列腺癌相关，而长RNA序列与前列腺的非恶性状态相关。 基于这两种PCA3 RNA序列的差异表达水平，提供了诊断前列腺疾病的方案。 本发明还涉及前列腺癌的治疗方法。

公开(公告)号：US08546551B2

公开(公告)日：2013-10-01

申请号：US13470451

申请日：2012-05-14

申请人： Yves Fradet ,  Camille Chypre ,  Lyson Piché ,  Geneviève Garon

发明人： Yves Fradet ,  Camille Chypre ,  Lyson Piché ,  Geneviève Garon

IPC分类号： C07H21/02

CPC分类号： C12Q1/6886 ,  C12Q2600/158 ,  C12Q2600/16

摘要： The present invention provides methods to detect prostate cancer by detecting the RNA encoded by PCA3. The disclosure provides a method for determining a predisposition, or presence of prostate cancer comprising: (a) contacting a sample with at least one oligonucleotide that hybridizes to a PCA3 polynucleotide; (b) detecting an amount of PCA3 and second prostate-specific polynucleotides; and (c) comparing the amount of PCA3 polynucleotide that hybridizes to the oligonucleotide to a predetermined cut off value, and determining the presence or absence of prostate cancer. Diagnostic kits are provided for detecting prostate cancer or the risk of developing same comprising: (a) at least one container means containing at least one oligonucleotide probe or primer that hybridizes to PCA3 (b) at least one oligonucleotide probe or primer that hybridizes with a second prostate specific nucleic acid; and (c) reagents for detecting PCA3 and the second prostate specific nucleic acid.

摘要翻译： 本发明提供通过检测由PCA3编码的RNA来检测前列腺癌的方法。 本公开提供了确定前列腺癌的倾向或存在的方法，包括：（a）使样品与至少一种与PCA3多核苷酸杂交的寡核苷酸接触; （b）检测PCA3和第二前列腺特异性多核苷酸的量; 和（c）将与寡核苷酸杂交的PCA3多核苷酸的量与预定的切断值进行比较，并确定前列腺癌的存在或不存在。 提供诊断试剂盒用于检测前列腺癌或发展相同的风险，其包括：（a）至少一个容器装置，其含有至少一种与PCA3杂交的寡核苷酸探针或引物（b）至少一种寡核苷酸探针或引物，其与 第二前列腺特异性核酸; 和（c）用于检测PCA3和第二前列腺特异性核酸的试剂。

公开(公告)号：US20120315634A1

公开(公告)日：2012-12-13

申请号：US13565044

申请日：2012-08-02

申请人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

发明人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  A01K2217/05 ,  C07H21/04 ,  C07K14/47 ,  C07K14/4748 ,  C07K16/3069 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/57434 ,  G01N2333/47 ,  G01N2800/56

摘要： This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.

摘要翻译： 本发明涉及两种不同PCA3 mRNA序列的发现。 这些序列中的一个对应于短的PCA3 mRNA分子，而另一个PCA3 RNA分子更长，因为它包含外显子3和外显子4a之间的另外的序列。 短RNA与前列腺癌相关，而长RNA序列与前列腺的非恶性状态相关。 基于这两种PCA3 RNA序列的差异表达水平，提供了诊断前列腺疾病的方案。 本发明还涉及前列腺癌的治疗方法。

公开(公告)号：US20140087384A1

公开(公告)日：2014-03-27

申请号：US14085425

申请日：2013-11-20

申请人： DiagnoCure Inc.

发明人： Ursula Busse ,  Camille Chypre ,  Yves Fradet

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  A01K2217/05 ,  C07H21/04 ,  C07K14/47 ,  C07K14/4748 ,  C07K16/3069 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/57434 ,  G01N2333/47 ,  G01N2800/56

摘要： This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.

摘要翻译： 本发明涉及两种不同PCA3 mRNA序列的发现。 这些序列中的一个对应于短的PCA3 mRNA分子，而另一个PCA3 RNA分子更长，因为它包含外显子3和外显子4a之间的另外的序列。 短RNA与前列腺癌相关，而长RNA序列与前列腺的非恶性状态相关。 基于这两种PCA3 RNA序列的差异表达水平，提供了诊断前列腺疾病的方案。 本发明还涉及前列腺癌的治疗方法。