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    SUBSTANCE FOR INCREASING THE PRODUCTION OF A SPECIFIC ACYL-CHAIN DIHYDROCERAMIDE(S) FOR IMPROVING THE EFFECTIVENESS OF CANCER TREATMENTS
    1.
    发明申请
    SUBSTANCE FOR INCREASING THE PRODUCTION OF A SPECIFIC ACYL-CHAIN DIHYDROCERAMIDE(S) FOR IMPROVING THE EFFECTIVENESS OF CANCER TREATMENTS 审中-公开
    增加特异性乙酰二氢叶酸（S）以改善癌症治疗有效性的物质

    公开(公告)号：WO2012068169A3

    公开(公告)日：2012-11-22

    申请号：PCT/US2011060864

    申请日：2011-11-15

    Applicant: UNIV TEXAS TECH ,  MAURER BARRY JAMES

    Inventor： MAURER BARRY JAMES

    IPC: A61K31/133 ,  A61K31/16 ,  A61K31/164 ,  A61K31/20 ,  A61K31/201 ,  A61P35/00

    CPC classification number: A61K31/202 ,  A61K31/07 ,  A61K31/20 ,  A61K31/201 ,  A61K31/203 ,  A61K45/06 ,  A61K2300/00

    Abstract: A substance for improving the effectiveness of cancer treatments that acts by increasing the production of specific ACYL-chain dihydroceramide(s). Increase of native chain-length dihydroceramides is directly cytotoxic to human acute lymphoblastic leukemia cell line MOLT-4 ALL cells with a cytotoxic potency that is dependent upon the specific fatty acid acyl-chain length and saturation of the dihydroceramides. The combination of sphinganine and GT-11 lead to cell death in the absence of an increase of reactive oxygen species, suggesting that the ability of fenretinide to increase cytotoxic ROS is mechanistically independent of dihydroceramides increase and related cytotoxicity. Most unexpectedly, supplementing the exposure of cancer cells to a dihydroceramide-increasing anti-hyperproliferative agent(s), such as fenretinide, with specifically-chosen fatty acids can increase the cytotoxicity of the anti-hyperproliferative agent to the cancer cells to a beneficial effect.

    Abstract translation: 用于提高通过增加特定ACYL-链二氢神经酰胺生产而起作用的癌症治疗有效性的物质。 天然链长二氢神经酰胺的增加直接对人急性淋巴细胞白血病细胞系MOLT-4 ALL细胞具有细胞毒性，其依赖于二氢神经酰胺的特定脂肪酸酰基链长度和饱和度。 在没有增加活性氧的情况下，鞘氨醇和GT-11的组合导致细胞死亡，表明芬维A胺增加细胞毒性ROS的能力在机械上与二重神经酰胺增加和相关的细胞毒性无关。 最意想不到的是，补充癌细胞暴露于具有特异选择的脂肪酸的二氢神经酰胺增加的抗过度增殖剂（如芬维利肽）的暴露可以增加抗过度增殖剂对癌细胞的细胞毒性，从而达到有益效果 。

    SUBSTANCE FOR INCREASING THE PRODUCTION OF A SPECIFIC ACYL-CHAIN DIHYDROCERAMIDE(S) FOR IMPROVING THE EFFECTIVENESS OF CANCER TREATMENTS
    2.
    发明申请
    SUBSTANCE FOR INCREASING THE PRODUCTION OF A SPECIFIC ACYL-CHAIN DIHYDROCERAMIDE(S) FOR IMPROVING THE EFFECTIVENESS OF CANCER TREATMENTS 审中-公开
    为提高癌症治疗的有效性而增加生产特定的酰胺链二酰胺（S）的物质

    公开(公告)号：WO2012068169A2

    公开(公告)日：2012-05-24

    申请号：PCT/US2011/060864

    申请日：2011-11-15

    Applicant: TEXAS TECH UNIVERSITY ,  MAURER, Barry James

    Inventor： MAURER, Barry James

    IPC: A61K31/133 ,  A61K31/164 ,  A61K31/16 ,  A61K31/201 ,  A61K31/20 ,  A61P35/00

    CPC classification number: A61K31/202 ,  A61K31/07 ,  A61K31/20 ,  A61K31/201 ,  A61K31/203 ,  A61K45/06 ,  A61K2300/00

    Abstract: A substance for improving the effectiveness of cancer treatments that acts by increasing the production of specific ACYL-chain dihydroceramide(s). Increase of native chain-length dihydroceramides is directly cytotoxic to human acute lymphoblastic leukemia cell line MOLT-4 ALL cells with a cytotoxic potency that is dependent upon the specific fatty acid acyl-chain length and saturation of the dihydroceramides. The combination of sphinganine and GT-11 lead to cell death in the absence of an increase of reactive oxygen species, suggesting that the ability of fenretinide to increase cytotoxic ROS is mechanistically independent of dihydroceramides increase and related cytotoxicity. Most unexpectedly, supplementing the exposure of cancer cells to a dihydroceramide-increasing anti-hyperproliferative agent(s), such as fenretinide, with specifically-chosen fatty acids can increase the cytotoxicity of the anti-hyperproliferative agent to the cancer cells to a beneficial effect.

    Abstract translation: 通过增加特定ACYL链二氢神经酰胺的产生来改善癌症治疗有效性的物质。 天然链长二氢神经酰胺的增加直接对人急性淋巴母细胞白血病细胞系MOLT-4 ALL细胞具有细胞毒性，细胞毒性效力取决于特定的脂肪酸酰基链长度和二氢神经酰胺的饱和度。 在不存在活性氧增加的情况下，二氢神经鞘氨醇和GT-11的组合导致细胞死亡，表明芬维A胺增加细胞毒性ROS的能力在机制上不依赖于二氢神经酰胺增加和相关的细胞毒性。 最出乎意料的是，用特异性选择的脂肪酸补充癌细胞暴露于增强二氢神经酰胺的抗过度增殖剂（例如芬维A胺）可增加抗过度增殖剂对癌细胞的细胞毒性，从而产生有益效果

    COMPOSITIONS AND METHODS FOR TREATING HYPERPROLIFERATIVE DISORDERS
    3.
    发明申请
    COMPOSITIONS AND METHODS FOR TREATING HYPERPROLIFERATIVE DISORDERS 审中-公开
    用于治疗高反应性疾病的组合物和方法

    公开(公告)号：WO2011060332A3

    公开(公告)日：2011-09-15

    申请号：PCT/US2010056626

    申请日：2010-11-12

    Applicant: UNIV TEXAS TECH ,  MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

    Inventor： MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

    IPC: C07C215/10 ,  A61K31/133 ,  A61K31/16 ,  A61P35/00

    CPC classification number: A61K31/133 ,  A61K31/131 ,  A61K31/167 ,  A61K31/5375

    Abstract: A method of treating a hyperproliferative disorder in a subject in need of such treatment, comprising administering to said subject, in combination, a treatment effective amount of: (a) a ceramide-increasing retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) compounds selected from the groups consisting of (i) a non-18 carbon chain length L-threo-sphinganine(s) or pharmaceuticeutically acceptable salt thereof, (ii) glucosylceramide or glucosyl(dihydro)ceramide synthesis inhibitor(s), and (iii) sphingomyelin or dihydrosphingomyelin synthase inhibitor(s). Preferred L-threo-sphinganines are of carbon chain length 17 carbons, 19 carbons and 20 carbons. A preferred glucosylceramide or glucosyl(dihydro)ceramide synthesis inhibitor is D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingomyelin or dihydrosphingomyelin synthesis inhibitor is D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred hyperproliferative disorder is brain cancers.

    Abstract translation: 一种治疗需要这种治疗的受试者的过度增殖性疾病的方法，包括给予所述受试者组合治疗有效量的：（a）神经酰胺增量的类视色素如芬维A胺或其药学上可接受的盐; 和（b）至少一种（以及在某些实施方案中为至少两种）选自以下的化合物：（i）非18碳链长的L-苏棱 - 鸟嘌呤或其药学上可接受的盐，（ii） （二氢）神经酰胺合成抑制剂，和（iii）鞘磷脂或二氢鞘磷脂合成酶抑制剂。 优选的L-苏式 - 鞘氨醇具有碳链长度为17个碳，19个碳和20个碳。 优选的葡萄糖神经酰胺或（二氢）神经酰胺合成抑制剂是D-苏式-1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。 优选的鞘磷脂或二氢鞘磷脂合成抑制剂是D-苏式-1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。 优选的过度增生性疾病是脑癌。

    PPMP AS A CERAMIDE CATABOLISM INHIBITOR FOR CANCER TREATMENT
    8.
    发明申请
    PPMP AS A CERAMIDE CATABOLISM INHIBITOR FOR CANCER TREATMENT 审中-公开

    公开(公告)号：WO2005049827A3

    公开(公告)日：2005-06-02

    申请号：PCT/US2004/037175

    申请日：2004-11-08

    Applicant: CHILDREN'S HOSPITAL LOS ANGELES ,  MAURER, Barry, James ,  REYNOLDS, Charles, Patrick

    Inventor： MAURER, Barry, James ,  REYNOLDS, Charles, Patrick

    IPC: C12N15/09

    Abstract: The present invention relates to a method of treating a hyperproliferative disorder comprising administering a ceramide generating retinoid comprising a retinoic acid derivative or a pharmaceutically acceptable salt thereof, and D-threo-PPMP as a ceramide degradation inhibitor or a pharmaceutically acceptable salt thereof, wherein the hyperproliferative disorder is a tumor; and wherein the ceramide generating retinoid is administered in an amount effective to produce necrosis, apoptosis or both in the tumor, and the ceramide degradation inhibitor is administered in an amount effective to increase the necrosis, apoptosis or both in the tumor over that expected to be produced by the sum of that produced by the ceramide generating retinoid and the ceramide degradation inhibitor when administered separately.

    PPMP AS A CERAMIDE CATABOLISM INHIBITOR FOR CANCER TREATMENT
    9.
    发明申请
    PPMP AS A CERAMIDE CATABOLISM INHIBITOR FOR CANCER TREATMENT 审中-公开
    PPMP作为一种用于癌症治疗的CERAMIDE可降解缓蚀剂

    公开(公告)号：WO2005049827A2

    公开(公告)日：2005-06-02

    申请号：PCT/US2004037175

    申请日：2004-11-08

    Applicant: CHILDREN S HOSPITAL LOS ANGELE ,  MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

    Inventor： MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

    IPC: A61K31/16 ,  A61K31/225 ,  A61K45/06 ,  C12N15/09

    CPC classification number: A61K45/06 ,  A61K31/16 ,  A61K31/225 ,  A61K2300/00

    Abstract: The present invention relates to a method of treating a hyperproliferative disorder comprising administering a ceramide generating retinoid comprising a retinoic acid derivative or a pharmaceutically acceptable salt thereof, and D-threo-PPMP as a ceramide degradation inhibitor or a pharmaceutically acceptable salt thereof, wherein the hyperproliferative disorder is a tumor; and wherein the ceramide generating retinoid is administered in an amount effective to produce necrosis, apoptosis or both in the tumor, and the ceramide degradation inhibitor is administered in an amount effective to increase the necrosis, apoptosis or both in the tumor over that expected to be produced by the sum of that produced by the ceramide generating retinoid and the ceramide degradation inhibitor when administered separately.

    Abstract translation: 本发明涉及治疗过度增殖性病症的方法，其包括施用神经酰胺产生性视黄酸，其包含视黄酸衍生物或其药学上可接受的盐和作为神经酰胺降解抑制剂的D-苏型-PPMP或其药学上可接受的盐，其中所述 过度增殖性疾病是一种肿瘤; 并且其中产生神经酰胺的视黄醇以有效产生肿瘤中的坏死，细胞凋亡或两者的量施用，神经酰胺降解抑制剂以有效增加肿瘤中的坏死，细胞凋亡或两者的量施用超过预期为 其产生量是神经酰胺产生类视黄醇和神经酰胺降解抑制剂单独给药产生的总和。

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