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    Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression
    1.
    发明申请
    Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression 有权
    苯甲嘧啶，甲巯咪唑衍生物和互变异构环状硫堇用于治疗与同样受体过表达相关的自身免疫/炎性疾病

    公开(公告)号：US20120238610A1

    公开(公告)日：2012-09-20

    申请号：US13370079

    申请日：2012-02-09

    申请人： Leonard D. Kohn ,  Norikazu Harii ,  Uruguaysito Benavides-Peratta ,  Mariana Gonzalez-Murguiondo ,  Christopher J. Lewis ,  Douglas J. Goetz

    发明人： Leonard D. Kohn ,  Norikazu Harii ,  Uruguaysito Benavides-Peratta ,  Mariana Gonzalez-Murguiondo ,  Christopher J. Lewis ,  Douglas J. Goetz

    IPC分类号： A61K31/4164 ,  A61P31/00 ,  A61P29/00 ,  A61P31/04

    CPC分类号： A61K31/4164 ,  A61K31/4166 ,  A61K31/56 ,  A61K45/06 ,  Y02A50/411

    摘要： Treatment of autoimmune and/or inflammatory diseases associated with overexpression of Toll-like receptor 3 (TLR3) as well as Toll-like receptor 4 (TLR4) and/or TLR3/TLR4 signaling in nonimmune cells, monocytes, macrophages, and/or dendritic cells in association with related pathologies. The use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune and inflammatory diseases associated with TLR3 as well as TLR4 and/or TLR3/TLR4 cellular signaling in association with related pathologies is disclosed. Methods of treating a subject having a disease or condition associated with abnormal TLR-3 as well as TLR-4 and/or TLR3/TLR4 cellular signaling in association with related pathologies are also disclosed. The present disclosure also relates to the treatment of autoimmune-inflammatory pathologies and chemokine and cytokine-mediated diseases associated with TLR overexpression and signaling. The disclosure also relates to pharmaceutical formulations capable of inhibiting the IRF-3/Type 1 IFN/STAT/ISRE/IRF-1 pathway associated with Toll-like receptor overexpression or signaling.

    摘要翻译： 治疗与非免疫细胞，单核细胞，巨噬细胞和/或树突状细胞中Toll样受体3（TLR3）以及Toll样受体4（TLR4）和/或TLR3 / TLR4信号传导过度表达相关的自身免疫和/或炎性疾病 细胞与相关病理相关。 公开了使用苯基甲基咪唑，甲巯咪唑衍生物和互变异构环状硫for素治疗与TLR3相关的自身免疫性和炎症性疾病以及与相关病理学有关的TLR4和/或TLR3 / TLR4细胞信号传导。 还公开了治疗具有与异常TLR-3以及与相关病理学相关的TLR-4和/或TLR3 / TLR4细胞信号传导相关疾病或病症的受试者的方法。 本公开还涉及治疗与TLR过表达和信号传导相关的自身免疫性炎症病症和趋化因子和细胞因子介导的疾病。 本公开还涉及能够抑制与Toll样受体过表达或信号传导相关的IRF-3/1型IFN / STAT / ISRE / IRF-1途径的药物制剂。

    In situ growth, freezing and testing of cultured cells
    2.
    发明授权
    In situ growth, freezing and testing of cultured cells 有权
    培养细胞的原位生长，冷冻和测试

    公开(公告)号：US06472206B1

    公开(公告)日：2002-10-29

    申请号：US09560548

    申请日：2000-04-28

    申请人： David R. Scholl ,  Francesco Saverio Ambesi-Impiombato ,  James L. Brown ,  Leonard D. Kohn ,  Joseph A. Jollick, Jr.

    发明人： David R. Scholl ,  Francesco Saverio Ambesi-Impiombato ,  James L. Brown ,  Leonard D. Kohn ,  Joseph A. Jollick, Jr.

    IPC分类号： C12N500

    CPC分类号： C12Q1/04 ,  G01N2333/33

    摘要： The present invention provides methods and compositions for the in situ growth, freezing and testing of cultured cells. In particular, the present invention provides methods and compositions for the long-term preservation of cells in ready-to-use formats for testing. In addition, the present invention provides rapid and easy to use means to diagnose viral and other infections. Furthermore, the present invention provides easy to use means to grow and store cells in situ for testing methods. Indeed, the present invention makes viral, chlamydial and other diagnostic methods accessible to small laboratories, including those without cell culture capabilities.

    摘要翻译： 本发明提供了培养细胞的原位生长，冷冻和测试的方法和组合物。 特别地，本发明提供用于长期保存用于测试的即用型格式的细胞的方法和组合物。 此外，本发明提供快速且易于使用的手段来诊断病毒和其他感染。 此外，本发明提供了易于使用的手段来生长和存储细胞在原位以用于测试方法。 实际上，本发明使得小型实验室可以使用病毒，衣原体和其他诊断方法，包括没有细胞培养能力的那些。

    Methimazole derivatives and tautomeric cyclic thiones to treat autoimmune diseases
    3.
    发明授权
    Methimazole derivatives and tautomeric cyclic thiones to treat autoimmune diseases 有权
    甲基咪唑衍生物和互变异构环状硫堇治疗自身免疫性疾病

    公开(公告)号：US06365616B1

    公开(公告)日：2002-04-02

    申请号：US09382960

    申请日：1999-08-25

    申请人： Leonard D. Kohn ,  Robert W. Curley ,  John M. Rice

    发明人： Leonard D. Kohn ,  Robert W. Curley ,  John M. Rice

    IPC分类号： A61K31415

    CPC分类号： C07D233/92 ,  A61K31/4164 ,  A61K31/4166 ,  A61K31/421 ,  A61K31/426 ,  C12Q1/6844 ,  C12Q1/6897

    摘要： The present invention provides methods for treating autoimmune diseases in mammals and for preventing or treating transplantation rejection in a transplant recipient. These methods utilize specifically-defined methimazole derivatives and tautomeric cyclic thione compounds, as well as pharmaceutical compositions containing those compounds. These compounds and compositions have been found to be at least as effective as methimazole in terms of pharmaceutical activity, while having less of an adverse affect on thyroid function. They are also more soluble in conventional pharmaceutical vehicles than methimazole. An assay for screening the activity of compounds useful against autoimmune diseases (ability to suppress expression of MHC Class I and II molecules) is also taught.

    摘要翻译： 本发明提供了用于治疗哺乳动物自身免疫疾病和预防或治疗移植受体中的移植排斥的方法。 这些方法使用特异性定点甲巯咪唑衍生物和互变异构环硫酸盐化合物，以及含有这些化合物的药物组合物。 已经发现这些化合物和组合物在药学活性方面至少与甲巯咪唑一样有效，而对甲状腺功能的影响较小。 它们在常规药物载体中也比甲巯咪唑更可溶。 还教导了用于筛选可用于抗自身免疫疾病的化合物的活性的测定（抑制MHC I类和II类分子的表达的能力）。

    In situ growth, freezing and testing of cultured cells
    7.
    发明授权
    In situ growth, freezing and testing of cultured cells 有权
    培养细胞的原位生长，冷冻和测试

    公开(公告)号：US07341829B2

    公开(公告)日：2008-03-11

    申请号：US10238522

    申请日：2002-09-09

    申请人： David R. Scholl ,  Francesco Saverio Ambesi-Impiombato ,  James L. Brown ,  Leonard D. Kohn ,  Joseph A. Jollick, Jr.

    发明人： David R. Scholl ,  Francesco Saverio Ambesi-Impiombato ,  James L. Brown ,  Leonard D. Kohn ,  Joseph A. Jollick, Jr.

    IPC分类号： C12Q1/00 ,  C12N5/08 ,  A61K39/08

    CPC分类号： C12Q1/04 ,  G01N2333/33

    摘要： The present invention provides methods and compositions for the in situ growth, freezing and testing of cultured cells. In particular, the present invention provides methods and compositions for the long-term preservation of cells in ready-to-use formats for testing. In addition, the present invention provides rapid and easy to use means to diagnose viral and other infections. Furthermore, the present invention provides easy to use means to grow and store cells in situ for testing methods. Indeed, the present invention makes viral, chlamydial and other diagnostic methods accessible to small laboratories, including those without cell culture capabilities.

    摘要翻译： 本发明提供了培养细胞的原位生长，冷冻和测试的方法和组合物。 特别地，本发明提供用于长期保存用于测试的即用型格式的细胞的方法和组合物。 此外，本发明提供快速且易于使用的手段来诊断病毒和其他感染。 此外，本发明提供了易于使用的手段来生长和存储细胞在原位以用于测试方法。 实际上，本发明使得小型实验室可以使用病毒，衣原体和其他诊断方法，包括没有细胞培养能力的那些。

    METHODS AND COMPOSITIONS FOR THE TREATMENT OF MALIGNANT MELANOMA, BREAST, PROSTATE, COLON, PAPILLARY THYROID AND PANCREATIC CANCER
    8.
    发明申请
    METHODS AND COMPOSITIONS FOR THE TREATMENT OF MALIGNANT MELANOMA, BREAST, PROSTATE, COLON, PAPILLARY THYROID AND PANCREATIC CANCER 审中-公开
    治疗恶性血友病，乳腺癌，前列腺癌，结肠癌，毛细血管癌和胰腺癌的方法和组合物

    公开(公告)号：US20100004304A1

    公开(公告)日：2010-01-07

    申请号：US12286880

    申请日：2008-10-01

    申请人： Leonard D. Kohn ,  Douglas J. Goetz ,  Kelly D. McCall ,  Anthony Schwartz ,  Frank Schwartz ,  Ramiro Malgor ,  Glorglo Napolitano ,  Cesidio Giullant

    发明人： Leonard D. Kohn ,  Douglas J. Goetz ,  Kelly D. McCall ,  Anthony Schwartz ,  Frank Schwartz ,  Ramiro Malgor ,  Glorglo Napolitano ,  Cesidio Giullant

    IPC分类号： A61K31/4164 ,  C12N5/06

    CPC分类号： A61K31/4166 ,  A61K31/4164

    摘要： It is now recognized that chronic inflammation is an important risk factor for the development of cancer. The proinflammatory cytokine IL-6 is implicated in cancer because it is important for the activation of STAT, a key regulator of cancer growth, survival, metastasis, immune evasion and angiogenesis. Increased IL-6 and Stat-3 exists in vitro in pancreatic cancer, malignant melanoma, papillary thyroid cancer, breast cancer, colon cancer, and prostate cancer cells with high basal expression of Toll-like receptor 3 (TLR3) and Wnt5a. IL6/STAT3 activation, mediated by overexpressed TLR3 signaling, appears important in the tumor growth process, it may increase Wnt5a signaling, and be associated with increased cellular growth and migration. Using a novel inhibitor of pathologic TLR3 signaling (5-phenylmethimazole [C10]) we have demonstrated decreases in these markers plus suppression of cell growth and migration in human pancreatic cancer, malignant melanoma, papillary thyroid cancer, breast cancer, colon cancer, and prostate cancer cells.

    摘要翻译： 现在认识到慢性炎症是癌症发展的重要危险因素。 促炎细胞因子IL-6涉及癌症，因为它对于STAT的活化是重要的，STAT是癌症生长，存活，转移，免疫逃避和血管生成的关键调节剂。 在胰腺癌，恶性黑素瘤，乳头状甲状腺癌，乳腺癌，结肠癌和前列腺癌细胞中，增加的IL-6和Stat-3在Toll样受体3（TLR3）和Wnt5a具有高基础表达。 由过表达的TLR3信号传导介导的IL6 / STAT3激活在肿瘤生长过程中似乎很重要，它可能增加Wnt5a信号传导，并且与增加的细胞生长和迁移相关。 使用新型的病理性TLR3信号抑制剂（5-苯基咪唑[C10]），我们已经证明这些标志物的减少加上抑制人胰腺癌，恶性黑素瘤，乳头状甲状腺癌，乳腺癌，结肠癌和前列腺癌细胞生长和迁移 癌细胞。