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result sql = CPT-11 (SN-38) chemotherapy may be selectively applicable to biliary tract cancer with low hMLH1 expression.
CPT-11 (SN-38) chemotherapy may be selectively applicable to biliary tract cancer with low hMLH1 expression.
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char = N;code = 78
char = -;code = 45
char = 3;code = 51
char = 8;code = 56
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
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
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = (;code = 40
char = S;code = 83
char = i;code = 105
char = );code = 41
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = q;code = 113
char = u;code = 117
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = T;code = 84
char = -;code = 45
char = P;code = 80
char = C;code = 67
char = R;code = 82
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = M;code = 77
char = L;code = 76
char = H;code = 72
char = 1;code = 49
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 = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
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 = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
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 = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = 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 = t;code = 116
char = h;code = 104
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 = 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
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = C;code = 67
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = S;code = 83
char = N;code = 78
char = -;code = 45
char = 3;code = 51
char = 8;code = 56
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = M;code = 77
char = L;code = 76
char = H;code = 72
char = 1;code = 49
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 = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = I;code = 73
char = C;code = 67
char = 5;code = 53
char = 0;code = 48
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = S;code = 83
char = N;code = 78
char = -;code = 45
char = 3;code = 51
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
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 = o;code = 111
char = n;code = 110
char = s;code = 115
char = h;code = 104
char = i;code = 105
char = p;code = 112
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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 = ;code = 32
char = (;code = 40
char = R;code = 82
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 7;code = 55
char = 1;code = 49
char = 7;code = 55
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 7;code = 55
char = 1;code = 49
char = 5;code = 53
char = );code = 41
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = i;code = 105
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
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 = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = (;code = 40
char = d;code = 100
char = s;code = 115
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = K;code = 75
char = M;code = 77
char = G;code = 71
char = -;code = 45
char = C;code = 67
char = ;code = 32
char = (;code = 40
char = g;code = 103
char = a;code = 97
char = l;code = 108
char = l;code = 108
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 = 41
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 = h;code = 104
char = M;code = 77
char = L;code = 76
char = H;code = 72
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
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 = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = 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 = h;code = 104
char = M;code = 77
char = L;code = 76
char = H;code = 72
char = 1;code = 49
char = ;code = 32
char = d;code = 100
char = s;code = 115
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = -;code = 45
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 = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = ;code = 32
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 = a;code = 97
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = n;code = 110
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 = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = s;code = 115
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = M;code = 77
char = L;code = 76
char = H;code = 72
char = 1;code = 49
char = ;code = 32
char = d;code = 100
char = s;code = 115
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
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 = a;code = 97
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = S;code = 83
char = N;code = 78
char = -;code = 45
char = 3;code = 51
char = 8;code = 56
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = o;code = 111
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 = e;code = 101
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 = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = N;code = 78
char = -;code = 45
char = 3;code = 51
char = 8;code = 56
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 = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = h;code = 104
char = M;code = 77
char = L;code = 76
char = H;code = 72
char = 1;code = 49
char = ;code = 32
char = d;code = 100
char = s;code = 115
char = R;code = 82
char = N;code = 78
char = A;code = 65
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 = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = G;code = 71
char = 1;code = 49
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = c;code = 99
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 = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = n;code = 110
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char = ;code = 32
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char = r;code = 114
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char = t;code = 116
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char = c;code = 99
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char = ;code = 32
char = m;code = 109
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char = d;code = 100
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char = ;code = 32
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char = d;code = 100
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char = c;code = 99
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result sql = Biliary tract cancer is of highly malignancy with a poor 5-year survival. However, established chemotherapeutic regimens have not yet been established. Previously, we have reported that hMLH1, a mismatch repair (MMR) gene was frequently (57%) found to be lacking in surgically resected biliary tract carcinomas and the patients lacking the expression of hMLH1 revealed a poorer prognosis than those patients who possessed it. The MMR gene has been considered to be associated with sensitivity to various chemotherapeutic agents that act on DNA. A loss of MMR expression has been reported to increase sensitivity to topoisomerase inhibitors such as etoposide (ETP) or camptothecins (CPT). In the present study, whether or not hMLH1 deficiency resulted in a higher sensitivity to irinotecan (CPT-11) active form (SN-38) was investigated using a short interfering (Si)RNA system. A quantitative reverse transcription-polymerase chain reaction (RT-PCR) was conducted to measure the levels of hMLH1 expression in seven cancer cell lines, and this was compared with the drug sensitivity (IC50) to SN-38. The hMLH1 expression was correlated with the IC50 for SN-38, although the relationship was not statistically significant (R = 0.717, p = 0.0715). SiRNA double strand RNA (dsRNA) was transiently transfected into KMG-C (gallbladder cancer) cells. hMLH1 mRNA expression was repressed by hMLH1 dsRNA in a dose-dependent manner in comparison to the control dsRNA. The cell growth of the hMLH1 dsRNA transfected group was decreased by approximately 50% by SN-38 exposure. Flow cytometry was also carried out to examine the effect of the SN-38 treatment on the cell cycle. Following hMLH1 dsRNA transfection, the subG1 fraction was increased in comparison with the control in a dose-dependent manner. In conclusion, a low expression of hMLH1 in biliary tract cancer may aid in predicting its responsiveness to CPT-11 (SN38).

Publication: Anticancer Res. 2007 Mar-Apr ;27(2)::865-72.
Publication Date: 2007 Mar-Apr
Study Author(s): Sato, Ken;Kitajima, Yoshihiko;Kohya, Naohiko;Koga, Yasuo;Ohtaka, Kazuma;Miyazaki, Kohji;
Institution: Department of Surgery, Saga University Faculty of Medicine, Nabeshima 5-1-1, Saga 849-8501, Japan.
Shortcut link to this study:
Biliary tract cancer is of highly malignancy with a poor 5-year survival. However, established chemotherapeutic regimens have not yet been established. Previously, we have reported that hMLH1, a mismatch repair (MMR) gene was frequently (57%) found to be lacking in surgically resected biliary tract carcinomas and the patients lacking the expression of hMLH1 revealed a poorer prognosis than those patients who possessed it. The MMR gene has been considered to be associated with sensitivity to various chemotherapeutic agents that act on DNA. A loss of MMR expression has been reported to increase sensitivity to topoisomerase inhibitors such as etoposide (ETP) or camptothecins (CPT). In the present study, whether or not hMLH1 deficiency resulted in a higher sensitivity to irinotecan (CPT-11) active form (SN-38) was investigated using a short interfering (Si)RNA system. A quantitative reverse transcription-polymerase chain reaction (RT-PCR) was conducted to measure the levels of hMLH1 expression in seven cancer cell lines, and this was compared with the drug sensitivity (IC50) to SN-38. The hMLH1 expression was correlated with the IC50 for SN-38, although the relationship was not statistically significant (R = 0.717, p = 0.0715). SiRNA double strand RNA (dsRNA) was transiently transfected into KMG-C (gallbladder cancer) cells. hMLH1 mRNA expression was repressed by hMLH1 dsRNA in a dose-dependent manner in comparison to the control dsRNA. The cell growth of the hMLH1 dsRNA transfected group was decreased by approximately 50% by SN-38 exposure. Flow cytometry was also carried out to examine the effect of the SN-38 treatment on the cell cycle. Following hMLH1 dsRNA transfection, the subG1 fraction was increased in comparison with the control in a dose-dependent manner. In conclusion, a low expression of hMLH1 in biliary tract cancer may aid in predicting its responsiveness to CPT-11 (SN38).
PMID: 17465213

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