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char = ;code = 32
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char = m;code = 109
char = a;code = 97
char = n;code = 110
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char = r;code = 114
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char = t;code = 116
char = ;code = 32
char = c;code = 99
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char = e;code = 101
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char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = i;code = 105
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char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = o;code = 111
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char = ;code = 32
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char = o;code = 111
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char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = o;code = 111
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char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
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char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
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char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
result sql = Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations.
Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations.
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char = e;code = 101
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char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 1;code = 49
char = :;code = 58
char = 3;code = 51
char = 1;code = 49
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = 2;code = 50
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = G;code = 71
char = E;code = 69
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = E;code = 69
char = 2;code = 50
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = O;code = 79
char = V;code = 86
char = A;code = 65
char = R;code = 82
char = I;code = 73
char = E;code = 69
char = C;code = 67
char = T;code = 84
char = O;code = 79
char = M;code = 77
char = I;code = 73
char = Z;code = 90
char = E;code = 69
char = D;code = 68
char = ;code = 32
char = M;code = 77
char = I;code = 73
char = C;code = 67
char = E;code = 69
char = ;code = 32
char = W;code = 87
char = E;code = 69
char = R;code = 82
char = E;code = 69
char = ;code = 32
char = D;code = 68
char = I;code = 73
char = V;code = 86
char = I;code = 73
char = D;code = 68
char = E;code = 69
char = D;code = 68
char = ;code = 32
char = I;code = 73
char = N;code = 78
char = T;code = 84
char = O;code = 79
char = ;code = 32
char = F;code = 70
char = O;code = 79
char = U;code = 85
char = R;code = 82
char = ;code = 32
char = G;code = 71
char = R;code = 82
char = O;code = 79
char = U;code = 85
char = P;code = 80
char = S;code = 83
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = p;code = 112
char = p;code = 112
char = m;code = 109
char = ;code = 32
char = G;code = 71
char = E;code = 69
char = N;code = 78
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = :;code = 58
char = 3;code = 51
char = 1;code = 49
char = ;code = 32
char = E;code = 69
char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = :;code = 58
char = 3;code = 51
char = 1;code = 49
char = ;code = 32
char = E;code = 69
char = 2;code = 50
char = ;code = 32
char = +;code = 43
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = p;code = 112
char = p;code = 112
char = m;code = 109
char = ;code = 32
char = G;code = 71
char = E;code = 69
char = N;code = 78
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = ;code = 32
char = 1;code = 49
char = 7;code = 55
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = 7;code = 55
char = .;code = 46
char = 6;code = 54
char = ,;code = 44
char = ;code = 32
char = 3;code = 51
char = 2;code = 50
char = .;code = 46
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = 6;code = 54
char = 7;code = 55
char = .;code = 46
char = 4;code = 52
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 6;code = 54
char = .;code = 46
char = 8;code = 56
char = ;code = 32
char = m;code = 109
char = m;code = 109
char = 2;code = 50
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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 = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = ;code = 32
char = <;code = 60
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 5;code = 53
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = p;code = 112
char = p;code = 112
char = m;code = 109
char = ;code = 32
char = G;code = 71
char = E;code = 69
char = N;code = 78
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
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 = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = 2;code = 50
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = h;code = 104
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = 2;code = 50
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = w;code = 119
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
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 = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
char = ;code = 32
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 = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = U;code = 85
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
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 = d;code = 100
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = G;code = 71
char = E;code = 69
char = N;code = 78
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = r;code = 114
char = c;code = 99
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 = E;code = 69
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
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result sql = We have demonstrated that genistein (GEN) stimulates growth of estrogen-dependent breast tumors in vivo. In this study, we evaluated whether dietary GEN can act in an additive manner with low circulating levels of 17beta-estradiol (E2). We developed an E2 delivery system using silastic implants that yield low circulating plasma E2 levels similar to those observed in postmenopausal women. We inserted various concentrations of E2 silastic implants (1:127, 1:63, 1:31, 1:15 and 1:7 = E2:cholesterol) and injected estrogen-dependent human breast cancer (MCF-7) cells into ovariectomized athymic mice. The E2 implants tested (1:127-1:7) generated 30.1-101.6 pM E2 in plasma, which is comparable to the E2 levels observed in postmenopausal women. The E2 implants stimulated MCF-7 tumor growth in a dose-dependent manner. We selected the 1:31 ratio of E2 implant to evaluate if dietary GEN acts in an additive manner with low E2 levels to influence the growth of MCF-7 tumors. OVARIECTOMIZED MICE WERE DIVIDED INTO FOUR GROUPS: MCF-7 control, 500 ppm GEN, 1:31 E2, and 1:31 E2 + 500 ppm GEN. At week 17, the average tumor sizes were 7.6, 32.1, 67.4 and 106.8 mm2 for these groups, respectively (P < 0.05), demonstrating that 500 ppm GEN additively stimulated MCF-7 tumor growth in the presence of low levels of E2. In summary, we established a preclinical mouse model that results in E2 blood concentrations similar to those found in postmenopausal women. Further, we observed that these concentrations regulate the growth rate of MCF-7 breast tumors. Using this model, we demonstrated that dietary GEN in the presence of low levels of circulating E2 act in an additive manner to stimulate estrogen-dependent tumor growth in vivo. Results from this study suggest that consumption of products containing GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.

Publication: Carcinogenesis 2006 Jun ;27(6)::1292-9.
Publication Date: 2006 Jun
Study Author(s): Ju, Young H;Allred, Kimberly F;Allred, Clinton D;Helferich, William G;
Institution: Department of Food Science and Human Nutrition, University of Illinois, 905 S Goodwin, Room 580 Bevier Hall, Urbana, IL, USA.
Shortcut link to this study:
We have demonstrated that genistein (GEN) stimulates growth of estrogen-dependent breast tumors in vivo. In this study, we evaluated whether dietary GEN can act in an additive manner with low circulating levels of 17beta-estradiol (E2). We developed an E2 delivery system using silastic implants that yield low circulating plasma E2 levels similar to those observed in postmenopausal women. We inserted various concentrations of E2 silastic implants (1:127, 1:63, 1:31, 1:15 and 1:7 = E2:cholesterol) and injected estrogen-dependent human breast cancer (MCF-7) cells into ovariectomized athymic mice. The E2 implants tested (1:127-1:7) generated 30.1-101.6 pM E2 in plasma, which is comparable to the E2 levels observed in postmenopausal women. The E2 implants stimulated MCF-7 tumor growth in a dose-dependent manner. We selected the 1:31 ratio of E2 implant to evaluate if dietary GEN acts in an additive manner with low E2 levels to influence the growth of MCF-7 tumors. OVARIECTOMIZED MICE WERE DIVIDED INTO FOUR GROUPS: MCF-7 control, 500 ppm GEN, 1:31 E2, and 1:31 E2 + 500 ppm GEN. At week 17, the average tumor sizes were 7.6, 32.1, 67.4 and 106.8 mm2 for these groups, respectively (P < 0.05), demonstrating that 500 ppm GEN additively stimulated MCF-7 tumor growth in the presence of low levels of E2. In summary, we established a preclinical mouse model that results in E2 blood concentrations similar to those found in postmenopausal women. Further, we observed that these concentrations regulate the growth rate of MCF-7 breast tumors. Using this model, we demonstrated that dietary GEN in the presence of low levels of circulating E2 act in an additive manner to stimulate estrogen-dependent tumor growth in vivo. Results from this study suggest that consumption of products containing GEN may not be safe for postmenopausal women with estrogen-dependent breast cancer.
PMID: 16537557

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