The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Keiji Wakabayashi - One of the best experts on this subject based on the ideXlab platform.
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suppression of azoxymethane induced colon cancer development in rats by a cyclooxygenase 1 selective inhibitor Mofezolac
Cancer Science, 2006Co-Authors: Naoko Niho, Tomohiro Kitamura, Mami Takahashi, Michihiro Mutoh, Hidetaka Sato, Mamoru Matsuura, Takashi Sugimura, Keiji WakabayashiAbstract:We demonstrated recently that Mofezolac, a cyclooxygenase-1 (COX-1) selective inhibitor, suppresses the development of azoxymethane (AOM)-induced colonic aberrant crypt foci in F344 rats and intestinal polyps in APC1309 mice. In the present study, we therefore investigated the effects of Mofezolac on colon cancer development. Male F344 rats were injected subcutaneously with 15 mg/kg body weight of AOM in the back twice at 7-day intervals from 5 weeks of age, and fed a diet containing 600 or 1200 ppm Mofezolac for 32 weeks, starting 1 day before the first dosing of AOM. Treatment with 1200 ppm Mofezolac significantly reduced the incidence, multiplicity and volume of colon carcinomas to 79%, 2.15 ± 1.65 and 7.5 ± 11.8 mm3, respectively, compared with 94%, 3.19 ± 1.87 and 23.7 ± 31.2 mm3 in the AOM treatment alone. Administration of 600 ppm Mofezolac showed only a slight reduction. No side effects were observed in any of the groups. These results confirm that COX-1, as well as COX-2, contributes to colon carcinogenesis and that Mofezolac may be a good chemopreventive agent for human colon cancer. (Cancer Sci 2006; 97: 1011–1014)
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combined effects of cyclooxygenase 1 and cyclooxygenase 2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice
International Journal of Cancer, 2004Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:As with cyclooxygenase (COX)-2, genetic disruption of COX-1 gene or pharmacologic inhibition of its activity has been shown to decrease the number of intestinal polyps in Apc gene-deficient mice. The present study was designed to investigate the combined effects of COX-1 and COX-2 selective inhibitors on spontaneous polyp formation in APC1309 female mice. The animals were treated with 300 or 600 ppm Mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm Mofezolac plus 200 ppm nimesulide, 600 ppm Mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks. Percentage inhibition of polyp area in the intestine was 17% with 600 ppm Mofezolac alone and 25% with 400 ppm nimesulide alone, their sum of 42% being almost equal to the 37% observed for the combination treatment. Administration of 300 ppm Mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30%. Moreover, the numbers of polyps more than 2.5 mm in diameter were markedly decreased by combined treatment of both COX inhibitors. With 10 ppm indomethacin, the dual inhibitor, polyp area was also clearly reduced by 46%. Our results indicate that COX-1 and COX-2 may to some extent contribute to polyp formation independently and inhibitor combination treatment thus has particular potential for chemoprevention of colon carcinogenesis. © 2004 Wiley-Liss, Inc.
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inhibitory effects of Mofezolac a cyclooxygenase 1 selective inhibitor on intestinal carcinogenesis
Carcinogenesis, 2002Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Takashi Sugimura, Toshihiko Kawamori, Naoaki Uchiya, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:Cyclooxygenase (COX)-2, one enzyme isoform responsible for producing prostanoids from arachidonic acid, contributes to colon carcinogenesis. Recently, genetic disruption of COX-1, the other isoform, was shown to decrease the number of intestinal polyps and prostaglandin E(2) levels in intestinal mucosa, like the case with COX-2 gene disruption, in Min mice. We therefore investigated whether a COX-1 selective inhibitor, Mofezolac, suppresses intestinal carcinogenesis in rodents. F344 male rats, receiving azoxymethane (AOM, 15 mg/kg body wt) s.c. injections at 5 and 6 weeks of age, were fed a diet containing 600 or 1200 p.p.m. Mofezolac for 4 weeks. The number of aberrant crypt foci (ACFs) per rat and the bromodeoxyuridine labeling index of the crypt epithelium were dose-dependently decreased by administration of Mofezolac, the value for the former at 1200 p.p.m. being 60% of control value. When Apc gene knockout mice (APC1309 mice) were given 600 or 1200 p.p.m. Mofezolac in their diet for 8 weeks, the numbers of intestinal polyps were also dose-dependently decreased, with reduction to 59% of that in the control diet group at the higher dose. Nimesulide, a COX-2 selective inhibitor used as positive control, showed similar suppressive effects on the development of ACFs in AOM-treated rats and polyps in Apc gene knockout mice. The data indicate that both COX-1 and COX-2 can contribute to intestinal tumorigenesis.
Tomohiro Kitamura - One of the best experts on this subject based on the ideXlab platform.
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suppression of azoxymethane induced colon cancer development in rats by a cyclooxygenase 1 selective inhibitor Mofezolac
Cancer Science, 2006Co-Authors: Naoko Niho, Tomohiro Kitamura, Mami Takahashi, Michihiro Mutoh, Hidetaka Sato, Mamoru Matsuura, Takashi Sugimura, Keiji WakabayashiAbstract:We demonstrated recently that Mofezolac, a cyclooxygenase-1 (COX-1) selective inhibitor, suppresses the development of azoxymethane (AOM)-induced colonic aberrant crypt foci in F344 rats and intestinal polyps in APC1309 mice. In the present study, we therefore investigated the effects of Mofezolac on colon cancer development. Male F344 rats were injected subcutaneously with 15 mg/kg body weight of AOM in the back twice at 7-day intervals from 5 weeks of age, and fed a diet containing 600 or 1200 ppm Mofezolac for 32 weeks, starting 1 day before the first dosing of AOM. Treatment with 1200 ppm Mofezolac significantly reduced the incidence, multiplicity and volume of colon carcinomas to 79%, 2.15 ± 1.65 and 7.5 ± 11.8 mm3, respectively, compared with 94%, 3.19 ± 1.87 and 23.7 ± 31.2 mm3 in the AOM treatment alone. Administration of 600 ppm Mofezolac showed only a slight reduction. No side effects were observed in any of the groups. These results confirm that COX-1, as well as COX-2, contributes to colon carcinogenesis and that Mofezolac may be a good chemopreventive agent for human colon cancer. (Cancer Sci 2006; 97: 1011–1014)
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combined effects of cyclooxygenase 1 and cyclooxygenase 2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice
International Journal of Cancer, 2004Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:As with cyclooxygenase (COX)-2, genetic disruption of COX-1 gene or pharmacologic inhibition of its activity has been shown to decrease the number of intestinal polyps in Apc gene-deficient mice. The present study was designed to investigate the combined effects of COX-1 and COX-2 selective inhibitors on spontaneous polyp formation in APC1309 female mice. The animals were treated with 300 or 600 ppm Mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm Mofezolac plus 200 ppm nimesulide, 600 ppm Mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks. Percentage inhibition of polyp area in the intestine was 17% with 600 ppm Mofezolac alone and 25% with 400 ppm nimesulide alone, their sum of 42% being almost equal to the 37% observed for the combination treatment. Administration of 300 ppm Mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30%. Moreover, the numbers of polyps more than 2.5 mm in diameter were markedly decreased by combined treatment of both COX inhibitors. With 10 ppm indomethacin, the dual inhibitor, polyp area was also clearly reduced by 46%. Our results indicate that COX-1 and COX-2 may to some extent contribute to polyp formation independently and inhibitor combination treatment thus has particular potential for chemoprevention of colon carcinogenesis. © 2004 Wiley-Liss, Inc.
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inhibitory effects of Mofezolac a cyclooxygenase 1 selective inhibitor on intestinal carcinogenesis
Carcinogenesis, 2002Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Takashi Sugimura, Toshihiko Kawamori, Naoaki Uchiya, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:Cyclooxygenase (COX)-2, one enzyme isoform responsible for producing prostanoids from arachidonic acid, contributes to colon carcinogenesis. Recently, genetic disruption of COX-1, the other isoform, was shown to decrease the number of intestinal polyps and prostaglandin E(2) levels in intestinal mucosa, like the case with COX-2 gene disruption, in Min mice. We therefore investigated whether a COX-1 selective inhibitor, Mofezolac, suppresses intestinal carcinogenesis in rodents. F344 male rats, receiving azoxymethane (AOM, 15 mg/kg body wt) s.c. injections at 5 and 6 weeks of age, were fed a diet containing 600 or 1200 p.p.m. Mofezolac for 4 weeks. The number of aberrant crypt foci (ACFs) per rat and the bromodeoxyuridine labeling index of the crypt epithelium were dose-dependently decreased by administration of Mofezolac, the value for the former at 1200 p.p.m. being 60% of control value. When Apc gene knockout mice (APC1309 mice) were given 600 or 1200 p.p.m. Mofezolac in their diet for 8 weeks, the numbers of intestinal polyps were also dose-dependently decreased, with reduction to 59% of that in the control diet group at the higher dose. Nimesulide, a COX-2 selective inhibitor used as positive control, showed similar suppressive effects on the development of ACFs in AOM-treated rats and polyps in Apc gene knockout mice. The data indicate that both COX-1 and COX-2 can contribute to intestinal tumorigenesis.
Mamoru Matsuura - One of the best experts on this subject based on the ideXlab platform.
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suppression of azoxymethane induced colon cancer development in rats by a cyclooxygenase 1 selective inhibitor Mofezolac
Cancer Science, 2006Co-Authors: Naoko Niho, Tomohiro Kitamura, Mami Takahashi, Michihiro Mutoh, Hidetaka Sato, Mamoru Matsuura, Takashi Sugimura, Keiji WakabayashiAbstract:We demonstrated recently that Mofezolac, a cyclooxygenase-1 (COX-1) selective inhibitor, suppresses the development of azoxymethane (AOM)-induced colonic aberrant crypt foci in F344 rats and intestinal polyps in APC1309 mice. In the present study, we therefore investigated the effects of Mofezolac on colon cancer development. Male F344 rats were injected subcutaneously with 15 mg/kg body weight of AOM in the back twice at 7-day intervals from 5 weeks of age, and fed a diet containing 600 or 1200 ppm Mofezolac for 32 weeks, starting 1 day before the first dosing of AOM. Treatment with 1200 ppm Mofezolac significantly reduced the incidence, multiplicity and volume of colon carcinomas to 79%, 2.15 ± 1.65 and 7.5 ± 11.8 mm3, respectively, compared with 94%, 3.19 ± 1.87 and 23.7 ± 31.2 mm3 in the AOM treatment alone. Administration of 600 ppm Mofezolac showed only a slight reduction. No side effects were observed in any of the groups. These results confirm that COX-1, as well as COX-2, contributes to colon carcinogenesis and that Mofezolac may be a good chemopreventive agent for human colon cancer. (Cancer Sci 2006; 97: 1011–1014)
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combined effects of cyclooxygenase 1 and cyclooxygenase 2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice
International Journal of Cancer, 2004Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:As with cyclooxygenase (COX)-2, genetic disruption of COX-1 gene or pharmacologic inhibition of its activity has been shown to decrease the number of intestinal polyps in Apc gene-deficient mice. The present study was designed to investigate the combined effects of COX-1 and COX-2 selective inhibitors on spontaneous polyp formation in APC1309 female mice. The animals were treated with 300 or 600 ppm Mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm Mofezolac plus 200 ppm nimesulide, 600 ppm Mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks. Percentage inhibition of polyp area in the intestine was 17% with 600 ppm Mofezolac alone and 25% with 400 ppm nimesulide alone, their sum of 42% being almost equal to the 37% observed for the combination treatment. Administration of 300 ppm Mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30%. Moreover, the numbers of polyps more than 2.5 mm in diameter were markedly decreased by combined treatment of both COX inhibitors. With 10 ppm indomethacin, the dual inhibitor, polyp area was also clearly reduced by 46%. Our results indicate that COX-1 and COX-2 may to some extent contribute to polyp formation independently and inhibitor combination treatment thus has particular potential for chemoprevention of colon carcinogenesis. © 2004 Wiley-Liss, Inc.
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inhibitory effects of Mofezolac a cyclooxygenase 1 selective inhibitor on intestinal carcinogenesis
Carcinogenesis, 2002Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Takashi Sugimura, Toshihiko Kawamori, Naoaki Uchiya, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:Cyclooxygenase (COX)-2, one enzyme isoform responsible for producing prostanoids from arachidonic acid, contributes to colon carcinogenesis. Recently, genetic disruption of COX-1, the other isoform, was shown to decrease the number of intestinal polyps and prostaglandin E(2) levels in intestinal mucosa, like the case with COX-2 gene disruption, in Min mice. We therefore investigated whether a COX-1 selective inhibitor, Mofezolac, suppresses intestinal carcinogenesis in rodents. F344 male rats, receiving azoxymethane (AOM, 15 mg/kg body wt) s.c. injections at 5 and 6 weeks of age, were fed a diet containing 600 or 1200 p.p.m. Mofezolac for 4 weeks. The number of aberrant crypt foci (ACFs) per rat and the bromodeoxyuridine labeling index of the crypt epithelium were dose-dependently decreased by administration of Mofezolac, the value for the former at 1200 p.p.m. being 60% of control value. When Apc gene knockout mice (APC1309 mice) were given 600 or 1200 p.p.m. Mofezolac in their diet for 8 weeks, the numbers of intestinal polyps were also dose-dependently decreased, with reduction to 59% of that in the control diet group at the higher dose. Nimesulide, a COX-2 selective inhibitor used as positive control, showed similar suppressive effects on the development of ACFs in AOM-treated rats and polyps in Apc gene knockout mice. The data indicate that both COX-1 and COX-2 can contribute to intestinal tumorigenesis.
Ikuo Morita - One of the best experts on this subject based on the ideXlab platform.
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Constitutive Expression and Involvement of
2016Co-Authors: Cyclooxygenase- In Human Megakaryocytopoiesis, Nobuhito Tanaka, Takahiro Sato, Hiroshi Fujita, Ikuo MoritaAbstract:produced via COX-1 induces platelet aggregation. The objectives of this study were to investigate the expression of COX-1 and COX-2 during platelet differentiation and to determine whether these enzymes are involved in the differentiation. Methods and Results—CD34 progenitor cells isolated from human cord blood were cultured with thrombopoietin and c-kit ligand. The cells differentiated into megakaryocytes (CD34/CD41) after 8 days of culture and into platelets (CD41/prodium iodide) after 14 days of culture. The CD34cells expressed a trace of COX-1 gene and no COX-2 gene. On day 5, COX-2 gene expression was observed and continued throughout the remainder of the culture. COX-1 gene expression increased after 8 days of culture. The treatment of this liquid culture with indomethacin, a dual inhibitor of COX-1 and COX-2, and NS-398, a COX-2–specific inhibitor, suppressed megakaryocyte differentiation. In contrast, at a dose of 107 M, Mofezolac, which is a highly selective inhibitor of COX-1, did not affect differentiation. NS-398–induced suppression of megakaryocyte differentiation was partly abrogated by stable analogues of TXA2
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constitutive expression and involvement of cyclooxygenase 2 in human megakaryocytopoiesis
Arteriosclerosis Thrombosis and Vascular Biology, 2004Co-Authors: Nobuhito Tanaka, Takahiro Sato, Hiroshi Fujita, Ikuo MoritaAbstract:Objective— Cyclooxygenase-1 (COX-1), but not COX-2, is expressed in human platelets, and thromboxane A2 (TXA2) produced via COX-1 induces platelet aggregation. The objectives of this study were to investigate the expression of COX-1 and COX-2 during platelet differentiation and to determine whether these enzymes are involved in the differentiation. Methods and Results— CD34+ progenitor cells isolated from human cord blood were cultured with thrombopoietin and c-kit ligand. The cells differentiated into megakaryocytes (CD34−/CD41+) after 8 days of culture and into platelets (CD41+/prodium iodide−) after 14 days of culture. The CD34+cells expressed a trace of COX-1 gene and no COX-2 gene. On day 5, COX-2 gene expression was observed and continued throughout the remainder of the culture. COX-1 gene expression increased after 8 days of culture. The treatment of this liquid culture with indomethacin, a dual inhibitor of COX-1 and COX-2, and NS-398, a COX-2–specific inhibitor, suppressed megakaryocyte differentiation. In contrast, at a dose of 10−7 M, Mofezolac, which is a highly selective inhibitor of COX-1, did not affect differentiation. NS-398–induced suppression of megakaryocyte differentiation was partly abrogated by stable analogues of TXA2. Conclusions— We report here that COX-2 and COX-1 are constitutively expressed in megakaryocytes, and TXA2 produced by COX-2 plays an important role in megakaryocytopoiesis.
Tetsuo Noda - One of the best experts on this subject based on the ideXlab platform.
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combined effects of cyclooxygenase 1 and cyclooxygenase 2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice
International Journal of Cancer, 2004Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:As with cyclooxygenase (COX)-2, genetic disruption of COX-1 gene or pharmacologic inhibition of its activity has been shown to decrease the number of intestinal polyps in Apc gene-deficient mice. The present study was designed to investigate the combined effects of COX-1 and COX-2 selective inhibitors on spontaneous polyp formation in APC1309 female mice. The animals were treated with 300 or 600 ppm Mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm Mofezolac plus 200 ppm nimesulide, 600 ppm Mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks. Percentage inhibition of polyp area in the intestine was 17% with 600 ppm Mofezolac alone and 25% with 400 ppm nimesulide alone, their sum of 42% being almost equal to the 37% observed for the combination treatment. Administration of 300 ppm Mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30%. Moreover, the numbers of polyps more than 2.5 mm in diameter were markedly decreased by combined treatment of both COX inhibitors. With 10 ppm indomethacin, the dual inhibitor, polyp area was also clearly reduced by 46%. Our results indicate that COX-1 and COX-2 may to some extent contribute to polyp formation independently and inhibitor combination treatment thus has particular potential for chemoprevention of colon carcinogenesis. © 2004 Wiley-Liss, Inc.
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inhibitory effects of Mofezolac a cyclooxygenase 1 selective inhibitor on intestinal carcinogenesis
Carcinogenesis, 2002Co-Authors: Tomohiro Kitamura, Mamoru Matsuura, Takashi Sugimura, Toshihiko Kawamori, Naoaki Uchiya, Masaki Itoh, Tetsuo Noda, Keiji WakabayashiAbstract:Cyclooxygenase (COX)-2, one enzyme isoform responsible for producing prostanoids from arachidonic acid, contributes to colon carcinogenesis. Recently, genetic disruption of COX-1, the other isoform, was shown to decrease the number of intestinal polyps and prostaglandin E(2) levels in intestinal mucosa, like the case with COX-2 gene disruption, in Min mice. We therefore investigated whether a COX-1 selective inhibitor, Mofezolac, suppresses intestinal carcinogenesis in rodents. F344 male rats, receiving azoxymethane (AOM, 15 mg/kg body wt) s.c. injections at 5 and 6 weeks of age, were fed a diet containing 600 or 1200 p.p.m. Mofezolac for 4 weeks. The number of aberrant crypt foci (ACFs) per rat and the bromodeoxyuridine labeling index of the crypt epithelium were dose-dependently decreased by administration of Mofezolac, the value for the former at 1200 p.p.m. being 60% of control value. When Apc gene knockout mice (APC1309 mice) were given 600 or 1200 p.p.m. Mofezolac in their diet for 8 weeks, the numbers of intestinal polyps were also dose-dependently decreased, with reduction to 59% of that in the control diet group at the higher dose. Nimesulide, a COX-2 selective inhibitor used as positive control, showed similar suppressive effects on the development of ACFs in AOM-treated rats and polyps in Apc gene knockout mice. The data indicate that both COX-1 and COX-2 can contribute to intestinal tumorigenesis.