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1. 发明申请

WO2013116331A1 BIOMARKERS FOR AGGRESSIVE PROSTATE CANCER 审中-公开
标题翻译：生物标志物用于肿瘤前列腺癌
公开(公告)号：WO2013116331A1
公开(公告)日：2013-08-08
申请号：PCT/US2013/023837
申请日：2013-01-30
申请人： THE JOHNS HOPKINS UNIVERSITY , LI, Danni , CHAN, Daniel, W. , ZHANG, Hui , WANG, Xiangchun
发明人： LI, Danni , CHAN, Daniel, W. , ZHANG, Hui , WANG, Xiangchun
IPC分类号： G01N33/574 , G01N33/68 , G01N33/563
CPC分类号： G01N33/57434 , G01N2333/8146 , G01N2333/948 , G01N2800/56
摘要： The present invention relates to the field of biomarkers. More specifically, the present invention relates to biomarkers useful in diagnosing aggressive prostate cancer. In one embodiment, a method for identifying patients as having or likely to have aggressive prostate cancer comprises the steps of (a) obtaining a biological sample from the patient; (b) performing an assay on the biological sample to detect fucosylated TIMP-1, fucosylated DPP-4, sTIE-2, sVEGFR-1, and FUT8; and (c) identifying the patient as having or likely to have aggressive prostate cancer if there is a statistically significant difference in the levels of fucosylated TIMP-1, fucosylated DPP-4, sTIE-2, sVEGFR-1 and FUT8.
摘要翻译：本发明涉及生物标志物领域。更具体地，本发明涉及可用于诊断侵袭性前列腺癌的生物标志物。在一个实施方案中，用于鉴定患者具有或可能具有侵袭性前列腺癌的方法包括以下步骤：（a）从患者获得生物样品; （b）对生物样品进行测定以检测岩藻糖基化的TIMP-1，岩藻糖基化DPP-4，sTIE-2，sVEGFR-1和FUT8; 如果岩藻糖基化的TIMP-1，岩藻糖基化DPP-4，sTIE-2，sVEGFR-1和FUT8的水平存在统计学显着差异，则（c）鉴定患者具有或可能具有侵袭性前列腺癌。

2. 发明申请

WO2012129408A2 BIOMARKERS FOR AGGRESSIVE PROSTATE CANCER 审中-公开
标题翻译：生物标志物用于肿瘤前列腺癌
公开(公告)号：WO2012129408A2
公开(公告)日：2012-09-27
申请号：PCT/US2012/030129
申请日：2012-03-22
申请人： THE JOHNS HOPKINS UNIVERSITY , ZHANG, Hui , TIAN, Yuan , CHAN, Daniel W. , CHEN, Jing
发明人： ZHANG, Hui , TIAN, Yuan , CHAN, Daniel W. , CHEN, Jing
IPC分类号： G01N33/53 , G01N33/68 , G01N33/574
CPC分类号： G01N33/6893 , G01N33/57434
摘要： The present invention relates to the field of biomarkers and, more specifically, to biomarkers useful in diagnosing aggressive prostate cancer. In specific embodiments, a method for diagnosing aggressive prostate cancer in a patient comprises (a) measuring the levels of one or more biomarkers in a sample collected from the patient; and (b) comparing the levels of the one or more biomarkers with predefined levels of the same biomarkers that correlate to a patient having aggressive prostate cancer and predefined levels of the same biomarkers that correlate to a patient not having aggressive prostate cancer, wherein a correlation to one of the predefined levels provides the diagnosis. In a specific embodiment, the one or more biomarkers may comprise cathepsin-L (CTSL), periostin, microfibrillar-associated protein 4 (MFAP4), collagen XII, neprilysin, clusterin, neutrophil gelatinase associated lipocalin (NGAL), epithelial cell activating molecule (EpCAM), prostate specific antigen (PSA), membrane metallo-endopeptidase (MME) and asporin (ASPN).
摘要翻译：本发明涉及生物标记领域，更具体地涉及可用于诊断侵略性前列腺癌的生物标志物。在具体实施方案中，用于诊断患者中侵袭性前列腺癌的方法包括（a）测量从患者收集的样品中的一种或多种生物标志物的水平; 和（b）将一种或多种生物标志物的水平与与具有侵袭性前列腺癌的患者相关的相同生物标志物的预定水平和与不具有侵袭性前列腺癌的患者相关的相同生物标志物的预定水平进行比较，其中相关性到其中一个预定义的级别提供诊断。在一个具体的实施方案中，一种或多种生物标志物可以包含组织蛋白酶-L（CTSL），骨膜素，微原纤维相关蛋白4（MFAP4），胶原XII，起泡蛋白，聚集蛋白，嗜中性粒细胞明胶酶相关脂质运载蛋白（NGAL），上皮细胞活化分子 EpCAM），前列腺特异性抗原（PSA），膜金属内肽酶（MME）和阿泊菌（ASPN）。

3. 发明申请

WO2010011357A2 DETECTION OF PROSTATE CANCER USING PSA GLYCOSYLATION PATTERNS 审中-公开
标题翻译：使用PSA糖蛋白模式检测前列腺癌
公开(公告)号：WO2010011357A2
公开(公告)日：2010-01-28
申请号：PCT/US2009/004365
申请日：2009-07-27
申请人： THE JOHNS HOPKINS UNIVERSITY , ZHANG, Hui , MEANY, Danni, Li , CHAN, Daniel, Wan-yui , ZHANG, Zhen , LI, Yan , SOKOLL, Lori, J.
发明人： ZHANG, Hui , MEANY, Danni, Li , CHAN, Daniel, Wan-yui , ZHANG, Zhen , LI, Yan , SOKOLL, Lori, J.
IPC分类号： G01N33/574 , C07K16/30
CPC分类号： G01N33/57434 , G01N2333/4724 , G01N2400/00
摘要： The present invention features novel methods for determining if a subject has prostate caner. The present invention is based on the development of lectin immunosorbant assays which analyze α2,6-linked sialylation of total serum PSA by sambucus nigra lectin (SNA) and α2,3 -linked sialylation of total and free serum PSA. These novel assays were used then to conduct a clinical investigation of the potential role of glycoprotein analysis in improving PSA's cancer specificity. The present invention also features kits for determining if a subject has prostate cancer comprising one or more lectins and a PSA specific antibody and instructions for use.
摘要翻译：本发明的特征在于确定受试者是否具有前列腺癌的新颖方法。本发明基于凝集素免疫吸附测定的发展，其通过黑曲霉凝集素（SNA）分析总血清PSA的a2,6连接唾液酸化和总和游离血清PSA的a2链连接唾液酸化。然后使用这些新型测定法对糖蛋白分析在改善PSA的癌症特异性中的潜在作用进行临床研究。本发明还具有用于确定受试者是否具有包含一种或多种凝集素和PSA特异性抗体的前列腺癌以及使用说明书的试剂盒。

4. 发明申请

WO2012170491A1 GLYCAN AND GLYCOPEPTIDE CAPTURE AND RELEASE USING REVERSIBLE HYDRAZONE-BASED METHOD 审中-公开
标题翻译：使用可逆的基于水力学方法的GLYCAN和GLYCOPEPTIDE捕获和释放
公开(公告)号：WO2012170491A1
公开(公告)日：2012-12-13
申请号：PCT/US2012/041050
申请日：2012-06-06
申请人： THE JOHNS HOPKINS UNIVERSITY , ZHANG, Hui , YANG, Shuang
发明人： ZHANG, Hui , YANG, Shuang
IPC分类号： C08B37/00 , C07K9/00 , C07K1/12 , C40B40/10 , C40B40/12 , G01N33/68
CPC分类号： G01N33/6842 , C07B2200/11 , C07K1/22 , C07K9/00 , C07K14/4725 , C08B37/00 , C08B37/0003 , C08H1/00 , C40B40/12 , C40B50/18 , G01N2400/10 , Y10T436/143333
摘要： Highly specific and novel methods for reversible hydrazone solid-phase extraction (rHSPE) are provided for glycan or glycopeptide isolation from proteins, peptides, and other contaminants for glycan and glycopeptide analysis. Glycans or glycopeptides in complex mixtures can be conjugated onto solid support or affinity or chemical tags via reversible hydrazone bond. The conjugation methods of the present invention are chemically specific and provide unique means for the removal of other non-glycan containing molecules in the complex sample before the glycans or glycopeptides are hydrolyzed and recovered for analysis. The hydrazone formation and hydrolysis of the novel methods allows for the analysis of glycans and glycopeptides. The hydrazide coating on the solid-phase surfaces are useful for surface glycan capture and on target glycan analysis. Uses of the information generated by the inventive methods for diagnosis and treatment are also disclosed.
摘要翻译：提供用于可逆腙固相萃取（rHSPE）的高度特异性和新颖的方法，用于从聚糖和糖肽分析的蛋白质，肽和其他污染物中分离聚糖或糖肽。复合混合物中的糖或糖肽可以通过可逆腙键缀合到固体支持物或亲和力或化学标签上。本发明的缀合方法是化学特异性的，并且在聚糖或糖肽被水解和回收用于分析之前提供用于去除复合物样品中其它非聚糖聚合分子的独特手段。腙的形成和水解的新方法允许分析聚糖和糖肽。固相表面上的酰肼涂层可用于表面聚糖捕获和目标聚糖分析。还公开了通过本发明的诊断和治疗方法产生的信息的使用。

5. 发明申请

WO2008151238A1 BIOMARKERS FOR PROSTATE CANCER 审中-公开
标题翻译：生物标志物为前列腺癌
公开(公告)号：WO2008151238A1
公开(公告)日：2008-12-11
申请号：PCT/US2008/065782
申请日：2008-06-04
申请人： THE JOHNS HOPKINS UNIVERSITY , ZHANG, Hui , LI, Yan , SOKOLL, Lori, J. , ZHANG, Zhen , CHAN, Daniel, Wan-Yui
发明人： ZHANG, Hui , LI, Yan , SOKOLL, Lori, J. , ZHANG, Zhen , CHAN, Daniel, Wan-Yui
IPC分类号： G01N33/574
CPC分类号： G01N33/57434 , G01N2333/9108 , G01N2333/96494
摘要： The instant invention provides methods and compositions for the detection of prostate cancer in a subject.
摘要翻译：本发明提供了用于检测受试者中前列腺癌的方法和组合物。

6. 发明申请

WO2014040072A1 ISOBARIC ALDEHYDE-REACTIVE TAGS FOR AND ANALYSIS OF GLYCANS USING SAME 审中-公开
标题翻译： ISOBARIC ALDEHYDE-反应标签及其分析
公开(公告)号：WO2014040072A1
公开(公告)日：2014-03-13
申请号：PCT/US2013/059057
申请日：2013-09-10
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： ZHANG, Hui , YANG, Shuang
IPC分类号： G01N33/50 , G01N33/68 , C08B37/00
CPC分类号： G01N33/58 , C07C237/22 , C08B37/00 , G01N33/50 , G01N33/6848 , G01N2400/00 , G01N2560/00 , Y10T436/143333
摘要： Highly specific and novel methods for analyzing glycans and proteoglycans are provided. Uses of the information generated by the inventive methods for diagnosis and treatment are also disclosed.
摘要翻译：提供了用于分析聚糖和蛋白聚糖的高度特异性和新颖的方法。还公开了通过本发明的诊断和治疗方法产生的信息的使用。

7. 发明申请

WO2014040066A1 SOLID PHASE GLYCAN AND GLYCOPEPTIDE ANALYSIS AND MICROFLUIDIC CHIP FOR GLYCOMIC EXTRACTION, ANALYSIS AND METHODS FOR USING SAME 审中-公开
标题翻译：固相萃取相关糖苷和糖蛋白分析及微流控芯片，分析方法及使用方法
公开(公告)号：WO2014040066A1
公开(公告)日：2014-03-13
申请号：PCT/US2013/059038
申请日：2013-09-10
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： ZHANG, Hui , YANG, Shuang , SHAH, Punit , SUN, Shisheng
IPC分类号： C07H1/06 , C08B37/00 , G01N33/50
CPC分类号： C08B37/0003 , G01N33/5308 , G01N2400/00
摘要： Highly specific and novel solid phase methods for analyzing glycans and proteoglycans using a solid phase system are provided. The present invention also provides an integrated apparatus and methods of use which comprises a high-throughput glycan isolation and reverse-phase liquid chromatography (RPLC) for on-chip glycan extraction, modification and separation. The coverage of detected N-glycans by the GIG-chip-LC apparatus of the present invention can be significantly improved, especially for the low abundant species. Chip-LC by PGC minimizes dynamic range of glycan concentrations in fractions, resulting in detection of low-abundance glycans. Glycan isomers were able to be separated by the chip-LC portion of the apparatus. The GIG-chip-LC apparatus of the present invention can be used to analyze glycans from tissue and sera samples, thus providing a reliable tool for glycomic analysis. The reproducible performance and ability to detect unique glycans from tissue samples provides a powerful means for discovery of abnormal glycans associated with disease states.
摘要翻译：提供了使用固相系统分析聚糖和蛋白聚糖的高度特异性和新颖的固相方法。本发明还提供了一种集成的装置和使用方法，其包括用于片内聚糖提取，改性和分离的高通量聚糖分离和反相液相色谱（RPLC）。通过本发明的GIG-chip-LC装置检测的N-聚糖的覆盖率可以显着提高，特别是对于低丰度物种。通过PGC的Chip-LC最小化部分中聚糖浓度的动态范围，导致检测到低丰度聚糖。甘氨酸异构体能够通过装置的芯片-LC部分分离。本发明的GIG-chip-LC装置可用于分析来自组织和血清样品的聚糖，从而为糖分析提供可靠的工具。从组织样品中检测独特聚糖的可重复性能和能力为发现与疾病状态相关的异常聚糖提供了有力的手段。

8. 发明申请

WO2022047305A1 URINARY GLYCOPROTEINS FOR THE EARLY DETECTION AND TREATMENT OF AGGRESSIVE PROSTATE CANCER 审中-公开
公开(公告)号：WO2022047305A1
公开(公告)日：2022-03-03
申请号：PCT/US2021/048234
申请日：2021-08-30
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： ZHANG, Hui , DONG, Mingming , LIH, Mamie
IPC分类号： G01N33/574 , G01N33/573
摘要： The present invention relates to the field of cancer. Specifically, the present invention provides compositions and methods useful for detecting and treating aggressive prostate cancer. In another embodiment, a method for identifying a subject as having aggressive prostate cancer comprises the step of measuring one or more of ACPP, CD63, KLK 11, ATRN, GP2, PTPRN2, NPTN, RNASE2, CPE, SERPINA1, DSC2, PTGDS, GRN, LRG1, UMOD, CLU, LOX, ORM1, CD97, PSA and AFM in a urine sample obtained from the subject, wherein a decreased level of one or more of ACPP, CD63, KLK 11, ATRN, GP2, PTPRN2, NPTN, RNASE2, PSA, CPE and/or an increased level of one or more of SERPINA1, DSC2, PTGDS, GRN, LRG1, UMOD, CLU, LOX, ORM1, CD97, and AFM relative to a control identifies the subject as having aggressive prostate cancer. In another embodiment, the method further comprises the step of treating the subject with a prostate cancer therapy.

9. 发明申请

WO2021041507A1 METHODS FOR IDENTIFYING O-LINKED GLYCOSYLATION SITES IN PROTEINS 审中-公开
公开(公告)号：WO2021041507A1
公开(公告)日：2021-03-04
申请号：PCT/US2020/047945
申请日：2020-08-26
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： ZHANG, Hui , YANG, Weiming
IPC分类号： G01N33/68 , C12P21/00 , C12N9/10
摘要： The present invention relates to the field of protein post-translational modification. More specifically, the present invention provides compositions and methods useful for identifying O-linked glycosylation sites in proteins. In one embodiment, the present invention provides a method for identifying O-linked glycosylation sites of Tn antigen in proteins comprising the steps of (a) digesting proteins present in a sample into peptides; (b) enriching for Tn-glycopeptides; (c) conjugating Tn-glycopeptides to solid phase; (d) labeling Tn using the glycosyltransferse enzyme C1GalT1 and a labeled uridine diphosphate galactose (UDP-Gal) substrate to produce labeled Tn-glycopeptides; (e) releasing the labeled Tn-glycopeptides from the solid-phase using an endopeptidase that cleaves peptides at the N-terminus of O-linked glycans at serine or threonine residues; and (f) mapping O-linked glycosylation sites of Tn antigen using liquid chromatography-mass spectrometry.

10. 发明申请

WO2015120416A1 BIOMARKERS FOR ASSESSING CANCER PATIENTS FOR TREATMENT 审中-公开
标题翻译：用于评估治疗癌症患者的生物标志物
公开(公告)号：WO2015120416A1
公开(公告)日：2015-08-13
申请号：PCT/US2015/015074
申请日：2015-02-09
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VELTRI, Robert W. , ZHANG, Hui , CHRISTUDASS, Christhunesa , LIU, Zhi , EPSTEIN, Jonathan I. , CARTER, H. Ballantine
IPC分类号： G01N33/53 , G01N33/574
CPC分类号： G01N33/57434 , G01N2800/60
摘要： A method for selecting treatment options for patients is provided. The method comprises a procedure for selecting patients that should not be placed on Active Surveillance (AS) but receive active treatment even though the morphologic analysis of the patient's biopsy may show a Gleason score that would traditionally have placed the patient in AS without any further treatment. In accordance with one embodiment, the patient is selected for active treatment if a biomarker associated with prostate cancer is detected. In yet a further embodiment, the patient is selected for additional treatment if the biomarker' s concentration is determined to be higher in the benign section of the tissue sample than in the cancerous section. In another embodiment, biochemical recurrence is predicted identifying patients for treatment.
摘要翻译：提供了一种选择患者治疗方案。该方法包括用于选择不应该被置于主动监视（AS）但接受积极治疗的患者的方法，即使患者活组织检查的形态学分析可以显示传统上将患者置于AS中而不进行任何进一步治疗的Gleason评分。根据一个实施方案，如果检测到与前列腺癌相关的生物标志物，则选择患者进行主动治疗。在又一个实施方案中，如果在组织样品的良性部分中确定生物标志物的浓度高于癌症部分，则选择患者进行额外的治疗。在另一个实施方案中，预测鉴定患者的生化复发以进行治疗。

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