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1. 发明申请

WO2005039492A2 IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS 审中-公开
标题翻译：改进组合治疗肿瘤的微生物治疗
公开(公告)号：WO2005039492A2
公开(公告)日：2005-05-06
申请号：PCT/US2004/034625
申请日：2004-10-21
申请人： THE JOHN HOPKINS UNIVERSITY , DANG, Long , BETTEGOWDA, Chetan , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： DANG, Long , BETTEGOWDA, Chetan , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： A61K
CPC分类号： A61K35/742 , A61K31/337 , A61K31/427 , A61K45/06 , Y10S435/842 , A61K2300/00
摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.
摘要翻译：目前用于治疗癌症的方法在一定程度上受到药物不能影响肿瘤血管不足的区域的限制。我们已经发现，厌氧细菌的孢子与与微管相互作用的药物组合可能导致肿瘤的血管和非血管性腔室的破坏。发现两类微管抑制剂发挥显着不同的作用。抑制微管合成的一些药物，如长春瑞滨，当与孢子结合使用时，引起快速，大规模的出血性坏死。相比之下，稳定微管（如紫杉烷多西紫杉醇）的药物导致肿瘤消退缓慢，导致大多数肿瘤细胞死亡。肿瘤不良灌注区域中的剩余细胞可以被杂音细菌消灭。机理研究表明，微管不稳定剂，而不是微管稳定剂，从根本上减少了流向肿瘤的血液，从而扩大了孢子可以发芽的缺氧生态位。在没有过量毒性的情况下，单次静脉注射孢子加选择的微管相互作用剂能够引起几种肿瘤的回归。

2. 发明申请

WO2005039491A2 CERTAIN IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS 审中-公开
标题翻译：某些改进的联合用于治疗肿瘤的细菌疗法治疗
公开(公告)号：WO2005039491A2
公开(公告)日：2005-05-06
申请号：PCT/US2004/034624
申请日：2004-10-21
申请人： THE JOHN HOPKINS UNIVERSITY , DANG, Long , BETTEGOWDA, Chetan , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： DANG, Long , BETTEGOWDA, Chetan , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： A61K
CPC分类号： A61K35/742 , A61K31/195 , A61K31/4045 , A61K38/06 , A61K2300/00
摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis such as HTI-286 and vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxanes docetaxel and MAC-321, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sporulated bacteria Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.
摘要翻译：目前用于治疗癌症的方法部分地由于药物不能影响肿瘤血管化程度差的区域而受到限制。我们发现厌氧菌的孢子与微管相互作用的药物联合使用会导致肿瘤血管和血管腔的破坏。发现两类微管抑制剂发挥显着不同的作用。一些抑制微管合成的药物如HTI-286和长春瑞滨，当与孢子结合使用时会引起快速，大量的出血性坏死。相反，稳定微管的药物，如紫杉类多西他赛和MAC-321，导致缓慢的肿瘤消退，从而杀死大多数肿瘤细胞。机体研究表明，微管去稳定剂，但不是微管稳定剂，从根本上减少了血液流向肿瘤，从而扩大了孢子可能发芽的低氧生态位。单次静脉注射孢子加选定的微管相互作用剂能够在没有过量毒性的情况下引起几种肿瘤的消退。

3. 发明申请

WO2013012927A2 OLIGODENDROGLIOMA DRIVER GENES 审中-公开
标题翻译： OLIGODENDROGLIOMA驱动器基因
公开(公告)号：WO2013012927A2
公开(公告)日：2013-01-24
申请号：PCT/US2012/047211
申请日：2012-07-18
申请人： THE JOHNS HOPKINS UNIVERSITY , DUKE UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , BETTEGOWDA, Chetan , AGRAWAL, Nishant , PAPADOPOULOS, Nickolas , BIGNER, Darell , YAN, Hai , MCLENDON, Roger
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , BETTEGOWDA, Chetan , AGRAWAL, Nishant , PAPADOPOULOS, Nickolas , BIGNER, Darell , YAN, Hai , MCLENDON, Roger
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158
摘要： Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.
摘要翻译：少突神经胶质瘤是成人中第二常见的恶性脑肿瘤。这些肿瘤通常包含染色体异常，涉及染色体1和染色体1的致晕体融合，导致前者的整个短臂和后者的长臂的损失。为了确定这种改变的分子遗传基础，我们对染色体1p和19q损失进行了7个分离性少突胶质细胞瘤的外切测序。在其他变化中，我们发现在七种病例中的六种中，染色体19q上的CIC（果蝇基因capicua的同系物）被体细胞突变，并且染色体1p上的FUBP1（远上游元件（FUSE）结合蛋白）在两个体系中被体细胞突变的七例。另外27例少突胶质细胞瘤的检查显示有12例和3例分别具有CIC和FUBP1突变的肿瘤，其中58％预计会导致编码蛋白的截短。这些结果表明这些基因在少突胶质细胞的生物学和病理学中的关键作用。

4. 发明申请

WO2006002142A2 IMAGING INFECTION WITH COMPOUNDS THAT BIND TO THYMIDINE KINASE 审中-公开
标题翻译：用与甲状腺素激酶结合的化合物成像感染
公开(公告)号：WO2006002142A2
公开(公告)日：2006-01-05
申请号：PCT/US2005/021888
申请日：2005-06-20
申请人： THE JOHNS HOPKINS UNIVERSITY , POMPER, Martin, G. , BETTEGOWDA, Chetan , FOSS, Catherine , ZHOU, Shibin , KINZLER, Kenneth , VOGELSTEIN, Bert
发明人： POMPER, Martin, G. , BETTEGOWDA, Chetan , FOSS, Catherine , ZHOU, Shibin , KINZLER, Kenneth , VOGELSTEIN, Bert
IPC分类号： A61K49/00
CPC分类号： A61K51/1241 , A61K51/0491 , A61K51/1231
摘要： The instant invention provides a method for diagnosing an infection in a subject by administering to the subject a compound suitable for imaging which binds to a thymidine kinase present in the infecting organism, and obtaining an image of the subject to determine the presence and location of the compound, wherein a localization of the compound is indicative that the subject has an infection.
摘要翻译：本发明提供了一种用于诊断受试者感染的方法，其通过向受试者施用适合于成像的化合物，其与存在于感染生物体中的胸苷激酶结合，并获得受试者的图像以确定化合物的存在和位置，其中化合物的定位表明该对象具有感染。

5. 发明申请

WO2013048952A1 METHODS AND COMPOSITIONS FOR DETECTING INFECTIONS 审中-公开
标题翻译：检测感染的方法和组合物
公开(公告)号：WO2013048952A1
公开(公告)日：2013-04-04
申请号：PCT/US2012/056865
申请日：2012-09-24
申请人： BIOMED VALLEY DISCOVERIES, INC. , SAHA, Saurabh , BETTEGOWDA, Chetan , TUNG, David
发明人： SAHA, Saurabh , BETTEGOWDA, Chetan , TUNG, David
IPC分类号： C12Q1/68
CPC分类号： C12Q1/16 , C12Q1/04 , C12Q1/18 , C12Q1/485 , C12Q1/689 , C12Q1/701
摘要： The present invention provides, inter alia, methods for detecting whether a subject has an infection. These methods include (a) incubating a test sample from a subject suspected of having an infection with a labeled molecule, such as a labeled nucleoside analog, that is preferentially incorporated into a pathogenic microorganism for a period of time sufficient for the pathogenic microorganism to incorporate the labeled molecule; (b) removing any unincorporated labeled molecule from the test sample; and (c) detecting the labeled molecule within the pathogenic microorganism, if any, in the test sample, wherein the presence of labeled molecule within the pathogenic microorganism indicates that the subject has an infection.
摘要翻译：本发明尤其提供用于检测受试者是否感染的方法。这些方法包括（a）将疑似患有感染标记分子例如标记的核苷类似物的受试者的测试样品温育，其优先并入病原微生物中足以使致病微生物掺入标记分子; （b）从测试样品中除去任何未结合的标记分子; 和（c）检测测试样品中病原微生物内的标记分子（如果有的话），其中标记分子在病原微生物中的存在表明受试者具有感染。

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