;PMID: 9345343 ;source_file_1406.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..37] = [t:0..37] ;1)sentence:[e:42..203] = [t:42..203] ;2)section:[e:207..256] = [t:207..256] ;3)section:[e:260..313] = [t:260..313] ;4)sentence:[e:317..327] = [t:317..327] ;5)sentence:[e:328..487] = [t:328..487] ;6)sentence:[e:488..496] = [t:488..496] ;7)sentence:[e:497..732] = [t:497..732] ;8)sentence:[e:733..884] = [t:733..884] ;9)sentence:[e:885..1005] = [t:885..1005] ;10)sentence:[e:1006..1014] = [t:1006..1014] ;11)sentence:[e:1015..1177] = [t:1015..1177] ;12)sentence:[e:1178..1355] = [t:1178..1355] ;13)sentence:[e:1356..1459] = [t:1356..1459] ;14)sentence:[e:1460..1471] = [t:1460..1471] ;15)sentence:[e:1472..1642] = [t:1472..1642] ;16)section:[e:1646..1690] = [t:1646..1690] ;section 0 Span:0..37 ;Am J Clin Oncol 1997 Oct;20(5):527-9 (SEC (FRAG (NNP:[0..2] Am) (NNP:[3..4] J) (NN:[5..9] Clin) (IN:[10..15] Oncol) (CD:[17..21] 1997) (CD:[22..29] Oct;20-LRB-) (CD:[29..30] 5) (-RRB-:[30..31] -RRB-) (CD:[31..35] :527) (::[35..36] -) (CD:[36..37] 9))) ;sentence 1 Span:42..203 ;Irinotecan hydrochloride (CPT-11) resistance identified by K-ras mutation in ;patients with progressive colon cancer after treatment with 5-fluorouracil ;(5-FU). ;[101..106]:gene-rna:"K-ras" ;[134..158]:malignancy:"progressive colon cancer" (SENT (NP-HLN (NP (NML (NML (NN:[42..52] Irinotecan) (NN:[53..66] hydrochloride)) (NML (-LRB-:[67..68] -LRB-) (NN:[68..74] CPT-11) (-RRB-:[74..75] -RRB-))) (NN:[76..86] resistance)) (VP (VBN:[87..97] identified) (NP (-NONE-:[97..97] *)) (PP-MNR (IN:[98..100] by) (NP (NN:[101..106] K-ras) (NN:[107..115] mutation))) (PP-LOC (IN:[116..118] in) (NP (NP (NNS:[120..128] patients)) (PP (IN:[129..133] with) (NP (JJ:[134..145] progressive) (NN:[146..151] colon) (NN:[152..158] cancer))))) (PP-TMP (IN:[159..164] after) (NP (NP (NN:[165..174] treatment)) (PP (IN:[175..179] with) (NP (NP (NN:[180..194] 5-fluorouracil)) (NP (-LRB-:[196..197] -LRB-) (NN:[197..201] 5-FU) (-RRB-:[201..202] -RRB-))))))) (.:[202..203] .))) ;section 2 Span:207..256 ;Nemunaitis J, Cox J, Meyer W, Courtney A, Mues G. (SEC (FRAG (NNP:[207..217] Nemunaitis) (NNP:[218..220] J,) (NNP:[221..224] Cox) (NNP:[225..227] J,) (NNP:[228..233] Meyer) (NNP:[234..235] W) (,:[235..236] ,) (NNP:[237..245] Courtney) (NNP:[246..247] A) (,:[247..248] ,) (NNP:[249..253] Mues) (NNP:[254..256] G.))) ;section 3 Span:260..313 ;Physician Reliance Network, Inc., Dallas, Texas, USA. (SEC (FRAG (DT:[260..269] Physician) (NNP:[270..278] Reliance) (NNP:[279..286] Network) (,:[286..287] ,) (NNP:[288..292] Inc.) (,:[292..293] ,) (NNP:[294..300] Dallas) (,:[300..301] ,) (NNP:[302..307] Texas) (,:[307..308] ,) (NNP:[309..312] USA) (.:[312..313] .))) ;sentence 4 Span:317..327 ;OBJECTIVE: (SENT (NP (NN:[317..326] OBJECTIVE) (::[326..327] :))) ;sentence 5 Span:328..487 ;To determine the prognostic role of a K-ras mutation in tumor tissue of ;patients with refractory colon cancer who received irinotecan hydrochloride ;(CPT-11). ;[366..371]:gene-rna:"K-ras" ;[415..438]:malignancy:"refractory colon cancer" (SENT (S (NP-SBJ (-NONE-:[328..328] *)) (VP (TO:[328..330] To) (VP (VB:[331..340] determine) (NP (NP (DT:[341..344] the) (JJ:[345..355] prognostic) (NN:[356..360] role)) (PP (IN:[361..363] of) (NP (DT:[364..365] a) (NN:[366..371] K-ras) (NN:[372..380] mutation)))) (PP-LOC (IN:[381..383] in) (NP (NP (NN:[384..389] tumor) (NN:[390..396] tissue)) (PP (IN:[398..400] of) (NP (NP (NP (NNS:[401..409] patients)) (PP (IN:[410..414] with) (NP (JJ:[415..425] refractory) (NN:[426..431] colon) (NN:[432..438] cancer)))) (SBAR (WHNP-1 (WP:[439..442] who)) (S (NP-SBJ-1 (-NONE-:[442..442] *T*)) (VP (VBD:[443..451] received) (NP (NP (NN:[452..462] irinotecan) (NN:[463..476] hydrochloride)) (NP (-LRB-:[478..479] -LRB-) (NN:[479..485] CPT-11) (-RRB-:[485..486] -RRB-))))))))))) (.:[486..487] .)))) ;sentence 6 Span:488..496 ;METHODS: (SENT (NP (NNS:[488..495] METHODS) (::[495..496] :))) ;sentence 7 Span:497..732 ;DNA was extracted from paraffin-stored tumor tissue of 35 patients with ;progressive colon cancer failing treatment with 5-fluorouracil who ;subsequently received CPT-11 (100 mg/m2 i.v. per week x 4 weeks with 2 weeks ;off per course). ;[570..594]:malignancy:"progressive colon cancer" (SENT (S (NP-SBJ-1 (NN:[497..500] DNA)) (VP (VBD:[501..504] was) (VP (VBN:[505..514] extracted) (NP-1 (-NONE-:[514..514] *)) (PP (IN:[515..519] from) (NP (NP (ADJP (NN:[520..528] paraffin) (HYPH:[528..529] -) (VBN:[529..535] stored)) (NN:[536..541] tumor) (NN:[542..548] tissue)) (PP (IN:[549..551] of) (NP (NP (NP (NP (CD:[552..554] 35) (NNS:[556..564] patients)) (PP (IN:[565..569] with) (NP (JJ:[570..581] progressive) (NN:[582..587] colon) (NN:[588..594] cancer)))) (VP (VBG:[595..602] failing) (NP (NP (NN:[603..612] treatment)) (PP (IN:[613..617] with) (NP (NN:[618..632] 5-fluorouracil)))))) (SBAR (WHNP-2 (WP:[633..636] who)) (S (NP-SBJ-2 (-NONE-:[636..636] *T*)) (ADVP (RB:[638..650] subsequently)) (VP (VBD:[651..659] received) (NP (NN:[660..666] CPT-11)) (PRN (-LRB-:[667..668] -LRB-) (NP (NP (CD:[668..671] 100) (NN:[672..674] mg)) (PP (SYM:[674..675] /) (NP (NP (NN:[675..677] m2)) (ADVP (RB:[678..682] i.v.)))) (PP (IN:[683..686] per) (NP (NN:[687..691] week))) (PP (SYM:[692..693] x) (NP (CD:[694..695] 4) (NNS:[696..701] weeks))) (PP (IN:[702..706] with) (NP (NP (NP (CD:[707..708] 2) (NNS:[709..714] weeks)) (ADJP (IN:[715..718] off))) (PP (IN:[720..723] per) (NP (NN:[724..730] course)))))) (-RRB-:[730..731] -RRB-))))))))))) (.:[731..732] .))) ;sentence 8 Span:733..884 ;The first exon of the K-ras gene was amplified by polymerase chain reaction ;by using K-ras-specific primers followed by mutant enrichment sequencing. ;[737..747]:variation-location:"first exon" ;[755..760]:gene-rna:"K-ras" ;[783..793]:gene-protein:"polymerase" ;[819..824]:gene-rna:"K-ras" (SENT (S (NP-SBJ-1 (NP (DT:[733..736] The) (JJ:[737..742] first) (NN:[743..747] exon)) (PP (IN:[748..750] of) (NP (DT:[751..754] the) (NN:[755..760] K-ras) (NN:[761..765] gene)))) (VP (VBD:[766..769] was) (VP (VBN:[770..779] amplified) (NP-1 (-NONE-:[779..779] *)) (PP (IN:[780..782] by) (NP-LGS (NN:[783..793] polymerase) (NN:[794..799] chain) (NN:[801..809] reaction))) (PP-MNR (IN:[810..812] by) (S-NOM (NP-SBJ (-NONE-:[812..812] *)) (VP (VBG:[813..818] using) (NP (ADJP (NN:[819..824] K-ras) (HYPH:[824..825] -) (JJ:[825..833] specific)) (NNS:[834..841] primers)) (S-ADV (NP-SBJ-2 (-NONE-:[841..841] *)) (VP (VBN:[842..850] followed) (NP-2 (-NONE-:[850..850] *)) (PP (IN:[851..853] by) (NP-LGS (NN:[854..860] mutant) (NN:[861..871] enrichment) (NN:[873..883] sequencing)))))))))) (.:[883..884] .))) ;sentence 9 Span:885..1005 ;Survival differences of patients with a K-ras mutation were compared with ;those of patients with a normal K-ras status. ;[925..930]:gene-rna:"K-ras" ;[992..997]:gene-rna:"K-ras" (SENT (S (NP-SBJ-1 (NP (NN:[885..893] Survival) (NNS:[894..905] differences)) (PP (IN:[906..908] of) (NP (NP (NNS:[909..917] patients)) (PP (IN:[918..922] with) (NP (DT:[923..924] a) (NN:[925..930] K-ras) (NN:[931..939] mutation)))))) (VP (VBD:[940..944] were) (VP (VBN:[945..953] compared) (NP-1 (-NONE-:[953..953] *)) (PP-CLR (IN:[955..959] with) (NP (NP (DT:[960..965] those)) (PP (IN:[966..968] of) (NP (NP (NNS:[969..977] patients)) (PP (IN:[978..982] with) (NP (DT:[983..984] a) (JJ:[985..991] normal) (NN:[992..997] K-ras) (NN:[998..1004] status))))))))) (.:[1004..1005] .))) ;sentence 10 Span:1006..1014 ;RESULTS: (SENT (NP (NNS:[1006..1013] RESULTS) (::[1013..1014] :))) ;sentence 11 Span:1015..1177 ;A total of 21 patients had a normal K-ras sequence and 14 patients had a ;K-ras mutation [GAT, n = 7; TGT, n = 3; and GCT, AGT, GTT, GAC (codon 13), n ;= 1 each]. ;[1052..1057]:gene-rna:"K-ras" ;[1089..1094]:gene-rna:"K-ras" ;[1095..1103]:variation-event:"mutation" ;[1105..1108]:variation-state-generic:"GAT" ;[1118..1121]:variation-state-generic:"TGT" ;[1134..1137]:variation-state-generic:"GCT" ;[1139..1142]:variation-state-generic:"AGT" ;[1144..1147]:variation-state-generic:"GTT" ;[1149..1152]:variation-state-generic:"GAC" ;[1154..1162]:variation-location:"codon 13" (SENT (S (S (NP-SBJ (NP (DT:[1015..1016] A) (NN:[1017..1022] total)) (PP (IN:[1023..1025] of) (NP (CD:[1026..1028] 21) (NNS:[1030..1038] patients)))) (VP (VBD:[1039..1042] had) (NP (DT:[1043..1044] a) (JJ:[1045..1051] normal) (NN:[1052..1057] K-ras) (NN:[1058..1066] sequence)))) (CC:[1067..1070] and) (S (NP-SBJ (CD:[1071..1073] 14) (NNS:[1074..1082] patients)) (VP (VBD:[1083..1086] had) (NP (NP (DT:[1087..1088] a) (NN:[1089..1094] K-ras) (NN:[1095..1103] mutation)) (PRN (-LRB-:[1104..1105] -LSB-) (FRAG (FRAG (NP (NN:[1105..1108] GAT)) (,:[1108..1109] ,) (S (NP-SBJ (NN:[1111..1112] n)) (VP (SYM:[1113..1114] =) (NP (CD:[1115..1116] 7))))) (::[1116..1117] ;) (FRAG (NP (NN:[1118..1121] TGT)) (,:[1121..1122] ,) (S (NP-SBJ (NN:[1123..1124] n)) (VP (SYM:[1125..1126] =) (NP (CD:[1127..1128] 3))))) (::[1128..1129] ;) (CC:[1130..1133] and) (FRAG (NP (NP (NN:[1134..1137] GCT)) (,:[1137..1138] ,) (NP (NN:[1139..1142] AGT)) (,:[1142..1143] ,) (NP (NN:[1144..1147] GTT)) (,:[1147..1148] ,) (NP (NN:[1149..1152] GAC) (PRN (-LRB-:[1153..1154] -LRB-) (NP (NN:[1154..1159] codon) (CD:[1160..1162] 13)) (-RRB-:[1162..1163] -RRB-)))) (,:[1163..1164] ,) (S (NP-SBJ (NN:[1165..1166] n)) (VP (SYM:[1167..1168] =) (NP (NP (CD:[1169..1170] 1)) (ADVP (DT:[1171..1175] each))))))) (-RRB-:[1175..1176] -RSB-))))) (.:[1176..1177] .))) ;sentence 12 Span:1178..1355 ;Median survival of patients with a normal ras sequence from time of ;treatment with CPT-11 was 332 days compared with 169 days for patients with ;a K-ras mutation (p = 0.0036). ;[1221..1224]:gene-rna:"ras" ;[1326..1331]:gene-rna:"K-ras" (SENT (S (NP-SBJ (NP (JJ:[1178..1184] Median) (NN:[1186..1194] survival)) (PP (IN:[1195..1197] of) (NP (NP (NNS:[1198..1206] patients)) (PP (IN:[1207..1211] with) (NP (DT:[1212..1213] a) (JJ:[1214..1220] normal) (NN:[1221..1224] ras) (NN:[1225..1233] sequence))))) (PP (IN:[1234..1238] from) (NP (NP (NN:[1239..1243] time)) (PP (IN:[1244..1246] of) (NP (NP (NN:[1247..1256] treatment)) (PP (IN:[1257..1261] with) (NP (NN:[1263..1269] CPT-11)))))))) (VP (VBD:[1270..1273] was) (NP-PRD (CD:[1274..1277] 332) (NNS:[1278..1282] days)) (S-ADV (NP-SBJ-1 (-NONE-:[1282..1282] *)) (VP (VBN:[1283..1291] compared) (NP-1 (-NONE-:[1291..1291] *)) (PP-CLR (IN:[1292..1296] with) (NP (NP (CD:[1297..1300] 169) (NNS:[1301..1305] days)) (PP (IN:[1306..1309] for) (NP (NP (NNS:[1310..1318] patients)) (PP (IN:[1319..1323] with) (NP (DT:[1324..1325] a) (NN:[1326..1331] K-ras) (NN:[1332..1340] mutation))))))) (PRN (-LRB-:[1341..1342] -LRB-) (S (NP-SBJ (NN:[1342..1343] p)) (VP (SYM:[1345..1346] =) (NP (CD:[1347..1353] 0.0036)))) (-RRB-:[1353..1354] -RRB-))))) (.:[1354..1355] .))) ;sentence 13 Span:1356..1459 ;No differences in age, sex, cancer stage, surgical treatment, or ;chemotherapy treatment were observed. (SENT (S (NP-SBJ-1 (NP (DT:[1356..1358] No) (NNS:[1359..1370] differences)) (PP (IN:[1371..1373] in) (NP (NP (NN:[1374..1377] age)) (,:[1377..1378] ,) (NP (NN:[1379..1382] sex)) (,:[1382..1383] ,) (NP (NN:[1384..1390] cancer) (NN:[1391..1396] stage)) (,:[1396..1397] ,) (NP (JJ:[1398..1406] surgical) (NN:[1407..1416] treatment)) (,:[1416..1417] ,) (CC:[1418..1420] or) (NP (NN:[1422..1434] chemotherapy) (NN:[1435..1444] treatment))))) (VP (VBD:[1445..1449] were) (VP (VBN:[1450..1458] observed) (NP-1 (-NONE-:[1458..1458] *)))) (.:[1458..1459] .))) ;sentence 14 Span:1460..1471 ;CONCLUSION: (SENT (NP (NN:[1460..1470] CONCLUSION) (::[1470..1471] :))) ;sentence 15 Span:1472..1642 ;Determination of the presence of a K-ras mutation may predict survival in ;patients with progressive colon cancer after treatment with 5-fluorouracil ;who receive CPT-11. ;[1508..1513]:gene-rna:"K-ras" ;[1561..1586]:malignancy:"progressive colon cancer" (SENT (S (NP-SBJ (NP (NN:[1472..1485] Determination)) (PP (IN:[1486..1488] of) (NP (NP (DT:[1489..1492] the) (NN:[1493..1501] presence)) (PP (IN:[1503..1505] of) (NP (DT:[1506..1507] a) (NN:[1508..1513] K-ras) (NN:[1514..1522] mutation)))))) (VP (MD:[1523..1526] may) (VP (VB:[1527..1534] predict) (NP (NN:[1535..1543] survival)) (PP-LOC (IN:[1544..1546] in) (NP (NP (NP (NNS:[1547..1555] patients)) (PP (IN:[1556..1560] with) (NP (NP (JJ:[1561..1572] progressive) (NN:[1573..1578] colon) (NN:[1580..1586] cancer)) (PP-TMP (IN:[1587..1592] after) (NP (NP (NN:[1593..1602] treatment)) (PP (IN:[1603..1607] with) (NP (NN:[1608..1622] 5-fluorouracil)))))))) (SBAR (WHNP-1 (WP:[1623..1626] who)) (S (NP-SBJ-1 (-NONE-:[1626..1626] *T*)) (VP (VBP:[1627..1634] receive) (NP (NN:[1635..1641] CPT-11))))))))) (.:[1641..1642] .))) ;section 16 Span:1646..1690 ;PMID: 9345343 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1646..1650] PMID) (::[1650..1651] :) (CD:[1652..1659] 9345343) (IN:[1660..1661] -LSB-) (NNP:[1661..1667] PubMed) (HYPH:[1668..1669] -) (JJ:[1670..1677] indexed) (IN:[1678..1681] for) (NNP:[1682..1690] MEDLINE-RSB-)))