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char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
result sql = The vitamin D analogue BXL-628 inhibits growth factor-stimulated proliferation and invasion of DU145 prostate cancer cells.

The vitamin D analogue BXL-628 inhibits growth factor-stimulated proliferation and invasion of DU145 prostate cancer cells.

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char = ;code = 32
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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 = n;code = 110
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char = r;code = 114
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char = g;code = 103
char = h;code = 104
char = ;code = 32
char = M;code = 77
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char = t;code = 116
char = r;code = 114
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char = g;code = 103
char = e;code = 101
char = l;code = 108
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = e;code = 101
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char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = s;code = 115
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = B;code = 66
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char = y;code = 121
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char = e;code = 101
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char = c;code = 99
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char = a;code = 97
char = m;code = 109
char = b;code = 98
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
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char = i;code = 105
char = t;code = 116
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = m;code = 109
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char = a;code = 97
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char = u;code = 117
char = r;code = 114
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char = d;code = 100
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char = i;code = 105
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char = m;code = 109
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char = o;code = 111
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char = n;code = 110
char = a;code = 97
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char = e;code = 101
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char = a;code = 97
char = s;code = 115
char = s;code = 115
char = a;code = 97
char = y;code = 121
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char = a;code = 97
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char = d;code = 100
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char = A;code = 65
char = K;code = 75
char = T;code = 84
char = ;code = 32
char = p;code = 112
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char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
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 = w;code = 119
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char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
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char = b;code = 98
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char = o;code = 111
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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 = K;code = 75
char = e;code = 101
char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = n;code = 110
char = o;code = 111
char = c;code = 99
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char = t;code = 116
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
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char = h;code = 104
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
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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
char = ;code = 32
char = (;code = 40
char = K;code = 75
char = G;code = 71
char = F;code = 70
char = R;code = 82
char = );code = 41
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
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 = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
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 = ;code = 32
char = w;code = 119
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = b;code = 98
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char = o;code = 111
char = t;code = 116
char = ;code = 32
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 = i;code = 105
char = m;code = 109
char = m;code = 109
char = u;code = 117
char = n;code = 110
char = o;code = 111
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = c;code = 99
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char = i;code = 105
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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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 = r;code = 114
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char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = .;code = 46
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char = b;code = 98
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char = >;code = 62
char = <;code = 60
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char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = B;code = 66
char = X;code = 88
char = L;code = 76
char = -;code = 45
char = 6;code = 54
char = 2;code = 50
char = 8;code = 56
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char = i;code = 105
char = s;code = 115
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char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = b;code = 98
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char = h;code = 104
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char = p;code = 112
char = r;code = 114
char = o;code = 111
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char = i;code = 105
char = f;code = 102
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = d;code = 100
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char = ;code = 32
char = D;code = 68
char = U;code = 85
char = 1;code = 49
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char = 5;code = 53
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char = c;code = 99
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char = b;code = 98
char = a;code = 97
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char = a;code = 97
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char = K;code = 75
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char = .;code = 46
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char = l;code = 108
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char = m;code = 109
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char = a;code = 97
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char = w;code = 119
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char = F;code = 70
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char = p;code = 112
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char = s;code = 115
char = s;code = 115
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char = o;code = 111
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char = o;code = 111
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char = ;code = 32
char = K;code = 75
char = G;code = 71
char = F;code = 70
char = R;code = 82
char = ;code = 32
char = a;code = 97
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char = t;code = 116
char = o;code = 111
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char = r;code = 114
char = a;code = 97
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char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = p;code = 112
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char = y;code = 121
char = l;code = 108
char = a;code = 97
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char = a;code = 97
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char = d;code = 100
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char = d;code = 100
char = o;code = 111
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char = n;code = 110
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = m;code = 109
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char = P;code = 80
char = I;code = 73
char = 3;code = 51
char = K;code = 75
char = /;code = 47
char = A;code = 65
char = K;code = 75
char = T;code = 84
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
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char = v;code = 118
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char = i;code = 105
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char = b;code = 98
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char = l;code = 108
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char = b;code = 98
char = r;code = 114
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char = e;code = 101
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char = f;code = 102
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char = F;code = 70
char = R;code = 82
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char = a;code = 97
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char = o;code = 111
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char = o;code = 111
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char = ;code = 32
char = R;code = 82
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char = A;code = 65
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char = t;code = 116
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char = a;code = 97
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char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = .;code = 46
char = <;code = 60
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char = >;code = 62
char = <;code = 60
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char = <;code = 60
char = b;code = 98
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char = C;code = 67
char = O;code = 79
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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
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char = <;code = 60
char = /;code = 47
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char = >;code = 62
char = O;code = 79
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char = r;code = 114
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char = e;code = 101
char = m;code = 109
char = o;code = 111
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result sql = PURPOSE : Suppression of the invasive phenotype is essential in developing new therapeutic tools to treat advanced prostate cancer (PC) indicating that androgen-independent prostate cancer (AI-PC) is characterized by increased metastatic potential. In the present study, we have investigated the effect of the nonhypercalcemic vitamin D analogue BXL-628 on proliferation and invasive properties of the human PC cell line DU145. In particular, the effect of the analogue was tested following stimulation with a potent growth factor, keratinocyte growth factor (KGF), which stimulates both proliferation and invasion of these cells. We have also evaluated the effect of the analogue on KGF stimulation of PI3K/AKT signaling pathway.

METHODS : Cell proliferation was determined by cell counting. Invasion through Matrigel was evaluated using Boyden chambers. PI3K activity was measured by immunokinase assay and AKT phosphorylation was evaluated by western blot analysis. Keratinocyte growth factor receptor (KGFR) autotransphosphorylation was evaluated by western blot after immunoprecipitation of the receptor.

RESULTS : BXL-628 is able to inhibit both proliferation and invasion of DU145 cells in basal conditions and in response to KGF. Following stimulation with KGF, the inhibition is due to suppression of KGFR autotransphosphorylation and downstream PI3K/AKT activation, both achieved following a brief (5 min) incubation with the analogue. This effect on KGFR autophosphorylation was still present when cells were treated with the alpha-amanitin, an inhibitor of RNA transcription, indicating a rapid, nongenomic effect.

CONCLUSIONS : Our results demonstrate that the vitamin D analogue BXL-628 is able to suppress KGF-induced proliferation and invasion of AI-PC cells in vitro, prospecting a possible use of the drug, which is currently in phase II clinical studies for benign prostatic hyperplasia, in the treatment of advanced prostate cancer.

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