|
|
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result sql = HYTAD1-p20: a new paclitaxel-hyaluronic acid hydrosoluble bioconjugate for treatment of superficial bladder cancer.
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char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
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
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = t;code = 116
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 = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
char = -;code = 45
char = p;code = 112
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = k;code = 107
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = g;code = 103
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 2;code = 50
char = -;code = 45
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = i;code = 105
char = s;code = 115
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
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 = a;code = 97
char = t;code = 116
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 = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
char = -;code = 45
char = p;code = 112
char = 2;code = 50
char = 0;code = 48
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 = t;code = 116
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = l;code = 108
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 = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = x;code = 120
char = e;code = 101
char = l;code = 108
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 = p;code = 112
char = r;code = 114
char = o;code = 111
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 = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = r;code = 114
char = u;code = 117
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = m;code = 109
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = i;code = 105
char = l;code = 108
char = t;code = 116
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
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 = 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
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 = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = m;code = 109
char = u;code = 117
char = n;code = 110
char = o;code = 111
char = d;code = 100
char = e;code = 101
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 = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = c;code = 99
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = R;code = 82
char = T;code = 84
char = -;code = 45
char = 1;code = 49
char = 1;code = 49
char = 2;code = 50
char = /;code = 47
char = 8;code = 56
char = 4;code = 52
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
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 = m;code = 109
char = a;code = 97
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = l;code = 108
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 = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = c;code = 99
char = o;code = 111
char = n;code = 110
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 = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = x;code = 120
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
char = -;code = 45
char = p;code = 112
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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 = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
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 = f;code = 102
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
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 = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
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 = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
char = -;code = 45
char = p;code = 112
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = d;code = 100
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 = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
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 = c;code = 99
char = o;code = 111
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = x;code = 120
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
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 = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
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 = 44
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 = b;code = 98
char = i;code = 105
char = o;code = 111
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = c;code = 99
char = o;code = 111
char = n;code = 110
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 = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
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 = l;code = 108
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = f;code = 102
char = u;code = 117
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result sql = OBJECTIVE : To report the development of a new water-soluble paclitaxel-hyaluronic acid bioconjugate, HYTAD1-p20, for intravesical treatment of superficial bladder cancer.
MATERIALS AND METHODS : HYTAD1-p20 was synthesized by carboxyl esterification of hyaluronic acid with paclitaxel, and its physicochemical and biologic properties were characterized.
RESULTS : Paclitaxel loading was optimized at 20% w/w; this procedure increased by 500-fold the paclitaxel concentration in the resulting water-soluble biomaterial. In vitro, HYTAD1-p20 exerted a much higher dose-dependent inhibitory effect against RT-4 and RT-112/84 bladder carcinoma cell growth than that of free drug, and directly interacted with CD44 expressed by bladder tumor cells. In vivo, results of pharmacokinetic studies performed in mice after bladder catheterization and intravesical instillation of HYTAD1-p20 disclosed that drug leakage was negligible during a 2-hour analysis. Histologic examination of drug-instilled bladders revealed that HYTAD1-p20 was extremely well tolerated, while paclitaxel alone produced mucosal disruption and submucosal infiltration of inflammatory cells. Treatment of severe combined immunodeficient mice bearing subcutaneous RT-112/84 tumors with maximum tolerated doses of bioconjugate or paclitaxel showed that HYTAD1-p20 exerted a therapeutic activity comparable to that of free drug.
CONCLUSIONS : These data suggest that HYTAD1-p20 significantly improved results obtained with conventional paclitaxel in terms of hydrosolubility, in vitro activity against human bladder cancer cells, and in vivo biocompatibility. This bioconjugate is a potentially useful treatment for superficial urothelial malignancy.
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result sql = HYTAD1-p20: a new paclitaxel-hyaluronic acid hydrosoluble bioconjugate for treatment of superficial bladder cancer.
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char = ;code = 32
char = d;code = 100
char = i;code = 105
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char = c;code = 99
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char = l;code = 108
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char = i;code = 105
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char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
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char = e;code = 101
char = d;code = 100
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = D;code = 68
char = 4;code = 52
char = 4;code = 52
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = e;code = 101
char = r;code = 114
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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 = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
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 = 44
char = ;code = 32
char = r;code = 114
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char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
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char = o;code = 111
char = f;code = 102
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
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
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char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = i;code = 105
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char = m;code = 109
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char = c;code = 99
char = e;code = 101
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char = a;code = 97
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = b;code = 98
char = l;code = 108
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = e;code = 101
char = r;code = 114
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char = c;code = 99
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
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char = i;code = 105
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = t;code = 116
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 = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
char = -;code = 45
char = p;code = 112
char = 2;code = 50
char = 0;code = 48
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = c;code = 99
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
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char = l;code = 108
char = e;code = 101
char = a;code = 97
char = k;code = 107
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = g;code = 103
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 2;code = 50
char = -;code = 45
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = i;code = 105
char = s;code = 115
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 = a;code = 97
char = m;code = 109
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char = n;code = 110
char = a;code = 97
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char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = g;code = 103
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char = s;code = 115
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = d;code = 100
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char = b;code = 98
char = l;code = 108
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = e;code = 101
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char = s;code = 115
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char = r;code = 114
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
char = -;code = 45
char = p;code = 112
char = 2;code = 50
char = 0;code = 48
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = e;code = 101
char = x;code = 120
char = t;code = 116
char = r;code = 114
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char = m;code = 109
char = e;code = 101
char = l;code = 108
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char = w;code = 119
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char = l;code = 108
char = l;code = 108
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char = t;code = 116
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char = a;code = 97
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char = t;code = 116
char = a;code = 97
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char = a;code = 97
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char = p;code = 112
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char = a;code = 97
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char = n;code = 110
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char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = l;code = 108
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char = m;code = 109
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char = y;code = 121
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char = c;code = 99
char = e;code = 101
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char = l;code = 108
char = s;code = 115
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char = ;code = 32
char = T;code = 84
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 = n;code = 110
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char = f;code = 102
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char = v;code = 118
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char = c;code = 99
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char = m;code = 109
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char = n;code = 110
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char = t;code = 116
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char = m;code = 109
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char = e;code = 101
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char = b;code = 98
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char = a;code = 97
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char = n;code = 110
char = g;code = 103
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char = s;code = 115
char = u;code = 117
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char = c;code = 99
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char = e;code = 101
char = o;code = 111
char = u;code = 117
char = s;code = 115
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char = R;code = 82
char = T;code = 84
char = -;code = 45
char = 1;code = 49
char = 1;code = 49
char = 2;code = 50
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char = 8;code = 56
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char = o;code = 111
char = r;code = 114
char = s;code = 115
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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 = 97
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char = i;code = 105
char = m;code = 109
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char = m;code = 109
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char = t;code = 116
char = o;code = 111
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char = e;code = 101
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char = a;code = 97
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char = f;code = 102
char = ;code = 32
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char = g;code = 103
char = a;code = 97
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char = e;code = 101
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char = p;code = 112
char = a;code = 97
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char = a;code = 97
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char = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
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char = p;code = 112
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
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char = :;code = 58
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char = T;code = 84
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char = a;code = 97
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char = H;code = 72
char = Y;code = 89
char = T;code = 84
char = A;code = 65
char = D;code = 68
char = 1;code = 49
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char = u;code = 117
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char = t;code = 116
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char = a;code = 97
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char = i;code = 105
char = v;code = 118
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char = g;code = 103
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char = d;code = 100
char = e;code = 101
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result sql = OBJECTIVE : To report the development of a new water-soluble paclitaxel-hyaluronic acid bioconjugate, HYTAD1-p20, for intravesical treatment of superficial bladder cancer.
MATERIALS AND METHODS : HYTAD1-p20 was synthesized by carboxyl esterification of hyaluronic acid with paclitaxel, and its physicochemical and biologic properties were characterized.
RESULTS : Paclitaxel loading was optimized at 20% w/w; this procedure increased by 500-fold the paclitaxel concentration in the resulting water-soluble biomaterial. In vitro, HYTAD1-p20 exerted a much higher dose-dependent inhibitory effect against RT-4 and RT-112/84 bladder carcinoma cell growth than that of free drug, and directly interacted with CD44 expressed by bladder tumor cells. In vivo, results of pharmacokinetic studies performed in mice after bladder catheterization and intravesical instillation of HYTAD1-p20 disclosed that drug leakage was negligible during a 2-hour analysis. Histologic examination of drug-instilled bladders revealed that HYTAD1-p20 was extremely well tolerated, while paclitaxel alone produced mucosal disruption and submucosal infiltration of inflammatory cells. Treatment of severe combined immunodeficient mice bearing subcutaneous RT-112/84 tumors with maximum tolerated doses of bioconjugate or paclitaxel showed that HYTAD1-p20 exerted a therapeutic activity comparable to that of free drug.
CONCLUSIONS : These data suggest that HYTAD1-p20 significantly improved results obtained with conventional paclitaxel in terms of hydrosolubility, in vitro activity against human bladder cancer cells, and in vivo biocompatibility. This bioconjugate is a potentially useful treatment for superficial urothelial malignancy.
Publication: Urol. Oncol. 2006 May-Jun ;24(3)::207-15.
Publication Date: 2006 May-Jun
Study Author(s): Rosato, Antonio;Banzato, Alessandra;De Luca, Gilda;Renier, Davide;Bettella, Fabio;Pagano, Claudio;Esposito, Giovanni;Zanovello, Paola;Bassi, PierFrancesco;
Institution: Department of Oncology and Surgical Sciences, Oncology Section, University of Padua, Padua, Italy. [email protected]
Shortcut link to this study:
Publication Date: 2006 May-Jun
Study Author(s): Rosato, Antonio;Banzato, Alessandra;De Luca, Gilda;Renier, Davide;Bettella, Fabio;Pagano, Claudio;Esposito, Giovanni;Zanovello, Paola;Bassi, PierFrancesco;
Institution: Department of Oncology and Surgical Sciences, Oncology Section, University of Padua, Padua, Italy. [email protected]
Shortcut link to this study:
OBJECTIVE : To report the development of a new water-soluble paclitaxel-hyaluronic acid bioconjugate, HYTAD1-p20, for intravesical treatment of superficial bladder cancer.
MATERIALS AND METHODS : HYTAD1-p20 was synthesized by carboxyl esterification of hyaluronic acid with paclitaxel, and its physicochemical and biologic properties were characterized.
RESULTS : Paclitaxel loading was optimized at 20% w/w; this procedure increased by 500-fold the paclitaxel concentration in the resulting water-soluble biomaterial. In vitro, HYTAD1-p20 exerted a much higher dose-dependent inhibitory effect against RT-4 and RT-112/84 bladder carcinoma cell growth than that of free drug, and directly interacted with CD44 expressed by bladder tumor cells. In vivo, results of pharmacokinetic studies performed in mice after bladder catheterization and intravesical instillation of HYTAD1-p20 disclosed that drug leakage was negligible during a 2-hour analysis. Histologic examination of drug-instilled bladders revealed that HYTAD1-p20 was extremely well tolerated, while paclitaxel alone produced mucosal disruption and submucosal infiltration of inflammatory cells. Treatment of severe combined immunodeficient mice bearing subcutaneous RT-112/84 tumors with maximum tolerated doses of bioconjugate or paclitaxel showed that HYTAD1-p20 exerted a therapeutic activity comparable to that of free drug.
CONCLUSIONS : These data suggest that HYTAD1-p20 significantly improved results obtained with conventional paclitaxel in terms of hydrosolubility, in vitro activity against human bladder cancer cells, and in vivo biocompatibility. This bioconjugate is a potentially useful treatment for superficial urothelial malignancy.
MATERIALS AND METHODS : HYTAD1-p20 was synthesized by carboxyl esterification of hyaluronic acid with paclitaxel, and its physicochemical and biologic properties were characterized.
RESULTS : Paclitaxel loading was optimized at 20% w/w; this procedure increased by 500-fold the paclitaxel concentration in the resulting water-soluble biomaterial. In vitro, HYTAD1-p20 exerted a much higher dose-dependent inhibitory effect against RT-4 and RT-112/84 bladder carcinoma cell growth than that of free drug, and directly interacted with CD44 expressed by bladder tumor cells. In vivo, results of pharmacokinetic studies performed in mice after bladder catheterization and intravesical instillation of HYTAD1-p20 disclosed that drug leakage was negligible during a 2-hour analysis. Histologic examination of drug-instilled bladders revealed that HYTAD1-p20 was extremely well tolerated, while paclitaxel alone produced mucosal disruption and submucosal infiltration of inflammatory cells. Treatment of severe combined immunodeficient mice bearing subcutaneous RT-112/84 tumors with maximum tolerated doses of bioconjugate or paclitaxel showed that HYTAD1-p20 exerted a therapeutic activity comparable to that of free drug.
CONCLUSIONS : These data suggest that HYTAD1-p20 significantly improved results obtained with conventional paclitaxel in terms of hydrosolubility, in vitro activity against human bladder cancer cells, and in vivo biocompatibility. This bioconjugate is a potentially useful treatment for superficial urothelial malignancy.
PMID: 16678050
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