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result sql = Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines.

Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines.

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char = h;code = 104
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char = b;code = 98
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char = b;code = 98
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char = g;code = 103
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char = e;code = 101
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char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = o;code = 111
char = m;code = 109
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char = i;code = 105
char = n;code = 110
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 = e;code = 101
char = a;code = 97
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = o;code = 111
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = R;code = 82
char = -;code = 45
char = T;code = 84
char = K;code = 75
char = I;code = 73
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = g;code = 103
char = e;code = 101
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char = i;code = 105
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = C;code = 67
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
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char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = s;code = 115
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char = a;code = 97
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char = s;code = 115
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = a;code = 97
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = o;code = 111
char = n;code = 110
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
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = R;code = 82
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = A;code = 65
char = k;code = 107
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = o;code = 111
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char = g;code = 103
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = s;code = 115
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 = 44
char = ;code = 32
char = E;code = 69
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = d;code = 100
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = G;code = 71
char = E;code = 69
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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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 = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = R;code = 82
char = -;code = 45
char = T;code = 84
char = K;code = 75
char = I;code = 73
char = s;code = 115
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char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = h;code = 104
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = l;code = 108
char = i;code = 105
char = n;code = 110
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = b;code = 98
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char = t;code = 116
char = ;code = 32
char = H;code = 72
char = 1;code = 49
char = 6;code = 54
char = 5;code = 53
char = 0;code = 48
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = H;code = 72
char = 1;code = 49
char = 7;code = 55
char = 8;code = 56
char = 1;code = 49
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char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = m;code = 109
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char = c;code = 99
char = h;code = 104
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char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
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char = t;code = 116
char = i;code = 105
char = v;code = 118
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char = ;code = 32
char = G;code = 71
char = e;code = 101
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char = i;code = 105
char = s;code = 115
char = t;code = 116
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char = e;code = 101
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char = o;code = 111
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = m;code = 109
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = u;code = 117
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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 = y;code = 121
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char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
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char = l;code = 108
char = i;code = 105
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
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char = e;code = 101
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char = h;code = 104
char = a;code = 97
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char = c;code = 99
char = e;code = 101
char = d;code = 100
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char = h;code = 104
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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 = o;code = 111
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char = a;code = 97
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char = d;code = 100
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char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = s;code = 115
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char = w;code = 119
char = h;code = 104
char = e;code = 101
char = n;code = 110
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char = c;code = 99
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char = m;code = 109
char = b;code = 98
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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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = R;code = 82
char = -;code = 45
char = T;code = 84
char = K;code = 75
char = I;code = 73
char = s;code = 115
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char = i;code = 105
char = n;code = 110
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char = e;code = 101
char = a;code = 97
char = c;code = 99
char = h;code = 104
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = b;code = 98
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = -;code = 45
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 = 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 = s;code = 115
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char = g;code = 103
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char = f;code = 102
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char = t;code = 116
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char = y;code = 121
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char = o;code = 111
char = r;code = 114
char = e;code = 101
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char = a;code = 97
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char = 3;code = 51
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char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = E;code = 69
char = G;code = 71
char = F;code = 70
char = R;code = 82
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char = ;code = 32
char = p;code = 112
char = A;code = 65
char = k;code = 107
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = O;code = 79
char = X;code = 88
char = -;code = 45
char = 2;code = 50
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = P;code = 80
char = G;code = 71
char = E;code = 69
char = (;code = 40
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char = );code = 41
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char = c;code = 99
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char = s;code = 115
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char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = t;code = 116
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char = w;code = 119
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char = h;code = 104
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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
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
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char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = a;code = 97
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char = t;code = 116
char = h;code = 104
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char = s;code = 115
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char = c;code = 99
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char = u;code = 117
char = d;code = 100
char = e;code = 101
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char = t;code = 116
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char = a;code = 97
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char = g;code = 103
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char = s;code = 115
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char = n;code = 110
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char = a;code = 97
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = f;code = 102
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 3;code = 51
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char = s;code = 115
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char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = S;code = 83
char = C;code = 67
char = L;code = 76
char = C;code = 67
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
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char = i;code = 105
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char = .;code = 46
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = p;code = 112
char = a;code = 97
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char = t;code = 116
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char = c;code = 99
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char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = g;code = 103
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char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = r;code = 114
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char = d;code = 100
char = u;code = 117
char = c;code = 99
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char = d;code = 100
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char = g;code = 103
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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
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char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = R;code = 82
char = -;code = 45
char = T;code = 84
char = K;code = 75
char = I;code = 73
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 = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = s;code = 115
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result sql = BACKGROUND : Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown modest clinical benefit in patients with relapsed nonsmall cell lung cancer (NSCLC). Down-regulation of Akt appears to correlate with the antitumor activity of EGFR-TKIs. Akt activates nuclear factor kappa B (NF-kappaB), which transcribes genes important for cell survival, invasion, and metastasis. The authors hypothesized that genistein, through the inhibition of NF-kappaB, could enhance the activity of EGFR-TKIs in NSCLCs.

METHODS : Three NSCLC cell lines with various EGFR mutation status and sensitivities to EGFR-TKIs were selected: H3255 (L858R), H1650 (del E746-A750), and H1781 (wild-type EGFR). Cells were treated with erlotinib, gefitinib, genistein, or the combination of each of the EGFR-TKIs with genistein. Cell survival and apoptosis were assessed, and expression levels of EGFR, pAkt, cyclooxygenase-2 (COX-2), E-cadherin, prostaglandin E(2) (PGE(2)), and NF-kappaB were measured.

RESULTS : Both EGFR-TKIs demonstrated growth inhibition and apoptosis in each of the cell lines, but H1650 and H1781 were much less sensitive. Genistein demonstrated some antitumor activity in all cell lines, but enhanced growth inhibition and apoptosis when combined with the EGFR-TKIs in each of the cell lines. Both combinations down-regulated NF-kappaB significantly more than either agent alone in H3255. In addition, the combinations reduced the expression of EGFR, pAkt, COX-2, and PGE(2,) consistent with inactivation of NF-kappaB.

CONCLUSIONS : The authors concluded that genistein enhances the antitumor effects of EGFR-TKIs in 3 separate NSCLC cell lines. This enhanced activity is in part because of greater reduction in the DNA-binding activity of NF-kappaB when EGFR-TKIs were combined with genistein.

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