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1. 发明授权

US09637796B2 Differential identification of pancreatic cysts 有权
公开(公告)号：US09637796B2
公开(公告)日：2017-05-02
申请号：US14359149
申请日：2012-11-12
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Jian Wu , Ralph Hruban , Anirban Maitra , Marco Dal Molin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6883 , C12Q2600/156
摘要： More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations, but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.

2. 发明申请

US20190256920A1 Differential Identification of Pancreatic Cysts 审中-公开
公开(公告)号：US20190256920A1
公开(公告)日：2019-08-22
申请号：US15583141
申请日：2017-05-01
申请人： The Johns Hopkins University
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Jian Wu , Ralph Hruban , Anirban Maitra , Marco Dal Molin
IPC分类号： C12Q1/6886 , C12Q1/6883
摘要： More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations, but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.

3. 发明公开

US20230338297A1 Encapsulated Agents that Bind to MCT-1 审中-公开
公开(公告)号：US20230338297A1
公开(公告)日：2023-10-26
申请号：US18024293
申请日：2021-08-31
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： Jordina RINCON-TORROELLA , Bert Vogelstein , Kenneth W. Kinzler , Shibin Zhou , Nickolas Papadopoulos , Marco Dal Molin , Surojit SUR
IPC分类号： A61K9/50 , A61P35/00 , A61K45/06 , G01N33/50 , A61K31/19
CPC分类号： A61K9/5036 , A61P35/00 , A61K45/06 , G01N33/5017 , A61K31/19
摘要： The present disclosure provides compositions comprising at least one cyclodextrin and at least one cytotoxic receptor binding small-molecule. Also disclosed are kits containing said compositions. The compositions of the present disclosure can be administered to a subject suffering from at least one type of cancer.

4. 发明申请

US20140323344A1 Differential Identification of Pancreatic Cysts 有权
标题翻译：胰腺囊肿的鉴别鉴别
公开(公告)号：US20140323344A1
公开(公告)日：2014-10-30
申请号：US14359149
申请日：2012-11-12
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Jian Wu , Ralph Hruban , Anirban Maitra , Marco Dal Molin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6883 , C12Q2600/156
摘要： More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations, but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.
摘要翻译：超过2％的成年人患有胰腺囊肿，其中一部分进展到具有致命后果的侵入性病变。为了评估胰腺肿瘤囊肿的基因组景观，我们确定了每个主要肿瘤性囊肿类型的八个手术切除的囊肿的肿瘤上皮的DNA的外显子序列：浆液性囊腺瘤（SCA），管内乳头状粘液性肿瘤（IPMN），粘液性囊性肿瘤（MCN）和固体假乳头状肿瘤（SPN）。 SPN是低度恶性肿瘤，IPMNs和MCNs而不是SCA具有进展为癌症的能力。我们发现SCA，IPMNs，MCNs和SPN分别包含10 = 4.6,27 = 12,16 = 7.6和2.9 = 2.1肿瘤体细胞突变。在确定的突变中，E3泛素连接酶组分特别值得注意。八个SCA中的四个包含VHL突变，VHL是VHL泛素连接酶复合物的关键组分，其先前已经与肾细胞癌，SCA和其他肿瘤相关。八个IPMN中的六个和八个MCN中的三个携带RNF43的突变，RNF43是编码具有内在E3泛素连接酶活性的蛋白质的基因，其在以前没有发现在任何人类癌症中被遗传改变。 RNF43失活突变的优势明确地将其确定为IPMNs和MCNs的抑制因子。 SPNs含有极少的遗传改变，但总是含有CTNNB1的突变，其先前证明可以通过E3泛素连接酶抑制编码的蛋白质（＆bgr-catenin）的降解。这些结果突出了泛素连接酶在这些肿瘤中的重要作用，对囊性肿瘤患者的诊断和治疗具有重要意义。

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