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result sql = Akt up-regulation increases resistance to microtubule-directed chemotherapeutic agents through mammalian target of rapamycin.
Akt up-regulation increases resistance to microtubule-directed chemotherapeutic agents through mammalian target of rapamycin.
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char = i;code = 105
char = n;code = 110
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char = t;code = 116
char = u;code = 117
char = t;code = 116
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char = v;code = 118
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char = a;code = 97
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char = v;code = 118
char = e;code = 101
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char = i;code = 105
char = s;code = 115
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char = k;code = 107
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char = a;code = 97
char = n;code = 110
char = t;code = 116
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
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char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
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char = e;code = 101
char = a;code = 97
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char = A;code = 65
char = k;code = 107
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
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char = ;code = 32
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char = m;code = 109
char = p;code = 112
char = t;code = 116
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char = v;code = 118
char = e;code = 101
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char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = l;code = 108
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char = w;code = 119
char = e;code = 101
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char = s;code = 115
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char = ;code = 32
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
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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 = A;code = 65
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char = t;code = 116
char = ;code = 32
char = a;code = 97
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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 = o;code = 111
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char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = l;code = 108
char = y;code = 121
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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 = s;code = 115
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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
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
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char = t;code = 116
char = u;code = 117
char = b;code = 98
char = u;code = 117
char = l;code = 108
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char = d;code = 100
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = d;code = 100
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 = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = c;code = 99
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char = i;code = 105
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = p;code = 112
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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 = 46
char = ;code = 32
char = A;code = 65
char = k;code = 107
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
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char = n;code = 110
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
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
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char = l;code = 108
char = y;code = 121
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char = i;code = 105
char = c;code = 99
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = i;code = 105
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char = r;code = 114
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char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
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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 = m;code = 109
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char = o;code = 111
char = t;code = 116
char = u;code = 117
char = b;code = 98
char = u;code = 117
char = l;code = 108
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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
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char = .;code = 46
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = p;code = 112
char = a;code = 97
char = m;code = 109
char = y;code = 121
char = c;code = 99
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char = n;code = 110
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char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
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char = t;code = 116
char = s;code = 115
char = ;code = 32
char = A;code = 65
char = k;code = 107
char = t;code = 116
char = -;code = 45
char = m;code = 109
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char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = d;code = 100
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char = e;code = 101
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char = l;code = 108
char = y;code = 121
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char = s;code = 115
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char = e;code = 101
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char = u;code = 117
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char = i;code = 105
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = t;code = 116
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char = e;code = 101
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char = t;code = 116
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char = a;code = 97
char = m;code = 109
char = m;code = 109
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char = l;code = 108
char = i;code = 105
char = a;code = 97
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char = ;code = 32
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char = a;code = 97
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char = g;code = 103
char = e;code = 101
char = t;code = 116
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char = f;code = 102
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = a;code = 97
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char = y;code = 121
char = c;code = 99
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char = n;code = 110
char = ;code = 32
char = (;code = 40
char = m;code = 109
char = T;code = 84
char = O;code = 79
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char = );code = 41
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = o;code = 111
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char = e;code = 101
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char = ;code = 32
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = T;code = 84
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
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char = t;code = 116
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char = f;code = 102
char = e;code = 101
char = r;code = 114
char = s;code = 115
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char = r;code = 114
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char = c;code = 99
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char = i;code = 105
char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = t;code = 116
char = u;code = 117
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char = l;code = 108
char = e;code = 101
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char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = n;code = 110
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char = o;code = 111
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char = e;code = 101
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char = h;code = 104
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char = e;code = 101
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char = e;code = 101
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = s;code = 115
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char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = o;code = 111
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char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = A;code = 65
char = k;code = 107
char = t;code = 116
char = -;code = 45
char = m;code = 109
char = T;code = 84
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = s;code = 115
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char = g;code = 103
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char = a;code = 97
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char = u;code = 117
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char = s;code = 115
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char = e;code = 101
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char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = g;code = 103
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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 = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = d;code = 100
char = a;code = 97
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char = a;code = 97
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char = p;code = 112
char = r;code = 114
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char = v;code = 118
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char = t;code = 116
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char = a;code = 97
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char = b;code = 98
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char = a;code = 97
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char = o;code = 111
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char = f;code = 102
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char = r;code = 114
char = a;code = 97
char = p;code = 112
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char = e;code = 101
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result sql = Chemotherapeutic agents induce apoptosis in cancer cells through effects on multiple intracellular targets. Recent observations suggest that a consistent cellular response to chemotherapeutic agents of disparate classes is down-regulation of glycolytic metabolism. Inhibition of glycolytic activity has been linked to apoptotic induction in several models. The serine/threonine kinase Akt (protein kinase B) promotes both glycolytic metabolism and survival, and these functions have been shown to be linked. Because of its key role in both glycolysis and survival, we examined the function of Akt in the cellular response to cytotoxic agents. Following exposure to any of several chemotherapeutic agents, an initial up-regulation in endogenous Akt activity is rapidly suppressed. Using cells containing constitutively active myristoylated Akt, dominant-negative kinase-dead Akt, or an empty vector control, we show here that Akt activation markedly increases resistance to microtubule-directed agents, including vincristine, colchicine, and paclitaxel. Akt also maintains increased glycolytic rate in response to antimicrotubule treatment. Rapamycin inhibits Akt-mediated maintenance of glycolysis and therapeutic resistance, indicating that these effects are dependent on mammalian target of rapamycin (mTOR). Furthermore, an activated mTOR mutant confers resistance to antimicrotubule agents. Taken together, these observations suggest that activation of the Akt-mTOR signaling pathway can augment glucose utilization and promote resistance to chemotherapeutic agents that do not directly target metabolic regulation. These data provide insight into potentially synergistic combinations of anticancer therapies.

Publication: Mol. Cancer Ther. 2004 Dec ;3(12)::1605-13.
Publication Date: 2004 Dec
Study Author(s): VanderWeele, David J;Zhou, Rixin;Rudin, Charles M;
Institution: Committee on Cancer Biology, University of Chicago, Illinois, USA.
Shortcut link to this study:
Chemotherapeutic agents induce apoptosis in cancer cells through effects on multiple intracellular targets. Recent observations suggest that a consistent cellular response to chemotherapeutic agents of disparate classes is down-regulation of glycolytic metabolism. Inhibition of glycolytic activity has been linked to apoptotic induction in several models. The serine/threonine kinase Akt (protein kinase B) promotes both glycolytic metabolism and survival, and these functions have been shown to be linked. Because of its key role in both glycolysis and survival, we examined the function of Akt in the cellular response to cytotoxic agents. Following exposure to any of several chemotherapeutic agents, an initial up-regulation in endogenous Akt activity is rapidly suppressed. Using cells containing constitutively active myristoylated Akt, dominant-negative kinase-dead Akt, or an empty vector control, we show here that Akt activation markedly increases resistance to microtubule-directed agents, including vincristine, colchicine, and paclitaxel. Akt also maintains increased glycolytic rate in response to antimicrotubule treatment. Rapamycin inhibits Akt-mediated maintenance of glycolysis and therapeutic resistance, indicating that these effects are dependent on mammalian target of rapamycin (mTOR). Furthermore, an activated mTOR mutant confers resistance to antimicrotubule agents. Taken together, these observations suggest that activation of the Akt-mTOR signaling pathway can augment glucose utilization and promote resistance to chemotherapeutic agents that do not directly target metabolic regulation. These data provide insight into potentially synergistic combinations of anticancer therapies.
PMID: 15634654

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