;PMID: 10661623 ;source_file_1361.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..34] = [t:0..34] ;1)sentence:[e:39..129] = [t:39..129] ;2)section:[e:133..252] = [t:133..252] ;3)section:[e:256..336] = [t:256..336] ;4)sentence:[e:340..507] = [t:340..507] ;5)sentence:[e:508..623] = [t:508..623] ;6)sentence:[e:624..780] = [t:624..780] ;7)sentence:[e:781..841] = [t:781..841] ;8)sentence:[e:842..900] = [t:842..900] ;9)sentence:[e:901..1100] = [t:901..1100] ;10)sentence:[e:1101..1231] = [t:1101..1231] ;11)sentence:[e:1232..1370] = [t:1232..1370] ;12)sentence:[e:1371..1502] = [t:1371..1502] ;13)sentence:[e:1503..1668] = [t:1503..1668] ;14)sentence:[e:1669..1831] = [t:1669..1831] ;15)section:[e:1835..1880] = [t:1835..1880] ;section 0 Span:0..34 ;Anal Cell Pathol 1999;19(1):39-46 (SEC (FRAG (NNP:[0..4] Anal) (NNP:[5..9] Cell) (NNP:[10..16] Pathol) (CD:[18..26] 1999;19-LRB-) (CD:[26..27] 1) (-RRB-:[27..28] -RRB-) (CD:[28..31] :39) (IN:[31..32] -) (CD:[32..34] 46))) ;sentence 1 Span:39..129 ;K-ras2 activation and genome instability increase proliferation and size of ;FAP adenomas. ;[39..45]:gene-rna:"K-ras2" ;[115..128]:malignancy:"FAP adenomas" (SENT (S-HLN (NP-SBJ (NP (NN:[39..45] K-ras2) (NN:[46..56] activation)) (CC:[57..60] and) (NP (NN:[61..67] genome) (NN:[68..79] instability))) (VP (VBP:[80..88] increase) (NP (NP (NN:[89..102] proliferation) (CC:[103..106] and) (NN:[107..111] size)) (PP (IN:[112..114] of) (NP (NN:[115..118] FAP) (NNS:[120..128] adenomas))))) (.:[128..129] .))) ;section 2 Span:133..252 ;Rapallo A, Sciutto A, Geido E, Orecchia R, Infusini E, Pujic N, d'Amore ES, ;Monaco R, Risio M, Rossini FP, Giaretti W. (SEC (FRAG (NNP:[133..140] Rapallo) (NNP:[141..142] A) (,:[142..143] ,) (NNP:[144..151] Sciutto) (NNP:[152..153] A) (,:[153..154] ,) (NNP:[155..160] Geido) (NNP:[161..162] E) (,:[162..163] ,) (NNP:[164..172] Orecchia) (NNP:[173..175] R,) (NNP:[176..184] Infusini) (NNP:[185..186] E) (,:[186..187] ,) (NNP:[188..193] Pujic) (NNP:[194..195] N) (,:[195..196] ,) (NNP:[197..204] d'Amore) (NNP:[205..207] ES) (,:[207..208] ,) (NNP:[210..216] Monaco) (NNP:[217..219] R,) (NNP:[220..225] Risio) (NNP:[226..228] M,) (NNP:[229..236] Rossini) (NNP:[237..239] FP) (,:[239..240] ,) (NNP:[241..249] Giaretti) (NNP:[250..252] W.))) ;section 3 Span:256..336 ;Laboratory of Biophysics and Cytometry, National Cancer Institute, Genoa, ;Italy. (SEC (FRAG (NN:[256..266] Laboratory) (IN:[267..269] of) (NNP:[270..280] Biophysics) (CC:[281..284] and) (NNP:[285..294] Cytometry) (,:[294..295] ,) (NNP:[296..304] National) (NNP:[305..311] Cancer) (NNP:[312..321] Institute) (,:[321..322] ,) (NNP:[323..328] Genoa) (,:[328..329] ,) (NNP:[330..335] Italy) (.:[335..336] .))) ;sentence 4 Span:340..507 ;The possible role of K-ras2 mutations and aneuploidy toward increase of ;proliferation and adenoma size in Familial Adenomatous Polyposis (FAP) ;adenomas is not known. ;[361..367]:gene-rna:"K-ras2" ;[382..392]:variation-type:"aneuploidy" ;[431..438]:malignancy:"adenoma" ;[447..492]:malignancy:"Familial Adenomatous Polyposis (FAP) adenomas" ;[479..482]:malignancy:"FAP" (SENT (S (NP-SBJ-1 (NP (DT:[340..343] The) (JJ:[344..352] possible) (NN:[353..357] role)) (PP (IN:[358..360] of) (NP (NP (NP (NN:[361..367] K-ras2) (NNS:[368..377] mutations)) (CC:[378..381] and) (NP (NN:[382..392] aneuploidy))) (PP (IN:[393..399] toward) (NP (NP (NN:[400..408] increase)) (PP (IN:[409..411] of) (NP (NP (NN:[413..426] proliferation)) (CC:[427..430] and) (NP (NN:[431..438] adenoma) (NN:[439..443] size)))) (PP (IN:[444..446] in) (NP (NML (NML (JJ:[447..455] Familial) (JJ:[456..467] Adenomatous) (NN:[468..477] Polyposis)) (NML (-LRB-:[478..479] -LRB-) (NN:[479..482] FAP) (-RRB-:[482..483] -RRB-))) (NNS:[484..492] adenomas)))))))) (VP (VBZ:[494..496] is) (RB:[497..500] not) (VP (VBN:[501..506] known) (NP-1 (-NONE-:[506..506] *)))) (.:[506..507] .))) ;sentence 5 Span:508..623 ;The present study addresses these issues by investigating 147 colorectal ;adenomas obtained from four FAP patients. ;[571..590]:malignancy:"colorectal adenomas" ;[610..613]:malignancy:"FAP" (SENT (S (NP-SBJ (DT:[508..511] The) (JJ:[512..519] present) (NN:[520..525] study)) (VP (VBZ:[526..535] addresses) (NP (DT:[536..541] these) (NNS:[542..548] issues)) (PP (IN:[549..551] by) (S-NOM (NP-SBJ (-NONE-:[551..551] *)) (VP (VBG:[552..565] investigating) (NP (NP (CD:[566..569] 147) (JJ:[571..581] colorectal) (NNS:[582..590] adenomas)) (VP (VBN:[591..599] obtained) (NP (-NONE-:[599..599] *)) (PP (IN:[600..604] from) (NP (CD:[605..609] four) (NN:[610..613] FAP) (NNS:[614..622] patients))))))))) (.:[622..623] .))) ;sentence 6 Span:624..780 ;The majority of adenomas had size lower than or equal to 10 mm (86%), low ;grade dysplasia (63%), and were preferentially located in the right colon ;(60%). ;[640..648]:malignancy:"adenomas" ;[695..714]:malignancy:"low grade dysplasia" (SENT (S (NP-SBJ-1 (NP (DT:[624..627] The) (NN:[628..636] majority)) (PP (IN:[637..639] of) (NP (NNS:[640..648] adenomas)))) (VP (VP (VBD:[650..653] had) (NP (NP (NP (NN:[654..658] size)) (NP (QP (JJR:[659..664] lower) (IN:[665..669] than) (CC:[670..672] or) (JJ:[673..678] equal) (TO:[679..681] to) (CD:[682..684] 10)) (NN:[685..687] mm) (PRN (-LRB-:[688..689] -LRB-) (NP (CD:[689..691] 86) (NN:[691..692] %)) (-RRB-:[692..693] -RRB-)))) (,:[693..694] ,) (NP (JJ:[695..698] low) (NN:[699..704] grade) (NN:[705..714] dysplasia) (PRN (-LRB-:[715..716] -LRB-) (NP (CD:[716..718] 63) (NN:[718..719] %)) (-RRB-:[719..720] -RRB-))))) (,:[720..721] ,) (CC:[722..725] and) (VP (VBD:[726..730] were) (ADVP (RB:[732..746] preferentially)) (VP (VBN:[747..754] located) (NP-1 (-NONE-:[754..754] *)) (PP-LOC (IN:[755..757] in) (NP (DT:[758..761] the) (JJ:[762..767] right) (NN:[768..773] colon))) (PRN (-LRB-:[774..775] -LRB-) (NP (CD:[775..777] 60) (NN:[777..778] %)) (-RRB-:[778..779] -RRB-))))) (.:[779..780] .))) ;sentence 7 Span:781..841 ;Normal mucosa samples were obtained from 19 healthy donors. (SENT (S (NP-SBJ-1 (JJ:[781..787] Normal) (NN:[788..794] mucosa) (NNS:[795..802] samples)) (VP (VBD:[803..807] were) (VP (VBN:[809..817] obtained) (NP-1 (-NONE-:[817..817] *)) (PP (IN:[818..822] from) (NP (CD:[823..825] 19) (JJ:[826..833] healthy) (NNS:[834..840] donors))))) (.:[840..841] .))) ;sentence 8 Span:842..900 ;Three synchronous adenocarcinomas were also investigated. ;[860..875]:malignancy:"adenocarcinomas" (SENT (S (NP-SBJ-1 (CD:[842..847] Three) (JJ:[848..859] synchronous) (NNS:[860..875] adenocarcinomas)) (VP (VBD:[876..880] were) (ADVP (RB:[881..885] also)) (VP (VBN:[887..899] investigated) (NP-1 (-NONE-:[899..899] *)))) (.:[899..900] .))) ;sentence 9 Span:901..1100 ;K-ras2 mutation spectrum was analysed by PCR and Sequence Specific ;Oligonucleotide (SSO) hybridization, while flow cytometry (FCM) was used for ;evaluating degree of DNA ploidy and S-phase fraction. ;[901..907]:gene-rna:"K-ras2" ;[1072..1078]:variation-type:"ploidy" (SENT (S (NP-SBJ-2 (NN:[901..907] K-ras2) (NN:[908..916] mutation) (NN:[917..925] spectrum)) (VP (VBD:[926..929] was) (VP (VBN:[930..938] analysed) (NP-2 (-NONE-:[938..938] *)) (PP-MNR (IN:[939..941] by) (NP (NP (NN:[942..945] PCR)) (CC:[946..949] and) (NP (NML (NML (NN:[950..958] Sequence) (JJ:[959..967] Specific) (NN:[969..984] Oligonucleotide)) (NML (-LRB-:[985..986] -LRB-) (NN:[986..989] SSO) (-RRB-:[989..990] -RRB-))) (NN:[991..1004] hybridization)))) (,:[1004..1005] ,) (SBAR-ADV (IN:[1006..1011] while) (S (NP-SBJ-1 (NP (NN:[1012..1016] flow) (NN:[1017..1026] cytometry)) (NP (-LRB-:[1027..1028] -LRB-) (NN:[1028..1031] FCM) (-RRB-:[1031..1032] -RRB-))) (VP (VBD:[1033..1036] was) (VP (VBN:[1037..1041] used) (NP-1 (-NONE-:[1041..1041] *)) (PP (IN:[1042..1045] for) (S-NOM (NP-SBJ (-NONE-:[1045..1045] *)) (VP (VBG:[1047..1057] evaluating) (NP (NP (NN:[1058..1064] degree)) (PP (IN:[1065..1067] of) (NP (NP (NN:[1068..1071] DNA) (NN:[1072..1078] ploidy)) (CC:[1079..1082] and) (NP (NN:[1083..1090] S-phase) (NN:[1091..1099] fraction)))))))))))))) (.:[1099..1100] .))) ;sentence 10 Span:1101..1231 ;Overall, incidences of K-ras2 mutations, DNA aneuploidy and high S-phase ;values (>7.2%) were 6.6%, 5.4% and 10.5%, respectively. ;[1125..1131]:gene-rna:"K-ras2" ;[1147..1157]:variation-type:"aneuploidy" (SENT (S (ADVP (RB:[1101..1108] Overall)) (,:[1108..1109] ,) (NP-SBJ (NP (NNS:[1110..1120] incidences)) (PP (IN:[1121..1123] of) (NP (NP (NN:[1125..1131] K-ras2) (NNS:[1132..1141] mutations)) (,:[1141..1142] ,) (NP (NN:[1143..1146] DNA) (NN:[1147..1157] aneuploidy)) (CC:[1158..1161] and) (NP (JJ:[1162..1166] high) (NN:[1167..1174] S-phase) (NNS:[1175..1181] values) (PRN (-LRB-:[1182..1183] -LRB-) (VP (SYM:[1183..1184] >) (NP (CD:[1184..1187] 7.2) (NN:[1187..1188] %))) (-RRB-:[1188..1189] -RRB-)))))) (VP (VBD:[1190..1194] were) (NP-PRD (NP (CD:[1195..1198] 6.6) (NN:[1198..1199] %)) (,:[1199..1200] ,) (NP (CD:[1201..1204] 5.4) (NN:[1204..1205] %)) (CC:[1207..1210] and) (NP (CD:[1211..1215] 10.5) (NN:[1215..1216] %))) (,:[1216..1217] ,) (ADVP (RB:[1218..1230] respectively))) (.:[1230..1231] .))) ;sentence 11 Span:1232..1370 ;In particular, among the adenomas with size lower than 5 mm, K-ras2 mutation ;and DNA aneuploidy frequencies were only slightly above 1%. ;[1257..1265]:malignancy:"adenomas" ;[1294..1300]:gene-rna:"K-ras2" ;[1318..1328]:variation-type:"aneuploidy" (SENT (S (PP (IN:[1232..1234] In) (NP (JJ:[1235..1245] particular))) (,:[1245..1246] ,) (PP (IN:[1247..1252] among) (NP (NP (DT:[1253..1256] the) (NNS:[1257..1265] adenomas)) (PP (IN:[1266..1270] with) (NP (NN:[1271..1275] size) (NML (QP (JJR:[1276..1281] lower) (IN:[1282..1286] than) (CD:[1288..1289] 5)) (NN:[1290..1292] mm)))))) (,:[1292..1293] ,) (NP-SBJ (NP (NN:[1294..1300] K-ras2) (NN:[1301..1309] mutation) (NML-1 (-NONE-:[1309..1309] *P*))) (CC:[1310..1313] and) (NP (NN:[1314..1317] DNA) (NN:[1318..1328] aneuploidy) (NML-1 (NNS:[1329..1340] frequencies)))) (VP (VBD:[1341..1345] were) (ADVP (RB:[1346..1350] only) (RB:[1351..1359] slightly)) (PP-PRD (IN:[1360..1365] above) (NP (CD:[1367..1368] 1) (NN:[1368..1369] %)))) (.:[1369..1370] .))) ;sentence 12 Span:1371..1502 ;Statistically significant correlations were found between K-ras2 and size, ;DNA ploidy and size and K-ras2 and S-phase (p < 0.001). ;[1429..1435]:gene-rna:"K-ras2" ;[1451..1457]:variation-type:"ploidy" ;[1471..1477]:gene-rna:"K-ras2" (SENT (S (NP-SBJ-1 (ADJP (RB:[1371..1384] Statistically) (JJ:[1385..1396] significant)) (NNS:[1397..1409] correlations)) (VP (VBD:[1410..1414] were) (VP (VBN:[1415..1420] found) (NP-1 (-NONE-:[1420..1420] *)) (PP (IN:[1421..1428] between) (NP (NP (NN:[1429..1435] K-ras2) (CC:[1436..1439] and) (NN:[1440..1444] size)) (,:[1444..1445] ,) (NP (NP (NN:[1447..1450] DNA) (NN:[1451..1457] ploidy)) (CC:[1458..1461] and) (NP (NN:[1462..1466] size))) (CC:[1467..1470] and) (NP (NN:[1471..1477] K-ras2) (CC:[1478..1481] and) (NN:[1482..1489] S-phase)))) (PRN (-LRB-:[1490..1491] -LRB-) (S (NP-SBJ (NN:[1491..1492] p)) (VP (SYM:[1493..1494] <) (NP (CD:[1495..1500] 0.001)))) (-RRB-:[1500..1501] -RRB-)))) (.:[1501..1502] .))) ;sentence 13 Span:1503..1668 ;In particular, among the wild type K-ras2 adenomas, high S-phase values were ;detected in 8% of the cases versus 57% among the K-ras2 mutated adenomas (p ;= 0.0005). ;[1539..1545]:gene-rna:"K-ras2" ;[1546..1554]:malignancy:"adenomas" ;[1631..1637]:gene-rna:"K-ras2" ;[1646..1654]:malignancy:"adenomas" (SENT (S (PP (IN:[1503..1505] In) (NP (JJ:[1506..1516] particular))) (,:[1516..1517] ,) (PP (IN:[1518..1523] among) (NP (DT:[1524..1527] the) (NML (JJ:[1529..1533] wild) (NN:[1534..1538] type)) (NN:[1539..1545] K-ras2) (NNS:[1546..1554] adenomas))) (,:[1554..1555] ,) (NP-SBJ-1 (JJ:[1556..1560] high) (NN:[1561..1568] S-phase) (NNS:[1569..1575] values)) (VP (VBD:[1576..1580] were) (VP (VBN:[1581..1589] detected) (NP-1 (-NONE-:[1589..1589] *)) (PP (IN:[1590..1592] in) (NP (NP (NP (CD:[1593..1594] 8) (NN:[1594..1595] %)) (PP (IN:[1596..1598] of) (NP (DT:[1599..1602] the) (NNS:[1603..1608] cases)))) (PP (IN:[1610..1616] versus) (NP (NP (CD:[1617..1619] 57) (NN:[1619..1620] %)) (PP (IN:[1621..1626] among) (NP (DT:[1627..1630] the) (NN:[1631..1637] K-ras2) (VBN:[1638..1645] mutated) (NNS:[1646..1654] adenomas))))))) (PRN (-LRB-:[1655..1656] -LRB-) (S (NP-SBJ (NN:[1656..1657] p)) (VP (SYM:[1658..1659] =) (NP (CD:[1660..1666] 0.0005)))) (-RRB-:[1666..1667] -RRB-)))) (.:[1667..1668] .))) ;sentence 14 Span:1669..1831 ;The present series of FAP adenomas indicates that K-ras2 activation and ;gross genomic changes play a role toward a proliferative gain and tumour ;growth in size. ;[1692..1704]:malignancy:"FAP adenomas" ;[1720..1726]:gene-rna:"K-ras2" (SENT (S (NP-SBJ (NP (DT:[1669..1672] The) (JJ:[1673..1680] present) (NN:[1681..1687] series)) (PP (IN:[1688..1690] of) (NP (NN:[1692..1695] FAP) (NNS:[1696..1704] adenomas)))) (VP (VBZ:[1705..1714] indicates) (SBAR (IN:[1715..1719] that) (S (NP-SBJ (NP (NN:[1720..1726] K-ras2) (NN:[1727..1737] activation)) (CC:[1738..1741] and) (NP (JJ:[1742..1747] gross) (JJ:[1748..1755] genomic) (NNS:[1756..1763] changes))) (VP (VBP:[1764..1768] play) (NP (NP (DT:[1769..1770] a) (NN:[1772..1776] role)) (PP (IN:[1777..1783] toward) (NP (NP (NP (DT:[1784..1785] a) (JJ:[1786..1799] proliferative) (NN:[1800..1804] gain)) (CC:[1805..1808] and) (NP (NN:[1809..1815] tumour) (NN:[1816..1822] growth))) (PP (IN:[1823..1825] in) (NP (NN:[1826..1830] size)))))))))) (.:[1830..1831] .))) ;section 15 Span:1835..1880 ;PMID: 10661623 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1835..1839] PMID) (::[1839..1840] :) (CD:[1841..1849] 10661623) (IN:[1850..1851] -LSB-) (NNP:[1851..1857] PubMed) (HYPH:[1858..1859] -) (JJ:[1860..1867] indexed) (IN:[1868..1871] for) (NNP:[1872..1880] MEDLINE-RSB-)))