0 10 Cortivazol Cortivazol NNP 11 19 mediated mediate VBD 20 29 induction induction NN 30 32 of of IN 33 47 glucocorticoid glucocorticoid NN 48 56 receptor receptor NN 57 66 messenger messenger NN 67 78 ribonucleic ribonucleic JJ 79 83 acid acid NN 84 86 in in IN 87 96 wild-type wild-type JJ 97 100 and and CC 101 124 dexamethasone-resistant dexamethasone-resistant JJ 125 130 human human JJ 131 139 leukemic leukemic JJ 140 141 ( ( ( 141 144 CEM CEM NNP 144 145 ) ) ) 146 151 cells cell NNS 151 152 . . . 154 164 Cortivazol Cortivazol NNP 165 167 is be VBZ 168 169 a a DT 170 184 phenylpyrazolo phenylpyrazolo JJ 185 199 glucocorticoid glucocorticoid NN 200 202 of of IN 203 207 high high JJ 208 215 potency potency NN 216 219 and and CC 220 227 unusual unusual JJ 228 237 structure structure NN 237 238 . . . 239 241 In in IN 242 246 both both CC 247 256 wild-type wild-type JJ 257 260 and and CC 261 267 highly highly RB 268 296 dexamethasone(dex)-resistant dexamethasone(dex)-resistant JJ 297 303 clones clone NNS 304 306 of of IN 307 310 the the DT 311 316 human human JJ 317 325 leukemic leukemic JJ 326 330 cell cell NN 331 335 line line NN 336 339 CEM CEM NNP 339 340 , , , 341 349 exposure exposure NN 350 352 to to TO 353 363 cortivazol cortivazol NN 364 369 leads lead VBZ 370 372 to to TO 373 377 cell cell NN 378 383 death death NN 383 384 . . . 385 387 It it PRP 388 391 has have VBZ 392 396 been be VBN 397 402 shown show VBN 403 411 recently recently RB 412 416 that that IN 417 419 in in IN 420 429 wild-type wild-type JJ 430 433 CEM CEM NNP 434 439 cells cell NNS 440 443 but but CC 444 447 not not RB 448 450 in in IN 451 452 a a DT 453 466 dex-resistant dex-resistant JJ 466 467 , , , 468 482 glucocorticoid glucocorticoid NN 483 505 receptor(GR)-defective receptor(gr)-defective JJ 506 511 clone clone NN 512 518 ICR-27 icr-27 NN 519 523 TK-3 tk-3 NN 523 524 , , , 525 528 dex dex NN 529 536 induces induce VBZ 537 539 GR GR NNP 540 544 mRNA mRNA NNP 544 545 . . . 546 548 To to TO 549 553 test test VB 554 557 the the DT 558 568 hypothesis hypothesis NN 569 573 that that IN 574 584 cortivazol cortivazol NN 585 589 acts act VBZ 590 592 in in IN 593 606 dex-resistant dex-resistant JJ 607 612 cells cell NNS 613 615 by by IN 616 622 making make VBG 623 626 use use NN 627 629 of of IN 630 633 the the DT 634 642 residual residual JJ 643 645 GR gr NN 646 651 found find VBN 652 657 there there RB 657 658 , , , 659 668 wild-type wild-type JJ 669 672 and and CC 673 686 dex-resistant dex-resistant JJ 687 693 clones clone NNS 694 698 were be VBD 699 706 treated treat VBN 707 711 with with IN 712 719 various various JJ 720 734 concentrations concentration NNS 735 737 of of IN 738 748 cortivazol cortivazol NN 749 752 and and CC 753 762 induction induction NN 763 765 of of IN 766 768 GR GR NNP 769 773 mRNA mRNA NNP 774 777 was be VBD 778 785 studied study VBN 785 786 . . . 787 797 Cortivazol Cortivazol NNP 798 811 significantly significantly RB 812 819 induced induce VBD 820 822 GR GR NNP 823 827 mRNA mRNA NNP 828 830 in in IN 831 834 the the DT 835 841 normal normal JJ 842 848 CEM-C7 cem-c7 NN 849 851 as as RB 852 856 well well RB 857 859 as as IN 860 862 in in IN 863 866 two two CD 867 874 classes class NNS 875 877 of of IN 878 891 dex-resistant dex-resistant JJ 892 898 clones clone NNS 898 899 , , , 900 908 although although IN 909 912 the the DT 913 926 dex-resistant dex-resistant JJ 927 933 clones clone NNS 934 940 needed need VBN 941 943 at at IN 944 949 least least JJS 950 952 10 10 CD 953 958 times time NNS 959 963 more more JJR 964 974 cortivazol cortivazol NN 975 979 than than IN 980 983 the the DT 984 990 normal normal JJ 991 996 cells cell NNS 997 1000 for for IN 1001 1012 significant significant JJ 1013 1015 GR GR NNP 1016 1020 mRNA mrna NN 1021 1030 induction induction NN 1030 1031 . . . 1032 1041 Increased increase VBN 1042 1048 levels level NNS 1049 1051 of of IN 1052 1054 GR GR NNP 1055 1059 mRNA mRNA NNP 1060 1064 were be VBD 1065 1072 noticed notice VBN 1073 1075 as as RB 1076 1081 early early RB 1082 1084 as as IN 1085 1086 3 3 CD 1087 1088 h h NN 1089 1094 after after IN 1095 1104 treatment treatment NN 1104 1105 . . . 1106 1107 A a DT 1108 1115 general general JJ 1116 1127 correlation correlation NN 1128 1135 between between IN 1136 1145 induction induction NN 1146 1148 of of IN 1149 1151 GR GR NNP 1152 1156 mRNA mRNA NNP 1157 1160 and and CC 1161 1166 lysis lysis NN 1167 1169 of of IN 1170 1173 the the DT 1174 1180 normal normal JJ 1181 1184 and and CC 1185 1198 dex-resistant dex-resistant JJ 1199 1204 cells cell NNS 1205 1208 was be VBD 1209 1214 found find VBN 1214 1215 . . . 1216 1224 Positive positive JJ 1225 1234 induction induction NN 1235 1237 of of IN 1238 1240 GR GR NNP 1241 1245 mRNA mRNA NNP 1246 1251 might might MD 1252 1254 be be VB 1255 1258 one one CD 1259 1261 of of IN 1262 1265 the the DT 1266 1274 earliest early JJS 1275 1282 crucial crucial JJ 1283 1288 steps step NNS 1289 1291 in in IN 1292 1295 the the DT 1296 1301 lysis lysis NN 1302 1304 of of IN 1305 1311 normal normal JJ 1312 1315 and and CC 1316 1329 dex-resistant dex-resistant JJ 1330 1333 CEM CEM NNP 1334 1339 cells cell NNS 1339 1340 , , , 1341 1343 or or CC 1344 1349 might might MD 1350 1355 serve serve VB 1356 1358 as as IN 1359 1360 a a DT 1361 1367 marker marker NN 1368 1371 for for IN 1372 1375 the the DT 1376 1383 process process NN 1383 1384 . . . 1385 1392 However however RB 1392 1393 , , , 1394 1397 the the DT 1398 1403 lysis lysis NN 1404 1411 pathway pathway NN 1412 1414 in in IN 1415 1418 the the DT 1419 1432 dex-resistant dex-resistant JJ 1433 1438 cells cell NNS 1439 1441 is be VBZ 1442 1451 defective defective JJ 1452 1454 in in IN 1455 1459 that that DT 1460 1473 dex-resistant dex-resistant JJ 1474 1480 clones clone NNS 1481 1487 needed need VBD 1488 1501 significantly significantly RB 1502 1506 more more JJR 1507 1517 cortivazol cortivazol NN 1518 1522 than than IN 1523 1526 the the DT 1527 1533 normal normal JJ 1534 1539 cells cell NNS 1540 1543 for for IN 1544 1549 lysis lysis NN 1550 1552 of of IN 1553 1556 the the DT 1557 1562 cells cell NNS 1562 1563 . . .