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result sql = A novel imaging-based high-throughput screening approach to anti-angiogenic drug discovery.

A novel imaging-based high-throughput screening approach to anti-angiogenic drug discovery.

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char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = -;code = 45
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = y;code = 121
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 = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = E;code = 69
char = C;code = 67
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = o;code = 111
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = s;code = 115
char = c;code = 99
char = l;code = 108
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
char = ;code = 32
char = (;code = 40
char = v;code = 118
char = S;code = 83
char = M;code = 77
char = C;code = 67
char = );code = 41
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = b;code = 98
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = o;code = 111
char = p;code = 112
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 = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = u;code = 117
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
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 = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = E;code = 69
char = C;code = 67
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = S;code = 83
char = M;code = 77
char = C;code = 67
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 = V;code = 86
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = i;code = 105
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
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 = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = V;code = 86
char = E;code = 69
char = G;code = 71
char = F;code = 70
char = -;code = 45
char = s;code = 115
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = E;code = 69
char = C;code = 67
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
char = s;code = 115
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 = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = V;code = 86
char = E;code = 69
char = G;code = 71
char = F;code = 70
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 = s;code = 115
char = ,;code = 44
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = C;code = 67
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
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 = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
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 = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = i;code = 105
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = a;code = 97
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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 = i;code = 105
char = r;code = 114
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char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
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char = o;code = 111
char = n;code = 110
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char = i;code = 105
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = z;code = 122
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
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 = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = C;code = 67
char = -;code = 45
char = v;code = 118
char = S;code = 83
char = M;code = 77
char = C;code = 67
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = -;code = 45
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
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 = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = -;code = 45
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = -;code = 45
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = p;code = 112
char = u;code = 117
char = t;code = 116
char = ;code = 32
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result sql = The successful progression to the clinic of angiogenesis inhibitors for cancer treatment has spurred interest in developing new classes of anti-angiogenic compounds. The resulting surge in available candidate therapeutics highlights the need for robust, high-throughput angiogenesis screening systems that adequately capture the complexity of new vessel formation while providing quantitative evaluation of the potency of these agents. Available in vitro angiogenesis assays are either cumbersome, impeding adaptation to high-throughput screening formats, or inadequately model the complex multistep process of new vessel formation. We therefore developed an organotypic endothelial-mural cell co-culture assay system that reflects several facets of angiogenesis while remaining compatible with high-throughput/high-content image screening. Co-culture of primary human endothelial cells (EC) and vascular smooth muscle cells (vSMC) results in assembly of a network of tubular endothelial structures enveloped with vascular basement membrane proteins, thus, comprising the three main components of blood vessels. Initially, EC are dependent on vSMC-derived VEGF and sensitive to clinical anti-angiogenic therapeutics. A subsequent phenotypic VEGF-switch renders EC networks resistant to anti-VEGF therapeutics, demarcating a mature vascular phenotype. Conversely, mature EC networks remain sensitive to vascular disrupting agents. Therefore, candidate anti-angiogenic compounds can be interrogated for their relative potency on immature and mature networks and classified as either vascular normalizing or vascular disrupting agents. Here, we demonstrate that the EC-vSMC co-culture assay represents a robust high-content imaging high-throughput screening system for identification of novel anti-angiogenic agents. A pilot high-throughput screening campaign was used to define informative imaging parameters and develop a follow-up dose-response scheme for hit characterization. High-throughput screening using the EC-vSMC co-culture assay establishes a new platform to screen for novel anti-angiogenic compounds for cancer therapy.

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