;PMID: 9853427 ;source_file_1381.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..40] = [t:0..40] ;1)sentence:[e:45..171] = [t:45..171] ;2)section:[e:175..299] = [t:175..299] ;3)section:[e:303..374] = [t:303..374] ;4)sentence:[e:378..514] = [t:378..514] ;5)sentence:[e:515..599] = [t:515..599] ;6)sentence:[e:600..704] = [t:600..704] ;7)sentence:[e:705..875] = [t:705..875] ;8)sentence:[e:876..963] = [t:876..963] ;9)sentence:[e:964..1049] = [t:964..1049] ;10)sentence:[e:1050..1126] = [t:1050..1126] ;11)sentence:[e:1127..1387] = [t:1127..1387] ;12)sentence:[e:1388..1549] = [t:1388..1549] ;13)section:[e:1553..1597] = [t:1553..1597] ;section 0 Span:0..40 ;Cell Prolif 1998 Jun-Aug;31(3-4):139-53 (SEC (FRAG (DT:[0..4] Cell) (NNP:[5..11] Prolif) (CD:[13..17] 1998) (NNP:[18..21] Jun) (HYPH:[21..22] -) (JJ:[22..30] Aug;31-LRB-3) (HYPH:[30..31] -) (JJ:[31..33] 4-RRB-) (CD:[33..37] :139) (HYPH:[37..38] -) (CD:[38..40] 53))) ;sentence 1 Span:45..171 ;Prognostic significance of proliferative activity, DNA-ploidy, p53 and Ki-ras ; point mutations in colorectal liver metastases. ;[108..111]:gene-rna:"p53" ;[116..122]:gene-rna:"Ki-ras" ;[124..139]:variation-type:"point mutations" ;[143..170]:malignancy:"colorectal liver metastases" (SENT (NP-HLN (NP (JJ:[45..55] Prognostic) (NN:[56..68] significance)) (PP (IN:[69..71] of) (NP (NP (JJ:[72..85] proliferative) (NN:[86..94] activity)) (,:[94..95] ,) (NP (NN:[96..99] DNA) (HYPH:[99..100] -) (NN:[100..106] ploidy)) (,:[106..107] ,) (NP (NN:[108..111] p53)) (CC:[112..115] and) (NP (NN:[116..122] Ki-ras) (NN:[124..129] point) (NNS:[130..139] mutations)))) (PP (IN:[140..142] in) (NP (JJ:[143..153] colorectal) (NN:[154..159] liver) (NNS:[160..170] metastases))) (.:[170..171] .))) ;section 2 Span:175..299 ;Russo A, Migliavacca M, Bazan V, Maturi N, Morello V, Dardanoni G, Modica G, ;Bazan P, Albanese I, La Farina M, Tomasino RM. (SEC (FRAG (NNP:[175..180] Russo) (NNP:[181..182] A) (,:[182..183] ,) (NNP:[184..195] Migliavacca) (NNP:[196..198] M,) (NNP:[199..204] Bazan) (NNP:[205..206] V) (,:[206..207] ,) (NNP:[208..214] Maturi) (NNP:[215..216] N) (,:[216..217] ,) (NNP:[218..225] Morello) (NNP:[226..227] V) (,:[227..228] ,) (NNP:[229..238] Dardanoni) (NNP:[239..240] G) (,:[240..241] ,) (NNP:[242..248] Modica) (NNP:[249..250] G) (,:[250..251] ,) (NNP:[253..258] Bazan) (NNP:[259..260] P) (,:[260..261] ,) (NNP:[262..270] Albanese) (NNP:[271..272] I) (,:[272..273] ,) (NNP:[274..276] La) (NNP:[277..283] Farina) (NNP:[284..286] M,) (NNP:[287..295] Tomasino) (NNP:[296..298] RM) (.:[298..299] .))) ;section 3 Span:303..374 ;Department of Clinical Oncology Research, University of Palermo, Italy. (SEC (FRAG (NNP:[303..313] Department) (IN:[314..316] of) (NNP:[317..325] Clinical) (NNP:[326..334] Oncology) (NNP:[335..343] Research) (,:[343..344] ,) (NNP:[345..355] University) (IN:[356..358] of) (NNP:[359..366] Palermo) (,:[366..367] ,) (NNP:[368..373] Italy) (.:[373..374] .))) ;sentence 4 Span:378..514 ;Paired colorectal liver metastases (CLM) and normal tissue samples from a ;consecutive series of 36 patients were studied prospectively. ;[385..412]:malignancy:"colorectal liver metastases" ;[414..417]:malignancy:"CLM" (SENT (S (NP-SBJ-1 (NP (VBN:[378..384] Paired) (NML (NML (NML (JJ:[385..395] colorectal) (NN:[396..401] liver) (NNS:[402..412] metastases)) (NML (-LRB-:[413..414] -LRB-) (NN:[414..417] CLM) (-RRB-:[417..418] -RRB-))) (CC:[419..422] and) (NML (JJ:[423..429] normal) (NN:[430..436] tissue) (NNS:[437..444] samples)))) (PP (IN:[445..449] from) (NP (NP (DT:[450..451] a) (JJ:[453..464] consecutive) (NN:[465..471] series)) (PP (IN:[472..474] of) (NP (CD:[475..477] 36) (NNS:[478..486] patients)))))) (VP (VBD:[487..491] were) (VP (VBN:[492..499] studied) (NP-1 (-NONE-:[499..499] *)) (ADVP (RB:[500..513] prospectively)))) (.:[513..514] .))) ;sentence 5 Span:515..599 ;MIB-1 expression was studied by immunohistochemistry on paraffin-embedded ;sections. ;[515..520]:gene-protein:"MIB-1" (SENT (S (NP-SBJ-1 (NN:[515..520] MIB-1) (NN:[521..531] expression)) (VP (VBD:[533..536] was) (VP (VBN:[537..544] studied) (NP-1 (-NONE-:[544..544] *)) (PP-MNR (IN:[545..547] by) (NP (NP (NN:[548..568] immunohistochemistry)) (PP (IN:[569..571] on) (NP (ADJP (NN:[572..580] paraffin) (HYPH:[580..581] -) (VBN:[581..589] embedded)) (NNS:[590..598] sections))))))) (.:[598..599] .))) ;sentence 6 Span:600..704 ;DNA ploidy and S-phase fraction (SPF) measurements were performed by flow ;cytometry on frozen tissues. (SENT (S (NP-SBJ-2 (NP (NML (NN:[600..603] DNA) (NN:[604..610] ploidy)) (NML-1 (-NONE-:[610..610] *P*))) (CC:[612..615] and) (NP (NML (NML (NN:[616..623] S-phase) (NN:[624..632] fraction)) (NML (-LRB-:[633..634] -LRB-) (NN:[634..637] SPF) (-RRB-:[637..638] -RRB-))) (NML-1 (NNS:[639..651] measurements)))) (VP (VBD:[652..656] were) (VP (VBN:[657..666] performed) (NP-2 (-NONE-:[666..666] *)) (PP-MNR (IN:[667..669] by) (NP (NN:[670..674] flow) (NN:[675..684] cytometry))) (PP (IN:[685..687] on) (NP (VBN:[689..695] frozen) (NNS:[696..703] tissues))))) (.:[703..704] .))) ;sentence 7 Span:705..875 ;Mutations within the p53 (exons 5-8) and c-Ki-ras (codons 12 and 13) genes ;were detected by PCR single-strand conformation polymorphism analysis ;followed by sequencing. ;[705..714]:variation-event:"Mutations" ;[726..729]:gene-rna:"p53" ;[731..740]:variation-location:"exons 5-8" ;[746..754]:gene-rna:"c-Ki-ras" ;[756..765]:variation-location:"codons 12" ;[756..762]...[771..773]:variation-location:"codons"..."13" (SENT (S (NP-SBJ-3 (NP (NNS:[705..714] Mutations)) (PP (IN:[715..721] within) (NP (DT:[722..725] the) (NML (NML (NN:[726..729] p53) (PRN (-LRB-:[730..731] -LRB-) (NP (NP (NML-4 (NNS:[731..736] exons)) (CD:[737..738] 5)) (PP (HYPH:[738..739] -) (NP (NML-4 (-NONE-:[739..739] *P*)) (CD:[739..740] 8)))) (-RRB-:[740..741] -RRB-)) (NML-2 (-NONE-:[741..741] *P*))) (CC:[742..745] and) (NML (NN:[746..754] c-Ki-ras) (PRN (-LRB-:[755..756] -LRB-) (NP (NP (NML-1 (NNS:[756..762] codons)) (CD:[763..765] 12)) (CC:[766..769] and) (NP (NML-1 (-NONE-:[769..769] *P*)) (CD:[771..773] 13))) (-RRB-:[773..774] -RRB-)) (NML-2 (NNS:[775..780] genes))))))) (VP (VBD:[781..785] were) (VP (VBN:[786..794] detected) (NP-3 (-NONE-:[794..794] *)) (PP-MNR (IN:[795..797] by) (NP (NP (NN:[798..801] PCR) (NML (JJ:[802..808] single) (HYPH:[808..809] -) (NN:[809..815] strand)) (NN:[816..828] conformation) (NN:[829..841] polymorphism) (NN:[842..850] analysis)) (VP (VBN:[852..860] followed) (NP-SBJ (-NONE-:[860..860] *)) (PP (IN:[861..863] by) (NP-LGS (NN:[864..874] sequencing)))))))) (.:[874..875] .))) ;sentence 8 Span:876..963 ;A high correlation was observed between the MIB-1 LI and SPF value ;(rho=0.81; P<0.01). ;[920..925]:gene-protein:"MIB-1" (SENT (S (NP-SBJ-1 (DT:[876..877] A) (JJ:[878..882] high) (NN:[883..894] correlation)) (VP (VBD:[895..898] was) (VP (VBN:[899..907] observed) (NP-1 (-NONE-:[907..907] *)) (PP (IN:[908..915] between) (NP (NP (DT:[916..919] the) (NN:[920..925] MIB-1) (NN:[926..928] LI)) (CC:[929..932] and) (NP (NN:[934..937] SPF) (NN:[938..943] value)))) (PRN (-LRB-:[944..945] -LRB-) (S (S (NP-SBJ (SYM:[945..948] rho)) (VP (SYM:[948..949] =) (NP (CD:[949..953] 0.81)))) (::[953..954] ;) (S (NP-SBJ (NN:[955..956] P)) (VP (SYM:[956..957] <) (NP (CD:[957..961] 0.01))))) (-RRB-:[961..962] -RRB-)))) (.:[962..963] .))) ;sentence 9 Span:964..1049 ;Moreover, p53 gene mutations were associated with either high MIB-1 LI and ;high SPF. ;[974..977]:gene-rna:"p53" ;[1027..1032]:gene-protein:"MIB-1" (SENT (S (ADVP (RB:[964..972] Moreover)) (,:[972..973] ,) (NP-SBJ-1 (NN:[974..977] p53) (NN:[978..982] gene) (NNS:[983..992] mutations)) (VP (VBD:[993..997] were) (VP (VBN:[998..1008] associated) (NP-1 (-NONE-:[1008..1008] *)) (PP-CLR (IN:[1009..1013] with) (NP (DT:[1015..1021] either) (NP (JJ:[1022..1026] high) (NN:[1027..1032] MIB-1) (NN:[1033..1035] LI)) (CC:[1036..1039] and) (NP (JJ:[1040..1044] high) (NN:[1045..1048] SPF)))))) (.:[1048..1049] .))) ;sentence 10 Span:1050..1126 ;In univariate analysis, SPF and MIB-1 levels were related to risk of death. ;[1082..1087]:gene-protein:"MIB-1" (SENT (S (PP (IN:[1050..1052] In) (NP (JJ:[1053..1063] univariate) (NN:[1064..1072] analysis))) (,:[1072..1073] ,) (NP-SBJ-2 (NP (NN:[1074..1077] SPF) (NML-1 (-NONE-:[1077..1077] *P*))) (CC:[1078..1081] and) (NP (NN:[1082..1087] MIB-1) (NML-1 (NNS:[1088..1094] levels)))) (VP (VBD:[1096..1100] were) (VP (VBN:[1101..1108] related) (NP-2 (-NONE-:[1108..1108] *)) (PP-CLR (TO:[1109..1111] to) (NP (NP (NN:[1112..1116] risk)) (PP (IN:[1117..1119] of) (NP (NN:[1120..1125] death))))))) (.:[1125..1126] .))) ;sentence 11 Span:1127..1387 ;The association between overall survival and DNA-ploidy or p53 mutations did ;not reach statistical significance, but a slightly better survival was ;observed for patients either with DNA-diploid tumours or without mutations ;(P=0.05 and P=0.06, respectively). ;[1187..1190]:gene-rna:"p53" ;[1311..1322]:variation-type:"DNA-diploid" ;[1324..1331]:malignancy:"tumours" (SENT (S (S (NP-SBJ (NP (DT:[1127..1130] The) (NN:[1131..1142] association)) (PP (IN:[1143..1150] between) (NP (NP (JJ:[1151..1158] overall) (NN:[1159..1167] survival)) (CC:[1168..1171] and) (NP (NP (NN:[1173..1176] DNA) (HYPH:[1176..1177] -) (NN:[1177..1183] ploidy)) (CC:[1184..1186] or) (NP (NN:[1187..1190] p53) (NNS:[1191..1200] mutations)))))) (VP (VBD:[1201..1204] did) (RB:[1205..1208] not) (VP (VB:[1209..1214] reach) (NP (JJ:[1215..1226] statistical) (NN:[1227..1239] significance))))) (,:[1239..1240] ,) (CC:[1241..1244] but) (S (NP-SBJ-1 (DT:[1245..1246] a) (ADJP (RB:[1248..1256] slightly) (JJR:[1257..1263] better)) (NN:[1264..1272] survival)) (VP (VBD:[1273..1276] was) (VP (VBN:[1277..1285] observed) (NP-1 (-NONE-:[1285..1285] *)) (PP (IN:[1286..1289] for) (NP (NP (NNS:[1290..1298] patients)) (PP (CC:[1299..1305] either) (PP (IN:[1306..1310] with) (NP (ADJP (NN:[1311..1314] DNA) (HYPH:[1314..1315] -) (JJ:[1315..1322] diploid)) (NNS:[1324..1331] tumours))) (CC:[1332..1334] or) (PP (IN:[1335..1342] without) (NP (NNS:[1343..1352] mutations)))))) (PRN (-LRB-:[1353..1354] -LRB-) (FRAG (S (NP-SBJ (NN:[1354..1355] P)) (VP (SYM:[1355..1356] =) (NP (CD:[1356..1360] 0.05)))) (CC:[1361..1364] and) (S (NP-SBJ (NN:[1365..1366] P)) (VP (SYM:[1366..1367] =) (NP (CD:[1367..1371] 0.06)))) (,:[1371..1372] ,) (ADVP (RB:[1373..1385] respectively))) (-RRB-:[1385..1386] -RRB-))))) (.:[1386..1387] .))) ;sentence 12 Span:1388..1549 ;SPF was shown by multivariate Cox model analysis to be an independent ;prognostic variable and thus it might be a useful prognostic factor in ;patients with CLM. ;[1545..1548]:malignancy:"CLM" (SENT (S (S (NP-SBJ-1 (NN:[1388..1391] SPF)) (VP (VBD:[1392..1395] was) (VP (VBN:[1396..1401] shown) (PP-MNR (IN:[1402..1404] by) (NP (JJ:[1406..1418] multivariate) (NNP:[1419..1422] Cox) (NN:[1423..1428] model) (NN:[1429..1437] analysis))) (S (NP-SBJ-1 (-NONE-:[1437..1437] *)) (VP (TO:[1438..1440] to) (VP (VB:[1441..1443] be) (NP-PRD (DT:[1444..1446] an) (JJ:[1447..1458] independent) (JJ:[1459..1469] prognostic) (NN:[1470..1478] variable)))))))) (CC:[1479..1482] and) (S (ADVP (RB:[1484..1488] thus)) (NP-SBJ (PRP:[1489..1491] it)) (VP (MD:[1492..1497] might) (VP (VB:[1498..1500] be) (NP-PRD (NP (DT:[1501..1502] a) (JJ:[1503..1509] useful) (JJ:[1510..1520] prognostic) (NN:[1521..1527] factor)) (PP (IN:[1528..1530] in) (NP (NP (NNS:[1531..1539] patients)) (PP (IN:[1540..1544] with) (NP (NN:[1545..1548] CLM))))))))) (.:[1548..1549] .))) ;section 13 Span:1553..1597 ;PMID: 9853427 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1553..1557] PMID) (::[1557..1558] :) (CD:[1559..1566] 9853427) (IN:[1567..1568] -LSB-) (NNP:[1568..1574] PubMed) (HYPH:[1575..1576] -) (JJ:[1577..1584] indexed) (IN:[1585..1588] for) (NNP:[1589..1597] MEDLINE-RSB-)))