char = L;code = 76
char = o;code = 111
char = n;code = 110
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char = -;code = 45
char = t;code = 116
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char = r;code = 114
char = m;code = 109
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = n;code = 110
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
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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 = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = r;code = 114
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 = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
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 = f;code = 102
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = .;code = 46
result sql = Long-term radioiodine retention and regression of liver cancer after sodium iodide symporter gene transfer in wistar rats.
Long-term radioiodine retention and regression of liver cancer after sodium iodide symporter gene transfer in wistar rats.
char = R;code = 82
char = a;code = 97
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char = i;code = 105
char = o;code = 111
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
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char = f;code = 102
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = t;code = 116
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char = d;code = 100
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 = s;code = 115
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
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char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = s;code = 115
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
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char = e;code = 101
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = N;code = 78
char = I;code = 73
char = S;code = 83
char = );code = 41
char = ;code = 32
char = g;code = 103
char = e;code = 101
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char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = o;code = 111
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char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
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 = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
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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
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char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = t;code = 116
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char = s;code = 115
char = e;code = 101
char = e;code = 101
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = t;code = 116
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char = b;code = 98
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
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char = c;code = 99
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char = e;code = 101
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char = b;code = 98
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char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = r;code = 114
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = e;code = 101
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char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = x;code = 120
char = e;code = 101
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char = o;code = 111
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char = r;code = 114
char = a;code = 97
char = f;code = 102
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
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char = p;code = 112
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char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
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char = i;code = 105
char = n;code = 110
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char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
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char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = i;code = 105
char = c;code = 99
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char = t;code = 116
char = u;code = 117
char = d;code = 100
char = y;code = 121
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = I;code = 73
char = S;code = 83
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = e;code = 101
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char = i;code = 105
char = c;code = 99
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char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = u;code = 117
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
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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 = g;code = 103
char = g;code = 103
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = i;code = 105
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char = e;code = 101
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char = m;code = 109
char = o;code = 111
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char = e;code = 101
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char = o;code = 111
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char = ;code = 32
char = h;code = 104
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char = p;code = 112
char = a;code = 97
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char = c;code = 99
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char = r;code = 114
char = c;code = 99
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char = h;code = 104
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char = r;code = 114
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char = s;code = 115
char = a;code = 97
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char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = u;code = 117
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char = o;code = 111
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char = r;code = 114
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char = b;code = 98
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char = r;code = 114
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char = ;code = 32
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char = h;code = 104
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char = (;code = 40
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char = i;code = 105
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char = ;code = 32
char = o;code = 111
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char = ;code = 32
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char = ;code = 32
char = f;code = 102
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char = i;code = 105
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char = a;code = 97
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char = N;code = 78
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char = S;code = 83
char = ;code = 32
char = p;code = 112
char = r;code = 114
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char = t;code = 116
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char = e;code = 101
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char = d;code = 100
char = ;code = 32
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char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = e;code = 101
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char = d;code = 100
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char = 1;code = 49
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char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
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char = s;code = 115
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char = t;code = 116
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char = t;code = 116
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char = s;code = 115
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char = i;code = 105
char = o;code = 111
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char = i;code = 105
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char = e;code = 101
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char = e;code = 101
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char = f;code = 102
char = l;code = 108
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char = x;code = 120
char = ;code = 32
char = f;code = 102
char = o;code = 111
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char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = o;code = 111
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char = i;code = 105
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char = h;code = 104
char = u;code = 117
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char = h;code = 104
char = e;code = 101
char = p;code = 112
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
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char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
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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
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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 = I;code = 73
char = S;code = 83
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = s;code = 115
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char = d;code = 100
char = i;code = 105
char = u;code = 117
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char = ;code = 32
char = p;code = 112
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char = c;code = 99
char = h;code = 104
char = l;code = 108
char = o;code = 111
char = r;code = 114
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char = l;code = 108
char = e;code = 101
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char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = a;code = 97
char = ;code = 32
char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
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char = e;code = 101
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char = f;code = 102
char = l;code = 108
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char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
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char = v;code = 118
char = e;code = 101
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char = i;code = 105
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
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char = o;code = 111
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = r;code = 114
char = i;code = 105
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char = b;code = 98
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char = e;code = 101
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char = t;code = 116
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char = ;code = 32
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char = t;code = 116
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char = o;code = 111
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char = c;code = 99
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char = s;code = 115
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char = ;code = 32
char = b;code = 98
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char = t;code = 116
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
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char = r;code = 114
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = r;code = 114
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char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = o;code = 111
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char = ;code = 32
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char = a;code = 97
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = p;code = 112
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 = l;code = 108
char = o;code = 111
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = .;code = 46
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = A;code = 65
char = d;code = 100
char = -;code = 45
char = C;code = 67
char = M;code = 77
char = V;code = 86
char = -;code = 45
char = r;code = 114
char = N;code = 78
char = I;code = 73
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
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 = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = h;code = 104
char = i;code = 105
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = g;code = 103
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 = 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 = 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 = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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 = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = -;code = 45
char = b;code = 98
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
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 = s;code = 115
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 = ;code = 32
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = I;code = 73
char = S;code = 83
char = -;code = 45
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = n;code = 110
char = t;code = 116
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 = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS) gene delivery has been proposed as a potential application of gene therapy. However, it seems to be precluded by the rapid efflux of taken up iodine from most transduced xenografted tumors. We present an in vivo kinetic study of NIS-related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body iodine distribution by repeated imaging of live animals. We constructed a rat NIS (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove expression of a functional NIS protein by hepatocytes and allowed marked (from 20 to 30% of the injected dose) and sustained (>11 days) iodine uptake. This contrasts with the massive iodine efflux found in vitro in human hepatic tumor cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a rapid iodine efflux from the liver, indicating that the sustained uptake was not attributable to an active retention mechanism but to permanent recycling of the effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the complete regression of small nodules, and prolonged survival of hepatocarcinoma-bearing rats. This demonstrates for the first time the efficacy of NIS-based radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.

Publication: Cancer Res. 2004 Nov 1 ;64(21)::8045-51.
Publication Date: 2004 Nov 1
Study Author(s): Faivre, Jamila;Clerc, Jérôme;Gérolami, René;Hervé, Julie;Longuet, Michèle;Liu, Bingkai;Roux, Jérôme;Moal, Frédéric;Perricaudet, Michel;Bréchot, Christian;
Institution: Department of Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unit 370, Paris V University, CHU Necker, Paris, France. [email protected]
Shortcut link to this study:
Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS) gene delivery has been proposed as a potential application of gene therapy. However, it seems to be precluded by the rapid efflux of taken up iodine from most transduced xenografted tumors. We present an in vivo kinetic study of NIS-related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body iodine distribution by repeated imaging of live animals. We constructed a rat NIS (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove expression of a functional NIS protein by hepatocytes and allowed marked (from 20 to 30% of the injected dose) and sustained (>11 days) iodine uptake. This contrasts with the massive iodine efflux found in vitro in human hepatic tumor cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a rapid iodine efflux from the liver, indicating that the sustained uptake was not attributable to an active retention mechanism but to permanent recycling of the effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the complete regression of small nodules, and prolonged survival of hepatocarcinoma-bearing rats. This demonstrates for the first time the efficacy of NIS-based radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.
PMID: 15520214

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