|
|
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result sql = Analogs of vitamin E epitomized by alpha-tocopheryl succinate for pancreatic cancer treatment: in vitro results induce caution for in vivo applications.
Analogs of vitamin E epitomized by alpha-tocopheryl succinate for pancreatic cancer treatment: in vitro results induce caution for in vivo applications.char = <;code = 60
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char = u;code = 117
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char = t;code = 116
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char = 1;code = 49
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char = D;code = 68
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char = P;code = 80
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char = y;code = 121
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char = ;code = 32
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char = o;code = 111
char = n;code = 110
char = t;code = 116
char = o;code = 111
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char = p;code = 112
char = h;code = 104
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char = o;code = 111
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = o;code = 111
char = m;code = 109
char = o;code = 111
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char = L;code = 76
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = %;code = 37
char = ;code = 32
char = F;code = 70
char = C;code = 67
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = /;code = 47
char = L;code = 76
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = F;code = 70
char = C;code = 67
char = S;code = 83
char = );code = 41
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = -;code = 45
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = /;code = 47
char = L;code = 76
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = T;code = 84
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = E;code = 69
char = F;code = 70
char = -;code = 45
char = W;code = 87
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = M;code = 77
char = E;code = 69
char = F;code = 70
char = -;code = 45
char = d;code = 100
char = o;code = 111
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = N;code = 78
char = 1;code = 49
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 = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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 = n;code = 110
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = 5;code = 53
char = -;code = 45
char = F;code = 70
char = U;code = 85
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = T;code = 84
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = M;code = 77
char = A;code = 65
char = D;code = 68
char = 4;code = 52
char = /;code = 47
char = D;code = 68
char = P;code = 80
char = C;code = 67
char = 4;code = 52
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = N;code = 78
char = 1;code = 49
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 = c;code = 99
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 = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
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 = 5;code = 53
char = -;code = 45
char = F;code = 70
char = U;code = 85
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = T;code = 84
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
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 = O;code = 79
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = C;code = 67
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 = a;code = 97
char = r;code = 114
char = e;code = 101
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = T;code = 84
char = O;code = 79
char = S;code = 83
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = y;code = 121
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 = i;code = 105
char = t;code = 116
char = y;code = 121
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char = a;code = 97
char = p;code = 112
char = p;code = 112
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 = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
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 = S;code = 83
char = M;code = 77
char = A;code = 65
char = D;code = 68
char = 4;code = 52
char = /;code = 47
char = D;code = 68
char = P;code = 80
char = C;code = 67
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = z;code = 122
char = y;code = 121
char = g;code = 103
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = e;code = 101
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 = B;code = 66
char = a;code = 97
char = x;code = 120
char = /;code = 47
char = B;code = 66
char = a;code = 97
char = k;code = 107
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
result sql = OBJECTIVES : alpha-Tocopheryl succinate (alpha-TOS) is thought to be toxic only for cancer cells. We ascertained in vitro alpha-TOS effects on pancreatic cancer (PC) and normal cell growth and verified whether the combination of nontoxic alpha-TOS and 5-fluorouracil (5-FU) doses causes cancer cell death and whether alpha-TOS effects are mediated by the proapoptotic proteins Bax/Bak and/or SMAD4/DPC4 status.
METHODS : Five PC cell lines, myoblasts, normal monocytes, wild-type (WT) and Bax/Bak double knockout mouse embryonic fibroblast (MEF) cells, and permanently SMAD4/DPC4-transfected PSN1 cells were cultured in 1% and 10% fetal calf serums (FCSs), without or with alpha-TOS (5-500 micromol/L). Nontoxic 5-FU (0.0001 mmol/L) and alpha-TOS alone or in combination were also evaluated.
RESULTS : Only PSN1 PC cell line, which had SMAD4/DPC4 homozygous deletion, was sensitive to nontoxic alpha-TOS doses (5 micromol/L in 1% FCS and 50 micromol/L in 10% FCS). A 20-micromol/L alpha-TOS inhibited MEF-WT, not MEF-double knockout growth. Only PSN1 cells were sensitive to nontoxic 5-FU and alpha-TOS combination. SMAD4/DPC4 transfection restored PSN1 resistance to the effects of combined 5-FU and alpha-TOS effects.
CONCLUSIONS : Only a minority of PC cells are sensitive to the antiproliferative effects of alpha-TOS, any sensitivity appearing to be correlated with SMAD4/DPC4 homozygous deletion and Bax/Bak expression.
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = ;code = 32
char = e;code = 101
char = p;code = 112
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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 = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = :;code = 58
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 = 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 = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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 = a;code = 97
char = p;code = 112
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = .;code = 46
result sql = Analogs of vitamin E epitomized by alpha-tocopheryl succinate for pancreatic cancer treatment: in vitro results induce caution for in vivo applications.
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char = >;code = 62
char = O;code = 79
char = B;code = 66
char = J;code = 74
char = E;code = 69
char = C;code = 67
char = T;code = 84
char = I;code = 73
char = V;code = 86
char = E;code = 69
char = S;code = 83
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char = a;code = 97
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char = f;code = 102
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char = a;code = 97
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char = l;code = 108
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char = W;code = 87
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char = a;code = 97
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char = t;code = 116
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char = d;code = 100
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char = r;code = 114
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char = p;code = 112
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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 = i;code = 105
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char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
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char = (;code = 40
char = P;code = 80
char = C;code = 67
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char = ;code = 32
char = a;code = 97
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char = a;code = 97
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = g;code = 103
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char = o;code = 111
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char = a;code = 97
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char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
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char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = c;code = 99
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char = b;code = 98
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char = n;code = 110
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
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = t;code = 116
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = l;code = 108
char = p;code = 112
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char = a;code = 97
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char = T;code = 84
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
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char = f;code = 102
char = l;code = 108
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char = o;code = 111
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char = o;code = 111
char = u;code = 117
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char = a;code = 97
char = c;code = 99
char = i;code = 105
char = l;code = 108
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char = F;code = 70
char = U;code = 85
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char = d;code = 100
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char = s;code = 115
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char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
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char = p;code = 112
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char = a;code = 97
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char = T;code = 84
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char = f;code = 102
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 = a;code = 97
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char = o;code = 111
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char = t;code = 116
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char = c;code = 99
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char = B;code = 66
char = a;code = 97
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char = a;code = 97
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char = P;code = 80
char = C;code = 67
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char = a;code = 97
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char = u;code = 117
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char = <;code = 60
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char = H;code = 72
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char = w;code = 119
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char = );code = 41
char = ;code = 32
char = a;code = 97
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char = B;code = 66
char = a;code = 97
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char = /;code = 47
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char = a;code = 97
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char = e;code = 101
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char = r;code = 114
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char = i;code = 105
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char = f;code = 102
char = i;code = 105
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char = b;code = 98
char = l;code = 108
char = a;code = 97
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char = M;code = 77
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char = F;code = 70
char = );code = 41
char = ;code = 32
char = c;code = 99
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char = l;code = 108
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char = y;code = 121
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char = S;code = 83
char = M;code = 77
char = A;code = 65
char = D;code = 68
char = 4;code = 52
char = /;code = 47
char = D;code = 68
char = P;code = 80
char = C;code = 67
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char = e;code = 101
char = d;code = 100
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char = P;code = 80
char = S;code = 83
char = N;code = 78
char = 1;code = 49
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char = c;code = 99
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char = l;code = 108
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char = e;code = 101
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char = m;code = 109
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char = C;code = 67
char = S;code = 83
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char = ,;code = 44
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char = .;code = 46
char = ;code = 32
char = N;code = 78
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char = t;code = 116
char = o;code = 111
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char = F;code = 70
char = U;code = 85
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char = 0;code = 48
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char = R;code = 82
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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
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char = <;code = 60
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char = O;code = 79
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char = l;code = 108
char = y;code = 121
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char = P;code = 80
char = S;code = 83
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char = 1;code = 49
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char = P;code = 80
char = C;code = 67
char = ;code = 32
char = c;code = 99
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char = h;code = 104
char = a;code = 97
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char = S;code = 83
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char = A;code = 65
char = D;code = 68
char = 4;code = 52
char = /;code = 47
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char = P;code = 80
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char = t;code = 116
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char = v;code = 118
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char = o;code = 111
char = ;code = 32
char = n;code = 110
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result sql = OBJECTIVES : alpha-Tocopheryl succinate (alpha-TOS) is thought to be toxic only for cancer cells. We ascertained in vitro alpha-TOS effects on pancreatic cancer (PC) and normal cell growth and verified whether the combination of nontoxic alpha-TOS and 5-fluorouracil (5-FU) doses causes cancer cell death and whether alpha-TOS effects are mediated by the proapoptotic proteins Bax/Bak and/or SMAD4/DPC4 status.
METHODS : Five PC cell lines, myoblasts, normal monocytes, wild-type (WT) and Bax/Bak double knockout mouse embryonic fibroblast (MEF) cells, and permanently SMAD4/DPC4-transfected PSN1 cells were cultured in 1% and 10% fetal calf serums (FCSs), without or with alpha-TOS (5-500 micromol/L). Nontoxic 5-FU (0.0001 mmol/L) and alpha-TOS alone or in combination were also evaluated.
RESULTS : Only PSN1 PC cell line, which had SMAD4/DPC4 homozygous deletion, was sensitive to nontoxic alpha-TOS doses (5 micromol/L in 1% FCS and 50 micromol/L in 10% FCS). A 20-micromol/L alpha-TOS inhibited MEF-WT, not MEF-double knockout growth. Only PSN1 cells were sensitive to nontoxic 5-FU and alpha-TOS combination. SMAD4/DPC4 transfection restored PSN1 resistance to the effects of combined 5-FU and alpha-TOS effects.
CONCLUSIONS : Only a minority of PC cells are sensitive to the antiproliferative effects of alpha-TOS, any sensitivity appearing to be correlated with SMAD4/DPC4 homozygous deletion and Bax/Bak expression.
Publication: Pancreas 2010 Jul ;39(5)::662-8. :doi: 10.1097/MPA.0b013e3181c8b48c.
Publication Date: 2010 Jul
Study Author(s): Greco, Eliana;Basso, Daniela;Fadi, Elisa;Padoan, Andrea;Fogar, Paola;Zambon, Carlo-Federico;Navaglia, Filippo;Bozzato, Dania;Moz, Stefania;Pedrazzoli, Sergio;Plebani, Mario;
Institution: Department of Laboratory Medicine, University of Padova, Padova, Italy.
Shortcut link to this study:
Publication Date: 2010 Jul
Study Author(s): Greco, Eliana;Basso, Daniela;Fadi, Elisa;Padoan, Andrea;Fogar, Paola;Zambon, Carlo-Federico;Navaglia, Filippo;Bozzato, Dania;Moz, Stefania;Pedrazzoli, Sergio;Plebani, Mario;
Institution: Department of Laboratory Medicine, University of Padova, Padova, Italy.
Shortcut link to this study:
OBJECTIVES : alpha-Tocopheryl succinate (alpha-TOS) is thought to be toxic only for cancer cells. We ascertained in vitro alpha-TOS effects on pancreatic cancer (PC) and normal cell growth and verified whether the combination of nontoxic alpha-TOS and 5-fluorouracil (5-FU) doses causes cancer cell death and whether alpha-TOS effects are mediated by the proapoptotic proteins Bax/Bak and/or SMAD4/DPC4 status.
METHODS : Five PC cell lines, myoblasts, normal monocytes, wild-type (WT) and Bax/Bak double knockout mouse embryonic fibroblast (MEF) cells, and permanently SMAD4/DPC4-transfected PSN1 cells were cultured in 1% and 10% fetal calf serums (FCSs), without or with alpha-TOS (5-500 micromol/L). Nontoxic 5-FU (0.0001 mmol/L) and alpha-TOS alone or in combination were also evaluated.
RESULTS : Only PSN1 PC cell line, which had SMAD4/DPC4 homozygous deletion, was sensitive to nontoxic alpha-TOS doses (5 micromol/L in 1% FCS and 50 micromol/L in 10% FCS). A 20-micromol/L alpha-TOS inhibited MEF-WT, not MEF-double knockout growth. Only PSN1 cells were sensitive to nontoxic 5-FU and alpha-TOS combination. SMAD4/DPC4 transfection restored PSN1 resistance to the effects of combined 5-FU and alpha-TOS effects.
CONCLUSIONS : Only a minority of PC cells are sensitive to the antiproliferative effects of alpha-TOS, any sensitivity appearing to be correlated with SMAD4/DPC4 homozygous deletion and Bax/Bak expression.
METHODS : Five PC cell lines, myoblasts, normal monocytes, wild-type (WT) and Bax/Bak double knockout mouse embryonic fibroblast (MEF) cells, and permanently SMAD4/DPC4-transfected PSN1 cells were cultured in 1% and 10% fetal calf serums (FCSs), without or with alpha-TOS (5-500 micromol/L). Nontoxic 5-FU (0.0001 mmol/L) and alpha-TOS alone or in combination were also evaluated.
RESULTS : Only PSN1 PC cell line, which had SMAD4/DPC4 homozygous deletion, was sensitive to nontoxic alpha-TOS doses (5 micromol/L in 1% FCS and 50 micromol/L in 10% FCS). A 20-micromol/L alpha-TOS inhibited MEF-WT, not MEF-double knockout growth. Only PSN1 cells were sensitive to nontoxic 5-FU and alpha-TOS combination. SMAD4/DPC4 transfection restored PSN1 resistance to the effects of combined 5-FU and alpha-TOS effects.
CONCLUSIONS : Only a minority of PC cells are sensitive to the antiproliferative effects of alpha-TOS, any sensitivity appearing to be correlated with SMAD4/DPC4 homozygous deletion and Bax/Bak expression.
PMID: 20562578
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