Immunogenic sugar moieties of prostate cancers

前列腺癌的免疫原性糖部分

• 批准号: 7692616
• 负责人: DENONG WANG
• 金额: $ 15.8万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692616
• 关键词: Antibodies; Antigens; Autoantibodies; Autoantigens; Benign Prostatic Hypertrophy; Biological Assay; Biological Markers; Biopsy; Cancer Patient; Carbohydrate Sequence; Carbohydrates; Cells; Characteristics; Class; Clinical; Clinical Research; Collection; Coupled; Detection; Development; Diagnosis; Diagnostic; Differential Diagnosis; Epitopes; Flow Cytometry; Gleason Grade for Prostate Cancer; Globo-H; Glycoproteins; Goals; Human; Immunoassay; Individual; International; Investigation; Ligands; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Mannose; Masks; Mass Spectrum Analysis; Measures; Monitor; Numbers; Oligosaccharides; Outcome; Patients; Polysaccharides; Prostate; Prostate-Specific Antigen; Proteins; Reagent; Records; Research; Research Personnel; Screening procedure; Serological; Serum; Serum Markers; Specimen; Standards of Weights and Measures; Technology; Therapeutic Intervention; Thompson-Friedenreich Antigen; Tissue Banks; Tissues; Tumor-Associated Carbohydrate Antigens; base; immunogenic; men; novel; outcome forecast; prognostic; programs; sugar; tumor progression; user-friendly

DESCRIPTION (provided by applicant): This project brings together researchers who have established research track records in high-throughput platforms of carbohydrate microarrays, neoglycolipid (NGL) technology coupled with mass spectrometry for carbohydrate ligand discovery, flow cytometry (Hi-D FACS) for highly-sensitive detection of cell and serum markers, and the first international standard for detection of prostate-specific antigen (PSA). The thrust of this team is identification and characterization of immunological biomarkers and development of highly sensitive assays for clinical and research applications. The ultimate goal of this project is to identify novel serum biomarkers for detection of prostate cancer and monitoring of cancer progression. In preliminary investigations, they have identified a number of carbohydrate-based biomarkers in prostate cancers. In addition, they have detected autoantibodies to some of these using carbohydrate microarrays. They hypothesize that these aberrantly expressed carbohydrates are immunogenic and are able to induce specific autoantibodies in prostate cancer subjects. Detection of such antibodies in serum could allow detection of prostate cancer and its aggressive progression. In this project, collaborating group plan to examine their hypotheses by characterizing a large-collection of well-categorized serum and tissue specimens preserved in their prostate cancer tissue banks. They plan to 1) determine whether anti-carbohydrate autoantibodies specific for Mannose-clusters and other A/-glycans not normally expressed can distinguish between men with BPH and prostate cancer and/or predict the aggressive and progressive prostate cancers; 2) determine whether serum antibodies specific for other carbohydrate autoantigens are present in prostate cancer subjects and evaluate their diagnostic and prognostic values; 3) determine whether the presence of certain anti-carbohydrate antibodies in the serum of an individual correlates with the aberrant expression of corresponding glyco-epitopes in the prostate cancer; 4) determine the carbohydrate O-glycan sequences of glyco-epitopes of HCA and other cancer-associated glycoproteins that are recognized by mAb AE3 and G1; and 5) establish highly sensitive and user-friendly immunoassays using novel serological markers to facilitate a large-scale clinical study of prostate cancer.

描述（由申请人提供）：该项目汇集了在碳水化合物微阵列的高通量平台中建立研究记录的研究人员抗原（PSA）。该团队的推力是免疫生物标志物的识别和表征以及用于临床和研究应用的高度敏感测定法。该项目的最终目标是确定新型的血清生物标志物来检测前列腺癌和监测癌症的进展。在初步研究中，他们已经确定了前列腺癌中许多基于碳水化合物的生物标志物。此外，他们使用碳水化合物微阵列检测到其中一些自身抗体。他们假设这些异常表达的碳水化合物具有免疫原性，并且能够在前列腺癌受试者中诱导特定的自身抗体。在血清中检测这种抗体可以允许检测前列腺癌及其侵袭性进展。在这个项目中，合作小组计划通过表征保留在前列腺癌组织库中的良好分类血清和组织标本的大量分类的血清和组织标本来检查其假设。他们计划1）确定针对甘露糖群和其他通常不表达的A/ - 聚糖特异性的抗碳水化合物自身抗体是否可以区分患有BPH和前列腺癌的男性和/或预测侵略性和累进的前列腺癌； 2）确定前列腺癌受试者中是否存在针对其他碳水化合物自身抗原特异性的血清抗体，并评估其诊断和预后值； 3）确定个体血清中某些抗碳水化合物抗体的存在是否与前列腺癌中相应的糖 - epepote的异常表达相关。 4）确定由MAB AE3和G1识别的HCA和其他与癌症相关的糖蛋白的糖 - 聚糖序列； 5）使用新型血清学标记物建立高度敏感和用户友好的免疫测定，以促进对前列腺癌的大规模临床研究。