|
|
char = R;code = 82
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char = c;code = 99
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char = .;code = 46
result sql = Receptor-mediated DNA-targeted photoimmunotherapy.
Receptor-mediated DNA-targeted photoimmunotherapy.char = W;code = 87
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char = A;code = 65
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result sql = We show the efficacy of a therapeutic strategy that combines the potency of a DNA-binding photosensitizer, UV(A)Sens, with the tumor-targeting potential of receptor-mediated endocytosis. The photosensitizer is an iodinated bibenzimidazole, which, when bound in the minor groove of DNA and excited by UV(A) irradiation, induces cytotoxic lesions attributed to a radical species resulting from photodehalogenation. Although reminiscent of photochemotherapy using psoralens and UV(A) irradiation, an established treatment modality in dermatology particularly for the treatment of psoriasis and cutaneous T-cell lymphoma, a critical difference is the extreme photopotency of the iodinated bibenzimidazole, approximately 1,000-fold that of psoralens. This feature prompted consideration of combination with the specificity of receptor-mediated targeting. Using two in vitro model systems, we show the UV(A) cytotoxicity of iodo ligand/protein conjugates, implying binding of the conjugate to cell receptors, internalization, and degradation of the conjugate-receptor complex, with release and translocation of the ligand to nuclear DNA. For ligand-transferrin conjugates, phototoxicity was inhibited by coincubation with excess native transferrin. Receptor-mediated UV(A)-induced cytotoxicity was also shown with the iodo ligand conjugate of an anti-human epidermal growth factor receptor monoclonal antibody, exemplifying the potential application of the strategy to other cancer-specific targets to thus improve the specificity of phototherapy of superficial lesions and for extracorporeal treatments.
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result sql = Receptor-mediated DNA-targeted photoimmunotherapy.
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char = i;code = 105
char = z;code = 122
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = U;code = 85
char = V;code = 86
char = (;code = 40
char = A;code = 65
char = );code = 41
char = S;code = 83
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = 45
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = t;code = 116
char = o;code = 111
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 = r;code = 114
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = i;code = 105
char = o;code = 111
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char = i;code = 105
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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 = 98
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char = b;code = 98
char = e;code = 101
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char = i;code = 105
char = m;code = 109
char = i;code = 105
char = d;code = 100
char = a;code = 97
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char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
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 = m;code = 109
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = U;code = 85
char = V;code = 86
char = (;code = 40
char = A;code = 65
char = );code = 41
char = ;code = 32
char = i;code = 105
char = r;code = 114
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = e;code = 101
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 = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = t;code = 116
char = o;code = 111
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 = y;code = 121
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char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = U;code = 85
char = V;code = 86
char = (;code = 40
char = A;code = 65
char = );code = 41
char = ;code = 32
char = i;code = 105
char = r;code = 114
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
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char = e;code = 101
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
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char = i;code = 105
char = s;code = 115
char = h;code = 104
char = e;code = 101
char = d;code = 100
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char = e;code = 101
char = a;code = 97
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char = o;code = 111
char = d;code = 100
char = a;code = 97
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char = t;code = 116
char = y;code = 121
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char = i;code = 105
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char = m;code = 109
char = a;code = 97
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char = l;code = 108
char = o;code = 111
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char = y;code = 121
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char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = a;code = 97
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char = l;code = 108
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char = f;code = 102
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char = r;code = 114
char = ;code = 32
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char = e;code = 101
char = a;code = 97
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char = ;code = 32
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char = a;code = 97
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char = i;code = 105
char = s;code = 115
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char = t;code = 116
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char = n;code = 110
char = e;code = 101
char = o;code = 111
char = u;code = 117
char = s;code = 115
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 = ;code = 32
char = l;code = 108
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = c;code = 99
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char = i;code = 105
char = c;code = 99
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char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = c;code = 99
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char = i;code = 105
char = s;code = 115
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = e;code = 101
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char = m;code = 109
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char = o;code = 111
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char = o;code = 111
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char = c;code = 99
char = y;code = 121
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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
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char = i;code = 105
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char = i;code = 105
char = n;code = 110
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = b;code = 98
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char = b;code = 98
char = e;code = 101
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char = z;code = 122
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = d;code = 100
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char = o;code = 111
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char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = r;code = 114
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char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
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char = e;code = 101
char = l;code = 108
char = y;code = 121
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char = 1;code = 49
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char = 0;code = 48
char = 0;code = 48
char = -;code = 45
char = f;code = 102
char = o;code = 111
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char = d;code = 100
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char = h;code = 104
char = a;code = 97
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char = f;code = 102
char = ;code = 32
char = p;code = 112
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char = r;code = 114
char = a;code = 97
char = l;code = 108
char = e;code = 101
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
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char = f;code = 102
char = e;code = 101
char = a;code = 97
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char = o;code = 111
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char = i;code = 105
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char = .;code = 46
char = ;code = 32
char = U;code = 85
char = s;code = 115
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = w;code = 119
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char = v;code = 118
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char = m;code = 109
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char = e;code = 101
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char = s;code = 115
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char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = s;code = 115
char = ,;code = 44
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char = w;code = 119
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char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = U;code = 85
char = V;code = 86
char = (;code = 40
char = A;code = 65
char = );code = 41
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
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char = o;code = 111
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char = i;code = 105
char = c;code = 99
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char = f;code = 102
char = ;code = 32
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char = d;code = 100
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char = a;code = 97
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = c;code = 99
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char = j;code = 106
char = u;code = 117
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = y;code = 121
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char = b;code = 98
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char = t;code = 116
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char = c;code = 99
char = o;code = 111
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char = j;code = 106
char = u;code = 117
char = g;code = 103
char = a;code = 97
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char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = c;code = 99
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char = l;code = 108
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char = r;code = 114
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char = c;code = 99
char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
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char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = a;code = 97
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char = z;code = 122
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char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
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result sql = We show the efficacy of a therapeutic strategy that combines the potency of a DNA-binding photosensitizer, UV(A)Sens, with the tumor-targeting potential of receptor-mediated endocytosis. The photosensitizer is an iodinated bibenzimidazole, which, when bound in the minor groove of DNA and excited by UV(A) irradiation, induces cytotoxic lesions attributed to a radical species resulting from photodehalogenation. Although reminiscent of photochemotherapy using psoralens and UV(A) irradiation, an established treatment modality in dermatology particularly for the treatment of psoriasis and cutaneous T-cell lymphoma, a critical difference is the extreme photopotency of the iodinated bibenzimidazole, approximately 1,000-fold that of psoralens. This feature prompted consideration of combination with the specificity of receptor-mediated targeting. Using two in vitro model systems, we show the UV(A) cytotoxicity of iodo ligand/protein conjugates, implying binding of the conjugate to cell receptors, internalization, and degradation of the conjugate-receptor complex, with release and translocation of the ligand to nuclear DNA. For ligand-transferrin conjugates, phototoxicity was inhibited by coincubation with excess native transferrin. Receptor-mediated UV(A)-induced cytotoxicity was also shown with the iodo ligand conjugate of an anti-human epidermal growth factor receptor monoclonal antibody, exemplifying the potential application of the strategy to other cancer-specific targets to thus improve the specificity of phototherapy of superficial lesions and for extracorporeal treatments.
Publication: Cancer Res. 2006 Nov 1 ;66(21)::10548-52.
Publication Date: 2006 Nov 1
Study Author(s): Karagiannis, Tom C;Lobachevsky, Pavel N;Leung, Brenda K Y;White, Jonathan M;Martin, Roger F;
Institution: Molecular Radiation Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Shortcut link to this study:
Publication Date: 2006 Nov 1
Study Author(s): Karagiannis, Tom C;Lobachevsky, Pavel N;Leung, Brenda K Y;White, Jonathan M;Martin, Roger F;
Institution: Molecular Radiation Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Shortcut link to this study:
We show the efficacy of a therapeutic strategy that combines the potency of a DNA-binding photosensitizer, UV(A)Sens, with the tumor-targeting potential of receptor-mediated endocytosis. The photosensitizer is an iodinated bibenzimidazole, which, when bound in the minor groove of DNA and excited by UV(A) irradiation, induces cytotoxic lesions attributed to a radical species resulting from photodehalogenation. Although reminiscent of photochemotherapy using psoralens and UV(A) irradiation, an established treatment modality in dermatology particularly for the treatment of psoriasis and cutaneous T-cell lymphoma, a critical difference is the extreme photopotency of the iodinated bibenzimidazole, approximately 1,000-fold that of psoralens. This feature prompted consideration of combination with the specificity of receptor-mediated targeting. Using two in vitro model systems, we show the UV(A) cytotoxicity of iodo ligand/protein conjugates, implying binding of the conjugate to cell receptors, internalization, and degradation of the conjugate-receptor complex, with release and translocation of the ligand to nuclear DNA. For ligand-transferrin conjugates, phototoxicity was inhibited by coincubation with excess native transferrin. Receptor-mediated UV(A)-induced cytotoxicity was also shown with the iodo ligand conjugate of an anti-human epidermal growth factor receptor monoclonal antibody, exemplifying the potential application of the strategy to other cancer-specific targets to thus improve the specificity of phototherapy of superficial lesions and for extracorporeal treatments.
PMID: 17079478
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