Glycopathology of HCC: identification of the source cells of serum fucosylation
HCC 糖病理学:血清岩藻糖基化来源细胞的鉴定
基本信息
- 批准号:9893835
- 负责人:
- 金额:$ 61.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-14 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:Annual ReportsAntibodiesBiological MarkersBloodCellsChoristomaChronicCirrhosisClinical DataCommunitiesDetectionDevelopmentDiagnosticEarly DiagnosisEtiologyFamilyFucoseGalactoseGeneticGenetic HeterogeneityGlycoproteinsGrantHepatitis BHepatitis C virusHeterogeneityImageKininogensLaboratoriesLectinLinkLiverLiver CirrhosisLiver FibrosisLiver diseasesMalignant NeoplasmsMalignant neoplasm of liverMalignant neoplasm of pancreasMethodsModificationMutationObesityPatientsPatternPerformancePolysaccharidesPositioning AttributePrimary carcinoma of the liver cellsProteinsProteomicsSamplingScreening for cancerSerumSialic AcidsSourceSpecificitySpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationStructureTestingTissue SampleTissuesUnited StatesValidationVirus DiseasesWomanalpha-Fetoproteinsarmbasebiomarker panelcancer biomarkerscancer geneticscancer heterogeneitycancer preventioncancer subtypesdiagnostic panelearly detection biomarkersfallsgenetic profilingglycoproteomicsglycosylationimprovedinterestmenmortalitynon-alcoholic fatty liver diseasenonalcoholic steatohepatitisnovelnovel markersugartumortumor heterogeneity
项目摘要
Abstract:
In the Annual Report to the Nation on the Status of Cancer, mortality from Hepatocellular
carcinoma (HCC) increased at an annual rate of 2.8% in men and 2.2% in women,
making it the cancer with the greatest increase in mortality in the United States (USA)
over the last 10 years. The occurrence of liver cancer is predicted to continue rising in
the USA and will exceed 50,000 cases by 2021. The majority of HCC arises in the
background of liver fibrosis and cirrhosis, usually associated with chronic viral infection
(hepatitis B and hepatitis C virus) or nonalcoholic fatty liver disease/nonalcoholic
steatohepatitis (NAFLD/NASH) associated with obesity.
Our laboratory has shown alterations in both core and outer-arm fucosylation in
HCC. These glycan modifications have promise as biomarkers of cancer and are actively
being commercialized by a number of groups (including us). We have a developed a
diagnostic panel that is comprised of clinical data along with one additional novel
biomarker, fucosylated kininogen, that dramatically improves upon the detection of HCC,
and in particular, the identification of those with early stage HCC.
In an effort to identify the source of fucosylated serum glycoprotein, we have
developed a novel method for tissue-based glycan analysis. In an analysis of 145 HCC
tissue and 112 adjacent control or cirrhotic tissue control samples, we have identified two
major changes in the N-linked glycan family that are associated with HCC. The first
change observed was increased levels of fucosylation, a modification also often
observed in serum of patients with HCC. However, ~50% of the tissue samples
analyzed had no increase in fucose. Often these tumors without increased fucosylation
had increases in tetra-antennary glycan. We hypothesize that the genetic heterogeneity
of the tumor might have an impact upon the glycan heterogeneity in the tissue and
serum. Consequently, the glycans may not only be used as biomarkers for the early
detection of cancer but offer information into the specific genetics of the cancer. In this
application, we will link the glycomic changes observed in both tissue and serum with the
underlying genetic changes. As we will have matching tissue and serum, we will be able
to determine if our current biomarker panel is capable of identifying fucose negative
HCC. Lastly, we will utilize several proteomic and glycomic methods to identify
biomarkers for cancer without increased levels of fucosylation.
摘要:
在国家癌症状况年度报告中,肝细胞癌的死亡率
肝癌(HCC)在男性中以2.8%的年增长率增加,在女性中以2.2%的年增长率增加,
使其成为美国死亡率增加最多的癌症(美国)
在过去的十年里肝癌的发病率预计将继续上升,
到2021年将超过50,000例。大多数HCC发生在
肝纤维化和肝硬化的背景,通常与慢性病毒感染有关
(乙型肝炎B和丙型肝炎病毒)或非酒精性脂肪肝/非酒精性
与肥胖相关的脂肪性肝炎(NAFLD/NASH)。
我们的实验室已经显示了在核心和外臂岩藻糖基化的改变,
HCC。这些聚糖修饰有希望作为癌症的生物标志物,并且被积极地用于治疗癌症。
被一些团体(包括我们)商业化。我们有发达的
诊断面板,由临床数据沿着一个额外的新
生物标志物,岩藻糖基化激肽原,显着提高了HCC的检测,
特别是早期HCC患者的鉴别。
为了鉴定岩藻糖基化血清糖蛋白的来源,我们
开发了一种基于组织的聚糖分析的新方法。在对145例HCC的分析中,
组织和112个相邻对照或异位组织对照样品,我们已经确定了两个
与HCC相关的N-连接聚糖家族的主要变化。第一
观察到的变化是岩藻糖基化水平增加,这种修饰也经常
在肝癌患者的血清中观察到。然而,约50%的组织样本
分析的岩藻糖没有增加。通常这些肿瘤没有增加岩藻糖基化
四触角聚糖增加。我们假设遗传异质性
可能对组织中的聚糖异质性产生影响,
血清的因此,聚糖不仅可以用作早期肿瘤的生物标志物,
检测癌症,但提供信息到特定的遗传学的癌症。在这
应用中,我们将在组织和血清中观察到的糖组学变化与
潜在的基因变化因为我们有匹配的组织和血清,我们就能
以确定我们目前的生物标志物小组是否能够识别岩藻糖阴性
HCC。最后,我们将利用几种蛋白质组学和糖组学方法来鉴定
癌症的生物标志物,而岩藻糖基化水平没有增加。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
RICHARD R. DRAKE其他文献
RICHARD R. DRAKE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('RICHARD R. DRAKE', 18)}}的其他基金
Targeted Isolation and Identification of Sialylated Glycoproteins in Cancer Tissues, Cells and Biofluids
癌症组织、细胞和生物液中唾液酸化糖蛋白的靶向分离和鉴定
- 批准号:
10358217 - 财政年份:2022
- 资助金额:
$ 61.56万 - 项目类别:
Targeted Isolation and Identification of Sialylated Glycoproteins in Cancer Tissues, Cells and Biofluids
癌症组织、细胞和生物液中唾液酸化糖蛋白的靶向分离和鉴定
- 批准号:
10592315 - 财政年份:2022
- 资助金额:
$ 61.56万 - 项目类别:
Glycopathology of HCC: identification of the source cells of serum fucosylation
HCC 糖病理学:血清岩藻糖基化来源细胞的鉴定
- 批准号:
10576851 - 财政年份:2019
- 资助金额:
$ 61.56万 - 项目类别:
Glycopathology of HCC: identification of the source cells of serum fucosylation
HCC 糖病理学:血清岩藻糖基化来源细胞的鉴定
- 批准号:
10361210 - 财政年份:2019
- 资助金额:
$ 61.56万 - 项目类别:
Detection and Histopathology Localization of O-Glycans and Glycosaminoglycans in Tissues
组织中 O-聚糖和糖胺聚糖的检测和组织病理学定位
- 批准号:
9320983 - 财政年份:2016
- 资助金额:
$ 61.56万 - 项目类别:
Detection and Histopathology Localization of O-Glycans and Glycosaminoglycans in Tissues
组织中 O-聚糖和糖胺聚糖的检测和组织病理学定位
- 批准号:
9166181 - 财政年份:2016
- 资助金额:
$ 61.56万 - 项目类别:
Defining an Integrated Allostatic Load Index with Immune and Tumor Microenvironment Factors
定义具有免疫和肿瘤微环境因素的综合稳态负荷指数
- 批准号:
9145866 - 财政年份:2016
- 资助金额:
$ 61.56万 - 项目类别:
Defining an Integrated Allostatic Load Index with Immune and Tumor Microenvironment Factors
定义具有免疫和肿瘤微环境因素的综合稳态负荷指数
- 批准号:
10562431 - 财政年份:2016
- 资助金额:
$ 61.56万 - 项目类别:
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 61.56万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 61.56万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 61.56万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 61.56万 - 项目类别:
Research Grant
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 61.56万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 61.56万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 61.56万 - 项目类别:
Grant for R&D
PLA2G2D Antibodies for Cancer Immunotherapy
用于癌症免疫治疗的 PLA2G2D 抗体
- 批准号:
10699504 - 财政年份:2023
- 资助金额:
$ 61.56万 - 项目类别:
Genetic adjuvants to elicit neutralizing antibodies against HIV
基因佐剂可引发抗艾滋病毒中和抗体
- 批准号:
10491642 - 财政年份:2023
- 资助金额:
$ 61.56万 - 项目类别:
Novel Immunogens to Elicit Broadly Cross-reactive Antibodies That Target the Hemagglutinin Head Trimer Interface
新型免疫原可引发针对血凝素头三聚体界面的广泛交叉反应抗体
- 批准号:
10782567 - 财政年份:2023
- 资助金额:
$ 61.56万 - 项目类别: