> top > docs > PubMed:20421921 > annotations

PubMed:20421921 JSONTXT

Annnotations TAB JSON ListView MergeView

PubMed_Structured_Abstracts

Id Subject Object Predicate Lexical cue
T1 105-388 BACKGROUND denotes While it is accepted that a majority of invasive breast cancer progresses from a ductal carcinoma in situ (DCIS) precursor stage, very little is known about the factors that promote survival of DCIS neoplastic cells within the hypoxic, nutrient deprived intraductal microenvironment.
T2 425-2151 RESULTS denotes We examined the hypothesis that fresh human DCIS lesions contain pre-existing carcinoma precursor cells. We characterized these cells by full genome molecular cytogenetics (Illumina HumanCytoSNP profile), and signal pathway profiling (Reverse Phase Protein Microarray, 59 endpoints), and demonstrated that autophagy is required for survival and anchorage independent growth of the cytogenetically abnormal tumorigenic DCIS cells. Ex vivo organoid culture of fresh human DCIS lesions, without enzymatic treatment or sorting, induced the emergence of neoplastic epithelial cells exhibiting the following characteristics: a) spontaneous generation of hundreds of spheroids and duct-like 3-D structures in culture within 2-4 weeks; b) tumorigenicity in NOD/SCID mice; c) cytogenetically abnormal (copy number loss or gain in chromosomes including 1, 5, 6, 8, 13, 17) compared to the normal karyotype of the non-neoplastic cells in the source patient's breast tissue; d) in vitro migration and invasion of autologous breast stroma; and e) up-regulation of signal pathways linked to, and components of, cellular autophagy. Multiple autophagy markers were present in the patient's original DCIS lesion and the mouse xenograft. We tested whether autophagy was necessary for survival of cytogenetically abnormal DCIS cells. The lysosomotropic inhibitor (chloroquine phosphate) of autophagy completely suppressed the generation of DCIS spheroids/3-D structures, suppressed ex vivo invasion of autologous stroma, induced apoptosis, suppressed autophagy associated proteins including Atg5, AKT/PI3 Kinase and mTOR, eliminated cytogenetically abnormal spheroid forming cells from the organ culture, and abrogated xenograft tumor formation.
T3 2165-2330 CONCLUSIONS denotes Cytogenetically abnormal spheroid forming, tumorigenic, and invasive neoplastic epithelial cells pre-exist in human DCIS and require cellular autophagy for survival.

c_corpus

Id Subject Object Predicate Lexical cue
T1 10-19 PR:000000230 denotes precursor
T2 10-19 PR:000000291 denotes precursor
T5 26-29 SO:0002045 denotes pre
T4 26-29 PR:Q8LLD0 denotes pre
T6 26-29 UBERON:0001782 denotes pre
T3 26-29 GO:0003904 denotes pre
T7 39-44 D006801 denotes human
T8 45-51 UBERON:0000310 denotes breast
T10 52-56 CVCL_5552 denotes DCIS
T9 52-56 D002285 denotes DCIS
T11 52-56 D002285 denotes DCIS
T12 69-78 GO:0016236 denotes autophagy
T13 69-78 GO:0006914 denotes autophagy
T14 154-160 UBERON:0000310 denotes breast
T15 154-167 D001943 denotes breast cancer
T16 154-167 D001943 denotes breast cancer
T19 186-210 D002285 denotes ductal carcinoma in situ
T20 186-210 D002285 denotes ductal carcinoma in situ
T26 212-216 CVCL_5552 denotes DCIS
T25 212-216 D002285 denotes DCIS
T27 212-216 D002285 denotes DCIS
T28 218-227 PR:000000230 denotes precursor
T29 218-227 PR:000000291 denotes precursor
T31 299-303 CVCL_5552 denotes DCIS
T30 299-303 D002285 denotes DCIS
T32 299-303 D002285 denotes DCIS
T33 341-349 CHEBI:33284 denotes nutrient
T34 401-404 1481724 denotes AND
T35 463-468 D006801 denotes human
T37 469-473 CVCL_5552 denotes DCIS
T36 469-473 D002285 denotes DCIS
T38 469-473 D002285 denotes DCIS
T41 490-493 SO:0002045 denotes pre
T40 490-493 PR:Q8LLD0 denotes pre
T42 490-493 UBERON:0001782 denotes pre
T39 490-493 GO:0003904 denotes pre
T43 503-512 D002277 denotes carcinoma
T44 503-512 D002277 denotes carcinoma
T45 513-522 PR:000000230 denotes precursor
T46 513-522 PR:000000291 denotes precursor
T47 567-573 SO:0001026 denotes genome
T48 634-640 SO:0000725 denotes signal
T49 634-640 SO:0000418 denotes signal
T50 641-648 CHEBI:34922 denotes pathway
T51 660-667 SO:0001031 denotes Reverse
T52 674-681 CHEBI:16541 denotes Protein
T53 731-740 GO:0016236 denotes autophagy
T54 731-740 GO:0006914 denotes autophagy
T55 770-798 CVCL_8483 denotes anchorage independent growth
T56 843-847 D002285 denotes DCIS
T58 843-847 D002285 denotes DCIS
T57 843-847 CVCL_5552 denotes DCIS
T59 889-894 D006801 denotes human
T61 895-899 CVCL_5552 denotes DCIS
T60 895-899 D002285 denotes DCIS
T62 895-899 D002285 denotes DCIS
T63 917-926 SO:0001185 denotes enzymatic
T64 1099-1103 UBERON:0000025 denotes duct
T65 1099-1103 UBERON:0000058 denotes duct
T66 1174-1177 C6LR75 denotes NOD
T67 1174-1177 PR:000022907 denotes NOD
T68 1174-1177 Q7NSD8 denotes NOD
T69 1174-1177 Q8Z4M3 denotes NOD
T70 1174-1177 Q7UIY1 denotes NOD
T71 1174-1177 Q57LF5 denotes NOD
T72 1174-1177 Q88PP0 denotes NOD
T73 1174-1177 Q9I0H4 denotes NOD
T74 1174-1177 Q8GAZ4 denotes NOD
T75 1174-1177 Q7TTP0 denotes NOD
T76 1174-1177 Q03331 denotes NOD
T77 1174-1177 E2RTZ4 denotes NOD
T78 1174-1177 P40609 denotes NOD
T80 1174-1177 Q7WUM8 denotes NOD
T81 1174-1177 P39662 denotes NOD
T82 1174-1177 Q5PIH6 denotes NOD
T83 1174-1177 Q6D245 denotes NOD
T84 1174-1177 Q6HLA6 denotes NOD
T85 1174-1177 Q6LM37 denotes NOD
T86 1174-1177 P26353 denotes NOD
T87 1174-1177 Q9URY5 denotes NOD
T88 1174-1177 Q8ZCR0 denotes NOD
T89 1174-1177 Q8FF30 denotes NOD
T90 1174-1177 P39676 denotes NOD
T91 1174-1177 Q9RC40 denotes NOD
T92 1174-1177 Q7ABK6 denotes NOD
T93 1174-1177 Q7N215 denotes NOD
T94 1174-1177 Q73B49 denotes NOD
T95 1174-1177 Q81T23 denotes NOD
T96 1174-1177 Q8ETH0 denotes NOD
T97 1174-1177 Q9KMY3 denotes NOD
T98 1174-1177 P24232 denotes NOD
T99 1174-1177 Q9PH91 denotes NOD
T100 1174-1177 P49852 denotes NOD
T101 1174-1177 Q47266 denotes NOD
T102 1174-1177 Q87F90 denotes NOD
T103 1174-1177 Q7MH09 denotes NOD
T104 1174-1177 Q81FW4 denotes NOD
T105 1174-1177 Q7C0F9 denotes NOD
T106 1174-1177 PR:P18105 denotes NOD
T107 1174-1177 Q8DCU2 denotes NOD
T108 1174-1177 Q59MV9 denotes NOD
T109 1174-1177 Q7TTP2 denotes NOD
T110 1174-1177 Q7WHW5 denotes NOD
T111 1174-1177 Q9RYR5 denotes NOD
T79 1174-1177 D020191 denotes NOD
T112 1178-1187 D016513 denotes SCID mice
T113 1183-1187 PR:000005054 denotes mice
T115 1183-1187 O89094 denotes mice
T117 1218-1234 SO:0001743 denotes copy number loss
T118 1238-1242 SO:0001742 denotes gain
T119 1373-1379 UBERON:0000310 denotes breast
T120 1380-1386 UBERON:0000479 denotes tissue
T121 1437-1443 UBERON:0000310 denotes breast
T122 1444-1450 UBERON:0003891 denotes stroma
T123 1462-1472 GO:0065007 denotes regulation
T124 1476-1482 SO:0000725 denotes signal
T125 1476-1482 SO:0000418 denotes signal
T126 1531-1540 GO:0016236 denotes autophagy
T127 1531-1540 GO:0006914 denotes autophagy
T128 1551-1560 GO:0016236 denotes autophagy
T129 1551-1560 GO:0006914 denotes autophagy
T131 1608-1612 CVCL_5552 denotes DCIS
T130 1608-1612 D002285 denotes DCIS
T132 1608-1612 D002285 denotes DCIS
T133 1628-1633 10090 denotes mouse
T134 1628-1633 D051379 denotes mouse
T135 1663-1672 GO:0016236 denotes autophagy
T136 1663-1672 GO:0006914 denotes autophagy
T138 1728-1732 CVCL_5552 denotes DCIS
T137 1728-1732 D002285 denotes DCIS
T139 1728-1732 D002285 denotes DCIS
T140 1759-1768 CHEBI:35222 denotes inhibitor
T149 1770-1791 20863 denotes chloroquine phosphate
T147 1770-1791 C023676 denotes chloroquine phosphate
T148 1770-1791 C023676 denotes chloroquine phosphate
T158 1796-1805 GO:0016236 denotes autophagy
T159 1796-1805 GO:0006914 denotes autophagy
T161 1846-1850 CVCL_5552 denotes DCIS
T160 1846-1850 D002285 denotes DCIS
T162 1846-1850 D002285 denotes DCIS
T163 1919-1925 UBERON:0003891 denotes stroma
T164 1935-1944 GO:0097194 denotes apoptosis
T165 1935-1944 GO:0006915 denotes apoptosis
T166 1957-1966 GO:0016236 denotes autophagy
T167 1957-1966 GO:0006914 denotes autophagy
T168 1978-1986 CHEBI:36080 denotes proteins
T169 1997-2001 PR:Q9FFI2 denotes Atg5
T170 1997-2001 PR:000004418 denotes Atg5
T171 1997-2001 Q96328 denotes Atg5
T172 1997-2001 PR:Q9W3R7 denotes Atg5
T173 1997-2001 PR:Q3MQ06 denotes Atg5
T174 1997-2001 PR:Q54GT9 denotes Atg5
T175 1997-2001 PR:Q96328 denotes Atg5
T176 1997-2001 PR:O74971 denotes Atg5
T177 1997-2001 PR:Q9H1Y0 denotes Atg5
T178 1997-2001 PR:Q59VY1 denotes Atg5
T179 1997-2001 PR:Q12380 denotes Atg5
T180 1997-2001 PR:Q99J83 denotes Atg5
T181 1997-2001 PR:Q3V5I7 denotes Atg5
T182 2003-2006 PR:000029189 denotes AKT
T183 2003-2006 PR:P54644 denotes AKT
T184 2003-2006 PR:P31750 denotes AKT
T185 2003-2006 PR:000002190 denotes AKT
T186 2003-2006 Q8INB9 denotes AKT
T192 2007-2017 P42348 denotes PI3 Kinase
T193 2007-2017 P54673 denotes PI3 Kinase
T194 2007-2017 P42347 denotes PI3 Kinase
T195 2007-2017 P54675 denotes PI3 Kinase
T196 2007-2017 P54674 denotes PI3 Kinase
T198 2007-2017 P54676 denotes PI3 Kinase
T197 2007-2017 D019869 denotes PI3 Kinase
T200 2022-2026 PR:A1Z8P9 denotes mTOR
T201 2022-2026 Q9JLN9 denotes mTOR
T202 2022-2026 PR:P42345 denotes mTOR
T203 2022-2026 P42346 denotes mTOR
T204 2022-2026 P42345 denotes mTOR
T205 2022-2026 PR:000003041 denotes mTOR
T206 2022-2026 PR:Q9JLN9 denotes mTOR
T207 2022-2026 PR:P42346 denotes mTOR
T208 2096-2101 UBERON:0000062 denotes organ
T209 2096-2101 UBERON:0003103 denotes organ
T210 2135-2140 D009369 denotes tumor
T211 2135-2140 D009369 denotes tumor
T212 2141-2150 GO:0009058 denotes formation
T215 2262-2265 SO:0002045 denotes pre
T214 2262-2265 PR:Q8LLD0 denotes pre
T216 2262-2265 UBERON:0001782 denotes pre
T213 2262-2265 GO:0003904 denotes pre
T217 2275-2280 D006801 denotes human
T219 2281-2285 CVCL_5552 denotes DCIS
T218 2281-2285 D002285 denotes DCIS
T220 2281-2285 D002285 denotes DCIS
T221 2307-2316 GO:0016236 denotes autophagy
T222 2307-2316 GO:0006914 denotes autophagy

DisGeNET

Id Subject Object Predicate Lexical cue
T0 1174-1177 gene:1822 denotes NOD
T1 1178-1182 disease:C0085110 denotes SCID
R1 T0 T1 associated_with NOD,SCID

PubmedHPO

Id Subject Object Predicate Lexical cue
T1 154-167 HP_0003002 denotes breast cancer
T2 154-167 HP_0100013 denotes breast cancer
T3 161-167 HP_0002664 denotes cancer

Allie

Id Subject Object Predicate Lexical cue
SS1_20421921_2_0 186-210 expanded denotes ductal carcinoma in situ
SS2_20421921_2_0 212-216 abbr denotes DCIS
AE1_20421921_2_0 SS1_20421921_2_0 SS2_20421921_2_0 abbreviatedTo ductal carcinoma in situ,DCIS

UseCases_ArguminSci_Discourse

Id Subject Object Predicate Lexical cue
T1 0-92 DRI_Background denotes Malignant precursor cells pre-exist in human breast DCIS and require autophagy for survival.
T2 105-388 DRI_Background denotes While it is accepted that a majority of invasive breast cancer progresses from a ductal carcinoma in situ (DCIS) precursor stage, very little is known about the factors that promote survival of DCIS neoplastic cells within the hypoxic, nutrient deprived intraductal microenvironment.
T3 425-529 DRI_Outcome denotes We examined the hypothesis that fresh human DCIS lesions contain pre-existing carcinoma precursor cells.
T4 530-854 DRI_Approach denotes We characterized these cells by full genome molecular cytogenetics (Illumina HumanCytoSNP profile), and signal pathway profiling (Reverse Phase Protein Microarray, 59 endpoints), and demonstrated that autophagy is required for survival and anchorage independent growth of the cytogenetically abnormal tumorigenic DCIS cells.
T5 855-1541 DRI_Outcome denotes Ex vivo organoid culture of fresh human DCIS lesions, without enzymatic treatment or sorting, induced the emergence of neoplastic epithelial cells exhibiting the following characteristics: a) spontaneous generation of hundreds of spheroids and duct-like 3-D structures in culture within 2-4 weeks; b) tumorigenicity in NOD/SCID mice; c) cytogenetically abnormal (copy number loss or gain in chromosomes including 1, 5, 6, 8, 13, 17) compared to the normal karyotype of the non-neoplastic cells in the source patient's breast tissue; d) in vitro migration and invasion of autologous breast stroma; and e) up-regulation of signal pathways linked to, and components of, cellular autophagy.
T6 1542-1644 DRI_Background denotes Multiple autophagy markers were present in the patient's original DCIS lesion and the mouse xenograft.
T7 1645-1739 DRI_Approach denotes We tested whether autophagy was necessary for survival of cytogenetically abnormal DCIS cells.
T8 1740-2151 DRI_Background denotes The lysosomotropic inhibitor (chloroquine phosphate) of autophagy completely suppressed the generation of DCIS spheroids/3-D structures, suppressed ex vivo invasion of autologous stroma, induced apoptosis, suppressed autophagy associated proteins including Atg5, AKT/PI3 Kinase and mTOR, eliminated cytogenetically abnormal spheroid forming cells from the organ culture, and abrogated xenograft tumor formation.
T9 2165-2330 DRI_Background denotes Cytogenetically abnormal spheroid forming, tumorigenic, and invasive neoplastic epithelial cells pre-exist in human DCIS and require cellular autophagy for survival.