;PMID: 9777951 ;source_file_1394.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..35] = [t:0..35] ;1)sentence:[e:40..185] = [t:40..185] ;2)section:[e:189..261] = [t:189..261] ;3)section:[e:265..407] = [t:265..407] ;4)sentence:[e:411..589] = [t:411..589] ;5)sentence:[e:590..734] = [t:590..734] ;6)sentence:[e:735..796] = [t:735..796] ;7)sentence:[e:797..889] = [t:797..889] ;8)sentence:[e:890..981] = [t:890..981] ;9)sentence:[e:982..1161] = [t:982..1161] ;10)sentence:[e:1162..1312] = [t:1162..1312] ;11)sentence:[e:1313..1394] = [t:1313..1394] ;12)sentence:[e:1395..1472] = [t:1395..1472] ;13)sentence:[e:1473..1540] = [t:1473..1540] ;14)sentence:[e:1541..1621] = [t:1541..1621] ;15)sentence:[e:1622..1774] = [t:1622..1774] ;16)sentence:[e:1775..1997] = [t:1775..1997] ;17)section:[e:2001..2045] = [t:2001..2045] ;section 0 Span:0..35 ;Am J Pathol 1998 Oct;153(4):1201-9 (SEC (FRAG (NNP:[0..2] Am) (NNP:[3..4] J) (NNP:[5..11] Pathol) (CD:[13..17] 1998) (.:[18..26] Oct;153-LRB-) (CD:[26..28] 4-RRB-) (CD:[28..33] :1201) (HYPH:[33..34] -) (CD:[34..35] 9))) ;sentence 1 Span:40..185 ;Specific K-ras2 mutations in human sporadic colorectal adenomas are ;associated with DNA near-diploid aneuploidy and inhibition of ;proliferation. ;[49..55]:gene-rna:"K-ras2" ;[75..103]:malignancy:"sporadic colorectal adenomas" ;[125..152]:variation-type:"DNA near-diploid aneuploidy" (SENT (S-HLN (NP-SBJ-1 (NP (JJ:[40..48] Specific) (NN:[49..55] K-ras2) (NNS:[56..65] mutations)) (PP-LOC (IN:[66..68] in) (NP (JJ:[69..74] human) (JJ:[75..83] sporadic) (JJ:[84..94] colorectal) (NNS:[95..103] adenomas)))) (VP (VBP:[104..107] are) (VP (VBN:[108..118] associated) (NP-1 (-NONE-:[118..118] *)) (PP-CLR (IN:[120..124] with) (NP (NP (NN:[125..128] DNA) (ADJP (JJ:[129..133] near) (HYPH:[133..134] -) (JJ:[134..141] diploid)) (NN:[142..152] aneuploidy)) (CC:[153..156] and) (NP (NP (NN:[157..167] inhibition)) (PP (IN:[168..170] of) (NP (NN:[171..184] proliferation)))))))) (.:[184..185] .))) ;section 2 Span:189..261 ;Giaretti W, Rapallo A, Geido E, Sciutto A, Merlo F, Risio M, Rossini FP. (SEC (FRAG (NNP:[189..197] Giaretti) (NNP:[198..199] W) (,:[199..200] ,) (NNP:[201..208] Rapallo) (NNP:[209..210] A) (,:[210..211] ,) (NNP:[212..217] Geido) (NNP:[218..219] E) (,:[219..220] ,) (NNP:[221..228] Sciutto) (NNP:[229..230] A) (,:[230..231] ,) (NNP:[232..237] Merlo) (NNP:[238..239] F) (,:[239..240] ,) (DT:[241..246] Risio) (NNP:[247..249] M,) (NNP:[250..257] Rossini) (NNP:[258..260] FP) (.:[260..261] .))) ;section 3 Span:265..407 ;Laboratory of Biophysics-Cytometry, National Institute for Cancer Research ;and Treatment, Candiolo, Genoa, Italy. giaretti@hp380.ist.unige.it (SEC (FRAG (NN:[265..275] Laboratory) (IN:[276..278] of) (NNP:[279..289] Biophysics) (HYPH:[289..290] -) (NNP:[290..299] Cytometry) (,:[299..300] ,) (NNP:[301..309] National) (NNP:[310..319] Institute) (IN:[320..323] for) (NNP:[324..330] Cancer) (NNP:[331..339] Research) (CC:[340..343] and) (NNP:[345..354] Treatment) (,:[354..355] ,) (NNP:[356..364] Candiolo) (,:[364..365] ,) (NNP:[366..371] Genoa) (,:[371..372] ,) (NNP:[373..378] Italy) (.:[378..379] .) ('':[380..398] giaretti@hp380.ist) (VBD:[398..404] .unige) (.:[404..407] .it))) ;sentence 4 Span:411..589 ;Recent studies indicate that p21ras proteins mediate their multiple cell ;functions through interactions with multiple effectors and that the number of ; new effectors is growing. ;[440..446]:gene-protein:"p21ras" (SENT (S (NP-SBJ (JJ:[411..417] Recent) (NNS:[418..425] studies)) (VP (VBP:[426..434] indicate) (SBAR (SBAR (IN:[435..439] that) (S (NP-SBJ (NN:[440..446] p21ras) (NNS:[447..455] proteins)) (VP (VBP:[456..463] mediate) (NP (PRP$:[464..469] their) (JJ:[470..478] multiple) (NN:[479..483] cell) (NNS:[485..494] functions)) (PP (IN:[495..502] through) (NP (NP (NNS:[503..515] interactions)) (PP (IN:[516..520] with) (NP (JJ:[521..529] multiple) (NNS:[530..539] effectors)))))))) (CC:[540..543] and) (SBAR (IN:[544..548] that) (S (NP-SBJ (NP (DT:[549..552] the) (NN:[553..559] number)) (PP (IN:[560..562] of) (NP (JJ:[564..567] new) (NNS:[568..577] effectors)))) (VP (VBZ:[578..580] is) (VP (VBG:[581..588] growing))))))) (.:[588..589] .))) ;sentence 5 Span:590..734 ;We recently reported that K-ras2 mutations in human colorectal adenomas were ;associated with chromosome instability and proliferation changes. ;[616..622]:gene-rna:"K-ras2" ;[643..662]:malignancy:"colorectal adenomas" (SENT (S (NP-SBJ (PRP:[590..592] We)) (ADVP-TMP (RB:[593..601] recently)) (VP (VBD:[602..610] reported) (SBAR (IN:[611..615] that) (S (NP-SBJ-1 (NP (NN:[616..622] K-ras2) (NNS:[623..632] mutations)) (PP-LOC (IN:[633..635] in) (NP (JJ:[636..641] human) (JJ:[643..653] colorectal) (NNS:[654..662] adenomas)))) (VP (VBD:[663..667] were) (VP (VBN:[668..678] associated) (NP-1 (-NONE-:[678..678] *)) (PP-CLR (IN:[679..683] with) (NP (NP (NN:[684..694] chromosome) (NN:[695..706] instability)) (CC:[707..710] and) (NP (NN:[712..725] proliferation) (NNS:[726..733] changes))))))))) (.:[733..734] .))) ;sentence 6 Span:735..796 ;In the present study, we extend these previous observations. (SENT (S (PP (IN:[735..737] In) (NP (DT:[738..741] the) (JJ:[742..749] present) (NN:[750..755] study))) (,:[755..756] ,) (NP-SBJ (PRP:[757..759] we)) (VP (VBP:[760..766] extend) (NP (DT:[767..772] these) (JJ:[773..781] previous) (NNS:[783..795] observations))) (.:[795..796] .))) ;sentence 7 Span:797..889 ;Hereditary and multiple (n > or = 5) adenomas and adenomas with early cancer ;were excluded. ;[797..807]...[834..842]:malignancy:"Hereditary"..."adenomas" ;[812..842]:malignancy:"multiple (n > or = 5) adenomas" ;[847..874]:malignancy:"adenomas with early cancer" (SENT (S (NP-SBJ-2 (NP (NP (JJ:[797..807] Hereditary) (NML-1 (-NONE-:[807..807] *P*))) (CC:[808..811] and) (NP (JJ:[812..820] multiple) (PRN (-LRB-:[821..822] -LRB-) (S (NP-SBJ (NN:[822..823] n)) (VP (SYM:[824..825] >) (CC:[826..828] or) (SYM:[829..830] =) (NP (CD:[831..832] 5)))) (-RRB-:[832..833] -RRB-)) (NML-1 (NNS:[834..842] adenomas)))) (CC:[843..846] and) (NP (NP (NNS:[847..855] adenomas)) (PP (IN:[856..860] with) (NP (JJ:[862..867] early) (NN:[868..874] cancer))))) (VP (VBD:[875..879] were) (VP (VBN:[880..888] excluded) (NP-2 (-NONE-:[888..888] *)))) (.:[888..889] .))) ;sentence 8 Span:890..981 ;Dysplasia was moderate in 91 cases and high in 25, and the median adenoma ;size was 1.5 cm. ;[890..899]:malignancy:"Dysplasia" ;[957..964]:malignancy:"adenoma" (SENT (S (S (NP-SBJ (NN:[890..899] Dysplasia)) (VP (VBD:[900..903] was) (ADJP-PRD (ADJP (JJ:[904..912] moderate) (PP (IN:[913..915] in) (NP (CD:[916..918] 91) (NNS:[919..924] cases)))) (CC:[925..928] and) (ADJP (JJ:[929..933] high) (PP (IN:[934..936] in) (NP (CD:[937..939] 25))))))) (,:[939..940] ,) (CC:[942..945] and) (S (NP-SBJ (DT:[946..949] the) (JJ:[950..956] median) (NN:[957..964] adenoma) (NN:[965..969] size)) (VP (VBD:[970..973] was) (NP-PRD (CD:[974..977] 1.5) (NN:[978..980] cm)))) (.:[980..981] .))) ;sentence 9 Span:982..1161 ;K-ras2 spectrum analysis was done by sequence-specific oligonucleotide ;hybridization using nuclear suspensions provided by analysis and sorting of ;multiparameter flow cytometry. ;[982..988]:gene-rna:"K-ras2" (SENT (S (NP-SBJ-1 (NN:[982..988] K-ras2) (NN:[989..997] spectrum) (NN:[998..1006] analysis)) (VP (VBD:[1007..1010] was) (VP (VBN:[1011..1015] done) (NP-1 (-NONE-:[1015..1015] *)) (PP (IN:[1016..1018] by) (NP (ADJP (NN:[1020..1028] sequence) (HYPH:[1028..1029] -) (JJ:[1029..1037] specific)) (NN:[1038..1053] oligonucleotide) (NN:[1054..1067] hybridization))) (S-ADV (NP-SBJ (-NONE-:[1067..1067] *)) (VP (VBG:[1068..1073] using) (NP (NP (JJ:[1074..1081] nuclear) (NNS:[1082..1093] suspensions)) (VP (VBN:[1095..1103] provided) (NP (-NONE-:[1103..1103] *)) (PP (IN:[1104..1106] by) (NP (NP (NP (NN:[1107..1115] analysis)) (CC:[1116..1119] and) (NP (NN:[1120..1127] sorting))) (PP (IN:[1128..1130] of) (NP (JJ:[1131..1145] multiparameter) (NN:[1146..1150] flow) (NN:[1151..1160] cytometry))))))))))) (.:[1160..1161] .))) ;sentence 10 Span:1162..1312 ;In particular, tissue inflammatory cells were separated for DNA diploid ;tumors, whereas DNA aneuploid epithelial subclones were analyzed ;separately. ;[1223..1234]:variation-type:"DNA diploid" ;[1235..1241]:malignancy:"tumors" ;[1252..1265]:variation-type:"DNA aneuploid" ;[1266..1286]:malignancy:"epithelial subclones" (SENT (S (PP (IN:[1162..1164] In) (ADJP (JJ:[1166..1176] particular))) (,:[1176..1177] ,) (NP-SBJ-2 (NN:[1178..1184] tissue) (JJ:[1185..1197] inflammatory) (NNS:[1198..1203] cells)) (VP (VBD:[1204..1208] were) (VP (VBN:[1209..1218] separated) (NP-2 (-NONE-:[1218..1218] *)) (PP (IN:[1219..1222] for) (NP (NN:[1223..1226] DNA) (JJ:[1227..1234] diploid) (NNS:[1235..1241] tumors))) (,:[1241..1242] ,) (SBAR-ADV (IN:[1244..1251] whereas) (S (NP-SBJ-1 (NN:[1252..1255] DNA) (JJ:[1256..1265] aneuploid) (JJ:[1266..1276] epithelial) (NNS:[1277..1286] subclones)) (VP (VBD:[1287..1291] were) (VP (VBN:[1292..1300] analyzed) (NP-1 (-NONE-:[1300..1300] *)) (ADVP (RB:[1301..1311] separately)))))))) (.:[1311..1312] .))) ;sentence 11 Span:1313..1394 ;K-ras2 mutations and DNA aneuploidy were both detected in 29 of 116 (25%) ;cases. ;[1313..1319]:gene-rna:"K-ras2" ;[1335..1349]:variation-type:"DNA aneuploidy" (SENT (S (NP-SBJ-1 (NP (NN:[1313..1319] K-ras2) (NNS:[1321..1330] mutations)) (CC:[1331..1334] and) (NP (NN:[1335..1338] DNA) (NN:[1339..1349] aneuploidy))) (VP (VBD:[1350..1354] were) (ADVP (DT:[1355..1359] both)) (VP (VBN:[1360..1368] detected) (NP-1 (-NONE-:[1368..1368] *)) (PP (IN:[1369..1371] in) (NP (NP (CD:[1372..1374] 29)) (PP (IN:[1375..1377] of) (NP (CD:[1378..1381] 116) (PRN (-LRB-:[1382..1383] -LRB-) (NP (CD:[1383..1385] 25) (NN:[1385..1386] %)) (-RRB-:[1386..1387] -RRB-)) (NNS:[1388..1393] cases))))))) (.:[1393..1394] .))) ;sentence 12 Span:1395..1472 ;DNA aneuploid index was in the near-diploid region in the majority of ;cases. ;[1427..1439]:variation-type:"near-diploid" (SENT (S (NP-SBJ (NN:[1395..1398] DNA) (JJ:[1400..1409] aneuploid) (NN:[1410..1415] index)) (VP (VBD:[1416..1419] was) (PP-PRD (IN:[1420..1422] in) (NP (DT:[1423..1426] the) (ADJP (JJ:[1427..1431] near) (HYPH:[1431..1432] -) (JJ:[1432..1439] diploid)) (NN:[1440..1446] region))) (PP (IN:[1447..1449] in) (NP (NP (DT:[1450..1453] the) (NN:[1454..1462] majority)) (PP (IN:[1463..1465] of) (NP (NNS:[1466..1471] cases)))))) (.:[1471..1472] .))) ;sentence 13 Span:1473..1540 ;DNA aneuploidy was strongly associated with G-->C/T transversions. ;[1473..1488]:variation-type:"DNA aneuploidy" ;[1518..1519]:variation-state-original:"G" ;[1522..1523]:variation-state-altered:"C" ;[1524..1525]:variation-state-altered:"T" ;[1526..1539]:variation-type:"transversions" (SENT (S (NP-SBJ-1 (NN:[1473..1476] DNA) (NN:[1478..1488] aneuploidy)) (VP (VBD:[1489..1492] was) (ADVP (RB:[1493..1501] strongly)) (VP (VBN:[1502..1512] associated) (NP-1 (-NONE-:[1512..1512] *)) (PP-CLR (IN:[1513..1517] with) (NP (NML (NML (NN:[1518..1519] G)) (PP (SYM:[1519..1522] -->) (NP (NN:[1522..1523] C) (SYM:[1523..1524] /) (NN:[1524..1525] T)))) (NNS:[1526..1539] transversions))))) (.:[1539..1540] .))) ;sentence 14 Span:1541..1621 ;An association was also found between low S-phase values and G-->A ;transitions. ;[1603..1604]:variation-state-original:"G" ;[1607..1608]:variation-state-altered:"A" ;[1609..1620]:variation-type:"transitions" (SENT (S (NP-SBJ-1 (DT:[1541..1543] An) (NN:[1544..1555] association)) (VP (VBD:[1557..1560] was) (ADVP (RB:[1561..1565] also)) (VP (VBN:[1566..1571] found) (NP-1 (-NONE-:[1571..1571] *)) (PP (IN:[1572..1579] between) (NP (NP (JJ:[1580..1583] low) (NN:[1584..1591] S-phase) (NNS:[1592..1598] values)) (CC:[1599..1602] and) (NP (NML (NML (NN:[1603..1604] G)) (PP (SYM:[1604..1607] -->) (NP (NN:[1607..1608] A)))) (NNS:[1609..1620] transitions)))))) (.:[1620..1621] .))) ;sentence 15 Span:1622..1774 ;These findings were confirmed using multivariate logistic regression ;analysis to account for the effects of size, dysplasia, site, type, age, and ;sex. ;[1738..1747]:malignancy:"dysplasia" (SENT (S (NP-SBJ-1 (DT:[1622..1627] These) (NNS:[1628..1636] findings)) (VP (VBD:[1638..1642] were) (VP (VBN:[1643..1652] confirmed) (NP-1 (-NONE-:[1652..1652] *)) (S-MNR (NP-SBJ (-NONE-:[1652..1652] *)) (VP (VBG:[1653..1658] using) (NP (JJ:[1659..1671] multivariate) (JJ:[1672..1680] logistic) (NN:[1681..1691] regression) (NN:[1692..1700] analysis)) (S-ADV (NP-SBJ (-NONE-:[1700..1700] *)) (VP (TO:[1701..1703] to) (VP (VB:[1704..1711] account) (PP (IN:[1712..1715] for) (NP (NP (DT:[1717..1720] the) (NNS:[1721..1728] effects)) (PP (IN:[1729..1731] of) (NP (NN:[1732..1736] size) (,:[1736..1737] ,) (NN:[1738..1747] dysplasia) (,:[1747..1748] ,) (NN:[1749..1753] site) (,:[1753..1754] ,) (NN:[1755..1759] type) (,:[1759..1760] ,) (NN:[1761..1764] age) (,:[1764..1765] ,) (CC:[1766..1769] and) (NN:[1770..1773] sex)))))))))))) (.:[1773..1774] .))) ;sentence 16 Span:1775..1997 ;These data suggest that specific K-ras2 mutations in a subgroup of human ;sporadic colorectal adenomas play a role in chromosome instability and, ;contrary to expectations, are associated with inhibition of proliferation. ;[1809..1815]:gene-rna:"K-ras2" ;[1849..1878]:malignancy:"sporadic colorectal adenomas" (SENT (S (NP-SBJ (DT:[1775..1780] These) (NNS:[1781..1785] data)) (VP (VBP:[1786..1793] suggest) (SBAR (IN:[1795..1799] that) (S (NP-SBJ-1 (NP (JJ:[1800..1808] specific) (NN:[1809..1815] K-ras2) (NNS:[1816..1825] mutations)) (PP (IN:[1826..1828] in) (NP (NP (DT:[1829..1830] a) (NN:[1831..1839] subgroup)) (PP (IN:[1840..1842] of) (NP (JJ:[1843..1848] human) (JJ:[1849..1857] sporadic) (JJ:[1858..1868] colorectal) (NNS:[1870..1878] adenomas)))))) (VP (VP (VBP:[1879..1883] play) (NP (DT:[1884..1885] a) (NN:[1886..1890] role)) (PP (IN:[1891..1893] in) (NP (NN:[1894..1904] chromosome) (NN:[1905..1916] instability)))) (CC:[1917..1920] and) (,:[1920..1921] ,) (S-ADV (NP-SBJ (-NONE-:[1921..1921] *)) (ADJP-PRD (JJ:[1922..1930] contrary) (PP (TO:[1931..1933] to) (NP (NNS:[1934..1946] expectations))))) (,:[1946..1947] ,) (VP (VBP:[1949..1952] are) (VP (VBN:[1953..1963] associated) (NP-1 (-NONE-:[1963..1963] *)) (PP-CLR (IN:[1964..1968] with) (NP (NP (NN:[1969..1979] inhibition)) (PP (IN:[1980..1982] of) (NP (NN:[1983..1996] proliferation))))))))))) (.:[1996..1997] .))) ;section 17 Span:2001..2045 ;PMID: 9777951 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2001..2005] PMID) (::[2005..2006] :) (CD:[2007..2014] 9777951) (IN:[2015..2016] -LSB-) (NNP:[2016..2022] PubMed) (HYPH:[2023..2024] -) (JJ:[2025..2032] indexed) (IN:[2033..2036] for) (NNP:[2037..2045] MEDLINE-RSB-)))