;PMID: 7576742 ;source_file_1179.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..29] = [t:0..29] ;1)sentence:[e:34..151] = [t:34..151] ;2)section:[e:155..227] = [t:155..227] ;3)section:[e:231..308] = [t:231..308] ;4)sentence:[e:312..477] = [t:312..477] ;5)sentence:[e:478..661] = [t:478..661] ;6)sentence:[e:662..784] = [t:662..784] ;7)sentence:[e:785..917] = [t:785..917] ;8)sentence:[e:918..1116] = [t:918..1116] ;9)sentence:[e:1117..1270] = [t:1117..1270] ;10)sentence:[e:1271..1376] = [t:1271..1376] ;11)sentence:[e:1377..1446] = [t:1377..1446] ;12)sentence:[e:1447..1744] = [t:1447..1744] ;13)section:[e:1748..1792] = [t:1748..1792] ;section 0 Span:0..29 ;Acta Oncol 1995;34(6):759-65 (SEC (FRAG (IN:[0..4] Acta) (NNP:[5..10] Oncol) (CD:[12..16] 1995) (.:[16..20] ;34-LRB-) (CD:[20..22] 6-RRB-) (CD:[22..26] :759) (HYPH:[26..27] -) (CD:[27..29] 65))) ;sentence 1 Span:34..151 ;Glutathione transferase P1-1 expression in human melanoma metastases: ;correlation to N-RAS mutations and expression. ;[34..62]:gene-protein:"Glutathione transferase P1-1" ;[83..102]:malignancy:"melanoma metastases" ;[120..125]:gene-rna:"N-RAS" (SENT (NP-HLN (NP (NP (NML (NML (NN:[34..45] Glutathione) (NN:[46..57] transferase)) (NN:[58..62] P1-1)) (NN:[63..73] expression)) (PP-LOC (IN:[74..76] in) (NP (JJ:[77..82] human) (NN:[83..91] melanoma) (NNS:[92..102] metastases)))) (::[102..103] :) (NP (NP (NN:[105..116] correlation)) (PP (TO:[117..119] to) (NP (NP (NML-1 (NN:[120..125] N-RAS)) (NNS:[126..135] mutations)) (CC:[136..139] and) (NP (NML-1 (-NONE-:[139..139] *P*)) (NN:[140..150] expression))))) (.:[150..151] .))) ;section 2 Span:155..227 ;Platz A, Jungnelius U, Grafstrom E, Lagerlof B, Mannervik B, Ringborg U. (SEC (FRAG (NNP:[155..160] Platz) (NNP:[161..162] A) (,:[162..163] ,) (NNP:[164..174] Jungnelius) (NNP:[175..176] U) (,:[176..177] ,) (NNP:[178..187] Grafstrom) (NNP:[188..189] E) (,:[189..190] ,) (NNP:[191..199] Lagerlof) (NNP:[200..201] B) (,:[201..202] ,) (NNP:[203..212] Mannervik) (NNP:[213..214] B) (,:[214..215] ,) (NNP:[216..224] Ringborg) (NNP:[225..227] U.))) ;section 3 Span:231..308 ;Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, ;Sweden. (SEC (FRAG (NNP:[231..241] Department) (IN:[242..244] of) (NNP:[245..253] Oncology) (,:[253..254] ,) (NNP:[255..267] Radiumhemmet) (,:[267..268] ,) (NNP:[269..279] Karolinska) (NNP:[280..288] Hospital) (,:[288..289] ,) (NNP:[290..299] Stockholm) (,:[299..300] ,) (NNP:[301..307] Sweden) (.:[307..308] .))) ;sentence 4 Span:312..477 ;Expression of the detoxication enzyme glutathione transferase P1-1 (GST P1-1) ;at elevated levels has been noted in many types of human tumors, including ;melanomas. ;[350..378]:gene-protein:"glutathione transferase P1-1" ;[380..388]:gene-protein:"GST P1-1" ;[467..476]:malignancy:"melanomas" (SENT (S (NP-SBJ-1 (NP (NN:[312..322] Expression)) (PP (IN:[323..325] of) (NP (NP (DT:[326..329] the) (NN:[330..342] detoxication) (NN:[343..349] enzyme)) (NP (NP (NML (NN:[350..361] glutathione) (NN:[362..373] transferase)) (NN:[374..378] P1-1)) (NP (-LRB-:[379..380] -LRB-) (NN:[380..383] GST) (NN:[384..388] P1-1) (-RRB-:[388..389] -RRB-))))) (PP (IN:[390..392] at) (NP (VBN:[394..402] elevated) (NNS:[403..409] levels)))) (VP (VBZ:[410..413] has) (VP (VBN:[414..418] been) (VP (VBN:[419..424] noted) (NP-1 (-NONE-:[424..424] *)) (PP-LOC (IN:[425..427] in) (NP (NP (JJ:[428..432] many) (NNS:[433..438] types)) (PP (IN:[439..441] of) (NP (NP (JJ:[442..447] human) (NNS:[448..454] tumors)) (,:[454..455] ,) (PP (VBG:[456..465] including) (NP (NNS:[467..476] melanomas)))))))))) (.:[476..477] .))) ;sentence 5 Span:478..661 ;The products of the human H-RAS, K-RAS and N-RAS genes play a key role in ;intracellular signal transduction leading to transcriptional activation of ;AP-1 (Fos/Jun) responsive genes. ;[504..509]:gene-rna:"H-RAS" ;[511..516]:gene-rna:"K-RAS" ;[521..526]:gene-rna:"N-RAS" ;[629..633]:gene-rna:"AP-1" ;[635..638]:gene-rna:"Fos" ;[639..642]:gene-rna:"Jun" (SENT (S (NP-SBJ (NP (DT:[478..481] The) (NNS:[482..490] products)) (PP (IN:[491..493] of) (NP (DT:[494..497] the) (NML (NML (ADJP-1 (JJ:[498..503] human)) (NN:[504..509] H-RAS) (NML-2 (-NONE-:[509..509] *P*))) (,:[509..510] ,) (NML (ADJP-1 (-NONE-:[510..510] *P*)) (NN:[511..516] K-RAS) (NML-2 (-NONE-:[516..516] *P*))) (CC:[517..520] and) (NML (ADJP-1 (-NONE-:[520..520] *P*)) (NN:[521..526] N-RAS) (NML-2 (NNS:[527..532] genes))))))) (VP (VBP:[533..537] play) (NP (DT:[538..539] a) (JJ:[540..543] key) (NN:[545..549] role)) (PP (IN:[550..552] in) (S-NOM (NP-SBJ (JJ:[553..566] intracellular) (NN:[567..573] signal) (NN:[574..586] transduction)) (VP (VBG:[587..594] leading) (PP-CLR (TO:[595..597] to) (NP (NP (JJ:[598..613] transcriptional) (NN:[614..624] activation)) (PP (IN:[626..628] of) (NP (ADJP (NN:[629..633] AP-1) (PRN (-LRB-:[634..635] -LRB-) (NP (NN:[635..638] Fos) (SYM:[638..639] /) (NN:[639..642] Jun)) (-RRB-:[642..643] -RRB-)) (JJ:[644..654] responsive)) (NNS:[655..660] genes))))))))) (.:[660..661] .))) ;sentence 6 Span:662..784 ;The oncogenic mutated forms of the ras proteins are constitutively active ;and interfere with normal signal transduction. ;[697..700]:gene-protein:"ras" (SENT (S (NP-SBJ (NP (DT:[662..665] The) (JJ:[666..675] oncogenic) (VBN:[676..683] mutated) (NNS:[684..689] forms)) (PP (IN:[690..692] of) (NP (DT:[693..696] the) (NN:[697..700] ras) (NNS:[702..710] proteins)))) (VP (VP (VBP:[711..714] are) (ADJP-PRD (RB:[715..729] constitutively) (JJ:[730..736] active))) (CC:[737..740] and) (VP (VBP:[741..750] interfere) (PP-CLR (IN:[751..755] with) (NP (JJ:[756..762] normal) (NN:[763..769] signal) (NN:[771..783] transduction))))) (.:[783..784] .))) ;sentence 7 Span:785..917 ;Mutated RAS genes as well as increased expression of wild-type ras proteins ;are common features in human tumors including melanoma. ;[793..796]:gene-rna:"RAS" ;[848..851]:gene-protein:"ras" ;[908..916]:malignancy:"melanoma" (SENT (S (NP-SBJ (NP (VBN:[785..792] Mutated) (NN:[793..796] RAS) (NNS:[797..802] genes)) (CONJP (RB:[803..805] as) (RB:[806..810] well) (IN:[811..813] as)) (NP (NP (VBN:[814..823] increased) (NN:[824..834] expression)) (PP (IN:[835..837] of) (NP (NML (JJ:[838..842] wild) (HYPH:[842..843] -) (NN:[843..847] type)) (NN:[848..851] ras) (NNS:[853..861] proteins))))) (VP (VBP:[862..865] are) (NP-PRD (JJ:[866..872] common) (NNS:[873..881] features)) (PP-LOC (IN:[882..884] in) (NP (NP (JJ:[885..890] human) (NNS:[891..897] tumors)) (PP (VBG:[898..907] including) (NP (NN:[908..916] melanoma)))))) (.:[916..917] .))) ;sentence 8 Span:918..1116 ;We have characterized 30 melanoma metastases from 23 melanoma patients with ;reference to N-RAS expression and mutation as well as to GST P1 expression ;(immunohistochemistry and genetic analysis). ;[944..963]:malignancy:"melanoma metastases" ;[972..980]:malignancy:"melanoma" ;[1009..1014]:gene-generic:"N-RAS" ;[1053..1059]:gene-protein:"GST P1" (SENT (S (NP-SBJ (PRP:[918..920] We)) (VP (VBP:[921..925] have) (VP (VBN:[927..940] characterized) (NP (NP (CD:[941..943] 30) (NN:[944..952] melanoma) (NNS:[953..963] metastases)) (PP (IN:[964..968] from) (NP (CD:[969..971] 23) (NN:[972..980] melanoma) (NNS:[981..989] patients))) (PP (IN:[990..994] with) (NP (NP (NN:[995..1004] reference)) (PP (PP (TO:[1005..1007] to) (NP (NP (NML-1 (NN:[1009..1014] N-RAS)) (NN:[1015..1025] expression)) (CC:[1026..1029] and) (NP (NML-1 (-NONE-:[1029..1029] *P*)) (NN:[1030..1038] mutation)))) (CONJP (RB:[1039..1041] as) (RB:[1042..1046] well) (IN:[1047..1049] as)) (PP (TO:[1050..1052] to) (NP (NML (NN:[1053..1056] GST) (NN:[1057..1059] P1)) (NN:[1060..1070] expression)))))) (PRN (-LRB-:[1072..1073] -LRB-) (NP (NP (NN:[1073..1093] immunohistochemistry)) (CC:[1094..1097] and) (NP (JJ:[1098..1105] genetic) (NN:[1106..1114] analysis))) (-RRB-:[1114..1115] -RRB-))))) (.:[1115..1116] .))) ;sentence 9 Span:1117..1270 ;Twenty-three of 30 samples (70%) had high N-Ras p21 and/or N-RAS codon 61 ;mutations and 18 of these 23 samples also had high GST P1-1 ;immunoreactivity. ;[1160..1169]:gene-protein:"N-Ras p21" ;[1177..1182]:gene-rna:"N-RAS" ;[1183..1191]:variation-location:"codon 61" ;[1192..1201]:variation-event:"mutations" ;[1244..1252]:gene-protein:"GST P1-1" (SENT (S (S (NP-SBJ (NP (CD:[1117..1129] Twenty-three)) (PP (IN:[1130..1132] of) (NP (CD:[1133..1135] 30) (NNS:[1136..1143] samples))) (PRN (-LRB-:[1144..1145] -LRB-) (NP (CD:[1145..1147] 70) (NN:[1147..1148] %)) (-RRB-:[1148..1149] -RRB-))) (VP (VBD:[1151..1154] had) (NP (NP (ADJP-2 (JJ:[1155..1159] high)) (NML (NN:[1160..1165] N-Ras) (NN:[1166..1169] p21)) (NML-1 (-NONE-:[1169..1169] *P*))) (CC:[1170..1176] and/or) (NP (ADJP-2 (-NONE-:[1176..1176] *P*)) (NML (NN:[1177..1182] N-RAS) (NN:[1183..1188] codon) (CD:[1189..1191] 61)) (NML-1 (NNS:[1192..1201] mutations)))))) (CC:[1202..1205] and) (S (NP-SBJ (NP (CD:[1206..1208] 18)) (PP (IN:[1209..1211] of) (NP (DT:[1212..1217] these) (CD:[1218..1220] 23) (NNS:[1221..1228] samples)))) (ADVP (RB:[1230..1234] also)) (VP (VBD:[1235..1238] had) (NP (JJ:[1239..1243] high) (NML (NN:[1244..1247] GST) (NN:[1248..1252] P1-1)) (NN:[1253..1269] immunoreactivity)))) (.:[1269..1270] .))) ;sentence 10 Span:1271..1376 ;Seven of 30 (23%) samples had low N-Ras p21 immunoreactivity and no ;detectable N-RAS codon 61 mutations. ;[1305..1315]:gene-protein:"N-Ras p21" ;[1351..1356]:gene-rna:"N-RAS" ;[1357..1365]:variation-location:"codon 61" ;[1366..1375]:variation-event:"mutations" (SENT (S (NP-SBJ (NP (CD:[1271..1276] Seven)) (PP (IN:[1277..1279] of) (NP (CD:[1280..1282] 30) (PRN (-LRB-:[1283..1284] -LRB-) (NP (CD:[1284..1286] 23) (NN:[1286..1287] %)) (-RRB-:[1287..1288] -RRB-)) (NNS:[1289..1296] samples)))) (VP (VBD:[1297..1300] had) (NP (NP (JJ:[1301..1304] low) (NML (NN:[1305..1310] N-Ras) (NN:[1312..1315] p21)) (NN:[1316..1332] immunoreactivity)) (CC:[1333..1336] and) (NP (DT:[1337..1339] no) (JJ:[1340..1350] detectable) (NML (NN:[1351..1356] N-RAS) (NN:[1357..1362] codon) (CD:[1363..1365] 61)) (NNS:[1366..1375] mutations)))) (.:[1375..1376] .))) ;sentence 11 Span:1377..1446 ;Six of these 7 samples (86%) also had low GST P1-1 immunoreactivity. ;[1420..1428]:gene-protein:"GST P1-1" (SENT (S (NP-SBJ (NP (CD:[1377..1380] Six)) (PP (IN:[1381..1383] of) (NP (DT:[1384..1389] these) (CD:[1390..1391] 7) (NNS:[1393..1400] samples))) (PRN (-LRB-:[1401..1402] -LRB-) (NP (CD:[1402..1404] 86) (NN:[1404..1405] %)) (-RRB-:[1405..1406] -RRB-))) (VP (ADVP (RB:[1407..1411] also)) (VBD:[1412..1415] had) (NP (JJ:[1416..1419] low) (NML (NN:[1420..1423] GST) (NN:[1424..1428] P1-1)) (NN:[1429..1445] immunoreactivity))) (.:[1445..1446] .))) ;sentence 12 Span:1447..1744 ;The results indicate a statistically significant correlation (Spearman ;correlation coefficient, r = 0.56, p = 0.001, 2-tailed test) and provide, ;for the first time, indirect evidence for a possible coregulation of N-RAS ;and GST P1 in human malignant melanoma which should be further evaluated. ;[1664..1669]:gene-rna:"N-RAS" ;[1674..1680]:gene-protein:"GST P1" ;[1690..1709]:malignancy:"malignant melanoma" (SENT (S (NP-SBJ (DT:[1447..1450] The) (NNS:[1451..1458] results)) (VP (VP (VBP:[1459..1467] indicate) (NP (DT:[1468..1469] a) (ADJP (RB:[1471..1484] statistically) (JJ:[1485..1496] significant)) (NN:[1497..1508] correlation)) (PRN (-LRB-:[1509..1510] -LRB-) (FRAG (FRAG (NP (NNP:[1510..1518] Spearman) (NN:[1519..1530] correlation) (NN:[1531..1542] coefficient)) (,:[1542..1543] ,) (S (NP-SBJ (NN:[1544..1545] r)) (VP (SYM:[1546..1547] =) (NP (CD:[1549..1553] 0.56))))) (,:[1553..1554] ,) (FRAG (S (NP-SBJ (NN:[1555..1556] p)) (VP (SYM:[1557..1558] =) (NP (CD:[1559..1564] 0.001)))) (,:[1564..1565] ,) (NP (NML (CD:[1566..1567] 2) (HYPH:[1567..1568] -) (JJ:[1568..1574] tailed)) (NN:[1575..1579] test)))) (-RRB-:[1579..1580] -RRB-))) (CC:[1581..1584] and) (VP (VBP:[1585..1592] provide) (,:[1592..1593] ,) (PP (IN:[1594..1597] for) (NP (DT:[1598..1601] the) (JJ:[1602..1607] first) (NN:[1608..1612] time))) (,:[1612..1613] ,) (NP (NP (JJ:[1614..1622] indirect) (NN:[1624..1632] evidence)) (PP (IN:[1633..1636] for) (NP (NP (DT:[1637..1638] a) (JJ:[1639..1647] possible) (NN:[1648..1660] coregulation)) (PP (IN:[1661..1663] of) (NP (NP (NN:[1664..1669] N-RAS)) (CC:[1670..1673] and) (NP (NN:[1674..1677] GST) (NN:[1678..1680] P1)))) (PP (IN:[1681..1683] in) (NP (NP (JJ:[1684..1689] human) (JJ:[1690..1699] malignant) (NN:[1701..1709] melanoma)) (SBAR (WHNP-1 (WDT:[1710..1715] which)) (S (NP-SBJ-1 (-NONE-:[1715..1715] *T*)) (VP (MD:[1716..1722] should) (VP (VB:[1723..1725] be) (ADVP (RBR:[1726..1733] further)) (VP (VBN:[1734..1743] evaluated) (NP-1 (-NONE-:[1743..1743] *)))))))))))))) (.:[1743..1744] .))) ;section 13 Span:1748..1792 ;PMID: 7576742 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1748..1752] PMID) (::[1752..1753] :) (CD:[1754..1761] 7576742) (IN:[1762..1763] -LSB-) (NNP:[1763..1769] PubMed) (HYPH:[1770..1771] -) (JJ:[1772..1779] indexed) (IN:[1780..1783] for) (NNP:[1784..1792] MEDLINE-RSB-)))