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    Wnt and frizzled receptors as targets for immunotherapy in head and neck squamous cell carcinomas
    52.
    发明授权
    Wnt and frizzled receptors as targets for immunotherapy in head and neck squamous cell carcinomas 有权
    Wnt和卷曲受体作为头颈部鳞状细胞癌免疫治疗的靶标

    公开(公告)号：US07713526B2

    公开(公告)日：2010-05-11

    申请号：US10285976

    申请日：2002-11-01

    申请人： Chae-Seo Rhee ,  Malini Sen ,  Christina Wu ,  Lorenzo M. Leoni ,  Maripat Corr ,  Dennis A. Carson

    发明人： Chae-Seo Rhee ,  Malini Sen ,  Christina Wu ,  Lorenzo M. Leoni ,  Maripat Corr ,  Dennis A. Carson

    IPC分类号： A61K39/395

    CPC分类号： C07K16/2863 ,  A61K2039/505 ,  C07K16/22 ,  C07K16/3015 ,  C07K16/3023 ,  C07K16/3061 ,  C07K2317/73 ,  C12Q1/6851 ,  C12Q1/6886 ,  C12Q2600/158

    摘要： The diverse receptor-ligand pairs of the Wnt and frizzled (Fzd) families play important roles during embryonic development, and thus may be overexpressed in cancers that arise from immature cells. The mRNA levels and expression levels of 5 Wnt (Wnt-1, 5a, 7a, 10b, 13) and 2 Fzd (Fzd-2, 5) genes in 10 head and neck squamous carcinoma cell lines (HNSCC) were investigated. In addition, anti-Wnt-1 antibodies were used to study the Wnt/Fzd signalling pathway. These results indicate that HNSCC cell lines overexpress one or more Wnt and Fzd genes, and the proliferation and survival of a subset of HNSCC may depend on the Wnt/Fzd pathway. Therefore, the Wnt and Fzd receptors may be useful targets for immunotherapy of this common cancer.

    摘要翻译： Wnt和卷曲（Fzd）家族的多种受体 - 配体对在胚胎发育过程中起重要作用，因此可能在由未成熟细胞产生的癌症中过表达。 研究了10个头颈鳞癌细胞系（HNSCC）中5个Wnt（Wnt-1,5a，7a，10b，13）和2个Fzd（Fzd-2,5）基因的mRNA水平和表达水平。 此外，使用抗Wnt-1抗体研究Wnt / Fzd信号通路。 这些结果表明，HNSCC细胞系过表达一个或多个Wnt和Fzd基因，HNSCC亚型的增殖和存活可能取决于Wnt / Fzd途径。 因此，Wnt和Fzd受体可能是这种常见癌症的免疫治疗的有用靶标。

    Wnt and frizzled receptors as targets for immunotherapy in head and neck squamous cell carcinomas
    53.
    发明授权
    Wnt and frizzled receptors as targets for immunotherapy in head and neck squamous cell carcinomas 失效
    Wnt和卷曲受体作为头颈部鳞状细胞癌免疫治疗的靶标

    公开(公告)号：US07682607B2

    公开(公告)日：2010-03-23

    申请号：US10381636

    申请日：2002-05-01

    申请人： Chae-Seo Rhee ,  Malini Sen ,  Christina Wu ,  Lorenzo M. Leoni ,  Maripat Corr ,  Dennis A. Carson

    发明人： Chae-Seo Rhee ,  Malini Sen ,  Christina Wu ,  Lorenzo M. Leoni ,  Maripat Corr ,  Dennis A. Carson

    IPC分类号： A61K39/395

    CPC分类号： C07K16/28 ,  C12Q1/6851 ,  C12Q1/6886 ,  C12Q2600/158

    摘要： The diverse receptor-ligand pairs of the Wnt and frizzled (Fzd) families play important roles during embryonic development, and thus may be overexpressed in cancers that arise from immature cells. The mRNA levels and expression levels of 5 Wnt (Wnt-1, 5a, 7a, 10b, 13) and 2 Fzd (Fzd-2, 5) genes in 10 head and neck squamous carcinoma cell lines (HNSCC) were investigated. In addition, anti-Wnt-1 antibodies were used to study the Wnt/Fzd signalling pathway. These results indicate that HNSCC cell lines overexpress one or more Wnt and Fzd genes, and the growth and survival of a subset of HNSCC may depend on the Wnt/Fzd pathway. Therefore, The Wnt and Fzd receptors may be useful targets for immunotherapy of this common cancer.

    摘要翻译： Wnt和卷曲（Fzd）家族的多种受体 - 配体对在胚胎发育过程中起重要作用，因此可能在由未成熟细胞产生的癌症中过表达。 研究了10个头颈鳞癌细胞系（HNSCC）中5个Wnt（Wnt-1,5a，7a，10b，13）和2个Fzd（Fzd-2,5）基因的mRNA水平和表达水平。 此外，使用抗Wnt-1抗体研究Wnt / Fzd信号通路。 这些结果表明，HNSCC细胞系过表达一个或多个Wnt和Fzd基因，HNSCC亚型的生长和存活可能取决于Wnt / Fzd途径。 因此，Wnt和Fzd受体可能是这种常见癌症的免疫治疗的有用靶标。

    Method for suppressing multiple drug resistance in cancer cells
    57.
    发明授权
    Method for suppressing multiple drug resistance in cancer cells 失效
    抑制癌细胞多重耐药性的方法

    公开(公告)号：US06210917B1

    公开(公告)日：2001-04-03

    申请号：US08956657

    申请日：1997-10-23

    申请人： Dennis A. Carson ,  Carlos J. Carrera

    发明人： Dennis A. Carson ,  Carlos J. Carrera

    IPC分类号： C12Q134

    CPC分类号： C07K16/40 ,  C12N9/1077 ,  C12Q1/25 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  G01N33/5005 ,  G01N33/573

    摘要： Methods for treating and preventing the onset and maintainance of multiple drug resistance (MDR) in animals undergoing chemotherapy for cancer are provided. According to the methods, target cells are depleted of adenosine 5′-monophosphate (AMP) and adenosine 5′-triphosphate (ATP) such that the cells are unable to support P-glycoprotein activity. According to one method, a population of target cells is obtained from a host and assayed for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. MTAse deficient cells are treated with a purine synthesis inhibitor, such as L-alanosine, which starves the cells of adenine and suppresses P-glycoprotein activity. MTAse competent cells are also treated for MDR with purine synthesis inhibitors. In conjunction with treatment according to the invention, MTAse competent and deficient cells are also treated for malignancy with other anti-cancer drugs. A method for protecting non-malignant cells from adenine starvation during treatment of malignant cells according to the invention is provided.

    摘要翻译： 提供了治疗和预防接受化疗癌症的动物多发耐药（MDR）发病和维持的方法。 根据该方法，靶细胞耗尽腺苷5'-单磷酸（AMP）和腺苷5'-三磷酸（ATP），使得细胞不能支持P-糖蛋白活性。 根据一种方法，从宿主获得靶细胞群并测定甲硫基腺苷磷酸化酶（MTAse）活性的损失。 MTAs将甲基硫代腺苷分解为腺嘌呤，用于内源性补救并入细胞内AMP库。 MTAse缺陷细胞用嘌呤合成抑制剂如L-肌氨酸处理，其使腺嘌呤的细胞饥饿并抑制P-糖蛋白活性。 MTAse感受态细胞也用嘌呤合成抑制剂治疗MDR。 结合根据本发明的治疗，MTAs感受态细胞和缺陷细胞也用其它抗癌药治疗恶性肿瘤。 提供了根据本发明的在恶性细胞治疗期间保护非恶性细胞免于腺嘌呤饥饿的方法。

    Method for selective methionine starvation of malignant cells in mammals
    58.
    发明授权
    Method for selective methionine starvation of malignant cells in mammals 失效
    哺乳动物恶性细胞选择性甲硫氨酸饥饿的方法

    公开(公告)号：US5571510A

    公开(公告)日：1996-11-05

    申请号：US176413

    申请日：1993-12-29

    申请人： Tsutomu Nobori ,  Dennis A. Carson

    发明人： Tsutomu Nobori ,  Dennis A. Carson

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/46 ,  A61K38/51 ,  A61K47/48 ,  A61P35/00 ,  C07H21/04 ,  C12N9/88 ,  C12N15/00 ,  C12N15/60 ,  C12Q1/48 ,  C12Q1/527 ,  C12Q1/68 ,  C12R1/19 ,  C12R1/40 ,  G01N33/573

    CPC分类号： A61K47/48215 ,  A61K38/51 ,  C12N9/88 ,  C12Q1/527

    摘要： An improved method for chemotherapy of mammalian malignant cells which have an absolute requirement for methionine but lack methylthioadenosine phosphorylase (MTAse). The method comprises detection of MTAse negative cells in a mammal, administration of methionine .gamma.-lyase in sufficient amounts to reduce the volume of MTAse negative cells in the mammal, and co-administration of methylthioadenosine in amounts sufficient to ensure the continued availability of methionine to the mammal's non-malignant cells. Means for detection of MTAse negative cells are provided. Means for production and use of recombinant chemotherapeutic agents are also provided.

    摘要翻译： 一种改进的哺乳动物恶性细胞化疗方法，对蛋氨酸具有绝对要求但缺乏甲硫基腺苷磷酸化酶（MTAse）。 该方法包括检测哺乳动物中MTAs阴性细胞，以足够量的量施用甲硫氨酸γ-裂解酶以减少哺乳动物中MTAs阴性细胞的体积，并以足以确保甲硫氨酸持续可用性的量共同给予甲硫基腺苷 哺乳动物的非恶性细胞。 提供了检测MTA阴性细胞的方法。 还提供了生产和使用重组化学治疗剂的方法。