;PMID: 10665646 ;source_file_1360.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..40] = [t:0..40] ;1)section:[e:45..94] = [t:45..94] ;2)section:[e:98..165] = [t:98..165] ;3)sentence:[e:169..272] = [t:169..272] ;4)section:[e:276..347] = [t:276..347] ;5)section:[e:351..420] = [t:351..420] ;6)sentence:[e:424..566] = [t:424..566] ;7)sentence:[e:567..730] = [t:567..730] ;8)sentence:[e:732..906] = [t:732..906] ;9)sentence:[e:907..1073] = [t:907..1073] ;10)sentence:[e:1074..1244] = [t:1074..1244] ;11)sentence:[e:1245..1387] = [t:1245..1387] ;12)sentence:[e:1388..1562] = [t:1388..1562] ;13)sentence:[e:1563..1934] = [t:1563..1934] ;14)section:[e:1938..1983] = [t:1938..1983] ;section 0 Span:0..40 ;Jpn J Cancer Res 1999 Dec;90(12):1301-9 (SEC (FRAG (NNP:[0..3] Jpn) (NNP:[4..5] J) (NNP:[6..12] Cancer) (NNP:[13..16] Res) (CD:[18..22] 1999) (-LRB-:[23..30] Dec;90-LRB-) (CD:[30..32] 12) (-RRB-:[32..33] -RRB-) (CD:[33..38] :1301) (::[38..39] -) (CD:[39..40] 9))) ;section 1 Span:45..94 ;Erratum in: Jpn J Cancer Res 2000 Feb;91(2):270 (SEC (FRAG (NNP:[45..52] Erratum) (IN:[53..55] in) (NNP:[55..56] :) (NNP:[59..62] Jpn) (NNP:[63..64] J) (NNP:[65..71] Cancer) (NNP:[72..75] Res) (CD:[76..80] 2000) (-LRB-:[81..88] Feb;91-LRB-) (CD:[88..89] 2) (-RRB-:[89..90] -RRB-) (.:[90..94] :270))) ;section 2 Span:98..165 ;Comment in: Jpn J Cancer Res. 1999 Dec;90(12):inside front cover. (SEC (FRAG (NNP:[98..105] Comment) (IN:[106..108] in) (NNP:[108..109] :) (NNP:[112..115] Jpn) (NNP:[116..117] J) (NNP:[118..124] Cancer) (NNP:[125..128] Res) (.:[128..129] .) (CD:[130..134] 1999) (CC:[135..142] Dec;90-LRB-) (CD:[142..144] 12) (NNS:[144..145] -RRB-) (RB:[145..152] :inside) (JJ:[153..158] front) (NN:[159..164] cover) (.:[164..165] .))) ;sentence 3 Span:169..272 ;Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in ;hepatocellular carcinoma. ;[169..181]:gene-protein:"Beta-catenin" ;[199..207]:variation-event:"mutation" ;[211..217]:variation-location:"exon 3" ;[225..237]:gene-rna:"beta-catenin" ;[247..271]:malignancy:"hepatocellular carcinoma" (SENT (NP-HLN (NP (NP (NN:[169..181] Beta-catenin) (NN:[182..194] accumulation)) (CC:[195..198] and) (NP (NP (NN:[199..207] mutation)) (PP (IN:[208..210] of) (NP (NP (NN:[211..215] exon) (CD:[216..217] 3)) (PP (IN:[218..220] of) (NP (DT:[221..224] the) (NN:[225..237] beta-catenin) (NN:[238..242] gene))))))) (PP (IN:[243..245] in) (NP (JJ:[247..261] hepatocellular) (NN:[262..271] carcinoma))) (.:[271..272] .))) ;section 4 Span:276..347 ;Kondo Y, Kanai Y, Sakamoto M, Genda T, Mizokami M, Ueda R, Hirohashi S. (SEC (FRAG (NNP:[276..281] Kondo) (NNP:[282..283] Y) (,:[283..284] ,) (NNP:[285..290] Kanai) (NNP:[291..292] Y) (,:[292..293] ,) (NNP:[294..302] Sakamoto) (VBD:[303..305] M,) (NNP:[306..311] Genda) (NNP:[312..313] T) (,:[313..314] ,) (NNP:[315..323] Mizokami) (NNP:[324..326] M,) (NNP:[327..331] Ueda) (NNP:[332..334] R,) (NNP:[335..344] Hirohashi) (NNP:[345..347] S.))) ;section 5 Span:351..420 ;Pathology Division, National Cancer Center Research Institute, Tokyo. (SEC (FRAG (NNP:[351..360] Pathology) (NNP:[361..369] Division) (,:[369..370] ,) (NNP:[371..379] National) (NNP:[380..386] Cancer) (NNP:[387..393] Center) (NNP:[394..402] Research) (NNP:[403..412] Institute) (,:[412..413] ,) (NNP:[414..419] Tokyo) (.:[419..420] .))) ;sentence 6 Span:424..566 ;A study was conducted to clarify the contribution of beta-catenin ;accumulation and mutation of the beta-catenin gene to hepatocarcinogenesis. ;[477..489]:gene-protein:"beta-catenin" ;[524..536]:gene-rna:"beta-catenin" (SENT (S (NP-SBJ-1 (NP (DT:[424..425] A) (NN:[426..431] study)) (SBAR-2 (-NONE-:[431..431] *ICH*))) (VP (VBD:[432..435] was) (VP (VBN:[436..445] conducted) (NP-1 (-NONE-:[445..445] *)) (SBAR-2 (WHNP (-NONE-:[445..445] 0)) (S (NP-SBJ (-NONE-:[445..445] *)) (VP (TO:[446..448] to) (VP (VB:[449..456] clarify) (NP (NP (DT:[457..460] the) (NN:[461..473] contribution)) (PP (IN:[474..476] of) (NP (NP (NN:[477..489] beta-catenin) (NN:[490..502] accumulation)) (CC:[504..507] and) (NP (NP (NN:[508..516] mutation)) (PP (IN:[517..519] of) (NP (DT:[520..523] the) (NN:[524..536] beta-catenin) (NN:[537..541] gene)))))) (PP (TO:[542..544] to) (NP (NN:[545..565] hepatocarcinogenesis)))))))))) (.:[565..566] .))) ;sentence 7 Span:567..730 ;Beta-catenin accumulation was examined immunohistochemically in 38 paired ;samples of hepatocellular carcinoma (HCC) and corresponding non-cancerous ;liver tissue. ;[567..579]:gene-protein:"Beta-catenin" ;[654..678]:malignancy:"hepatocellular carcinoma" ;[680..683]:malignancy:"HCC" (SENT (S (NP-SBJ-1 (NN:[567..579] Beta-catenin) (NN:[581..593] accumulation)) (VP (VBD:[594..597] was) (VP (VBN:[598..606] examined) (NP-1 (-NONE-:[606..606] *)) (ADVP-MNR (RB:[607..628] immunohistochemically)) (PP (IN:[629..631] in) (NP (NP (NP (CD:[632..634] 38) (VBN:[635..641] paired) (NNS:[642..649] samples)) (PP (IN:[650..652] of) (NP (NP (JJ:[654..668] hepatocellular) (NN:[669..678] carcinoma)) (NP (-LRB-:[679..680] -LRB-) (NN:[680..683] HCC) (-RRB-:[683..684] -RRB-))))) (CC:[685..688] and) (NP (VBG:[689..702] corresponding) (ADJP (AFX:[703..706] non) (HYPH:[706..707] -) (JJ:[707..716] cancerous)) (NN:[717..722] liver) (NN:[723..729] tissue)))))) (.:[729..730] .))) ;sentence 8 Span:732..906 ;Gene mutation was analyzed by polymerase chain reaction-single strand ;conformation polymorphism (PCR-SSCP) and direct sequencing using intronic ;primers encompassing exon 3. ;[762..772]:gene-protein:"polymerase" ;[899..905]:variation-location:"exon 3" (SENT (S (NP-SBJ-1 (NN:[732..736] Gene) (NN:[737..745] mutation)) (VP (VBD:[746..749] was) (VP (VBN:[750..758] analyzed) (NP-1 (-NONE-:[758..758] *)) (PP-MNR (IN:[759..761] by) (NP (NP (NP (NML (NN:[762..772] polymerase) (NN:[773..778] chain) (NN:[779..787] reaction)) (HYPH:[787..788] -) (NML (NML (JJ:[788..794] single) (NN:[795..801] strand)) (NN:[803..815] conformation) (NN:[816..828] polymorphism))) (NP (-LRB-:[829..830] -LRB-) (NML (NN:[830..833] PCR)) (HYPH:[833..834] -) (NML (NN:[834..838] SSCP)) (-RRB-:[838..839] -RRB-))) (CC:[840..843] and) (NP (JJ:[844..850] direct) (NN:[851..861] sequencing)))) (S-ADV (NP-SBJ (-NONE-:[861..861] *)) (VP (VBG:[862..867] using) (NP (NP (JJ:[868..876] intronic) (NNS:[878..885] primers)) (VP (VBG:[886..898] encompassing) (NP (NN:[899..903] exon) (CD:[904..905] 3)))))))) (.:[905..906] .))) ;sentence 9 Span:907..1073 ;Neither accumulation nor mutation was detected in non-cancerous liver ;tissues that showed no remarkable histological features, chronic hepatitis ;or liver cirrhosis. ;[1036..1053]:malignancy:"chronic hepatitis" (SENT (S (NP-SBJ-2 (CC:[907..914] Neither) (NN:[915..927] accumulation) (CC:[928..931] nor) (NN:[932..940] mutation)) (VP (VBD:[941..944] was) (VP (VBN:[945..953] detected) (NP-2 (-NONE-:[953..953] *)) (PP-LOC (IN:[954..956] in) (NP (NP (ADJP (AFX:[958..961] non) (HYPH:[961..962] -) (JJ:[962..971] cancerous)) (NN:[972..977] liver) (NNS:[978..985] tissues)) (SBAR (WHNP-1 (WDT:[986..990] that)) (S (NP-SBJ-1 (-NONE-:[990..990] *T*)) (VP (VBD:[991..997] showed) (NP (DT:[998..1000] no) (NML (NML (JJ:[1001..1011] remarkable) (JJ:[1012..1024] histological) (NNS:[1025..1033] features)) (,:[1033..1034] ,) (NML (JJ:[1036..1043] chronic) (NN:[1044..1053] hepatitis)) (CC:[1054..1056] or) (NML (NN:[1057..1062] liver) (NN:[1063..1072] cirrhosis))))))))))) (.:[1072..1073] .))) ;sentence 10 Span:1074..1244 ;Accumulation of beta-catenin was seen in the nucleus, cytoplasm or cell ;membrane in 15 of 38 (39%) HCC samples, and gene mutation was seen in 9 of ;38 (24%) HCC samples. ;[1090..1102]:gene-protein:"beta-catenin" ;[1174..1177]:malignancy:"HCC" ;[1232..1235]:malignancy:"HCC" (SENT (S (S (NP-SBJ-2 (NP (NN:[1074..1086] Accumulation)) (PP (IN:[1087..1089] of) (NP (NN:[1090..1102] beta-catenin)))) (VP (VBD:[1103..1106] was) (VP (VBN:[1107..1111] seen) (NP-2 (-NONE-:[1111..1111] *)) (PP-LOC (IN:[1112..1114] in) (NP (NP (DT:[1116..1119] the) (NN:[1120..1127] nucleus)) (,:[1127..1128] ,) (NP (NN:[1129..1138] cytoplasm)) (CC:[1139..1141] or) (NP (NN:[1142..1146] cell) (NN:[1147..1155] membrane)))) (PP (IN:[1156..1158] in) (NP (NP (CD:[1159..1161] 15)) (PP (IN:[1162..1164] of) (NP (CD:[1165..1167] 38) (PRN (-LRB-:[1168..1169] -LRB-) (NP (CD:[1169..1171] 39) (NN:[1171..1172] %)) (-RRB-:[1172..1173] -RRB-)) (NN:[1174..1177] HCC) (NNS:[1178..1185] samples)))))))) (,:[1185..1186] ,) (CC:[1187..1190] and) (S (NP-SBJ-1 (NN:[1191..1195] gene) (NN:[1197..1205] mutation)) (VP (VBD:[1206..1209] was) (VP (VBN:[1210..1214] seen) (NP-1 (-NONE-:[1214..1214] *)) (PP (IN:[1215..1217] in) (NP (NP (CD:[1218..1219] 9)) (PP (IN:[1220..1222] of) (NP (CD:[1223..1225] 38) (PRN (-LRB-:[1226..1227] -LRB-) (NP (CD:[1227..1229] 24) (NN:[1229..1230] %)) (-RRB-:[1230..1231] -RRB-)) (NN:[1232..1235] HCC) (NNS:[1236..1243] samples)))))))) (.:[1243..1244] .))) ;sentence 11 Span:1245..1387 ;Although there was a significant correlation between accumulation and ;mutation (P<0.01), six HCCs without mutation also showed accumulation. ;[1339..1343]:malignancy:"HCCs" (SENT (S (SBAR-ADV (IN:[1245..1253] Although) (S (NP-SBJ (EX:[1254..1259] there)) (VP (VBD:[1260..1263] was) (NP-PRD (NP (DT:[1264..1265] a) (JJ:[1266..1277] significant) (NN:[1279..1290] correlation)) (PP (IN:[1291..1298] between) (NP (NN:[1299..1311] accumulation) (CC:[1312..1315] and) (NN:[1316..1324] mutation)))) (PRN (-LRB-:[1325..1326] -LRB-) (S (NP-SBJ (NN:[1326..1327] P)) (PP (SYM:[1327..1328] <) (NP (CD:[1328..1332] 0.01)))) (-RRB-:[1332..1333] -RRB-))))) (,:[1333..1334] ,) (NP-SBJ (NP (CD:[1335..1338] six) (NNS:[1339..1343] HCCs)) (PP (IN:[1344..1351] without) (NP (NN:[1353..1361] mutation)))) (ADVP (RB:[1362..1366] also)) (VP (VBD:[1367..1373] showed) (NP (NN:[1374..1386] accumulation))) (.:[1386..1387] .))) ;sentence 12 Span:1388..1562 ;Samples of early HCC showed neither accumulation nor mutation, and ;accumulation and mutation were each correlated significantly with portal ;vein tumor involvement (P<0.05). ;[1399..1408]:malignancy:"early HCC" ;[1523..1540]:malignancy:"portal vein tumor" (SENT (S (S (NP-SBJ (NP (NNS:[1388..1395] Samples)) (PP (IN:[1396..1398] of) (NP (JJ:[1399..1404] early) (NN:[1405..1408] HCC)))) (VP (VBD:[1409..1415] showed) (NP (CC:[1416..1423] neither) (NN:[1425..1437] accumulation) (CC:[1438..1441] nor) (NN:[1442..1450] mutation)))) (,:[1450..1451] ,) (CC:[1452..1455] and) (S (NP-SBJ-1 (NN:[1456..1468] accumulation) (CC:[1469..1472] and) (NN:[1473..1481] mutation)) (VP (VBD:[1482..1486] were) (ADVP (DT:[1487..1491] each)) (VP (VBN:[1492..1502] correlated) (NP-1 (-NONE-:[1502..1502] *)) (ADVP (RB:[1504..1517] significantly)) (PP-CLR (IN:[1518..1522] with) (NP (NML (JJ:[1523..1529] portal) (NN:[1530..1534] vein)) (NN:[1535..1540] tumor) (NN:[1541..1552] involvement))) (PRN (-LRB-:[1553..1554] -LRB-) (S (NP-SBJ (NN:[1554..1555] P)) (VP (SYM:[1555..1556] <) (NP (CD:[1556..1560] 0.05)))) (-RRB-:[1560..1561] -RRB-))))) (.:[1561..1562] .))) ;sentence 13 Span:1563..1934 ;The present results indicate that (1) mutation of exon 3 of the beta-catenin ;gene can lead to beta-catenin accumulation, although other mechanisms of ;accumulation may also operate in HCC, and (2) beta-catenin accumulation and ;mutation of the beta-catenin gene are not early events in ;hepatocarcinogenesis, and may be associated with the malignant progression ;of HCC. ;[1602..1610]:variation-event:"mutation" ;[1614..1620]:variation-location:"exon 3" ;[1628..1640]:gene-rna:"beta-catenin" ;[1659..1671]:gene-protein:"beta-catenin" ;[1749..1752]:malignancy:"HCC" ;[1762..1774]:gene-protein:"beta-catenin" ;[1809..1821]:gene-rna:"beta-catenin" ;[1930..1933]:malignancy:"HCC" (SENT (S (NP-SBJ (DT:[1563..1566] The) (JJ:[1567..1574] present) (NNS:[1575..1582] results)) (VP (VBP:[1584..1592] indicate) (SBAR (IN:[1593..1597] that) (S (S (LST (LS:[1598..1601] -LRB-1-RRB-)) (NP-SBJ (NP (NN:[1602..1610] mutation)) (PP (IN:[1611..1613] of) (NP (NP (NN:[1614..1618] exon) (CD:[1619..1620] 3)) (PP (IN:[1621..1623] of) (NP (DT:[1624..1627] the) (NN:[1628..1640] beta-catenin) (NN:[1641..1645] gene)))))) (VP (MD:[1646..1649] can) (VP (VB:[1650..1654] lead) (PP-CLR (TO:[1655..1657] to) (NP (NN:[1659..1671] beta-catenin) (NN:[1672..1684] accumulation))) (,:[1684..1685] ,) (SBAR-ADV (IN:[1686..1694] although) (S (NP-SBJ (NP (JJ:[1695..1700] other) (NNS:[1701..1711] mechanisms)) (PP (IN:[1712..1714] of) (NP (NN:[1715..1727] accumulation)))) (VP (MD:[1728..1731] may) (ADVP (RB:[1732..1736] also)) (VP (VB:[1738..1745] operate) (PP (IN:[1746..1748] in) (NP (NN:[1749..1752] HCC)))))))))) (,:[1752..1753] ,) (CC:[1754..1757] and) (S (LST (LS:[1758..1761] -LRB-2-RRB-)) (NP-SBJ-1 (NP (NN:[1762..1774] beta-catenin) (NN:[1775..1787] accumulation)) (CC:[1788..1791] and) (NP (NP (NN:[1792..1800] mutation)) (PP (IN:[1801..1803] of) (NP (DT:[1804..1807] the) (NN:[1809..1821] beta-catenin) (NN:[1822..1826] gene))))) (VP (VP (VBP:[1827..1830] are) (RB:[1831..1834] not) (NP-PRD (NP (JJ:[1835..1840] early) (NNS:[1841..1847] events)) (PP (IN:[1848..1850] in) (NP (NN:[1851..1871] hepatocarcinogenesis))))) (,:[1871..1872] ,) (CC:[1873..1876] and) (VP (MD:[1877..1880] may) (VP (VB:[1881..1883] be) (VP (VBN:[1885..1895] associated) (NP-1 (-NONE-:[1895..1895] *)) (PP-CLR (IN:[1896..1900] with) (NP (NP (DT:[1901..1904] the) (JJ:[1905..1914] malignant) (NN:[1915..1926] progression)) (PP (IN:[1927..1929] of) (NP (NN:[1930..1933] HCC))))))))))))) (.:[1933..1934] .))) ;section 14 Span:1938..1983 ;PMID: 10665646 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1938..1942] PMID) (::[1942..1943] :) (CD:[1944..1952] 10665646) (IN:[1953..1954] -LSB-) (NNP:[1954..1960] PubMed) (HYPH:[1961..1962] -) (JJ:[1963..1970] indexed) (IN:[1971..1974] for) (NNP:[1975..1983] MEDLINE-RSB-)))