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    RTVP based compositions and methods for the treatment of prostate cancer
    2.
    发明授权
    RTVP based compositions and methods for the treatment of prostate cancer 有权
    基于RTVP的组合物和治疗前列腺癌的方法

    公开(公告)号：US07645452B2

    公开(公告)日：2010-01-12

    申请号：US10417727

    申请日：2003-04-17

    申请人： Timothy C. Thompson ,  Chengzhen Ren

    发明人： Timothy C. Thompson ,  Chengzhen Ren

    IPC分类号： A61K39/00

    CPC分类号： C07K14/4747 ,  A61K38/00 ,  A61K39/00 ,  C07K14/705

    摘要： This invention relates to a gene encoding RTVP that has been shown to be up-regulated by p53 using differential display-PCR and subsequently by co-transfection studies. RTVP-1 mRNA is abundant in normal mouse and human prostatic epithelial cells and primary tumors, but is significantly down regulated in metastatic mouse and human prostate cancer. In prostate cancer cells overexpression of the mouse RTVP-1 gene (mRTVP-1) induced apoptosis that was accompanied by increased caspase 8, 9 and 3 activities. mRTVP-1-stimulated apoptosis was also associated with increased levels of bax, bad and activated BID; reduced levels of bcl-2 and bcl-XL; and cytosolic cytochrome c accumulation. Adenoviral-vector-mediated mRTVP-1 expression lead to potent growth suppression and antimetastatic activities in an orthotopic mouse model of prostate cancer in vivo. These therapeutic activities were associated with anti-angiogenic effects and importantly a local and systemic immune response. Accordingly, p53 was linked with suppression of metastasis through its induction of mRTVP-1, which can concurrently induce apoptosis, suppress angiogenesis and stimulate an antitumor immune response. Thus, the invention includes compositions and methods, based on RTVP nucleic acid, polypeptides, and antibodies, for use in the treatment, prevention and detection of neoplastic disease and, specifically, metastatic prostatic neoplasia.

    摘要翻译： 本发明涉及编码RTVP的基因，已被证明是通过差异显示PCR而被p53上调，随后通过共转染研究。 RTVP-1 mRNA在正常小鼠和人前列腺上皮细胞和原发性肿瘤中丰富，但在转移性小鼠和人前列腺癌中显着下调。 在前列腺癌细胞中，小鼠RTVP-1基因（mRTVP-1）的过表达诱导凋亡，其伴随着半胱天冬酶8,9和3活性的增加。 mRTVP-1刺激的细胞凋亡也与bax，坏和活化的BID水平升高相关; 降低bcl-2和bcl-XL的水平; 和胞质细胞色素C积累。 腺病毒载体介导的mRTVP-1表达导致在体内前列腺癌的原位小鼠模型中有效的生长抑制和抗转移活性。 这些治疗活动与抗血管生成作用相关，重要的是局部和全身免疫应答。 因此，p53通过诱导mRTVP-1与抑制转移相关，可以同时诱导凋亡，抑制血管发生和刺激抗肿瘤免疫反应。 因此，本发明包括基于RTVP核酸，多肽和抗体的组合物和方法，用于治疗，预防和检测肿瘤疾病，特别是转移性前列腺肿瘤。

    RTVP based compositions and methods for the treatment of prostate cancer
    3.
    发明授权
    RTVP based compositions and methods for the treatment of prostate cancer 有权

    公开(公告)号：US07824685B2

    公开(公告)日：2010-11-02

    申请号：US11038285

    申请日：2005-01-19

    申请人： Timothy C. Thompson ,  Chengzhen Ren

    发明人： Timothy C. Thompson ,  Chengzhen Ren

    IPC分类号： A61K39/00

    CPC分类号： C07K14/47 ,  A61K38/00

    摘要： This invention relates to a gene encoding RTVP that has been shown to be up-regulated by p53 using differential display-PCR and subsequently by co-transfection studies. RTVP-1 mRNA is abundant in normal mouse and human prostatic epithelial cells and primary tumors, but is significantly down regulated in metastatic mouse and human prostate cancer. In prostate cancer cells overexpression of the mouse RTVP-1 gene (mRTVP-1) induced apoptosis that was accompanied by increased caspase 8, 9 and 3 activities. mRTVP-1-stimulated apoptosis was also associated with increased levels of bax, bad and activated BID; reduced levels of bcl-2 and bcl-XL; and cytosolic cytochrome c accumulation. Adenoviral-vector-mediated mRTVP-1 expression lead to potent growth suppression and antimetastatic activities in an orthotopic mouse model of prostate cancer in vivo. These therapeutic activities were associated with anti-angiogenic effects and importantly a local and systemic immune response. Accordingly, p53 was linked with suppression of metastasis through its induction of mRTVP-1, which can concurrently induce apoptosis, suppress angiogenesis and stimulate an antitumor immune response. Thus, the invention includes compositions and methods, based on RTVP nucleic acid, polypeptides, and antibodies, for use in the treatment, prevention and detection of neoplastic disease and, specifically, metastatic prostatic neoplasia.

    DNA sequence encoding the p99 gene and kits for the detection of neoplasia
    5.
    发明授权
    DNA sequence encoding the p99 gene and kits for the detection of neoplasia 失效
    编码p99基因的DNA序列和用于检测瘤形成的试剂盒

    公开(公告)号：US06545139B1

    公开(公告)日：2003-04-08

    申请号：US09266764

    申请日：1999-03-12

    申请人： Timothy C. Thompson ,  Chengzhen Ren

    发明人： Timothy C. Thompson ,  Chengzhen Ren

    IPC分类号： C07H2104

    CPC分类号： G01N33/57434 ,  A61K38/00 ,  A61K38/2013 ,  A61K38/208 ,  A61K38/44 ,  A61K38/45 ,  A61K48/00 ,  C07K14/47 ,  C07K16/18 ,  C07K16/28 ,  C12N15/113 ,  C12Y104/03013 ,  C12Y207/01021 ,  G01N33/50

    摘要： The invention relates to methods for the isolation of metastatic sequences and the isolated sequences. Cells from a cell line or an animal tissue are treated to form a cell line predisposed to cancer. Treated cells are implanted in an animal and incubated for a period of time sufficient for the cells to proliferate and develop malignant transplants. RNA from the malignant transplant and the primary tumor are analyzed by differential display polymerase chain reaction. Differentially expressed genes are cloned, reanalyzed, and sequenced. These genes and sequences can be used as probes in the diagnosis of neoplastic disorders, as probes to isolate metastatic sequences and as a therapeutic agent in the treatment of neoplastic disorders. The metastatic sequence may be a dominant metastatic sequence or a recessive metastatic sequence.

    摘要翻译： 本发明涉及分离转移序列和分离序列的方法。 处理来自细胞系或动物组织的细胞以形成易患癌症的细胞系。 将处理的细胞植入动物中并孵育足以使细胞增殖并形成恶性移植物的一段时间。 通过差异显示聚合酶链反应分析来自恶性移植物和原发性肿瘤的RNA。 差异表达的基因被克隆，重新分析和测序。 这些基因和序列可用作诊断肿瘤性疾病的探针，作为分离转移序列的探针和治疗肿瘤性疾病的治疗剂。 转移序列可以是主要转移序列或隐性转移序列。

    RTVP based compositions and methods for the treatment of prostate cancer
    8.
    发明申请
    RTVP based compositions and methods for the treatment of prostate cancer 有权

    公开(公告)号：US20060057602A1

    公开(公告)日：2006-03-16

    申请号：US11038285

    申请日：2005-01-19

    申请人： Timothy Thompson ,  Chengzhen Ren

    发明人： Timothy Thompson ,  Chengzhen Ren

    IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12P21/06 ,  C07K14/82 ,  C12N5/06

    CPC分类号： C07K14/47 ,  A61K38/00

    摘要： This invention relates to a gene encoding RTVP that has been shown to be up-regulated by p53 using differential display-PCR and subsequently by co-transfection studies. RTVP-1 mRNA is abundant in normal mouse and human prostatic epithelial cells and primary tumors, but is significantly down regulated in metastatic mouse and human prostate cancer. In prostate cancer cells overexpression of the mouse RTVP-1 gene (mRTVP-1) induced apoptosis that was accompanied by increased caspase 8, 9 and 3 activities. mRTVP-1-stimulated apoptosis was also associated with increased levels of bax, bad and activated BID; reduced levels of bcl-2 and bcl-XL; and cytosolic cytochrome c accumulation. Adenoviral-vector-mediated mRTVP-1 expression lead to potent growth suppression and antimetastatic activities in an orthotopic mouse model of prostate cancer in vivo. These therapeutic activities were associated with anti-angiogenic effects and importantly a local and systemic immune response. Accordingly, p53 was linked with suppression of metastasis through its induction of mRTVP-1, which can concurrently induce apoptosis, suppress angiogenesis and stimulate an antitumor immune response. Thus, the invention includes compositions and methods, based on RTVP nucleic acid, polypeptides, and antibodies, for use in the treatment, prevention and detection of neoplastic disease and, specifically, metastatic prostatic neoplasia.