|
|
char = E;code = 69
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char = x;code = 120
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result sql = Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.
Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.char = <;code = 60
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char = t;code = 116
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char = e;code = 101
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char = S;code = 83
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char = L;code = 76
char = T;code = 84
char = S;code = 83
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char = a;code = 97
char = c;code = 99
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char = D;code = 68
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char = x;code = 120
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char = t;code = 116
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char = n;code = 110
char = s;code = 115
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char = t;code = 116
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char = l;code = 108
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char = t;code = 116
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char = e;code = 101
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = s;code = 115
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char = i;code = 105
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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 = o;code = 111
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char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
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char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
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char = a;code = 97
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char = e;code = 101
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char = e;code = 101
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char = e;code = 101
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result sql = BACKGROUND : The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector.
RESULTS : Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents.
CONCLUSIONS : We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.
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char = J;code = 74
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char = .;code = 46
result sql = Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.
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char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
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 = m;code = 109
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = J;code = 74
char = u;code = 117
char = r;code = 114
char = k;code = 107
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = T;code = 84
char = -;code = 45
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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 = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = y;code = 121
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 = c;code = 99
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 = D;code = 68
char = a;code = 97
char = x;code = 120
char = x;code = 120
char = -;code = 45
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = D;code = 68
char = a;code = 97
char = x;code = 120
char = x;code = 120
char = -;code = 45
char = n;code = 110
char = e;code = 101
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
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 = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = A;code = 65
char = s;code = 115
char = s;code = 115
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 = 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 = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = D;code = 68
char = a;code = 97
char = x;code = 120
char = x;code = 120
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
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 = w;code = 119
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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 = D;code = 68
char = a;code = 97
char = x;code = 120
char = x;code = 120
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = N;code = 78
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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 = D;code = 68
char = a;code = 97
char = x;code = 120
char = x;code = 120
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = B;code = 66
char = I;code = 73
char = D;code = 68
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 = D;code = 68
char = a;code = 97
char = x;code = 120
char = x;code = 120
char = -;code = 45
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = J;code = 74
char = u;code = 117
char = r;code = 114
char = k;code = 107
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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 = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = -;code = 45
char = 1;code = 49
char = 0;code = 48
char = ,;code = 44
char = ;code = 32
char = -;code = 45
char = 9;code = 57
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
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 = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
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 = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = X;code = 88
char = I;code = 73
char = A;code = 65
char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = I;code = 73
char = A;code = 65
char = P;code = 80
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = -;code = 45
char = 2;code = 50
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 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 = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = u;code = 117
char = b;code = 98
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = D;code = 68
char = a;code = 97
char = x;code = 120
char = x;code = 120
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
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 = a;code = 97
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = ;code = 32
char = J;code = 74
char = u;code = 117
char = r;code = 114
char = k;code = 107
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = T;code = 84
char = -;code = 45
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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 = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
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
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 = 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
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result sql = BACKGROUND : The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector.
RESULTS : Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents.
CONCLUSIONS : We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.
Publication: Pharmacol. Res. 2005 Apr ;51(4)::367-74.
Publication Date: 2005 Apr
Study Author(s): Boehrer, Simone;Nowak, Daniel;Kukoc-Zivojnov, Natasa;Hochmuth, Simone;Kim, Soo-Zin;Hoelzer, Dieter;Mitrou, Paris S;Weidmann, Eckhart;Chow, Kai Uwe;
Institution: Department of Internal Medicine III, Hematology and Oncology, Johann Wolfgang Goethe-University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Shortcut link to this study:
Publication Date: 2005 Apr
Study Author(s): Boehrer, Simone;Nowak, Daniel;Kukoc-Zivojnov, Natasa;Hochmuth, Simone;Kim, Soo-Zin;Hoelzer, Dieter;Mitrou, Paris S;Weidmann, Eckhart;Chow, Kai Uwe;
Institution: Department of Internal Medicine III, Hematology and Oncology, Johann Wolfgang Goethe-University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Shortcut link to this study:
BACKGROUND : The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector.
RESULTS : Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents.
CONCLUSIONS : We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.
RESULTS : Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents.
CONCLUSIONS : We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.
PMID: 15683751
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