;PMID: 11571630 ;source_file_2858.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..37] = [t:0..37] ;1)sentence:[e:43..151] = [t:43..151] ;2)section:[e:155..258] = [t:155..258] ;3)section:[e:262..335] = [t:262..335] ;4)sentence:[e:339..412] = [t:339..412] ;5)sentence:[e:413..600] = [t:413..600] ;6)sentence:[e:601..745] = [t:601..745] ;7)sentence:[e:746..865] = [t:746..865] ;8)sentence:[e:866..971] = [t:866..971] ;9)sentence:[e:973..1092] = [t:973..1092] ;10)sentence:[e:1093..1179] = [t:1093..1179] ;11)sentence:[e:1180..1316] = [t:1180..1316] ;12)section:[e:1320..1365] = [t:1320..1365] ;section 0 Span:0..37 ;Neoplasia. 2001 Jul-Aug;3(4):304-13. (SEC (FRAG (NNP:[0..9] Neoplasia) (.:[9..10] .) (CD:[12..16] 2001) (CC:[17..21] Jul-) (IN:[21..25] Aug;) (CC:[25..27] 3-LRB-) (CD:[27..28] 4) (-RRB-:[28..29] -RRB-) (::[29..30] :) (CD:[30..36] 304-13) (.:[36..37] .))) ;sentence 1 Span:43..151 ;Bcl-2 and M-Myc coexpression increases IGF-IR and features of malignant ;growth in neuroblastoma cell lines. ;[43..48]:gene-generic:"Bcl-2" ;[53..58]:gene-generic:"M-Myc" ;[82..88]:gene-protein:"IGF-IR" ;[105..114]:malignancy-clinical-stage:"malignant" ;[126..139]:malignancy-type:"neuroblastoma" (SENT (S-HLN (NP-SBJ (NML (NN:[43..48] Bcl-2) (CC:[49..52] and) (NN:[53..58] M-Myc)) (NN:[59..71] coexpression)) (VP (VBZ:[72..81] increases) (NP (NP (NN:[82..88] IGF-IR)) (CC:[89..92] and) (NP (NP (NNS:[93..101] features)) (PP (IN:[102..104] of) (NP (JJ:[105..114] malignant) (NN:[115..121] growth))))) (PP-LOC (IN:[123..125] in) (NP (NN:[126..139] neuroblastoma) (NN:[140..144] cell) (NNS:[145..150] lines)))) (.:[150..151] .))) ;section 2 Span:155..258 ;Jasty R, van Golen C, Lin HJ, Solomon G, Heidelberger K, Polverini P, Opipari ;A, Feldman E, Castle VP. (SEC (FRAG (NNP:[155..160] Jasty) (NNP:[161..162] R) (,:[162..163] ,) (NNP:[164..167] van) (NNP:[168..173] Golen) (NNP:[174..175] C) (,:[175..176] ,) (NNP:[177..180] Lin) (NNP:[181..183] HJ) (,:[183..184] ,) (NNP:[185..192] Solomon) (NNP:[193..194] G) (,:[194..195] ,) (NNP:[196..208] Heidelberger) (NNP:[209..211] K,) (NNP:[212..221] Polverini) (NNP:[222..224] P,) (NNP:[225..232] Opipari) (NNP:[233..234] A) (,:[234..235] ,) (NNP:[237..244] Feldman) (NNP:[245..246] E) (,:[246..247] ,) (NNP:[248..254] Castle) (NN:[255..257] VP) (.:[257..258] .))) ;section 3 Span:262..335 ;Department of Pediatrics, Medical College of Ohio, Toledo, OH 43614, USA. (SEC (FRAG (NNP:[262..272] Department) (IN:[273..275] of) (NNP:[276..286] Pediatrics) (,:[286..287] ,) (NNP:[288..295] Medical) (NNP:[296..303] College) (IN:[304..306] of) (NNP:[307..311] Ohio) (,:[311..312] ,) (NNP:[313..319] Toledo) (,:[319..320] ,) (NNP:[321..323] OH) (CD:[324..329] 43614) (,:[329..330] ,) (NNP:[331..334] USA) (.:[334..335] .))) ;sentence 4 Span:339..412 ;The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. ;[343..348]:gene-rna:"bcl-2" ;[353..358]:gene-rna:"c-myc" (SENT (S (NP-SBJ-2 (DT:[339..342] The) (NML (NML (NN:[343..348] bcl-2) (NML-1 (-NONE-:[348..348] *P*))) (CC:[349..352] and) (NML (NN:[353..358] c-myc) (NML-1 (NNS:[359..368] oncogenes))))) (VP (VBP:[369..378] cooperate) (S-PRP (NP-SBJ-2 (-NONE-:[378..378] *)) (VP (TO:[379..381] to) (VP (VB:[382..391] transform) (NP (JJ:[392..400] multiple) (NN:[401..405] cell) (NNS:[406..411] types)))))) (.:[411..412] .))) ;sentence 5 Span:413..600 ;In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with ;a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as ;a result of gene amplification. ;[421..430]:malignancy-developmental-state:"pediatric" ;[442..447]:malignancy-type:"NB(2)" ;[449..454]:gene-protein:"Bcl-2" ;[510..515]:gene-protein:"N-Myc" ;[541..546]:gene-protein:"c-Myc" ;[586..599]:variation-type:"amplification" (SENT (S (PP (IN:[413..415] In) (NP (NP (DT:[416..419] the) (JJ:[421..430] pediatric) (NN:[431..441] malignancy)) (NP (NN:[442..447] NB-LRB-2-RRB-)))) (,:[447..448] ,) (NP-SBJ-1 (NN:[449..454] Bcl-2)) (VP (VBZ:[455..457] is) (ADVP (RB:[458..464] highly)) (VP (VBN:[465..474] expressed) (NP-1 (-NONE-:[474..474] *)))) (.:[474..475] .)) (S (PP-LOC (IN:[476..478] In) (NP (NP (NNS:[479..485] tumors)) (PP (IN:[486..490] with) (NP (DT:[491..492] a) (JJ:[493..497] poor) (NN:[499..508] prognosis))))) (,:[508..509] ,) (NP-SBJ-2 (NP (NN:[510..515] N-Myc)) (,:[515..516] ,) (NP (NP (DT:[517..518] a) (NN:[519..526] protein)) (ADJP (JJ:[527..537] homologous) (PP (TO:[538..540] to) (NP (NN:[541..546] c-Myc)))))) (,:[546..547] ,) (VP (VBZ:[548..550] is) (VP (VBN:[551..564] overexpressed) (NP-2 (-NONE-:[564..564] *)) (PP (IN:[565..567] as) (NP (NP (DT:[568..569] a) (NN:[570..576] result)) (PP (IN:[577..579] of) (NP (NN:[581..585] gene) (NN:[586..599] amplification))))))) (.:[599..600] .))) ;ERROR_Sentence has multiple Children (Sentence Error)[413..600]::S:S: ;sentence 6 Span:601..745 ;The present study was designed to determine whether Bcl-2 cooperates with ;N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB) cells. ;[653..658]:gene-protein:"Bcl-2" ;[676..681]:gene-protein:"N-Myc" ;[719..732]:malignancy-type:"neuroblastoma" ;[734..736]:malignancy-type:"NB" (SENT (S (NP-SBJ-1 (DT:[601..604] The) (JJ:[605..612] present) (NN:[613..618] study)) (VP (VBD:[619..622] was) (VP (VBN:[623..631] designed) (NP-1 (-NONE-:[631..631] *)) (S-PRP (NP-SBJ (-NONE-:[631..631] *)) (VP (TO:[632..634] to) (VP (VB:[635..644] determine) (SBAR (IN:[645..652] whether) (S (NP-SBJ (NN:[653..658] Bcl-2)) (VP (VBZ:[660..670] cooperates) (PP-CLR (IN:[671..675] with) (NP (NN:[676..681] N-Myc))) (S-PRP (NP-SBJ (-NONE-:[681..681] *)) (VP (TO:[682..684] to) (VP (VB:[685..691] bestow) (NP (DT:[692..693] a) (JJ:[694..705] tumorigenic) (NN:[706..715] phenotype)) (PP-CLR (TO:[716..718] to) (NP (NML (NML (NN:[719..732] neuroblastoma)) (NML (-LRB-:[733..734] -LRB-) (NN:[734..736] NB) (-RRB-:[736..737] -RRB-))) (NNS:[739..744] cells)))))))))))))) (.:[744..745] .))) ;sentence 7 Span:746..865 ;NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably ;transfected to express these gene products. ;[746..748]:malignancy-type:"NB" ;[793..798]:gene-protein:"Bcl-2" ;[803..808]:gene-protein:"N-Myc" (SENT (S (NP-SBJ-2 (NP (NN:[746..748] NB) (NN:[749..753] cell) (NNS:[754..759] lines)) (SBAR (WHNP-1 (WDT:[760..764] that)) (S (NP-SBJ-1 (-NONE-:[764..764] *T*)) (PP (IN:[765..767] at) (NP (NN:[768..776] baseline))) (VP (VBP:[777..784] express) (NP (CC:[785..792] neither) (NN:[793..798] Bcl-2) (CC:[799..802] nor) (NN:[803..808] N-Myc)))))) (VP (VBD:[809..813] were) (ADVP (RB:[815..821] stably)) (VP (VBN:[822..833] transfected) (NP-2 (-NONE-:[833..833] *)) (S-PRP (NP-SBJ-2 (-NONE-:[833..833] *)) (VP (TO:[834..836] to) (VP (VB:[837..844] express) (NP (DT:[845..850] these) (NN:[851..855] gene) (NNS:[856..864] products))))))) (.:[864..865] .))) ;sentence 8 Span:866..971 ;In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis ;induced by serum withdrawal. ;[890..895]:gene-protein:"Bcl-2" ;[905..910]:gene-protein:"N-Myc" (SENT (S (PP (IN:[866..868] In) (NP (DT:[869..873] this) (NN:[874..879] model))) (,:[879..880] ,) (NP-SBJ (PRP:[881..883] we)) (VP (VBD:[884..889] found) (SBAR (-NONE-:[889..889] 0) (S (NP-SBJ (NN:[890..895] Bcl-2)) (VP (VBZ:[897..904] rescues) (NP (ADJP (NN:[905..910] N-Myc) (HYPH:[910..911] -) (VBG:[911..921] expressing)) (NNS:[922..927] cells)) (PP (IN:[928..932] from) (NP (NP (NN:[933..942] apoptosis)) (VP (VBN:[943..950] induced) (NP (-NONE-:[950..950] *)) (PP (IN:[951..953] by) (NP-LGS (NN:[954..959] serum) (NN:[960..970] withdrawal)))))))))) (.:[970..971] .))) ;sentence 9 Span:973..1092 ;Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and ;anchorage-independent growth in soft agar. ;[989..994]:gene-protein:"Bcl-2" ;[999..1004]:gene-protein:"N-Myc" (SENT (S (NP-SBJ (NP (NN:[973..985] Coexpression)) (PP (IN:[986..988] of) (NP (NN:[989..994] Bcl-2) (CC:[995..998] and) (NN:[999..1004] N-Myc)))) (VP (VBZ:[1005..1013] supports) (NP (NP (NN:[1014..1020] growth)) (PP (IN:[1021..1023] in) (NP (JJ:[1024..1027] low) (NN:[1028..1033] serum) (NNS:[1034..1044] conditions)))) (CC:[1045..1048] and) (NP (NP (ADJP (NN:[1050..1059] anchorage) (HYPH:[1059..1060] -) (JJ:[1060..1071] independent)) (NN:[1072..1078] growth)) (PP (IN:[1079..1081] in) (NP (JJ:[1082..1086] soft) (NN:[1087..1091] agar))))) (.:[1091..1092] .))) ;sentence 10 Span:1093..1179 ;Similarly, in vivo tumorigenic and angiogenic activity was dependent on ;coexpression. (SENT (S (ADVP (RB:[1093..1102] Similarly)) (,:[1102..1103] ,) (NP-SBJ (ADJP (FW:[1104..1106] in) (FW:[1107..1111] vivo)) (ADJP (JJ:[1112..1123] tumorigenic) (CC:[1124..1127] and) (JJ:[1129..1139] angiogenic)) (NN:[1140..1148] activity)) (VP (VBD:[1149..1152] was) (ADJP-PRD (JJ:[1153..1162] dependent) (PP (IN:[1163..1165] on) (NP (NN:[1166..1178] coexpression))))) (.:[1178..1179] .))) ;sentence 11 Span:1180..1316 ;Our data further suggests that the mechanism underlying these changes ;involves the receptor for insulin growth factor type I (IGF-IR). ;[1264..1306]:gene-protein:"receptor for insulin growth factor type I" ;[1308..1314]:gene-protein:"IGF-IR" (SENT (S (NP-SBJ (PRP$:[1180..1183] Our) (NNS:[1184..1188] data)) (ADVP (RBR:[1189..1196] further)) (VP (VBZ:[1197..1205] suggests) (SBAR (IN:[1207..1211] that) (S (NP-SBJ (NP (DT:[1212..1215] the) (NN:[1216..1225] mechanism)) (VP (VBG:[1226..1236] underlying) (NP (DT:[1237..1242] these) (NNS:[1243..1250] changes)))) (VP (VBZ:[1251..1259] involves) (NP (DT:[1260..1263] the) (NML (NML (NML (NN:[1264..1272] receptor)) (PP (IN:[1273..1276] for) (NP (NML (NN:[1277..1284] insulin) (NN:[1286..1292] growth) (NN:[1293..1299] factor)) (NN:[1300..1304] type) (CD:[1305..1306] I)))) (NML (-LRB-:[1307..1308] -LRB-) (NN:[1308..1314] IGF-IR) (-RRB-:[1314..1315] -RRB-)))))))) (.:[1315..1316] .))) ;section 12 Span:1320..1365 ;PMID: 11571630 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1320..1324] PMID) (::[1324..1325] :) (CD:[1326..1334] 11571630) (NN:[1335..1336] -LSB-) (NNP:[1336..1342] PubMed) (::[1343..1344] -) (NN:[1345..1352] indexed) (IN:[1353..1356] for) (NNP:[1357..1365] MEDLINE-RSB-)))