;PMID: 1581890 ;source_file_1192.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..38] = [t:0..38] ;1)sentence:[e:43..135] = [t:43..135] ;2)section:[e:139..208] = [t:139..208] ;3)section:[e:212..288] = [t:212..288] ;4)sentence:[e:292..528] = [t:292..528] ;5)sentence:[e:529..707] = [t:529..707] ;6)sentence:[e:708..876] = [t:708..876] ;7)sentence:[e:877..954] = [t:877..954] ;8)sentence:[e:955..1141] = [t:955..1141] ;9)sentence:[e:1142..1240] = [t:1142..1240] ;10)sentence:[e:1241..1395] = [t:1241..1395] ;11)sentence:[e:1396..1604] = [t:1396..1604] ;12)sentence:[e:1606..1769] = [t:1606..1769] ;13)section:[e:1773..1817] = [t:1773..1817] ;section 0 Span:0..38 ;Cancer Res 1992 May 15;52(10):2777-81 (SEC (FRAG (NN:[0..6] Cancer) (NNP:[7..10] Res) (CC:[12..16] 1992) (NNP:[17..20] May) (CD:[21..27] 15;52-LRB-) (CD:[27..29] 10) (-RRB-:[29..30] -RRB-) (CD:[30..35] :2777) (CC:[35..36] -) (CD:[36..38] 81))) ;sentence 1 Span:43..135 ;Clinical implications of K-ras mutations in malignant epithelial tumors of ;the endometrium. ;[68..73]:gene-rna:"K-ras" ;[87..134]:malignancy:"malignant epithelial tumors of the endometrium" (SENT (NP-HLN (NP (JJ:[43..51] Clinical) (NNS:[52..64] implications)) (PP (IN:[65..67] of) (NP (NP (NN:[68..73] K-ras) (NNS:[74..83] mutations)) (PP (IN:[84..86] in) (NP (NP (JJ:[87..96] malignant) (JJ:[97..107] epithelial) (NNS:[108..114] tumors)) (PP (IN:[115..117] of) (NP (DT:[118..121] the) (NN:[123..134] endometrium))))))) (.:[134..135] .))) ;section 2 Span:139..208 ;Mizuuchi H, Nasim S, Kudo R, Silverberg SG, Greenhouse S, Garrett CT. (SEC (FRAG (NNP:[139..147] Mizuuchi) (NNP:[148..149] H) (,:[149..150] ,) (NNP:[151..156] Nasim) (NNP:[157..159] S,) (NNP:[160..164] Kudo) (NNP:[165..167] R,) (NNP:[168..178] Silverberg) (NNP:[179..181] SG) (,:[181..182] ,) (NNP:[183..193] Greenhouse) (NNP:[194..196] S,) (NNP:[197..204] Garrett) (NNP:[205..208] CT.))) ;section 3 Span:212..288 ;Department of Pathology, George Washington University, Washington, DC 20037. (SEC (FRAG (NNP:[212..222] Department) (IN:[223..225] of) (NNP:[226..235] Pathology) (,:[235..236] ,) (NNP:[237..243] George) (NNP:[244..254] Washington) (NNP:[255..265] University) (,:[265..266] ,) (NNP:[267..277] Washington) (,:[277..278] ,) (NNP:[279..281] DC) (CD:[282..287] 20037) (.:[287..288] .))) ;sentence 4 Span:292..528 ;Tumorigenesis in humans and experimental animals appears to involve the ;activation of ras protooncogenes for a number of organ systems and seems to ;be important to the development of the metastatic phenotype in several model ; systems. ;[379..382]:gene-rna:"ras" (SENT (S (NP-SBJ-1 (NP (NN:[292..305] Tumorigenesis)) (PP (IN:[306..308] in) (NP (NP (NNS:[309..315] humans)) (CC:[316..319] and) (NP (JJ:[320..332] experimental) (NNS:[333..340] animals))))) (VP (VP (VBZ:[341..348] appears) (S (NP-SBJ-1 (-NONE-:[348..348] *)) (VP (TO:[349..351] to) (VP (VB:[352..359] involve) (NP (NP (DT:[360..363] the) (NN:[365..375] activation)) (PP (IN:[376..378] of) (NP (NP (NN:[379..382] ras) (NNS:[383..397] protooncogenes)) (PP (IN:[398..401] for) (NP (NP (DT:[402..403] a) (NN:[404..410] number)) (PP (IN:[411..413] of) (NP (NN:[414..419] organ) (NNS:[420..427] systems)))))))))))) (CC:[428..431] and) (VP (VBZ:[432..437] seems) (S (NP-SBJ-1 (-NONE-:[437..437] *)) (VP (TO:[438..440] to) (VP (VB:[441..443] be) (ADJP-PRD (JJ:[445..454] important) (PP (TO:[455..457] to) (NP (NP (DT:[458..461] the) (NN:[462..473] development)) (PP (IN:[474..476] of) (NP (DT:[477..480] the) (JJ:[481..491] metastatic) (NN:[492..501] phenotype)))))) (PP (IN:[502..504] in) (NP (JJ:[505..512] several) (NN:[513..518] model) (NNS:[520..527] systems)))))))) (.:[527..528] .))) ;sentence 5 Span:529..707 ;Clinically, the presence of activated ras protooncogenes has been reported ;to be a negative prognostic factor in the myelodysplastic syndrome and in ;adenocarcinoma of the lung. ;[567..570]:gene-rna:"ras" ;[647..671]:malignancy:"myelodysplastic syndrome" ;[680..706]:malignancy:"adenocarcinoma of the lung" (SENT (S (ADVP (RB:[529..539] Clinically)) (,:[539..540] ,) (NP-SBJ-1 (NP (DT:[541..544] the) (NN:[545..553] presence)) (PP (IN:[554..556] of) (NP (VBN:[557..566] activated) (NN:[567..570] ras) (NNS:[571..585] protooncogenes)))) (VP (VBZ:[586..589] has) (VP (VBN:[590..594] been) (VP (VBN:[596..604] reported) (S (NP-SBJ-1 (-NONE-:[604..604] *)) (VP (TO:[605..607] to) (VP (VB:[608..610] be) (NP-PRD (DT:[611..612] a) (JJ:[613..621] negative) (JJ:[622..632] prognostic) (NN:[633..639] factor)) (PP (PP (IN:[640..642] in) (NP (DT:[643..646] the) (JJ:[647..662] myelodysplastic) (NN:[663..671] syndrome))) (CC:[672..675] and) (PP (IN:[677..679] in) (NP (NP (NN:[680..694] adenocarcinoma)) (PP (IN:[695..697] of) (NP (DT:[698..701] the) (NN:[702..706] lung)))))))))))) (.:[706..707] .))) ;sentence 6 Span:708..876 ;In the present study we examined 49 cases of endometrial carcinoma for ;mutations in the first exon of K-ras using the polymerase chain reaction and ;direct sequencing. ;[754..775]:malignancy:"endometrial carcinoma" ;[780..789]:variation-event:"mutations" ;[797..807]:variation-location:"first exon" ;[811..816]:gene-rna:"K-ras" ;[828..838]:gene-protein:"polymerase" (SENT (S (PP (IN:[708..710] In) (NP (DT:[711..714] the) (JJ:[715..722] present) (NN:[723..728] study))) (NP-SBJ (PRP:[729..731] we)) (VP (VBD:[732..740] examined) (NP (NP (CD:[741..743] 49) (NNS:[744..749] cases)) (PP (IN:[750..752] of) (NP (JJ:[754..765] endometrial) (NN:[766..775] carcinoma)))) (PP (IN:[776..779] for) (NP (NP (NNS:[780..789] mutations)) (PP (IN:[790..792] in) (NP (NP (DT:[793..796] the) (JJ:[797..802] first) (NN:[803..807] exon)) (PP (IN:[808..810] of) (NP (NN:[811..816] K-ras))))))) (S-ADV (NP-SBJ (-NONE-:[816..816] *)) (VP (VBG:[817..822] using) (NP (NP (DT:[823..826] the) (NN:[828..838] polymerase) (NN:[839..844] chain) (NN:[845..853] reaction)) (CC:[854..857] and) (NP (JJ:[858..864] direct) (NN:[865..875] sequencing)))))) (.:[875..876] .))) ;sentence 7 Span:877..954 ;Mutations in codon 12 or 13 of K-ras were detected in 6 of 49 cases ;(12.2%). ;[877..886]:variation-event:"Mutations" ;[890..898]:variation-location:"codon 12" ;[890..895]...[902..904]:variation-location:"codon"..."13" ;[909..914]:gene-rna:"K-ras" (SENT (S (NP-SBJ-2 (NP (NNS:[877..886] Mutations)) (PP (IN:[887..889] in) (NP (NP (NP (NML-1 (NN:[890..895] codon)) (CD:[896..898] 12)) (CC:[899..901] or) (NP (NML-1 (-NONE-:[901..901] *P*)) (CD:[902..904] 13))) (PP (IN:[905..907] of) (NP (NN:[909..914] K-ras)))))) (VP (VBD:[915..919] were) (VP (VBN:[920..928] detected) (NP-2 (-NONE-:[928..928] *)) (PP (IN:[929..931] in) (NP (NP (CD:[932..933] 6)) (PP (IN:[934..936] of) (NP (CD:[937..939] 49) (NNS:[940..945] cases) (PRN (-LRB-:[946..947] -LRB-) (NP (CD:[947..951] 12.2) (NN:[951..952] %)) (-RRB-:[952..953] -RRB-)))))))) (.:[953..954] .))) ;sentence 8 Span:955..1141 ;These six cases consisted of five endometrioid endometrial carcinomas, each ;of which had a mutation in codon 12, and one case of clear cell carcinoma, ;which had a mutation in codon 13. ;[990..1025]:malignancy:"endometrioid endometrial carcinomas" ;[1047..1055]:variation-event:"mutation" ;[1059..1067]:variation-location:"codon 12" ;[1086..1106]:malignancy:"clear cell carcinoma" ;[1120..1128]:variation-event:"mutation" ;[1132..1140]:variation-location:"codon 13" (SENT (S (NP-SBJ (DT:[955..960] These) (CD:[961..964] six) (NNS:[965..970] cases)) (VP (VBD:[971..980] consisted) (PP-CLR (IN:[981..983] of) (NP (NP (NP (CD:[984..988] five) (JJ:[990..1002] endometrioid) (JJ:[1003..1014] endometrial) (NNS:[1015..1025] carcinomas)) (,:[1025..1026] ,) (SBAR (WHNP-1 (NP (DT:[1027..1031] each)) (WHPP (IN:[1032..1034] of) (WHNP (WDT:[1035..1040] which)))) (S (NP-SBJ-1 (-NONE-:[1040..1040] *T*)) (VP (VBD:[1041..1044] had) (NP (NP (DT:[1045..1046] a) (NN:[1047..1055] mutation)) (PP-LOC (IN:[1056..1058] in) (NP (NN:[1059..1064] codon) (CD:[1065..1067] 12)))))))) (,:[1067..1068] ,) (CC:[1070..1073] and) (NP (NP (NP (CD:[1074..1077] one) (NN:[1078..1082] case)) (PP (IN:[1083..1085] of) (NP (JJ:[1086..1091] clear) (NN:[1092..1096] cell) (NN:[1097..1106] carcinoma)))) (,:[1106..1107] ,) (SBAR (WHNP-2 (WDT:[1108..1113] which)) (S (NP-SBJ-2 (-NONE-:[1113..1113] *T*)) (VP (VBD:[1114..1117] had) (NP (NP (DT:[1118..1119] a) (NN:[1120..1128] mutation)) (PP-LOC (IN:[1129..1131] in) (NP (NN:[1132..1137] codon) (CD:[1138..1140] 13))))))))))) (.:[1140..1141] .))) ;sentence 9 Span:1142..1240 ;In our study the presence of mutations in K-ras appeared to be an ;unfavorable prognostic factor. ;[1185..1190]:gene-rna:"K-ras" (SENT (S (PP (IN:[1142..1144] In) (NP (PRP$:[1145..1148] our) (NN:[1150..1155] study))) (NP-SBJ (NP (DT:[1156..1159] the) (NN:[1160..1168] presence)) (PP (IN:[1169..1171] of) (NP (NNS:[1172..1181] mutations))) (PP (IN:[1182..1184] in) (NP (NN:[1185..1190] K-ras)))) (VP (VBD:[1191..1199] appeared) (S (NP-SBJ (-NONE-:[1199..1199] *)) (VP (TO:[1200..1202] to) (VP (VB:[1203..1205] be) (NP-PRD (DT:[1206..1208] an) (JJ:[1209..1220] unfavorable) (JJ:[1222..1232] prognostic) (NN:[1233..1239] factor)))))) (.:[1239..1240] .))) ;sentence 10 Span:1241..1395 ;Three of six patients with the mutation died during follow-up, while only 7% ;of the 43 patients without K-ras mutations expired during this same period. ;[1272..1280]:variation-event:"mutation" ;[1346..1351]:gene-rna:"K-ras" (SENT (S (NP-SBJ (NP (CD:[1241..1246] Three)) (PP (IN:[1247..1249] of) (NP (NP (CD:[1250..1253] six) (NNS:[1254..1262] patients)) (PP (IN:[1263..1267] with) (NP (DT:[1268..1271] the) (NN:[1272..1280] mutation)))))) (VP (VBD:[1281..1285] died) (PP-TMP (IN:[1286..1292] during) (NP (VB:[1294..1300] follow) (HYPH:[1300..1301] -) (RP:[1301..1303] up))) (,:[1303..1304] ,) (SBAR-ADV (IN:[1305..1310] while) (S (NP-SBJ (NP (RB:[1311..1315] only) (CD:[1316..1317] 7) (NN:[1317..1318] %)) (PP (IN:[1319..1321] of) (NP (NP (DT:[1322..1325] the) (CD:[1326..1328] 43) (NNS:[1329..1337] patients)) (PP (IN:[1338..1345] without) (NP (NN:[1346..1351] K-ras) (NNS:[1352..1361] mutations)))))) (VP (VBD:[1362..1369] expired) (PP-TMP (IN:[1371..1377] during) (NP (DT:[1378..1382] this) (JJ:[1383..1387] same) (NN:[1388..1394] period))))))) (.:[1394..1395] .))) ;sentence 11 Span:1396..1604 ;In multivariate analysis using the Cox proportional hazard model, K-ras ;activation appeared to be an independent risk factor when compared with ;clinical stage, depth of myometrial invasion, and patient age. ;[1463..1468]:gene-rna:"K-ras" (SENT (S (PP (IN:[1396..1398] In) (NP (NP (JJ:[1399..1411] multivariate) (NN:[1412..1420] analysis)) (VP (VBG:[1421..1426] using) (NP (DT:[1427..1430] the) (NML (NNP:[1431..1434] Cox) (JJ:[1435..1447] proportional) (NN:[1449..1455] hazard)) (NN:[1456..1461] model))))) (,:[1461..1462] ,) (NP-SBJ-1 (NN:[1463..1468] K-ras) (NN:[1469..1479] activation)) (VP (VBD:[1480..1488] appeared) (S (NP-SBJ-1 (-NONE-:[1488..1488] *)) (VP (TO:[1489..1491] to) (VP (VB:[1492..1494] be) (NP-PRD (DT:[1495..1497] an) (JJ:[1498..1509] independent) (NN:[1510..1514] risk) (NN:[1515..1521] factor)) (SBAR-ADV (WHADVP-3 (WRB:[1522..1526] when)) (S (NP-SBJ-2 (-NONE-:[1526..1526] *)) (VP (VBN:[1528..1536] compared) (NP-2 (-NONE-:[1536..1536] *)) (PP-CLR (IN:[1537..1541] with) (NP (NP (JJ:[1542..1550] clinical) (NN:[1551..1556] stage)) (,:[1556..1557] ,) (NP (NP (NN:[1558..1563] depth)) (PP (IN:[1564..1566] of) (NP (JJ:[1567..1577] myometrial) (NN:[1578..1586] invasion)))) (,:[1586..1587] ,) (CC:[1588..1591] and) (NP (NN:[1592..1599] patient) (NN:[1600..1603] age)))) (ADVP-TMP-3 (-NONE-:[1603..1603] *T*))))))))) (.:[1603..1604] .))) ;sentence 12 Span:1606..1769 ;Thus, our findings support the hypothesis that K-ras protooncogene activation ; plays an important role in determining the aggressiveness of endometrial ;carcinoma. ;[1653..1658]:gene-rna:"K-ras" ;[1746..1768]:malignancy:"endometrial carcinoma" (SENT (S (ADVP (RB:[1606..1610] Thus)) (,:[1610..1611] ,) (NP-SBJ (PRP$:[1612..1615] our) (NNS:[1616..1624] findings)) (VP (VBP:[1625..1632] support) (NP (NP (DT:[1633..1636] the) (NN:[1637..1647] hypothesis)) (SBAR (IN:[1648..1652] that) (S (NP-SBJ (NN:[1653..1658] K-ras) (NN:[1659..1672] protooncogene) (NN:[1673..1683] activation)) (VP (VBZ:[1685..1690] plays) (NP (DT:[1691..1693] an) (JJ:[1694..1703] important) (NN:[1704..1708] role)) (PP (IN:[1709..1711] in) (S-NOM (NP-SBJ (-NONE-:[1711..1711] *)) (VP (VBG:[1712..1723] determining) (NP (NP (DT:[1724..1727] the) (NN:[1728..1742] aggressiveness)) (PP (IN:[1743..1745] of) (NP (JJ:[1746..1757] endometrial) (NN:[1759..1768] carcinoma)))))))))))) (.:[1768..1769] .))) ;section 13 Span:1773..1817 ;PMID: 1581890 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1773..1777] PMID) (::[1777..1778] :) (CD:[1779..1786] 1581890) (IN:[1787..1788] -LSB-) (NNP:[1788..1794] PubMed) (HYPH:[1795..1796] -) (JJ:[1797..1804] indexed) (IN:[1805..1808] for) (NNP:[1809..1817] MEDLINE-RSB-)))