scholarly journals Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

2015 ◽  
Vol 28 (6) ◽  
pp. 1144-1155 ◽  
Author(s):  
Julia E. Rager ◽  
Sloane K. Tilley ◽  
Samantha E. Tulenko ◽  
Lisa Smeester ◽  
Paul D. Ray ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Urothelial Cells ◽  
Novel Gene

scholarly journals A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Weimei Ruan ◽  
Xu Chen ◽  
Ming Huang ◽  
Hong Wang ◽  
Jiaxin Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Risk Stratification ◽  
Early Stage ◽  
Operative Risk ◽  
Low Grade ◽  
Single Center ◽  
Detection Model ◽  
Methylation Assay ◽  
Muscle Invasive

Abstract Background Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. Methods A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. Results The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7–77.8% vs. 0.0–22.2%, 0.0–22.2%), Ta tumor (83.3% vs. 22.2–41.2%, 44.4–52.9%) and non-muscle invasive BC (NMIBC) (80.0–89.7% vs. 51.5–52.0%, 59.4–72.0%) in both cohorts. The assay also had higher accuracies (88.9–95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6–70.8%) and FISH (72.2–77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. Conclusions The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

scholarly journals Metallothionein-1 and -2 Expression in Cadmium- or Arsenic-Derived Human Malignant Urothelial Cells and Tumor Heterotransplants and as a Prognostic Indicator in Human Bladder Cancer

2006 ◽  
Vol 91 (2) ◽  
pp. 467-475 ◽  
Author(s):  
Xu Dong Zhou ◽  
Donald A. Sens ◽  
Mary Ann Sens ◽  
Venugopal B. R. K. Namburi ◽  
Rajendra K. Singh ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Indicator ◽  
Human Bladder Cancer ◽  
Urothelial Cells ◽  
Human Bladder

scholarly journals DNA Hypermethylation of a panel of genes as an urinary biomarker for bladder cancer diagnosis

2021 ◽  
Author(s):  
Petros Georgopoulos ◽  
Maria Papaioannou ◽  
Soultana Markopoulou ◽  
Aikaterini Fragou ◽  
George Kouvatseas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Smoking Status ◽  
Gene Promoter ◽  
Control Group ◽  
Gene Promoters ◽  
Dna Hypermethylation ◽  
Diagnostic Potential ◽  
Specificity And Sensitivity ◽  
Promoter Dna

Abstract PurposeThe aim of this study was to explore the diagnostic potential of a panel of five hypermethylated gene promoters in bladder cancer. Individuals with primary BCa and control individuals matching the gender, age and smoking status of the cancer patients were recruited. DNA methylation was assessed for the gene promoters of RASSF1, RARβ, DAPK, hTERT and APC in urine samples collected by spontaneous urination. Fifty patients and 35 healthy controls were recruited, with average age of 70.26 years and average smoking status of 44.78 pack-years. In the BCa group, DNA methylation was detected in 27(61.4%) samples. RASSF1 was methylated in 52.2% of samples. Only 3(13.6%) samples from the control group were methylated, all in the RASSF1 gene promoter. The specificity and sensitivity of this panel of genes to diagnose BCa was 86% and 61% respectively. The RASSF1 gene could diagnose BCa with specificity 86.4% and sensitivity 52.3%. Promoter DNA methylation of this panel of five genes could be further investigated as urine biomarker for the diagnosis of BCa. The RASSF1 could be a single candidate biomarker for predicting BCa patients versus controls. Studies are required in order to develop a geographically adjusted diagnostic biomarker for BCa.Trial registration: ACTRN12620000258954

scholarly journals Antioxidants and selenocompounds inhibit 3,5-dimethylaminophenol toxicity to human urothelial cells

2019 ◽  
Vol 70 (1) ◽  
pp. 18-29 ◽  
Author(s):  
Pinar Erkekoglu ◽  
Ming-Wei Chao ◽  
Chia-Yi Tseng ◽  
Bevin P. Engelward ◽  
Ozge Kose ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Mammalian Cells ◽  
Antioxidant Enzyme Activities ◽  
Urothelial Cells ◽  
Dna Breaks ◽  
Primary Metabolite ◽  
Stress Changes

AbstractExposure to alkyl anilines may lead to bladder cancer, which is the second most frequent cancer of the urogenital tract. 3,5-dimethylaniline is highly used in industry. Studies on its primary metabolite 3,5-dimethylaminophenol (3,5-DMAP) showed that this compound causes oxidative stress, changes antioxidant enzyme activities, and leads to death of different mammalian cells. However, there is no in vitro study to show the direct effects of 3,5-DMAP on human bladder and urothelial cells. Selenocompounds are suggested to decrease oxidative stress caused by some chemicals, and selenium supplementation was shown to reduce the risk of bladder cancer. The main aim of this study was to investigate whether selenocompounds organic selenomethionine (SM, 10 µmol/L) or inorganic sodium selenite (SS, 30 nmol/L) could reduce oxidative stress, DNA damage, and apoptosis in UROtsa cells exposed to 3,5-DMAP. 3,5-DMAP caused a dose-dependent increase in intracellular generation of reactive oxygen species, and its dose of 50 µmol/L caused lipid peroxidation, protein oxidation, and changes in antioxidant enzyme activities in different cellular fractions. The comet assay also showed single-strand DNA breaks induced by the 3,5-DMAP dose of 50 µmol/L, but no changes in double-strand DNA breaks. Apoptosis was also triggered. Both selenocompounds provided partial protection against the cellular toxicity of 3,5-DMAP. Low selenium status along with exposure to alkyl anilines can be a major factor in the development of bladder cancer. More mechanistic studies are needed to specify the role of selenium in bladder cancer.

scholarly journals Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Nadine Bonberg ◽  
Beate Pesch ◽  
Thomas Behrens ◽  
Georg Johnen ◽  
Dirk Taeger ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Cells ◽  
Chromosomal Alterations ◽  
Healthy Men ◽  
Screening Study

scholarly journals Kaempferol Modulates DNA Methylation and Downregulates DNMT3B in Bladder Cancer

2017 ◽  
Vol 41 (4) ◽  
pp. 1325-1335 ◽  
Author(s):  
Wei Qiu ◽  
Jun Lin ◽  
Yichen Zhu ◽  
Jian Zhang ◽  
Liping Zeng ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Genomic Dna ◽  
Fruits And Vegetables ◽  
Dna Methyltransferases ◽  
Protein Levels ◽  
Anti Cancer ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Illumina Infinium Humanmethylation

Background: Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear. Methods: Nude mice bearing bladder cancer were treated with Kae for 31 days. The genomic DNA was extracted from xenografts and the methylation changes was determined using an Illumina Infinium HumanMethylation 450 BeadChip Array. The ubiquitination was detected using immuno-precipitation assay. Results: Our data indicated that Kae modulated DNA methylation in bladder cancer, inducing 103 differential DNA methylation positions (dDMPs) associated with genes (50 hyper-methylated and 53 hypo-methylated). DNA methylation is mostly relied on the levels of DNMTs. We observed that Kae specifically inhibited the protein levels of DNMT3B without altering the expression of DNMT1 or DNMT3A. However, Kae did not downregulate the transcription of DNMT3B. Interestingly, we observed that Kae induced a premature degradation of DNMT3B by inhibiting protein synthesis with cycloheximide (CHX). By blocking proteasome with MG132, we observed that Kae induced an increased ubiquitination of DNMT3B. These results suggested that Kae could induce the degradation of DNMT3B through ubiquitin-proteasome pathway. Conclusion: Our data indicated that Kae is a novel DNMT3B inhibitor, which may promote the degradation of DNMT3B in bladder cancer.

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