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Michael Elkin - One of the best experts on this subject based on the ideXlab platform.
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periodontal pathogens porphyromonas gingivalis and fusobacterium nucleatum promote tumor progression in an oral specific Chemical Carcinogenesis model
Oncotarget, 2015Co-Authors: Adi Binder Gallimidi, Stuart Fischman, Brurya Revach, Raanan Bulvik, Alina Maliutina, Ariel M Rubinstein, Gabriel Nussbaum, Michael ElkinAbstract:// Adi Binder Gallimidi 1, 2 , Stuart Fischman 2 , Brurya Revach 1 , Raanan Bulvik 1 , Alina Maliutina 2 , Ariel M. Rubinstein 1 , Gabriel Nussbaum 2, * , Michael Elkin 1, * 1 Sharett Oncology Institute, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 2 Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel * These authors have contributed equally to this work Correspondence to: Michael Elkin, e-mail: melkin@hadassah.org.il Gabriel Nussbaum, e-mail: gabrieln@ekmd.huji.ac.il Keywords: oral cancer, TLR2, STAT3, IL-6, periodontitis Received: April 16, 2015 Accepted: May 26, 2015 Published: June 08, 2015 ABSTRACT Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in Chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.
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periodontal pathogens porphyromonas gingivalis and fusobacterium nucleatum promote tumor progression in an oral specific Chemical Carcinogenesis model
Oncotarget, 2015Co-Authors: Adi Binder Gallimidi, Stuart Fischman, Brurya Revach, Raanan Bulvik, Alina Maliutina, Gabriel Nussbaum, Ariel Rubinstein, Michael ElkinAbstract:Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in Chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.
Kenji Mizutani - One of the best experts on this subject based on the ideXlab platform.
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cancer preventive agents part 8 chemopreventive effects of stevioside and related compounds
Bioorganic & Medicinal Chemistry, 2009Co-Authors: Midori Takasaki, Mutsuo Kozuka, Takao Konoshima, Harukuni Tokuda, Masazumi Miyakoshi, Kenji MizutaniAbstract:Abstract In a search for potential cancer chemopreventive agents from natural resources, stevioside ( 1 ), a sweetener, and six related compounds, including two aglycones steviol ( 6 ) and isosteviol ( 7 ), were screened in an in vitro assay for inhibitory effects on Epstein–Barr virus early antigen activation. Compounds 1 , 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage Carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[ a ]anthracene (DMBA) and 12- O -tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin Carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1 , as well as 6 and 7 , could be valuable as chemopreventive agents for Chemical Carcinogenesis.
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cancer preventive agents part 8 chemopreventive effects of stevioside and related compounds
Bioorganic & Medicinal Chemistry, 2009Co-Authors: Midori Takasaki, Mutsuo Kozuka, Takao Konoshima, Harukuni Tokuda, Masazumi Miyakoshi, Kenji Mizutani, Junko Takayasu, Hoyoku Nishino, Kuo Hsiung LeeAbstract:In a search for potential cancer chemopreventive agents from natural resources, stevioside (1), a sweetener, and six related compounds, including two aglycones steviol (6) and isosteviol (7), were screened in an in vitro assay for inhibitory effects on Epstein-Barr virus early antigen activation. Compounds 1, 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage Carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin Carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1, as well as 6 and 7, could be valuable as chemopreventive agents for Chemical Carcinogenesis.
Midori Takasaki - One of the best experts on this subject based on the ideXlab platform.
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cancer preventive agents part 8 chemopreventive effects of stevioside and related compounds
Bioorganic & Medicinal Chemistry, 2009Co-Authors: Midori Takasaki, Mutsuo Kozuka, Takao Konoshima, Harukuni Tokuda, Masazumi Miyakoshi, Kenji Mizutani, Junko Takayasu, Hoyoku Nishino, Kuo Hsiung LeeAbstract:In a search for potential cancer chemopreventive agents from natural resources, stevioside (1), a sweetener, and six related compounds, including two aglycones steviol (6) and isosteviol (7), were screened in an in vitro assay for inhibitory effects on Epstein-Barr virus early antigen activation. Compounds 1, 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage Carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin Carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1, as well as 6 and 7, could be valuable as chemopreventive agents for Chemical Carcinogenesis.
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cancer preventive agents part 8 chemopreventive effects of stevioside and related compounds
Bioorganic & Medicinal Chemistry, 2009Co-Authors: Midori Takasaki, Mutsuo Kozuka, Takao Konoshima, Harukuni Tokuda, Masazumi Miyakoshi, Kenji MizutaniAbstract:Abstract In a search for potential cancer chemopreventive agents from natural resources, stevioside ( 1 ), a sweetener, and six related compounds, including two aglycones steviol ( 6 ) and isosteviol ( 7 ), were screened in an in vitro assay for inhibitory effects on Epstein–Barr virus early antigen activation. Compounds 1 , 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage Carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[ a ]anthracene (DMBA) and 12- O -tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin Carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1 , as well as 6 and 7 , could be valuable as chemopreventive agents for Chemical Carcinogenesis.
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anti carcinogenic activity of taraxacum plant i
Biological & Pharmaceutical Bulletin, 1999Co-Authors: Midori Takasaki, Takao Konoshima, Harukuni Tokuda, Kazuo Masuda, Yoko Arai, Kenji Shiojima, Hiroyuki AgetaAbstract:An extract of the roots of Taraxacum japonicum (Compositae) exhibited strong anti-tumor-promoting activities on the two-stage Carcinogenesis of mouse skin tumor induced by dimethylbenz[a]anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter, as well as on that induced by DMBA and fumonisin B1. Further, the extract exhibited anti-tumor-initiating activity on the two-stage Carcinogenesis of mouse skin tumor induced by (±)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide (NOR-1) as an initiator and TPA as a promoter. These results suggested that an extract of the roots of the Taraxacum plant could be a valuable chemopreventive agent against Chemical Carcinogenesis.
Adi Binder Gallimidi - One of the best experts on this subject based on the ideXlab platform.
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periodontal pathogens porphyromonas gingivalis and fusobacterium nucleatum promote tumor progression in an oral specific Chemical Carcinogenesis model
Oncotarget, 2015Co-Authors: Adi Binder Gallimidi, Stuart Fischman, Brurya Revach, Raanan Bulvik, Alina Maliutina, Ariel M Rubinstein, Gabriel Nussbaum, Michael ElkinAbstract:// Adi Binder Gallimidi 1, 2 , Stuart Fischman 2 , Brurya Revach 1 , Raanan Bulvik 1 , Alina Maliutina 2 , Ariel M. Rubinstein 1 , Gabriel Nussbaum 2, * , Michael Elkin 1, * 1 Sharett Oncology Institute, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 2 Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel * These authors have contributed equally to this work Correspondence to: Michael Elkin, e-mail: melkin@hadassah.org.il Gabriel Nussbaum, e-mail: gabrieln@ekmd.huji.ac.il Keywords: oral cancer, TLR2, STAT3, IL-6, periodontitis Received: April 16, 2015 Accepted: May 26, 2015 Published: June 08, 2015 ABSTRACT Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in Chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.
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periodontal pathogens porphyromonas gingivalis and fusobacterium nucleatum promote tumor progression in an oral specific Chemical Carcinogenesis model
Oncotarget, 2015Co-Authors: Adi Binder Gallimidi, Stuart Fischman, Brurya Revach, Raanan Bulvik, Alina Maliutina, Gabriel Nussbaum, Ariel Rubinstein, Michael ElkinAbstract:Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in Chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.
James E Klaunig - One of the best experts on this subject based on the ideXlab platform.
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oxidative stress and oxidative damage in Chemical Carcinogenesis
Toxicology and Applied Pharmacology, 2011Co-Authors: James E Klaunig, Zemin Wang, Xinzhu Pu, Shaoyu ZhouAbstract:Reactive oxygen species (ROS) are induced through a variety of endogenous and exogenous sources. Overwhelming of antioxidant and DNA repair mechanisms in the cell by ROS may result in oxidative stress and oxidative damage to the cell. This resulting oxidative stress can damage critical cellular macromolecules and/or modulate gene expression pathways. Cancer induction by Chemical and physical agents involves a multi-step process. This process includes multiple molecular and cellular events to transform a normal cell to a malignant neoplastic cell. Oxidative damage resulting from ROS generation can participate in all stages of the cancer process. An association of ROS generation and human cancer induction has been shown. It appears that oxidative stress may both cause as well as modify the cancer process. Recently association between polymorphisms in oxidative DNA repair genes and antioxidant genes (single nucleotide polymorphisms) and human cancer susceptibility has been shown.
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the role of oxidative stress in Carcinogenesis
Annual Review of Pharmacology and Toxicology, 2004Co-Authors: James E Klaunig, Lisa M KamendulisAbstract:▪ Abstract Chemical Carcinogenesis follows a multistep process involving both mutation and increased cell proliferation. Oxidative stress can occur through overproduction of reactive oxygen and nitrogen species through either endogenous or exogenous insults. Important to Carcinogenesis, the unregulated or prolonged production of cellular oxidants has been linked to mutation (induced by oxidant-induced DNA damage), as well as modification of gene expression. In particular, signal transduction pathways, including AP-1 and NFκB, are known to be activated by reactive oxygen species, and they lead to the transcription of genes involved in cell growth regulatory pathways. This review examines the evidence of cellular oxidants' involvement in the Carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species.
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the role of oxidative stress in Chemical Carcinogenesis
Environmental Health Perspectives, 1998Co-Authors: James E Klaunig, Jason S Isenberg, Stephen Bachowski, Kyle L Kolaja, Jiazhong Jiang, Donald E Stevenson, Earl F WalborgAbstract:Oxidative stress results when the balance between the production of reactive oxygen species (ROS) overrides the antioxidant capability of the target cell; oxidative damage from the interaction of reactive oxygen with critical cellular macromolecules may occur. ROS may interact with and modify cellular protein, lipid, and DNA, which results in altered target cell function. The accumulation of oxidative damage has been implicated in both acute and chronic cell injury including possible participation in the formation of cancer. Acute oxidative injury may produce selective cell death and a compensatory increase in cell proliferation. This stimulus may result in the formation of newly initiated preneoplastic cells and/or enhance the selective clonal expansion of latent initiated preneoplastic cells. Similarly, sublethal acute oxidative injury may produce unrepaired DNA damage and result in the formation of new mutations and, potentially, new initiated cells. In contrast, sustained chronic oxidative injury may lead to a nonlethal modification of normal cellular growth control mechanisms. Cellular oxidative stress can modify intercellular communication, protein kinase activity, membrane structure and function, and gene expression, and result in modulation of cell growth. We examined the role of oxidative stress as a possible mechanism by which nongenotoxic carcinogens may function. In studies with the selective mouse liver carcinogen dieldrin, a species-specific and dose-dependent decrease in liver antioxidant concentrations with a concomitant increase in ROS formation and oxidative damage was seen. This increase in oxidative stress correlated with an increase in hepatocyte DNA synthesis. Antioxidant supplementation prevented the dieldrin-induced cellular changes. Our findings suggest that the effect of nongenotoxic carcinogens (if they function through oxidative mechanisms) may be amplified in rodents but not in primates because of rodents' greater sensitivity to ROS. These results and findings reported by others support a potential role for oxidative-induced injury in the cancer process specifically during the promotion stage.
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the role of oxidative stress in Chemical Carcinogenesis
Environmental Health Perspectives, 1998Co-Authors: James E Klaunig, Jason S Isenberg, Stephen Bachowski, Kyle L Kolaja, Jiazhong Jiang, Donald E Stevenson, Yong Xu, Earl F WalborgAbstract:Oxidative stress results when the balance between the production of reactive oxygen species (ROS) overrides the antioxidant capability of the target cell; oxidative damage from the interaction of r...