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Myung Hee Chung - One of the best experts on this subject based on the ideXlab platform.
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8 Hydroxydeoxyguanosine not mere biomarker for oxidative stress but remedy for oxidative stress implicated gastrointestinal diseases
World Journal of Gastroenterology, 2012Co-Authors: Chan Young Ock, Eunhee Kim, Duck Joo Choi, Hojae Lee, Ki Baik Hahm, Myung Hee ChungAbstract:Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-Hydroxydeoxyguanosine (8-OHdG), which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdG is generally regarded as a biomarker of mutagenesis consequent to oxidative stress. For example, higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdG can paradoxically reduce ROS production, attenuate the nuclear factor-κB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1, IL-6, cyclo-oxygenase-2, and inducible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1, NOX organizer-1 and NOX activator-1 in various conditions of inflammation-based gastrointestinal (GI) diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carcinogenesis. Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases, as well as the prevention of inflammation-associated GI cancer. In this editorial review, the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.
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8 Hydroxydeoxyguanosine suppresses no production and cox 2 activity via rac1 stats signaling in lps induced brain microglia
Free Radical Biology and Medicine, 2006Co-Authors: Hong Sook Kim, Joo Eun Jung, Ik Hyun Cho, Donghyun Kim, Seongwon Choi, Yong Sik Kim, Chung Gyu Park, Taeyoon Kim, Jung Weon Lee, Myung Hee ChungAbstract:Free 8-Hydroxydeoxyguanosine (oh(8)dG), a nucleoside of 8-hydroxyguanine (oh(8)Gua), present in cytosol is not incorporated into DNA. However, nothing is known about its biological function when it presents in cytosol as a free form. We demonstrate here for the first time that oh(8)dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh(8)dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1beta, IL-6, and TNF-alpha, in activated BV2 cells. We also found that oh(8)dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh(8)dG suppressed recruitment of STATs and p300 to the iNOS and COX-2 promoters, and inhibited H3 histone acetylation. Taken together, these results provide new aspects of oh(8)dG as an anti-inflammatory agent.
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anti inflammatory effects of 8 Hydroxydeoxyguanosine in lps induced microglia activation suppression of stat3 mediated intercellular adhesion molecule 1 expression
Experimental and Molecular Medicine, 2006Co-Authors: Joo Eun Jung, Taekyu Park, Young Mok Yang, Seungyong Seong, Sang Kyu Ye, Myung Hee ChungAbstract:Anti-inflammatory effects of 8-Hydroxydeoxyguanosine in LPS-induced microglia activation: suppression of STAT3-mediated intercellular adhesion molecule-1 expression
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anti inflammatory effects of 8 Hydroxydeoxyguanosine in lps induced microglia activation suppression of stat3 mediated intercellular adhesion molecule 1 expression
Experimental and Molecular Medicine, 2006Co-Authors: Dae Yong Kim, Joo Eun Jung, Taekyu Park, Young Mok Yang, Seungyong Seong, Hong Sook Kim, Ik Hyun Cho, Jaeun Kim, Kwang Ho Lee, Myung Hee ChungAbstract:To elucidate the roles of 8-Hydroxydeoxyguanosine (oh(8)dG), the nucleoside of 8-hydroxyguanine (oh(8)Gua), we examined the effects of oh(8)dG upon LPS-induced intercellular adhesion molecule-1 (ICAM-1) expression and the underlying mechanisms in brain microglial cells. We found that oh(8)dG reduces LPS-induced reactive oxygen species (ROS) production, STAT3 activation, and ICAM-1 expression. oh(8)dG also suppresses pro-inflammatory cytokines, such as TNF-alpha, IL-6 and IFN-gamma. Overexpression of dominant negative STAT3 completely diminshed STAT3-mediated ICAM-1 transcriptional activity. Chromatin immunoprecipitation studies revealed that oh(8)dG inhibited recruitment of STAT3 to the ICAM-1 promoter, followed by a decrease in ICAM-1 expression. Using mice lacking a functional Toll-like receptor 4 (TLR4), we demonstrated that, while TLR4+/+ microglia were activated by LPS, TLR4-/- microglia exhibited inactivated STAT3 in response to LPS. Evidently, LPS modulates STAT3-dependent ICAM-1 induction through TLR4-mdiated cellular responses. Oh(8)dG apparently plays a role in anti-inflammatory actions via suppression of ICAM-1 gene expression by blockade of the TLR4-STAT3 signal cascade in inflammation-enhanced brain microglia. Therefore, oh(8)dG in the cytosol probably functions as an anti-inflammatory molecule and should be considered as a candidate for development of anti-inflammatory agents.
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leukemic cell line kg 1 has a functional loss of hogg1 enzyme due to a point mutation and 8 Hydroxydeoxyguanosine can kill kg 1
Oncogene, 2000Co-Authors: Jinwon Hyun, Jeongyun Choi, Huihui Zeng, Yunsil Lee, Hyunsook Kim, Sunhee Yoon, Myung Hee ChungAbstract:We tested the cytotoxic action of 8-hydroxyguanine (8ohG) by observing the viability of several leukemic cell lines (KG-1, U937, Jurkat and K 562) in the presence of 8-Hydroxydeoxyguanosine (8ohdG), a nucleoside of 8ohG. It was found that 8ohdG showed cytotoxic action only to KG-1 and that only KG-1 showed a homozygous arginine 209 to glutamine mutation in the hOGG1 gene with an almost negligible hOGG1 enzyme activity. Possibly, the selective cytotoxicity in 8ohdG to KG-1 may be due to its low capacity to cope with an increase in the 8ohG level in DNA resulting from the incorporation of 8ohdG present in the culture media. The mutational impairment of hOGG1 in KG-1 is the first report in leukemic cell lines. Using KG-1 with impaired hOGG1, we demonstrated cytotoxicity of 8ohdG probably due to its incorporation into cellular DNA. This new property of KG-1 may allow it to serve as an useful tool for studies of OGG1, oxidative DNA damage and the cytotoxic action of 8ohG. Oncogene (2000) 19, 4476 - 4479.
Hiroshi Kasai - One of the best experts on this subject based on the ideXlab platform.
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lower serum levels of total cholesterol are associated with higher urinary levels of 8 Hydroxydeoxyguanosine
Nutrition & Metabolism, 2013Co-Authors: Hiroyuki Kikuchi, Hiroshi Kasai, Akiko Nanri, Ai Hori, Masao Sato, Kazuaki Kawai, Tetsuya MizoueAbstract:Background: Lower serum total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterols (LDL-C) have been linked to an increased risk of cancer in various sites, but its underlying mechanism remains unclear. In an attempt to clarify the association between cholesterol levels and oxidative DNA damage, we investigated the relationship between serum cholesterol and urinary 8-Hydroxydeoxyguanosine levels in a Japanese working population. Methods: The study subjects were 294 men and 209 women aged 21-66 years in two Japanese municipal offices. Urinary 8-Hydroxydeoxyguanosine (8-OHdG) was measured using an automated high-pressure liquid chromatography. Linear regression analysis was used to examine the associations of urinary 8-OHdG with TC, HDL-C and LDL-C levels with adjustment for sex, age, smoking and body mass index. Subgroup analyses were conducted by smoking status in men and age in women. Analysis of covariance was employed to estimate adjusted means of urinary 8-OHdG across TC category. Results: After multivariate adjustment, urinary 8-OHdG levels were inversely associated with serum TC levels (β= −0.0015, p < 0.05) and LDL-C levels (β = −0.0012, p = 0.07). The inverse association with TC was apparent among smoking men (β = −0.0017, p < 0.05) and among women aged less than 48 years (β = −0.0040, p < 0.01). 8-OHdG decreased as TC increased (up to 219 mg/dL); subjects with TC levels of <160 mg/dL had a 17.4% higher adjusted mean of 8-OHdG than did those with TC levels of 200–219 mg/dL. Conclusion: Results suggest that circulating low TC levels are associated with higher oxidative DNA damage.
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effect of age smoking and other lifestyle factors on urinary 7 methylguanine and 8 Hydroxydeoxyguanosine
Cancer Science, 2009Co-Authors: Kazuyoshi Tamae, Kazuaki Kawai, Sayumi Yamasaki, Kiyoshi Kawanami, Masato Ikeda, Ken Takahashi, Toshiaki Miyamoto, Noritada Kato, Hiroshi KasaiAbstract:Urinary 8-Hydroxydeoxyguanosine (8-OH-dG) and 7-methylguanine (m7Gua) were measured by a column-switching high performance liquid chromatography method as markers of oxidative and methylating DNA damage, respectively. We investigated the associations between urinary 8-OH-dG or m7Gua and various lifestyle and demographic factors, such as age and sex. The urinary 8-OH-dG excretion level was positively correlated with cigarette smoking, but inversely correlated with fruit consumption, physical activity and total energy consumed per day. A multiple regression analysis revealed that daily physical activity and healthy meal combinations decreased the urinary 8-OH-dG level, whereas alcohol consumption increased it. In terms of the urinary m7Gua measurement, cigarette smoking, age and consumption of meat, fish, egg, soybean, etc. were positively correlated with the urinary m7Gua level, whereas body weight, BMI, physical activity, and dietary index score, which indicates good nutritional balance, were negatively correlated with the amount of m7Gua. Based on a multiple regression analysis, cigarette smoking and age correlated with the m7Gua level, while high BMI and healthy meal combinations have significant reducing effects on m7Gua level. Therefore, the urinary m7Gua level is considered to be a useful marker of DNA methylation, not only from smoking, but also from aging and unhealthy dietary habits.
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8 Hydroxydeoxyguanosine generated in the earthworm eisenia fetida grown in metal containing soil
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2008Co-Authors: Tamiji Nakashima, Hiroshi Kasai, Kazuaki Kawai, Toshihiro Okada, Junpei Asahi, Akihisa Yamashita, Koji Matsuno, Shinobu Gamou, Takeshi HiranoAbstract:Heavy metal pollution of soil causes biological problems, such as mutagenicity to living organisms, including human beings. However, few methods have been developed to assess metal mutagenicity in soil. To avoid metal mutagenicity, an adequate bio-monitoring method is required. In the present study, to determine if the analysis of oxidative DNA damage generated in the earthworm is a useful bio-monitoring method for soil mutagenicity, the accumulation of 8-Hydroxydeoxyguanosine (8-OH-dG), a major form of oxidative DNA damage, in Eisenia fetida (Savigny, 1826) treated with cadmium chloride (CdCl2) or nickel chloride (NiCl2) was analyzed. E. fetida was treated with Cd (10 or 200 microg/g soil) or Ni (10 or 200 microg/g soil) for 1, 2, and 3 weeks or 3 months. After metal exposure, the metal concentration in E. fetida was analyzed by atomic absorption spectrometry and the 8-OH-dG accumulated in E. fetida was analyzed by HPLC analyses and immunohistochemistry. Atomic absorption spectrometry revealed that Cd, but not Ni, accumulated within E. fetida. The 8-OH-dG levels in the DNA of E. fetida treated with Cd for 3 months were significantly higher than those in control E. fetida. Moreover, immunohistochemical analyses revealed that positive signals for 8-OH-dG accumulation in seminal vesicles were detected only in E. fetida treated with 10 microg of Cd for 3 months. Although some points remain unresolved, a bio-monitoring system analyzing the DNA damage generated in the earthworm might be useful for the assessment of the mutagenicity of soil contaminated with various heavy metals, such as Cd.
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changes of urinary 8 Hydroxydeoxyguanosine levels during a two day ultramarathon race period in japanese non professional runners
International Journal of Sports Medicine, 2008Co-Authors: Machiko Miyata, Hiroshi Kasai, Kazuaki Kawai, N Yamada, Mizuho Tokudome, Hiromitsu Ichikawa, Chiho Goto, Yuko Tokudome, Kiyonori Kuriki, Hideki HoshinoAbstract:Using the urinary 8-Hydroxydeoxyguanosine (8-OHdG) concentration, effects of participation in a two-day ultramarathon race period on oxidative DNA damage were investigated in Japanese nonprofessional runners. Before the first day (baseline), after the first day (mid-race) of 40-km running, and after the second day (post-race) of 90 km running, biomaterials were successfully sampled from 95 participants (males, 79; females, 16) who completed the full race. We analyzed urine for 8-OHdG and blood for aspartate aminotransferase (AST), creatine phosphokinase (CPK) and myoglobin, and evaluated fluctuation in the values at three sampling time points. Adjusted baseline urinary 8-OHdG levels (microg/g creatinine) (mean +/- standard deviation) showed no significant differences between males and females, at 2.85 +/- 1.17 and 3.04 +/- 1.56, respectively. In males, mid-race urinary 8-OHdG levels rose to 3.29 +/- 1.15 (p < 0.01), but then returned to 2.73 +/- 1.16 at the post-race time point (p < 0.01). In females, a similar increase to 3.32 +/- 1.47 and subsequent decline to 2.80 +/- 1.47 were noted. In contrast, AST, CPK and myoglobin were increased at both mid- and post-time points and particularly the latter, independent of the sex. Extreme prolonged exercise in a two-day ultramarathon race period causes oxidative DNA damage but antioxidant repair systems are apparently induced to protect against oxidative DNA stress with physical exercise.
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occupational and lifestyle factors and urinary 8 Hydroxydeoxyguanosine
Cancer Science, 2005Co-Authors: Masahiro Irie, Kazuyoshi Tamae, Naoko Iwamototanaka, Hiroshi KasaiAbstract:The amount of 8-Hydroxydeoxyguanosine (8-OH-dG) excreted in urine can be used not only as an indicator of DNA repair capacity, but also as a potential marker of oxidative DNA damage. To clarify the oxidation-related factors, in consideration of cancer risk, this study investigated how urinary 8-OH-dG was associated with occupational and lifestyle factors in 372 healthy workers. The creatinine-adjusted urinary 8-OH-dG level was significantly higher in male subjects, smokers and drinkers compared with their counterparts. There were significant positive correlations of the 8-OH-dG level with average number of working hours, involvement in work, average number of cigarettes smoked, average volume of alcohol consumed and serum cortisol level, and there were significant negative correlations of the 8-OH-dG level with body mass index (BMI) and consumption of soybean products, rice and light-colored vegetables. Multiple regression analysis showed that average number of working hours and average number of cigarettes smoked were significant predictors of increased 8-OH-dG levels, whereas being female and BMI were significant predictors of decreased 8-OH-dG levels. Working hours, BMI and smoking were significant predictors of urinary 8-OH-dG in male subjects, whereas age and BMI were significant predictors in female subjects. We suggest that several occupational and lifestyle factors, particularly long working hours and cigarette smoking, are linked to the formation of 8-OH-dG in workers.
Peeter Karihtala - One of the best experts on this subject based on the ideXlab platform.
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preoperative serum 8 Hydroxydeoxyguanosine is associated with chemoresistance and is a powerful prognostic factor in endometrioid type epithelial ovarian cancer
BMC Cancer, 2015Co-Authors: Marjo Pylvaseerola, Peeter Karihtala, Ulla PuistolaAbstract:Background Oxidative stress is a widely seen phenomenon in several carcinomas. Increasing evidence also suggests that it has a significant role in the development of epithelial ovarian carcinoma (EOC). 8-Hydroxydeoxyguanosine (8-OHdG) is one of the main indicators of oxidative stress and increased expression of 8-OHdG has previously been seen in EOC. DJ-1 is an oncoprotein connected to oxidative stress regulation, but its role in ovarian cancer is not well known. We investigated redox status in different histotypes of EOC by measuring serum 8-OHdG and DJ-1 concentrations and their associations with known prognostic factors.
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divergent behaviour of oxidative stress markers 8 Hydroxydeoxyguanosine 8 ohdg and 4 hydroxy 2 nonenal hne in breast carcinogenesis
Histopathology, 2011Co-Authors: Peeter Karihtala, Saila Kauppila, Ulla Puistola, Arja JukkolavuorinenAbstract:Karihtala P, Kauppila S, Puistola U & Jukkola-Vuorinen A (2011) Histopathology58, 854–862 Divergent behaviour of oxidative stress markers 8-Hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE) in breast carcinogenesis Aims: To clarify the role of oxidative stress during breast carcinogenesis by studying the expression of 8-Hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative DNA damage) and 4-hydroxy-2-nonenal (HNE) (a marker of lipid peroxidation) during the different phases of breast carcinogenesis. Methods and results: The study material consisted of a total of 219 patients: 31 with usual ductal hyperplasia (UDH), 25 with atypical ductal hyperplasia (ADH), 30 with ductal carcinoma in situ (DCIS) and 133 with invasive carcinoma. The expression of 8-OHdG and HNE were evaluated immunohistochemically. Both 8-OHdG (77.4%) and HNE (45.8%) expression was already seen in UDH lesions. Interestingly, the trend of these two immunostainings during breast carcinogenesis was diverse. 8-OHdG expression diminished significantly in invasive breast carcinomas compared to non-invasive lesions (P < 0.005 when set against non-invasive cohorts). Also within the same lesions, 8-OHdG expression was the most intensive in benign cells. Conversely, HNE immunostaining was strongest in invasive breast carcinomas (UDH versus invasive cohort, P = 0.015). Conclusions: 4-hydroxy-2-nonenal as a marker of lipid peroxidation increases during breast carcinogenesis, reflecting the role of oxidative stress in the pathogenesis of breast cancer. However, 8-OHdG shows diminished levels in carcinomas, possibly resulting from the induction of DNA repair in these invasive lesions.
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divergent behaviour of oxidative stress markers 8 Hydroxydeoxyguanosine 8 ohdg and 4 hydroxy 2 nonenal hne in breast carcinogenesis
Histopathology, 2011Co-Authors: Peeter Karihtala, Saila Kauppila, Ulla Puistola, Arja JukkolavuorinenAbstract:Aims To clarify the role of oxidative stress during breast carcinogenesis by studying the expression of 8-Hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative DNA damage) and 4-hydroxy-2-nonenal (HNE) (a marker of lipid peroxidation) during the different phases of breast carcinogenesis. Methods and results The study material consisted of a total of 219 patients: 31 with usual ductal hyperplasia (UDH), 25 with atypical ductal hyperplasia (ADH), 30 with ductal carcinoma in situ (DCIS) and 133 with invasive carcinoma. The expression of 8-OHdG and HNE were evaluated immunohistochemically. Both 8-OHdG (77.4%) and HNE (45.8%) expression was already seen in UDH lesions. Interestingly, the trend of these two immunostainings during breast carcinogenesis was diverse. 8-OHdG expression diminished significantly in invasive breast carcinomas compared to non-invasive lesions (P Conclusions 4-hydroxy-2-nonenal as a marker of lipid peroxidation increases during breast carcinogenesis, reflecting the role of oxidative stress in the pathogenesis of breast cancer. However, 8-OHdG shows diminished levels in carcinomas, possibly resulting from the induction of DNA repair in these invasive lesions.
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8 Hydroxydeoxyguanosine a new potential independent prognostic factor in breast cancer
British Journal of Cancer, 2010Co-Authors: Henri Sova, Saila Kauppila, Arja Jukkolavuorinen, Ulla Puistola, Peeter KarihtalaAbstract:8-Hydroxydeoxyguanosine (8-oxodG) is the commonly used marker of oxidative stress-derived DNA damage. 8-OxodG formation is regulated by local antioxidant capacity and DNA repair enzyme activity. Earlier studies have reported contradictory data on the function of 8-oxodG as a prognostic factor in different cancer types. We assessed pre-operative serum 8-oxodG levels with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OxodG expression in the nuclei of cancer cells from 150 of these patients was examined by immunohistochemistry. The serum 8-oxodG levels and immunohistochemical 8-oxodG expression were in concordance with each other (P<0.05). Negative 8-oxodG immunostaining was an independent prognostic factor for poor breast cancer-specific survival according to the multivariate analysis (P<0.01). This observation was even more remarkable when ductal carcinomas only (n=140) were considered (P<0.001). A low serum 8-oxodG level was associated statistically significantly with lymphatic vessel invasion and a positive lymph node status. Low serum 8-oxodG levels and a low immunohistochemical 8-oxodG expression were associated with an aggressive breast cancer phenotype. In addition, negative 8-oxodG immunostaining was a powerful prognostic factor for breast cancer-specific death in breast carcinoma patients.
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dna adduct 8 Hydroxydeoxyguanosine a novel putative marker of prognostic significance in ovarian carcinoma
International Journal of Gynecological Cancer, 2009Co-Authors: Peeter Karihtala, Ylermi Soini, Liisa Vaskivuo, Risto Bloigu, Ulla PuistolaAbstract:Objectives: Previous studies have suggested the importance of reactive oxygen species in all the steps of carcinogenesis. Antioxidant enzymes are considered as the most specific and efficient way to protect cells from reactive oxygen species. The purpose of the current study was to identify the role of oxidative stress and major antioxidant enzymes in ovarian carcinomas. Methods: The material consisted of 68 invasive ovarian carcinomas which were studied by immunohistochemistry with antibodies to antioxidant enzymes peroxiredoxins (Prxs) I-VI and thioredoxin and oxidative stress markers nitrotyrosine and 8-Hydroxydeoxyguanosine (8-OHdG). Both the intensity and the extent of the stainings were assessed, and the nuclear and cytoplasmic expressions were evaluated separately. Results: The study revealed the hydroxyl radical-derived oxidative stress marker in DNA, 8-OHdG, to be a powerful prognostic factor in ovarian carcinoma (Kaplan-Meier survival log-rank-analysis P = 0.003; risk of death to ovarian carcinoma 2.69; 95% confidence interval 1.35-5.35. 8-OHdG was also associated with poor differentiation (P = 0.053), higher stage (P Conclusions: 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.
Arja Jukkolavuorinen - One of the best experts on this subject based on the ideXlab platform.
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divergent behaviour of oxidative stress markers 8 Hydroxydeoxyguanosine 8 ohdg and 4 hydroxy 2 nonenal hne in breast carcinogenesis
Histopathology, 2011Co-Authors: Peeter Karihtala, Saila Kauppila, Ulla Puistola, Arja JukkolavuorinenAbstract:Karihtala P, Kauppila S, Puistola U & Jukkola-Vuorinen A (2011) Histopathology58, 854–862 Divergent behaviour of oxidative stress markers 8-Hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE) in breast carcinogenesis Aims: To clarify the role of oxidative stress during breast carcinogenesis by studying the expression of 8-Hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative DNA damage) and 4-hydroxy-2-nonenal (HNE) (a marker of lipid peroxidation) during the different phases of breast carcinogenesis. Methods and results: The study material consisted of a total of 219 patients: 31 with usual ductal hyperplasia (UDH), 25 with atypical ductal hyperplasia (ADH), 30 with ductal carcinoma in situ (DCIS) and 133 with invasive carcinoma. The expression of 8-OHdG and HNE were evaluated immunohistochemically. Both 8-OHdG (77.4%) and HNE (45.8%) expression was already seen in UDH lesions. Interestingly, the trend of these two immunostainings during breast carcinogenesis was diverse. 8-OHdG expression diminished significantly in invasive breast carcinomas compared to non-invasive lesions (P < 0.005 when set against non-invasive cohorts). Also within the same lesions, 8-OHdG expression was the most intensive in benign cells. Conversely, HNE immunostaining was strongest in invasive breast carcinomas (UDH versus invasive cohort, P = 0.015). Conclusions: 4-hydroxy-2-nonenal as a marker of lipid peroxidation increases during breast carcinogenesis, reflecting the role of oxidative stress in the pathogenesis of breast cancer. However, 8-OHdG shows diminished levels in carcinomas, possibly resulting from the induction of DNA repair in these invasive lesions.
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divergent behaviour of oxidative stress markers 8 Hydroxydeoxyguanosine 8 ohdg and 4 hydroxy 2 nonenal hne in breast carcinogenesis
Histopathology, 2011Co-Authors: Peeter Karihtala, Saila Kauppila, Ulla Puistola, Arja JukkolavuorinenAbstract:Aims To clarify the role of oxidative stress during breast carcinogenesis by studying the expression of 8-Hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative DNA damage) and 4-hydroxy-2-nonenal (HNE) (a marker of lipid peroxidation) during the different phases of breast carcinogenesis. Methods and results The study material consisted of a total of 219 patients: 31 with usual ductal hyperplasia (UDH), 25 with atypical ductal hyperplasia (ADH), 30 with ductal carcinoma in situ (DCIS) and 133 with invasive carcinoma. The expression of 8-OHdG and HNE were evaluated immunohistochemically. Both 8-OHdG (77.4%) and HNE (45.8%) expression was already seen in UDH lesions. Interestingly, the trend of these two immunostainings during breast carcinogenesis was diverse. 8-OHdG expression diminished significantly in invasive breast carcinomas compared to non-invasive lesions (P Conclusions 4-hydroxy-2-nonenal as a marker of lipid peroxidation increases during breast carcinogenesis, reflecting the role of oxidative stress in the pathogenesis of breast cancer. However, 8-OHdG shows diminished levels in carcinomas, possibly resulting from the induction of DNA repair in these invasive lesions.
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8 Hydroxydeoxyguanosine a new potential independent prognostic factor in breast cancer
British Journal of Cancer, 2010Co-Authors: Henri Sova, Saila Kauppila, Arja Jukkolavuorinen, Ulla Puistola, Peeter KarihtalaAbstract:8-Hydroxydeoxyguanosine (8-oxodG) is the commonly used marker of oxidative stress-derived DNA damage. 8-OxodG formation is regulated by local antioxidant capacity and DNA repair enzyme activity. Earlier studies have reported contradictory data on the function of 8-oxodG as a prognostic factor in different cancer types. We assessed pre-operative serum 8-oxodG levels with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OxodG expression in the nuclei of cancer cells from 150 of these patients was examined by immunohistochemistry. The serum 8-oxodG levels and immunohistochemical 8-oxodG expression were in concordance with each other (P<0.05). Negative 8-oxodG immunostaining was an independent prognostic factor for poor breast cancer-specific survival according to the multivariate analysis (P<0.01). This observation was even more remarkable when ductal carcinomas only (n=140) were considered (P<0.001). A low serum 8-oxodG level was associated statistically significantly with lymphatic vessel invasion and a positive lymph node status. Low serum 8-oxodG levels and a low immunohistochemical 8-oxodG expression were associated with an aggressive breast cancer phenotype. In addition, negative 8-oxodG immunostaining was a powerful prognostic factor for breast cancer-specific death in breast carcinoma patients.
Ulla Puistola - One of the best experts on this subject based on the ideXlab platform.
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preoperative serum 8 Hydroxydeoxyguanosine is associated with chemoresistance and is a powerful prognostic factor in endometrioid type epithelial ovarian cancer
BMC Cancer, 2015Co-Authors: Marjo Pylvaseerola, Peeter Karihtala, Ulla PuistolaAbstract:Background Oxidative stress is a widely seen phenomenon in several carcinomas. Increasing evidence also suggests that it has a significant role in the development of epithelial ovarian carcinoma (EOC). 8-Hydroxydeoxyguanosine (8-OHdG) is one of the main indicators of oxidative stress and increased expression of 8-OHdG has previously been seen in EOC. DJ-1 is an oncoprotein connected to oxidative stress regulation, but its role in ovarian cancer is not well known. We investigated redox status in different histotypes of EOC by measuring serum 8-OHdG and DJ-1 concentrations and their associations with known prognostic factors.
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divergent behaviour of oxidative stress markers 8 Hydroxydeoxyguanosine 8 ohdg and 4 hydroxy 2 nonenal hne in breast carcinogenesis
Histopathology, 2011Co-Authors: Peeter Karihtala, Saila Kauppila, Ulla Puistola, Arja JukkolavuorinenAbstract:Karihtala P, Kauppila S, Puistola U & Jukkola-Vuorinen A (2011) Histopathology58, 854–862 Divergent behaviour of oxidative stress markers 8-Hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE) in breast carcinogenesis Aims: To clarify the role of oxidative stress during breast carcinogenesis by studying the expression of 8-Hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative DNA damage) and 4-hydroxy-2-nonenal (HNE) (a marker of lipid peroxidation) during the different phases of breast carcinogenesis. Methods and results: The study material consisted of a total of 219 patients: 31 with usual ductal hyperplasia (UDH), 25 with atypical ductal hyperplasia (ADH), 30 with ductal carcinoma in situ (DCIS) and 133 with invasive carcinoma. The expression of 8-OHdG and HNE were evaluated immunohistochemically. Both 8-OHdG (77.4%) and HNE (45.8%) expression was already seen in UDH lesions. Interestingly, the trend of these two immunostainings during breast carcinogenesis was diverse. 8-OHdG expression diminished significantly in invasive breast carcinomas compared to non-invasive lesions (P < 0.005 when set against non-invasive cohorts). Also within the same lesions, 8-OHdG expression was the most intensive in benign cells. Conversely, HNE immunostaining was strongest in invasive breast carcinomas (UDH versus invasive cohort, P = 0.015). Conclusions: 4-hydroxy-2-nonenal as a marker of lipid peroxidation increases during breast carcinogenesis, reflecting the role of oxidative stress in the pathogenesis of breast cancer. However, 8-OHdG shows diminished levels in carcinomas, possibly resulting from the induction of DNA repair in these invasive lesions.
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divergent behaviour of oxidative stress markers 8 Hydroxydeoxyguanosine 8 ohdg and 4 hydroxy 2 nonenal hne in breast carcinogenesis
Histopathology, 2011Co-Authors: Peeter Karihtala, Saila Kauppila, Ulla Puistola, Arja JukkolavuorinenAbstract:Aims To clarify the role of oxidative stress during breast carcinogenesis by studying the expression of 8-Hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative DNA damage) and 4-hydroxy-2-nonenal (HNE) (a marker of lipid peroxidation) during the different phases of breast carcinogenesis. Methods and results The study material consisted of a total of 219 patients: 31 with usual ductal hyperplasia (UDH), 25 with atypical ductal hyperplasia (ADH), 30 with ductal carcinoma in situ (DCIS) and 133 with invasive carcinoma. The expression of 8-OHdG and HNE were evaluated immunohistochemically. Both 8-OHdG (77.4%) and HNE (45.8%) expression was already seen in UDH lesions. Interestingly, the trend of these two immunostainings during breast carcinogenesis was diverse. 8-OHdG expression diminished significantly in invasive breast carcinomas compared to non-invasive lesions (P Conclusions 4-hydroxy-2-nonenal as a marker of lipid peroxidation increases during breast carcinogenesis, reflecting the role of oxidative stress in the pathogenesis of breast cancer. However, 8-OHdG shows diminished levels in carcinomas, possibly resulting from the induction of DNA repair in these invasive lesions.
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8 Hydroxydeoxyguanosine a new potential independent prognostic factor in breast cancer
British Journal of Cancer, 2010Co-Authors: Henri Sova, Saila Kauppila, Arja Jukkolavuorinen, Ulla Puistola, Peeter KarihtalaAbstract:8-Hydroxydeoxyguanosine (8-oxodG) is the commonly used marker of oxidative stress-derived DNA damage. 8-OxodG formation is regulated by local antioxidant capacity and DNA repair enzyme activity. Earlier studies have reported contradictory data on the function of 8-oxodG as a prognostic factor in different cancer types. We assessed pre-operative serum 8-oxodG levels with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OxodG expression in the nuclei of cancer cells from 150 of these patients was examined by immunohistochemistry. The serum 8-oxodG levels and immunohistochemical 8-oxodG expression were in concordance with each other (P<0.05). Negative 8-oxodG immunostaining was an independent prognostic factor for poor breast cancer-specific survival according to the multivariate analysis (P<0.01). This observation was even more remarkable when ductal carcinomas only (n=140) were considered (P<0.001). A low serum 8-oxodG level was associated statistically significantly with lymphatic vessel invasion and a positive lymph node status. Low serum 8-oxodG levels and a low immunohistochemical 8-oxodG expression were associated with an aggressive breast cancer phenotype. In addition, negative 8-oxodG immunostaining was a powerful prognostic factor for breast cancer-specific death in breast carcinoma patients.
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dna adduct 8 Hydroxydeoxyguanosine a novel putative marker of prognostic significance in ovarian carcinoma
International Journal of Gynecological Cancer, 2009Co-Authors: Peeter Karihtala, Ylermi Soini, Liisa Vaskivuo, Risto Bloigu, Ulla PuistolaAbstract:Objectives: Previous studies have suggested the importance of reactive oxygen species in all the steps of carcinogenesis. Antioxidant enzymes are considered as the most specific and efficient way to protect cells from reactive oxygen species. The purpose of the current study was to identify the role of oxidative stress and major antioxidant enzymes in ovarian carcinomas. Methods: The material consisted of 68 invasive ovarian carcinomas which were studied by immunohistochemistry with antibodies to antioxidant enzymes peroxiredoxins (Prxs) I-VI and thioredoxin and oxidative stress markers nitrotyrosine and 8-Hydroxydeoxyguanosine (8-OHdG). Both the intensity and the extent of the stainings were assessed, and the nuclear and cytoplasmic expressions were evaluated separately. Results: The study revealed the hydroxyl radical-derived oxidative stress marker in DNA, 8-OHdG, to be a powerful prognostic factor in ovarian carcinoma (Kaplan-Meier survival log-rank-analysis P = 0.003; risk of death to ovarian carcinoma 2.69; 95% confidence interval 1.35-5.35. 8-OHdG was also associated with poor differentiation (P = 0.053), higher stage (P Conclusions: 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.
