DNA Adduct 8-Hydroxydeoxyguanosine, a Novel Putative Marker of Prognostic Significance in Ovarian Carcinoma

Karihtala, Peeter; Soini, Ylermi; Vaskivuo, Liisa; Bloigu, Risto; Puistola, Ulla

doi:10.1111/igc.0b013e3181ad0f0d

Cited by 59 publications

(50 citation statements)

References 18 publications

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“…H 2 O 2 is further decomposed into molecular oxygen and water by "H 2 O 2 -detoxifying enzymes" (such as catalase and thioredoxin) to prevent the formation of highly reactive hydroxyl radicals by excess H 2 O 2 . Both of these steps are crucial, as hydroxyl radicals can readily generate DNA adducts, principally 8-oxo-7,8-dihydro-2 0 -deoxyguanosine (8-oxo-dG), if not prevented by antioxidant enzymes (40,41). In contrast to SOD2, FTEb(S) samples show decreased expression of thioredoxin and catalase relative to the remaining luteal phase samples (not shown).…”

Section: Discussionmentioning

confidence: 99%

Prolonged Postovulatory Proinflammatory Signaling in the Fallopian Tube Epithelium May Be Mediated through a BRCA1/DAB2 Axis

Tone

Virtanen

Shaw

et al. 2012

Clinical Cancer Research

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Purpose: To assess inflammation-related gene expression in nonmalignant fallopian tube epithelium (FTE) from BRCA1/2 mutation carriers and control patients obtained during the luteal and follicular phase, and to determine the impact of BRCA1 and disabled homolog 2 (DAB2) on NF-kB-mediated proinflammatory signaling.Experimental Design: A list of inflammation-related and NF-kB-responsive genes was compiled through gene set enrichment and PubMed database search, corresponding probes identified, and unpaired t tests conducted to identify differentially expressed genes in previously profiled FTE samples. ES2 and A549 cells were cotransfected with DAB2-or BRCA1-targeting siRNA and an NF-kB-responsive luciferase reporter, treated with TNF-a and luciferase activity determined. To determine whether DAB2 or BRCA1 alters mRNA expression of NF-kB target genes, cells were transfected with siRNA, treated with TNF-a, and harvested for total RNA extraction and quantitative real-time PCR.Results: A subset of BRCA1-mutated luteal phase samples previously found to group with adnexal highgrade serous carcinomas (HGSCs) differentially expressed 124 inflammation-associated probesets relative to remaining FTE samples. These samples also differentially expressed 264 probes relative to other luteal phase samples exposed to the same postovulatory environment. Both BRCA1-and DAB2-targeting siRNA increased TNF-a-induced NF-kB activity and mRNA expression of NF-kB-dependent target gene SOD2 relative to nontargeting siRNA, suggesting that both proteins repress proinflammatory signaling.Conclusions: These data provide evidence of elevated proinflammatory signaling in a subset of BRCA1-mutated luteal phase FTE, consistent with an altered response to ovulation-associated cytokines. Furthermore, both BRCA1 and DAB2 affect NF-kB activity, indicating a novel link between BRCA mutation status, ovulation, and predisposition to HGSC.

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Section: Discussionmentioning

confidence: 99%

Prolonged Postovulatory Proinflammatory Signaling in the Fallopian Tube Epithelium May Be Mediated through a BRCA1/DAB2 Axis

Tone

Virtanen

Shaw

et al. 2012

Clinical Cancer Research

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“…However, only a limited number of studies have focused on the relationship between oxidative markers and HCC prognosis (13)(14)(15)(16). Since 8-OHdG has been used as a biomarker with prognostic significance for several types of cancer (17)(18)(19), we assessed the predictive power of 8-OHdG on HBV-HCC prognosis and examined the correlation between 8-OHdG and clinical characteristics of HBV-HCC. The post-operative HCC patients enrolled in this study were followed up with regular visits in our hospital.…”

Section: Introductionmentioning

confidence: 99%

8-Hydroxy-2′-deoxyguanosine expression predicts hepatocellular carcinoma outcome

Wang

et al. 2011

Oncology Letters

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Abstract. Hepatocellular carcinoma (HCC) is characterized by increased oxidative stress and the production of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is one of the main mutagenic modifications of DNA by oxidative stress. We analyzed the association of 8-OHdG with post-operative survival and revealed that low levels of 8-OHdG are associated with significantly shorter survival time. Moreover, levels of 8-OHdG were associated with HCC characteristics, including tumor size, tumor quantity, clinical staging, Child classification, portal vein thrombosis and ascites. These results suggest that oxidative damage is a useful prognostic marker in HCC when other clinical characteristics are present with 8-OHdG.

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“…There is strong evidence suggesting that ROS are an important factor in carcinogenesis [21,22]. It is known that severe oxidative stress does not only cause damage and mutation in tumour suppressor genes, but also plays a significant role in carcinogenesis [7,8].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Apoptotic Activity Dysregulation and Oxidative Stress in the Development of Epithelial Ovarian Cancer: A Case-Controlled Descriptive Analysis

Incebiyik

Camuzcuoğlu²,

Vural³

et al. 2015

Gynecol Obstet Invest

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Aim: In the present study, we aimed to assess whether oxidative stress and apoptotic activity play a role in the development of epithelial ovarian cancer (EOC). Methods: The study group included patients with EOC (n = 26) and benign ovarian tumour (BOT) (n = 25), while 30 healthy women were employed as a control group. Venous blood samples were drawn to evaluate oxidative stress parameters and serum M30/M65 antigen levels before surgery. In addition, blood samples were taken for the second time on postoperative day 8 to analyse whether the postoperative tumour load was decreased. Results: When the groups were assessed regarding oxidative stress, the highest values were detected in patients with EOC. Serum M30/M65 levels were found to be higher in patients with EOC when compared to the other groups (p < 0.001). A significant decrease was determined in the M30/M65 levels of serum samples taken on postoperative day 8 from the patients in the EOC and BOT groups (p < 0.001). Conclusion: Our results suggest that dysregulation of apoptotic activity could be effective in the development of ovarian tumoural tissue, whereas oxidative stress could be effective in malignant transformation.

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DNA Adduct 8-Hydroxydeoxyguanosine, a Novel Putative Marker of Prognostic Significance in Ovarian Carcinoma

Abstract: To conclude, it appears that hydroxyl radical-derived oxidative stress, but not nitric oxide radical-derived oxidative stress, plays a significant role in ovarian carcinogenesis. Immunohistochemical assessment of 8-OHdG could provide a useful prognostic marker in ovarian cancer.

Cited by 59 publications

References 18 publications

Prolonged Postovulatory Proinflammatory Signaling in the Fallopian Tube Epithelium May Be Mediated through a BRCA1/DAB2 Axis

Prolonged Postovulatory Proinflammatory Signaling in the Fallopian Tube Epithelium May Be Mediated through a BRCA1/DAB2 Axis

8-Hydroxy-2′-deoxyguanosine expression predicts hepatocellular carcinoma outcome

Assessment of Apoptotic Activity Dysregulation and Oxidative Stress in the Development of Epithelial Ovarian Cancer: A Case-Controlled Descriptive Analysis

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