|
|
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result sql = Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog.
Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog.char = A;code = 65
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char = t;code = 116
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char = S;code = 83
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char = j;code = 106
char = e;code = 101
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char = u;code = 117
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char = n;code = 110
char = c;code = 99
char = o;code = 111
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char = i;code = 105
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char = t;code = 116
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char = t;code = 116
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char = u;code = 117
char = c;code = 99
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
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char = ;code = 32
char = N;code = 78
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
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char = r;code = 114
char = p;code = 112
char = i;code = 105
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char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
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char = ;code = 32
char = T;code = 84
char = a;code = 97
char = k;code = 107
char = e;code = 101
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char = e;code = 101
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char = e;code = 101
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char = ;code = 32
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char = d;code = 100
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char = m;code = 109
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = a;code = 97
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char = f;code = 102
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char = s;code = 115
char = e;code = 101
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char = H;code = 72
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char = w;code = 119
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char = t;code = 116
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char = n;code = 110
char = ;code = 32
char = H;code = 72
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char = V;code = 86
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char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
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char = ;code = 32
char = o;code = 111
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char = e;code = 101
char = d;code = 100
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result sql = Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol.
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char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
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char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = H;code = 72
char = C;code = 67
char = V;code = 86
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = n;code = 110
char = c;code = 99
char = o;code = 111
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char = e;code = 101
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char = e;code = 101
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
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char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
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char = n;code = 110
char = g;code = 103
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char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = N;code = 78
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = g;code = 103
char = .;code = 46
result sql = Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog.
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result sql = Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol.
Publication: Proc. Natl. Acad. Sci. U.S.A. 2009 Feb 3 ;106(5)::1548-53. :doi: 10.1073/pnas.0807390106.
Publication Date: 2009 Feb 3
Study Author(s): Machida, Keigo;Tsukamoto, Hidekazu;Mkrtchyan, Hasmik;Duan, Lewei;Dynnyk, Alla;Liu, Helene Minyi;Asahina, Kinji;Govindarajan, Sugantha;Ray, Ratna;Ou, Jing-Hsiung James;Seki, Ekihiro;Deshaies, Raymond;Miyake, Kensuke;Lai, Michael M-C;
Institution: Southern California Research Center for Alcoholic, Liver, and Pancreatic Diseases and Cirrhosis, and Department of Molecular Microbiology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Shortcut link to this study:
Publication Date: 2009 Feb 3
Study Author(s): Machida, Keigo;Tsukamoto, Hidekazu;Mkrtchyan, Hasmik;Duan, Lewei;Dynnyk, Alla;Liu, Helene Minyi;Asahina, Kinji;Govindarajan, Sugantha;Ray, Ratna;Ou, Jing-Hsiung James;Seki, Ekihiro;Deshaies, Raymond;Miyake, Kensuke;Lai, Michael M-C;
Institution: Southern California Research Center for Alcoholic, Liver, and Pancreatic Diseases and Cirrhosis, and Department of Molecular Microbiology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Shortcut link to this study:
Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol.
PMID: 19171902
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