|
|
char = C;code = 67
char = h;code = 104
char = e;code = 101
char = m;code = 109
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 = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = d;code = 100
char = r;code = 114
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char = g;code = 103
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
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char = i;code = 105
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = i;code = 105
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char = s;code = 115
char = o;code = 111
char = m;code = 109
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char = i;code = 105
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char = g;code = 103
char = e;code = 101
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char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
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char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
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char = .;code = 46
result sql = Chemotherapeutic drugs inhibit ribosome biogenesis at various levels.
Chemotherapeutic drugs inhibit ribosome biogenesis at various levels.char = D;code = 68
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char = ;code = 32
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char = r;code = 114
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char = a;code = 97
char = p;code = 112
char = y;code = 121
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char = d;code = 100
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char = f;code = 102
char = e;code = 101
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char = .;code = 46
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char = ;code = 32
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char = f;code = 102
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char = a;code = 97
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char = o;code = 111
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = a;code = 97
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = g;code = 103
char = u;code = 117
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = d;code = 100
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char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
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char = H;code = 72
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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 = o;code = 111
char = c;code = 99
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char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
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char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
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char = b;code = 98
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char = e;code = 101
char = s;code = 115
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char = s;code = 115
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char = a;code = 97
char = s;code = 115
char = ;code = 32
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char = e;code = 101
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char = ;code = 32
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char = ;code = 32
char = a;code = 97
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char = a;code = 97
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char = i;code = 105
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char = t;code = 116
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char = o;code = 111
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char = ;code = 32
char = c;code = 99
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char = m;code = 109
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char = h;code = 104
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char = r;code = 114
char = a;code = 97
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char = u;code = 117
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char = i;code = 105
char = c;code = 99
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char = r;code = 114
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char = g;code = 103
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = e;code = 101
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char = n;code = 110
char = e;code = 101
char = d;code = 100
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char = i;code = 105
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char = i;code = 105
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 3;code = 51
char = 6;code = 54
char = ;code = 32
char = c;code = 99
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char = e;code = 101
char = m;code = 109
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char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = u;code = 117
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char = i;code = 105
char = c;code = 99
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char = d;code = 100
char = r;code = 114
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char = g;code = 103
char = s;code = 115
char = ;code = 32
char = f;code = 102
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char = r;code = 114
char = a;code = 97
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char = c;code = 99
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char = p;code = 112
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char = s;code = 115
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char = g;code = 103
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = i;code = 105
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 = l;code = 108
char = a;code = 97
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = e;code = 101
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char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = n;code = 110
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
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char = y;code = 121
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char = g;code = 103
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char = i;code = 105
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char = m;code = 109
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char = g;code = 103
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char = o;code = 111
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char = r;code = 114
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char = g;code = 103
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char = o;code = 111
char = n;code = 110
char = i;code = 105
char = n;code = 110
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char = .;code = 46
char = ;code = 32
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char = l;code = 108
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char = k;code = 107
char = a;code = 97
char = g;code = 103
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
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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
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char = p;code = 112
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 = r;code = 114
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = s;code = 115
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char = c;code = 99
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char = s;code = 115
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char = d;code = 100
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = g;code = 103
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 = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = p;code = 112
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = f;code = 102
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = l;code = 108
char = a;code = 97
char = v;code = 118
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
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 = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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 = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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 = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
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char = e;code = 101
char = ;code = 32
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char = ;code = 32
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char = y;code = 121
char = ;code = 32
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char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = u;code = 117
char = t;code = 116
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char = t;code = 116
char = o;code = 111
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char = f;code = 102
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char = c;code = 99
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char = ;code = 32
char = o;code = 111
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char = ;code = 32
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char = p;code = 112
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char = u;code = 117
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char = c;code = 99
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char = g;code = 103
char = i;code = 105
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char = /;code = 47
char = >;code = 62
result sql = Drugs for cancer therapy belong to different categories of chemical substances. The cellular targets for the therapeutic efficacy are often not unambiguously identified. Here, we describe the process of ribosome biogenesis as a target of a large variety of chemotherapeutic drugs. We determined the inhibitory concentration of 36 chemotherapeutic drugs for transcription and processing of ribosomal RNA by in vivo labeling experiments. Inhibitory drug concentrations were correlated to the loss of nucleolar integrity. The synergism of drugs inhibiting ribosomal RNA synthesis at different levels was studied. Drugs inhibited ribosomal RNA synthesis either at the level of (i) rRNA transcription (e.g. oxaliplatin, doxorubicin, mitoxantrone, methotrexate), (ii) early rRNA processing (e.g. camptothecin, flavopiridol, roscovitine), or (iii) late rRNA processing (e.g. 5-fluorouracil, MG-132, homoharringtonine). Blockage of rRNA transcription or early rRNA processing steps caused nucleolar disintegration, whereas blockage of late rRNA processing steps left the nucleolus intact. Flavopiridol and 5-fluorouracil showed a strong synergism for inhibition of rRNA processing. We conclude that inhibition of ribosome biogenesis by chemotherapeutic drugs potentially may contribute to the efficacy of therapeutic regimens.
char = h;code = 104
char = e;code = 101
char = m;code = 109
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 = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
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 = ;code = 32
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = i;code = 105
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 = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
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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 = 46
result sql = Chemotherapeutic drugs inhibit ribosome biogenesis at various levels.
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char = f;code = 102
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char = c;code = 99
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char = c;code = 99
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char = h;code = 104
char = e;code = 101
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char = p;code = 112
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char = o;code = 111
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char = f;code = 102
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char = c;code = 99
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char = e;code = 101
char = g;code = 103
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char = e;code = 101
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char = ;code = 32
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char = ;code = 32
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char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
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 = 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 = 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 = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = i;code = 105
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 = l;code = 108
char = a;code = 97
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
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 = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
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 = 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 = r;code = 114
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 = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
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 = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = t;code = 116
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 = ;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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
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 = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = (;code = 40
char = i;code = 105
char = );code = 41
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
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 = (;code = 40
char = e;code = 101
char = .;code = 46
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = r;code = 114
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = (;code = 40
char = i;code = 105
char = i;code = 105
char = );code = 41
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = (;code = 40
char = e;code = 101
char = .;code = 46
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = v;code = 118
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = c;code = 99
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = i;code = 105
char = i;code = 105
char = i;code = 105
char = );code = 41
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = (;code = 40
char = e;code = 101
char = .;code = 46
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = M;code = 77
char = G;code = 71
char = -;code = 45
char = 1;code = 49
char = 3;code = 51
char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = t;code = 116
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = );code = 41
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
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 = o;code = 111
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = p;code = 112
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = g;code = 103
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 = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = p;code = 112
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = f;code = 102
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = l;code = 108
char = a;code = 97
char = v;code = 118
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
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 = s;code = 115
char = y;code = 121
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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 = r;code = 114
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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 = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = i;code = 105
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 = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
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 = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
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result sql = Drugs for cancer therapy belong to different categories of chemical substances. The cellular targets for the therapeutic efficacy are often not unambiguously identified. Here, we describe the process of ribosome biogenesis as a target of a large variety of chemotherapeutic drugs. We determined the inhibitory concentration of 36 chemotherapeutic drugs for transcription and processing of ribosomal RNA by in vivo labeling experiments. Inhibitory drug concentrations were correlated to the loss of nucleolar integrity. The synergism of drugs inhibiting ribosomal RNA synthesis at different levels was studied. Drugs inhibited ribosomal RNA synthesis either at the level of (i) rRNA transcription (e.g. oxaliplatin, doxorubicin, mitoxantrone, methotrexate), (ii) early rRNA processing (e.g. camptothecin, flavopiridol, roscovitine), or (iii) late rRNA processing (e.g. 5-fluorouracil, MG-132, homoharringtonine). Blockage of rRNA transcription or early rRNA processing steps caused nucleolar disintegration, whereas blockage of late rRNA processing steps left the nucleolus intact. Flavopiridol and 5-fluorouracil showed a strong synergism for inhibition of rRNA processing. We conclude that inhibition of ribosome biogenesis by chemotherapeutic drugs potentially may contribute to the efficacy of therapeutic regimens.
Publication: J. Biol. Chem. 2010 Apr 16 ;285(16)::12416-25.
Publication Date: 2010 Apr 16
Study Author(s): Burger, Kaspar;Mühl, Bastian;Harasim, Thomas;Rohrmoser, Michaela;Malamoussi, Anastassia;Orban, Mathias;Kellner, Markus;Gruber-Eber, Anita;Kremmer, Elisabeth;Hölzel, Michael;Eick, Dirk;
Institution: Institute for Clinical Molecular Biology and Tumor Genetics, Center for Integrated Protein Science Munich (CIPSM), Germany.
Shortcut link to this study:
Publication Date: 2010 Apr 16
Study Author(s): Burger, Kaspar;Mühl, Bastian;Harasim, Thomas;Rohrmoser, Michaela;Malamoussi, Anastassia;Orban, Mathias;Kellner, Markus;Gruber-Eber, Anita;Kremmer, Elisabeth;Hölzel, Michael;Eick, Dirk;
Institution: Institute for Clinical Molecular Biology and Tumor Genetics, Center for Integrated Protein Science Munich (CIPSM), Germany.
Shortcut link to this study:
Drugs for cancer therapy belong to different categories of chemical substances. The cellular targets for the therapeutic efficacy are often not unambiguously identified. Here, we describe the process of ribosome biogenesis as a target of a large variety of chemotherapeutic drugs. We determined the inhibitory concentration of 36 chemotherapeutic drugs for transcription and processing of ribosomal RNA by in vivo labeling experiments. Inhibitory drug concentrations were correlated to the loss of nucleolar integrity. The synergism of drugs inhibiting ribosomal RNA synthesis at different levels was studied. Drugs inhibited ribosomal RNA synthesis either at the level of (i) rRNA transcription (e.g. oxaliplatin, doxorubicin, mitoxantrone, methotrexate), (ii) early rRNA processing (e.g. camptothecin, flavopiridol, roscovitine), or (iii) late rRNA processing (e.g. 5-fluorouracil, MG-132, homoharringtonine). Blockage of rRNA transcription or early rRNA processing steps caused nucleolar disintegration, whereas blockage of late rRNA processing steps left the nucleolus intact. Flavopiridol and 5-fluorouracil showed a strong synergism for inhibition of rRNA processing. We conclude that inhibition of ribosome biogenesis by chemotherapeutic drugs potentially may contribute to the efficacy of therapeutic regimens.
PMID: 20159984
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