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Xiaoxin Chen - One of the best experts on this subject based on the ideXlab platform.
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involvement of the 5 lipoxygenase leukotriene a4 hydrolase pathway in 7 12 dimethylbenz a anthracene dmba induced oral Carcinogenesis in hamster cheek pouch and inhibition of Carcinogenesis by its inhibitors
Carcinogenesis, 2006Co-Authors: Zheng Sun, Sandeep Sood, Divya Ramji, Peiying Yang, Robert A Newman, Chung S Yang, Xiaoxin ChenAbstract:Previous studies have shown that aberrant arachidonic acid (AA) metabolism, especially cyclooxygenase-2 (Cox-2) and 5-lipoxygenase (5-Lox) pathways, are activated during oral Carcinogenesis, and can be targeted for cancer prevention. This study was designed to investigate the importance of 5-Lox/leukotriene A4 hydrolase (LTA4H) pathway of AA metabolism in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch Carcinogenesis. In a short-term study, topical application of DMBA for 3 weeks induced severe inflammation and aberrant AA metabolism. Subsequent topical treatment with zileuton, celecoxib, or their combination for 1 week significantly suppressed aberrant AA metabolism and cell proliferation in the oral epithelium. Interestingly, zileuton was effective in inhibiting biosynthesis of multiple AA metabolites, including leukotriene B4 (LTB4), 5-, 12-, 15-hydroxyeicosatetraenoic acid and prostaglandin E2 (PGE2), while celecoxib only suppressed PGE2 biosynthesis significantly at a high dose. In a long-term Carcinogenesis study topical application of LTB4 or PGE2 enhanced oral Carcinogenesis by increasing the incidence and volume of visible tumors, and the incidence of squamous cell carcinoma (SCC). To further examine the role of LTB4 in oral Carcinogenesis, two LTA4H inhibitors, bestatin and SA6541, were evaluated in a long-term chemoprevention experiment. Both agents significantly inhibited SCC, and such an inhibition correlated with reduced levels of LTB4 in hamster cheek pouch. In summary, our studies have demonstrated that 5-Lox/LTA4H pathway is one of the major AA-metabolizing pathways involved in DMBA-induced oral Carcinogenesis in hamsters, and may be targeted for chemoprevention.
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overexpression of 5 lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib
Clinical Cancer Research, 2005Co-Authors: Ning Li, Sandeep Sood, Chung S Yang, Su Wang, Mingzhu Fang, Peng Wang, Xiaoxin ChenAbstract:Purpose: Previous studies have suggested an important role of aberrant arachidonic acid metabolism, especially the cyclooxygenase (Cox) pathway, in oral Carcinogenesis. However, it is unknown whether the 5-lipoxygenase (5-Lox) pathway contributes to oral Carcinogenesis, and whether combination of inhibitors of both pathways may have synergistic or additive effects of chemoprevention. Experimental Design: 5-Lox expression was examined in 7,12-dimethylbenz[ a ]anthracene (DMBA)–induced hamster and human oral cancer tissues by immunohistochemistry, and Cox2 expression was investigated in hamster oral tissues using in situ hybridization. Zileuton (a specific 5-Lox inhibitor) and celecoxib (a specific Cox2 inhibitor), either alone or in combination, were investigated for their chemopreventive effects on the DMBA-induced hamster model at the post-initiation stage through topical application. Results: 5-Lox was overexpressed during oral Carcinogenesis in hamsters and humans, as well as Cox2 in the hamster tissues. In a chemoprevention study using the post-initiation DMBA model, incidence of hamster oral squamous cell carcinoma was reduced from 76.9% (20 of 26) to 45.8% (11 of 24, P P P > 0.05) and 50% (12 of 24, P P Conclusions: The results clearly showed that both 5-Lox and Cox2 played important roles in oral Carcinogenesis. Zileuton and celecoxib prevented oral Carcinogenesis at the post-initiation stage through their inhibitory effects on arachidonic acid metabolism.
Yusuke Hiraku - One of the best experts on this subject based on the ideXlab platform.
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Formation of 8-nitroguanine, a nitrative DNA lesion, in inflammation-related Carcinogenesis and its significance
Environmental Health and Preventive Medicine, 2010Co-Authors: Yusuke HirakuAbstract:Chronic infection and inflammation contribute to a substantial part of environmental Carcinogenesis. Recently, it has been estimated that chronic inflammation accounts for approximately 25% of cancer cases. Various infectious diseases and physical, chemical, and immunological factors participate in inflammation-related Carcinogenesis. Under inflammatory conditions, reactive oxygen and nitrogen species, which are generated from inflammatory and epithelial cells, may play an important role in Carcinogenesis by causing DNA damage. 8-Nitroguanine is a mutagenic DNA lesion formed during chronic inflammation. In an earlier publication, our group reported the results of an immunohistochemical analysis of animals infected with the liver fluke Opisthorchis viverrini and demonstrated for the first time that 8-nitroguanine was formed at the sites of Carcinogenesis. This DNA lesion was found to accumulate in the carcinogenic process in clinical specimens of cancer-prone inflammatory diseases caused by various pathogens, including human papillomavirus and Epstein–Barr virus. Moreover, strong 8-nitroguanine formation in tumor tissues was closely associated with a poor prognosis. On the basis of these findings, 8-nitroguanine could be a potential biomarker to evaluate the risk of inflammation-related Carcinogenesis and the prognosis of cancer patients. In this review, the significance of 8-nitroguanine formation in inflammation-related Carcinogenesis and tumor progression will be discussed.
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immunohistochemical analysis of 8 nitroguanine a nitrative dna lesion in relation to inflammation associated Carcinogenesis
Methods of Molecular Biology, 2009Co-Authors: Yusuke Hiraku, Shosuke KawanishiAbstract:Chronic inflammation is induced by various infectious/infected agents and by many physical, chemical and immunological factors. Many malignancies arise from areas of infection and inflammation. Reactive oxygen species and reactive nitrogen species are considered to play the key role in inflammation-associated Carcinogenesis by causing oxidative and nitrative DNA damage. 8-Nitroguanine is a mutagenic nitrative DNA lesion formed during inflammation. Development of a detection method for 8-nitroguanine would provide an insight into the mechanism of inflammation-associated Carcinogenesis and the assessment of carcinogenic risk in patients with inflammatory diseases. We established the method to produce highly sensitive and specific anti-8-nitroguanine rabbit polyclonal antibody, and detect 8-nitroguanine formation in biopsy specimens and animal tissues by immunohistochemistry. We have found that 8-nitroguanine is formed at the sites of Carcinogenesis regardless of etiology, and proposed the possibility that 8-nitroguanine is a potential biomarker to evaluate the risk of inflammation-associated Carcinogenesis. In this paper, we describe the procedures of these experiments and the application to clinical specimens and animal tissues.
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oxidative and nitrative dna damage in animals and patients with inflammatory diseases in relation to inflammation related Carcinogenesis
Biological Chemistry, 2006Co-Authors: Shosuke Kawanishi, Yusuke Hiraku, Somchai PinlaorAbstract:Infection and chronic inflammation are proposed to contribute to Carcinogenesis through inflammation-related mechanisms. Infection with hepatitis C virus, Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are important risk factors for hepatocellular carcinoma (HCC), gastric cancer and cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with colon Carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We performed a double immunofluorescence labeling study and found that nitrative and oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS) was expressed in epithelial cells and inflammatory cells at the site of Carcinogenesis in humans and animal models. Antibacterial, antiviral and antiparasitic drugs dramatically diminished the formation of these DNA lesion markers and iNOS expression. These results suggest that oxidative and nitrative DNA damage occurs at the sites of Carcinogenesis, regardless of etiology. Therefore, it is considered that excessive amounts of reactive nitrogen species produced via iNOS during chronic inflammation may play a key role in Carcinogenesis by causing DNA damage. On the basis of our results, we propose that 8-nitroguanine is a promising biomarker to evaluate the potential risk of inflammation-mediated Carcinogenesis.
Xiaoqiu Liang - One of the best experts on this subject based on the ideXlab platform.
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expression of trf1 trf2 tin2 tert ku70 and brca1 proteins is associated with telomere shortening and may contribute to multistage Carcinogenesis of gastric cancer
Journal of Cancer Research and Clinical Oncology, 2010Co-Authors: Yang Zhang, Mei Zou, Shuai Yang, Xiaoqiu LiangAbstract:Purpose Telomere dysfunction is believed to be a significant factor in Carcinogenesis. To elucidate the Carcinogenesis mechanism in gastric cancer, the expression of telomeric proteins and changes in telomere length were investigated during multistage Carcinogenesis of gastric cancer.
Shosuke Kawanishi - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical analysis of 8 nitroguanine a nitrative dna lesion in relation to inflammation associated Carcinogenesis
Methods of Molecular Biology, 2009Co-Authors: Yusuke Hiraku, Shosuke KawanishiAbstract:Chronic inflammation is induced by various infectious/infected agents and by many physical, chemical and immunological factors. Many malignancies arise from areas of infection and inflammation. Reactive oxygen species and reactive nitrogen species are considered to play the key role in inflammation-associated Carcinogenesis by causing oxidative and nitrative DNA damage. 8-Nitroguanine is a mutagenic nitrative DNA lesion formed during inflammation. Development of a detection method for 8-nitroguanine would provide an insight into the mechanism of inflammation-associated Carcinogenesis and the assessment of carcinogenic risk in patients with inflammatory diseases. We established the method to produce highly sensitive and specific anti-8-nitroguanine rabbit polyclonal antibody, and detect 8-nitroguanine formation in biopsy specimens and animal tissues by immunohistochemistry. We have found that 8-nitroguanine is formed at the sites of Carcinogenesis regardless of etiology, and proposed the possibility that 8-nitroguanine is a potential biomarker to evaluate the risk of inflammation-associated Carcinogenesis. In this paper, we describe the procedures of these experiments and the application to clinical specimens and animal tissues.
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oxidative and nitrative dna damage in animals and patients with inflammatory diseases in relation to inflammation related Carcinogenesis
Biological Chemistry, 2006Co-Authors: Shosuke Kawanishi, Yusuke Hiraku, Somchai PinlaorAbstract:Infection and chronic inflammation are proposed to contribute to Carcinogenesis through inflammation-related mechanisms. Infection with hepatitis C virus, Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are important risk factors for hepatocellular carcinoma (HCC), gastric cancer and cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with colon Carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We performed a double immunofluorescence labeling study and found that nitrative and oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS) was expressed in epithelial cells and inflammatory cells at the site of Carcinogenesis in humans and animal models. Antibacterial, antiviral and antiparasitic drugs dramatically diminished the formation of these DNA lesion markers and iNOS expression. These results suggest that oxidative and nitrative DNA damage occurs at the sites of Carcinogenesis, regardless of etiology. Therefore, it is considered that excessive amounts of reactive nitrogen species produced via iNOS during chronic inflammation may play a key role in Carcinogenesis by causing DNA damage. On the basis of our results, we propose that 8-nitroguanine is a promising biomarker to evaluate the potential risk of inflammation-mediated Carcinogenesis.
Somchai Pinlaor - One of the best experts on this subject based on the ideXlab platform.
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oxidative and nitrative dna damage in animals and patients with inflammatory diseases in relation to inflammation related Carcinogenesis
Biological Chemistry, 2006Co-Authors: Shosuke Kawanishi, Yusuke Hiraku, Somchai PinlaorAbstract:Infection and chronic inflammation are proposed to contribute to Carcinogenesis through inflammation-related mechanisms. Infection with hepatitis C virus, Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are important risk factors for hepatocellular carcinoma (HCC), gastric cancer and cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with colon Carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We performed a double immunofluorescence labeling study and found that nitrative and oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS) was expressed in epithelial cells and inflammatory cells at the site of Carcinogenesis in humans and animal models. Antibacterial, antiviral and antiparasitic drugs dramatically diminished the formation of these DNA lesion markers and iNOS expression. These results suggest that oxidative and nitrative DNA damage occurs at the sites of Carcinogenesis, regardless of etiology. Therefore, it is considered that excessive amounts of reactive nitrogen species produced via iNOS during chronic inflammation may play a key role in Carcinogenesis by causing DNA damage. On the basis of our results, we propose that 8-nitroguanine is a promising biomarker to evaluate the potential risk of inflammation-mediated Carcinogenesis.