权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Oxidized redox state, a new potential biomarker for prostate cancer progression

氧化还原态，前列腺癌进展的新潜在生物标志物

基本信息

批准号：
9039015
负责人：
Luksana Chaiswing
金额：
$ 20.62万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9039015
关键词：
4 hydroxynonenal Acceleration Advanced Malignant Neoplasm Affect Antibodies Antioxidants Benign Biochemical Biological Biological Markers Cancer Etiology Cations Cells Cessation of life Characteristics Clinical Couples Cysteine Cystine DNA Sequence Alteration Deoxyguanosine Detection Development Diagnosis Disease Disseminated Malignant Neoplasm Environment Epigenetic Process Epithelial Epithelium Equilibrium Exhibits Freezing Future Gleason Grade for Prostate Cancer Glutathione Glutathione Disulfide Health High Pressure Liquid Chromatography Human Image Image Analysis Imaging technology Immunohistochemistry LNCaP Lead Life Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Measures Metabolic Metastatic Neoplasm to the Bone Metastatic Prostate Cancer Methods Molecular Monitor Mus Mutation Neoplasm Metastasis Nuclear Nude Mice Oxidants Oxidation-Reduction Oxidative Stress PC3 cell line Pathologic Pathologic Processes Pathological Staging Patients Post-Translational Protein Processing Production Property Prostate Proteins Public Health Reactive Nitrogen Species Reactive Oxygen Species Resolution Role Sampling Scanning Sensitivity and Specificity Signal Transduction Site Staging Staining method Stains Sulfhydryl Compounds System TXN gene Techniques Time Tissue Microarray Tissues Transplantation Tumor Suppressor Genes Variant Western Blotting Xenograft procedure base cancer diagnosis clinically relevant comparative extracellular imaging modality improved in vivo interest liquid crystal polymer male men mortality outcome forecast overexpression oxidation oxidative DNA damage oxidative damage potential biomarker prognostic protein expression response sensor specific biomarkers standard of care targeted treatment tempol therapeutic target tool tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer (PCa) is an increasingly common malignancy worldwide; progression to advanced cancer is highly unpredictable, resulting in a need for new clinically relevant biomarkers or diagnosis tools. A better understanding of PCa pathologic progression would allow development of more sensitive and specific biomarkers. Based on preliminary results from analyses of human PCa tissues, oxidized redox state and posttranslational modification of thioredoxin 1 (Trx1) protein levels were significantly increased in primary PCa with high Gleason scores and metastatic PCa in comparison to adjacent benign tissues. We hypothesize that increased oxidized redox state is contributed to redox imbalance in PCa, leading to increased production of reactive oxygen species/reactive nitrogen species, oxidative DNA damage, mutation of tumor suppressor genes, epigenetic changes, and subsequent PCa progression. To fully understand the relationship of oxidized redox state and PCa progression, a first step involves determining the correlation of oxidized redox state with PCa progression in patient samples. In Specific Aim 1, human PCa-tumor microarrays with different pathological stages will be constructed, stained with oxidative damage products and analyzed using Vectra/Nuance system. Additionally, thiol redox couples will be measured in human prostate frozen tissues with different pathological stages compared to adjacent benign epithelial prostate tissues. Defining the redox state of PCa and its correlation with disease stage is a necessary first step to determine 1) if oxidized redox state may potentially be used as biomarker for PCa diagnosis and 2) whether oxidized redox state is the cause or consequence of PCa progression. Biochemical analyses of redox state in Aim 1 are time-and labor-intensive and require a large amount of tissues. To overcome these problems, Specific Aim 2 will evaluate if TEMPOL-enhanced MRI could potentially be used in the diagnosis of intracellular redox state of prostate cancer in vivo. TEMPOL can undergo oxidation to the corresponding oxoammonium cation by variant oxidants and its paramagnetism property can be captured by MRI. Oxidizing tissues will exhibit longer-lived MRI signal than reducing tissues. We will scan nude mice with orthotopic xenograft transplant LNCaP-luc-M6 or PC3M-luc-C6 cells to evaluate the possibility and validity of TEMPOL-enhanced MRI. To our knowledge, the present proposal will be the first to 1) attempting correlate tissue redox status with the aggressiveness of PCa in patient samples and 2) use cutting edge technique, TEMPOL enhanced MRI to visualize redox state and diagnosis of PCa. Upon completion of these studies, a better understanding of PCa pathologic/metabolic progression may allow development of more sensitive, more relevant, and more specific biomarkers for early prediction or prognosis of those patients destined for clinical cancer progression.