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1. 发明授权

US10711310B2 Tert promoter mutations in gliomas and a subset of tumors 有权
公开(公告)号：US10711310B2
公开(公告)日：2020-07-14
申请号：US14765692
申请日：2014-02-18
申请人： DUKE UNIVERSITY , THE JOHNS HOPKINS UNIVERSITY
发明人： Hai Yan , Bert Vogelstein , Nickolas Papadopoulos , Kenneth W. Kinzler , Yuchen Jiao , Chetan Bettegowda , Darell D. Bigner , Zachary J. Reitman , Patrick J. Killela
IPC分类号： C12Q1/6886 , C12P19/34
摘要： We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (

2. 发明授权

US10619217B2 Oligodendroglioma drive genes 有权
公开(公告)号：US10619217B2
公开(公告)日：2020-04-14
申请号：US15834886
申请日：2017-12-07
申请人： The Johns Hopkins University , Duke University
发明人： Bert Vogelstein , Kenneth W. Kinzler , Chetan Bettegowda , Nishant Agrawal , Nickolas Papadopoulos , Darell Bigner , Hai Yan , Roger McLendon
IPC分类号： C12Q1/68 , C12Q1/6886
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.

3. 发明授权

US11306364B2 TERT promoter mutations in gliomas and a subset of tumors 有权
公开(公告)号：US11306364B2
公开(公告)日：2022-04-19
申请号：US16928164
申请日：2020-07-14
申请人： Duke University , The Johns Hopkins University
发明人： Hai Yan , Bert Vogelstein , Nickolas Papadopoulos , Kenneth W. Kinzler , Yuchen Jiao , Chetan Bettegowda , Darell D. Bigner , Zachary J. Reitman , Patrick J. Killela
IPC分类号： C12Q1/6886 , C07H21/04
摘要： We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (

4. 发明申请

US20180195132A1 OLIGODENDROGLIOMA DRIVE GENES 审中-公开
公开(公告)号：US20180195132A1
公开(公告)日：2018-07-12
申请号：US15834886
申请日：2017-12-07
申请人： The Johns Hopkins University , Duke University
发明人： Bert Vogelstein , Kenneth W. Kinzler , Chetan Bettegowda , Nishant Agrawal , Nickolas Papadopoulos , Darell Bigner , Hai Yan , Roger McLendon
IPC分类号： C12Q1/6886
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.

5. 发明授权

US11525163B2 Papanicolaou test for ovarian and endometrial cancers 有权
公开(公告)号：US11525163B2
公开(公告)日：2022-12-13
申请号：US14439041
申请日：2013-10-17
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： Isaac Kinde , Kenneth W. Kinzler , Bert Vogelstein , Nickolas Papadopoulos , Luis Diaz , Chetan Bettegowda , Yuxuan Wang
IPC分类号： C12Q1/68 , C12Q1/6886 , G01N33/574 , C12Q1/6851
摘要： The recently developed liquid-based Papanicolaou (Pap) smear allows not only cytologic evaluation but also collection of DNA for detection of HPV, the causative agent of cervical cancer. We tested these samples to detect somatic mutations present in rare tumor cells that might accumulate in the cervix once shed from endometrial and ovarian cancers. A panel of commonly mutated genes in endometrial and ovarian cancers was assembled and used to identify mutations in all 46 endometrial or cervical cancer tissue samples. We were able also able to identify the same mutations in the DNA from liquid Pap smears in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). We developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear without prior knowledge of the tumor's genotype.

6. 发明授权

US12054781B2 Detection of tumor-derived DNA in cerebrospinal fluid 有权
公开(公告)号：US12054781B2
公开(公告)日：2024-08-06
申请号：US15744299
申请日：2016-07-12
申请人： The Johns Hopkins University
发明人： Chetan Bettegowda , Kenneth W. Kinzler , Bert Vogelstein , Yuxuan Wang , Luis Diaz , Nickolas Papadopoulos
IPC分类号： C07H21/04 , C12Q1/68 , C12Q1/6886
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

7. 发明公开

US20230250483A1 PAPANICOLAOU TEST FOR OVARIAN AND ENDOMETRIAL CANCERS 审中-公开
公开(公告)号：US20230250483A1
公开(公告)日：2023-08-10
申请号：US18050809
申请日：2022-10-28
申请人： The Johns Hopkins University
发明人： Isaac Kinde , Kenneth W. Kinzler , Bert Vogelstein , Nickolas Papadopoulos , Luis Diaz , Chetan Bettegowda , Yuxuan Wang
IPC分类号： C12Q1/6886 , G01N33/574
CPC分类号： C12Q1/6886 , G01N33/57442 , G01N33/57449 , C12Q2600/16 , C12Q2600/154 , C12Q1/6851
摘要： The recently developed liquid-based Papanicolaou (Pap) smear allows not only cytologic evaluation but also collection of DNA for detection of HPV, the causative agent of cervical cancer. We tested these samples to detect somatic mutations present in rare tumor cells that might accumulate in the cervix once shed from endometrial and ovarian cancers. A panel of commonly mutated genes in endometrial and ovarian cancers was assembled and used to identify mutations in all 46 endometrial or cervical cancer tissue samples. We were able also able to identify the same mutations in the DNA from liquid Pap smears in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). We developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear without prior knowledge of the tumor's genotype.

8. 发明授权

US10174384B2 Use of the ZMIZ1 marker in directing treatment and predicting survival in cancer 有权
公开(公告)号：US10174384B2
公开(公告)日：2019-01-08
申请号：US15071800
申请日：2016-03-16
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： Dimitrios Mathios , Michael Lim , Patrick Ha , Chetan Bettegowda , Taeyoung Hwang , Chul-Kee Park
IPC分类号： C12Q1/6886
摘要： The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions for treating cancer and predicting patient survival. In one embodiment, a method comprises (a) obtaining a biological sample from the patient; and (b) detecting hypermethylation of ZMIZ1 using primers that specifically bind to CpG island 139 at the alternative promoter of the ZMIZ1 gene.

9. 发明申请

US20170056075A1 A SPINAL PROBE INCORPORATING AN ELECTROMECHANICAL SYSTEM FOR DETECTION AND PREVENTION OF BREACHES DURING SURGERY 审中-公开
标题翻译：手术检测和防治手术的电子探针系统
公开(公告)号：US20170056075A1
公开(公告)日：2017-03-02
申请号：US15308885
申请日：2015-05-06
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： Anvesh Annadanam , Robert Allen , Chetan Bettegowda , Ravi Gaddipati , Luis Herrera , Bradley Isaacs , Sheng-fu Lo , Eric Xie , Clay Andrews , Adarsha Malla , Erica Schwarz
IPC分类号： A61B17/70 , A61B90/00 , A61B17/34
CPC分类号： A61B17/7074 , A61B17/3472 , A61B17/7092 , A61B90/06 , A61B2017/00115 , A61B2090/064 , A61B2090/066
摘要： The present invention is directed to an innovative pedicle probe that uses a force-sensing electromechanical system coupled with haptic and visual feedback. The probe of the present invention reduces the rate of pedicle screw breaches during spinal fusion surgery. The probe provides an effective guidance system to aid surgeons in detecting and preventing cortical bone breaches, thereby minimizing risk of intraoperative injury to the patient. Moreover, the probe invention decreases surgeon reliance on intraoperative radiation, reducing harmful exposure to both patients and surgeons.
摘要翻译：本发明涉及一种创新的椎弓根探针，其使用与触觉和视觉反馈耦合的力感测机电系统。本发明的探针降低脊柱融合手术期间椎弓根螺钉破裂的发生率。该探针提供了有效的指导系统，以帮助外科医生检测和预防皮质骨破裂，从而将患者术中损伤的风险降至最低。此外，探针发明减少了外科医生对术中辐射的依赖，减少了患者和外科医生的有害暴露。

10. 发明授权

US09572843B2 Combination bacteriolytic therapy for the treatment of tumors 有权
标题翻译：联合溶菌治疗肿瘤治疗
公开(公告)号：US09572843B2
公开(公告)日：2017-02-21
申请号：US14106987
申请日：2013-12-16
申请人： The Johns Hopkins University
发明人： Long Dang , Chetan Bettegowda , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： A61K35/742 , A61K31/337 , A61K31/427 , A61K45/06
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 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。肿瘤不良灌注区域的剩余细胞可以被孢子细菌消灭。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。

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