Increased Oxidative Stress in the Proximal Stomach of Patients with Barrett’s Esophagus and Adenocarcinoma of the Esophagus and Esophagogastric Junction

Kauppi, Juha; Räsänen, Jari; Sihvo, Eero; Nieminen, U; Arkkila, Perttu; Ahotupa, Markku; Salo, Jarmo A.

doi:10.1016/j.tranon.2016.06.004

Cited by 16 publications

(11 citation statements)

References 34 publications

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“…Signature 17 is most prominent in gastric cancers and esophageal adenocarcinoma (EAC), where it appears early during disease development [ 42 ], and it is also present in Barrett’s esophagus (BE), a precursor to EAC [ 43 ]. Due to the importance of gastro-esophageal and duodeno-gastric reflux in the development of BE and EAC [ 44 – 46 ] and the resulting oxidative stress [ 47 – 50 ], it has been speculated that oxidative damage could cause the mutation patterns characteristic for signature 17 [ 51 , 52 ]. Increased oxidative damage to guanine has been reported in the epithelial cells of dysplastic BE as well as after incubation of BE tissue with a cocktail mimicking bile reflux [ 50 ].…”

Section: Resultsmentioning

confidence: 99%

Mutational signature distribution varies with DNA replication timing and strand asymmetry

et al. 2018

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BackgroundDNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures—each representing a mutagenic process—derived from 3056 patients spanning 19 cancer types to quantify the strand asymmetry of mutational signatures around replication origins and between early and late replicating regions.ResultsWe observe that most of the detected mutational signatures are significantly correlated with the timing or direction of DNA replication. The properties of these associations are distinct for different signatures and shed new light on several mutagenic processes. For example, our results suggest that oxidative damage to the nucleotide pool substantially contributes to the mutational landscape of esophageal adenocarcinoma.ConclusionsTogether, our results indicate an interaction between DNA replication, the associated damage repair, and most mutagenic processes.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1509-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Mutational signature distribution varies with DNA replication timing and strand asymmetry

et al. 2018

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“…We should be careful the elevated levels of 8-oxodG in CAG patients and prevent the potentially occurrence of cancer. Kauppi et al demonstrated that ROS was elevated in the proximal stomach of Barrett’s esophagus and adenocarcinoma patients, which stimulates the proximal stomach mucosa, contributing to the development of cancer in the end [ 27 ]. Ma et al found that the level of 8-oxodG in gastric cancer patients was sharply higher than that in normal [ 28 ].…”

Section: Potential Application In Detection Of Diseasesmentioning

confidence: 99%

Potential application of the oxidative nucleic acid damage biomarkers in detection of diseases

et al. 2017

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Reactive oxygen species (ROS) are generated after exposure to harmful environmental factors and during normal cellular metabolic processes. The balance of the generating and scavenging of ROS plays a significant role in living cells. The accumulation of ROS will lead to oxidative damage to biomolecules including nucleic acid. Although many types of oxidative nucleic acid damage products have been identified, 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoG) has been commonly chosen as the biomarkers of oxidative damage to DNA and RNA, respectively. It has been demonstrated that oxidative damage to nucleic acid is an initiator in pathogenesis of numerous diseases. Thus, oxidative nucleic acid damage biomarkers have the potential to be utilized for detection of diseases. Herein, we reviewed the relationship of oxidative nucleic acid damage and development of various diseases including cancers (colorectal cancer, gastrointestinal cancer, breast cancer, lung cancer, epithelial ovarian carcinoma, esophageal squamous cell carcinoma), neurodegenerative disorders and chronic diseases (diabetes and its complications, cardiovascular diseases). The potential of oxidative nucleic acid damage biomarkers for detection of diseases and drug development were described. Moreover, the approaches for detection of these biomarkers were also summarized.

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“…30 Several studies have revealed the correlation of 8-OHdG with Barrett's esophagus, adenocarcinoma of the esophagus and stomach, gastric atrophy and intestinal metaplasia. 31,32 Therefore, this result is thought to be a demonstration of the antioxidative and gastric protective effect of GCWB104, because 8-OHdG has been significantly decreased in the test group, although it is difficult to interpret that it contributes directly to improving GI function.…”

Section: Discussionmentioning

confidence: 89%

The Efficacy and Safety of GCWB104 (<i>Flos</i> Lonicera Extract) in Functional Dyspepsia: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Study

et al. 2020

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Background/Aims: The Flos Lonicera extract GCWB104 has been shown to have significant protective effects against gastritis and gastric ulcers in vivo. The aim of this study was to investigate the efficacy and safety of GCWB104 in subjects with functional dyspepsia (FD). Methods: In this singlecenter, double-blind, randomized clinical trial, 92 subjects diagnosed with FD using the Rome III criteria were allocated to either the test group (300 mg of GCWB104, containing 125 mg of Flos Lonicera extract, twice daily) or the placebo group (300 mg placebo, twice daily). The total score improvement on the Gastrointestinal Symptom Rating Scale (GSRS) for individual symptoms, changes in antioxidant levels, changes in dyspepsia-related quality of life according to the Nepean Dyspepsia Index (NDI), and adverse effects were compared before and after 8 weeks of treatment. Results: The differences in total GSRS scores and score improvements after 8 weeks of treatment were significant between the GCWB104 and control groups (p=0.0452 and p=0.0486, respectively). Thirteen of 15 individual symptoms on the GSRS improved in the GCWB104 group, while six symptoms improved in the control group. In addition, statistically significant changes in rumbling, loose stool, and stool urgency were observed in the GCWB104 group. Blood 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, known as antioxidants, showed significant reductions after 8 weeks of administration of GCWB104. There were no adverse events related to treatment with GCWB104. Conclusions: GCWB104 safely contributed to improvements in mild to moderate FD and irritable bowel syndrome symptoms. Antioxidant effects of GCWB104 were also suggested (Clinicaltrials.gov number NCT04008901).

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Increased Oxidative Stress in the Proximal Stomach of Patients with Barrett’s Esophagus and Adenocarcinoma of the Esophagus and Esophagogastric Junction

Cited by 16 publications

References 34 publications

Mutational signature distribution varies with DNA replication timing and strand asymmetry

Mutational signature distribution varies with DNA replication timing and strand asymmetry

Potential application of the oxidative nucleic acid damage biomarkers in detection of diseases

The Efficacy and Safety of GCWB104 (<i>Flos</i> Lonicera Extract) in Functional Dyspepsia: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Study

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