|
|
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = F;code = 70
char = -;code = 45
char = k;code = 107
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = a;code = 97
char = B;code = 66
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
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char = s;code = 115
char = ;code = 32
char = (;code = 40
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char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = z;code = 122
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char = i;code = 105
char = b;code = 98
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = D;code = 68
char = H;code = 72
char = M;code = 77
char = E;code = 69
char = Q;code = 81
char = );code = 41
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 = s;code = 115
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = b;code = 98
char = -;code = 45
char = r;code = 114
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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 = t;code = 116
char = ;code = 32
char = A;code = 65
char = I;code = 73
char = D;code = 68
char = S;code = 83
char = -;code = 45
char = B;code = 66
char = -;code = 45
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = H;code = 72
char = o;code = 111
char = d;code = 100
char = g;code = 103
char = k;code = 107
char = i;code = 105
char = n;code = 110
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 = t;code = 116
char = o;code = 111
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 = b;code = 98
char = y;code = 121
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = o;code = 111
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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 = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = .;code = 46
result sql = The NF-kappaB inhibitors (bortezomib and DHMEQ) sensitise rituximab-resistant AIDS-B-non-Hodgkin lymphoma to apoptosis by various chemotherapeutic drugs.
The NF-kappaB inhibitors (bortezomib and DHMEQ) sensitise rituximab-resistant AIDS-B-non-Hodgkin lymphoma to apoptosis by various chemotherapeutic drugs.char = R;code = 82
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = b;code = 98
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
char = i;code = 105
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 = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
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char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 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
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char = o;code = 111
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char = ;code = 32
char = p;code = 112
char = a;code = 97
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char = e;code = 101
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char = s;code = 115
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 = I;code = 73
char = D;code = 68
char = S;code = 83
char = -;code = 45
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
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = B;code = 66
char = -;code = 45
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = n;code = 110
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char = n;code = 110
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char = H;code = 72
char = o;code = 111
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char = k;code = 107
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char = l;code = 108
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char = m;code = 109
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char = h;code = 104
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = N;code = 78
char = H;code = 72
char = L;code = 76
char = );code = 41
char = ;;code = 59
char = ;code = 32
char = h;code = 104
char = o;code = 111
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char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
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char = ;code = 32
char = d;code = 100
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char = n;code = 110
char = o;code = 111
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char = ;code = 32
char = r;code = 114
char = e;code = 101
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char = p;code = 112
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char = ;code = 32
char = d;code = 100
char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = o;code = 111
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char = ;code = 32
char = r;code = 114
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char = i;code = 105
char = s;code = 115
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char = f;code = 102
char = o;code = 111
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char = l;code = 108
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char = w;code = 119
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char = g;code = 103
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = T;code = 84
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char = a;code = 97
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char = i;code = 105
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char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = r;code = 114
char = i;code = 105
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char = a;code = 97
char = b;code = 98
char = -;code = 45
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 = t;code = 116
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = R;code = 82
char = );code = 41
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = l;code = 108
char = d;code = 100
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char = t;code = 116
char = y;code = 121
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char = e;code = 101
char = ;code = 32
char = (;code = 40
char = w;code = 119
char = T;code = 84
char = );code = 41
char = ;code = 32
char = 2;code = 50
char = F;code = 70
char = 7;code = 55
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
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char = ;code = 32
char = 2;code = 50
char = F;code = 70
char = 7;code = 55
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char = R;code = 82
char = R;code = 82
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = t;code = 116
char = s;code = 115
char = ;code = 32
char = r;code = 114
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char = s;code = 115
char = e;code = 101
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char = o;code = 111
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char = t;code = 116
char = m;code = 109
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char = ;code = 32
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char = l;code = 108
char = ;code = 32
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char = s;code = 115
char = ;code = 32
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char = i;code = 105
char = t;code = 116
char = u;code = 117
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char = h;code = 104
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char = w;code = 119
char = T;code = 84
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char = ,;code = 44
char = ;code = 32
char = 2;code = 50
char = F;code = 70
char = 7;code = 55
char = -;code = 45
char = R;code = 82
char = R;code = 82
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char = s;code = 115
char = ;code = 32
char = C;code = 67
char = D;code = 68
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char = s;code = 115
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char = ;code = 32
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char = i;code = 105
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char = ;code = 32
char = (;code = 40
char = C;code = 67
char = D;code = 68
char = C;code = 67
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char = a;code = 97
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char = i;code = 105
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char = f;code = 102
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char = l;code = 108
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char = i;code = 105
char = n;code = 110
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char = .;code = 46
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char = I;code = 73
char = n;code = 110
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char = a;code = 97
char = d;code = 100
char = d;code = 100
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char = ,;code = 44
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char = f;code = 102
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result sql = Rituximab in combination with chemotherapy is considered for the treatment of patients with AIDS-associated B-cell non-Hodgkin lymphoma (NHL); however, a subgroup of patients does not respond or develops resistance following initial treatments. To address the mechanism of rituximab-resistance, we have generated rituximab-resistant (RR) clones from wild-type (wT) 2F7. A representative 2F7-RR1 clone was examined for its response to rituximab treatment as well as rituximab-mediated chemosensitisation. In comparison with wT-2F7, 2F7-RR1 had less CD20 cell surface expression and failed to respond to rituximab-induced complement-dependent cytotoxicity (CDC) and apoptosis following cross-linking. In addition, rituximab failed to inhibit the constitutively activated p38 MAPK/NF-kappaB pathways and failed to sensitise 2F7-RR1 to various chemotherapeutic drugs (examples: taxol, vincristine, VP16, CDDP). In contrast to rituximab, treatment of 2F7-RR1 with the proteasome inhibitor, bortezomib, and the NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), resulted in inhibition of Bcl-2 expression and sensitisation of 2F7-RR1 to apoptosis by chemotherapeutic drugs. These findings demonstrate that rituximab resistance may be due to failure of rituximab to modify survival pathways. However, pharmacologic inhibitors that inhibit survival pathways can reverse RR tumor cells and sensitise the cells to apoptosis by various chemotherapeutic drugs. These findings offer novel potential therapeutic applications in the reversal of rituximab/drug resistant AIDS-derived B-NHL.
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char = i;code = 105
char = s;code = 115
char = e;code = 101
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char = t;code = 116
char = u;code = 117
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char = b;code = 98
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char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = A;code = 65
char = I;code = 73
char = D;code = 68
char = S;code = 83
char = -;code = 45
char = B;code = 66
char = -;code = 45
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = H;code = 72
char = o;code = 111
char = d;code = 100
char = g;code = 103
char = k;code = 107
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char = l;code = 108
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char = m;code = 109
char = a;code = 97
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char = t;code = 116
char = o;code = 111
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
char = ;code = 32
char = b;code = 98
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char = ;code = 32
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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 = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
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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 = 46
result sql = The NF-kappaB inhibitors (bortezomib and DHMEQ) sensitise rituximab-resistant AIDS-B-non-Hodgkin lymphoma to apoptosis by various chemotherapeutic drugs.
char = i;code = 105
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char = u;code = 117
char = x;code = 120
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char = b;code = 98
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
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char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = w;code = 119
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char = h;code = 104
char = ;code = 32
char = c;code = 99
char = h;code = 104
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
char = p;code = 112
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char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = d;code = 100
char = e;code = 101
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
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char = ;code = 32
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char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = m;code = 109
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char = t;code = 116
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char = f;code = 102
char = ;code = 32
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char = A;code = 65
char = I;code = 73
char = D;code = 68
char = S;code = 83
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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 = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = B;code = 66
char = -;code = 45
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = n;code = 110
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char = n;code = 110
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char = H;code = 72
char = o;code = 111
char = d;code = 100
char = g;code = 103
char = k;code = 107
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char = n;code = 110
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char = l;code = 108
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char = h;code = 104
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = N;code = 78
char = H;code = 72
char = L;code = 76
char = );code = 41
char = ;;code = 59
char = ;code = 32
char = h;code = 104
char = o;code = 111
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char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
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char = t;code = 116
char = s;code = 115
char = ;code = 32
char = d;code = 100
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char = e;code = 101
char = s;code = 115
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char = n;code = 110
char = o;code = 111
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char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
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char = n;code = 110
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = p;code = 112
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
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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 = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
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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
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char = .;code = 46
char = ;code = 32
char = T;code = 84
char = o;code = 111
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char = a;code = 97
char = d;code = 100
char = d;code = 100
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = r;code = 114
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char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = b;code = 98
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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 = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = b;code = 98
char = -;code = 45
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 = t;code = 116
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = R;code = 82
char = );code = 41
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = l;code = 108
char = d;code = 100
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char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = w;code = 119
char = T;code = 84
char = );code = 41
char = ;code = 32
char = 2;code = 50
char = F;code = 70
char = 7;code = 55
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = F;code = 70
char = 7;code = 55
char = -;code = 45
char = R;code = 82
char = R;code = 82
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
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
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = b;code = 98
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 = 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 = r;code = 114
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char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = b;code = 98
char = -;code = 45
char = m;code = 109
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char = e;code = 101
char = d;code = 100
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char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
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char = s;code = 115
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char = s;code = 115
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char = t;code = 116
char = i;code = 105
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
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char = c;code = 99
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = w;code = 119
char = T;code = 84
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char = 2;code = 50
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char = 7;code = 55
char = ,;code = 44
char = ;code = 32
char = 2;code = 50
char = F;code = 70
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char = R;code = 82
char = R;code = 82
char = 1;code = 49
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char = d;code = 100
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char = s;code = 115
char = ;code = 32
char = C;code = 67
char = D;code = 68
char = 2;code = 50
char = 0;code = 48
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char = c;code = 99
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char = l;code = 108
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char = c;code = 99
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char = u;code = 117
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char = d;code = 100
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char = C;code = 67
char = D;code = 68
char = C;code = 67
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char = l;code = 108
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char = g;code = 103
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char = k;code = 107
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char = n;code = 110
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char = .;code = 46
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char = I;code = 73
char = n;code = 110
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char = a;code = 97
char = d;code = 100
char = d;code = 100
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char = ,;code = 44
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char = p;code = 112
char = 3;code = 51
char = 8;code = 56
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char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = /;code = 47
char = N;code = 78
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char = a;code = 97
char = B;code = 66
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char = o;code = 111
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char = ;code = 32
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char = a;code = 97
char = p;code = 112
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char = i;code = 105
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char = r;code = 114
char = u;code = 117
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char = e;code = 101
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char = i;code = 105
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char = e;code = 101
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char = x;code = 120
char = i;code = 105
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char = b;code = 98
char = ;code = 32
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char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = y;code = 121
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char = u;code = 117
char = r;code = 114
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char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = o;code = 111
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char = o;code = 111
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char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = R;code = 82
char = R;code = 82
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
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char = a;code = 97
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char = ;code = 32
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char = t;code = 116
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = ;code = 32
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char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = o;code = 111
char = ;code = 32
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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 = b;code = 98
char = y;code = 121
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
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char = p;code = 112
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char = c;code = 99
char = ;code = 32
char = d;code = 100
char = r;code = 114
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char = e;code = 101
char = ;code = 32
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = l;code = 108
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 = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = 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 = p;code = 112
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = i;code = 105
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 = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = b;code = 98
char = /;code = 47
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
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 = t;code = 116
char = ;code = 32
char = A;code = 65
char = I;code = 73
char = D;code = 68
char = S;code = 83
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = B;code = 66
char = -;code = 45
char = N;code = 78
char = H;code = 72
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char = .;code = 46
char = <;code = 60
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result sql = Rituximab in combination with chemotherapy is considered for the treatment of patients with AIDS-associated B-cell non-Hodgkin lymphoma (NHL); however, a subgroup of patients does not respond or develops resistance following initial treatments. To address the mechanism of rituximab-resistance, we have generated rituximab-resistant (RR) clones from wild-type (wT) 2F7. A representative 2F7-RR1 clone was examined for its response to rituximab treatment as well as rituximab-mediated chemosensitisation. In comparison with wT-2F7, 2F7-RR1 had less CD20 cell surface expression and failed to respond to rituximab-induced complement-dependent cytotoxicity (CDC) and apoptosis following cross-linking. In addition, rituximab failed to inhibit the constitutively activated p38 MAPK/NF-kappaB pathways and failed to sensitise 2F7-RR1 to various chemotherapeutic drugs (examples: taxol, vincristine, VP16, CDDP). In contrast to rituximab, treatment of 2F7-RR1 with the proteasome inhibitor, bortezomib, and the NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), resulted in inhibition of Bcl-2 expression and sensitisation of 2F7-RR1 to apoptosis by chemotherapeutic drugs. These findings demonstrate that rituximab resistance may be due to failure of rituximab to modify survival pathways. However, pharmacologic inhibitors that inhibit survival pathways can reverse RR tumor cells and sensitise the cells to apoptosis by various chemotherapeutic drugs. These findings offer novel potential therapeutic applications in the reversal of rituximab/drug resistant AIDS-derived B-NHL.
Publication: Leuk. Lymphoma 2008 Oct ;49(10)::1982-94. :doi: 10.1080/10428190802357071.
Publication Date: 2008 Oct
Study Author(s): Vega, Mario I;Martinez-Paniagua, Melissa;Jazirehi, Ali R;Huerta-Yepez, Sara;Umezawa, Kazuo;Martinez-Maza, Otoniel;Bonavida, Benjamin;
Institution: Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095-1747, USA.
Shortcut link to this study:
Publication Date: 2008 Oct
Study Author(s): Vega, Mario I;Martinez-Paniagua, Melissa;Jazirehi, Ali R;Huerta-Yepez, Sara;Umezawa, Kazuo;Martinez-Maza, Otoniel;Bonavida, Benjamin;
Institution: Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095-1747, USA.
Shortcut link to this study:
Rituximab in combination with chemotherapy is considered for the treatment of patients with AIDS-associated B-cell non-Hodgkin lymphoma (NHL); however, a subgroup of patients does not respond or develops resistance following initial treatments. To address the mechanism of rituximab-resistance, we have generated rituximab-resistant (RR) clones from wild-type (wT) 2F7. A representative 2F7-RR1 clone was examined for its response to rituximab treatment as well as rituximab-mediated chemosensitisation. In comparison with wT-2F7, 2F7-RR1 had less CD20 cell surface expression and failed to respond to rituximab-induced complement-dependent cytotoxicity (CDC) and apoptosis following cross-linking. In addition, rituximab failed to inhibit the constitutively activated p38 MAPK/NF-kappaB pathways and failed to sensitise 2F7-RR1 to various chemotherapeutic drugs (examples: taxol, vincristine, VP16, CDDP). In contrast to rituximab, treatment of 2F7-RR1 with the proteasome inhibitor, bortezomib, and the NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), resulted in inhibition of Bcl-2 expression and sensitisation of 2F7-RR1 to apoptosis by chemotherapeutic drugs. These findings demonstrate that rituximab resistance may be due to failure of rituximab to modify survival pathways. However, pharmacologic inhibitors that inhibit survival pathways can reverse RR tumor cells and sensitise the cells to apoptosis by various chemotherapeutic drugs. These findings offer novel potential therapeutic applications in the reversal of rituximab/drug resistant AIDS-derived B-NHL.
PMID: 18949621
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