scholarly journals Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 668
Author(s):  
Andrej Veljković ◽  
Jovan Hadži-Dokić ◽  
Dušan Sokolović ◽  
Dragoslav Bašić ◽  
Ljubinka Veličković-Janković ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Xanthine Oxidase ◽  
Dehydrogenase Activity ◽  
Tumor Tissue ◽  
Specific Antigen ◽  
Cancer Tissue ◽  
Prostate Carcinogenesis ◽  
Promising Treatment

Prostate cancer (PC) is one of the most frequent malignancies. Better biomarkers are constantly wanted, such as those which can help with the prediction of cancer behavior. What is also needed is a marker which may serve as a possible therapeutic target. Oxidative stress (OS), which is a hallmark of cancer, is included in the pathogenesis and progression of PC. We have conducted the present study to determine whether xanthine oxidase/dehydrogenase activity is the source of OS in prostate tissue. We have also determined the concentration of TBA-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as well as the activity of catalase. Xanthine oxidase (XO) activity is significantly higher (p < 0.001) in tumor tissue when compared to the control healthy tissue. The concentration of TBARS (p < 0.001) and AOPP (p < 0.05) are also higher in tumor tissue. Catalase has raised its activity (p < 0.05) versus the control. There is also a strong correlation between XO activity and prostate-specific antigen (PSA) levels in the serum. These results indicate a significant role of XO activity in OS in prostate carcinogenesis, and it could be a possible theranostic biomarker, which can be important for a better understanding of the disease, its evolution, and prognosis. A promising treatment may be using XO inhibitors such as allopurinol as adjuvant therapy.

scholarly journals ERβ and NFκB—Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 199 ◽  
Author(s):  
Karolina Kowalska ◽  
Dominika Ewa Habrowska-Górczyńska ◽  
Kamila Domińska ◽  
Kinga Anna Urbanek ◽  
Agnieszka Wanda Piastowska-Ciesielska
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
M Cell ◽  
Androgen Independence ◽  
Prostate Carcinogenesis ◽  
Cycle Arrest ◽  
Light Chain Enhancer

Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) is commonly expressed in prostate cancer (PCa) cells and is associated with increased proliferation, metastases and androgen independence. Zearalenone (ZEA) is one of the most common mycotoxins contaminating food, which might mimic estrogens and bind to estrogen receptors (ERs). The ratio of androgens to estrogens in men decreases physiologically with age, and is believed to participate in prostate carcinogenesis. In this study, we evaluated the role of NFκB and ERβ in the induction of oxidative stress in human PCa cells by ZEA. As observed, ZEA at a dose of 30 µM induces oxidative stress in PCa cells associated with DNA damage and G2/M cell cycle arrest. We also observed that the inhibition of ERβ and NFΚB via specific inhibitors (PHTPP and BAY 117082) significantly increased ZEA-induced oxidative stress, although the mechanism seems to be different for androgen-dependent and androgen-independent cells. Based on our findings, it is possible that the activation of ERβ and NFΚB in PCa might protect cancer cells from ZEA-induced oxidative stress. We therefore shed new light on the mechanism of ZEA toxicity in human cells.

scholarly journals Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion

2010 ◽  
Vol 17 (3) ◽  
pp. 675-689 ◽  
Author(s):  
Yuet-Kin Leung ◽  
Hung-Ming Lam ◽  
Shulin Wu ◽  
Dan Song ◽  
Linda Levin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Specific Antigen ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Independent Prognostic Marker ◽  
Prostate Carcinogenesis ◽  
Kaplan Meier ◽  
Cell Invasiveness

Estrogens play a pivotal role in the development and progression of prostate cancer (PCa). Their actions are mediated by estrogen receptors (ERs), particularly ERβ in the prostate epithelium. With the discovery of ERβ isoforms, data from previous studies that focused principally on the wild-type ERβ (ERβ1) may not be adequate in explaining the still controversial role of ERβ(s) in prostate carcinogenesis. In this study, using newly generated isoform-specific antibodies, immunohistochemistry (IHC) was performed on a tumor microarray comprised of 144 specimens. IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ERβ1, ERβ2, and ERβ5 in PCa. ERβ2 was commonly found in the cytoplasm and was the most abundant isoform followed by ERβ1 localized predominantly in the nucleus, and ERβ5 was primarily located in the cytoplasm. Logistic regression analyses demonstrated that nuclear ERβ2 (nERβ2) is an independent prognostic marker for prostate specific antigen (PSA) failure and postoperative metastasis (POM). In a Kaplan–Meier analysis, the combined expression of both nERβ2 and cytoplasmic ERβ5 identified a group of patients with the shortest POM-free survival. Cox proportional hazard models revealed that nERβ2 predicted shorter time to POM. In concordance with IHC data, stable, ectopic expression of ERβ2 or ERβ5 enhanced PCa cell invasiveness but only PCa cells expressing ERβ5 exhibited augmented cell migration. This is the first study to uncover a metastasis-promoting role of ERβ2 and ERβ5 in PCa, and show that the two isoforms, singularly and conjointly, have prognostic values for PCa progression. These findings may aid future clinical management of PCa.

The Role of Chromogranin A (CgA) in Monitoring Patients with Prostate Cancer Under Androgen Deprivation Therapy: Comparison with Prostatic Specific Antigen (PSA)

2008 ◽  
Vol 1 (2) ◽  
pp. 115-119
Author(s):  
Athanasios Bantis ◽  
Petros Sountoulides ◽  
Athanasios Zissimopoulos ◽  
Christos Kalaitzis ◽  
Stilianos Giannakopoulos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Chromogranin A ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Prostatic Specific Antigen

Personalizing Therapy for Metastatic Prostate Cancer: The Role of Solid and Liquid Tumor Biopsies

2017 ◽  
pp. 358-369 ◽  
Author(s):  
Terence W. Friedlander ◽  
Colin C. Pritchard ◽  
Himisha Beltran
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Tumor Tissue ◽  
Neuroendocrine Differentiation ◽  
Metastatic Tumor ◽  
Metastatic Lesion ◽  
Phenotypic Changes ◽  
Tumor Biopsies ◽  
Bioinformatic Approach

Although biopsies of metastatic prostate cancer are rarely undertaken in the clinical setting, there is increasing interest in developing personalized approaches to therapy by taking into account the genetic and phenotypic changes in an individual tumor. Indeed, analysis of metastatic prostate tumors can predict sensitivity to agents that inhibit DNA repair and resistance to novel hormonal agents, such as abiraterone and enzalutamide, and identify phenotypic changes, such as neuroendocrine differentiation, that have important clinical implications. Although obtaining metastatic tumor tissue is necessary for this genomic and molecular profiling, knowing when to biopsy, selecting the appropriate metastatic lesion, and interpreting the results are major challenges facing clinicians today. In this article, we discuss the rationale for obtaining metastatic tumor tissue, review the bioinformatic approach to analyzing these specimens, discuss the timing and approach to solid and liquid tumor biopsies, review the challenges associated with obtaining and acting on clinically relevant results, and discuss opportunities for the future.

scholarly journals Proteomics in Diagnosis of Prostate Cancer/ Протеомика Во Дијагноза На Простатниот Карцином

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 5-36 ◽  
Author(s):  
Katarina Davalieva ◽  
Momir Polenakovic
Keyword(s):  
Prostate Cancer ◽  
Tumor Tissue ◽  
Biomarker Discovery ◽  
Molecular Level ◽  
Specific Antigen ◽  
Shotgun Proteomics ◽  
Comparative Proteomics ◽  
Label Free ◽  
The Past ◽  
Proteomics Research

Abstract Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa.

Role of ultrasensitive prostate-specific antigen in the follow-up of prostate cancer after radical prostatectomy

2015 ◽  
Vol 33 (1) ◽  
pp. 16.e1-16.e7 ◽  
Author(s):  
Heikki Seikkula ◽  
Kari T. Syvänen ◽  
Samu Kurki ◽  
Tuomas Mirtti ◽  
Pekka Taimen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Prostate Specific Antigen ◽  
Specific Antigen

scholarly journals Associations Between Polymorphisms in Genes Related to Oxidative Stress and DNA Repair, Interactions With Serum Antioxidants, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

2022 ◽  
Vol 11 ◽  
Author(s):  
Zhihong Gong ◽  
Mary E. Platek ◽  
Cathee Till ◽  
Phyllis J. Goodman ◽  
Catherine M. Tangen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Prevention ◽  
Prostate Cancer Risk ◽  
Minor Allele ◽  
Cancer Etiology ◽  
Lower Serum ◽  
Prostate Cancer Prevention

Study of polymorphisms in genes related to the generation and removal of oxidative stress and repair of oxidative DNA damage will lead to new insights into the genetic basis of prostate cancer. In the Prostate Cancer Prevention Trial (PCPT), a double-blind, randomized controlled trial testing finasteride versus placebo for prostate cancer prevention, we intend to investigate the role of oxidative stress/DNA repair mechanisms in prostate cancer etiology and whether these polymorphisms modify prostate cancer risk by interacting with antioxidant status in both placebo and finasteride arms. We evaluated associations of selected candidate polymorphisms in genes in these pathways, and interactions with pre-diagnostic serum antioxidants, and the risk of prostate cancer among 1,598 cases and 1,706 frequency-matched controls enrolled in the PCPT. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. While there were no statistically significant associations observed in the placebo arm, several SNPs were associated with prostate cancer in the finasteride arm. Specifically, APEX1-rs1760944 was associated with increased risk of total prostate cancer (per minor allele: p-trend=0.04). OGG1-rs1052133 was positively (CG/GG vs. CC: OR=1.32, 95% CI: 1.01-1.73) and NOS3-rs1799983 was inversely (per minor allele: p-trend=0.04) associated with risk of low-grade prostate cancer. LIG3-rs1052536 and XRCC1-rs25489 were suggestively associated with reduced risk of high-grade prostate cancer (per minor allele: both p-trend=0.04). In the placebo arm, significant associations were observed among men with higher serum lycopene for APEX1-rs1760944 and NQO1-rs1800566, or higher serum β-cryptoxanthin for ERCC4-rs1800067. In the finasteride arm, stronger associations were observed among men with lower serum lycopene for NOS3-rs1799983, higher serum α-carotene, β-carotene, and β-cryptoxanthin for LIG3-rs1052536, or lower serum retinol for SOD2-rs1799725. These results suggest that germline variations in oxidative stress and DNA repair pathways may contribute to prostate carcinogenesis and that these associations may differ by intraprostatic sex steroid hormone status and be further modified by antioxidant status. Findings provide insights into the complex role of gene, gene-antioxidant and -finasteride interactions in prostate cancer etiology, and thus may lead to the development of preventative strategies.

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