|
|
char = T;code = 84
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char = ;code = 32
char = N;code = 78
char = V;code = 86
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char = 5;code = 53
char = 4;code = 52
char = 1;code = 49
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char = m;code = 109
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char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = .;code = 46
result sql = Treatment of biliary tract cancer with NVP-AEW541: mechanisms of action and resistance.
Treatment of biliary tract cancer with NVP-AEW541: mechanisms of action and resistance.char = <;code = 60
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char = y;code = 121
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char = B;code = 66
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result sql = AIM : To investigate in vitro treatment with NVP-AEW541, a small molecule inhibitor of insulin-like growth factor-1 receptor (IGF-1R), in biliary tract cancer (BTC), since this disease is associated with a poor prognosis due to wide resistance to chemotherapeutic agents and radiotherapy.
METHODS : Cell growth inhibition by NVP-AEW541 was studied in vitro in 7 human BTC cell lines by automated cell counting. In addition, the anti-tumoral mechanism of NVP-AEW541 was studied by Western blotting, cell cycle analysis and reverse transcription-polymerase chain reaction (RT-PCR). Anti-tumoral drug effect in combination with gemcitabine, 5-fluorouracil (5-FU) and Polo-like kinase 1 inhibitor BI2536 was also studied.
RESULTS : In vitro treatment with NVP-AEW541 suppressed growth in all human BTC cell lines, however response was lower in gallbladder cancer. Treatment with NVP-AEW541 was associated with dephosphorylation of IGF-1R and AKT. In contrast, phosphorylation of p42/p44 and Stat3 and expression of Bcl-xL were inconsistently downregulated. In addition, treated cells showed cell cycle arrest at the G1/S-checkpoint and an increase in sub-G1 peak. Moreover, IGF-1R and its ligands IGF-1 and IGF-2 were co-expressed in RT-PCR, suggesting an autocrine loop of tumor cell activation. Combined with gemcitabine, NVP-AEW541 exerted synergistic effects, particularly at low concentrations, while effects of combination with 5-FU or BI 2536 were only additive.
CONCLUSION : Our findings suggest that NVP-AEW541 is active against BTC in vitro and potentiates the efficacy of gemcitabine.
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char = f;code = 102
char = ;code = 32
char = a;code = 97
char = c;code = 99
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 = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = .;code = 46
result sql = Treatment of biliary tract cancer with NVP-AEW541: mechanisms of action and resistance.
char = b;code = 98
char = >;code = 62
char = A;code = 65
char = I;code = 73
char = M;code = 77
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 = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = N;code = 78
char = V;code = 86
char = P;code = 80
char = -;code = 45
char = A;code = 65
char = E;code = 69
char = W;code = 87
char = 5;code = 53
char = 4;code = 52
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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 = m;code = 109
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
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char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = 1;code = 49
char = R;code = 82
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = B;code = 66
char = T;code = 84
char = C;code = 67
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
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 = a;code = 97
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = n;code = 110
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
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char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
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 = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
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 = 46
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 = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = M;code = 77
char = E;code = 69
char = T;code = 84
char = H;code = 72
char = O;code = 79
char = D;code = 68
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 = C;code = 67
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = 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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = N;code = 78
char = V;code = 86
char = P;code = 80
char = -;code = 45
char = A;code = 65
char = E;code = 69
char = W;code = 87
char = 5;code = 53
char = 4;code = 52
char = 1;code = 49
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 = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 7;code = 55
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 = B;code = 66
char = T;code = 84
char = C;code = 67
char = ;code = 32
char = c;code = 99
char = e;code = 101
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
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
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 = N;code = 78
char = V;code = 86
char = P;code = 80
char = -;code = 45
char = A;code = 65
char = E;code = 69
char = W;code = 87
char = 5;code = 53
char = 4;code = 52
char = 1;code = 49
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 = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = l;code = 108
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char = t;code = 116
char = i;code = 105
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char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
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char = a;code = 97
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char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
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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 = 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
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char = -;code = 45
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = c;code = 99
char = h;code = 104
char = a;code = 97
char = i;code = 105
char = n;code = 110
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char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = T;code = 84
char = -;code = 45
char = P;code = 80
char = C;code = 67
char = R;code = 82
char = );code = 41
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = t;code = 116
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char = m;code = 109
char = o;code = 111
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = r;code = 114
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char = g;code = 103
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = c;code = 99
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char = m;code = 109
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char = i;code = 105
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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 = m;code = 109
char = c;code = 99
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char = t;code = 116
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char = b;code = 98
char = i;code = 105
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char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = 5;code = 53
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char = f;code = 102
char = l;code = 108
char = u;code = 117
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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 = (;code = 40
char = 5;code = 53
char = -;code = 45
char = F;code = 70
char = U;code = 85
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = -;code = 45
char = l;code = 108
char = i;code = 105
char = k;code = 107
char = e;code = 101
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char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = 1;code = 49
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 = o;code = 111
char = r;code = 114
char = ;code = 32
char = B;code = 66
char = I;code = 73
char = 2;code = 50
char = 5;code = 53
char = 3;code = 51
char = 6;code = 54
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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 = 60
char = b;code = 98
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char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = <;code = 60
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char = R;code = 82
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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
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char = <;code = 60
char = /;code = 47
char = b;code = 98
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char = I;code = 73
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char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = r;code = 114
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = N;code = 78
char = V;code = 86
char = P;code = 80
char = -;code = 45
char = A;code = 65
char = E;code = 69
char = W;code = 87
char = 5;code = 53
char = 4;code = 52
char = 1;code = 49
char = ;code = 32
char = s;code = 115
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char = p;code = 112
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char = e;code = 101
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char = i;code = 105
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char = a;code = 97
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char = l;code = 108
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char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
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char = B;code = 66
char = T;code = 84
char = C;code = 67
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
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
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char = s;code = 115
char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = r;code = 114
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char = i;code = 105
char = n;code = 110
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char = g;code = 103
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = d;code = 100
char = d;code = 100
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
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char = ;code = 32
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char = c;code = 99
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result sql = AIM : To investigate in vitro treatment with NVP-AEW541, a small molecule inhibitor of insulin-like growth factor-1 receptor (IGF-1R), in biliary tract cancer (BTC), since this disease is associated with a poor prognosis due to wide resistance to chemotherapeutic agents and radiotherapy.
METHODS : Cell growth inhibition by NVP-AEW541 was studied in vitro in 7 human BTC cell lines by automated cell counting. In addition, the anti-tumoral mechanism of NVP-AEW541 was studied by Western blotting, cell cycle analysis and reverse transcription-polymerase chain reaction (RT-PCR). Anti-tumoral drug effect in combination with gemcitabine, 5-fluorouracil (5-FU) and Polo-like kinase 1 inhibitor BI2536 was also studied.
RESULTS : In vitro treatment with NVP-AEW541 suppressed growth in all human BTC cell lines, however response was lower in gallbladder cancer. Treatment with NVP-AEW541 was associated with dephosphorylation of IGF-1R and AKT. In contrast, phosphorylation of p42/p44 and Stat3 and expression of Bcl-xL were inconsistently downregulated. In addition, treated cells showed cell cycle arrest at the G1/S-checkpoint and an increase in sub-G1 peak. Moreover, IGF-1R and its ligands IGF-1 and IGF-2 were co-expressed in RT-PCR, suggesting an autocrine loop of tumor cell activation. Combined with gemcitabine, NVP-AEW541 exerted synergistic effects, particularly at low concentrations, while effects of combination with 5-FU or BI 2536 were only additive.
CONCLUSION : Our findings suggest that NVP-AEW541 is active against BTC in vitro and potentiates the efficacy of gemcitabine.
Publication: World J. Gastroenterol. 2010 Jan 14 ;16(2)::156-66.
Publication Date: 2010 Jan 14
Study Author(s): Wolf, Samuel;Lorenz, Jana;Mössner, Joachim;Wiedmann, Marcus;
Institution: Department of Internal Medicine II, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
Shortcut link to this study:
Publication Date: 2010 Jan 14
Study Author(s): Wolf, Samuel;Lorenz, Jana;Mössner, Joachim;Wiedmann, Marcus;
Institution: Department of Internal Medicine II, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
Shortcut link to this study:
AIM : To investigate in vitro treatment with NVP-AEW541, a small molecule inhibitor of insulin-like growth factor-1 receptor (IGF-1R), in biliary tract cancer (BTC), since this disease is associated with a poor prognosis due to wide resistance to chemotherapeutic agents and radiotherapy.
METHODS : Cell growth inhibition by NVP-AEW541 was studied in vitro in 7 human BTC cell lines by automated cell counting. In addition, the anti-tumoral mechanism of NVP-AEW541 was studied by Western blotting, cell cycle analysis and reverse transcription-polymerase chain reaction (RT-PCR). Anti-tumoral drug effect in combination with gemcitabine, 5-fluorouracil (5-FU) and Polo-like kinase 1 inhibitor BI2536 was also studied.
RESULTS : In vitro treatment with NVP-AEW541 suppressed growth in all human BTC cell lines, however response was lower in gallbladder cancer. Treatment with NVP-AEW541 was associated with dephosphorylation of IGF-1R and AKT. In contrast, phosphorylation of p42/p44 and Stat3 and expression of Bcl-xL were inconsistently downregulated. In addition, treated cells showed cell cycle arrest at the G1/S-checkpoint and an increase in sub-G1 peak. Moreover, IGF-1R and its ligands IGF-1 and IGF-2 were co-expressed in RT-PCR, suggesting an autocrine loop of tumor cell activation. Combined with gemcitabine, NVP-AEW541 exerted synergistic effects, particularly at low concentrations, while effects of combination with 5-FU or BI 2536 were only additive.
CONCLUSION : Our findings suggest that NVP-AEW541 is active against BTC in vitro and potentiates the efficacy of gemcitabine.
METHODS : Cell growth inhibition by NVP-AEW541 was studied in vitro in 7 human BTC cell lines by automated cell counting. In addition, the anti-tumoral mechanism of NVP-AEW541 was studied by Western blotting, cell cycle analysis and reverse transcription-polymerase chain reaction (RT-PCR). Anti-tumoral drug effect in combination with gemcitabine, 5-fluorouracil (5-FU) and Polo-like kinase 1 inhibitor BI2536 was also studied.
RESULTS : In vitro treatment with NVP-AEW541 suppressed growth in all human BTC cell lines, however response was lower in gallbladder cancer. Treatment with NVP-AEW541 was associated with dephosphorylation of IGF-1R and AKT. In contrast, phosphorylation of p42/p44 and Stat3 and expression of Bcl-xL were inconsistently downregulated. In addition, treated cells showed cell cycle arrest at the G1/S-checkpoint and an increase in sub-G1 peak. Moreover, IGF-1R and its ligands IGF-1 and IGF-2 were co-expressed in RT-PCR, suggesting an autocrine loop of tumor cell activation. Combined with gemcitabine, NVP-AEW541 exerted synergistic effects, particularly at low concentrations, while effects of combination with 5-FU or BI 2536 were only additive.
CONCLUSION : Our findings suggest that NVP-AEW541 is active against BTC in vitro and potentiates the efficacy of gemcitabine.
PMID: 20066734
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