|
|
char = S;code = 83
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
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char = f;code = 102
char = i;code = 105
char = e;code = 101
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
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char = t;code = 116
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char = ;code = 32
char = b;code = 98
char = o;code = 111
char = n;code = 110
char = e;code = 101
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char = a;code = 97
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char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = .;code = 46
result sql = Selenium modifies the osteoblast inflammatory stress response to bone metastatic breast cancer.
Selenium modifies the osteoblast inflammatory stress response to bone metastatic breast cancer.char = B;code = 66
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char = ;code = 32
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char = n;code = 110
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char = f;code = 102
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
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char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = m;code = 109
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char = a;code = 97
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char = a;code = 97
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char = i;code = 105
char = z;code = 122
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = h;code = 104
char = e;code = 101
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char = s;code = 115
char = k;code = 107
char = e;code = 101
char = l;code = 108
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char = t;code = 116
char = o;code = 111
char = n;code = 110
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char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
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char = i;code = 105
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char = g;code = 103
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
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char = d;code = 100
char = e;code = 101
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char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
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char = d;code = 100
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char = e;code = 101
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char = o;code = 111
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char = e;code = 101
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char = c;code = 99
char = l;code = 108
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char = ;code = 32
char = a;code = 97
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char = i;code = 105
char = v;code = 118
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char = M;code = 77
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char = a;code = 97
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char = t;code = 116
char = a;code = 97
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char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
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char = o;code = 111
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char = d;code = 100
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char = w;code = 119
char = n;code = 110
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = b;code = 98
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char = u;code = 117
char = i;code = 105
char = l;code = 108
char = d;code = 100
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char = n;code = 110
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char = f;code = 102
char = u;code = 117
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char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = e;code = 101
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char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
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char = s;code = 115
char = .;code = 46
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char = M;code = 77
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char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
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char = t;code = 116
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char = b;code = 98
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char = i;code = 105
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char = m;code = 109
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char = o;code = 111
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char = y;code = 121
char = ;code = 32
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char = r;code = 114
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char = s;code = 115
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char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = i;code = 105
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char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
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char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
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char = a;code = 97
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = L;code = 76
char = );code = 41
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char = 6;code = 54
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char = m;code = 109
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char = e;code = 101
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char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
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char = t;code = 116
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char = M;code = 77
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char = c;code = 99
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char = o;code = 111
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char = e;code = 101
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = n;code = 110
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char = i;code = 105
char = c;code = 99
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char = d;code = 100
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char = s;code = 115
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char = h;code = 104
char = a;code = 97
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char = e;code = 101
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char = (;code = 40
char = i;code = 105
char = N;code = 78
char = O;code = 79
char = S;code = 83
char = );code = 41
char = ,;code = 44
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char = s;code = 115
char = e;code = 101
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char = s;code = 115
char = ;code = 32
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char = e;code = 101
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char = ;code = 32
char = h;code = 104
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char = ;code = 32
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char = l;code = 108
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char = M;code = 77
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char = (;code = 40
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char = l;code = 108
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char = a;code = 97
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char = N;code = 78
char = F;code = 70
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char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = .;code = 46
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char = C;code = 67
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = c;code = 99
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char = a;code = 97
char = c;code = 99
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char = p;code = 112
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char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = a;code = 97
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char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
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char = o;code = 111
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char = e;code = 101
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = d;code = 100
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char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = a;code = 97
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char = t;code = 116
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char = s;code = 115
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char = e;code = 101
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char = i;code = 105
char = f;code = 102
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char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
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char = s;code = 115
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char = i;code = 105
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char = m;code = 109
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char = n;code = 110
char = o;code = 111
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char = l;code = 108
char = o;code = 111
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char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = p;code = 112
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char = 5;code = 53
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char = ;code = 32
char = n;code = 110
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char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
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char = f;code = 102
char = r;code = 114
char = a;code = 97
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char = t;code = 116
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char = a;code = 97
char = s;code = 115
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char = w;code = 119
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char = l;code = 108
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char = a;code = 97
char = s;code = 115
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
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char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 6;code = 54
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = P;code = 80
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char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = 3;code = 51
char = T;code = 84
char = 3;code = 51
char = -;code = 45
char = E;code = 69
char = 1;code = 49
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = h;code = 104
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char = s;code = 115
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char = l;code = 108
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
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char = a;code = 97
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char = A;code = 65
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char = ;code = 32
char = (;code = 40
char = 0;code = 48
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char = c;code = 99
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char = t;code = 116
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char = ;code = 32
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char = c;code = 99
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char = a;code = 97
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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 = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
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char = e;code = 101
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char = I;code = 73
char = L;code = 76
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char = ;code = 32
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char = P;code = 80
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char = C;code = 67
char = O;code = 79
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char = 2;code = 50
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char = a;code = 97
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char = O;code = 79
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char = i;code = 105
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char = A;code = 65
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char = M;code = 77
char = B;code = 66
char = -;code = 45
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char = d;code = 100
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char = o;code = 111
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char = M;code = 77
char = S;code = 83
char = A;code = 65
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char = t;code = 116
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char = o;code = 111
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char = a;code = 97
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char = s;code = 115
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char = a;code = 97
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char = t;code = 116
char = l;code = 108
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char = a;code = 97
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char = 1;code = 49
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char = p;code = 112
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char = e;code = 101
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char = i;code = 105
char = o;code = 111
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char = o;code = 111
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char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
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char = g;code = 103
char = g;code = 103
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char = a;code = 97
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char = a;code = 97
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char = i;code = 105
char = t;code = 116
char = e;code = 101
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char = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
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char = e;code = 101
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char = .;code = 46
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char = H;code = 72
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char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = t;code = 116
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char = A;code = 65
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char = a;code = 97
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char = s;code = 115
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char = e;code = 101
char = d;code = 100
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char = b;code = 98
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char = N;code = 78
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char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
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char = a;code = 97
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char = t;code = 116
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char = v;code = 118
char = a;code = 97
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char = w;code = 119
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char = f;code = 102
char = f;code = 102
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = b;code = 98
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char = M;code = 77
char = S;code = 83
char = A;code = 65
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char = e;code = 101
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char = t;code = 116
char = h;code = 104
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char = g;code = 103
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char = o;code = 111
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char = t;code = 116
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result sql = Breast cancer frequently metastasizes to the skeleton resulting in bone degradation due to osteoclast activation. Metastases also downregulate differentiation and the bone-rebuilding function of osteoblasts. Moreover, cancer cells trigger osteoblast inflammatory stress responses. Pro-inflammatory mediators such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), expressed by osteoblasts (MC3T3-E1) stimulated with human breast cancer cell (MDA-MB-231) conditioned medium, are pivotal to osteoclast activation and metastasis. Given that these genes are regulated by nuclear factor-kappaB (NF-kappaB), a redox-sensitive transcription factor, we hypothesized that selenium (Se) could abrogate the inflammatory response to metastatic breast cancer cells by modulating NF-kappaB. Caffeic acid phenethyl ester and parthenolide inhibited NF-kappaB activation, as seen by gel shift assays and immunoblotting for p65 in nuclear fractions, as well as decreased production of IL-6 and MCP-1. Supplementation of MC3T3-E1 with methylseleninic acid (MSA) (0.5 microM to 4 microM) reduced the activation of NF-kappaB leading to a decrease in IL-6, MCP-1, COX-2 and iNOS in response to MDA-MB-231 conditioned medium. Addition of MSA to osteoblasts for as little as 15 min suppressed activation of NF-kappaB suggesting that short-lived active metabolites might be involved. However, brief exposure to MSA also brought about an increase in selenoprotein glutathione peroxidase 1. In summary, our data indicate that the osteoblast response to metastatic breast cancer cells is regulated by NF-kappaB activation, which can be effectively suppressed by MSA either through short-lived active metabolites and/or selenoproteins. Thus, Se supplementation may prevent the osteoblast inflammatory response or dampen the vicious cycle established when breast cancer cells, osteoblasts and osteoclasts interact.
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result sql = Selenium modifies the osteoblast inflammatory stress response to bone metastatic breast cancer.
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char = e;code = 101
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char = e;code = 101
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char = p;code = 112
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char = t;code = 116
char = a;code = 97
char = l;code = 108
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char = t;code = 116
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char = ;code = 32
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = c;code = 99
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = ;code = 32
char = (;code = 40
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
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char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = o;code = 111
char = x;code = 120
char = -;code = 45
char = s;code = 115
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char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = (;code = 40
char = S;code = 83
char = e;code = 101
char = );code = 41
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
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 = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
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char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = i;code = 105
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char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = s;code = 115
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = b;code = 98
char = y;code = 121
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char = g;code = 103
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = s;code = 115
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char = i;code = 105
char = f;code = 102
char = t;code = 116
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char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = u;code = 117
char = n;code = 110
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = o;code = 111
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char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = 6;code = 54
char = 5;code = 53
char = ;code = 32
char = i;code = 105
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char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = c;code = 99
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char = o;code = 111
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char = s;code = 115
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char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
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char = l;code = 108
char = l;code = 108
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char = a;code = 97
char = s;code = 115
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 6;code = 54
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = 3;code = 51
char = T;code = 84
char = 3;code = 51
char = -;code = 45
char = E;code = 69
char = 1;code = 49
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = c;code = 99
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char = d;code = 100
char = ;code = 32
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char = M;code = 77
char = S;code = 83
char = A;code = 65
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char = ;code = 32
char = (;code = 40
char = 0;code = 48
char = .;code = 46
char = 5;code = 53
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char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
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char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = d;code = 100
char = i;code = 105
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char = t;code = 116
char = o;code = 111
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char = a;code = 97
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char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = L;code = 76
char = -;code = 45
char = 6;code = 54
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ,;code = 44
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char = C;code = 67
char = O;code = 79
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char = -;code = 45
char = 2;code = 50
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char = a;code = 97
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char = d;code = 100
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char = i;code = 105
char = N;code = 78
char = O;code = 79
char = S;code = 83
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char = i;code = 105
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char = s;code = 115
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char = t;code = 116
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char = M;code = 77
char = D;code = 68
char = A;code = 65
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char = M;code = 77
char = B;code = 66
char = -;code = 45
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char = 3;code = 51
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char = c;code = 99
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char = d;code = 100
char = i;code = 105
char = t;code = 116
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char = e;code = 101
char = d;code = 100
char = i;code = 105
char = u;code = 117
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char = ;code = 32
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char = d;code = 100
char = i;code = 105
char = t;code = 116
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char = o;code = 111
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = S;code = 83
char = A;code = 65
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char = t;code = 116
char = o;code = 111
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char = o;code = 111
char = s;code = 115
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char = e;code = 101
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char = b;code = 98
char = l;code = 108
char = a;code = 97
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char = t;code = 116
char = s;code = 115
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char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = a;code = 97
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char = i;code = 105
char = t;code = 116
char = t;code = 116
char = l;code = 108
char = e;code = 101
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char = a;code = 97
char = s;code = 115
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char = 1;code = 49
char = 5;code = 53
char = ;code = 32
char = m;code = 109
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char = n;code = 110
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char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = a;code = 97
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char = v;code = 118
char = a;code = 97
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
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char = s;code = 115
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char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
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char = ;code = 32
char = t;code = 116
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char = a;code = 97
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char = ;code = 32
char = s;code = 115
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char = r;code = 114
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char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = a;code = 97
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char = v;code = 118
char = e;code = 101
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char = m;code = 109
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char = t;code = 116
char = a;code = 97
char = b;code = 98
char = o;code = 111
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char = i;code = 105
char = t;code = 116
char = e;code = 101
char = s;code = 115
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char = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
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char = b;code = 98
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
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char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = f;code = 102
char = ;code = 32
char = e;code = 101
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char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
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result sql = Breast cancer frequently metastasizes to the skeleton resulting in bone degradation due to osteoclast activation. Metastases also downregulate differentiation and the bone-rebuilding function of osteoblasts. Moreover, cancer cells trigger osteoblast inflammatory stress responses. Pro-inflammatory mediators such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), expressed by osteoblasts (MC3T3-E1) stimulated with human breast cancer cell (MDA-MB-231) conditioned medium, are pivotal to osteoclast activation and metastasis. Given that these genes are regulated by nuclear factor-kappaB (NF-kappaB), a redox-sensitive transcription factor, we hypothesized that selenium (Se) could abrogate the inflammatory response to metastatic breast cancer cells by modulating NF-kappaB. Caffeic acid phenethyl ester and parthenolide inhibited NF-kappaB activation, as seen by gel shift assays and immunoblotting for p65 in nuclear fractions, as well as decreased production of IL-6 and MCP-1. Supplementation of MC3T3-E1 with methylseleninic acid (MSA) (0.5 microM to 4 microM) reduced the activation of NF-kappaB leading to a decrease in IL-6, MCP-1, COX-2 and iNOS in response to MDA-MB-231 conditioned medium. Addition of MSA to osteoblasts for as little as 15 min suppressed activation of NF-kappaB suggesting that short-lived active metabolites might be involved. However, brief exposure to MSA also brought about an increase in selenoprotein glutathione peroxidase 1. In summary, our data indicate that the osteoblast response to metastatic breast cancer cells is regulated by NF-kappaB activation, which can be effectively suppressed by MSA either through short-lived active metabolites and/or selenoproteins. Thus, Se supplementation may prevent the osteoblast inflammatory response or dampen the vicious cycle established when breast cancer cells, osteoblasts and osteoclasts interact.
Publication: Carcinogenesis 2009 Nov ;30(11)::1941-8. :doi: 10.1093/carcin/bgp227.
Publication Date: 2009 Nov
Study Author(s): Chen, Yu-Chi;Sosnoski, Donna M;Gandhi, Ujjawal H;Novinger, Leah J;Prabhu, K Sandeep;Mastro, Andrea M;
Institution: Department of Biochemistry and Molecular Biology, 431 South Frear Building, Penn State University, University Park, PA 16802, USA.
Shortcut link to this study:
Publication Date: 2009 Nov
Study Author(s): Chen, Yu-Chi;Sosnoski, Donna M;Gandhi, Ujjawal H;Novinger, Leah J;Prabhu, K Sandeep;Mastro, Andrea M;
Institution: Department of Biochemistry and Molecular Biology, 431 South Frear Building, Penn State University, University Park, PA 16802, USA.
Shortcut link to this study:
Breast cancer frequently metastasizes to the skeleton resulting in bone degradation due to osteoclast activation. Metastases also downregulate differentiation and the bone-rebuilding function of osteoblasts. Moreover, cancer cells trigger osteoblast inflammatory stress responses. Pro-inflammatory mediators such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), expressed by osteoblasts (MC3T3-E1) stimulated with human breast cancer cell (MDA-MB-231) conditioned medium, are pivotal to osteoclast activation and metastasis. Given that these genes are regulated by nuclear factor-kappaB (NF-kappaB), a redox-sensitive transcription factor, we hypothesized that selenium (Se) could abrogate the inflammatory response to metastatic breast cancer cells by modulating NF-kappaB. Caffeic acid phenethyl ester and parthenolide inhibited NF-kappaB activation, as seen by gel shift assays and immunoblotting for p65 in nuclear fractions, as well as decreased production of IL-6 and MCP-1. Supplementation of MC3T3-E1 with methylseleninic acid (MSA) (0.5 microM to 4 microM) reduced the activation of NF-kappaB leading to a decrease in IL-6, MCP-1, COX-2 and iNOS in response to MDA-MB-231 conditioned medium. Addition of MSA to osteoblasts for as little as 15 min suppressed activation of NF-kappaB suggesting that short-lived active metabolites might be involved. However, brief exposure to MSA also brought about an increase in selenoprotein glutathione peroxidase 1. In summary, our data indicate that the osteoblast response to metastatic breast cancer cells is regulated by NF-kappaB activation, which can be effectively suppressed by MSA either through short-lived active metabolites and/or selenoproteins. Thus, Se supplementation may prevent the osteoblast inflammatory response or dampen the vicious cycle established when breast cancer cells, osteoblasts and osteoclasts interact.
PMID: 19759193
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