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result sql = The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo.
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result sql = PURPOSE : This study was designed to test the ability of the Bcl-2 family inhibitor ABT-263 to potentiate commonly used chemotherapeutic agents and regimens in hematologic tumor models.
METHODS : Models of B-cell lymphoma and multiple myeloma were tested in vitro and in vivo with ABT-263 in combination with standard chemotherapeutic regimens, including VAP, CHOP and R-CHOP, as well as single cytotoxic agents including etoposide, rituximab, bortezomib and cyclophosphamide. Alterations in Bcl-2 family member expression patterns were analyzed to define mechanisms of potentiation.
RESULTS : ABT-263 was additive with etoposide, vincristine and VAP in vitro in the diffuse large B-cell lymphoma line (DLBCL) DoHH-2, while rituximab potentiated its activity in SuDHL-4. Bortezomib strongly synergized with ABT-263 in the mantle cell lymphoma line Granta 519. Treatment of DoHH-2 with etoposide was associated with an increase in Puma expression, while bortezomib upregulated Noxa expression in Granta 519. Combination of ABT-263 with cytotoxic agents demonstrated superior tumor growth inhibition and delay in multiple models versus cytotoxic therapy alone, along with significant improvements in tumor response rates.
CONCLUSIONS : Inhibition of the Bcl-2 family of proteins by ABT-263 enhances the cytotoxicity of multiple chemotherapeutics in hematologic tumors and represents a promising addition to the therapeutic arsenal for treatment of these diseases.
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result sql = The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo.
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = B;code = 66
char = c;code = 99
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char = 2;code = 50
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char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = y;code = 121
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
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char = A;code = 65
char = B;code = 66
char = T;code = 84
char = -;code = 45
char = 2;code = 50
char = 6;code = 54
char = 3;code = 51
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = l;code = 108
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char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
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
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = c;code = 99
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char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
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char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = 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 = M;code = 77
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = B;code = 66
char = -;code = 45
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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 = m;code = 109
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
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 = a;code = 97
char = n;code = 110
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 = v;code = 118
char = o;code = 111
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 = 65
char = B;code = 66
char = T;code = 84
char = -;code = 45
char = 2;code = 50
char = 6;code = 54
char = 3;code = 51
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
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char = n;code = 110
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 = s;code = 115
char = t;code = 116
char = a;code = 97
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char = d;code = 100
char = a;code = 97
char = r;code = 114
char = d;code = 100
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 = r;code = 114
char = e;code = 101
char = g;code = 103
char = i;code = 105
char = m;code = 109
char = e;code = 101
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
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char = c;code = 99
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char = u;code = 117
char = d;code = 100
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char = n;code = 110
char = g;code = 103
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char = V;code = 86
char = A;code = 65
char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = C;code = 67
char = H;code = 72
char = O;code = 79
char = P;code = 80
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = R;code = 82
char = -;code = 45
char = C;code = 67
char = H;code = 72
char = O;code = 79
char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
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char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = c;code = 99
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char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = e;code = 101
char = t;code = 116
char = o;code = 111
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char = o;code = 111
char = s;code = 115
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ,;code = 44
char = ;code = 32
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char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
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char = b;code = 98
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char = r;code = 114
char = t;code = 116
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char = z;code = 122
char = o;code = 111
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char = i;code = 105
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char = c;code = 99
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char = c;code = 99
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char = p;code = 112
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char = h;code = 104
char = a;code = 97
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char = i;code = 105
char = d;code = 100
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char = l;code = 108
char = t;code = 116
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = s;code = 115
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char = i;code = 105
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char = B;code = 66
char = c;code = 99
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char = f;code = 102
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char = l;code = 108
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char = e;code = 101
char = m;code = 109
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char = s;code = 115
char = s;code = 115
char = i;code = 105
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char = a;code = 97
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char = t;code = 116
char = e;code = 101
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char = s;code = 115
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char = a;code = 97
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char = e;code = 101
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char = f;code = 102
char = i;code = 105
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char = m;code = 109
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char = c;code = 99
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char = a;code = 97
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char = i;code = 105
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char = m;code = 109
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
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char = t;code = 116
char = i;code = 105
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = .;code = 46
char = <;code = 60
char = b;code = 98
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = A;code = 65
char = B;code = 66
char = T;code = 84
char = -;code = 45
char = 2;code = 50
char = 6;code = 54
char = 3;code = 51
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char = w;code = 119
char = a;code = 97
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char = t;code = 116
char = h;code = 104
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char = t;code = 116
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char = p;code = 112
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char = e;code = 101
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char = s;code = 115
char = t;code = 116
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char = n;code = 110
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = V;code = 86
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char = ;code = 32
char = i;code = 105
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char = i;code = 105
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char = e;code = 101
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char = i;code = 105
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char = L;code = 76
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char = C;code = 67
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char = H;code = 72
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char = i;code = 105
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char = S;code = 83
char = u;code = 117
char = D;code = 68
char = H;code = 72
char = L;code = 76
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char = 4;code = 52
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char = e;code = 101
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char = b;code = 98
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
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char = A;code = 65
char = B;code = 66
char = T;code = 84
char = -;code = 45
char = 2;code = 50
char = 6;code = 54
char = 3;code = 51
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char = a;code = 97
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char = c;code = 99
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char = l;code = 108
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char = p;code = 112
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char = a;code = 97
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char = n;code = 110
char = e;code = 101
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char = G;code = 71
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
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char = 5;code = 53
char = 1;code = 49
char = 9;code = 57
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
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char = n;code = 110
char = t;code = 116
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char = o;code = 111
char = f;code = 102
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char = D;code = 68
char = o;code = 111
char = H;code = 72
char = H;code = 72
char = -;code = 45
char = 2;code = 50
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = o;code = 111
char = p;code = 112
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char = s;code = 115
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char = d;code = 100
char = e;code = 101
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char = w;code = 119
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char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
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char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
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char = i;code = 105
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char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
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result sql = PURPOSE : This study was designed to test the ability of the Bcl-2 family inhibitor ABT-263 to potentiate commonly used chemotherapeutic agents and regimens in hematologic tumor models.
METHODS : Models of B-cell lymphoma and multiple myeloma were tested in vitro and in vivo with ABT-263 in combination with standard chemotherapeutic regimens, including VAP, CHOP and R-CHOP, as well as single cytotoxic agents including etoposide, rituximab, bortezomib and cyclophosphamide. Alterations in Bcl-2 family member expression patterns were analyzed to define mechanisms of potentiation.
RESULTS : ABT-263 was additive with etoposide, vincristine and VAP in vitro in the diffuse large B-cell lymphoma line (DLBCL) DoHH-2, while rituximab potentiated its activity in SuDHL-4. Bortezomib strongly synergized with ABT-263 in the mantle cell lymphoma line Granta 519. Treatment of DoHH-2 with etoposide was associated with an increase in Puma expression, while bortezomib upregulated Noxa expression in Granta 519. Combination of ABT-263 with cytotoxic agents demonstrated superior tumor growth inhibition and delay in multiple models versus cytotoxic therapy alone, along with significant improvements in tumor response rates.
CONCLUSIONS : Inhibition of the Bcl-2 family of proteins by ABT-263 enhances the cytotoxicity of multiple chemotherapeutics in hematologic tumors and represents a promising addition to the therapeutic arsenal for treatment of these diseases.
Publication: Cancer Chemother. Pharmacol. 2010 Oct ;66(5)::869-80. :doi: 10.1007/s00280-009-1232-1.
Publication Date: 2010 Oct
Study Author(s): Ackler, Scott;Mitten, Michael J;Foster, Kelly;Oleksijew, Anatol;Refici, Marion;Tahir, Stephen K;Xiao, Yu;Tse, Christin;Frost, David J;Fesik, Stephen W;Rosenberg, Saul H;Elmore, Steven W;Shoemaker, Alexander R;
Institution: Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA. [email protected]
Shortcut link to this study:
Publication Date: 2010 Oct
Study Author(s): Ackler, Scott;Mitten, Michael J;Foster, Kelly;Oleksijew, Anatol;Refici, Marion;Tahir, Stephen K;Xiao, Yu;Tse, Christin;Frost, David J;Fesik, Stephen W;Rosenberg, Saul H;Elmore, Steven W;Shoemaker, Alexander R;
Institution: Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA. [email protected]
Shortcut link to this study:
PURPOSE : This study was designed to test the ability of the Bcl-2 family inhibitor ABT-263 to potentiate commonly used chemotherapeutic agents and regimens in hematologic tumor models.
METHODS : Models of B-cell lymphoma and multiple myeloma were tested in vitro and in vivo with ABT-263 in combination with standard chemotherapeutic regimens, including VAP, CHOP and R-CHOP, as well as single cytotoxic agents including etoposide, rituximab, bortezomib and cyclophosphamide. Alterations in Bcl-2 family member expression patterns were analyzed to define mechanisms of potentiation.
RESULTS : ABT-263 was additive with etoposide, vincristine and VAP in vitro in the diffuse large B-cell lymphoma line (DLBCL) DoHH-2, while rituximab potentiated its activity in SuDHL-4. Bortezomib strongly synergized with ABT-263 in the mantle cell lymphoma line Granta 519. Treatment of DoHH-2 with etoposide was associated with an increase in Puma expression, while bortezomib upregulated Noxa expression in Granta 519. Combination of ABT-263 with cytotoxic agents demonstrated superior tumor growth inhibition and delay in multiple models versus cytotoxic therapy alone, along with significant improvements in tumor response rates.
CONCLUSIONS : Inhibition of the Bcl-2 family of proteins by ABT-263 enhances the cytotoxicity of multiple chemotherapeutics in hematologic tumors and represents a promising addition to the therapeutic arsenal for treatment of these diseases.
METHODS : Models of B-cell lymphoma and multiple myeloma were tested in vitro and in vivo with ABT-263 in combination with standard chemotherapeutic regimens, including VAP, CHOP and R-CHOP, as well as single cytotoxic agents including etoposide, rituximab, bortezomib and cyclophosphamide. Alterations in Bcl-2 family member expression patterns were analyzed to define mechanisms of potentiation.
RESULTS : ABT-263 was additive with etoposide, vincristine and VAP in vitro in the diffuse large B-cell lymphoma line (DLBCL) DoHH-2, while rituximab potentiated its activity in SuDHL-4. Bortezomib strongly synergized with ABT-263 in the mantle cell lymphoma line Granta 519. Treatment of DoHH-2 with etoposide was associated with an increase in Puma expression, while bortezomib upregulated Noxa expression in Granta 519. Combination of ABT-263 with cytotoxic agents demonstrated superior tumor growth inhibition and delay in multiple models versus cytotoxic therapy alone, along with significant improvements in tumor response rates.
CONCLUSIONS : Inhibition of the Bcl-2 family of proteins by ABT-263 enhances the cytotoxicity of multiple chemotherapeutics in hematologic tumors and represents a promising addition to the therapeutic arsenal for treatment of these diseases.
PMID: 20099064
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