0 5 Renal renal JJ 6 10 cell cell NN 11 28 carcinoma-derived carcinoma-derived JJ 29 41 gangliosides ganglioside NNS 42 50 suppress suppress VBP 51 58 nuclear nuclear JJ 59 72 factor-kappaB factor-kappab NN 73 83 activation activation NN 84 86 in in IN 87 88 T t NN 89 94 cells cell NNS 94 95 . . . 97 107 Activation Activation NNP 108 110 of of IN 111 114 the the DT 115 128 transcription transcription NN 129 135 factor factor NN 136 143 nuclear nuclear JJ 144 157 factor-kappaB factor-kappaB NNP 158 159 ( ( ( 159 167 NFkappaB NFkappaB NNP 167 168 ) ) ) 169 171 is be VBZ 172 180 impaired impair VBN 181 183 in in IN 184 185 T t NN 186 191 cells cell NNS 192 196 from from IN 197 205 patients patient NNS 206 210 with with IN 211 216 renal renal JJ 217 221 cell cell NN 222 232 carcinomas carcinoma NNS 233 234 ( ( ( 234 238 RCCs RCC NNP 238 239 ) ) ) 239 240 . . . 241 243 In in IN 244 255 circulating circulate VBG 256 257 T t NN 258 263 cells cell NNS 264 268 from from IN 269 270 a a DT 271 277 subset subset NN 278 280 of of IN 281 289 patients patient NNS 290 294 with with IN 295 299 RCCs RCC NNP 299 300 , , , 301 304 the the DT 305 316 suppression suppression NN 317 319 of of IN 320 328 NFkappaB NFkappaB NNP 329 336 binding binding NN 337 345 activity activity NN 346 348 is be VBZ 349 359 downstream downstream RB 360 364 from from IN 365 368 the the DT 369 385 stimulus-induced stimulus-induced JJ 386 397 degradation degradation NN 398 400 of of IN 401 404 the the DT 405 416 cytoplasmic cytoplasmic JJ 417 423 factor factor NN 424 436 IkappaBalpha IkappaBalpha NNP 436 437 . . . 438 451 Tumor-derived tumor-derived JJ 452 459 soluble soluble JJ 460 468 products product NNS 469 473 from from IN 474 482 cultured culture VBN 483 486 RCC RCC NNP 487 495 explants explant NNS 496 503 inhibit inhibit VBP 504 512 NFkappaB NFkappaB NNP 513 521 activity activity NN 522 524 in in IN 525 526 T t NN 527 532 cells cell NNS 533 537 from from IN 538 545 healthy healthy JJ 546 556 volunteers volunteer NNS 556 557 , , , 558 565 despite despite IN 566 567 a a DT 568 574 normal normal JJ 575 580 level level NN 581 583 of of IN 584 600 stimulus-induced stimulus-induced JJ 601 613 IkappaBalpha IkappaBalpha NNP 614 625 degradation degradation NN 626 628 in in IN 629 634 these these DT 635 640 cells cell NNS 640 641 . . . 642 645 The the DT 646 656 inhibitory inhibitory JJ 657 662 agent agent NN 663 666 has have VBZ 667 674 several several JJ 675 683 features feature NNS 684 698 characteristic characteristic JJ 699 701 of of IN 702 703 a a DT 704 715 ganglioside ganglioside NN 715 716 , , , 717 726 including include VBG 727 738 sensitivity sensitivity NN 739 741 to to TO 742 755 neuraminidase neuraminidase NN 756 759 but but CC 760 763 not not RB 764 772 protease protease NN 773 782 treatment treatment NN 782 783 ; ; : 784 798 hydrophobicity hydrophobicity NN 798 799 ; ; : 800 803 and and CC 804 813 molecular molecular JJ 814 820 weight weight NN 821 825 less less JJR 826 830 than than IN 831 832 3 3 CD 833 836 kDa kda NN 836 837 . . . 838 844 Indeed indeed RB 844 845 , , , 846 848 we we PRP 849 857 detected detect VBD 858 870 gangliosides ganglioside NNS 871 873 in in IN 874 886 supernatants supernatant NNS 887 891 from from IN 892 895 RCC RCC NNP 896 904 explants explant NNS 905 908 and and CC 909 912 not not RB 913 917 from from IN 918 926 adjacent adjacent JJ 927 933 normal normal JJ 934 940 kidney kidney NN 941 947 tissue tissue NN 947 948 . . . 949 961 Gangliosides ganglioside NNS 962 970 prepared prepare VBN 971 975 from from IN 976 979 RCC RCC NNP 980 992 supernatants supernatant NNS 992 993 , , , 994 996 as as RB 997 1001 well well RB 1002 1004 as as IN 1005 1008 the the DT 1009 1017 purified purify VBN 1018 1024 bovine bovine JJ 1025 1037 gangliosides ganglioside NNS 1038 1043 G(m1) G(m1) NNP 1044 1047 and and CC 1048 1054 G(d1a) G(d1a) NNP 1054 1055 , , , 1056 1066 suppressed suppress VBD 1067 1075 NFkappaB NFkappaB NNP 1076 1083 binding binding NN 1084 1092 activity activity NN 1093 1095 in in IN 1096 1097 T t NN 1098 1103 cells cell NNS 1104 1107 and and CC 1108 1115 reduced reduce VBN 1116 1126 expression expression NN 1127 1129 of of IN 1130 1133 the the DT 1134 1143 cytokines cytokine NNS 1144 1148 IL-2 il-2 NN 1149 1152 and and CC 1153 1162 IFN-gamma IFN-gamma NNP 1162 1163 . . . 1164 1169 Taken take VBN 1170 1178 together together RB 1178 1179 , , , 1180 1183 our our PRP$ 1184 1192 findings finding NNS 1193 1200 suggest suggest VBP 1201 1205 that that IN 1206 1219 tumor-derived tumor-derived JJ 1220 1232 gangliosides ganglioside NNS 1233 1236 may may MD 1237 1242 blunt blunt VB 1243 1252 antitumor antitumor JJ 1253 1259 immune immune JJ 1260 1269 responses response NNS 1270 1272 in in IN 1273 1281 patients patient NNS 1282 1286 with with IN 1287 1291 RCCs RCC NNP 1291 1292 . . .