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[ { "id": "PMID-7511490__text", "type": "abstract", "text": [ "Additional tests of interest to the dermatologist.\nThe carcinoid syndrome and its clinical manifestations have been discussed. The standard laboratory test for making that diagnosis is urinary 5-HIAA levels but newer, more sensitive tests may also be available.\n" ], "offsets": [ [ 0, 262 ] ] } ]

[ { "id": "PMID-7511490_T1", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 185, 192 ] ], "normalized": [] } ]

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[ { "id": "PMID-15193260__text", "type": "abstract", "text": [ "Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. \nWe identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.\n" ], "offsets": [ [ 0, 907 ] ] } ]

[ { "id": "PMID-15193260_T3", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 79, 88 ] ], "normalized": [] }, { "id": "PMID-15193260_T10", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 254, 258 ] ], "normalized": [] }, { "id": "PMID-15193260_T23", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 625, 634 ] ], "normalized": [] }, { "id": "PMID-15193260_T24", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 649, 668 ] ], "normalized": [] }, { "id": "PMID-15193260_T27", "type": "Cancer", "text": [ "breast tumors" ], "offsets": [ [ 727, 740 ] ], "normalized": [] }, { "id": "PMID-15193260_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 760, 764 ] ], "normalized": [] }, { "id": "PMID-15193260_T31", "type": "Cancer", "text": [ "cancerous" ], "offsets": [ [ 885, 894 ] ], "normalized": [] } ]

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[ { "id": "PMC-3173373-caption-02__text", "type": "caption", "text": [ "Parameters derived from normalized averaged data across participants\n" ], "offsets": [ [ 0, 69 ] ] } ]

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[ { "id": "PMID-10913166__text", "type": "abstract", "text": [ "TEL, a putative tumor suppressor, modulates cell growth and cell morphology of ras-transformed cells while repressing the transcription of stromelysin-1. \nTEL is a member of the ETS family of transcription factors that interacts with the mSin3 and SMRT corepressors to regulate transcription. TEL is biallelically disrupted in acute leukemia, and loss of heterozygosity at the TEL locus has been observed in various cancers. Here we show that expression of TEL in Ras-transformed NIH 3T3 cells inhibits cell growth in soft agar and in normal cultures. Unexpectedly, cells expressing both Ras and TEL grew as aggregates. To begin to explain the morphology of Ras-plus TEL-expressing cells, we demonstrated that the endogenous matrix metalloproteinase stromelysin-1 was repressed by TEL. TEL bound sequences in the stromelysin-1 promoter and repressed the promoter in transient-expression assays, suggesting that it is a direct target for TEL-mediated regulation. Mutants of TEL that removed a binding site for the mSin3A corepressor but retained the ETS domain failed to repress stromelysin-1. When BB-94, a matrix metalloproteinase inhibitor, was added to the culture medium of Ras-expressing cells, it caused a cell aggregation phenotype similar to that caused by TEL expression. In addition, TEL inhibited the invasiveness of Ras-transformed cells in vitro and in vivo. Our results suggest that TEL acts as a tumor suppressor, in part, by transcriptional repression of stromelysin-1.\n" ], "offsets": [ [ 0, 1486 ] ] } ]

[ { "id": "PMID-10913166_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "PMID-10913166_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 44, 48 ] ], "normalized": [] }, { "id": "PMID-10913166_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 60, 64 ] ], "normalized": [] }, { "id": "PMID-10913166_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 95, 100 ] ], "normalized": [] }, { "id": "PMID-10913166_T13", "type": "Cancer", "text": [ "acute leukemia" ], "offsets": [ [ 327, 341 ] ], "normalized": [] }, { "id": "PMID-10913166_T15", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 416, 423 ] ], "normalized": [] }, { "id": "PMID-10913166_T18", "type": "Cell", "text": [ "NIH 3T3 cells" ], "offsets": [ [ 480, 493 ] ], "normalized": [] }, { "id": "PMID-10913166_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 503, 507 ] ], "normalized": [] }, { "id": "PMID-10913166_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 566, 571 ] ], "normalized": [] }, { "id": "PMID-10913166_T25", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-10913166_T37", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "PMID-10913166_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1212, 1216 ] ], "normalized": [] }, { "id": "PMID-10913166_T42", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1344, 1349 ] ], "normalized": [] }, { "id": "PMID-10913166_T44", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1411, 1416 ] ], "normalized": [] }, { "id": "PMID-10913166_T1", "type": "Cell", "text": [ "cultures" ], "offsets": [ [ 542, 550 ] ], "normalized": [] } ]

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[ { "id": "PMID-12484699__text", "type": "abstract", "text": [ "Regulation of transforming growth factor-beta signaling and vascular diseases.\nPURPOSE: Members of the transforming growth factor (TGF)-beta superfamily play critical roles in regulation of various cellular functions. Dysregulation of the signaling mechanisms of the TGF-beta superfamily proteins is associated with clinical diseases such as cancer, fibrotic diseases, and vascular disorders. Therefore, understanding these signaling mechanisms may provide us with novel ways to develop strategies for treating clinical diseases induced by these cytokines. METHODS: This review discusses our current understanding of the mechanisms of TGF-beta signaling, focusing on the roles of TGF-beta in regulation of vascular wall cells and on the regulation of TGF-beta superfamily signals by inhibitory Smads.\n" ], "offsets": [ [ 0, 801 ] ] } ]

[ { "id": "PMID-12484699_T2", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 60, 68 ] ], "normalized": [] }, { "id": "PMID-12484699_T4", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 198, 206 ] ], "normalized": [] }, { "id": "PMID-12484699_T6", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 342, 348 ] ], "normalized": [] }, { "id": "PMID-12484699_T7", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 373, 381 ] ], "normalized": [] }, { "id": "PMID-12484699_T10", "type": "Cell", "text": [ "vascular wall cells" ], "offsets": [ [ 706, 725 ] ], "normalized": [] } ]

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[ { "id": "PMC-2727579-sec-09__text", "type": "sec", "text": [ "Conclusions and policy implications\nEarly postnatal home visit is one strategy for providing critical interventions to improve newborn survival. Given the compelling data in this study, we recommend that in developing countries, especially those where home delivery with unskilled attendants is the norm, all newborns should receive a home visit and undergo assessment by a trained worker as soon as possible, preferably on the day of birth but no later than 48 hours after birth. The impact of this approach is likely to be dependent on the content, quality, and coverage of the technical interventions included. Reaching neonates within first day or first two days of life is a challenge. Given that the community health workers in this study were not skilled birth attendants and attended only about 5% of deliveries, a complementary strategy will be to ensure skilled attendance at delivery that is linked to essential obstetric care.31 32 Further operational research will be needed to develop context specific strategies to reach all newborns as soon as possible after birth.\n\n" ], "offsets": [ [ 0, 1083 ] ] } ]

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[ { "id": "PMC-2837610-sec-05__text", "type": "sec", "text": [ "1. Background\nThe United Republic of Tanzania, is among the many countries in sub-Saharan Africa facing a human resources crisis in its health sector, with a small and inequitably distributed health workforce [1] that shoulders a disproportionately high burden of disease[2]. Although all poor countries in the world face a severe human resource crisis in their health sectors [3,4], the problem is most acute in Sub-Saharan Africa, in which an estimated workforce of 750 000 health workers in the region serves 682 million people [2]. By comparison, the ratio is 10 to 15 times higher in developed countries. Moreover, this estimated workforce of doctors, nurses and allied health workers in Sub-Saharan Africa constitutes 1.3% of the world's health workforce, while Africa suffers from 25% of the world's burden of disease [2].\nA minimum level of a health workforce of 2.5 health workers per 1000 people is required to achieve the Millennium Development Goals [5]. Africa is far from this level with a health workforce density that only averages 0.8 worker per 1000 people, while the world median density of health personnel is 5 per 1000 people [5].\nThere is a positive correlation between health worker density and various health indices, most notably infant mortality rate, maternal mortality rates, and various disease specific mortality and morbidity rates [6,7]. An increase in the number of health workers per capita is associated with a notable decline in the rates mentioned above. As a consequence, it has been argued that health worker shortages have impeded the implementation of development goals in many poor countries [8].\n\n" ], "offsets": [ [ 0, 1641 ] ] } ]

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[ { "id": "PMC-3267723-sec-02__text", "type": "sec", "text": [ "Results\n\n" ], "offsets": [ [ 0, 9 ] ] } ]

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[ { "id": "PMID-16268479__text", "type": "abstract", "text": [ "Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt.\nDomain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the P13-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response toVEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3alpha HKa and D5 inhibit phosphorylation of Akt and GSK-3alpha after stimulation withVEGF and S1P. Inhibitors of Akt and P13-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters P13-kinase-Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.\n" ], "offsets": [ [ 0, 1758 ] ] } ]

[ { "id": "PMID-16268479_T2", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 61, 77 ] ], "normalized": [] }, { "id": "PMID-16268479_T6", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 198, 214 ] ], "normalized": [] }, { "id": "PMID-16268479_T7", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "PMID-16268479_T9", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 304, 320 ] ], "normalized": [] }, { "id": "PMID-16268479_T11", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 448, 464 ] ], "normalized": [] }, { "id": "PMID-16268479_T20", "type": "Cell", "text": [ "pulmonary artery endothelial cell" ], "offsets": [ [ 634, 667 ] ], "normalized": [] }, { "id": "PMID-16268479_T21", "type": "Cell", "text": [ "BPAE" ], "offsets": [ [ 669, 673 ] ], "normalized": [] }, { "id": "PMID-16268479_T22", "type": "Cell", "text": [ "human umbilical vein endothelial cell" ], "offsets": [ [ 678, 715 ] ], "normalized": [] }, { "id": "PMID-16268479_T28", "type": "Cell", "text": [ "BPAE cell" ], "offsets": [ [ 934, 943 ] ], "normalized": [] }, { "id": "PMID-16268479_T33", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1100, 1115 ] ], "normalized": [] }, { "id": "PMID-16268479_T36", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1173, 1186 ] ], "normalized": [] }, { "id": "PMID-16268479_T48", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1471, 1487 ] ], "normalized": [] }, { "id": "PMID-16268479_T50", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1539, 1554 ] ], "normalized": [] }, { "id": "PMID-16268479_T56", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1687, 1703 ] ], "normalized": [] }, { "id": "PMID-16268479_T57", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1741, 1756 ] ], "normalized": [] } ]

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[ { "id": "PMC-2719750-sec-10__text", "type": "sec", "text": [ "Quantitative reverse transcription PCR\nReverse transcription was performed using 0.2 mug of total RNA from muscle of 10 week-old and 19 month-old C57Bl6 mice (five animals per group), a Core kit (RT-RTCK-03, Eurogentec) according to manufacturer's instruction and a mix of random primers (9 mers) and oligodT. qPCR was performed on SDS7900HT (Applied Biosystem) using Mesagreen qPCR kit for SYBR (Eurogentec) and the following primers: \nPPARbeta: 5'-AGATGGTGGCAGAGCTATGACC-3'; 5'-TCCTCCTGTGGCTGTTCC-3'.\nCatalase: 5'-GGATCCTGACATGGTCTGGG-3'; 5'-TGGAGAGACTCGGGACGAAG-3'.\nPDK4: 5'-GCATTTCTACTCGGATGCTCAATG-3'; 5'-CCAATGTGGCTTGGGTTTCC-3'.\n36B4: 5'-TCCAGGCTTTGGGCATCA-3'; 5'-CTTTATCAGCTGCACATCACTCAGA-3'.\nData were all normalised using 36B4 as housekeeping gene.\n" ], "offsets": [ [ 0, 758 ] ] } ]

[ { "id": "PMC-2719750-sec-10_T1", "type": "Tissue", "text": [ "muscle" ], "offsets": [ [ 107, 113 ] ], "normalized": [] } ]

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[ { "id": "PMID-11121230__text", "type": "abstract", "text": [ "RNA damage and inhibition of neoplastic endothelial cell growth: effects of human and amphibian ribonucleases.\nAngiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels. This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening of potential anti-angiogenic compounds on endothelial cells. To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et al., Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC(50) = 0.3-1.0 microM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC(50) = 0.02-0.06 microM) than on primary HUVECs (IC(50) > 0.1 microM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds.\n" ], "offsets": [ [ 0, 1275 ] ] } ]

[ { "id": "PMID-11121230_T1", "type": "Cell", "text": [ "neoplastic endothelial cell" ], "offsets": [ [ 29, 56 ] ], "normalized": [] }, { "id": "PMID-11121230_T4", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 187, 203 ] ], "normalized": [] }, { "id": "PMID-11121230_T5", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 212, 225 ] ], "normalized": [] }, { "id": "PMID-11121230_T6", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 286, 292 ] ], "normalized": [] }, { "id": "PMID-11121230_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 358, 363 ] ], "normalized": [] }, { "id": "PMID-11121230_T8", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 452, 469 ] ], "normalized": [] }, { "id": "PMID-11121230_T11", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 594, 610 ] ], "normalized": [] }, { "id": "PMID-11121230_T12", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 655, 672 ] ], "normalized": [] }, { "id": "PMID-11121230_T15", "type": "Cell", "text": [ "human umbilical vein endothelial cells" ], "offsets": [ [ 711, 749 ] ], "normalized": [] }, { "id": "PMID-11121230_T16", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 751, 757 ] ], "normalized": [] }, { "id": "PMID-11121230_T20", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 792, 797 ] ], "normalized": [] }, { "id": "PMID-11121230_T21", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 858, 864 ] ], "normalized": [] }, { "id": "PMID-11121230_T23", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 922, 932 ] ], "normalized": [] }, { "id": "PMID-11121230_T25", "type": "Cell", "text": [ "HUVEC cell lines" ], "offsets": [ [ 1010, 1026 ] ], "normalized": [] }, { "id": "PMID-11121230_T26", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1071, 1077 ] ], "normalized": [] }, { "id": "PMID-11121230_T27", "type": "Cell", "text": [ "endothelial cell type" ], "offsets": [ [ 1169, 1190 ] ], "normalized": [] } ]

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[ { "id": "PMID-12610665__text", "type": "abstract", "text": [ "Arteriogenesis: the development and growth of collateral arteries.\nIn patients with atherosclerotic vascular diseases, collateral vessels bypassing major arterial obstructions have frequently been observed. This may explain why some patients remain without symptoms or signs of ischemia. The term \"arteriogenesis\" was introduced to differentiate the formation of collateral arteries from angiogenesis, which mainly occurs in the ischemic, collateral flow-dependent tissue. Many observations in various animal models and humans support that the remodeling of preexisting collateral vessels is the mechanism of collateral artery formation. This remodeling process seems to be mainly flow-mediated. It involves endothelial cell activation, basal membrane degradation, leukocyte invasion, proliferation of vascular cells, neointima formation (in most species studied), and changes of the extracellular matrix. The contribution of ischemia to arteriogenesis is still unclear, but arteriogenesis clearly can occur in the absence of any significant ischemia. It is questionable, whether collateral arteries also form de novo in ischemic vascular diseases. A better understanding of the mechanisms of arteriogenesis will be important for the design of more effective strategies for the treatment of patients with ischemic vascular diseases.\n" ], "offsets": [ [ 0, 1333 ] ] } ]

[ { "id": "PMID-12610665_T1", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 46, 65 ] ], "normalized": [] }, { "id": "PMID-12610665_T3", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 100, 108 ] ], "normalized": [] }, { "id": "PMID-12610665_T4", "type": "Multi-tissue_structure", "text": [ "collateral vessels" ], "offsets": [ [ 119, 137 ] ], "normalized": [] }, { "id": "PMID-12610665_T5", "type": "Pathological_formation", "text": [ "arterial obstructions" ], "offsets": [ [ 154, 175 ] ], "normalized": [] }, { "id": "PMID-12610665_T7", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 363, 382 ] ], "normalized": [] }, { "id": "PMID-12610665_T8", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 465, 471 ] ], "normalized": [] }, { "id": "PMID-12610665_T10", "type": "Multi-tissue_structure", "text": [ "collateral vessels" ], "offsets": [ [ 570, 588 ] ], "normalized": [] }, { "id": "PMID-12610665_T11", "type": "Multi-tissue_structure", "text": [ "collateral artery" ], "offsets": [ [ 609, 626 ] ], "normalized": [] }, { "id": "PMID-12610665_T12", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 708, 724 ] ], "normalized": [] }, { "id": "PMID-12610665_T13", "type": "Cellular_component", "text": [ "basal membrane" ], "offsets": [ [ 737, 751 ] ], "normalized": [] }, { "id": "PMID-12610665_T14", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 765, 774 ] ], "normalized": [] }, { "id": "PMID-12610665_T15", "type": "Cell", "text": [ "vascular cells" ], "offsets": [ [ 802, 816 ] ], "normalized": [] }, { "id": "PMID-12610665_T16", "type": "Tissue", "text": [ "neointima" ], "offsets": [ [ 818, 827 ] ], "normalized": [] }, { "id": "PMID-12610665_T17", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 884, 904 ] ], "normalized": [] }, { "id": "PMID-12610665_T18", "type": "Multi-tissue_structure", "text": [ "collateral arteries" ], "offsets": [ [ 1080, 1099 ] ], "normalized": [] }, { "id": "PMID-12610665_T19", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1130, 1138 ] ], "normalized": [] }, { "id": "PMID-12610665_T21", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] } ]

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[ { "id": "PMID-20978953__text", "type": "abstract", "text": [ "Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome. \nBACKGROUND: Recently, the desmoplastic reaction has been implicated as having an important function in epithelial solid tumor biology. There have been no reports showing the relativity of invasive breast cancer and the desmoplastic reaction by a quantitative analysis of the myofibroblasts that were an important player in the desmoplastic reaction. The purpose of this study was to immunohistochemically investigate the correlation between the desmoplastic reaction and the clinicopathology of invasive breast cancer. METHODS: The study included 60 patients with a known prognosis of invasive breast cancer. We quantified the expression of alpha-SMA as a marker of myofibroblasts in the invasive breast cancer. After staining samples for alpha-SMA, their expression was extracted and quantified as a relative percentage by computer-assisted image analysis. RESULTS: There was relatively wide variation in the expression of alpha-SMA with the percentage of the area from 0.68 to 28.15% (mean 8.48 +/- 5.40%). The metastasis group showed significantly higher alpha-SMA expression compared with the no metastasis group (p < 0.001). When the patients were divided into two groups according to their alpha-SMA expression using a cutoff point at the mean value of 8.48%, the high alpha-SMA group had a significantly poorer overall survival rate (p < 0.001). Multivariate analysis demonstrated that alpha-SMA and lymph node metastasis were identified as independent predictive factors of metastasis. CONCLUSION: Myofibroblasts represent an important prognostic factor for invasive growth that is translated into a poor clinical prognosis for patients with invasive breast cancer.\n" ], "offsets": [ [ 0, 1821 ] ] } ]

[ { "id": "PMID-20978953_T1", "type": "Cell", "text": [ "stromal myofibroblasts" ], "offsets": [ [ 8, 30 ] ], "normalized": [] }, { "id": "PMID-20978953_T2", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 34, 56 ] ], "normalized": [] }, { "id": "PMID-20978953_T3", "type": "Cell", "text": [ "stromal" ], "offsets": [ [ 58, 65 ] ], "normalized": [] }, { "id": "PMID-20978953_T5", "type": "Cancer", "text": [ "epithelial solid tumor" ], "offsets": [ [ 250, 272 ] ], "normalized": [] }, { "id": "PMID-20978953_T6", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 335, 357 ] ], "normalized": [] }, { "id": "PMID-20978953_T7", "type": "Cell", "text": [ "myofibroblasts" ], "offsets": [ [ 422, 436 ] ], "normalized": [] }, { "id": "PMID-20978953_T8", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 642, 664 ] ], "normalized": [] }, { "id": "PMID-20978953_T10", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 732, 754 ] ], "normalized": [] }, { "id": "PMID-20978953_T12", "type": "Cell", "text": [ "myofibroblasts" ], "offsets": [ [ 813, 827 ] ], "normalized": [] }, { "id": "PMID-20978953_T13", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 835, 857 ] ], "normalized": [] }, { "id": "PMID-20978953_T21", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1554, 1564 ] ], "normalized": [] }, { "id": "PMID-20978953_T22", "type": "Cell", "text": [ "Myofibroblasts" ], "offsets": [ [ 1653, 1667 ] ], "normalized": [] }, { "id": "PMID-20978953_T24", "type": "Cancer", "text": [ "invasive breast cancer" ], "offsets": [ [ 1797, 1819 ] ], "normalized": [] }, { "id": "PMID-20978953_T44", "type": "Cancer", "text": [ "samples" ], "offsets": [ [ 874, 881 ] ], "normalized": [] } ]

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[ { "id": "PMID-16165242__text", "type": "abstract", "text": [ "Enhancement of skin permeation of ketotifen by supersaturation generated by amorphous form of the drug.\nPressure sensitive adhesive (PSA) matrices containing amorphous ketotifen were prepared and evaluated for enhanced skin permeability of the drug. A solvent casting method using silicone-typed PSA was employed, and n-hexane, an original solvent for the PSA and one more solvent, dichloromethane, tetrahydrofuran, acetone, ethyl acetate or toluene, were used for complete dissolution of ketotifen and high dispersion in an amorphous state of the drug. Presence of the amorphous form was judged based on the in vitro drug release rate from the matrix. As a result, dichloromethane and tetrahudrofuran were selected as appropriate dilution solvents. In vitro permeation experiments through excised hairless mouse skin revealed that the steady-state flux from the amorphous ketotifen-dispersed matrices was about five times greater than that of the crystalline ketotifen-dispersed matrices, and that the enhancement ratio was in good agreement with the solubility ratio of the amorphous to crystalline form of the drug. Comparison of the skin permeation profiles of amorphous ketotifen-dispersed matrices between two different drug contents suggested that the steady-state flux was not influenced by the drug content. In addition, at both drug contents, the period of the steady-state permeation coincided with the time until the amorphous drug was depleted from the matrix. These results suggest that the increase in skin permeation of ketotifen from PSA matrix was due to the supersaturation generated by amorphous form, and that the amorphous form was stable during the application period.\n" ], "offsets": [ [ 0, 1692 ] ] } ]

[ { "id": "PMID-16165242_T1", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 15, 19 ] ], "normalized": [] }, { "id": "PMID-16165242_T2", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 219, 223 ] ], "normalized": [] }, { "id": "PMID-16165242_T3", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 813, 817 ] ], "normalized": [] }, { "id": "PMID-16165242_T4", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1137, 1141 ] ], "normalized": [] }, { "id": "PMID-16165242_T5", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1517, 1521 ] ], "normalized": [] } ]

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[ { "id": "PMID-7474113__text", "type": "abstract", "text": [ "The inhibition of cultured myoblast differentiation by the simian virus 40 large T antigen occurs after myogenin expression and Rb up-regulation and is not exerted by transformation-competent cytoplasmic mutants. \nWe have investigated the mechanism by which the simian virus 40 large T antigen (SVLT) interferes with the differentiation of C2 myoblasts. SVLT mutants, defective either in the Rb binding site, near the N-terminal end, in a region that affects binding to p53, or in the nuclear transport signal, were also employed to determine whether the interference was especially dependent on these functional domains. It was found that wild-type (wt) SVLT strongly inhibited the terminal differentiation of mouse C2 myoblasts, but this arrest occurred only after the synthesis of myogenin, an initial step in biochemical differentiation. Neither the synthesis nor some basic activities of MyoD appeared to be affected by wt SVLT. In these transformants, mitogen depletion elicited an increase in the Rb level comparable to that in normal C2 cells; wt SVLT, however, promoted the phosphorylation of a large part of the induced Rb. Mutations affecting nuclear transport were far more critical for the ability to interfere with myogenic differentiation than were those affecting the transforming potential; cytoplasmic SVLT expression was fully compatible with the terminal differentiation of C2 cells, despite enabling them to grow in semisolid medium, thus showing that the myogenesis-inhibiting property can be dissociated from transforming competence. The remaining SVLT mutants presented different degrees of ability to inhibit differentiation (as shown by the expression of tissue-specific markers in transformants). The inhibiting mutants, including the Rb binding site mutant, were able to promote a higher state of Rb phosphorylation than that observed in either normal cells or cytoplasmic-SVLT transformants.\n" ], "offsets": [ [ 0, 1921 ] ] } ]

[ { "id": "PMID-7474113_T1", "type": "Cell", "text": [ "myoblast" ], "offsets": [ [ 27, 35 ] ], "normalized": [] }, { "id": "PMID-7474113_T6", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 192, 203 ] ], "normalized": [] }, { "id": "PMID-7474113_T10", "type": "Cell", "text": [ "C2 myoblasts" ], "offsets": [ [ 340, 352 ] ], "normalized": [] }, { "id": "PMID-7474113_T16", "type": "Cell", "text": [ "C2 myoblasts" ], "offsets": [ [ 717, 729 ] ], "normalized": [] }, { "id": "PMID-7474113_T20", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 943, 956 ] ], "normalized": [] }, { "id": "PMID-7474113_T22", "type": "Cell", "text": [ "C2 cells" ], "offsets": [ [ 1042, 1050 ] ], "normalized": [] }, { "id": "PMID-7474113_T25", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1154, 1161 ] ], "normalized": [] }, { "id": "PMID-7474113_T26", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1308, 1319 ] ], "normalized": [] }, { "id": "PMID-7474113_T28", "type": "Cell", "text": [ "C2 cells" ], "offsets": [ [ 1394, 1402 ] ], "normalized": [] }, { "id": "PMID-7474113_T30", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1681, 1687 ] ], "normalized": [] }, { "id": "PMID-7474113_T31", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 1708, 1721 ] ], "normalized": [] }, { "id": "PMID-7474113_T34", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1880, 1885 ] ], "normalized": [] }, { "id": "PMID-7474113_T35", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1889, 1900 ] ], "normalized": [] }, { "id": "PMID-7474113_T37", "type": "Cell", "text": [ "transformants" ], "offsets": [ [ 1906, 1919 ] ], "normalized": [] }, { "id": "PMID-7474113_T74", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 485, 492 ] ], "normalized": [] } ]

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[ { "id": "PMID-17462601__text", "type": "abstract", "text": [ "An antibody directed against PDGF receptor beta enhances the antitumor and the anti-angiogenic activities of an anti-VEGF receptor 2 antibody.\nPlatelet-derived growth factor (PDGF) and its receptors (PDGFR) play important roles in tumorigenesis through stimulating tumor growth and promoting angiogenesis via enhancing pericyte recruitment and vessel maturation. Here we produced a neutralizing antibody, 1B3, directed against mouse PDGFRbeta. 1B3 binds to PDGFRbeta with high affinity (9x10(-11)M) and blocks PDGF-BB from binding to the receptor with an IC(50) of approximately 1.2 nM. The antibody also blocks ligand-stimulated activation of PDGFRbeta and downstream signaling molecules, including Akt and MAPK p42/44, in tumor cells. In animal studies, 1B3 significantly enhanced the antitumor and the anti-angiogenic activities of DC101, an antibody directed against mouse vascular endothelial growth factor receptor 2, in a pancreatic (BxPC-3) and a non-small cell lung (NCI-H460) tumor xenograft models. Treatment with the combination of 1B3 and DC101 in BxPC-3 xenograft-bearing mice resulted in tumor regression in 58% of mice compared to that in 18% of mice treated with DC101 alone. Taken together, these results lend great support to use PDGFRbeta antagonists in combinations with other antitumor and/or anti-angiogenic agents in the treatment of a variety of cancers.\n" ], "offsets": [ [ 0, 1380 ] ] } ]

[ { "id": "PMID-17462601_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 65, 70 ] ], "normalized": [] }, { "id": "PMID-17462601_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 265, 270 ] ], "normalized": [] }, { "id": "PMID-17462601_T8", "type": "Cell", "text": [ "pericyte" ], "offsets": [ [ 319, 327 ] ], "normalized": [] }, { "id": "PMID-17462601_T9", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 344, 350 ] ], "normalized": [] }, { "id": "PMID-17462601_T19", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 724, 735 ] ], "normalized": [] }, { "id": "PMID-17462601_T21", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 791, 796 ] ], "normalized": [] }, { "id": "PMID-17462601_T25", "type": "Cancer", "text": [ "pancreatic" ], "offsets": [ [ 929, 939 ] ], "normalized": [] }, { "id": "PMID-17462601_T26", "type": "Cancer", "text": [ "BxPC-3" ], "offsets": [ [ 941, 947 ] ], "normalized": [] }, { "id": "PMID-17462601_T27", "type": "Cancer", "text": [ "non-small cell lung (NCI-H460) tumor xenograft" ], "offsets": [ [ 955, 1001 ] ], "normalized": [] }, { "id": "PMID-17462601_T30", "type": "Cancer", "text": [ "BxPC-3 xenograft" ], "offsets": [ [ 1061, 1077 ] ], "normalized": [] }, { "id": "PMID-17462601_T32", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1103, 1108 ] ], "normalized": [] }, { "id": "PMID-17462601_T37", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1302, 1307 ] ], "normalized": [] }, { "id": "PMID-17462601_T38", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 1371, 1378 ] ], "normalized": [] } ]

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[ { "id": "PMID-19369582__text", "type": "abstract", "text": [ "Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets.\nAngiogenesis is a fundamental process to normal and abnormal tissue growth and repair, which consists of recruiting endothelial cells toward an angiogenic stimulus. The cells subsequently proliferate and differentiate to form endothelial tubes and capillary-like structures. Little is known about the metabolic adaptation of endothelial cells through such a transformation. We studied the metabolic changes of endothelial cell activation by growth factors using human umbilical vein endothelial cells (HUVECs), [1,2-(13)C(2)]-glucose and mass isotopomer distribution analysis. The metabolism of [1,2-(13)C(2)]-glucose by HUVEC allows us to trace many of the main glucose metabolic pathways, including glycogen synthesis, the pentose cycle and the glycolytic pathways. So we established that these pathways were crucial to endothelial cell proliferation under vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) stimulation. A specific VEGF receptor-2 inhibitor demonstrated the importance of glycogen metabolism and pentose cycle pathway. Furthermore, we showed that glycogen was depleted in a low glucose medium, but conserved under hypoxic conditions. Finally, we demonstrated that direct inhibition of key enzymes to glycogen metabolism and pentose phosphate pathways reduced HUVEC viability and migration. In this regard, inhibitors of these pathways have been shown to be effective antitumoral agents. To sum up, our data suggest that the inhibition of metabolic pathways offers a novel and powerful therapeutic approach, which simultaneously inhibits tumor cell proliferation and tumor-induced angiogenesis.\n" ], "offsets": [ [ 0, 1782 ] ] } ]

[ { "id": "PMID-19369582_T1", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 204, 210 ] ], "normalized": [] }, { "id": "PMID-19369582_T2", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 259, 276 ] ], "normalized": [] }, { "id": "PMID-19369582_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 312, 317 ] ], "normalized": [] }, { "id": "PMID-19369582_T4", "type": "Tissue", "text": [ "endothelial tubes" ], "offsets": [ [ 369, 386 ] ], "normalized": [] }, { "id": "PMID-19369582_T5", "type": "Tissue", "text": [ "capillary-like structures" ], "offsets": [ [ 391, 416 ] ], "normalized": [] }, { "id": "PMID-19369582_T6", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 468, 485 ] ], "normalized": [] }, { "id": "PMID-19369582_T7", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 553, 569 ] ], "normalized": [] }, { "id": "PMID-19369582_T8", "type": "Cell", "text": [ "human umbilical vein endothelial cells" ], "offsets": [ [ 605, 643 ] ], "normalized": [] }, { "id": "PMID-19369582_T9", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 645, 651 ] ], "normalized": [] }, { "id": "PMID-19369582_T12", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 764, 769 ] ], "normalized": [] }, { "id": "PMID-19369582_T16", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 965, 981 ] ], "normalized": [] }, { "id": "PMID-19369582_T28", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 1447, 1452 ] ], "normalized": [] }, { "id": "PMID-19369582_T29", "type": "Cancer", "text": [ "tumoral" ], "offsets": [ [ 1559, 1566 ] ], "normalized": [] }, { "id": "PMID-19369582_T30", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1725, 1735 ] ], "normalized": [] }, { "id": "PMID-19369582_T31", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1754, 1759 ] ], "normalized": [] } ]

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[ { "id": "PMID-10589785__text", "type": "abstract", "text": [ "The antiangiogenic agent linomide inhibits the growth rate of von Hippel-Lindau paraganglioma xenografts to mice.\nThe aim of this study was to ascertain the potential usefulness of the antiangiogenic compound linomide for treatment of von Hippel-Lindau (VHL)-related tumors. Paraganglioma tissue fragments obtained at surgery from a VHL type 2a patient were transplanted s.c. to male BALB/c nu/nu (nude) mice: (a) 2-3-mm fragments for \"prevention\" experiments; and (b) 2-3-mm fragments allowed to grow to 1 cm for \"intervention\" studies. Both groups received either 0.5 mg/ml linomide in drinking water or acidified water and were followed until tumor diameter reached 3 cm or for 4 weeks. In both the prevention and intervention experiments, a significant diminution of tumor size and weight was observed in the drug-treated animals. In vivo nuclear magnetic resonance analysis of tumor blood flow in linomide-treated animals showed localization of blood vessels almost exclusively to the periphery of the poorly vascularized tumors with a significant reduction of both vascular functionality and vasodilation. Histological examination of tumors from linomide-treated animals revealed marked avascularity. Treated animals also displayed a 2.4-fold reduction of tumor vascular endothelial growth factor mRNA levels. Taken together, our data indicate that in VHL disease, therapy directed at inhibition of constitutively expressed VEGF induction of angiogenesis by VHL tumors may constitute an effective medical treatment.\n" ], "offsets": [ [ 0, 1522 ] ] } ]

[ { "id": "PMID-10589785_T2", "type": "Cancer", "text": [ "von Hippel-Lindau paraganglioma xenografts" ], "offsets": [ [ 62, 104 ] ], "normalized": [] }, { "id": "PMID-10589785_T5", "type": "Cancer", "text": [ "von Hippel-Lindau (VHL)-related tumors" ], "offsets": [ [ 235, 273 ] ], "normalized": [] }, { "id": "PMID-10589785_T6", "type": "Tissue", "text": [ "Paraganglioma tissue fragments" ], "offsets": [ [ 275, 305 ] ], "normalized": [] }, { "id": "PMID-10589785_T10", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 646, 651 ] ], "normalized": [] }, { "id": "PMID-10589785_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 771, 776 ] ], "normalized": [] }, { "id": "PMID-10589785_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 882, 887 ] ], "normalized": [] }, { "id": "PMID-10589785_T13", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 888, 893 ] ], "normalized": [] }, { "id": "PMID-10589785_T15", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 950, 963 ] ], "normalized": [] }, { "id": "PMID-10589785_T16", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1027, 1033 ] ], "normalized": [] }, { "id": "PMID-10589785_T17", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1071, 1079 ] ], "normalized": [] }, { "id": "PMID-10589785_T18", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1140, 1146 ] ], "normalized": [] }, { "id": "PMID-10589785_T20", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1262, 1267 ] ], "normalized": [] }, { "id": "PMID-10589785_T23", "type": "Cancer", "text": [ "VHL tumors" ], "offsets": [ [ 1464, 1474 ] ], "normalized": [] }, { "id": "PMID-10589785_T1", "type": "Tissue", "text": [ "fragments" ], "offsets": [ [ 421, 430 ] ], "normalized": [] }, { "id": "PMID-10589785_T3", "type": "Tissue", "text": [ "fragments" ], "offsets": [ [ 476, 485 ] ], "normalized": [] } ]

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[ { "id": "PMID-12140030__text", "type": "abstract", "text": [ "Optimizing treatment of choroidal neovascularization feeder vessels associated with age-related macular degeneration.\nPURPOSE: To optimize the method of treating choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). DESIGN: Experimental study and interventional case series. METHODS: The parameters associated with locating and then photocoagulating CNV feeder vessels were identified and optimized using published data and data derived from modeling the choroidal vasculature. Based on these optimized parameters, a prototype diagnostic/treatment system was designed that captures high-speed indocyanine green (ICG) angiogram images and facilitates analysis of the images by enhancing visualization of dye movement through CNV feeder vessels (FVs). The system also permits precise aiming and delivery of 810- nm wavelength photocoagulation laser energy to target FVs on a real-time ICG angiogram image of the choroidal vasculature. Target FVs are tracked by a joy-stick controlled laser aiming beam until an intravenously-injected high-concentration ICG dye bolus is observed to enter the target vessel, at which time the laser is fired. Proof of principle of the combined diagnosis/treatment system design for performing dye-enhanced photocoagulation (DEP) in the clinical setting and determination of the minimum DEP laser energy needed to close CNV FVs was made in 11 AMD patients requiring treatment of CNV, but for whom other treatment was not appropriate. RESULTS: Using ICG-DEP, CNV feeder vessels were closed with single pulse laser energy, delivering as little as 0.6 to 1.8 J of energy to the fundus, producing no visible change in the fundus. Successful FV closure was usually indicated immediately by presence of incarcerated ICG dye in the vessel adjacent to the burn site. The prototype system proved relatively easy to operate. After acquiring and interpreting diagnostic angiograms and repositioning a patient in front of the device, feeder vessel DEP and treatment evaluation required 15 to 20 minutes. CONCLUSIONS: Indocyanine green dye-enhanced photocoagulation of CNV feeder vessels, facilitated by use of a device that permits real-time visualization of the choroidal circulation while aiming the treatment laser beam, appears to minimize the amount of energy applied to the fundus and the volume of fundus tissue affected by treatment, compared with other treatment modalities. The combination diagnosis/treatment device should be useful in optimizing FV treatment and in refining and evaluating the efficacy of DEP in future clinical trials.\n" ], "offsets": [ [ 0, 2603 ] ] } ]

[ { "id": "PMID-12140030_T1", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 24, 33 ] ], "normalized": [] }, { "id": "PMID-12140030_T2", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 53, 67 ] ], "normalized": [] }, { "id": "PMID-12140030_T3", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 96, 103 ] ], "normalized": [] }, { "id": "PMID-12140030_T4", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 162, 171 ] ], "normalized": [] }, { "id": "PMID-12140030_T5", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 225, 232 ] ], "normalized": [] }, { "id": "PMID-12140030_T6", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 391, 405 ] ], "normalized": [] }, { "id": "PMID-12140030_T7", "type": "Multi-tissue_structure", "text": [ "choroidal vasculature" ], "offsets": [ [ 492, 513 ] ], "normalized": [] }, { "id": "PMID-12140030_T10", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 765, 779 ] ], "normalized": [] }, { "id": "PMID-12140030_T11", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 781, 784 ] ], "normalized": [] }, { "id": "PMID-12140030_T12", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 901, 904 ] ], "normalized": [] }, { "id": "PMID-12140030_T14", "type": "Multi-tissue_structure", "text": [ "choroidal vasculature" ], "offsets": [ [ 947, 968 ] ], "normalized": [] }, { "id": "PMID-12140030_T15", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 977, 980 ] ], "normalized": [] }, { "id": "PMID-12140030_T16", "type": "Immaterial_anatomical_entity", "text": [ "intravenously" ], "offsets": [ [ 1046, 1059 ] ], "normalized": [] }, { "id": "PMID-12140030_T18", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1134, 1140 ] ], "normalized": [] }, { "id": "PMID-12140030_T19", "type": "Multi-tissue_structure", "text": [ "FVs" ], "offsets": [ [ 1390, 1393 ] ], "normalized": [] }, { "id": "PMID-12140030_T22", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 1528, 1542 ] ], "normalized": [] }, { "id": "PMID-12140030_T23", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 1641, 1647 ] ], "normalized": [] }, { "id": "PMID-12140030_T24", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 1684, 1690 ] ], "normalized": [] }, { "id": "PMID-12140030_T25", "type": "Multi-tissue_structure", "text": [ "FV" ], "offsets": [ [ 1703, 1705 ] ], "normalized": [] }, { "id": "PMID-12140030_T27", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1791, 1797 ] ], "normalized": [] }, { "id": "PMID-12140030_T29", "type": "Multi-tissue_structure", "text": [ "feeder vessel" ], "offsets": [ [ 1988, 2001 ] ], "normalized": [] }, { "id": "PMID-12140030_T31", "type": "Multi-tissue_structure", "text": [ "feeder vessels" ], "offsets": [ [ 2126, 2140 ] ], "normalized": [] }, { "id": "PMID-12140030_T32", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 2217, 2226 ] ], "normalized": [] }, { "id": "PMID-12140030_T33", "type": "Multi-tissue_structure", "text": [ "fundus" ], "offsets": [ [ 2334, 2340 ] ], "normalized": [] }, { "id": "PMID-12140030_T34", "type": "Tissue", "text": [ "fundus tissue" ], "offsets": [ [ 2359, 2372 ] ], "normalized": [] }, { "id": "PMID-12140030_T35", "type": "Multi-tissue_structure", "text": [ "FV" ], "offsets": [ [ 2512, 2514 ] ], "normalized": [] }, { "id": "PMID-12140030_T8", "type": "Multi-tissue_structure", "text": [ "site" ], "offsets": [ [ 1819, 1823 ] ], "normalized": [] } ]

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[ { "id": "PMID-21596785__text", "type": "abstract", "text": [ "mirAct: a web tool for evaluating microRNA activity based on gene expression data.\nMicroRNAs (miRNAs) are critical regulators in the complex cellular networks. The mirAct web server (http://sysbio.ustc.edu.cn/software/mirAct) is a tool designed to investigate miRNA activity based on gene-expression data by using the negative regulation relationship between miRNAs and their target genes. mirAct supports multiple-class data and enables clustering analysis based on computationally determined miRNA activity. Here, we describe the framework of mirAct, demonstrate its performance by comparing with other similar programs and exemplify its applications using case studies.\n" ], "offsets": [ [ 0, 673 ] ] } ]

[ { "id": "PMID-21596785_T1", "type": "Multi-tissue_structure", "text": [ "cellular networks" ], "offsets": [ [ 141, 158 ] ], "normalized": [] } ]

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[ { "id": "PMID-11238633__text", "type": "abstract", "text": [ "IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk.\nIn vivo IL-12-dependent tumor inhibition rests on the ability of IL-12 to activate a CD8-mediated cytotoxicity, inhibit angiogenesis, and cause vascular injury. Although in vivo studies have shown that such inhibition stems from complex interactions of immune cells and the production of IFN-gamma and other downstream angiostatic chemokines, the mechanisms involved are still poorly defined. Here we show that IL-12 activates an anti-angiogenic program in Con A-activated mouse spleen cells (activated spc) or human PBMC (activated PBMC). The soluble factors they release in its presence arrest the cycle of endothelial cells (EC), inhibit in vitro angiogenesis, negatively modulate the production of matrix metalloproteinase-9, and the ability of EC to adhere to vitronectin and up-regulate ICAM-1 and VCAM-1 expression. These effects do not require direct cell-cell contact, yet result from continuous interaction between activated lymphoid cells and EC. We used neutralizing Abs to show that the IFN-inducible protein-10 and monokine-induced by IFN-gamma chemokines are pivotal in inducing these effects. Experiments with nu/nu mice, nonobese diabetic-SCID mice, or activated spc enriched in specific cell subpopulations demonstrated that CD4(+), CD8(+), and NK cells are all needed to mediate the full anti-angiogenetic effect of IL-12.\n" ], "offsets": [ [ 0, 1457 ] ] } ]

[ { "id": "PMID-11238633_T2", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 20, 36 ] ], "normalized": [] }, { "id": "PMID-11238633_T3", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 75, 85 ] ], "normalized": [] }, { "id": "PMID-11238633_T4", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 86, 102 ] ], "normalized": [] }, { "id": "PMID-11238633_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 139, 144 ] ], "normalized": [] }, { "id": "PMID-11238633_T9", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 259, 267 ] ], "normalized": [] }, { "id": "PMID-11238633_T10", "type": "Cell", "text": [ "immune cells" ], "offsets": [ [ 368, 380 ] ], "normalized": [] }, { "id": "PMID-11238633_T15", "type": "Cell", "text": [ "spleen cells" ], "offsets": [ [ 594, 606 ] ], "normalized": [] }, { "id": "PMID-11238633_T16", "type": "Cell", "text": [ "spc" ], "offsets": [ [ 618, 621 ] ], "normalized": [] }, { "id": "PMID-11238633_T18", "type": "Cell", "text": [ "PBMC" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "PMID-11238633_T19", "type": "Cell", "text": [ "PBMC" ], "offsets": [ [ 648, 652 ] ], "normalized": [] }, { "id": "PMID-11238633_T20", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 724, 741 ] ], "normalized": [] }, { "id": "PMID-11238633_T21", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 743, 745 ] ], "normalized": [] }, { "id": "PMID-11238633_T23", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 864, 866 ] ], "normalized": [] }, { "id": "PMID-11238633_T29", "type": "Cell", "text": [ "lymphoid cells" ], "offsets": [ [ 1050, 1064 ] ], "normalized": [] }, { "id": "PMID-11238633_T30", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1069, 1071 ] ], "normalized": [] }, { "id": "PMID-11238633_T34", "type": "Cell", "text": [ "spc" ], "offsets": [ [ 1295, 1298 ] ], "normalized": [] }, { "id": "PMID-11238633_T35", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1320, 1324 ] ], "normalized": [] }, { "id": "PMID-11238633_T37", "type": "Cell", "text": [ "CD4(+)" ], "offsets": [ [ 1358, 1364 ] ], "normalized": [] }, { "id": "PMID-11238633_T39", "type": "Cell", "text": [ "CD8(+)" ], "offsets": [ [ 1366, 1372 ] ], "normalized": [] }, { "id": "PMID-11238633_T40", "type": "Cell", "text": [ "NK cells" ], "offsets": [ [ 1378, 1386 ] ], "normalized": [] }, { "id": "PMID-11238633_T1", "type": "Cellular_component", "text": [ "cell-cell contact" ], "offsets": [ [ 974, 991 ] ], "normalized": [] } ]

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[ { "id": "PMID-10823148__text", "type": "abstract", "text": [ "Application of microsatellite PCR techniques in the identification of mixed up tissue specimens in surgical pathology.\nA fragment of tumour was erroneously mixed up with an endometrial biopsy. Micro-satellite polymerase chain reaction (PCR) clearly demonstrated the extraneous nature of the fragment. Micro-satellite PCR may be useful for the identification of mis-labelled or mismatched tissue fragments in surgical pathology specimens.\n" ], "offsets": [ [ 0, 438 ] ] } ]

[ { "id": "PMID-10823148_T1", "type": "Tissue", "text": [ "tissue specimens" ], "offsets": [ [ 79, 95 ] ], "normalized": [] }, { "id": "PMID-10823148_T2", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 133, 139 ] ], "normalized": [] }, { "id": "PMID-10823148_T3", "type": "Tissue", "text": [ "tissue fragments" ], "offsets": [ [ 388, 404 ] ], "normalized": [] }, { "id": "PMID-10823148_T4", "type": "Tissue", "text": [ "specimens" ], "offsets": [ [ 427, 436 ] ], "normalized": [] }, { "id": "PMID-10823148_T5", "type": "Tissue", "text": [ "endometrial biopsy" ], "offsets": [ [ 173, 191 ] ], "normalized": [] }, { "id": "PMID-10823148_T6", "type": "Cancer", "text": [ "fragment" ], "offsets": [ [ 121, 129 ] ], "normalized": [] }, { "id": "PMID-10823148_T7", "type": "Cancer", "text": [ "fragment" ], "offsets": [ [ 291, 299 ] ], "normalized": [] } ]

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[ { "id": "PMID-16310808__text", "type": "abstract", "text": [ "Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells.\nAngiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 microM and 10 microM inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 microM increased cell migration, while at 10 microM, it decreased cell migration. Thalidomide in concentrations from 0.1 microM to 10 microM did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion.\n" ], "offsets": [ [ 0, 1659 ] ] } ]

[ { "id": "PMID-16310808_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 48, 52 ] ], "normalized": [] }, { "id": "PMID-16310808_T4", "type": "Tissue", "text": [ "capillary tube" ], "offsets": [ [ 77, 91 ] ], "normalized": [] }, { "id": "PMID-16310808_T6", "type": "Cell", "text": [ "endothelial EA.hy 926 cells" ], "offsets": [ [ 111, 138 ] ], "normalized": [] }, { "id": "PMID-16310808_T7", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 158, 170 ] ], "normalized": [] }, { "id": "PMID-16310808_T8", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 271, 288 ] ], "normalized": [] }, { "id": "PMID-16310808_T9", "type": "Tissue", "text": [ "capillary microvessels" ], "offsets": [ [ 343, 365 ] ], "normalized": [] }, { "id": "PMID-16310808_T10", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 377, 385 ] ], "normalized": [] }, { "id": "PMID-16310808_T11", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 402, 414 ] ], "normalized": [] }, { "id": "PMID-16310808_T12", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 495, 507 ] ], "normalized": [] }, { "id": "PMID-16310808_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 881, 885 ] ], "normalized": [] }, { "id": "PMID-16310808_T19", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 920, 929 ] ], "normalized": [] }, { "id": "PMID-16310808_T21", "type": "Cell", "text": [ "endothelial cell line EA.hy 926" ], "offsets": [ [ 949, 980 ] ], "normalized": [] }, { "id": "PMID-16310808_T24", "type": "Tissue", "text": [ "capillary tubes" ], "offsets": [ [ 1120, 1135 ] ], "normalized": [] }, { "id": "PMID-16310808_T25", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1150, 1154 ] ], "normalized": [] }, { "id": "PMID-16310808_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1253, 1257 ] ], "normalized": [] }, { "id": "PMID-16310808_T29", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1302, 1306 ] ], "normalized": [] }, { "id": "PMID-16310808_T31", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1392, 1396 ] ], "normalized": [] }, { "id": "PMID-16310808_T32", "type": "Cell", "text": [ "cell cultures" ], "offsets": [ [ 1419, 1432 ] ], "normalized": [] }, { "id": "PMID-16310808_T35", "type": "Tissue", "text": [ "capillary microvessel" ], "offsets": [ [ 1546, 1567 ] ], "normalized": [] }, { "id": "PMID-16310808_T36", "type": "Cell", "text": [ "EA.hy 926 cells" ], "offsets": [ [ 1619, 1634 ] ], "normalized": [] }, { "id": "PMID-16310808_T1", "type": "Organism_substance", "text": [ "supernatants" ], "offsets": [ [ 1075, 1087 ] ], "normalized": [] } ]

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[ { "id": "PMID-15811263__text", "type": "abstract", "text": [ "[Uncommon etiology of gastrointestinal bleeding: duodenal metastases from renal cell carcinoma].\nBecause of its unpredictable behavior, renal cell carcinoma is one of the most controversial neoplasms. On the one hand, patients frequently show metastases at diagnosis because of its slight manifestations, while on the other, the neoplasm can remain stable after nephrectomy and can then metastasize many years later. When this happens, the metastases usually involve more than 2 organs. The most frequent sites of metastases are the lung and lymph nodes, followed by the bones and liver, while duodenal involvement is rare. Indeed, intestinal metastases are found in only 2% of autopsies and of these, renal cell carcinoma metastases account for 7.1%. We present a case of a solitary late recurrence presenting as upper gastrointestinal bleeding 19 years after nephrectomy for clear cell renal carcinoma.\n" ], "offsets": [ [ 0, 905 ] ] } ]

[ { "id": "PMID-15811263_T1", "type": "Organism_subdivision", "text": [ "gastrointestinal" ], "offsets": [ [ 22, 38 ] ], "normalized": [] }, { "id": "PMID-15811263_T2", "type": "Cancer", "text": [ "duodenal metastases" ], "offsets": [ [ 49, 68 ] ], "normalized": [] }, { "id": "PMID-15811263_T3", "type": "Cancer", "text": [ "renal cell carcinoma" ], "offsets": [ [ 74, 94 ] ], "normalized": [] }, { "id": "PMID-15811263_T4", "type": "Cancer", "text": [ "renal cell carcinoma" ], "offsets": [ [ 136, 156 ] ], "normalized": [] }, { "id": "PMID-15811263_T5", "type": "Cancer", "text": [ "neoplasms" ], "offsets": [ [ 190, 199 ] ], "normalized": [] }, { "id": "PMID-15811263_T7", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 243, 253 ] ], "normalized": [] }, { "id": "PMID-15811263_T8", "type": "Cancer", "text": [ "neoplasm" ], "offsets": [ [ 329, 337 ] ], "normalized": [] }, { "id": "PMID-15811263_T9", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 440, 450 ] ], "normalized": [] }, { "id": "PMID-15811263_T10", "type": "Organ", "text": [ "organs" ], "offsets": [ [ 479, 485 ] ], "normalized": [] }, { "id": "PMID-15811263_T11", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 514, 524 ] ], "normalized": [] }, { "id": "PMID-15811263_T12", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 533, 537 ] ], "normalized": [] }, { "id": "PMID-15811263_T13", "type": "Multi-tissue_structure", "text": [ "lymph nodes" ], "offsets": [ [ 542, 553 ] ], "normalized": [] }, { "id": "PMID-15811263_T14", "type": "Organ", "text": [ "bones" ], "offsets": [ [ 571, 576 ] ], "normalized": [] }, { "id": "PMID-15811263_T15", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 581, 586 ] ], "normalized": [] }, { "id": "PMID-15811263_T16", "type": "Organ", "text": [ "duodenal" ], "offsets": [ [ 594, 602 ] ], "normalized": [] }, { "id": "PMID-15811263_T17", "type": "Cancer", "text": [ "intestinal metastases" ], "offsets": [ [ 632, 653 ] ], "normalized": [] }, { "id": "PMID-15811263_T18", "type": "Cancer", "text": [ "renal cell carcinoma metastases" ], "offsets": [ [ 702, 733 ] ], "normalized": [] }, { "id": "PMID-15811263_T19", "type": "Organism_subdivision", "text": [ "gastrointestinal" ], "offsets": [ [ 820, 836 ] ], "normalized": [] }, { "id": "PMID-15811263_T20", "type": "Cancer", "text": [ "clear cell renal carcinoma" ], "offsets": [ [ 877, 903 ] ], "normalized": [] }, { "id": "PMID-15811263_T6", "type": "Multi-tissue_structure", "text": [ "sites" ], "offsets": [ [ 505, 510 ] ], "normalized": [] } ]

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[ { "id": "PMID-16855378__text", "type": "abstract", "text": [ "Differential mechanisms of radiosensitization by 2-deoxy-D-glucose in the monolayers and multicellular spheroids of a human glioma cell line.\nIn vitro studies using monolayer cultures of human tumor cell lines have shown that 2-DG selectively inhibits energy-dependent DNA repair and cellular recovery processes in cancer cells. However, monolayer cultures differ greatly from the complex environmental conditions generated in solid tumors that develop inhomogeneous hypoxic and necrotic regions. In contrast, multicellular spheroids mimic heterogeneous cellular behavior and the consequent functional characteristics of in vivo solid tumors, and serve as important in vitro model to investigate tumor biology and responses to potential therapeutic agents. The present study compares the radiomodification by 2-DG in monolayer cultures and spheroids of a human glioma cell line (BMG-1) to gain insight into the effects in solid tumors. In spheroids, the glucose consumption (2.1 p mole/cell/h) and lactate production (3.67 p mole/cell/h) was nearly 2-3 fold higher than in monolayer cells (0.83 and 1.43 p mole/cell/h respectively). Presence of 2-DG (5 mM) for 2-4 h inhibited the glucose usage and lactate production by 70% in spheroids, while a 35% reduction was observed in monolayer cells. Under these conditions, 2-DG drastically enhanced the radiation-induced cell death of spheroids (by 2-3 folds); while a 40% increase was observed in monolayer cells. Radiosensitization by 2-DG in monolayer cells was primarily due to an increase in mitotic death (23%) linked to cytogenetic damage (micronuclei), whereas a profound induction of apoptosis (40%) accounted for the sensitization in spheroids. Although the Bcl-2 and Bax levels were significantly higher in spheroids, Bcl-2/Bax ratio was similar in monolayers and spheroids. Comet assay revealed a late onset of DNA breaks in the presence of 2- DG following irradiation only in spheroids, which corroborated well with the late onset of oxidative stress. 2-DG did not induce a significant cell cycle delay in monolayers, while a transient G(2) delay was apparent in spheroids.\n" ], "offsets": [ [ 0, 2132 ] ] } ]

[ { "id": "PMID-16855378_T2", "type": "Cell", "text": [ "monolayers" ], "offsets": [ [ 74, 84 ] ], "normalized": [] }, { "id": "PMID-16855378_T3", "type": "Cell", "text": [ "multicellular spheroids" ], "offsets": [ [ 89, 112 ] ], "normalized": [] }, { "id": "PMID-16855378_T5", "type": "Cell", "text": [ "glioma cell line" ], "offsets": [ [ 124, 140 ] ], "normalized": [] }, { "id": "PMID-16855378_T6", "type": "Cell", "text": [ "monolayer cultures" ], "offsets": [ [ 165, 183 ] ], "normalized": [] }, { "id": "PMID-16855378_T8", "type": "Cell", "text": [ "tumor cell lines" ], "offsets": [ [ 193, 209 ] ], "normalized": [] }, { "id": "PMID-16855378_T11", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 284, 292 ] ], "normalized": [] }, { "id": "PMID-16855378_T12", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 315, 327 ] ], "normalized": [] }, { "id": "PMID-16855378_T13", "type": "Cell", "text": [ "monolayer cultures" ], "offsets": [ [ 338, 356 ] ], "normalized": [] }, { "id": "PMID-16855378_T14", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 427, 439 ] ], "normalized": [] }, { "id": "PMID-16855378_T15", "type": "Pathological_formation", "text": [ "inhomogeneous hypoxic" ], "offsets": [ [ 453, 474 ] ], "normalized": [] }, { "id": "PMID-16855378_T16", "type": "Pathological_formation", "text": [ "necrotic regions" ], "offsets": [ [ 479, 495 ] ], "normalized": [] }, { "id": "PMID-16855378_T17", "type": "Cell", "text": [ "multicellular spheroids" ], "offsets": [ [ 510, 533 ] ], "normalized": [] }, { "id": "PMID-16855378_T18", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 554, 562 ] ], "normalized": [] }, { "id": "PMID-16855378_T19", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 629, 641 ] ], "normalized": [] }, { "id": "PMID-16855378_T20", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 696, 701 ] ], "normalized": [] }, { "id": "PMID-16855378_T22", "type": "Cell", "text": [ "monolayer cultures" ], "offsets": [ [ 817, 835 ] ], "normalized": [] }, { "id": "PMID-16855378_T23", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 840, 849 ] ], "normalized": [] }, { "id": "PMID-16855378_T25", "type": "Cell", "text": [ "glioma cell line" ], "offsets": [ [ 861, 877 ] ], "normalized": [] }, { "id": "PMID-16855378_T26", "type": "Cell", "text": [ "BMG-1" ], "offsets": [ [ 879, 884 ] ], "normalized": [] }, { "id": "PMID-16855378_T27", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 922, 934 ] ], "normalized": [] }, { "id": "PMID-16855378_T28", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 939, 948 ] ], "normalized": [] }, { "id": "PMID-16855378_T31", "type": "Cell", "text": [ "monolayer cells" ], "offsets": [ [ 1073, 1088 ] ], "normalized": [] }, { "id": "PMID-16855378_T35", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1228, 1237 ] ], "normalized": [] }, { "id": "PMID-16855378_T36", "type": "Cell", "text": [ "monolayer cells" ], "offsets": [ [ 1277, 1292 ] ], "normalized": [] }, { "id": "PMID-16855378_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1366, 1370 ] ], "normalized": [] }, { "id": "PMID-16855378_T39", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1380, 1389 ] ], "normalized": [] }, { "id": "PMID-16855378_T40", "type": "Cell", "text": [ "monolayer cells" ], "offsets": [ [ 1443, 1458 ] ], "normalized": [] }, { "id": "PMID-16855378_T42", "type": "Cell", "text": [ "monolayer cells" ], "offsets": [ [ 1490, 1505 ] ], "normalized": [] }, { "id": "PMID-16855378_T43", "type": "Cellular_component", "text": [ "micronuclei" ], "offsets": [ [ 1592, 1603 ] ], "normalized": [] }, { "id": "PMID-16855378_T44", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1689, 1698 ] ], "normalized": [] }, { "id": "PMID-16855378_T47", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1763, 1772 ] ], "normalized": [] }, { "id": "PMID-16855378_T50", "type": "Cell", "text": [ "monolayers" ], "offsets": [ [ 1805, 1815 ] ], "normalized": [] }, { "id": "PMID-16855378_T51", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1820, 1829 ] ], "normalized": [] }, { "id": "PMID-16855378_T54", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 1934, 1943 ] ], "normalized": [] }, { "id": "PMID-16855378_T56", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 2044, 2048 ] ], "normalized": [] }, { "id": "PMID-16855378_T57", "type": "Cell", "text": [ "monolayers" ], "offsets": [ [ 2064, 2074 ] ], "normalized": [] }, { "id": "PMID-16855378_T58", "type": "Cell", "text": [ "spheroids" ], "offsets": [ [ 2121, 2130 ] ], "normalized": [] } ]

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[ { "id": "PMID-15725689__text", "type": "abstract", "text": [ "Role of thrombogenic factors in the development of atherosclerosis.\nHemostatic factors play a crucial role in generating thrombotic plugs at sites of vascular damage (atherothrombosis). However, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis remains uncertain. Autopsy studies have revealed that intimal thickening represents the first stage of atherosclerosis and that lipid-rich plaque arises from such lesions. Several factors contribute to the start of intimal thickening. Platelets release several growth factors and bioactive agents that play a central role in development of not only thrombus but also of intimal thickening. We have been investigating which coagulation factors simultaneously, or subsequently with platelet aggregation, participate in thrombus formation. Tissue factor (TF) is an essential initiator of blood coagulation that is expressed in various stages of atherosclerotic lesions in humans and other animals. Factors including thrombin and fibrin, which are downstream of the coagulation cascade activated by TF, also contribute to atherosclerosis. TF is involved in cell migration, embryogenesis and angiogenesis. Thus TF, in addition to factors downstream of the coagulation cascade and the protease-activated receptor 2 activation system, would be a multifactorial regulator of atherogenesis.\n" ], "offsets": [ [ 0, 1377 ] ] } ]

[ { "id": "PMID-15725689_T3", "type": "Pathological_formation", "text": [ "thrombotic plugs" ], "offsets": [ [ 121, 137 ] ], "normalized": [] }, { "id": "PMID-15725689_T4", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 150, 158 ] ], "normalized": [] }, { "id": "PMID-15725689_T6", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 349, 356 ] ], "normalized": [] }, { "id": "PMID-15725689_T7", "type": "Pathological_formation", "text": [ "lipid-rich plaque" ], "offsets": [ [ 423, 440 ] ], "normalized": [] }, { "id": "PMID-15725689_T8", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 458, 465 ] ], "normalized": [] }, { "id": "PMID-15725689_T9", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "PMID-15725689_T10", "type": "Cell", "text": [ "Platelets" ], "offsets": [ [ 530, 539 ] ], "normalized": [] }, { "id": "PMID-15725689_T11", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 644, 652 ] ], "normalized": [] }, { "id": "PMID-15725689_T12", "type": "Tissue", "text": [ "intimal" ], "offsets": [ [ 665, 672 ] ], "normalized": [] }, { "id": "PMID-15725689_T13", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 775, 783 ] ], "normalized": [] }, { "id": "PMID-15725689_T14", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 812, 820 ] ], "normalized": [] }, { "id": "PMID-15725689_T17", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 880, 885 ] ], "normalized": [] }, { "id": "PMID-15725689_T18", "type": "Pathological_formation", "text": [ "atherosclerotic lesions" ], "offsets": [ [ 937, 960 ] ], "normalized": [] }, { "id": "PMID-15725689_T24", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1148, 1152 ] ], "normalized": [] }, { "id": "PMID-15725689_T1", "type": "Multi-tissue_structure", "text": [ "sites" ], "offsets": [ [ 141, 146 ] ], "normalized": [] } ]

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[ { "id": "PMID-9206208__text", "type": "abstract", "text": [ "[Expression of metastasis suppressor gene nm23 in human hepatocellular carcinoma]. \nFor the purpose of investigating the relationship between the metastatic potential of the tumor as well as the expression of nm23-H1 mRNA, and for determing the location of the positive sites in the cells, tumor metastasis suppressor gene nm23-H1 in human hepatocellular carcinoma (and the nonneoplastic area surrounding the tumor) was detected by in situ hybridization using digoxiginin-labeled nm23-H1 antisense complementary RNA probe. The primary results indicated (i) positive results of in situ hybridization are presence of granules or masses in the cytoplasm; (ii) the less expression of nm23-H1 mRNA, the higher metastatic rate of the human hepatocellular carcinoma (P < 0.05); (iii) expression of nm23-H1 mRNA dose not correlate with some other factors such as tumor size and the background of other liver diseases.\n" ], "offsets": [ [ 0, 910 ] ] } ]

[ { "id": "PMID-9206208_T3", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 56, 80 ] ], "normalized": [] }, { "id": "PMID-9206208_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 174, 179 ] ], "normalized": [] }, { "id": "PMID-9206208_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 283, 288 ] ], "normalized": [] }, { "id": "PMID-9206208_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 290, 295 ] ], "normalized": [] }, { "id": "PMID-9206208_T10", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 340, 364 ] ], "normalized": [] }, { "id": "PMID-9206208_T11", "type": "Multi-tissue_structure", "text": [ "nonneoplastic area" ], "offsets": [ [ 374, 392 ] ], "normalized": [] }, { "id": "PMID-9206208_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 409, 414 ] ], "normalized": [] }, { "id": "PMID-9206208_T15", "type": "Cellular_component", "text": [ "granules" ], "offsets": [ [ 615, 623 ] ], "normalized": [] }, { "id": "PMID-9206208_T16", "type": "Organism_substance", "text": [ "cytoplasm" ], "offsets": [ [ 641, 650 ] ], "normalized": [] }, { "id": "PMID-9206208_T19", "type": "Cancer", "text": [ "hepatocellular carcinoma" ], "offsets": [ [ 734, 758 ] ], "normalized": [] }, { "id": "PMID-9206208_T21", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 855, 860 ] ], "normalized": [] }, { "id": "PMID-9206208_T22", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "PMID-9206208_T32", "type": "Cancer", "text": [ "masses" ], "offsets": [ [ 627, 633 ] ], "normalized": [] } ]

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[ { "id": "PMID-18662848__text", "type": "abstract", "text": [ "Reversal of the malignant phenotype of ovarian cancer A2780 cells through transfection with wild-type PTEN gene. \nOBJECTIVE: PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor gene identified on human chromosome 10q23. Substantial studies have demonstrated that PTEN can inhibit cell proliferation, migration and invasion of many cancer cells. The purpose of this study was to determine whether upregulation of PTEN gene by transfection wild-type PTEN gene to ovarian cancer cells can inhibit growth and migration and to explore the potential for PTEN gene therapy of ovarian cancers. METHOD: Wild-type and phosphatase-inactive (C124A) PTEN plasmids were transfected into ovarian epithelial cancer A2780 cells, and their effects on cell apoptosis, cell proliferation, cell migration and cell invasion were analyzed by flow cytometry analysis, TUNEL assay, MTT assay, wound-healing assay and transwell assay. RESULTS: Both wild-type and mutant PTEN can upregulate the expression of PTEN gene dramatically; however, it is wild-type PTEN not phosphatase-inactive PTEN that can induce apoptosis and decrease cell migration, invasion and proliferation in ovarian cancer cells. CONCLUSION: These results demonstrated that PTEN had played an important role in the cell proliferation, cell migration and invasion dependent on its phosphatase activity. Enhanced expression of PTEN by gene transfer is sufficient to reverse the malignant phenotype of ovarian cancer cells and transfection of ovarian cancer cells with wild-type PTEN gene might be another novel approach for therapeutic intervention in ovarian cancer.\n" ], "offsets": [ [ 0, 1644 ] ] } ]

[ { "id": "PMID-18662848_T1", "type": "Cell", "text": [ "ovarian cancer A2780 cells" ], "offsets": [ [ 39, 65 ] ], "normalized": [] }, { "id": "PMID-18662848_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 195, 200 ] ], "normalized": [] }, { "id": "PMID-18662848_T7", "type": "Cellular_component", "text": [ "chromosome 10q23" ], "offsets": [ [ 237, 253 ] ], "normalized": [] }, { "id": "PMID-18662848_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 315, 319 ] ], "normalized": [] }, { "id": "PMID-18662848_T10", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 366, 378 ] ], "normalized": [] }, { "id": "PMID-18662848_T13", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 496, 516 ] ], "normalized": [] }, { "id": "PMID-18662848_T15", "type": "Cancer", "text": [ "ovarian cancers" ], "offsets": [ [ 604, 619 ] ], "normalized": [] }, { "id": "PMID-18662848_T17", "type": "Cell", "text": [ "ovarian epithelial cancer A2780 cells" ], "offsets": [ [ 708, 745 ] ], "normalized": [] }, { "id": "PMID-18662848_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "PMID-18662848_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 784, 788 ] ], "normalized": [] }, { "id": "PMID-18662848_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 804, 808 ] ], "normalized": [] }, { "id": "PMID-18662848_T21", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 823, 827 ] ], "normalized": [] }, { "id": "PMID-18662848_T22", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 903, 908 ] ], "normalized": [] }, { "id": "PMID-18662848_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1140, 1144 ] ], "normalized": [] }, { "id": "PMID-18662848_T29", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 1186, 1206 ] ], "normalized": [] }, { "id": "PMID-18662848_T31", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "PMID-18662848_T32", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "PMID-18662848_T34", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 1477, 1497 ] ], "normalized": [] }, { "id": "PMID-18662848_T35", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 1518, 1538 ] ], "normalized": [] }, { "id": "PMID-18662848_T37", "type": "Cancer", "text": [ "ovarian cancer" ], "offsets": [ [ 1628, 1642 ] ], "normalized": [] }, { "id": "PMID-18662848_T72", "type": "Cellular_component", "text": [ "plasmids" ], "offsets": [ [ 677, 685 ] ], "normalized": [] } ]

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[ { "id": "PMID-2541348__text", "type": "abstract", "text": [ "Energy supply of the mitotic cell cycle and the Na+/H+-antiport in ascites tumors.\nThe activation of Na+ transport is due to the exchange of protons formed via glucose conversion into lactate for Na+, i.e., to the stimulation of the Na+/H+-antiport. Experimental results and theoretical calculations suggest that in glucose-containing medium the Na+ transport increases from 0.75 to 1.78 pmol/hour per cell. The permeability of plasma membranes for K+ increases 2.75 fold, while the passive flux of Na+ diminishes. The intensity of O2 adsorption by ascites tumor cells does not practically depend on the monovalent cation concentration gradient between the cells and the culture medium, whereas the rate of glycolysis decreases simultaneously with the diminution of the concentration gradient. In synchronized cultures at the beginning of the mitotic cycle, the bulk of ATP resynthesized via glycolysis is utilized for the synthesis of biopolymers, whereas that at the end of the S-phase and in the G2-phase is utilized for cation transport across plasma membranes. From 35 to 100% of the whole amount of ATP resynthesized via glycolysis is utilized for transport purposes. It is concluded that the observed increase in the Na+/K+ ratio in ascites tumor cells is connected with their enhanced ability to synthesize lactic acid. Presumably, glycolysis is one of the regulatory mechanisms of intracellular ratios of monovalent cations.\n" ], "offsets": [ [ 0, 1434 ] ] } ]

[ { "id": "PMID-2541348_T3", "type": "Cancer", "text": [ "ascites tumors" ], "offsets": [ [ 67, 81 ] ], "normalized": [] }, { "id": "PMID-2541348_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 402, 406 ] ], "normalized": [] }, { "id": "PMID-2541348_T14", "type": "Cellular_component", "text": [ "plasma membranes" ], "offsets": [ [ 428, 444 ] ], "normalized": [] }, { "id": "PMID-2541348_T18", "type": "Cell", "text": [ "ascites tumor cells" ], "offsets": [ [ 549, 568 ] ], "normalized": [] }, { "id": "PMID-2541348_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 657, 662 ] ], "normalized": [] }, { "id": "PMID-2541348_T21", "type": "Cell", "text": [ "cultures" ], "offsets": [ [ 810, 818 ] ], "normalized": [] }, { "id": "PMID-2541348_T24", "type": "Cellular_component", "text": [ "plasma membranes" ], "offsets": [ [ 1048, 1064 ] ], "normalized": [] }, { "id": "PMID-2541348_T28", "type": "Cell", "text": [ "ascites tumor cells" ], "offsets": [ [ 1240, 1259 ] ], "normalized": [] }, { "id": "PMID-2541348_T30", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1390, 1403 ] ], "normalized": [] }, { "id": "PMID-2541348_T50", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 29, 33 ] ], "normalized": [] } ]

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[ { "id": "PMID-10771470__text", "type": "abstract", "text": [ "Active hair growth (anagen) is associated with angiogenesis.\nAfter the completion of skin development, angiogenesis, i.e., the growth of new capillaries from pre-existing blood vessels, is held to occur in the skin only under pathologic conditions. It has long been noted, however, that hair follicle cycling is associated with prominent changes in skin perfusion, that the epithelial hair bulbs of anagen follicles display angiogenic properties, and that the follicular dermal papilla can produce angiogenic factors. Despite these suggestive observations, no formal proof is as yet available for the concept that angiogenesis is a physiologic event that occurs all over the mature mammalian integument whenever hair follicles switch from resting (telogen) to active growth (anagen). This study uses quantitative histomorphometry and double-immunohistologic detection techniques for the demarcation of proliferating endothelial cells, to show that synchronized hair follicle cycling in adolescent C57BL/6 mice is associated with substantial angiogenesis, and that inhibiting angiogenesis in vivo by the intraperitoneal application of a fumagillin derivative retards experimentally induced anagen development in these mice. Thus, angiogenesis is a physiologic event in normal postnatal murine skin, apparently is dictated by the hair follicle, and appears to be required for normal anagen development. Anagen-associated angiogenesis offers an attractive model for identifying the physiologic controls of cutaneous angiogenesis, and an interesting system for screening the effects of potential antiangiogenic drugs in vivo.\n" ], "offsets": [ [ 0, 1622 ] ] } ]

[ { "id": "PMID-10771470_T1", "type": "Multi-tissue_structure", "text": [ "hair" ], "offsets": [ [ 7, 11 ] ], "normalized": [] }, { "id": "PMID-10771470_T2", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 85, 89 ] ], "normalized": [] }, { "id": "PMID-10771470_T3", "type": "Tissue", "text": [ "capillaries" ], "offsets": [ [ 141, 152 ] ], "normalized": [] }, { "id": "PMID-10771470_T4", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 171, 184 ] ], "normalized": [] }, { "id": "PMID-10771470_T5", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 210, 214 ] ], "normalized": [] }, { "id": "PMID-10771470_T6", "type": "Multi-tissue_structure", "text": [ "hair follicle" ], "offsets": [ [ 287, 300 ] ], "normalized": [] }, { "id": "PMID-10771470_T7", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 349, 353 ] ], "normalized": [] }, { "id": "PMID-10771470_T8", "type": "Tissue", "text": [ "epithelial hair bulbs" ], "offsets": [ [ 374, 395 ] ], "normalized": [] }, { "id": "PMID-10771470_T9", "type": "Multi-tissue_structure", "text": [ "anagen follicles" ], "offsets": [ [ 399, 415 ] ], "normalized": [] }, { "id": "PMID-10771470_T10", "type": "Tissue", "text": [ "follicular dermal papilla" ], "offsets": [ [ 460, 485 ] ], "normalized": [] }, { "id": "PMID-10771470_T11", "type": "Multi-tissue_structure", "text": [ "hair follicles" ], "offsets": [ [ 712, 726 ] ], "normalized": [] }, { "id": "PMID-10771470_T12", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 916, 933 ] ], "normalized": [] }, { "id": "PMID-10771470_T13", "type": "Multi-tissue_structure", "text": [ "hair follicle" ], "offsets": [ [ 961, 974 ] ], "normalized": [] }, { "id": "PMID-10771470_T15", "type": "Immaterial_anatomical_entity", "text": [ "intraperitoneal" ], "offsets": [ [ 1103, 1118 ] ], "normalized": [] }, { "id": "PMID-10771470_T17", "type": "Multi-tissue_structure", "text": [ "anagen" ], "offsets": [ [ 1189, 1195 ] ], "normalized": [] }, { "id": "PMID-10771470_T20", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1292, 1296 ] ], "normalized": [] }, { "id": "PMID-10771470_T21", "type": "Multi-tissue_structure", "text": [ "hair follicle" ], "offsets": [ [ 1328, 1341 ] ], "normalized": [] }, { "id": "PMID-10771470_T22", "type": "Organism_subdivision", "text": [ "cutaneous" ], "offsets": [ [ 1503, 1512 ] ], "normalized": [] }, { "id": "PMID-10771470_T52", "type": "Multi-tissue_structure", "text": [ "anagen" ], "offsets": [ [ 1381, 1387 ] ], "normalized": [] } ]

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[ { "id": "PMC-3256136-sec-15__text", "type": "sec", "text": [ "Discussion\nWe estimated the future acceptability of PrEP, examining the attitudes and preferences of potential user groups from different countries towards hypothetical and known PrEP attributes. Our results show that participants were generally willing to accept PrEP and adopt it as soon as it becomes available. Surprisingly, participants were also willing to take PrEP even when reminded of potential side effects, cost, condom use, and frequent HIV testing. These findings indicate participants' motivation to overcome barriers which can have a considerable impact on uptake. In contrast, participants mentioned that the thought of taking PrEP made them feel anxious, although they also indicated that taking PrEP would not be embarrassing and they would want their partner or partners to know. Participants' anxiety may be explained by the hypothetical nature of most of the presented PrEP characteristics, the stigma associated with HIV [34], and in some settings, the criminalization of sex work, injected drug use and homosexuality [35]. Most participants, nonetheless, subsequently indicated that PrEP would give them hope, which suggests that their initial willingness to take it remained largely unscathed.\nFemale participants indicated a higher level of willingness to take PrEP than male participants, which may be explained by women's difficulty negotiating the use of condoms and awareness of their and/or their partners' risk of becoming infected with HIV [36]. We also found that younger participants and those with fewer children, those who reported adherence to past medication, more frequent condom usage, having been tested for HIV in the past and never injecting drugs, reported greater willingness to take PrEP. These promising findings suggest that those who are currently bearing the brunt of HIV [1], have higher perceived risk, and are most likely to adhere to a comprehensive PrEP program, are also the most motivated to enroll. Yet, while participants stated not being interested in selling PrEP, the majority reported intentions to share it. Therefore, information and counseling about the risks of sharing PrEP should be readily available as part of any implementation program.\nResults from the conjoint analysis reveal trends in participants' preferences which deserve consideration. PrEP route of administration was the most important attribute, and bi-monthly and monthly injections were the preferred alternatives. This finding is encouraging from a policy perspective if such modalities become available; since it may reduce users' likelihood of sharing, selling or forgetting to take PrEP, but it also raises questions regarding participants' willingness to take oral PrEP. HIV testing was the second most important attribute, and a test every six months was, as expected, the preferred alternative. Interestingly, dispensing sites were more important than any other attribute for some groups, particularly in Africa. This may indicate concerns about social stigma and access [37]. However, it is encouraging that most participants were willing to receive PrEP at a healthcare facility, which can facilitate synergies between PrEP and other existing prevention services. Time spent obtaining PrEP and frequency of pick up, which we used as a proxy measure for cost-opportunity, were generally less important, consistent with participants' willingness to pay for PrEP.\nOur findings are broadly consistent with the work of Guest et al. and Galea et al [18], [19]. However, specific comparisons are not advisable as the composition and size of the samples, recruitment methods, measures and statistical analyses differ greatly. Previous work on PrEP implementation suggests that delivery programs will need to meet a number of requirements in order to be effective, including: prioritization of groups at higher risk of infection; delivery of PrEP in combination with other prevention services, including risk reduction and medication adherence counseling, condoms provision, diagnosis and treatment of other sexually transmitted infections, and frequent HIV testing; and monitoring of side effects, adherence and risk behaviors [8], [38], [39], [40], [41], [42]. Our results provide valuable clues that can help countries to deliver PrEP more effectively, should they decide to implement it, by focusing their efforts on the aspects that need more attention.\nThis is the first multinational study, to our knowledge, that integrates different disciplines to shed light on a question that we believe is of global importance. Our study complements previous work on PrEP by examining potential users' perspective and offering insights into their attitudes and preferences. We note that it may not be possible to generalize the observed PrEP acceptability to other settings and our results should be considered within the context of this study's limitations. Given the sensitive nature of the addressed questions, and despite all our efforts to reduce social desirability bias, there is an unavoidable risk that participants may have felt at times compelled to provide what they felt was the \"right\" answer. Additionally, our data collection took place in urban areas, where HIV incidence is normally higher, thus current findings may not be generalizable to rural settings. Finally, examining acceptability among users enrolled in pilot programs is much deserving, as actual acceptability may differ from potential willingness to take PrEP, especially if relevant attributes of a product or program are modified, as observed in other comparable interventions [43].\n\n" ], "offsets": [ [ 0, 5598 ] ] } ]

[ { "id": "PMC-3256136-sec-15_T1", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 2701, 2705 ] ], "normalized": [] } ]

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[ { "id": "PMC-3041925-caption-05__text", "type": "caption", "text": [ "Intact mass analysis of a mixed population of proteins. A mixture of the membrane protein KCNJ12, the soluble TEV protease used to cleave the fusion tag, and the membrane protein HVCN1, which occurred as a contaminant from an earlier analysis on the same LC column.\n" ], "offsets": [ [ 0, 266 ] ] } ]

[ { "id": "PMC-3041925-caption-05_T1", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 73, 81 ] ], "normalized": [] }, { "id": "PMC-3041925-caption-05_T2", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 162, 170 ] ], "normalized": [] } ]

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[ { "id": "PMID-18835936__text", "type": "abstract", "text": [ "Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity.\nOBJECTIVE: The expansion of adipose tissue is linked to the development of its vasculature. However, the regulation of adipose tissue angiogenesis in humans has not been extensively studied. Our aim was to compare the angiogenesis associated with subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from the same obese patients in an in vivo model. RESEARCH DESIGN AND METHODS: Adipose tissue samples from visceral (VAT) and subcutaneous (SAT) sites, obtained from 36 obese patients (mean BMI 46.5 kg/m(2)) during bariatric surgery, were layered on chick chorioallantoic membrane (CAM). RESULTS: Both SAT and VAT expressed angiogenic factors without significant difference for vascular endothelial growth factor (VEGF) expression. Adipose tissue layered on CAM stimulated angiogenesis. Angiogenic stimulation was macroscopically detectable, with engulfment of the samples, in 39% and was evidenced by angiography in 59% of the samples. A connection between CAM and adipose tissue vessels was evidenced by immunohistochemistry, with recruitment of both avian and human endothelial cells. The angiogenic potency of adipose tissue was not related to its localization (with an angiogenic stimulation in 60% of SAT samples and 61% of VAT samples) or to adipocyte size or inflammatory infiltrate assessed in adipose samples before the graft on CAM. Stimulation of angiogenesis by adipose tissue was nearly abolished by bevacizumab, which specifically targets human VEGF. CONCLUSIONS: We have established a model to study the regulation of angiogenesis by human adipose tissue. This model highlighted the role of VEGF in angiogenesis in both SAT and VAT.\n" ], "offsets": [ [ 0, 1759 ] ] } ]

[ { "id": "PMID-18835936_T1", "type": "Tissue", "text": [ "visceral" ], "offsets": [ [ 29, 37 ] ], "normalized": [] }, { "id": "PMID-18835936_T2", "type": "Tissue", "text": [ "subcutaneous adipose tissue" ], "offsets": [ [ 42, 69 ] ], "normalized": [] }, { "id": "PMID-18835936_T4", "type": "Tissue", "text": [ "adipose tissue" ], "offsets": [ [ 123, 137 ] ], "normalized": [] }, { "id": "PMID-18835936_T5", "type": "Multi-tissue_structure", "text": [ "vasculature" ], "offsets": [ [ 174, 185 ] ], "normalized": [] }, { "id": "PMID-18835936_T6", "type": "Tissue", "text": [ "adipose tissue" ], "offsets": [ [ 214, 228 ] ], "normalized": [] }, { "id": "PMID-18835936_T8", "type": "Tissue", "text": [ "subcutaneous adipose tissue" ], "offsets": [ [ 342, 369 ] ], "normalized": [] }, { "id": "PMID-18835936_T9", "type": "Tissue", "text": [ "SAT" ], "offsets": [ [ 371, 374 ] ], "normalized": [] }, { "id": "PMID-18835936_T10", "type": "Tissue", "text": [ "visceral adipose tissue" ], "offsets": [ [ 380, 403 ] ], "normalized": [] }, { "id": "PMID-18835936_T11", "type": "Tissue", "text": [ "VAT" ], "offsets": [ [ 405, 408 ] ], "normalized": [] }, { "id": "PMID-18835936_T13", "type": "Tissue", "text": [ "Adipose tissue samples" ], "offsets": [ [ 489, 511 ] ], "normalized": [] }, { "id": "PMID-18835936_T14", "type": "Tissue", "text": [ "visceral" ], "offsets": [ [ 517, 525 ] ], "normalized": [] }, { "id": "PMID-18835936_T15", "type": "Tissue", "text": [ "VAT" ], "offsets": [ [ 527, 530 ] ], "normalized": [] }, { "id": "PMID-18835936_T16", "type": "Tissue", "text": [ "subcutaneous (SAT) sites" ], "offsets": [ [ 536, 560 ] ], "normalized": [] }, { "id": "PMID-18835936_T19", "type": "Multi-tissue_structure", "text": [ "chorioallantoic membrane" ], "offsets": [ [ 666, 690 ] ], "normalized": [] }, { "id": "PMID-18835936_T20", "type": "Multi-tissue_structure", "text": [ "CAM" ], "offsets": [ [ 692, 695 ] ], "normalized": [] }, { "id": "PMID-18835936_T21", "type": "Tissue", "text": [ "SAT" ], "offsets": [ [ 712, 715 ] ], "normalized": [] }, { "id": "PMID-18835936_T22", "type": "Tissue", "text": [ "VAT" ], "offsets": [ [ 720, 723 ] ], "normalized": [] }, { "id": "PMID-18835936_T25", "type": "Tissue", "text": [ "Adipose tissue" ], "offsets": [ [ 842, 856 ] ], "normalized": [] }, { "id": "PMID-18835936_T26", "type": "Multi-tissue_structure", "text": [ "CAM" ], "offsets": [ [ 868, 871 ] ], "normalized": [] }, { "id": "PMID-18835936_T27", "type": "Multi-tissue_structure", "text": [ "CAM" ], "offsets": [ [ 1068, 1071 ] ], "normalized": [] }, { "id": "PMID-18835936_T28", "type": "Tissue", "text": [ "adipose tissue vessels" ], "offsets": [ [ 1076, 1098 ] ], "normalized": [] }, { "id": "PMID-18835936_T31", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1179, 1196 ] ], "normalized": [] }, { "id": "PMID-18835936_T32", "type": "Tissue", "text": [ "adipose tissue" ], "offsets": [ [ 1224, 1238 ] ], "normalized": [] }, { "id": "PMID-18835936_T33", "type": "Tissue", "text": [ "SAT samples" ], "offsets": [ [ 1317, 1328 ] ], "normalized": [] }, { "id": "PMID-18835936_T34", "type": "Tissue", "text": [ "VAT samples" ], "offsets": [ [ 1340, 1351 ] ], "normalized": [] }, { "id": "PMID-18835936_T35", "type": "Cell", "text": [ "adipocyte" ], "offsets": [ [ 1359, 1368 ] ], "normalized": [] }, { "id": "PMID-18835936_T36", "type": "Tissue", "text": [ "adipose samples" ], "offsets": [ [ 1413, 1428 ] ], "normalized": [] }, { "id": "PMID-18835936_T37", "type": "Tissue", "text": [ "graft" ], "offsets": [ [ 1440, 1445 ] ], "normalized": [] }, { "id": "PMID-18835936_T38", "type": "Multi-tissue_structure", "text": [ "CAM" ], "offsets": [ [ 1449, 1452 ] ], "normalized": [] }, { "id": "PMID-18835936_T39", "type": "Tissue", "text": [ "adipose tissue" ], "offsets": [ [ 1485, 1499 ] ], "normalized": [] }, { "id": "PMID-18835936_T44", "type": "Tissue", "text": [ "adipose tissue" ], "offsets": [ [ 1666, 1680 ] ], "normalized": [] }, { "id": "PMID-18835936_T46", "type": "Tissue", "text": [ "SAT" ], "offsets": [ [ 1746, 1749 ] ], "normalized": [] }, { "id": "PMID-18835936_T47", "type": "Tissue", "text": [ "VAT" ], "offsets": [ [ 1754, 1757 ] ], "normalized": [] }, { "id": "PMID-18835936_T3", "type": "Tissue", "text": [ "samples" ], "offsets": [ [ 975, 982 ] ], "normalized": [] }, { "id": "PMID-18835936_T7", "type": "Tissue", "text": [ "samples" ], "offsets": [ [ 1038, 1045 ] ], "normalized": [] } ]

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[ { "id": "PMID-16101297__text", "type": "abstract", "text": [ "A novel conotoxin from Conus delessertii with posttranslationally modified lysine residues.\nA major peptide, de13a from the crude venom of Conus delessertii collected in the Yucatan Channel, Mexico, was purified. The peptide had a high content of posttranslationally modified amino acids, including 6-bromotryptophan and a nonstandard amino acid that proved to be 5-hydroxylysine. This is the first report of 5-hydroxylysine residues in conotoxins. The sequence analysis, together with cDNA cloning and a mass determination (monoisotopic mass of 3486.76 Da), established that the mature toxin has the sequence DCOTSCOTTCANGWECCKGYOCVNKACSGCTH, where O is 4-hydroxyproline, W 6-bromotryptophan, and K 5-hydroxylysine, the asterisk represents the amidated C-terminus, and the calculated monoisotopic mass is 3487.09 Da. The eight Cys residues are arranged in a pattern (C-C-C-CC-C-C-C) not described previously in conotoxins. This arrangement, for which we propose the designation of framework #13 or XIII, differs from the ones (C-C-CC-CC-C-C and C-C-C-C-CC-C-C) present in other conotoxins which also contain eight Cys residues. This peptide thus defines a novel class of conotoxins, with a new posttranslational modification not previously found in other Conus peptide families.\n" ], "offsets": [ [ 0, 1280 ] ] } ]

[ { "id": "PMID-16101297_T1", "type": "Organism_substance", "text": [ "venom" ], "offsets": [ [ 130, 135 ] ], "normalized": [] } ]

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[ { "id": "PMID-20676141__text", "type": "abstract", "text": [ "Adenovirus 5 E1A enhances histone deacetylase inhibitors-induced apoptosis through Egr-1-mediated Bim upregulation. \nHistone deacetylase inhibitors (HDACi) are potent anti-cancer agents for variety of cancer types. Suberoylanilide hydroxamic acid (SAHA) has been approved as a drug to treat cutaneous T cell lymphoma, and the combination of HDACi and other agents have been actively tested in many clinical trials. Adenovirus 5 early region 1A (E1A) has been shown to exhibit high tumor suppressor activity, and gene therapy using E1A has been tested in clinical trials. Here, we showed that proapoptotic activity of HDACi was robustly enhanced by E1A in multiple cancer cells, but not in normal cells. Moreover, we showed that combination of E1A gene therapy and SAHA showed high therapeutic efficacy with low toxicity in vivo ovarian and breast xenograft models. SAHA downregulated Bcl-XL and upregulated proapoptotic BH3-only protein Bim, whose expression was further enhanced by E1A in cancer cells. These alterations of Bcl-2 family proteins were critical for apoptosis induced by the combination in cancer cells. SAHA enhanced acetylation of histone H3 in Bim promoter region, while E1A upregulated Egr-1, which was directly involved in Bim transactivation. Together, our results provide not only a novel insight into the mechanisms underlying anti-tumor activity of E1A, but also a rationale for the combined HDACi and E1A gene therapy in future clinical trials.\n" ], "offsets": [ [ 0, 1470 ] ] } ]

[ { "id": "PMID-20676141_T7", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 172, 178 ] ], "normalized": [] }, { "id": "PMID-20676141_T8", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 201, 207 ] ], "normalized": [] }, { "id": "PMID-20676141_T11", "type": "Cancer", "text": [ "cutaneous T cell lymphoma" ], "offsets": [ [ 291, 316 ] ], "normalized": [] }, { "id": "PMID-20676141_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 481, 486 ] ], "normalized": [] }, { "id": "PMID-20676141_T18", "type": "Cell", "text": [ "multiple cancer cells" ], "offsets": [ [ 655, 676 ] ], "normalized": [] }, { "id": "PMID-20676141_T19", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 696, 701 ] ], "normalized": [] }, { "id": "PMID-20676141_T22", "type": "Cancer", "text": [ "ovarian" ], "offsets": [ [ 828, 835 ] ], "normalized": [] }, { "id": "PMID-20676141_T23", "type": "Cancer", "text": [ "breast xenograft" ], "offsets": [ [ 840, 856 ] ], "normalized": [] }, { "id": "PMID-20676141_T28", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 990, 1002 ] ], "normalized": [] }, { "id": "PMID-20676141_T30", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 1105, 1117 ] ], "normalized": [] }, { "id": "PMID-20676141_T37", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1355, 1360 ] ], "normalized": [] } ]

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[ { "id": "PMID-12823209__text", "type": "abstract", "text": [ "Prognostic value of p53 protein expression and vascular endothelial growth factor expression in resected squamous cell carcinoma of the esophagus.\nThe most common genetic alterations found in a wide variety of cancers are p53 tumor suppressor gene mutations. p53 appears to be a nuclear transcription factor that plays a role in the control of cell proliferation, apoptosis, and the maintenance of genetic stability. Angiogenesis is a critical process in solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator. Few studies have investigated the association between p53 and VEGF expressions and prognosis in esophageal carcinoma. Forty-seven specimens resected from patients with stage II and III squamous cell carcinoma (SCC) of the esophagus were studied using immunohistochemical staining. VEGF and p53 expressions were observed in 40% and 53% of the tumors, respectively. The p53 and VEGF staining statuses were coincident in only 21% of the tumors, and no significant correlation was found between p53 and VEGF statuses. No clinicopathologic factors were significantly correlated with p53 or VEGF expression. No significant association between p53 and VEGF expressions and poor prognosis was found. In conclusion, p53 and VEGF were not correlated with prognosis in patients with stage II and III SCC of the esophagus.\n" ], "offsets": [ [ 0, 1465 ] ] } ]

[ { "id": "PMID-12823209_T3", "type": "Cancer", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 105, 128 ] ], "normalized": [] }, { "id": "PMID-12823209_T4", "type": "Organ", "text": [ "esophagus" ], "offsets": [ [ 136, 145 ] ], "normalized": [] }, { "id": "PMID-12823209_T5", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 210, 217 ] ], "normalized": [] }, { "id": "PMID-12823209_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 226, 231 ] ], "normalized": [] }, { "id": "PMID-12823209_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 344, 348 ] ], "normalized": [] }, { "id": "PMID-12823209_T10", "type": "Cancer", "text": [ "solid tumor" ], "offsets": [ [ 455, 466 ] ], "normalized": [] }, { "id": "PMID-12823209_T13", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 624, 629 ] ], "normalized": [] }, { "id": "PMID-12823209_T16", "type": "Cancer", "text": [ "esophageal carcinoma" ], "offsets": [ [ 750, 770 ] ], "normalized": [] }, { "id": "PMID-12823209_T18", "type": "Cancer", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 839, 862 ] ], "normalized": [] }, { "id": "PMID-12823209_T19", "type": "Cancer", "text": [ "SCC" ], "offsets": [ [ 864, 867 ] ], "normalized": [] }, { "id": "PMID-12823209_T20", "type": "Organ", "text": [ "esophagus" ], "offsets": [ [ 876, 885 ] ], "normalized": [] }, { "id": "PMID-12823209_T23", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 996, 1002 ] ], "normalized": [] }, { "id": "PMID-12823209_T26", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1088, 1094 ] ], "normalized": [] }, { "id": "PMID-12823209_T36", "type": "Cancer", "text": [ "SCC" ], "offsets": [ [ 1443, 1446 ] ], "normalized": [] }, { "id": "PMID-12823209_T37", "type": "Organ", "text": [ "esophagus" ], "offsets": [ [ 1454, 1463 ] ], "normalized": [] }, { "id": "PMID-12823209_T57", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 279, 286 ] ], "normalized": [] }, { "id": "PMID-12823209_T58", "type": "Multi-tissue_structure", "text": [ "specimens" ], "offsets": [ [ 784, 793 ] ], "normalized": [] } ]

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[ { "id": "PMID-10487573__text", "type": "abstract", "text": [ "External beam radiotherapy for subretinal neovascularization in age-related macular degeneration: is this treatment efficient?\nPURPOSE: Control of the natural course of subretinal neovascularization (SRNV) in age-related macular degeneration (AMD) is difficult. Only a subset of patients is suitable for laser coagulation. This prospective study aimed to determine the efficacy and individual benefit of external beam radiotherapy (EBRT). METHODS AND MATERIALS: The prospective trial included 287 patients with subfoveal neovascularization due to AMD which was verified by fluorescein angiography. Patients have been treated between January 1996 and October 1997. All patients received a total dose of 16 Gy in 2-Gy daily fractions with 5-6 MeV photons based on computerized treatment planning in individual head mask fixation. This first analysis is based on 73 patients (50 women, 23 men, median age 74.3 years), with a median follow-up of 13.3 months and a minimum follow-up of 11 months. RESULTS: All patients completed therapy and tolerability was good. First clinical control with second angiography was performed 6 weeks after irradiation, then in 3-month intervals. Eighteen patients with SRNV refusing radiotherapy served as a control group and were matched with 18 irradiated patients. After 7 months median visual acuity (VA) was 20/160 for the irradiated and 20/400 for the untreated patients. One year after radiotherapy final median VA was 20/400 in both groups. CONCLUSION: These results suggest that 16 Gy of conventionally fractionated external beam irradiation slows down the visual loss in exudative AMD for only a few months. Patients' reading vision could not be saved for a long-term run.\n" ], "offsets": [ [ 0, 1711 ] ] } ]

[ { "id": "PMID-10487573_T1", "type": "Immaterial_anatomical_entity", "text": [ "subretinal" ], "offsets": [ [ 31, 41 ] ], "normalized": [] }, { "id": "PMID-10487573_T2", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 76, 83 ] ], "normalized": [] }, { "id": "PMID-10487573_T3", "type": "Immaterial_anatomical_entity", "text": [ "subretinal" ], "offsets": [ [ 169, 179 ] ], "normalized": [] }, { "id": "PMID-10487573_T4", "type": "Tissue", "text": [ "macular" ], "offsets": [ [ 221, 228 ] ], "normalized": [] }, { "id": "PMID-10487573_T10", "type": "Organism_subdivision", "text": [ "head" ], "offsets": [ [ 808, 812 ] ], "normalized": [] } ]

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[ { "id": "PMID-7828172__text", "type": "abstract", "text": [ "Differential effects of carbachol on calcium entry and release in CHO cells expressing the m3 muscarinic receptor.\nCalcium signalling was examined in CHO-k1 cells that stably express the m3 subtype of the muscarinic receptor. The calcium indicator Fura-2 was retained in these cells only in the presence of probenecid (1 mM), suggesting that Fura-2 efflux was mediated by an organic anion transporter. The addition of carbachol (CCh) to Fura-2 loaded cells in suspension caused a rapid transient increase in intracellular calcium [Ca]i followed by a smaller sustained plateau phase. The transient rise in [Ca]i was dose-dependent with a threshold response of 89 +/- 18 nM above baseline with 10 nM CCh and a maximum stimulation of 734 +/- 46 nM with 10 microM CCh. This phase was accompanied by a similar dose-dependent stimulation of total inositol phosphate production and was assumed to be generated by release from intracellular stores of the endoplasmic reticulum (ER). The sustained increase in [Ca]i was generated by entry from the extracellular bath since it was blocked by pretreatment with La3+ (1 microM) and was absent when bath calcium was chelated with EGTA. This phase was not dependent on CCh dose, and a stimulation of [Ca]i of approximately 90 nM above baseline was observed with CCh concentrations between 50 nM and 10 microM. With this dose range, the rate of Mn2+ quenching of Fura-2 at the Ca-insensitive excitation wavelength of 360 nm was likewise maximally stimulated. At lower CCh concentrations (10-50 nM), it was clear that the activation of Ca entry could not be dissociated from a threshold release of Ca from intracellular stores. The phorbol ester PMA, which uncouples the muscarinic receptor from phospholipase C, reduced the transient rise in [Ca]i by approximately 50% with little or no effect on Ca entry at higher CCh levels (> or = 1 microM). At lower CCh concentrations (< or = 100 nM) however, pretreatment with PMA completely blocked all Ca mobilization and supports the contention that Ca entry is coupled to Ca release from stores or to store depletion. The emptying of inositol trisphosphate-sensitive stores with thapsigargin (10 nM) stimulated Ca entry and also the rate of Mn2+ quenching. Store depletion by incubation in Ca-free media likewise stimulated Mn2+ uptake without a rise in [Ca]i. Our data are therefore consistent with a 'capacitative' coupling model, whereby the activation of the plasma membrane receptor leads to an InsP3-induced change in the degree of filling of the ER Ca pool.(ABSTRACT TRUNCATED AT 400 WORDS)\n" ], "offsets": [ [ 0, 2577 ] ] } ]

[ { "id": "PMID-7828172_T1", "type": "Cell", "text": [ "CHO cells" ], "offsets": [ [ 66, 75 ] ], "normalized": [] }, { "id": "PMID-7828172_T2", "type": "Cell", "text": [ "CHO-k1 cells" ], "offsets": [ [ 150, 162 ] ], "normalized": [] }, { "id": "PMID-7828172_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 277, 282 ] ], "normalized": [] }, { "id": "PMID-7828172_T4", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "PMID-7828172_T7", "type": "Cellular_component", "text": [ "endoplasmic reticulum" ], "offsets": [ [ 947, 968 ] ], "normalized": [] }, { "id": "PMID-7828172_T8", "type": "Cellular_component", "text": [ "ER" ], "offsets": [ [ 970, 972 ] ], "normalized": [] }, { "id": "PMID-7828172_T9", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 1039, 1052 ] ], "normalized": [] }, { "id": "PMID-7828172_T10", "type": "Cellular_component", "text": [ "plasma membrane" ], "offsets": [ [ 2442, 2457 ] ], "normalized": [] }, { "id": "PMID-7828172_T5", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 508, 521 ] ], "normalized": [] }, { "id": "PMID-7828172_T6", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 919, 932 ] ], "normalized": [] }, { "id": "PMID-7828172_T11", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1640, 1653 ] ], "normalized": [] }, { "id": "PMID-7828172_T12", "type": "Cellular_component", "text": [ "ER" ], "offsets": [ [ 2532, 2534 ] ], "normalized": [] } ]

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[ { "id": "PMID-15202612__text", "type": "abstract", "text": [ "Novel insights into the pathogenesis of uric acid nephrolithiasis.\nPURPOSE OF REVIEW:\nThe factors involved in the pathogenesis of uric acid nephrolithiasis are well known. A low urinary pH is the most significant element in the generation of stones, with hyperuricosuria being a less common finding. The underlying mechanism(s) responsible for these disturbances remain poorly characterized. This review summarizes previous knowledge and highlights some recent developments in the pathophysiology of low urine pH and hyperuricosuria.\nRECENT FINDINGS:\nEpidemiological and metabolic studies have indicated an association between uric acid nephrolithiasis and insulin resistance. Some potential mechanisms include impaired ammoniagenesis caused by resistance to insulin action in the renal proximal tubule, or substrate competition by free fatty acids. The evaluation of a large Sicilian kindred recently revealed a putative genetic locus linked to uric acid stone disease. The identification of novel complementary DNA has provided an interesting insight into the renal handling of uric acid, including one genetic cause of renal uric acid wasting.\nSUMMARY:\nThe recognition of metabolic, molecular, and genetic factors that influence urinary pH, and uric acid metabolism and excretion, will provide novel insights into the pathogenesis of uric acid stones, and open the way for new therapeutic strategies.\n" ], "offsets": [ [ 0, 1404 ] ] } ]

[ { "id": "PMID-15202612_T1", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 178, 185 ] ], "normalized": [] }, { "id": "PMID-15202612_T2", "type": "Organism_substance", "text": [ "urine" ], "offsets": [ [ 504, 509 ] ], "normalized": [] }, { "id": "PMID-15202612_T3", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 1062, 1067 ] ], "normalized": [] }, { "id": "PMID-15202612_T4", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 1122, 1127 ] ], "normalized": [] }, { "id": "PMID-15202612_T5", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 1232, 1239 ] ], "normalized": [] }, { "id": "PMID-15202612_T6", "type": "Multi-tissue_structure", "text": [ "renal proximal tubule" ], "offsets": [ [ 781, 802 ] ], "normalized": [] }, { "id": "PMID-15202612_T7", "type": "Organism_substance", "text": [ "uric acid stone" ], "offsets": [ [ 946, 961 ] ], "normalized": [] }, { "id": "PMID-15202612_T8", "type": "Organism_substance", "text": [ "stones" ], "offsets": [ [ 242, 248 ] ], "normalized": [] }, { "id": "PMID-15202612_T9", "type": "Organism_substance", "text": [ "uric acid stones" ], "offsets": [ [ 1337, 1353 ] ], "normalized": [] } ]

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[ { "id": "PMID-12884381__text", "type": "abstract", "text": [ "Stereoselective synthesis of 1-aminoalkanephosphonic acids with two chiral centers and their activity towards leucine aminopeptidase.\nThe stereoselective synthesis of 1-amino-2-alkylalkanephosphonic acids, namely, compounds bearing two chiral centers, was achieved by the condensation of hypophosphorous acid salts of (R)(+) or (S)(-)-N-alpha-methylbenzylamine with the appropriate aldehydes in isopropanol. Simultaneous deprotection and oxidation by the action of bromine water provided equimolar mixtures of the RS:RR and SR:SS diastereomers of desired acids. They appeared to act as moderate inhibitors of kidney leucine aminopeptidase with potency dependent on the absolute configuration of both centers of chirality.\n" ], "offsets": [ [ 0, 722 ] ] } ]

[ { "id": "PMID-12884381_T1", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 609, 615 ] ], "normalized": [] } ]

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[ { "id": "PMID-21135106__text", "type": "abstract", "text": [ "The disintegrin-like and cysteine-rich domains of ADAM-9 mediate interactions between melanoma cells and fibroblasts. \nA characteristic of malignant cells is their capacity to invade their surrounding and to metastasize to distant organs. During these processes, proteolytic activities of tumor and stromal cells modify the extracellular matrix to produce a microenvironment suitable for their growth and migration. In recent years the family of ADAM proteases has been ascribed important roles in these processes. ADAM-9 is expressed in human melanoma at the tumor-stroma border where direct or indirect interactions between tumor cells and fibroblasts occur. To analyze the role of ADAM-9 for the interaction between melanoma cells and stromal fibroblasts, we produced the recombinant disintegrin-like and cysteine-rich domain of ADAM-9 (DC-9). Melanoma cells and human fibroblasts adhered to immobilized DC-9 in a Mn(2+)-dependent fashion suggesting an integrin-mediated process. Inhibition studies showed that adhesion of fibroblasts was mediated by several beta1 integrin receptors independent of the RGD and ECD recognition motif. Furthermore, interaction of fibroblasts and high invasive melanoma cells with soluble recombinant DC-9 resulted in enhanced expression of MMP-1 and MMP-2. Silencing of ADAM-9 in melanoma cells significantly reduced cell adhesion to fibroblasts. Ablation of ADAM-9 in fibroblasts almost completely abolished these cellular interactions and melanoma cell invasion in vitro. In summary, these results suggest that ADAM-9 expression plays an important role in mediating cell-cell contacts between fibroblasts and melanoma cells and that these interactions contribute to proteolytic activities required during invasion of melanoma cells.\n" ], "offsets": [ [ 0, 1770 ] ] } ]

[ { "id": "PMID-21135106_T4", "type": "Cell", "text": [ "melanoma cells" ], "offsets": [ [ 86, 100 ] ], "normalized": [] }, { "id": "PMID-21135106_T5", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 105, 116 ] ], "normalized": [] }, { "id": "PMID-21135106_T6", "type": "Cell", "text": [ "malignant cells" ], "offsets": [ [ 139, 154 ] ], "normalized": [] }, { "id": "PMID-21135106_T7", "type": "Organ", "text": [ "organs" ], "offsets": [ [ 231, 237 ] ], "normalized": [] }, { "id": "PMID-21135106_T8", "type": "Cell", "text": [ "tumor" ], "offsets": [ [ 289, 294 ] ], "normalized": [] }, { "id": "PMID-21135106_T9", "type": "Cell", "text": [ "stromal cells" ], "offsets": [ [ 299, 312 ] ], "normalized": [] }, { "id": "PMID-21135106_T10", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 324, 344 ] ], "normalized": [] }, { "id": "PMID-21135106_T14", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 544, 552 ] ], "normalized": [] }, { "id": "PMID-21135106_T15", "type": "Tissue", "text": [ "tumor-stroma border" ], "offsets": [ [ 560, 579 ] ], "normalized": [] }, { "id": "PMID-21135106_T16", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 626, 637 ] ], "normalized": [] }, { "id": "PMID-21135106_T17", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 642, 653 ] ], "normalized": [] }, { "id": "PMID-21135106_T19", "type": "Cell", "text": [ "melanoma cells" ], "offsets": [ [ 719, 733 ] ], "normalized": [] }, { "id": "PMID-21135106_T20", "type": "Cell", "text": [ "stromal fibroblasts" ], "offsets": [ [ 738, 757 ] ], "normalized": [] }, { "id": "PMID-21135106_T24", "type": "Cell", "text": [ "Melanoma cells" ], "offsets": [ [ 847, 861 ] ], "normalized": [] }, { "id": "PMID-21135106_T26", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 872, 883 ] ], "normalized": [] }, { "id": "PMID-21135106_T29", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1026, 1037 ] ], "normalized": [] }, { "id": "PMID-21135106_T31", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1165, 1176 ] ], "normalized": [] }, { "id": "PMID-21135106_T32", "type": "Cell", "text": [ "high invasive melanoma cells" ], "offsets": [ [ 1181, 1209 ] ], "normalized": [] }, { "id": "PMID-21135106_T36", "type": "Cell", "text": [ "melanoma cells" ], "offsets": [ [ 1315, 1329 ] ], "normalized": [] }, { "id": "PMID-21135106_T37", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1352, 1356 ] ], "normalized": [] }, { "id": "PMID-21135106_T38", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1369, 1380 ] ], "normalized": [] }, { "id": "PMID-21135106_T40", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1404, 1415 ] ], "normalized": [] }, { "id": "PMID-21135106_T41", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1450, 1458 ] ], "normalized": [] }, { "id": "PMID-21135106_T42", "type": "Cell", "text": [ "melanoma cell" ], "offsets": [ [ 1476, 1489 ] ], "normalized": [] }, { "id": "PMID-21135106_T46", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1630, 1641 ] ], "normalized": [] }, { "id": "PMID-21135106_T47", "type": "Cell", "text": [ "melanoma cells" ], "offsets": [ [ 1646, 1660 ] ], "normalized": [] }, { "id": "PMID-21135106_T48", "type": "Cell", "text": [ "melanoma cells" ], "offsets": [ [ 1754, 1768 ] ], "normalized": [] }, { "id": "PMID-21135106_T1", "type": "Cellular_component", "text": [ "cell-cell contacts" ], "offsets": [ [ 1603, 1621 ] ], "normalized": [] } ]

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[ { "id": "PMC-3012732-sec-15__text", "type": "sec", "text": [ "Reagents and antibodies\nMaxisorp strips (NunC, Roskilde, Denmark), GST-PNMA2 recombinant protein (Abnova, Taipei, Taiwan); 3,3',5,5-tetramethylbenzidine (TMB) + substrate (Dako, Glostrup, Denmark), Peroxidase with dakocytomation peroxidase block (Dako), Dakocytomation envision(R) system labeled polymer-HRP anti-rabbit kit and 3-3'-diaminobenzidine (Dako), Mayer's hematoxylin (Histolab Product AB, Gothenburg, Sweden), Graded alcohol (Kemetyl, Vestby, Norway), Xylen (Solveco, Rosersberg, Sweden), Pertex(R) (Histolab, Gothenburg, Sweden), Tris-Glycine blotting buffer (Amresco, Solon, OH), Western blotting (WB) reagent and Lumi-Light WB substrate (Roche, Basel, Switzerland), EasyTag Methionine-L-35S, NEG709A005MC (PerkinElmer, Waltham, MA), Full-length cDNA clone for human PNMA2, ID6580976 (BioScience Geneservice, Cambridge, UK), TnT(R) SP6 Quick Coupled Transcription/Translation System (Promega, Madison, WI), Protein G-Sepharose beads (GE Healthcare, Little Chalfont, Buckinghamshire, UK), Peroxidase (HRP)-conjugated rabbit anti human IgG (anti-IgG) (Dako), rabbit polyclonal antibody anti-PNMA2 (Atlas Antibodies, Stockholm, Sweden), monoclonal mouse anti-GST, sc-138, polyclonal goat anti-human Ma2, sc-68099, HRP-donkey anti-goat, sc-2020, (Santa Cruz Biotechnology, Santa Cruz, CA), HRP-goat anti-rabbit, P0448, (Dako) and Ravo PNS-Blot, (Ravo Diagnostika GmbH, Freiburg, Germany).\n" ], "offsets": [ [ 0, 1398 ] ] } ]

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[ { "id": "PMID-6920468__text", "type": "abstract", "text": [ "Relationship of self-concept during late pregnancy to neonatal perception and parenting profile.\nThirty-one gravidas were studied to examine the relationship between a woman's feelings about herself during late pregnancy, her perception of her newborn, and her profile of parenting. The Tennessee Self-Concept Scale was completed during the third trimester of pregnancy, the Neonatal Perception Inventory I at one-to-two days postpartum, and the Neonatal Perception Inventory II and the Michigan Screening Profile of Parenting at four-to-six weeks postpartum. When considered separately, no positive significant relationships were found between scores on these variables. However, all subjects with negative scores on both self-concept and neonatal perception had negative scores on at least two subscales of the parenting profile.\n" ], "offsets": [ [ 0, 832 ] ] } ]

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[ { "id": "PMID-15327827__text", "type": "abstract", "text": [ "Convergence of p53 and TGF-beta signaling networks. \np53 is a protein with many talents. One of the most fundamental is the ability to act as essential growth checkpoint that protects cells against cellular transformation. p53 does so through the induction of genes leading to growth arrest or apoptosis. Most of the studies focusing on the mechanisms of p53 activity have been performed in cultured cells upon treatment with well-established p53-activating inputs, such as high doses of radiations, DNA-damaging drugs and activated oncogenes. However, how the tumor suppressive functions of p53 become concerted with the extracellular cues arriving at the cell surface during tissue homeostasis, remains largely unknown. Intriguingly, two recent papers have shed new light into this unexplored field, indicating that p53 plays a key role in TGF-beta-induced growth arrest and, unexpectedly, in the developmental effects of TGF-beta in early embryos. Here we review and comment on these findings and on their implications for cancer biology.\n" ], "offsets": [ [ 0, 1042 ] ] } ]

[ { "id": "PMID-15327827_T4", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 184, 189 ] ], "normalized": [] }, { "id": "PMID-15327827_T5", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 198, 206 ] ], "normalized": [] }, { "id": "PMID-15327827_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 400, 405 ] ], "normalized": [] }, { "id": "PMID-15327827_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 561, 566 ] ], "normalized": [] }, { "id": "PMID-15327827_T13", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 622, 635 ] ], "normalized": [] }, { "id": "PMID-15327827_T14", "type": "Cellular_component", "text": [ "cell surface" ], "offsets": [ [ 657, 669 ] ], "normalized": [] }, { "id": "PMID-15327827_T15", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 677, 683 ] ], "normalized": [] }, { "id": "PMID-15327827_T19", "type": "Developing_anatomical_structure", "text": [ "embryos" ], "offsets": [ [ 942, 949 ] ], "normalized": [] }, { "id": "PMID-15327827_T20", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1026, 1032 ] ], "normalized": [] } ]

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[ { "id": "PMC-3052613-caption-01__text", "type": "caption", "text": [ "Modified radiology-guided percutaneous gastrostomy technique.\nA. 21G fine needle punctured localized collection of air, which was visible in collapsed stomach under fluoroscopy-guided gastrostomy. Needle tip is then gradually withdrawn while injecting small amounts of water-soluble contrast medium. Location of stomach is confirmed by visualization of opacified gastric rugae. B. Stomach was inflated with approximately 600-800 mL of room air through 21G fine needle. C. 100-cm stainless steel guide wire is inserted through needle, and gastro-percutaneous tract is gradually dilated. D. Insertion of 14-Fr pigtail gastrostomy catheter and injection of small amount of water-soluble contrast medium via pigtail catheter confirmed that gastrostomy catheter is correctly placed within stomach.\n" ], "offsets": [ [ 0, 793 ] ] } ]

[ { "id": "PMC-3052613-caption-01_T1", "type": "Organ", "text": [ "stomach" ], "offsets": [ [ 151, 158 ] ], "normalized": [] }, { "id": "PMC-3052613-caption-01_T2", "type": "Organ", "text": [ "stomach" ], "offsets": [ [ 312, 319 ] ], "normalized": [] }, { "id": "PMC-3052613-caption-01_T3", "type": "Organ", "text": [ "gastric" ], "offsets": [ [ 363, 370 ] ], "normalized": [] }, { "id": "PMC-3052613-caption-01_T4", "type": "Organ", "text": [ "Stomach" ], "offsets": [ [ 381, 388 ] ], "normalized": [] }, { "id": "PMC-3052613-caption-01_T5", "type": "Organ", "text": [ "gastro" ], "offsets": [ [ 538, 544 ] ], "normalized": [] }, { "id": "PMC-3052613-caption-01_T6", "type": "Organ", "text": [ "stomach" ], "offsets": [ [ 784, 791 ] ], "normalized": [] }, { "id": "PMC-3052613-caption-01_T7", "type": "Immaterial_anatomical_entity", "text": [ "percutaneous" ], "offsets": [ [ 26, 38 ] ], "normalized": [] }, { "id": "PMC-3052613-caption-01_T8", "type": "Immaterial_anatomical_entity", "text": [ "percutaneous" ], "offsets": [ [ 545, 557 ] ], "normalized": [] } ]

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[ { "id": "PMID-10080451__text", "type": "abstract", "text": [ "Ventricular fibrillation due to long QT syndrome probably caused by clindamycin.\nProlongation of QT time interval may be provoked by a limited number of drugs, especially macrolide antibiotics. We describe a case of QT time interval prolongation induced by clindamycin with subsequent repeated ventricular fibrillation and resuscitation; there is no previous report in the literature of QT time prolongation caused by lincosamides.\n" ], "offsets": [ [ 0, 432 ] ] } ]

[ { "id": "PMID-10080451_T1", "type": "Multi-tissue_structure", "text": [ "Ventricular" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-10080451_T2", "type": "Multi-tissue_structure", "text": [ "ventricular" ], "offsets": [ [ 294, 305 ] ], "normalized": [] } ]

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[ { "id": "PMID-19752254__text", "type": "abstract", "text": [ "Magnesium for treatment of asthma in children.\nQUESTION: Magnesium is considered adjuvant therapy for moderate to severe asthma exacerbations in adults, but can it be used to treat children? ANSWER: Magnesium seems to be beneficial in the treatment of moderate to severe asthma in children. It is a safe drug to administer, but there have been minor side effects reported, such as epigastric or facial warmth, flushing, pain and numbness at the infusion site, dry mouth, malaise, and hypotension. Owing to its bronchodilating and anti-inflammatory effects, magnesium is an encouraging adjuvant therapy for pediatric patients who do not respond to conventional treatment in acute severe exacerbations. Future studies should focus on establishing the optimal dosage for maximal benefits and the best route of administration. Magnesium should also be considered as a prophylactic treatment.\n" ], "offsets": [ [ 0, 888 ] ] } ]

[ { "id": "PMID-19752254_T1", "type": "Organism_subdivision", "text": [ "epigastric" ], "offsets": [ [ 381, 391 ] ], "normalized": [] }, { "id": "PMID-19752254_T2", "type": "Organism_subdivision", "text": [ "facial" ], "offsets": [ [ 395, 401 ] ], "normalized": [] }, { "id": "PMID-19752254_T3", "type": "Organism_subdivision", "text": [ "mouth" ], "offsets": [ [ 464, 469 ] ], "normalized": [] }, { "id": "PMID-19752254_T4", "type": "Multi-tissue_structure", "text": [ "site" ], "offsets": [ [ 454, 458 ] ], "normalized": [] } ]

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[ { "id": "PMC-3168770-caption-05__text", "type": "caption", "text": [ "Challenges to creating and implementing a perioperative glycemic control protocol.\n" ], "offsets": [ [ 0, 83 ] ] } ]

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[ { "id": "PMC-2769146-sec-05__text", "type": "sec", "text": [ "3.2.\nCell line and culture\nDU145 (prostate cancer) cell line was used in this assay. DU145 was grown in DMEM/F-12 medium (Gibco BRL Life Technologies, San Diego, CA., USA) supplemented with 10% fetal calf serum and kept in a humidified 37 degreesC, 5% CO2 incubator.\n" ], "offsets": [ [ 0, 267 ] ] } ]

[ { "id": "PMC-2769146-sec-05_T1", "type": "Cell", "text": [ "Cell line" ], "offsets": [ [ 5, 14 ] ], "normalized": [] }, { "id": "PMC-2769146-sec-05_T2", "type": "Cell", "text": [ "DU145 (prostate cancer) cell line" ], "offsets": [ [ 27, 60 ] ], "normalized": [] }, { "id": "PMC-2769146-sec-05_T3", "type": "Cell", "text": [ "DU145" ], "offsets": [ [ 85, 90 ] ], "normalized": [] }, { "id": "PMC-2769146-sec-05_T4", "type": "Organism_substance", "text": [ "fetal calf serum" ], "offsets": [ [ 194, 210 ] ], "normalized": [] } ]

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[ { "id": "PMID-1505125__text", "type": "abstract", "text": [ "NIH3T3 transfectant containing human K-ras oncogene shows enhanced metastatic activity after in vivo tumor growth or co-culture with fibroblasts. \nA clone of NIH3T3 transformant (H-3), obtained by transfecting genomic DNA of a human colon carcinoma cell line, contains human K-ras oncogene and yields metastatic pulmonary nodules after intravenous injection of the cells into nude mice. This metastatic ability was enhanced remarkably after in vivo tumor growth (subcutaneous tumor formation in nude mice) accompanied by increased mRNA expression and gene amplification of the human-derived K-ras oncogene, while it declined gradually as the passage number increased in vitro, with corresponding decreases of gene amplification and mRNA expression. Six subclones were randomly selected from H-3 cells which had been subcultured to passage 22. All of the clones in culture showed almost the same low level of metastatic ability and exhibited little K-ras oncogene amplification with correspondingly low mRNA expression. However, after they formed tumors in nude mice, every clone acquired high metastatic ability and the gene amplification increased, with elevated mRNA expression. These experimental facts indicated that acquisition of metastatic ability coupled with the function of K-ras oncogene was conditional in nature, being strongly affected by in vivo tumor circumstances. The low metastatic and G-418-resistant H-3 cells were co-cultured with BALB/c3T3 fibroblasts for 2-4 weeks. After removal of fibroblasts by exposure to G-418, the tumor cells exhibited increased metastatic ability and human K-ras oncogene mRNA, suggesting an intimate interaction between H-3 cells and fibroblasts influencing the function of transfected human K-ras oncogene. Fibroblasts of the host animal may thus have an important role in generating enhanced metastatic activity of H-3 cells.\n" ], "offsets": [ [ 0, 1878 ] ] } ]

[ { "id": "PMID-1505125_T1", "type": "Cell", "text": [ "NIH3T3 transfectant" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "PMID-1505125_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 101, 106 ] ], "normalized": [] }, { "id": "PMID-1505125_T5", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 133, 144 ] ], "normalized": [] }, { "id": "PMID-1505125_T6", "type": "Cell", "text": [ "clone" ], "offsets": [ [ 149, 154 ] ], "normalized": [] }, { "id": "PMID-1505125_T7", "type": "Cell", "text": [ "NIH3T3 transformant" ], "offsets": [ [ 158, 177 ] ], "normalized": [] }, { "id": "PMID-1505125_T8", "type": "Cell", "text": [ "H-3" ], "offsets": [ [ 179, 182 ] ], "normalized": [] }, { "id": "PMID-1505125_T11", "type": "Cell", "text": [ "colon carcinoma cell line" ], "offsets": [ [ 233, 258 ] ], "normalized": [] }, { "id": "PMID-1505125_T14", "type": "Cancer", "text": [ "metastatic pulmonary nodules" ], "offsets": [ [ 301, 329 ] ], "normalized": [] }, { "id": "PMID-1505125_T15", "type": "Immaterial_anatomical_entity", "text": [ "intravenous" ], "offsets": [ [ 336, 347 ] ], "normalized": [] }, { "id": "PMID-1505125_T16", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 365, 370 ] ], "normalized": [] }, { "id": "PMID-1505125_T18", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 449, 454 ] ], "normalized": [] }, { "id": "PMID-1505125_T19", "type": "Cancer", "text": [ "subcutaneous tumor" ], "offsets": [ [ 463, 481 ] ], "normalized": [] }, { "id": "PMID-1505125_T23", "type": "Cell", "text": [ "subclones" ], "offsets": [ [ 753, 762 ] ], "normalized": [] }, { "id": "PMID-1505125_T24", "type": "Cell", "text": [ "H-3 cells" ], "offsets": [ [ 791, 800 ] ], "normalized": [] }, { "id": "PMID-1505125_T25", "type": "Cell", "text": [ "clones" ], "offsets": [ [ 854, 860 ] ], "normalized": [] }, { "id": "PMID-1505125_T27", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1046, 1052 ] ], "normalized": [] }, { "id": "PMID-1505125_T29", "type": "Cell", "text": [ "clone" ], "offsets": [ [ 1073, 1078 ] ], "normalized": [] }, { "id": "PMID-1505125_T31", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1361, 1366 ] ], "normalized": [] }, { "id": "PMID-1505125_T33", "type": "Cell", "text": [ "H-3 cells" ], "offsets": [ [ 1421, 1430 ] ], "normalized": [] }, { "id": "PMID-1505125_T34", "type": "Cell", "text": [ "BALB/c3T3 fibroblasts" ], "offsets": [ [ 1453, 1474 ] ], "normalized": [] }, { "id": "PMID-1505125_T35", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1507, 1518 ] ], "normalized": [] }, { "id": "PMID-1505125_T37", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1545, 1556 ] ], "normalized": [] }, { "id": "PMID-1505125_T40", "type": "Cell", "text": [ "H-3 cells" ], "offsets": [ [ 1670, 1679 ] ], "normalized": [] }, { "id": "PMID-1505125_T41", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1684, 1695 ] ], "normalized": [] }, { "id": "PMID-1505125_T44", "type": "Cell", "text": [ "Fibroblasts" ], "offsets": [ [ 1758, 1769 ] ], "normalized": [] }, { "id": "PMID-1505125_T46", "type": "Cell", "text": [ "H-3 cells" ], "offsets": [ [ 1867, 1876 ] ], "normalized": [] } ]

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[ { "id": "PMID-2607031__text", "type": "abstract", "text": [ "Screening method for insecticidal activity using first instars of black blow fly (Diptera: Calliphoridae).\nA bioassay method suitable for rapid mass screening of fermentation and synthetic organic compounds for insecticidal activity is described. The test, which uses first instars of susceptible black blow fly, Phormia regina (Meigen), in a bovine serum medium, detects insecticidal activity with reproducible results. It is capable of selecting the most active compound in structure-activity relationships by minimum effective dose concentration studies. The bioassay system is easy to operate and requires only a minute quantity of chemical compound.\n" ], "offsets": [ [ 0, 655 ] ] } ]

[ { "id": "PMID-2607031_T1", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 350, 355 ] ], "normalized": [] } ]

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[ { "id": "PMID-11587364__text", "type": "abstract", "text": [ "Oncogenic mechanisms of Evi-1 protein. \nAlthough Evi-1 is thought to promote growth or block differentiation in some cell types, its biological functions have not been elucidated. To explore the mechanisms underlying Evi-1-induced oncogenesis, we investigated whether Evi-1 affects the signaling of transforming growth factor beta (TGF-beta), which inhibits proliferation of a wide range of cell types and is one of the most studied growth regulatory factors. We demonstrated that Evi-1 represses TGF-beta signaling and antagonizes its growth-inhibitory effects. Two separate regions of Evi-1 are responsible for this repression, one of which is the first zinc-finger domain. Through this domain, Evi-1 physically interacts with Smad3, an intracellular mediator of TGF-beta signaling, thereby suppressing the transcriptional activity of Smad3. These results define a novel function of Evi-1 as a repressor of signaling components of TGF-beta. We also demonstrated that Evi-1 represses Smad-induced transcriptional activation by recruiting CtBP as a corepressor. Evi-1 associates with CtBP1 through one of the CtBP-binding consensus motifs within the region from amino acid 544 to 607, and this association is required for the efficient inhibition of TGF-beta signaling. A specific histone deacetylase (HDAc) inhibitor, trichostatin A (TSA), alleviates Evi-1-mediated repression of TGF-beta signaling, suggesting that HDAc is involved in transcriptional repression by Evi-1. This identifies a novel function of Evi-1 as a member of corepressor complexes and suggests that aberrant recruitment of corepressors is one of the mechanisms involved in Evi-1-induced leukemogenesis. These results indicate that specific HDAc inhibitors may be useful in the treatment of Evi-1-induced neoplastic tumors, including myeloid leukemias.\n" ], "offsets": [ [ 0, 1824 ] ] } ]

[ { "id": "PMID-11587364_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 117, 121 ] ], "normalized": [] }, { "id": "PMID-11587364_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMID-11587364_T14", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 739, 752 ] ], "normalized": [] }, { "id": "PMID-11587364_T40", "type": "Cancer", "text": [ "neoplastic tumors" ], "offsets": [ [ 1776, 1793 ] ], "normalized": [] }, { "id": "PMID-11587364_T41", "type": "Cancer", "text": [ "myeloid leukemias" ], "offsets": [ [ 1805, 1822 ] ], "normalized": [] } ]

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[ { "id": "PMID-9671543__text", "type": "abstract", "text": [ "Acylase I-catalyzed deacetylation of N-acetyl-L-cysteine and S-alkyl-N-acetyl-L-cysteines.\nThe aminoacylase that catalyzes the hydrolysis of N-acetyl-L-cysteine (NAC) was identified as acylase I after purification by column chromatography and electrophoretic analysis. Rat kidney cytosol was fractionated by ammonium sulfate precipitation, and the proteins were separated by ion-exchange column chromatography, gel-filtration column chromatography, and hydrophobic interaction column chromatography. Acylase activity with NAC and N-acetyl-L-methionine (NAM), a known substrate for acylase I, as substrates coeluted during all chromatographic steps. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the protein was purified to near homogeneity and had a subunit Mr of 43 000, which is identical with the Mr of acylase I from porcine kidney and bovine liver. n-Butylmalonic acid was a slow-binding inhibitor of acylase I and inhibited the deacetylation of NAC with a Ki of 192 +/- 27 microM. These results show that acylase I catalyzes the deacetylation of NAC. The acylase I-catalyzed deacetylation of a range of S-alkyl-N-acetyl-L-cysteines, their carbon and oxygen analogues, and the selenium analogue of NAM was also studied with porcine kidney acylase I. The specific activity of the acylase I-catalyzed deacetylation of these substrates was related to their calculated molar volumes and log P values. The S-alkyl-N-acetyl-L-cysteines with short (C0-C3) and unbranched S-alkyl substituents were good acylase I substrates, whereas the S-alkyl-N-acetyl-L-cysteines with long (>C3) and branched S-alkyl substituents were poLr acylase I substrates. The carbon and oxygen analogues of S-methyl-N-acetyl-L-cysteine and the carbon analogue of S-ethyl-N-acetyl-L-cysteine were poor acylase I substrates, whereas the selenium analogue of NAM was a good acylase I substrate.\n" ], "offsets": [ [ 0, 1889 ] ] } ]

[ { "id": "PMID-9671543_T1", "type": "Organism_substance", "text": [ "kidney cytosol" ], "offsets": [ [ 273, 287 ] ], "normalized": [] }, { "id": "PMID-9671543_T2", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 853, 859 ] ], "normalized": [] }, { "id": "PMID-9671543_T3", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 871, 876 ] ], "normalized": [] }, { "id": "PMID-9671543_T4", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 1261, 1267 ] ], "normalized": [] } ]

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[ { "id": "PMID-16773443__text", "type": "abstract", "text": [ "Fluoro-Jade B staining following zymosan microinjection into the spinal cord white matter.\n1. The fluorescein derivate Fluoro-Jade B (FJB), which primarily labels dead or dying neurons, was used to study the acute focal inflammation in the spinal cord white matter. Inflammation was induced by microinjection of the yeast particulate zymosan to evaluate the biological effects of intraspinal macrophages activation without the confounding effects of physical trauma. 2. A single bolus of zymosan (Sigma, 75 nL) was stereotaxically injected at the thoracic level into the lateral white matter of rat spinal cord. A standard Fluoro-Jade B staining protocol was applied to spinal cord sections at 6, 12, 24 h and 2, 4 days postinjection. Neutral Red, NADPH-diaphorase, Iba1-IR, and DAPI staining protocols accomplished examination of the cells participating in the acute inflammatory response. 3. Zymosan caused formation of clearly delineated inflammation lesions localized in the lateral white matter of the spinal cord. Fluoro-Jade B stained cells in the area of inflammation were not observed at 12 h postinjection while mild FJB staining appeared at 24 h and intense staining was observed at 2 and 4 days postinjection. 4. This study shows that the acute response to zymosan-induced inflammation in the rat spinal cord white matter causes a gradual appearance of phagocytic microglia/macrophages and delayed FJB staining of the inflammatory cells. 5. FJB, a reliable marker of dying neurons, is a more universal agent than formerly believed. One possible explanation for the gradual appearance of FJB-stained cells in the area of inflammation is that specific time is required for sufficient levels of proteins and/or myelin debris of axonal origin to appear in the cytoplasm of phagocytic microglia/macrophages.\n" ], "offsets": [ [ 0, 1815 ] ] } ]

[ { "id": "PMID-16773443_T1", "type": "Multi-tissue_structure", "text": [ "spinal cord white matter" ], "offsets": [ [ 65, 89 ] ], "normalized": [] }, { "id": "PMID-16773443_T2", "type": "Cell", "text": [ "neurons" ], "offsets": [ [ 177, 184 ] ], "normalized": [] }, { "id": "PMID-16773443_T3", "type": "Multi-tissue_structure", "text": [ "spinal cord white matter" ], "offsets": [ [ 240, 264 ] ], "normalized": [] }, { "id": "PMID-16773443_T4", "type": "Multi-tissue_structure", "text": [ "lateral white matter" ], "offsets": [ [ 571, 591 ] ], "normalized": [] }, { "id": "PMID-16773443_T5", "type": "Organ", "text": [ "spinal cord" ], "offsets": [ [ 599, 610 ] ], "normalized": [] }, { "id": "PMID-16773443_T6", "type": "Multi-tissue_structure", "text": [ "spinal cord sections" ], "offsets": [ [ 670, 690 ] ], "normalized": [] }, { "id": "PMID-16773443_T7", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-16773443_T8", "type": "Organ", "text": [ "spinal cord" ], "offsets": [ [ 1007, 1018 ] ], "normalized": [] }, { "id": "PMID-16773443_T9", "type": "Multi-tissue_structure", "text": [ "lateral white matter" ], "offsets": [ [ 979, 999 ] ], "normalized": [] }, { "id": "PMID-16773443_T10", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1042, 1047 ] ], "normalized": [] }, { "id": "PMID-16773443_T11", "type": "Multi-tissue_structure", "text": [ "spinal cord white matter" ], "offsets": [ [ 1309, 1333 ] ], "normalized": [] }, { "id": "PMID-16773443_T12", "type": "Cell", "text": [ "phagocytic microglia" ], "offsets": [ [ 1365, 1385 ] ], "normalized": [] }, { "id": "PMID-16773443_T13", "type": "Cell", "text": [ "macrophages" ], "offsets": [ [ 1386, 1397 ] ], "normalized": [] }, { "id": "PMID-16773443_T14", "type": "Cell", "text": [ "inflammatory cells" ], "offsets": [ [ 1430, 1448 ] ], "normalized": [] }, { "id": "PMID-16773443_T15", "type": "Cell", "text": [ "neurons" ], "offsets": [ [ 1485, 1492 ] ], "normalized": [] }, { "id": "PMID-16773443_T16", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1611, 1616 ] ], "normalized": [] }, { "id": "PMID-16773443_T17", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 954, 961 ] ], "normalized": [] }, { "id": "PMID-16773443_T20", "type": "Organism_substance", "text": [ "cytoplasm" ], "offsets": [ [ 1768, 1777 ] ], "normalized": [] }, { "id": "PMID-16773443_T21", "type": "Cell", "text": [ "phagocytic microglia" ], "offsets": [ [ 1781, 1801 ] ], "normalized": [] }, { "id": "PMID-16773443_T22", "type": "Cell", "text": [ "macrophages" ], "offsets": [ [ 1802, 1813 ] ], "normalized": [] }, { "id": "PMID-16773443_T24", "type": "Cell", "text": [ "intraspinal macrophages" ], "offsets": [ [ 380, 403 ] ], "normalized": [] }, { "id": "PMID-16773443_T25", "type": "Multi-tissue_structure", "text": [ "thoracic" ], "offsets": [ [ 547, 555 ] ], "normalized": [] }, { "id": "PMID-16773443_T23", "type": "Multi-tissue_structure", "text": [ "area" ], "offsets": [ [ 1055, 1059 ] ], "normalized": [] }, { "id": "PMID-16773443_T18", "type": "Multi-tissue_structure", "text": [ "area" ], "offsets": [ [ 1624, 1628 ] ], "normalized": [] } ]

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[ { "id": "PMID-19953879__text", "type": "abstract", "text": [ "[Reconstruction of hepatic artery in adult to adult living donor liver transplantation in 104 patients].\nOBJECTIVE:\nTo report the experience of hepatic artery reconstruction with adult-to-adult living donor liver transplantation (ALDLT) using right lobe liver grafts.\nMETHODS:\nFrom January 2002 to August 2007, 104 patients underwent ALDLT using right lobe grafts. Hepatic arteries of donors and recipients were assessed carefully with spiral CT angiography and DSA before ALDLT. All patients underwent reconstruction of hepatic artery between right lobe liver grafts of donor and recipient which included the anastomosis between right hepatic artery of donors and recipients; the reconstruction of right hepatic artery between donor grafts and left hepatic artery of recipients; interpositional bypass using autogenous saphenous vein and cryopreserved iliac artery between right hepatic artery of donors and hepatic artery, common hepatic artery and abdominal aorta of recipients. The microsurgical technique was employed under the magnification of 3.5 times and operative microscope of 5-10 times.\nRESULTS:\nIn these series, HAT occurred in 2 recipients at Days 1 and 7 post-ALDLT (1.9%). Both were revascularized with autogenous saphenous vein between right hepatic artery of donor and abdominal aorta of recipient. HAT occurred in 1 recipient at Days 90 post-ALDLT, but no symptom was presented. There was no severe complication and mortality related to hepatic artery reconstruction in recipients. No HAT, hepatic artery stenosis and aneurysm occurred during the follow-up period of 2-60 months. The 1, 2 and 3-year survival rates were 89.3%, 76.0% and 69.3% respectively.\nCONCLUSION:\nCareful evaluation of hepatic artery condition and using microsurgical techniques are important for safer arterial reconstruction and a long-term patency of hepatic artery in living donor liver transplantation in adults using right lobe liver grafts.\n" ], "offsets": [ [ 0, 1940 ] ] } ]

[ { "id": "PMID-19953879_T1", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 19, 33 ] ], "normalized": [] }, { "id": "PMID-19953879_T2", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 65, 70 ] ], "normalized": [] }, { "id": "PMID-19953879_T3", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 144, 158 ] ], "normalized": [] }, { "id": "PMID-19953879_T4", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 207, 212 ] ], "normalized": [] }, { "id": "PMID-19953879_T5", "type": "Multi-tissue_structure", "text": [ "right lobe liver grafts" ], "offsets": [ [ 243, 266 ] ], "normalized": [] }, { "id": "PMID-19953879_T6", "type": "Multi-tissue_structure", "text": [ "right lobe grafts" ], "offsets": [ [ 346, 363 ] ], "normalized": [] }, { "id": "PMID-19953879_T7", "type": "Multi-tissue_structure", "text": [ "Hepatic arteries" ], "offsets": [ [ 365, 381 ] ], "normalized": [] }, { "id": "PMID-19953879_T8", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 521, 535 ] ], "normalized": [] }, { "id": "PMID-19953879_T9", "type": "Multi-tissue_structure", "text": [ "right lobe liver grafts" ], "offsets": [ [ 544, 567 ] ], "normalized": [] }, { "id": "PMID-19953879_T10", "type": "Multi-tissue_structure", "text": [ "right hepatic artery" ], "offsets": [ [ 630, 650 ] ], "normalized": [] }, { "id": "PMID-19953879_T11", "type": "Multi-tissue_structure", "text": [ "right hepatic artery" ], "offsets": [ [ 699, 719 ] ], "normalized": [] }, { "id": "PMID-19953879_T12", "type": "Multi-tissue_structure", "text": [ "grafts" ], "offsets": [ [ 734, 740 ] ], "normalized": [] }, { "id": "PMID-19953879_T13", "type": "Multi-tissue_structure", "text": [ "left hepatic artery" ], "offsets": [ [ 745, 764 ] ], "normalized": [] }, { "id": "PMID-19953879_T14", "type": "Multi-tissue_structure", "text": [ "saphenous vein" ], "offsets": [ [ 820, 834 ] ], "normalized": [] }, { "id": "PMID-19953879_T15", "type": "Multi-tissue_structure", "text": [ "iliac artery" ], "offsets": [ [ 853, 865 ] ], "normalized": [] }, { "id": "PMID-19953879_T16", "type": "Multi-tissue_structure", "text": [ "right hepatic artery" ], "offsets": [ [ 874, 894 ] ], "normalized": [] }, { "id": "PMID-19953879_T17", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 909, 923 ] ], "normalized": [] }, { "id": "PMID-19953879_T18", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 932, 946 ] ], "normalized": [] }, { "id": "PMID-19953879_T19", "type": "Multi-tissue_structure", "text": [ "abdominal aorta" ], "offsets": [ [ 951, 966 ] ], "normalized": [] }, { "id": "PMID-19953879_T20", "type": "Multi-tissue_structure", "text": [ "saphenous vein" ], "offsets": [ [ 1231, 1245 ] ], "normalized": [] }, { "id": "PMID-19953879_T21", "type": "Multi-tissue_structure", "text": [ "right hepatic artery" ], "offsets": [ [ 1254, 1274 ] ], "normalized": [] }, { "id": "PMID-19953879_T22", "type": "Multi-tissue_structure", "text": [ "abdominal aorta" ], "offsets": [ [ 1288, 1303 ] ], "normalized": [] }, { "id": "PMID-19953879_T23", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 1457, 1471 ] ], "normalized": [] }, { "id": "PMID-19953879_T24", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 1510, 1524 ] ], "normalized": [] }, { "id": "PMID-19953879_T25", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 1711, 1725 ] ], "normalized": [] }, { "id": "PMID-19953879_T26", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 1795, 1803 ] ], "normalized": [] }, { "id": "PMID-19953879_T27", "type": "Multi-tissue_structure", "text": [ "hepatic artery" ], "offsets": [ [ 1846, 1860 ] ], "normalized": [] }, { "id": "PMID-19953879_T28", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 1877, 1882 ] ], "normalized": [] }, { "id": "PMID-19953879_T29", "type": "Multi-tissue_structure", "text": [ "right lobe liver grafts" ], "offsets": [ [ 1915, 1938 ] ], "normalized": [] }, { "id": "PMID-19953879_T30", "type": "Pathological_formation", "text": [ "aneurysm" ], "offsets": [ [ 1538, 1546 ] ], "normalized": [] } ]

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[ { "id": "PMID-10978899__text", "type": "abstract", "text": [ "Urokinase receptor: a molecular organizer in cellular communication.\nIn a variety of cell types, the glycolipid-anchored urokinase receptor (uPAR) is colocalized pericellularly with components of the plasminogen activation system and endocytosis receptors. uPAR is also coexpressed with caveolin and members of the integrin adhesion receptor superfamily. The formation of functional units with these various proteins allows the uPAR to mediate the focused proteolysis required for cell migration and invasion and to contribute both directly and indirectly to cell adhesive processes in a non-proteolytic fashion. This dual activity, together with the initiation of signal transduction pathways by uPAR, is believed to influence cellular behaviour in angiogenesis, inflammation, wound repair and tumor progression/metastasis and open up the way for uPAR-based therapeutic approaches.\n" ], "offsets": [ [ 0, 883 ] ] } ]

[ { "id": "PMID-10978899_T2", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 45, 53 ] ], "normalized": [] }, { "id": "PMID-10978899_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 85, 89 ] ], "normalized": [] }, { "id": "PMID-10978899_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 481, 485 ] ], "normalized": [] }, { "id": "PMID-10978899_T12", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 559, 563 ] ], "normalized": [] }, { "id": "PMID-10978899_T14", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 728, 736 ] ], "normalized": [] }, { "id": "PMID-10978899_T15", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 778, 783 ] ], "normalized": [] }, { "id": "PMID-10978899_T16", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 795, 800 ] ], "normalized": [] }, { "id": "PMID-10978899_T1", "type": "Immaterial_anatomical_entity", "text": [ "pericellularly" ], "offsets": [ [ 162, 176 ] ], "normalized": [] } ]

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[ { "id": "PMID-2314900__text", "type": "abstract", "text": [ "Overexpression confers an oncogenic potential upon the eph gene. \nThe eph gene encodes a putative receptor tyrosine kinase for an as yet unknown ligand. Some human cancer cells have been found to overexpress eph mRNAs without gene amplification. We show here that NIH3T3 cells acquire tumorigenic ability in nude mice and make colonies in soft agar with a viral LTR (Long Terminal Repeat)-driven artificial expression of the eph gene to a high level. This result supports the alleged contribution of overexpressed receptor tyrosine kinases to cell transformation.\n" ], "offsets": [ [ 0, 564 ] ] } ]

[ { "id": "PMID-2314900_T5", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 164, 176 ] ], "normalized": [] }, { "id": "PMID-2314900_T7", "type": "Cell", "text": [ "NIH3T3 cells" ], "offsets": [ [ 264, 276 ] ], "normalized": [] }, { "id": "PMID-2314900_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 543, 547 ] ], "normalized": [] }, { "id": "PMID-2314900_T24", "type": "Cellular_component", "text": [ "LTR" ], "offsets": [ [ 362, 365 ] ], "normalized": [] }, { "id": "PMID-2314900_T25", "type": "Cellular_component", "text": [ "Long Terminal Repeat" ], "offsets": [ [ 367, 387 ] ], "normalized": [] }, { "id": "PMID-2314900_T1", "type": "Cell", "text": [ "colonies" ], "offsets": [ [ 327, 335 ] ], "normalized": [] } ]

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[ { "id": "PMC-3245051-caption-01__text", "type": "caption", "text": [ "The growth in the number of database publications per year. Each bar shows the number of research articles with the keyword 'database' appearing in the article title in the given year. The count only covers articles indexed in PubMed. The increase shows an exponential trend that will produce nearly 2000 database publications per year by 2015.\n" ], "offsets": [ [ 0, 345 ] ] } ]

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[ { "id": "PMID-2704697__text", "type": "abstract", "text": [ "Early post-mortem metabolism and muscle shortening in the Pectoralis major muscle of broiler chickens.\nThree experiments were conducted to examine the effects of sodium pentobarbital (SP), iodoacetate (IO), tubocurarine (TC), and surgical denervation (DN) on early rigor development in broiler breast muscle. In Experiment 1, birds were either anesthetized or not with SP before receiving an injection of IO or TC or maintained as noninjected controls. Experiment 2 was identical except that a treatment of denervation of the breast muscle was added. Experiment 3 was conducted to contrast birds at 1 day (DN1) and 3 days (DN3) denervation prior to slaughter to nonoperated controls. Measurements of muscle lactate, ATP, R value (ratio of inosine to adenine nucleotides), pH, sarcomere lengths, and shear were used to evaluate treatment effects. Results for Experiment 1 showed no significant differences among treatment and control groups for ATP and lactate contents, R values, or sarcomere lengths; however, significantly lower pH and higher shear values were observed for control birds. In Experiment 2, no significant differences were observed among the treatment groups for ATP, R values, or sarcomere lengths. However, lactate and shear values were significantly lower, and pH higher, for the DN and SP treated birds. Experiment 3 resulted in lower lactate and higher pH values for the DN3 treatment in comparison with both DN1 and control groups. Results of these studies indicate that the use of SP and DN can be used to alter the early profiles of rigor development.\n" ], "offsets": [ [ 0, 1577 ] ] } ]

[ { "id": "PMID-2704697_T1", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 33, 39 ] ], "normalized": [] }, { "id": "PMID-2704697_T2", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 75, 81 ] ], "normalized": [] }, { "id": "PMID-2704697_T3", "type": "Organ", "text": [ "breast muscle" ], "offsets": [ [ 294, 307 ] ], "normalized": [] }, { "id": "PMID-2704697_T4", "type": "Organ", "text": [ "breast muscle" ], "offsets": [ [ 526, 539 ] ], "normalized": [] }, { "id": "PMID-2704697_T5", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 700, 706 ] ], "normalized": [] }, { "id": "PMID-2704697_T6", "type": "Tissue", "text": [ "sarcomere" ], "offsets": [ [ 776, 785 ] ], "normalized": [] }, { "id": "PMID-2704697_T7", "type": "Tissue", "text": [ "sarcomere" ], "offsets": [ [ 983, 992 ] ], "normalized": [] }, { "id": "PMID-2704697_T8", "type": "Tissue", "text": [ "sarcomere" ], "offsets": [ [ 1198, 1207 ] ], "normalized": [] } ]

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[ { "id": "PMID-16398404__text", "type": "abstract", "text": [ "The differential regulation of human telomerase reverse transcriptase and vascular endothelial growth factor may contribute to the clinically more aggressive behavior of p63-positive breast carcinomas.\np63, a p53 homologue, is a myoepithelial cell marker in the normal mammary gland but p63-positive neoplastic cells may be found in up to 11% of invasive breast carcinomas. This study aims to verify the relationship between p63 expression and several clinicopathological features and tumor markers of clinical significance in breast pathology including key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors. Immunohistochemistry with 27 primary antibodies was performed in 100 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. p63-positive cells were found in 16% of carcinomas. p63-positive carcinomas were poorly differentiated, hormone receptor-negative neoplasms with a high proliferation rate. p63 also correlated with advanced pathological stage, tumor size, and the expression of human telomerase reverse transcriptase (hTERT), tissue inhibitor of matrix metalloproteinase 1 (TIMP1) and vascular endothelial growth factor (VEGF). The expression of TIMP1 suggests that the anti-proteolytic stimuli may be preponderant in p63-positive carcinomas. hTERT activity is associated with nodal metastases and cellular proliferation. VEGF regulates angiogenesis, which is also a fundamental event in the process of tumor growth and metastatic dissemination. Thus, the differential regulation of hTERT and VEGF in p63-positive breast carcinomas may contribute to the clinically more aggressive behavior of these neoplasms.\n" ], "offsets": [ [ 0, 1701 ] ] } ]

[ { "id": "PMID-16398404_T4", "type": "Cancer", "text": [ "p63-positive breast carcinomas" ], "offsets": [ [ 170, 200 ] ], "normalized": [] }, { "id": "PMID-16398404_T8", "type": "Cell", "text": [ "myoepithelial cell" ], "offsets": [ [ 229, 247 ] ], "normalized": [] }, { "id": "PMID-16398404_T9", "type": "Organ", "text": [ "mammary gland" ], "offsets": [ [ 269, 282 ] ], "normalized": [] }, { "id": "PMID-16398404_T10", "type": "Cell", "text": [ "p63-positive neoplastic cells" ], "offsets": [ [ 287, 316 ] ], "normalized": [] }, { "id": "PMID-16398404_T12", "type": "Cancer", "text": [ "invasive breast carcinomas" ], "offsets": [ [ 346, 372 ] ], "normalized": [] }, { "id": "PMID-16398404_T14", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 485, 490 ] ], "normalized": [] }, { "id": "PMID-16398404_T15", "type": "Cancer", "text": [ "breast pathology" ], "offsets": [ [ 527, 543 ] ], "normalized": [] }, { "id": "PMID-16398404_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 576, 580 ] ], "normalized": [] }, { "id": "PMID-16398404_T18", "type": "Cancer", "text": [ "invasive ductal carcinomas" ], "offsets": [ [ 781, 807 ] ], "normalized": [] }, { "id": "PMID-16398404_T19", "type": "Cell", "text": [ "p63-positive cells" ], "offsets": [ [ 809, 827 ] ], "normalized": [] }, { "id": "PMID-16398404_T21", "type": "Cancer", "text": [ "carcinomas" ], "offsets": [ [ 849, 859 ] ], "normalized": [] }, { "id": "PMID-16398404_T22", "type": "Cancer", "text": [ "p63-positive carcinomas" ], "offsets": [ [ 861, 884 ] ], "normalized": [] }, { "id": "PMID-16398404_T24", "type": "Cancer", "text": [ "neoplasms" ], "offsets": [ [ 939, 948 ] ], "normalized": [] }, { "id": "PMID-16398404_T26", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1035, 1040 ] ], "normalized": [] }, { "id": "PMID-16398404_T35", "type": "Cancer", "text": [ "p63-positive carcinomas" ], "offsets": [ [ 1309, 1332 ] ], "normalized": [] }, { "id": "PMID-16398404_T38", "type": "Cancer", "text": [ "nodal metastases" ], "offsets": [ [ 1368, 1384 ] ], "normalized": [] }, { "id": "PMID-16398404_T39", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1389, 1397 ] ], "normalized": [] }, { "id": "PMID-16398404_T41", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1494, 1499 ] ], "normalized": [] }, { "id": "PMID-16398404_T44", "type": "Cancer", "text": [ "p63-positive breast carcinomas" ], "offsets": [ [ 1592, 1622 ] ], "normalized": [] }, { "id": "PMID-16398404_T46", "type": "Cancer", "text": [ "neoplasms" ], "offsets": [ [ 1690, 1699 ] ], "normalized": [] }, { "id": "PMID-16398404_T66", "type": "Cancer", "text": [ "samples" ], "offsets": [ [ 770, 777 ] ], "normalized": [] } ]

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[ { "id": "PMID-19236257__text", "type": "abstract", "text": [ "Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors.\nBACKGROUND: Aberrant angiogenesis is a landmark feature in cancer, which is important for proliferation, growth and metastasis, and is mediated by various pro-angiogenic factors. The VEGF pathway is one of the most important and best-studied angiogenic pathways. Inhibition of this pathway may provide clinical benefits to cancer patients. OBJECTIVES: Strategies to inhibit the VEGF pathway, including antibodies to VEGF, antibodies to the extracellular domain of VEGFR-1 or VEGFR-2, decoy receptors for VEGF and tyrosine kinase inhibitors of VEGFRs, are summarized. METHODS: This review outlines and compares the latest development of these strategies, with emphasis on aflibercept, a novel decoy fusion protein of domain 2 of VEGFR-1 and domain 3 of VEGFR-2 with the Fc fragment of IgG1. RESULTS: Aflibercept was shown to have early clinical activity. Multiple studies are ongoing to determine the clinical benefits of aflibercept in cancer patients.\n" ], "offsets": [ [ 0, 1075 ] ] } ]

[ { "id": "PMID-19236257_T3", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 62, 68 ] ], "normalized": [] }, { "id": "PMID-19236257_T5", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 181, 187 ] ], "normalized": [] }, { "id": "PMID-19236257_T7", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 445, 451 ] ], "normalized": [] }, { "id": "PMID-19236257_T22", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1058, 1064 ] ], "normalized": [] }, { "id": "PMID-19236257_T1", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 562, 575 ] ], "normalized": [] } ]

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[ { "id": "PMID-9778569__text", "type": "abstract", "text": [ "Glucose and lactate metabolism in C6 glioma cells: evidence for the preferential utilization of lactate for cell oxidative metabolism.\n13C and 1H nuclear magnetic resonance spectroscopy (NMR) was used to investigate the metabolism of L-lactate and D-glucose in C6 glioma cells. The 13C enrichment of cell metabolites was examined after a 4-h incubation in media containing 5.5 mM glucose and 11 mM lactate, each metabolite being alternatively labelled with either [1-13C]D-glucose or [3-13C]L-lactate. The results indicated that exogenous lactate was the major substrate for oxidative metabolism. They were consistent with the concept of the existence of 2 pools of both lactate and pyruvate, of which 1 pool was closely connected with exogenous lactate and oxidative metabolism, and the other pool was closely related to glycolysis and disconnected from oxidative metabolism. The molecular basis of this behaviour could be related to different locations for the lactate dehydrogenase isoenzymes, as suggested by their immunohistochemical labelling.\n" ], "offsets": [ [ 0, 1050 ] ] } ]

[ { "id": "PMID-9778569_T3", "type": "Cell", "text": [ "C6 glioma cells" ], "offsets": [ [ 34, 49 ] ], "normalized": [] }, { "id": "PMID-9778569_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 108, 112 ] ], "normalized": [] }, { "id": "PMID-9778569_T10", "type": "Cell", "text": [ "C6 glioma cells" ], "offsets": [ [ 261, 276 ] ], "normalized": [] }, { "id": "PMID-9778569_T12", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 300, 304 ] ], "normalized": [] } ]

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[ { "id": "PMID-17960624__text", "type": "abstract", "text": [ "Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion.\nThe role of the pro-inflammatory peptide, LL-37, and its pro-form, human cationic antimicrobial protein 18 (hCAP-18), in cancer development and progression is poorly understood. In damaged and inflamed tissue, LL-37 functions as a chemoattractant, mitogen and pro-angiogenic factor suggesting that the peptide may potentiate tumor progression. The aim of this study was to characterize the distribution of hCAP-18/LL-37 in normal and cancerous ovarian tissue and to examine the effects of LL-37 on ovarian cancer cells. Expression of hCAP-18/LL-37 was localized to immune and granulosa cells of normal ovarian tissue. By contrast, ovarian tumors displayed significantly higher levels of hCAP-18/LL-37 where expression was observed in tumor and stromal cells. Protein expression was statistically compared to the degree of immune cell infiltration and microvessel density in epithelial-derived ovarian tumors and a significant correlation was observed for both. It was demonstrated that ovarian tumor tissue lysates and ovarian cancer cell lines express hCAP-18/LL-37. Treatment of ovarian cancer cell lines with recombinant LL-37 stimulated proliferation, chemotaxis, invasion and matrix metalloproteinase expression. These data demonstrate for the first time that hCAP-18/LL-37 is significantly overexpressed in ovarian tumors and suggest LL-37 may contribute to ovarian tumorigenesis through direct stimulation of tumor cells, initiation of angiogenesis and recruitment of immune cells. These data provide further evidence of the existing relationship between pro-inflammatory molecules and ovarian cancer progression.\n" ], "offsets": [ [ 0, 1766 ] ] } ]

[ { "id": "PMID-17960624_T1", "type": "Cancer", "text": [ "Ovarian cancers" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "PMID-17960624_T4", "type": "Cell", "text": [ "ovarian cancer cell" ], "offsets": [ [ 97, 116 ] ], "normalized": [] }, { "id": "PMID-17960624_T8", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 266, 272 ] ], "normalized": [] }, { "id": "PMID-17960624_T9", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 347, 353 ] ], "normalized": [] }, { "id": "PMID-17960624_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 470, 475 ] ], "normalized": [] }, { "id": "PMID-17960624_T14", "type": "Cancer", "text": [ "cancerous ovarian tissue" ], "offsets": [ [ 579, 603 ] ], "normalized": [] }, { "id": "PMID-17960624_T16", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 643, 663 ] ], "normalized": [] }, { "id": "PMID-17960624_T19", "type": "Cell", "text": [ "immune" ], "offsets": [ [ 710, 716 ] ], "normalized": [] }, { "id": "PMID-17960624_T20", "type": "Cell", "text": [ "granulosa cells" ], "offsets": [ [ 721, 736 ] ], "normalized": [] }, { "id": "PMID-17960624_T21", "type": "Tissue", "text": [ "ovarian tissue" ], "offsets": [ [ 747, 761 ] ], "normalized": [] }, { "id": "PMID-17960624_T22", "type": "Cancer", "text": [ "ovarian tumors" ], "offsets": [ [ 776, 790 ] ], "normalized": [] }, { "id": "PMID-17960624_T25", "type": "Cell", "text": [ "tumor" ], "offsets": [ [ 879, 884 ] ], "normalized": [] }, { "id": "PMID-17960624_T26", "type": "Cell", "text": [ "stromal cells" ], "offsets": [ [ 889, 902 ] ], "normalized": [] }, { "id": "PMID-17960624_T27", "type": "Cell", "text": [ "immune cell" ], "offsets": [ [ 967, 978 ] ], "normalized": [] }, { "id": "PMID-17960624_T28", "type": "Tissue", "text": [ "microvessel" ], "offsets": [ [ 996, 1007 ] ], "normalized": [] }, { "id": "PMID-17960624_T29", "type": "Cancer", "text": [ "epithelial-derived ovarian tumors" ], "offsets": [ [ 1019, 1052 ] ], "normalized": [] }, { "id": "PMID-17960624_T30", "type": "Organism_substance", "text": [ "ovarian tumor tissue lysates" ], "offsets": [ [ 1131, 1159 ] ], "normalized": [] }, { "id": "PMID-17960624_T31", "type": "Cell", "text": [ "ovarian cancer cell lines" ], "offsets": [ [ 1164, 1189 ] ], "normalized": [] }, { "id": "PMID-17960624_T34", "type": "Cell", "text": [ "ovarian cancer cell lines" ], "offsets": [ [ 1226, 1251 ] ], "normalized": [] }, { "id": "PMID-17960624_T39", "type": "Cancer", "text": [ "ovarian tumors" ], "offsets": [ [ 1458, 1472 ] ], "normalized": [] }, { "id": "PMID-17960624_T41", "type": "Organ", "text": [ "ovarian" ], "offsets": [ [ 1509, 1516 ] ], "normalized": [] }, { "id": "PMID-17960624_T42", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1561, 1572 ] ], "normalized": [] }, { "id": "PMID-17960624_T43", "type": "Cell", "text": [ "immune cells" ], "offsets": [ [ 1620, 1632 ] ], "normalized": [] }, { "id": "PMID-17960624_T44", "type": "Cancer", "text": [ "ovarian cancer" ], "offsets": [ [ 1738, 1752 ] ], "normalized": [] } ]

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[ { "id": "PMID-17662274__text", "type": "abstract", "text": [ "Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: implications for oral carcinogenesis. \nIn oral cancers, cytoplasmic BAG-1 overexpression is a marker of poor prognosis. BAG-1 regulates cellular growth, differentiation and survival through interactions with diverse proteins, including the vitamin D receptor (VDR), a key regulator of keratinocyte growth and differentiation. BAG-1 is expressed ubiquitously in human cells as three major isoforms of 50 kDa (BAG-1L), 46 kDa (BAG-1M) and 36 kDa (BAG-1S) from a single mRNA. In oral keratinocytes BAG-1L, but not BAG-1M and BAG-1S, enhanced VDR transactivation in response to 1alpha,25-dihydroxyvitamin D3. BAG-1L was nucleoplasmic and nucleolar, whereas BAG-1S and BAG-1M were cytoplasmic and nucleoplasmic in localisation. Having identified the nucleolar localisation sequence in BAG-1L, we showed that mutation of this sequence did not prevent BAG-1L from potentiating VDR activity. BAG-1L also potentiated transactivation of known vitamin-D-responsive gene promoters, osteocalcin and 24-hydroxylase, and enhanced VDR-dependent transcription and protein expression of the keratinocyte differentiation marker, involucrin. These results demonstrate endogenous gene regulation by BAG-1L by potentiating nuclear hormone receptor function and suggest a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1alpha,25-dihydroxyvitamin D3. By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis.\n" ], "offsets": [ [ 0, 1638 ] ] } ]

[ { "id": "PMID-17662274_T4", "type": "Cell", "text": [ "oral keratinocytes" ], "offsets": [ [ 129, 147 ] ], "normalized": [] }, { "id": "PMID-17662274_T5", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 166, 170 ] ], "normalized": [] }, { "id": "PMID-17662274_T6", "type": "Cancer", "text": [ "oral cancers" ], "offsets": [ [ 191, 203 ] ], "normalized": [] }, { "id": "PMID-17662274_T7", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 205, 216 ] ], "normalized": [] }, { "id": "PMID-17662274_T10", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 285, 293 ] ], "normalized": [] }, { "id": "PMID-17662274_T13", "type": "Cell", "text": [ "keratinocyte" ], "offsets": [ [ 434, 446 ] ], "normalized": [] }, { "id": "PMID-17662274_T16", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 516, 521 ] ], "normalized": [] }, { "id": "PMID-17662274_T20", "type": "Cell", "text": [ "oral keratinocytes" ], "offsets": [ [ 625, 643 ] ], "normalized": [] }, { "id": "PMID-17662274_T27", "type": "Organism_substance", "text": [ "nucleoplasmic" ], "offsets": [ [ 765, 778 ] ], "normalized": [] }, { "id": "PMID-17662274_T28", "type": "Cellular_component", "text": [ "nucleolar" ], "offsets": [ [ 783, 792 ] ], "normalized": [] }, { "id": "PMID-17662274_T31", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 825, 836 ] ], "normalized": [] }, { "id": "PMID-17662274_T32", "type": "Organism_substance", "text": [ "nucleoplasmic" ], "offsets": [ [ 841, 854 ] ], "normalized": [] }, { "id": "PMID-17662274_T33", "type": "Cellular_component", "text": [ "nucleolar" ], "offsets": [ [ 894, 903 ] ], "normalized": [] }, { "id": "PMID-17662274_T42", "type": "Cell", "text": [ "keratinocyte" ], "offsets": [ [ 1222, 1234 ] ], "normalized": [] }, { "id": "PMID-17662274_T49", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1475, 1483 ] ], "normalized": [] }, { "id": "PMID-17662274_T50", "type": "Cell", "text": [ "oral keratinocytes" ], "offsets": [ [ 1496, 1514 ] ], "normalized": [] }, { "id": "PMID-17662274_T52", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1568, 1579 ] ], "normalized": [] }, { "id": "PMID-17662274_T90", "type": "Cellular_component", "text": [ "Subcellular" ], "offsets": [ [ 0, 11 ] ], "normalized": [] } ]

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[ { "id": "PMID-9840923__text", "type": "abstract", "text": [ "Tumors of the retinal pigment epithelium metastasize to inguinal lymph nodes and spleen in tyrosinase-related protein 1/SV40 T antigen transgenic mice. \nThe pigment epithelium of the retina (RPE) is derived from the optic cup and is essential for function and development of the eye. We produced a transgenic mouse line that expresses simian virus (SV40) transforming sequences under control of the 1.4 kb tyrosinase-related protein 1 (TRP-1) promoter, targeting expression of T antigen (Tag) to the RPE. In transgenic embryos, RPE cells proliferated in the anterior part of the eye and near the optic nerve. This resulted in formation of tumors, which were pigmented and of epithelial origin. In 3 months-old mice, pigmented cells were detected in spleen and inguinal lymph nodes. In spleen, tyrosinase, TRP-1 and SV40 Tag were expressed and tyrosinase was enzymatically active. Pigmented regions were positive for an epithelial marker, cytokeratin. Cell lines were established from tumor and metastases and kept in culture for more than 2 months. These were pigmented, and maintained expression of tyrosinase, TRP-1, cytokeratin and SV40 Tag. This demonstrates that RPE tumor cells metastasize to lymph node and spleen. In conclusion, the metastasis from TRP-1/Tag RPE tumors towards spleen and lymph nodes serves as potential tool to investigate biology and metastasis of tumors derived from the pigment epithelium.\n" ], "offsets": [ [ 0, 1419 ] ] } ]

[ { "id": "PMID-9840923_T1", "type": "Cancer", "text": [ "Tumors" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "PMID-9840923_T2", "type": "Tissue", "text": [ "retinal pigment epithelium" ], "offsets": [ [ 14, 40 ] ], "normalized": [] }, { "id": "PMID-9840923_T3", "type": "Multi-tissue_structure", "text": [ "inguinal lymph nodes" ], "offsets": [ [ 56, 76 ] ], "normalized": [] }, { "id": "PMID-9840923_T4", "type": "Organ", "text": [ "spleen" ], "offsets": [ [ 81, 87 ] ], "normalized": [] }, { "id": "PMID-9840923_T8", "type": "Tissue", "text": [ "pigment epithelium" ], "offsets": [ [ 157, 175 ] ], "normalized": [] }, { "id": "PMID-9840923_T9", "type": "Multi-tissue_structure", "text": [ "retina" ], "offsets": [ [ 183, 189 ] ], "normalized": [] }, { "id": "PMID-9840923_T10", "type": "Tissue", "text": [ "RPE" ], "offsets": [ [ 191, 194 ] ], "normalized": [] }, { "id": "PMID-9840923_T11", "type": "Multi-tissue_structure", "text": [ "optic cup" ], "offsets": [ [ 216, 225 ] ], "normalized": [] }, { "id": "PMID-9840923_T12", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 279, 282 ] ], "normalized": [] }, { "id": "PMID-9840923_T20", "type": "Tissue", "text": [ "RPE" ], "offsets": [ [ 500, 503 ] ], "normalized": [] }, { "id": "PMID-9840923_T21", "type": "Developing_anatomical_structure", "text": [ "embryos" ], "offsets": [ [ 519, 526 ] ], "normalized": [] }, { "id": "PMID-9840923_T22", "type": "Cell", "text": [ "RPE cells" ], "offsets": [ [ 528, 537 ] ], "normalized": [] }, { "id": "PMID-9840923_T23", "type": "Multi-tissue_structure", "text": [ "anterior part" ], "offsets": [ [ 558, 571 ] ], "normalized": [] }, { "id": "PMID-9840923_T24", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 579, 582 ] ], "normalized": [] }, { "id": "PMID-9840923_T25", "type": "Multi-tissue_structure", "text": [ "optic nerve" ], "offsets": [ [ 596, 607 ] ], "normalized": [] }, { "id": "PMID-9840923_T26", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 639, 645 ] ], "normalized": [] }, { "id": "PMID-9840923_T27", "type": "Tissue", "text": [ "epithelial" ], "offsets": [ [ 675, 685 ] ], "normalized": [] }, { "id": "PMID-9840923_T29", "type": "Cell", "text": [ "pigmented cells" ], "offsets": [ [ 716, 731 ] ], "normalized": [] }, { "id": "PMID-9840923_T30", "type": "Organ", "text": [ "spleen" ], "offsets": [ [ 749, 755 ] ], "normalized": [] }, { "id": "PMID-9840923_T31", "type": "Multi-tissue_structure", "text": [ "inguinal lymph nodes" ], "offsets": [ [ 760, 780 ] ], "normalized": [] }, { "id": "PMID-9840923_T32", "type": "Organ", "text": [ "spleen" ], "offsets": [ [ 785, 791 ] ], "normalized": [] }, { "id": "PMID-9840923_T38", "type": "Tissue", "text": [ "epithelial" ], "offsets": [ [ 919, 929 ] ], "normalized": [] }, { "id": "PMID-9840923_T40", "type": "Cell", "text": [ "Cell lines" ], "offsets": [ [ 951, 961 ] ], "normalized": [] }, { "id": "PMID-9840923_T41", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 984, 989 ] ], "normalized": [] }, { "id": "PMID-9840923_T47", "type": "Cell", "text": [ "RPE tumor cells" ], "offsets": [ [ 1168, 1183 ] ], "normalized": [] }, { "id": "PMID-9840923_T48", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1199, 1209 ] ], "normalized": [] }, { "id": "PMID-9840923_T49", "type": "Organ", "text": [ "spleen" ], "offsets": [ [ 1214, 1220 ] ], "normalized": [] }, { "id": "PMID-9840923_T51", "type": "Cancer", "text": [ "TRP-1/Tag RPE tumors" ], "offsets": [ [ 1257, 1277 ] ], "normalized": [] }, { "id": "PMID-9840923_T53", "type": "Organ", "text": [ "spleen" ], "offsets": [ [ 1286, 1292 ] ], "normalized": [] }, { "id": "PMID-9840923_T54", "type": "Multi-tissue_structure", "text": [ "lymph nodes" ], "offsets": [ [ 1297, 1308 ] ], "normalized": [] }, { "id": "PMID-9840923_T55", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1375, 1381 ] ], "normalized": [] }, { "id": "PMID-9840923_T56", "type": "Tissue", "text": [ "pigment epithelium" ], "offsets": [ [ 1399, 1417 ] ], "normalized": [] }, { "id": "PMID-9840923_T5", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 994, 1004 ] ], "normalized": [] } ]

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[ { "id": "PMC-3087566-caption-11__text", "type": "caption", "text": [ "Representative time histories of the estimated SatO2 levels of normal cortex (black) and tumor (grey) from all six patients.\n" ], "offsets": [ [ 0, 125 ] ] } ]

[ { "id": "PMC-3087566-caption-11_T1", "type": "Multi-tissue_structure", "text": [ "cortex" ], "offsets": [ [ 70, 76 ] ], "normalized": [] }, { "id": "PMC-3087566-caption-11_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 89, 94 ] ], "normalized": [] } ]

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[ { "id": "PMID-2418866__text", "type": "abstract", "text": [ "Retinal revascularisation in diabetic retinopathy.\nThe case history of a 33-year-old diabetic patient who has had diabetes for 24 years is presented. When first seen in 1975 he had bilateral proliferative retinopathy with new vessels in the retinal periphery. He had large areas of capillary non-perfusion lateral to the macula in the right eye associated with the new vessels. Nine years later, after extensive repeated photocoagulation, revascularisation of large areas previously not perfused were seen. The vessels are in the plane of the retina and do not have the appearance of new vessels.\n" ], "offsets": [ [ 0, 597 ] ] } ]

[ { "id": "PMID-2418866_T2", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 226, 233 ] ], "normalized": [] }, { "id": "PMID-2418866_T3", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 282, 291 ] ], "normalized": [] }, { "id": "PMID-2418866_T4", "type": "Organ", "text": [ "right eye" ], "offsets": [ [ 335, 344 ] ], "normalized": [] }, { "id": "PMID-2418866_T5", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 369, 376 ] ], "normalized": [] }, { "id": "PMID-2418866_T7", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 511, 518 ] ], "normalized": [] }, { "id": "PMID-2418866_T8", "type": "Multi-tissue_structure", "text": [ "retina" ], "offsets": [ [ 543, 549 ] ], "normalized": [] }, { "id": "PMID-2418866_T9", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 588, 595 ] ], "normalized": [] }, { "id": "PMID-2418866_T10", "type": "Tissue", "text": [ "macula" ], "offsets": [ [ 321, 327 ] ], "normalized": [] }, { "id": "PMID-2418866_T11", "type": "Tissue", "text": [ "retinal periphery" ], "offsets": [ [ 241, 258 ] ], "normalized": [] }, { "id": "PMID-2418866_T13", "type": "Multi-tissue_structure", "text": [ "Retinal" ], "offsets": [ [ 0, 7 ] ], "normalized": [] } ]

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[ { "id": "PMID-17432972__text", "type": "abstract", "text": [ "The relationship between brain activity and peak grip force is modulated by corticospinal system integrity after subcortical stroke.\nIn healthy human subjects, the relative contribution of cortical regions to motor performance varies with the task parameters. Additionally, after stroke, recruitment of cortical areas during a simple motor task varies with corticospinal system integrity. We investigated whether the pattern of motor system recruitment in a task involving increasingly forceful hand grips is influenced by the degree of corticospinal system damage. Nine chronic subcortical stroke patients and nine age-matched controls underwent functional magnetic brain imaging whilst performing repetitive isometric hand grips. Target grip forces were varied between 15% and 45% of individual maximum grip force. Corticospinal system functional integrity was assessed with transcranial magnetic stimulation. Averaged across all forces, there was more task-related activation compared with rest in the secondary motor areas of patients with greater corticospinal system damage, confirming previous reports. However, here we were primarily interested in regional brain activation, which covaried with the amount of force generated, implying a prominent executive role in force production. We found that in control subjects and patients with lesser corticospinal system damage, signal change increased linearly with increasing force output in contralateral primary motor cortex, supplementary motor area and ipsilateral cerebellum. In contrast, in patients with greater corticospinal system damage, force-related signal changes were seen mainly in contralesional dorsolateral premotor cortex, bilateral ventrolateral premotor cortices and contralesional cerebellum, but not ipsilesional primary motor cortex. These findings suggest that the premotor cortices might play a new and functionally relevant role in controlling force production in patients with more severe corticospinal system disruption.\n" ], "offsets": [ [ 0, 2002 ] ] } ]

[ { "id": "PMID-17432972_T1", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 25, 30 ] ], "normalized": [] }, { "id": "PMID-17432972_T2", "type": "Multi-tissue_structure", "text": [ "cortical regions" ], "offsets": [ [ 189, 205 ] ], "normalized": [] }, { "id": "PMID-17432972_T3", "type": "Multi-tissue_structure", "text": [ "cortical areas" ], "offsets": [ [ 303, 317 ] ], "normalized": [] }, { "id": "PMID-17432972_T4", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 495, 499 ] ], "normalized": [] }, { "id": "PMID-17432972_T5", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 667, 672 ] ], "normalized": [] }, { "id": "PMID-17432972_T6", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 720, 724 ] ], "normalized": [] }, { "id": "PMID-17432972_T7", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 1165, 1170 ] ], "normalized": [] }, { "id": "PMID-17432972_T8", "type": "Multi-tissue_structure", "text": [ "contralateral primary motor cortex" ], "offsets": [ [ 1444, 1478 ] ], "normalized": [] }, { "id": "PMID-17432972_T9", "type": "Multi-tissue_structure", "text": [ "ipsilateral cerebellum" ], "offsets": [ [ 1509, 1531 ] ], "normalized": [] }, { "id": "PMID-17432972_T10", "type": "Anatomical_system", "text": [ "corticospinal system" ], "offsets": [ [ 1571, 1591 ] ], "normalized": [] }, { "id": "PMID-17432972_T11", "type": "Multi-tissue_structure", "text": [ "contralesional dorsolateral premotor cortex" ], "offsets": [ [ 1649, 1692 ] ], "normalized": [] }, { "id": "PMID-17432972_T12", "type": "Multi-tissue_structure", "text": [ "bilateral ventrolateral premotor cortices" ], "offsets": [ [ 1694, 1735 ] ], "normalized": [] }, { "id": "PMID-17432972_T13", "type": "Multi-tissue_structure", "text": [ "contralesional cerebellum" ], "offsets": [ [ 1740, 1765 ] ], "normalized": [] }, { "id": "PMID-17432972_T14", "type": "Multi-tissue_structure", "text": [ "ipsilesional primary motor cortex" ], "offsets": [ [ 1775, 1808 ] ], "normalized": [] }, { "id": "PMID-17432972_T15", "type": "Multi-tissue_structure", "text": [ "premotor cortices" ], "offsets": [ [ 1842, 1859 ] ], "normalized": [] }, { "id": "PMID-17432972_T16", "type": "Anatomical_system", "text": [ "corticospinal system" ], "offsets": [ [ 1969, 1989 ] ], "normalized": [] }, { "id": "PMID-17432972_T17", "type": "Anatomical_system", "text": [ "corticospinal system" ], "offsets": [ [ 76, 96 ] ], "normalized": [] }, { "id": "PMID-17432972_T18", "type": "Anatomical_system", "text": [ "corticospinal system" ], "offsets": [ [ 357, 377 ] ], "normalized": [] }, { "id": "PMID-17432972_T19", "type": "Anatomical_system", "text": [ "corticospinal system" ], "offsets": [ [ 537, 557 ] ], "normalized": [] }, { "id": "PMID-17432972_T20", "type": "Anatomical_system", "text": [ "corticospinal system" ], "offsets": [ [ 1052, 1072 ] ], "normalized": [] }, { "id": "PMID-17432972_T21", "type": "Anatomical_system", "text": [ "corticospinal system" ], "offsets": [ [ 1350, 1370 ] ], "normalized": [] }, { "id": "PMID-17432972_T22", "type": "Multi-tissue_structure", "text": [ "subcortical" ], "offsets": [ [ 113, 124 ] ], "normalized": [] }, { "id": "PMID-17432972_T23", "type": "Multi-tissue_structure", "text": [ "subcortical" ], "offsets": [ [ 579, 590 ] ], "normalized": [] }, { "id": "PMID-17432972_T24", "type": "Multi-tissue_structure", "text": [ "supplementary motor area" ], "offsets": [ [ 1480, 1504 ] ], "normalized": [] } ]

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[ { "id": "PMID-3492269__text", "type": "abstract", "text": [ "Growth state-dependent regulation of protein kinase C in normal and transformed murine cells. \nWe determined whether growth state can influence the action of protein kinase C by measuring protein kinase C activity in growing and stationary cultures of normal and transformed cells. Two approaches were used to measure protein kinase C: assay of intact cells for inhibition of epidermal growth factor (EGF) binding in response to phorbol dibutyrate (PDBu); and assay of detergent extracts for total calcium, phospholipid-dependent kinase activity. In extracts of growing and stationary Swiss 3T3 cells, the total amount of protein kinase C activity was similar, indicating that growth state does not alter the level of enzyme in the cell. The short-term response of Swiss 3T3 cells to an activator of protein kinase C also appeared to be independent of growth state, since the 50% effective dose for PDBu inhibition of EGF binding to its receptor was approximately 7 nM for both growth conditions. In contrast, the response of cells to long-term treatment with PDBu was significantly different depending upon the initial growth state of the cells. In both growth states, PDBu caused loss of protein kinase C activity, which reflected a loss in protein mass as determined by immunoblotting with antiserum to protein kinase C. However, the maximum decrease approached 100% in stationary cultures versus approximately 75% in growing cells. Protein kinase C levels in several transformed cell lines were subject to down modulation in a similar growth state-dependent manner. Further, the inhibition of EGF binding by tumor promoters following long-term treatment of Swiss 3T3 cells with PDBu also varied with growth state. In down modulated growing cells, PDBu caused almost complete inhibition of EGF binding, whereas in down modulated stationary cells, minimal inhibition of EGF binding by PDBu was observed. These results suggest that prolonged treatment with tumor promoters alters the sensitivity of cells to activators of protein kinase C in a growth state-dependent manner.\n" ], "offsets": [ [ 0, 2076 ] ] } ]

[ { "id": "PMID-3492269_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 87, 92 ] ], "normalized": [] }, { "id": "PMID-3492269_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 275, 280 ] ], "normalized": [] }, { "id": "PMID-3492269_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 352, 357 ] ], "normalized": [] }, { "id": "PMID-3492269_T13", "type": "Organism_substance", "text": [ "extracts" ], "offsets": [ [ 479, 487 ] ], "normalized": [] }, { "id": "PMID-3492269_T16", "type": "Organism_substance", "text": [ "extracts" ], "offsets": [ [ 550, 558 ] ], "normalized": [] }, { "id": "PMID-3492269_T17", "type": "Cell", "text": [ "Swiss 3T3 cells" ], "offsets": [ [ 585, 600 ] ], "normalized": [] }, { "id": "PMID-3492269_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 732, 736 ] ], "normalized": [] }, { "id": "PMID-3492269_T20", "type": "Cell", "text": [ "Swiss 3T3 cells" ], "offsets": [ [ 765, 780 ] ], "normalized": [] }, { "id": "PMID-3492269_T24", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1026, 1031 ] ], "normalized": [] }, { "id": "PMID-3492269_T26", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1140, 1145 ] ], "normalized": [] }, { "id": "PMID-3492269_T29", "type": "Organism_substance", "text": [ "antiserum" ], "offsets": [ [ 1293, 1302 ] ], "normalized": [] }, { "id": "PMID-3492269_T31", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1429, 1434 ] ], "normalized": [] }, { "id": "PMID-3492269_T33", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1483, 1493 ] ], "normalized": [] }, { "id": "PMID-3492269_T35", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1612, 1617 ] ], "normalized": [] }, { "id": "PMID-3492269_T36", "type": "Cell", "text": [ "Swiss 3T3 cells" ], "offsets": [ [ 1661, 1676 ] ], "normalized": [] }, { "id": "PMID-3492269_T38", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1744, 1749 ] ], "normalized": [] }, { "id": "PMID-3492269_T41", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1843, 1848 ] ], "normalized": [] }, { "id": "PMID-3492269_T44", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1958, 1963 ] ], "normalized": [] }, { "id": "PMID-3492269_T45", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 2000, 2005 ] ], "normalized": [] }, { "id": "PMID-3492269_T1", "type": "Cell", "text": [ "cultures" ], "offsets": [ [ 240, 248 ] ], "normalized": [] }, { "id": "PMID-3492269_T2", "type": "Cell", "text": [ "cultures" ], "offsets": [ [ 1384, 1392 ] ], "normalized": [] } ]

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[ { "id": "PMID-10890377__text", "type": "abstract", "text": [ "The value of serum S-100beta and interleukins as tumour markers in advanced melanoma. \nRecently serum S-100beta has shown promise as a tumour marker in melanoma; however, its use as a prognostic marker in the advanced stage needs to be confirmed. Interleukins (ILs) may mediate regression or progression of cancer. In order to study their relation to the metastatic profile and survival, we evaluated the association between pretreatment serum levels of S-100beta, IL-6, IL-10 and IL-12 and metastatic site and survival in 50 patients with advanced melanoma who were to receive chemoimmunotherapy. Patients with liver and/or bone metastases had significantly higher median concentrations of S-100beta, IL-6 and IL-10 than those with only skin, nodal and/or lung involvement. The differences in IL-12 levels were unremarkable. Using univariate analysis, the S-100beta level and metastatic profile were found to be statistically significant prognostic factors for survival. Using multivariate analysis the S-100beta level was the most powerful prognostic indicator, while the metastatic profile was found to be significant after exclusion of S-100beta. The findings suggest that elevated serum levels of S-100beta, IL-6 and IL-10 reflect concurrent liver or bone metastases in melanoma. S-100beta is also an independent prognostic marker. Pretreatment IL levels were not associated with outcome.\n" ], "offsets": [ [ 0, 1394 ] ] } ]

[ { "id": "PMID-10890377_T1", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 13, 18 ] ], "normalized": [] }, { "id": "PMID-10890377_T4", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 49, 55 ] ], "normalized": [] }, { "id": "PMID-10890377_T5", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 76, 84 ] ], "normalized": [] }, { "id": "PMID-10890377_T6", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 96, 101 ] ], "normalized": [] }, { "id": "PMID-10890377_T8", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 135, 141 ] ], "normalized": [] }, { "id": "PMID-10890377_T9", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 152, 160 ] ], "normalized": [] }, { "id": "PMID-10890377_T12", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 307, 313 ] ], "normalized": [] }, { "id": "PMID-10890377_T13", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 438, 443 ] ], "normalized": [] }, { "id": "PMID-10890377_T19", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 549, 557 ] ], "normalized": [] }, { "id": "PMID-10890377_T21", "type": "Cancer", "text": [ "liver" ], "offsets": [ [ 612, 617 ] ], "normalized": [] }, { "id": "PMID-10890377_T22", "type": "Cancer", "text": [ "bone metastases" ], "offsets": [ [ 625, 640 ] ], "normalized": [] }, { "id": "PMID-10890377_T26", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 738, 742 ] ], "normalized": [] }, { "id": "PMID-10890377_T27", "type": "Multi-tissue_structure", "text": [ "nodal" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "PMID-10890377_T28", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 757, 761 ] ], "normalized": [] }, { "id": "PMID-10890377_T33", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1186, 1191 ] ], "normalized": [] }, { "id": "PMID-10890377_T37", "type": "Cancer", "text": [ "liver" ], "offsets": [ [ 1247, 1252 ] ], "normalized": [] }, { "id": "PMID-10890377_T38", "type": "Cancer", "text": [ "bone metastases" ], "offsets": [ [ 1256, 1271 ] ], "normalized": [] }, { "id": "PMID-10890377_T39", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 1275, 1283 ] ], "normalized": [] }, { "id": "PMID-10890377_T2", "type": "Cancer", "text": [ "metastatic site" ], "offsets": [ [ 491, 506 ] ], "normalized": [] } ]

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[ { "id": "PMID-2331105__text", "type": "abstract", "text": [ "The enlarging clinical spectrum of Lyme disease: Lyme cerebral vasculitis, a new disease entity.\nThe case of a patient with cerebral vasculitis with a right thalamic infarct associated with cerebral spinal fluid Lyme disease is presented. This entity has not been described in the United States, and only one similar case in the world literature could be found. The patient presented with a progressive headache and subsequent development of grand mal seizure activity. Lyme disease has been associated with cranial nerve palsies, peripheral and cranial radiculopathies, aseptic meningitis, encephalitic symptoms, chorea, and demyelinating polyneuropathy presenting like Guillain-Barre syndrome. These syndromes can occur separately or in combination. Stroke and strokelike syndromes have been attributed to Lyme disease. The literature concerning the neurologic manifestations of Lyme disease is reviewed.\n" ], "offsets": [ [ 0, 907 ] ] } ]

[ { "id": "PMID-2331105_T1", "type": "Organ", "text": [ "cerebral" ], "offsets": [ [ 54, 62 ] ], "normalized": [] }, { "id": "PMID-2331105_T2", "type": "Organ", "text": [ "cerebral" ], "offsets": [ [ 124, 132 ] ], "normalized": [] }, { "id": "PMID-2331105_T3", "type": "Organism_substance", "text": [ "cerebral spinal fluid" ], "offsets": [ [ 190, 211 ] ], "normalized": [] }, { "id": "PMID-2331105_T4", "type": "Multi-tissue_structure", "text": [ "cranial nerve" ], "offsets": [ [ 508, 521 ] ], "normalized": [] }, { "id": "PMID-2331105_T5", "type": "Organism_subdivision", "text": [ "cranial" ], "offsets": [ [ 546, 553 ] ], "normalized": [] }, { "id": "PMID-2331105_T6", "type": "Multi-tissue_structure", "text": [ "right thalamic" ], "offsets": [ [ 151, 165 ] ], "normalized": [] }, { "id": "PMID-2331105_T7", "type": "Anatomical_system", "text": [ "neurologic" ], "offsets": [ [ 852, 862 ] ], "normalized": [] } ]

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[ { "id": "PMC-2984323-caption-02__text", "type": "caption", "text": [ "Characteristics of fistula lesions\n" ], "offsets": [ [ 0, 35 ] ] } ]

[ { "id": "PMC-2984323-caption-02_T1", "type": "Pathological_formation", "text": [ "fistula lesions" ], "offsets": [ [ 19, 34 ] ], "normalized": [] } ]

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[ { "id": "PMID-8707513__text", "type": "abstract", "text": [ "The impact of multiskilling on quality of care.\nHospital finances in the USA are in a crisis. While profits earned from the healthcare industry appear to be at an all-time high, individual hospitals are going bankrupt. Hospitals are not generating sufficient income to pay their expenses given how they have traditionally operated. Hence, we are witnessing the merger and consolidation of competitors, resulting in significantly fewer hospital beds in certain geographical areas. In addition to the strategy of closing hospital beds, severe budget restrictions are impacting upon all remaining services within the hospitals.\n" ], "offsets": [ [ 0, 625 ] ] } ]

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[ { "id": "PMID-8633524__text", "type": "abstract", "text": [ "Pancreatic somatostatin-secreting gangliocytic paraganglioma with lymph node metastases. \nGangliocytic paraganglioma (GPG) with local lymph node metastasis was found in the pancreas of a 74-yr-old female who presented with diarrhea, steatorrhea, vomiting, nausea, and abdominal pain. A Whipple procedure led to a complete resolution of these symptoms and a return of an elevated stomatostatin level to normal. This is the first description of GPG in this location and the first endocrinologically active GPG.\n" ], "offsets": [ [ 0, 509 ] ] } ]

[ { "id": "PMID-8633524_T1", "type": "Organ", "text": [ "Pancreatic" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "PMID-8633524_T3", "type": "Cancer", "text": [ "gangliocytic paraganglioma" ], "offsets": [ [ 34, 60 ] ], "normalized": [] }, { "id": "PMID-8633524_T5", "type": "Cancer", "text": [ "Gangliocytic paraganglioma" ], "offsets": [ [ 90, 116 ] ], "normalized": [] }, { "id": "PMID-8633524_T6", "type": "Cancer", "text": [ "GPG" ], "offsets": [ [ 118, 121 ] ], "normalized": [] }, { "id": "PMID-8633524_T7", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 134, 144 ] ], "normalized": [] }, { "id": "PMID-8633524_T8", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 173, 181 ] ], "normalized": [] }, { "id": "PMID-8633524_T10", "type": "Organism_subdivision", "text": [ "abdominal" ], "offsets": [ [ 268, 277 ] ], "normalized": [] }, { "id": "PMID-8633524_T12", "type": "Cancer", "text": [ "GPG" ], "offsets": [ [ 443, 446 ] ], "normalized": [] }, { "id": "PMID-8633524_T13", "type": "Cancer", "text": [ "GPG" ], "offsets": [ [ 504, 507 ] ], "normalized": [] }, { "id": "PMID-8633524_T2", "type": "Cancer", "text": [ "lymph node metastases" ], "offsets": [ [ 66, 87 ] ], "normalized": [] } ]

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[ { "id": "PMID-3027568__text", "type": "abstract", "text": [ "Elevated levels of diacylglycerol and decreased phorbol ester sensitivity in ras-transformed fibroblasts. \nDiacylglycerol (DG) plays a central role in phospholipid metabolism and is an endogenous activator of protein kinase C. We have suggested that constitutive activation of this kinase is one mechanism by which oncogenes transform cells. The ras-encoded proteins are similar to regulatory G-proteins and are candidates for the unknown G-protein that modulates phosphatidylinositol (PI) turnover. Differences in polyphosphoinositide metabolism have been reported for ras-transformed cells. But because these experiments were performed on confluent cultures of established cell lines, the differences are difficult to attribute to ras transformation. Here we show that exponentially growing NIH 3T3 fibroblasts recently transformed by Ha-ras or Ki-ras possess elevated DG concentrations without significant alterations in the levels of other polyphosphoinositide metabolites. The basal phosphorylation of protein kinase C substrate of relative molecular mass (Mr) 80,000 (80K) is significantly increased in all the ras-transformed cell lines. Surprisingly, however, further phosphorylation of this protein on addition of phorbol ester was greatly reduced. Ha-ras cells also show less binding of phorbol ester than control cells, suggesting that elevation of DG causes partial down-regulation in addition to activation of protein kinase C.\n" ], "offsets": [ [ 0, 1441 ] ] } ]

[ { "id": "PMID-3027568_T4", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 93, 104 ] ], "normalized": [] }, { "id": "PMID-3027568_T9", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 335, 340 ] ], "normalized": [] }, { "id": "PMID-3027568_T17", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 586, 591 ] ], "normalized": [] }, { "id": "PMID-3027568_T18", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 675, 685 ] ], "normalized": [] }, { "id": "PMID-3027568_T20", "type": "Cell", "text": [ "NIH 3T3 fibroblasts" ], "offsets": [ [ 793, 812 ] ], "normalized": [] }, { "id": "PMID-3027568_T27", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1133, 1143 ] ], "normalized": [] }, { "id": "PMID-3027568_T30", "type": "Cell", "text": [ "Ha-ras cells" ], "offsets": [ [ 1258, 1270 ] ], "normalized": [] }, { "id": "PMID-3027568_T32", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1324, 1329 ] ], "normalized": [] }, { "id": "PMID-3027568_T1", "type": "Cell", "text": [ "cultures" ], "offsets": [ [ 651, 659 ] ], "normalized": [] } ]

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[ { "id": "PMID-16740157__text", "type": "abstract", "text": [ "Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer. \nBACKGROUND: Abnormal hemostasis in cancer patients has previously been described, however the correlation between the plasma fibrinogen level and cancer metastasis and prognosis has not been reported in a large-scale clinical study. METHODS: Preoperative plasma fibrinogen levels were retrospectively examined in 405 patients who underwent surgery for advanced gastric cancer. The association of fibrinogen levels with clinical/pathological findings and clinical outcome was evaluated. RESULTS: There was a positive correlation between plasma fibrinogen levels and the depth of invasion (p < 0.05). Hyperfibrinogenemia (>310 mg/dl) was independently associated with lymph node (Odds Ratio; 2.342, P = 0.0032) and liver (Odds Ratio; 2.933, P = 0.0147) metastasis, not with peritoneal metastasis in this series. Patients with hyperfibrinogenemia showed worse clinical outcome in T2 gastric cancer, however, there was no correlation of plasma fibrinogen level with prognosis in T3/T4 gastric cancer. CONCLUSION: Our results might support the idea that hyperfibrinogenemia can augment lymphatic and hematogeneous metastasis of advanced gastric cancer, which is major determinant of the prognosis in T2 gastric cancer. Therefore, in the situation without peritoneal involvement, hyperfibrinogenemia is a useful biomarker to predict the possible metastasis and worse clinical outcome in T2 gastric cancer.\n" ], "offsets": [ [ 0, 1534 ] ] } ]

[ { "id": "PMID-16740157_T1", "type": "Multi-tissue_structure", "text": [ "lymphatic" ], "offsets": [ [ 39, 48 ] ], "normalized": [] }, { "id": "PMID-16740157_T2", "type": "Cancer", "text": [ "T2 gastric cancer" ], "offsets": [ [ 114, 131 ] ], "normalized": [] }, { "id": "PMID-16740157_T3", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 169, 175 ] ], "normalized": [] }, { "id": "PMID-16740157_T5", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 252, 258 ] ], "normalized": [] }, { "id": "PMID-16740157_T7", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 280, 286 ] ], "normalized": [] }, { "id": "PMID-16740157_T8", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 389, 395 ] ], "normalized": [] }, { "id": "PMID-16740157_T11", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 495, 509 ] ], "normalized": [] }, { "id": "PMID-16740157_T13", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 670, 676 ] ], "normalized": [] }, { "id": "PMID-16740157_T15", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 800, 810 ] ], "normalized": [] }, { "id": "PMID-16740157_T16", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 847, 852 ] ], "normalized": [] }, { "id": "PMID-16740157_T17", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 906, 916 ] ], "normalized": [] }, { "id": "PMID-16740157_T19", "type": "Cancer", "text": [ "T2 gastric cancer" ], "offsets": [ [ 1011, 1028 ] ], "normalized": [] }, { "id": "PMID-16740157_T20", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 1067, 1073 ] ], "normalized": [] }, { "id": "PMID-16740157_T22", "type": "Cancer", "text": [ "T3/T4 gastric cancer" ], "offsets": [ [ 1109, 1129 ] ], "normalized": [] }, { "id": "PMID-16740157_T23", "type": "Cell", "text": [ "lymphatic" ], "offsets": [ [ 1215, 1224 ] ], "normalized": [] }, { "id": "PMID-16740157_T24", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 1266, 1280 ] ], "normalized": [] }, { "id": "PMID-16740157_T25", "type": "Cancer", "text": [ "T2 gastric cancer" ], "offsets": [ [ 1329, 1346 ] ], "normalized": [] }, { "id": "PMID-16740157_T26", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 1384, 1394 ] ], "normalized": [] }, { "id": "PMID-16740157_T27", "type": "Cancer", "text": [ "T2 gastric cancer" ], "offsets": [ [ 1515, 1532 ] ], "normalized": [] } ]

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[ { "id": "PMID-16893130__text", "type": "abstract", "text": [ "[Autologous bone marrow stem cell or peripheral blood endothelial progenitor cell therapy in patients with peripheral limb ischaemia]\nNo effective medical therapies have been developed sofar to enhance blood flow in the legs of patients with peripheral arterial disease (PAD). For patients with limb threatening ischaemia the only option for relief of rest pain or gangraena is amputation. There is evidence in experimental and clinical studies that adult bone marrow-derived stem cells and endothelial progenitor cells participate in the development of new blood vessels, called neoangiogenesis or neovascularization. Clinical results induced by autologous bone marrow stem cells or angiogenic growth/differentiation factors in end-stage patients with PAD are summarized. Considering the relatively few number of patients treated by angiogenic therapy, the interpretation of clinical results needs cautiousness.\n" ], "offsets": [ [ 0, 913 ] ] } ]

[ { "id": "PMID-16893130_T1", "type": "Cell", "text": [ "bone marrow stem cell" ], "offsets": [ [ 12, 33 ] ], "normalized": [] }, { "id": "PMID-16893130_T2", "type": "Cell", "text": [ "peripheral blood endothelial progenitor cell" ], "offsets": [ [ 37, 81 ] ], "normalized": [] }, { "id": "PMID-16893130_T4", "type": "Organism_subdivision", "text": [ "limb" ], "offsets": [ [ 118, 122 ] ], "normalized": [] }, { "id": "PMID-16893130_T5", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 202, 207 ] ], "normalized": [] }, { "id": "PMID-16893130_T6", "type": "Organism_subdivision", "text": [ "legs" ], "offsets": [ [ 220, 224 ] ], "normalized": [] }, { "id": "PMID-16893130_T8", "type": "Multi-tissue_structure", "text": [ "peripheral arterial" ], "offsets": [ [ 242, 261 ] ], "normalized": [] }, { "id": "PMID-16893130_T10", "type": "Organism_subdivision", "text": [ "limb" ], "offsets": [ [ 295, 299 ] ], "normalized": [] }, { "id": "PMID-16893130_T11", "type": "Cell", "text": [ "bone marrow-derived stem cells" ], "offsets": [ [ 456, 486 ] ], "normalized": [] }, { "id": "PMID-16893130_T12", "type": "Cell", "text": [ "endothelial progenitor cells" ], "offsets": [ [ 491, 519 ] ], "normalized": [] }, { "id": "PMID-16893130_T13", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 558, 571 ] ], "normalized": [] }, { "id": "PMID-16893130_T14", "type": "Cell", "text": [ "bone marrow stem cells" ], "offsets": [ [ 658, 680 ] ], "normalized": [] } ]

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[ { "id": "PMID-3763732__text", "type": "abstract", "text": [ "Unsatisfactory forehead scar following face lift.\nThe W-plasty scar revision technique has been found to be effective in the repair of the difficult and cosmetically unsatisfactory hairline scar following the ill-advised face lift technique that excises forehead skin.\n" ], "offsets": [ [ 0, 269 ] ] } ]

[ { "id": "PMID-3763732_T1", "type": "Pathological_formation", "text": [ "forehead scar" ], "offsets": [ [ 15, 28 ] ], "normalized": [] }, { "id": "PMID-3763732_T2", "type": "Organism_subdivision", "text": [ "face" ], "offsets": [ [ 39, 43 ] ], "normalized": [] }, { "id": "PMID-3763732_T3", "type": "Pathological_formation", "text": [ "scar" ], "offsets": [ [ 63, 67 ] ], "normalized": [] }, { "id": "PMID-3763732_T4", "type": "Pathological_formation", "text": [ "hairline scar" ], "offsets": [ [ 181, 194 ] ], "normalized": [] }, { "id": "PMID-3763732_T5", "type": "Organism_subdivision", "text": [ "face" ], "offsets": [ [ 221, 225 ] ], "normalized": [] }, { "id": "PMID-3763732_T6", "type": "Multi-tissue_structure", "text": [ "forehead skin" ], "offsets": [ [ 254, 267 ] ], "normalized": [] } ]

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[ { "id": "PMC-3238981-sec-11__text", "type": "sec", "text": [ "Figures\nFig. 1.\nA view of (I) with displacement ellipsoids drawn at the 30% probability level.\nFig. 2.\nStereoview of the sheet formed by C--H...pi interactions. Hydrogen atoms not involved in the motifs are not included.\n" ], "offsets": [ [ 0, 221 ] ] } ]

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[ { "id": "PMID-19050907__text", "type": "abstract", "text": [ "Evaluation of electrical stimulation for ischemic wound therapy: a feasibility study using the lapine wound model.\nChronic wounds are a major secondary complication for many people with impaired mobility. Electrical stimulation (ES) has been recommended as a adjunctive therapy, however optimal treatment paradigms have not been established. Our group seeks to determine the basic mechanisms underlying ES wound therapy, an area where understanding is currently limited. A feasibility study was carried out to develop the Ahn/Mustoe lapine wound model for systematic investigation of the effects of electrical stimulation on ischemic wound therapy. A standardized surgical procedure incorporated a hybrid stimulation system comprising an implantable mini-stimulator and surface electrodes, with creation of repeatable ischemic wounds. Twenty mature male New Zealand white rabbits (3 kg weight) were employed to evaluate the effects of two empirically selected stimulation paradigms applied continuously for 7-21 days, using each animal as its own control. Outcomes measures included transcutaneous blood gas levels, histology, total RNA content and analysis of alpha2 (I) collagen (COL-I), type IV collagen (COL-IV), alpha1 (V) collagen (COL-V), and vascular endothelial growth factor (VEGF) expression using real-time quantitative PCR. All markers for stimulated wounds showed increased activity relative to non-stimulated control wounds between 7 and 14 days following injury, with peak activity at 14 days. By 21 days post-injury, all activity had returned to near baseline level. VEGF and COL-IV levels were found to be significantly higher for pattern A (110 mus pulse width) compared to pattern B (5 mus pulse width) at 14 days, implying that pattern A may be more effective at promoting angiogenesis. All wounds were fully re-epithelialized by 10 days post-injury. Both COL-I and COL-V showed statistically significant (P less than 0.05) increased activity between day 7 and day 14 for pattern A, potentially indicating a continued effect on matrix remodeling. The early closure of all wounds implies that the rabbit ear model may not be valid for chronic wound studies.\n" ], "offsets": [ [ 0, 2180 ] ] } ]

[ { "id": "PMID-19050907_T1", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 50, 55 ] ], "normalized": [] }, { "id": "PMID-19050907_T3", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 102, 107 ] ], "normalized": [] }, { "id": "PMID-19050907_T4", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 123, 129 ] ], "normalized": [] }, { "id": "PMID-19050907_T6", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 406, 411 ] ], "normalized": [] }, { "id": "PMID-19050907_T8", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 540, 545 ] ], "normalized": [] }, { "id": "PMID-19050907_T9", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 634, 639 ] ], "normalized": [] }, { "id": "PMID-19050907_T10", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 827, 833 ] ], "normalized": [] }, { "id": "PMID-19050907_T12", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1098, 1103 ] ], "normalized": [] }, { "id": "PMID-19050907_T21", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 1364, 1370 ] ], "normalized": [] }, { "id": "PMID-19050907_T22", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 1432, 1438 ] ], "normalized": [] }, { "id": "PMID-19050907_T25", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 1812, 1818 ] ], "normalized": [] }, { "id": "PMID-19050907_T28", "type": "Cellular_component", "text": [ "matrix" ], "offsets": [ [ 2051, 2057 ] ], "normalized": [] }, { "id": "PMID-19050907_T29", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 2095, 2101 ] ], "normalized": [] }, { "id": "PMID-19050907_T31", "type": "Organ", "text": [ "ear" ], "offsets": [ [ 2126, 2129 ] ], "normalized": [] }, { "id": "PMID-19050907_T32", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 2165, 2170 ] ], "normalized": [] }, { "id": "PMID-19050907_T2", "type": "Immaterial_anatomical_entity", "text": [ "transcutaneous" ], "offsets": [ [ 1083, 1097 ] ], "normalized": [] } ]

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[ { "id": "PMID-19422607__text", "type": "abstract", "text": [ "Met amplification and tumor progression in Cdkn2a-deficient melanocytes. \nWhile many genetic alterations have been identified in melanoma, the relevant molecular events that contribute to disease progression are poorly understood. Most primary human melanomas exhibit loss of expression of the CDKN2A locus in addition to activation of the canonical mitogen-activated protein kinase signaling pathway. In this study, we used a Cdkn2a-deficient mouse melanocyte cell line to screen for secondary genetic events in melanoma tumor progression. Upon investigation, intrachromosomal gene amplification of Met, a receptor tyrosine kinase implicated in melanoma progression, was identified in Cdkn2a-deficient tumors. RNA interference targeting Met in these tumor cells resulted in a significant delay in tumor growth in vivo compared with the control cells. MET expression is rarely detected in primary human melanoma but is frequently observed in metastatic disease. This study validates a role for Met activation in melanoma tumor progression in the context of Cdkn2a deficiency.\n" ], "offsets": [ [ 0, 1076 ] ] } ]

[ { "id": "PMID-19422607_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 22, 27 ] ], "normalized": [] }, { "id": "PMID-19422607_T4", "type": "Cell", "text": [ "Cdkn2a-deficient melanocytes" ], "offsets": [ [ 43, 71 ] ], "normalized": [] }, { "id": "PMID-19422607_T5", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 129, 137 ] ], "normalized": [] }, { "id": "PMID-19422607_T7", "type": "Cancer", "text": [ "primary human melanomas" ], "offsets": [ [ 236, 259 ] ], "normalized": [] }, { "id": "PMID-19422607_T12", "type": "Cell", "text": [ "melanocyte cell line" ], "offsets": [ [ 450, 470 ] ], "normalized": [] }, { "id": "PMID-19422607_T13", "type": "Cancer", "text": [ "melanoma tumor" ], "offsets": [ [ 513, 527 ] ], "normalized": [] }, { "id": "PMID-19422607_T14", "type": "Cellular_component", "text": [ "intrachromosomal" ], "offsets": [ [ 561, 577 ] ], "normalized": [] }, { "id": "PMID-19422607_T17", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 646, 654 ] ], "normalized": [] }, { "id": "PMID-19422607_T19", "type": "Cancer", "text": [ "Cdkn2a-deficient tumors" ], "offsets": [ [ 686, 709 ] ], "normalized": [] }, { "id": "PMID-19422607_T21", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 751, 762 ] ], "normalized": [] }, { "id": "PMID-19422607_T22", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 798, 803 ] ], "normalized": [] }, { "id": "PMID-19422607_T23", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 845, 850 ] ], "normalized": [] }, { "id": "PMID-19422607_T26", "type": "Cancer", "text": [ "primary human melanoma" ], "offsets": [ [ 889, 911 ] ], "normalized": [] }, { "id": "PMID-19422607_T27", "type": "Cancer", "text": [ "metastatic disease" ], "offsets": [ [ 942, 960 ] ], "normalized": [] }, { "id": "PMID-19422607_T29", "type": "Cancer", "text": [ "melanoma tumor" ], "offsets": [ [ 1012, 1026 ] ], "normalized": [] } ]

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[ { "id": "PMID-7566959__text", "type": "abstract", "text": [ "Bicistronic retroviral vector reveals capacity of v-erbA to induce erythroleukemia and to co-operate with v-myb. \nPrevious studies have shown that v-erbA and v-myb can induce the proliferation of avian erythroid cells in culture. To study the combined effects of v-erbA and v-myb, the two oncogenes were engineered into a retrovirus bicistronic vector with an internal ribosomal entry site (IRES) or into a vector with a splice acceptor (SPL). This allowed coexpression of the two proteins and a comparison with the same vector containing either v-erbA or v-myb only. Both the erbA IRES and the erbA/myb IRES virus constructs transformed erythroid cells after infection of bone marrow or blastoderm cultures. The erbA/myb IRES virus exhibited a 5-10-fold higher transformed colony forming efficiency than the erbA IRES virus in the blastoderm assay. Surprisingly, when injected into chicken embryos in the presence of helper virus, both viruses induced an erythroleukemia in about half of the animals. In contrast, no leukemia was observed with a myb IRES virus, with spliced vectors containing v-erbA alone or v-erbA in combination with v-myb, nor with erbA IRES and erbA/myb IRES viruses produced in the absence of helper virus. The average latency of leukemia induction was shorter for the erbA/myb IRES virus (3.5 weeks) than for the erbA IRES virus (5 weeks). Nevertheless, for both viruses the leukemic blasts retained full factor dependence for growth. These results show that v-erbA is capable of inducing an erythroleukemia when expressed by a high titer bicistronic retrovirus under conditions of virus spreading and that its in vitro and in vivo transforming potential can be enhanced by v-myb.\n" ], "offsets": [ [ 0, 1706 ] ] } ]

[ { "id": "PMID-7566959_T2", "type": "Cancer", "text": [ "erythroleukemia" ], "offsets": [ [ 67, 82 ] ], "normalized": [] }, { "id": "PMID-7566959_T6", "type": "Cell", "text": [ "erythroid cells" ], "offsets": [ [ 202, 217 ] ], "normalized": [] }, { "id": "PMID-7566959_T9", "type": "Cellular_component", "text": [ "ribosomal" ], "offsets": [ [ 369, 378 ] ], "normalized": [] }, { "id": "PMID-7566959_T17", "type": "Cell", "text": [ "erythroid cells" ], "offsets": [ [ 638, 653 ] ], "normalized": [] }, { "id": "PMID-7566959_T18", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 673, 684 ] ], "normalized": [] }, { "id": "PMID-7566959_T19", "type": "Cell", "text": [ "blastoderm cultures" ], "offsets": [ [ 688, 707 ] ], "normalized": [] }, { "id": "PMID-7566959_T25", "type": "Cell", "text": [ "blastoderm" ], "offsets": [ [ 832, 842 ] ], "normalized": [] }, { "id": "PMID-7566959_T27", "type": "Developing_anatomical_structure", "text": [ "embryos" ], "offsets": [ [ 891, 898 ] ], "normalized": [] }, { "id": "PMID-7566959_T28", "type": "Cancer", "text": [ "erythroleukemia" ], "offsets": [ [ 956, 971 ] ], "normalized": [] }, { "id": "PMID-7566959_T29", "type": "Cancer", "text": [ "leukemia" ], "offsets": [ [ 1018, 1026 ] ], "normalized": [] }, { "id": "PMID-7566959_T40", "type": "Cancer", "text": [ "leukemia" ], "offsets": [ [ 1254, 1262 ] ], "normalized": [] }, { "id": "PMID-7566959_T46", "type": "Cell", "text": [ "leukemic blasts" ], "offsets": [ [ 1400, 1415 ] ], "normalized": [] }, { "id": "PMID-7566959_T48", "type": "Cancer", "text": [ "erythroleukemia" ], "offsets": [ [ 1517, 1532 ] ], "normalized": [] }, { "id": "PMID-7566959_T71", "type": "Cell", "text": [ "colony" ], "offsets": [ [ 774, 780 ] ], "normalized": [] } ]

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[ { "id": "PMID-3134031__text", "type": "abstract", "text": [ "Differential secretion of proteins and glycoproteins by livers of immature and adult rats. Effect of antimicrotubule drugs.\nThis study was initiated to re-examine reported differences in the action of antimicrotubule agents on plasma protein secretion from livers of immature versus adult rats. The aim was (1) to determine the composition and to monitor the secretion of various plasma proteins and glycoproteins from liver slices labeled in vitro with specific amino acids and sugar residues, and (2) to correlate observed differences in secretion of these proteins with structural changes in the hepatocytes of the different aged animals. For the most part, slices of liver from fetal (term), neonatal (4- to 5 days old), and adult rats (70 days old) were incubated with radioactive amino acids or various tritiated sugars specific for N-linked core oligosaccharide and/or N-linked terminal oligosaccharide chains. Our findings indicate that liver slices of fetal and neonatal rats are efficient in synthesizing plasma proteins including fully glycosylated glycoproteins. The secretion of glycosylated and nonglycosylated proteins believed to be processed through Golgi complexes was inhibited to the same extent (approximately 70-80%) by antimicrotubule agents, regardless of the age of the host animal. However, other proteins and glycoproteins secreted by livers of immature rats were found to be relatively insensitive (i.e. inhibited to only 30-40%) to the action of various antimicrotubule drugs. The glycoproteins were found to lack N-linked terminal sugars (although the glycoproteins did contain N-linked core sugars), and it is likely that the drug-insensitive proteins bypassed critical glycosylating sites in the Golgi compartment prior to release. Overall, these findings support earlier data showing that antimicrotubule drugs have a special impact on Golgi-associated events in liver cells. To what extent these findings are related to the action of microtubules remains to be seen.\n" ], "offsets": [ [ 0, 2001 ] ] } ]

[ { "id": "PMID-3134031_T1", "type": "Organ", "text": [ "livers" ], "offsets": [ [ 56, 62 ] ], "normalized": [] }, { "id": "PMID-3134031_T2", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 105, 116 ] ], "normalized": [] }, { "id": "PMID-3134031_T3", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 205, 216 ] ], "normalized": [] }, { "id": "PMID-3134031_T4", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 227, 233 ] ], "normalized": [] }, { "id": "PMID-3134031_T5", "type": "Organ", "text": [ "livers" ], "offsets": [ [ 257, 263 ] ], "normalized": [] }, { "id": "PMID-3134031_T6", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 380, 386 ] ], "normalized": [] }, { "id": "PMID-3134031_T7", "type": "Multi-tissue_structure", "text": [ "liver slices" ], "offsets": [ [ 419, 431 ] ], "normalized": [] }, { "id": "PMID-3134031_T8", "type": "Cell", "text": [ "hepatocytes" ], "offsets": [ [ 599, 610 ] ], "normalized": [] }, { "id": "PMID-3134031_T9", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "PMID-3134031_T10", "type": "Multi-tissue_structure", "text": [ "slices" ], "offsets": [ [ 661, 667 ] ], "normalized": [] }, { "id": "PMID-3134031_T11", "type": "Developing_anatomical_structure", "text": [ "fetal" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-3134031_T12", "type": "Multi-tissue_structure", "text": [ "liver slices" ], "offsets": [ [ 945, 957 ] ], "normalized": [] }, { "id": "PMID-3134031_T13", "type": "Developing_anatomical_structure", "text": [ "fetal" ], "offsets": [ [ 961, 966 ] ], "normalized": [] }, { "id": "PMID-3134031_T14", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 1015, 1021 ] ], "normalized": [] }, { "id": "PMID-3134031_T15", "type": "Cellular_component", "text": [ "Golgi complexes" ], "offsets": [ [ 1167, 1182 ] ], "normalized": [] }, { "id": "PMID-3134031_T16", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 1246, 1257 ] ], "normalized": [] }, { "id": "PMID-3134031_T17", "type": "Organ", "text": [ "livers" ], "offsets": [ [ 1362, 1368 ] ], "normalized": [] }, { "id": "PMID-3134031_T18", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 1487, 1498 ] ], "normalized": [] }, { "id": "PMID-3134031_T19", "type": "Cellular_component", "text": [ "Golgi compartment" ], "offsets": [ [ 1728, 1745 ] ], "normalized": [] }, { "id": "PMID-3134031_T20", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 1826, 1837 ] ], "normalized": [] }, { "id": "PMID-3134031_T21", "type": "Cellular_component", "text": [ "Golgi" ], "offsets": [ [ 1869, 1874 ] ], "normalized": [] }, { "id": "PMID-3134031_T22", "type": "Cell", "text": [ "liver cells" ], "offsets": [ [ 1896, 1907 ] ], "normalized": [] }, { "id": "PMID-3134031_T23", "type": "Cellular_component", "text": [ "microtubules" ], "offsets": [ [ 1968, 1980 ] ], "normalized": [] } ]

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[ { "id": "PMID-877612__text", "type": "abstract", "text": [ "Acetaminophen and hepatic dysfunction in infectious mononucleosis.\nTwo family members developed severe hepatitic dysfunction in association with infectious mononucleosis and acetaminophen administration. Since severe hepatitis is an extremely rare complication of infectious mononucleosis, we postulate that the hepatic dysfunction was induced by acetaminophen.\n" ], "offsets": [ [ 0, 362 ] ] } ]

[ { "id": "PMID-877612_T1", "type": "Organ", "text": [ "hepatic" ], "offsets": [ [ 18, 25 ] ], "normalized": [] }, { "id": "PMID-877612_T2", "type": "Organ", "text": [ "hepatic" ], "offsets": [ [ 312, 319 ] ], "normalized": [] } ]

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[ { "id": "PMID-10295626__text", "type": "abstract", "text": [ "Decontamination of medical equipment--manufacturer's problems.\n1. Small items sent via the post present a much greater hidden hazard and a higher potential for catching people unawares. 2. Large items accompanied by a Decontamination Certificate need to be treated with caution because only those surfaces which are accessible will have been cleaned; as soon as engineers start dismantling equipment, areas which are still soiled become exposed. 3. Total co-operation between hospital staff and service engineers is necessary to resolve these problems-neither can work safely without the assistance of the other. 4. Many products in use in hospitals may be up to 20 years old and clearly were not designed to facilitate decontamination and therefore present far greater risk to all concerned. 5. For the future there a clearly a responsibility with manufacturers to give more thought to the design of their equipment so that decontamination can be achieved more effectively.\n" ], "offsets": [ [ 0, 975 ] ] } ]

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[ { "id": "PMC-3158436-sec-06__text", "type": "sec", "text": [ "2.1.3\nPixel Classification\nThe feature vector of a grid, which consists of nine features, is normalized to [0, 1], and the position features are scaled by the weighting coefficient wpos. Then, taking the nine dimensional vector of each grid as the input of the classifier, the ROI and non-ROI background in ultrasonic breast tumor images can be distinguished.\nIn this section, the self-organizing feature map neural network (SOMNN) [25], proposed by Kohonen according to characteristics of the nervous system, is used for the classification of these grids to detect the ROI automatically. The SOM is trained by the unsupervised learning to produce a low-dimensional discretized representation of the input space of the training samples, and it uses a neighborhood function to preserve the topological properties of the input space, which makes it different from other artificial neural networks.\nIn this way, the SOM is able to classify the sub-blocks into n clusters only by the unsupervised learning. In our study, the output layer number n is set to 2 (ROI and non-ROI output) and the feature vector extracted from each grid is taken as the input. To map the sorted sub-blocks back to the size of the original ultrasonic images, the initial result of ROI detection can be represented by a binary image as shown in Fig. (2d), where white areas indicate the ROI candidates while black areas the non-ROIs.\n" ], "offsets": [ [ 0, 1406 ] ] } ]

[ { "id": "PMC-3158436-sec-06_T1", "type": "Cancer", "text": [ "breast tumor" ], "offsets": [ [ 318, 330 ] ], "normalized": [] }, { "id": "PMC-3158436-sec-06_T3", "type": "Anatomical_system", "text": [ "nervous system" ], "offsets": [ [ 494, 508 ] ], "normalized": [] } ]

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[ { "id": "PMID-6327760__text", "type": "abstract", "text": [ "Use of monoclonal antibodies to investigate a possible role of thyroglobulin in the pathogenesis of Graves' ophthalmopathy.\nOne possible mechanism for Graves' ophthalmopathy is that the progressive orbital inflammation is initiated by formation of thyroglobulin (Tg)-anti-Tg immune complexes at sites of Tg binding to extraocular muscle membranes. In this study monoclonal antibodies (MCAB) against human Tg were used as probes (1) to identify Tg in eye muscle membranes prepared from normal subjects and (2) to measure binding of human Tg and Tg-anti-Tg immune complexes to eye muscle membranes. Reactivity of anti-Tg MCAB with Tg, thyroid, and eye muscle membranes was determined by binding of [125I]anti-Tg monoclonal antibody, an enzyme-linked immunosorbent assay (ELISA), and the indirect immunofluorescence technique. Seven membrane fractions, prepared by differential sucrose gradient centrifugation, were used. Whereas [125I]anti-Tg MCAB bound to all thyroid membrane fractions tested, no [125I]anti-Tg bound to eye muscle membranes. Similarly, reactivity of anti-Tg MCAB with eye muscle membranes was not demonstrated in ELISA or immunofluorescence tests. Although Tg-anti-Tg immune complexes bound to thyroid membranes, such complexes did not bind to eye muscle membranes. Significant binding of [125I]human Tg to eye muscle or thyroid membranes was not demonstrated for any membrane preparation. On the other hand moderate, but significant, binding to skeletal muscle was shown. Similar results were found using an ELISA. Binding of [125I]anti-Tg-Tg complexes of [125I]Tg to thyroid and eye muscle membranes was not affected by the presence of normal human serum, phosphate ions, pH, or incubation temperature, conditions claimed by others to be critical for Tg and Tg-anti-Tg immune complex binding. Since Tg is not present in normal human eye muscle a major role of Tg, or Tg-anti-Tg immune complexes, in the pathogenesis of Graves' ophthalmopathy appears to have been excluded by these findings.\n" ], "offsets": [ [ 0, 2010 ] ] } ]

[ { "id": "PMID-6327760_T1", "type": "Immaterial_anatomical_entity", "text": [ "orbital" ], "offsets": [ [ 198, 205 ] ], "normalized": [] }, { "id": "PMID-6327760_T2", "type": "Tissue", "text": [ "extraocular muscle membranes" ], "offsets": [ [ 318, 346 ] ], "normalized": [] }, { "id": "PMID-6327760_T3", "type": "Tissue", "text": [ "eye muscle membranes" ], "offsets": [ [ 450, 470 ] ], "normalized": [] }, { "id": "PMID-6327760_T4", "type": "Tissue", "text": [ "eye muscle membranes" ], "offsets": [ [ 575, 595 ] ], "normalized": [] }, { "id": "PMID-6327760_T5", "type": "Tissue", "text": [ "eye muscle membranes" ], "offsets": [ [ 646, 666 ] ], "normalized": [] }, { "id": "PMID-6327760_T6", "type": "Organism_substance", "text": [ "membrane fractions" ], "offsets": [ [ 830, 848 ] ], "normalized": [] }, { "id": "PMID-6327760_T7", "type": "Tissue", "text": [ "eye muscle membranes" ], "offsets": [ [ 1085, 1105 ] ], "normalized": [] }, { "id": "PMID-6327760_T8", "type": "Tissue", "text": [ "thyroid membranes" ], "offsets": [ [ 1211, 1228 ] ], "normalized": [] }, { "id": "PMID-6327760_T9", "type": "Tissue", "text": [ "eye muscle membranes" ], "offsets": [ [ 1261, 1281 ] ], "normalized": [] }, { "id": "PMID-6327760_T10", "type": "Tissue", "text": [ "eye muscle" ], "offsets": [ [ 1324, 1334 ] ], "normalized": [] }, { "id": "PMID-6327760_T11", "type": "Tissue", "text": [ "thyroid membranes" ], "offsets": [ [ 1338, 1355 ] ], "normalized": [] }, { "id": "PMID-6327760_T12", "type": "Tissue", "text": [ "membrane preparation" ], "offsets": [ [ 1385, 1405 ] ], "normalized": [] }, { "id": "PMID-6327760_T14", "type": "Tissue", "text": [ "eye muscle membranes" ], "offsets": [ [ 1020, 1040 ] ], "normalized": [] }, { "id": "PMID-6327760_T15", "type": "Organ", "text": [ "skeletal muscle" ], "offsets": [ [ 1463, 1478 ] ], "normalized": [] }, { "id": "PMID-6327760_T16", "type": "Tissue", "text": [ "eye muscle membranes" ], "offsets": [ [ 1598, 1618 ] ], "normalized": [] }, { "id": "PMID-6327760_T17", "type": "Tissue", "text": [ "thyroid" ], "offsets": [ [ 1586, 1593 ] ], "normalized": [] }, { "id": "PMID-6327760_T18", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1668, 1673 ] ], "normalized": [] }, { "id": "PMID-6327760_T19", "type": "Tissue", "text": [ "eye muscle" ], "offsets": [ [ 1852, 1862 ] ], "normalized": [] }, { "id": "PMID-6327760_T20", "type": "Organism_substance", "text": [ "thyroid membrane fractions" ], "offsets": [ [ 959, 985 ] ], "normalized": [] }, { "id": "PMID-6327760_T21", "type": "Tissue", "text": [ "thyroid" ], "offsets": [ [ 633, 640 ] ], "normalized": [] } ]

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[ { "id": "PMID-12724285__text", "type": "abstract", "text": [ "Possible role of cyclooxygenase II in the acquisition of ovarian luteal function in rodents.\nThe development of the corpus luteum (CL), which involves angiogenesis, is essential for the establishment of early pregnancy. We investigated the roles of the prostaglandin synthases cyclooxygenase (COX) I and COX-II in angiogenesis and progesterone production in the newly formed CL, using inhibitors of the COX enzymes and the gonadotropin-induced pseudopregnant rat as a model. Injection of indomethacin, a nonselective COX inhibitor, on the day of ovulation and the following day decreased serum levels of progesterone, as did injection of the selective COX-II inhibitor NS-398. In contrast, a selective COX-I inhibitor, SC-560, had no effect on serum progesterone concentrations. None of the inhibitors had any effect on the weight of the superovulated ovaries or on the synthesis of progesterone by cultured luteal cells. To determine whether changes in angiogenesis are responsible for the decrease in progesterone synthesis, we measured hemoglobin and CD34 levels in luteinized ovaries following injection of COX inhibitors and measured the relative frequency of cells positive for platelet-endothelial cell adhesion molecule as a specific marker for endothelial cells. All of these parameters were reduced by the COX-II inhibitors, suggesting that changes in the vasculature are responsible for the decrease in serum progesterone. Histological examination of ovarian corrosion casts indicated that NS-398 inhibited the establishment of luteal capillary vessels following the injection of hCG. The results are consistent with the hypothesis that the activity of COX-II is associated with the formation of functional CL via its stimulation of angiogenesis.\n" ], "offsets": [ [ 0, 1758 ] ] } ]

[ { "id": "PMID-12724285_T2", "type": "Multi-tissue_structure", "text": [ "ovarian luteal" ], "offsets": [ [ 57, 71 ] ], "normalized": [] }, { "id": "PMID-12724285_T3", "type": "Multi-tissue_structure", "text": [ "corpus luteum" ], "offsets": [ [ 116, 129 ] ], "normalized": [] }, { "id": "PMID-12724285_T4", "type": "Multi-tissue_structure", "text": [ "CL" ], "offsets": [ [ 131, 133 ] ], "normalized": [] }, { "id": "PMID-12724285_T9", "type": "Multi-tissue_structure", "text": [ "CL" ], "offsets": [ [ 375, 377 ] ], "normalized": [] }, { "id": "PMID-12724285_T15", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 588, 593 ] ], "normalized": [] }, { "id": "PMID-12724285_T21", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "PMID-12724285_T23", "type": "Organ", "text": [ "superovulated ovaries" ], "offsets": [ [ 838, 859 ] ], "normalized": [] }, { "id": "PMID-12724285_T25", "type": "Cell", "text": [ "cultured luteal cells" ], "offsets": [ [ 899, 920 ] ], "normalized": [] }, { "id": "PMID-12724285_T29", "type": "Organ", "text": [ "ovaries" ], "offsets": [ [ 1080, 1087 ] ], "normalized": [] }, { "id": "PMID-12724285_T31", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1165, 1170 ] ], "normalized": [] }, { "id": "PMID-12724285_T33", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1253, 1270 ] ], "normalized": [] }, { "id": "PMID-12724285_T35", "type": "Multi-tissue_structure", "text": [ "vasculature" ], "offsets": [ [ 1366, 1377 ] ], "normalized": [] }, { "id": "PMID-12724285_T36", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1414, 1419 ] ], "normalized": [] }, { "id": "PMID-12724285_T38", "type": "Organ", "text": [ "ovarian" ], "offsets": [ [ 1462, 1469 ] ], "normalized": [] }, { "id": "PMID-12724285_T40", "type": "Multi-tissue_structure", "text": [ "luteal capillary vessels" ], "offsets": [ [ 1539, 1563 ] ], "normalized": [] }, { "id": "PMID-12724285_T43", "type": "Multi-tissue_structure", "text": [ "CL" ], "offsets": [ [ 1718, 1720 ] ], "normalized": [] } ]

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[ { "id": "PMID-6312919__text", "type": "abstract", "text": [ "The genetics of transformation by SV 40. \nExperiments using the tsA 58 allele of the SV 40-A gene have demonstrated that the SV 40 large T-antigen is strictly required both for immortalization and induction anchorage independence of cells. It has been suggested that the immortalized phenotype is mediated by an extra cellular factor. The synthesis and/or the excretion of this factor in a medium is controlled by the A gene.\n" ], "offsets": [ [ 0, 426 ] ] } ]

[ { "id": "PMID-6312919_T7", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 233, 238 ] ], "normalized": [] }, { "id": "PMID-6312919_T8", "type": "Immaterial_anatomical_entity", "text": [ "extra cellular" ], "offsets": [ [ 312, 326 ] ], "normalized": [] } ]

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[ { "id": "PMID-19605361__text", "type": "abstract", "text": [ "MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover.\nThe formation of new blood vessels from pre-existing ones requires highly coordinated restructuring of endothelial cells (EC) and the surrounding extracellular matrix. Directed EC migration is a central step in this process and depends on cellular signaling cascades that initiate and control the structural rearrangements. On the basis of earlier findings that ERK5 deficiency in mouse EC results in massive defects in vessel architecture, we focused on the impact of the MEK5/ERK5 signaling pathway on EC migration. Using a retroviral gene transfer approach, we found that constitutive activation of MEK5/ERK5 signaling strongly inhibits EC migration and results in massive morphological changes. The area covered by spread EC was dramatically enlarged, accompanied by an increase in focal contacts and altered organization of actin filaments. Consequently, cells were more rigid and show reduced motility. This phenotype was most likely based on decreased focal contact turnover caused by reduced expression of p130Cas, a key player in directed cell migration. We demonstrate for the first time that ERK5 signaling not only is involved in EC survival and stress response but also controls migration and morphology of EC.\n" ], "offsets": [ [ 0, 1309 ] ] } ]

[ { "id": "PMID-19605361_T3", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 30, 46 ] ], "normalized": [] }, { "id": "PMID-19605361_T4", "type": "Cellular_component", "text": [ "focal contact" ], "offsets": [ [ 61, 74 ] ], "normalized": [] }, { "id": "PMID-19605361_T5", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 106, 119 ] ], "normalized": [] }, { "id": "PMID-19605361_T6", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 188, 205 ] ], "normalized": [] }, { "id": "PMID-19605361_T7", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 207, 209 ] ], "normalized": [] }, { "id": "PMID-19605361_T8", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 231, 251 ] ], "normalized": [] }, { "id": "PMID-19605361_T9", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 262, 264 ] ], "normalized": [] }, { "id": "PMID-19605361_T10", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 324, 332 ] ], "normalized": [] }, { "id": "PMID-19605361_T13", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 472, 474 ] ], "normalized": [] }, { "id": "PMID-19605361_T14", "type": "Multi-tissue_structure", "text": [ "vessel architecture" ], "offsets": [ [ 505, 524 ] ], "normalized": [] }, { "id": "PMID-19605361_T17", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 589, 591 ] ], "normalized": [] }, { "id": "PMID-19605361_T20", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 725, 727 ] ], "normalized": [] }, { "id": "PMID-19605361_T21", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 811, 813 ] ], "normalized": [] }, { "id": "PMID-19605361_T22", "type": "Cellular_component", "text": [ "focal contacts" ], "offsets": [ [ 871, 885 ] ], "normalized": [] }, { "id": "PMID-19605361_T24", "type": "Cellular_component", "text": [ "filaments" ], "offsets": [ [ 920, 929 ] ], "normalized": [] }, { "id": "PMID-19605361_T25", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 945, 950 ] ], "normalized": [] }, { "id": "PMID-19605361_T26", "type": "Cellular_component", "text": [ "focal contact" ], "offsets": [ [ 1044, 1057 ] ], "normalized": [] }, { "id": "PMID-19605361_T28", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1133, 1137 ] ], "normalized": [] }, { "id": "PMID-19605361_T30", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1227, 1229 ] ], "normalized": [] }, { "id": "PMID-19605361_T31", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1305, 1307 ] ], "normalized": [] } ]

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[ { "id": "PMID-12556444__text", "type": "abstract", "text": [ "Inhibition of glucose metabolism sensitizes tumor cells to death receptor-triggered apoptosis through enhancement of death-inducing signaling complex formation and apical procaspase-8 processing. \nTumors display a high rate of glucose uptake and glycolysis. We investigated how inhibition of glucose metabolism could affect death receptor-mediated apoptosis in human tumor cells of diverse origin. We show that both substitution of glucose for pyruvate and treatment with 2-deoxyglucose enhanced apoptosis induced by tumor necrosis factor (TNF)-alpha, CD95 agonistic antibody, and TNF-related apoptosis-inducing ligand (TRAIL). Inhibition of glucose metabolism enhanced killing of myeloid leukemia U937, cervical carcinoma HeLa, and breast carcinoma MCF-7 cells upon death receptor ligation. Caspase activation, mitochondrial depolarization, and cytochrome c release were increased under these conditions. Glucose deprivation-mediated sensitization to apoptosis was prevented in MCF-7 cells overexpressing BCL-2. Interestingly, the human B-lymphoblastoid cell line SKW6.4, a prototype for mitochondria-independent death receptor-induced apoptosis, was also sensitized to anti-CD95 and TRAIL-induced apoptosis under glucose-free conditions. Changes in c-FLIP(L) and cFLIPs levels were observed in some but not all the cell lines studied following glucose deprivation. Glucose deprivation enhanced death receptor-triggered formation of death-inducing signaling complex and early processing of procaspase-8. Altogether, these results suggest that the glycolytic pathway may be an important target for therapeutic intervention to sensitize tumor cells to selectively toxic soluble death ligands or death ligand-expressing cells of the immune system by facilitating the activation of initiator caspase-8.\n" ], "offsets": [ [ 0, 1800 ] ] } ]

[ { "id": "PMID-12556444_T2", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 44, 55 ] ], "normalized": [] }, { "id": "PMID-12556444_T5", "type": "Cancer", "text": [ "Tumors" ], "offsets": [ [ 197, 203 ] ], "normalized": [] }, { "id": "PMID-12556444_T9", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 367, 378 ] ], "normalized": [] }, { "id": "PMID-12556444_T18", "type": "Cell", "text": [ "myeloid leukemia U937" ], "offsets": [ [ 681, 702 ] ], "normalized": [] }, { "id": "PMID-12556444_T19", "type": "Cell", "text": [ "cervical carcinoma HeLa" ], "offsets": [ [ 704, 727 ] ], "normalized": [] }, { "id": "PMID-12556444_T20", "type": "Cell", "text": [ "breast carcinoma MCF-7 cells" ], "offsets": [ [ 733, 761 ] ], "normalized": [] }, { "id": "PMID-12556444_T22", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 812, 825 ] ], "normalized": [] }, { "id": "PMID-12556444_T25", "type": "Cell", "text": [ "MCF-7 cells" ], "offsets": [ [ 979, 990 ] ], "normalized": [] }, { "id": "PMID-12556444_T28", "type": "Cell", "text": [ "B-lymphoblastoid cell line SKW6.4" ], "offsets": [ [ 1038, 1071 ] ], "normalized": [] }, { "id": "PMID-12556444_T29", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 1089, 1101 ] ], "normalized": [] }, { "id": "PMID-12556444_T35", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1317, 1327 ] ], "normalized": [] }, { "id": "PMID-12556444_T40", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1636, 1647 ] ], "normalized": [] }, { "id": "PMID-12556444_T41", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1718, 1723 ] ], "normalized": [] }, { "id": "PMID-12556444_T42", "type": "Anatomical_system", "text": [ "immune system" ], "offsets": [ [ 1731, 1744 ] ], "normalized": [] } ]

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[ { "id": "PMID-2777242__text", "type": "abstract", "text": [ "Anaplastic and sarcomatoid carcinoma of the small intestine: a clinicopathologic study.\nCarcinomas involving the jejunum and ileum are rare tumors. During a review of small intestinal neoplasms, six primary carcinomas of jejunum or ileum with an anaplastic and sarcomatoid histology were identified. At presentation, three of the patients had symptoms related to metastatic disease and three had symptoms referable to the local tumor. The tumors were large (greater than 4.5 cm in diameter), usually endophytic masses composed of large cells with eosinophilic cytoplasm, anaplastic nuclei, and prominent nucleoli. In many areas, the cells had a spindled configuration. Mucin positivity was identified in all six cases. Electron microscopic findings in two cases were indicative of epithelial differentiation. The tumors behaved aggressively; all five patients for whom there was clinical follow-up died of metastases within 40 months. The six anaplastic and sarcomatoid carcinomas were compared with 29 typical adenocarcinomas arising in the jejunum or ileum. Only two of the latter group had symptoms referable to distant metastases at presentation. These tumors also tended to be smaller at presentation (11 tumors were less than 4 cm in greatest dimension). Of 25 patients with typical adenocarcinomas who had acceptable follow-up, 18 (72%) died of disease and five (20%) were alive with no evidence of disease after 5 years. We conclude that anaplastic and sarcomatoid carcinoma is a rare variant of small intestinal carcinoma with an aggressive clinical course.\n" ], "offsets": [ [ 0, 1567 ] ] } ]

[ { "id": "PMID-2777242_T1", "type": "Cancer", "text": [ "Anaplastic and sarcomatoid carcinoma" ], "offsets": [ [ 0, 36 ] ], "normalized": [] }, { "id": "PMID-2777242_T2", "type": "Organ", "text": [ "small intestine" ], "offsets": [ [ 44, 59 ] ], "normalized": [] }, { "id": "PMID-2777242_T3", "type": "Cancer", "text": [ "Carcinomas" ], "offsets": [ [ 88, 98 ] ], "normalized": [] }, { "id": "PMID-2777242_T4", "type": "Multi-tissue_structure", "text": [ "jejunum" ], "offsets": [ [ 113, 120 ] ], "normalized": [] }, { "id": "PMID-2777242_T5", "type": "Multi-tissue_structure", "text": [ "ileum" ], "offsets": [ [ 125, 130 ] ], "normalized": [] }, { "id": "PMID-2777242_T6", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 140, 146 ] ], "normalized": [] }, { "id": "PMID-2777242_T7", "type": "Cancer", "text": [ "small intestinal neoplasms" ], "offsets": [ [ 167, 193 ] ], "normalized": [] }, { "id": "PMID-2777242_T8", "type": "Cancer", "text": [ "primary carcinomas" ], "offsets": [ [ 199, 217 ] ], "normalized": [] }, { "id": "PMID-2777242_T9", "type": "Multi-tissue_structure", "text": [ "jejunum" ], "offsets": [ [ 221, 228 ] ], "normalized": [] }, { "id": "PMID-2777242_T10", "type": "Multi-tissue_structure", "text": [ "ileum" ], "offsets": [ [ 232, 237 ] ], "normalized": [] }, { "id": "PMID-2777242_T11", "type": "Pathological_formation", "text": [ "sarcomatoid" ], "offsets": [ [ 261, 272 ] ], "normalized": [] }, { "id": "PMID-2777242_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 428, 433 ] ], "normalized": [] }, { "id": "PMID-2777242_T13", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 439, 445 ] ], "normalized": [] }, { "id": "PMID-2777242_T14", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 536, 541 ] ], "normalized": [] }, { "id": "PMID-2777242_T15", "type": "Organism_substance", "text": [ "eosinophilic cytoplasm" ], "offsets": [ [ 547, 569 ] ], "normalized": [] }, { "id": "PMID-2777242_T16", "type": "Cellular_component", "text": [ "nuclei" ], "offsets": [ [ 582, 588 ] ], "normalized": [] }, { "id": "PMID-2777242_T17", "type": "Cellular_component", "text": [ "nucleoli" ], "offsets": [ [ 604, 612 ] ], "normalized": [] }, { "id": "PMID-2777242_T18", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 633, 638 ] ], "normalized": [] }, { "id": "PMID-2777242_T19", "type": "Tissue", "text": [ "epithelial" ], "offsets": [ [ 781, 791 ] ], "normalized": [] }, { "id": "PMID-2777242_T20", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 813, 819 ] ], "normalized": [] }, { "id": "PMID-2777242_T21", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 906, 916 ] ], "normalized": [] }, { "id": "PMID-2777242_T22", "type": "Cancer", "text": [ "anaplastic and sarcomatoid carcinomas" ], "offsets": [ [ 943, 980 ] ], "normalized": [] }, { "id": "PMID-2777242_T23", "type": "Cancer", "text": [ "adenocarcinomas" ], "offsets": [ [ 1011, 1026 ] ], "normalized": [] }, { "id": "PMID-2777242_T24", "type": "Multi-tissue_structure", "text": [ "jejunum" ], "offsets": [ [ 1042, 1049 ] ], "normalized": [] }, { "id": "PMID-2777242_T25", "type": "Multi-tissue_structure", "text": [ "ileum" ], "offsets": [ [ 1053, 1058 ] ], "normalized": [] }, { "id": "PMID-2777242_T26", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 1123, 1133 ] ], "normalized": [] }, { "id": "PMID-2777242_T27", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1157, 1163 ] ], "normalized": [] }, { "id": "PMID-2777242_T28", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1210, 1216 ] ], "normalized": [] }, { "id": "PMID-2777242_T29", "type": "Cancer", "text": [ "adenocarcinomas" ], "offsets": [ [ 1289, 1304 ] ], "normalized": [] }, { "id": "PMID-2777242_T30", "type": "Cancer", "text": [ "anaplastic and sarcomatoid carcinoma" ], "offsets": [ [ 1446, 1482 ] ], "normalized": [] }, { "id": "PMID-2777242_T31", "type": "Cancer", "text": [ "small intestinal carcinoma" ], "offsets": [ [ 1504, 1530 ] ], "normalized": [] }, { "id": "PMID-2777242_T33", "type": "Cancer", "text": [ "masses" ], "offsets": [ [ 511, 517 ] ], "normalized": [] }, { "id": "PMID-2777242_T32", "type": "Cancer", "text": [ "metastatic disease" ], "offsets": [ [ 363, 381 ] ], "normalized": [] } ]

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[ { "id": "PMC-1852096-sec-05__text", "type": "sec", "text": [ "Case Presentation\nThe patient is an 80 year old male with diabetes mellitus and hypertension, who at age 74 (March 2001) had received a living non-related donor kidney transplant. At that time he was discharged with a double immunosuppressive therapy consisting of prednisone 20 mg/day and mophetil mycophenolate 1.5 gr/day. No calcineurin inhibitor was administered. His prednisone dose was further decreased to 5 mg/day and mophetil mycophenolate doses sustained. In November 2001 he developed cutaneous purple elevated lesions in his lower limbs that were diagnosed as KS by skin biopsy. He received 19 administrations of vincristine (1 mg) and bleomycin (15 mg) weekly that resulted in flattening and fading of the lesions. Treatment was discontinued for two months, and KS recurred, with pain and edema in both legs.\nOn July 2002, with an almost 100% involvement of his lower limbs skin with KS but no visceral involvement he received 50 mg of liposomal-adriamycin. In addition, he was then prescribed valganciclovir 450 mg BID (corrected for creatinine clearance) [7] and three additional administrations of liposomal-adriamycin, up to December 2002. He showed 40% response again with early relapse. On January 2003 the patient developed disseminated herpes zoster, which was treated with IV acyclovir.\nIn May 2003 KS progression was observed and received radiotherapy with no benefit Figure 1. In August 2003 he started oral etoposide at 50 mg QD for two weeks followed by two weeks off until May 2004 achieving a very slow 50% response. Tolerance was good and serum creatinine remain stable at around 1,4 mg/dl. Mophetil mycophenolate dose was reduced to 1 g/day and prednisone to 2.5 mg/day.\nFigure 1\nKaposi's sarcoma progressions after chemotherapy withdrawal, both lower limbs were completely covered with Kaposi's Sarcoma (June 2003).\nOn May 2004 the patient requested a second opinion and was prescribed Imatinib 200 mg qd for two weeks followed by 400 mg qd. After four weeks of Imatinib, his health deteriorated rapidly, he developed anasarca, worsening of KS, his serum creatinine increased from 1.4 mg/dl to 2.3 mg/dl and he developed grade 4 granulocytopenia (Figure 2). The patient was hospitalized with fever and was started on IV antibiotics and daily G-CSF for four days after which his WBC count normalized. Two weeks later the creatinine level returned to 1.5 mg/dl. On February 2005 he was started on 30 mg of paclitaxel IV every three weeks. After three courses with no clinical benefit he developed a skin rash that prompted discontinuation.\nFigure 2\nPatient developed anasarca with rapid progression of Kaposi's Sarcoma after four weeks of taking Imatinib (June 2004).\nOn April 2005, he was started on Sirolimus 2 mg a day, and after 8 weeks escalated to 4 mg a day. Three weeks later mophetil mycophenolate and prednisone were discontinued. Sustained and significant KS regression was evident after 16 weeks, but he developed a basal cell carcinoma and pneumonia that required hospital admission; Sirolimus dose was lowered to 2 mg a day. Thereafter his clinical course has been satisfactory with continuous and progressive regression of KS lesions (Figure 3). His serum creatinine has remained under 1.6 mg/dl and he has not developed new infectious episodes.\nFigure 3\nExtensive regression of Kaposi Sarcoma after immune-suppression was changed to Sirolimus, (14 months later), he only has hyperpigmented areas at knee levels, skin looks thin and delicate and easily bruised (July 2006).\n" ], "offsets": [ [ 0, 3518 ] ] } ]

[ { "id": "PMC-1852096-sec-05_T1", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 161, 167 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T2", "type": "Pathological_formation", "text": [ "cutaneous purple elevated lesions" ], "offsets": [ [ 496, 529 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T3", "type": "Organism_subdivision", "text": [ "lower limbs" ], "offsets": [ [ 537, 548 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T4", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 578, 582 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T5", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 719, 726 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T6", "type": "Pathological_formation", "text": [ "edema" ], "offsets": [ [ 802, 807 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T7", "type": "Organism_subdivision", "text": [ "legs" ], "offsets": [ [ 816, 820 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T8", "type": "Organ", "text": [ "lower limbs skin" ], "offsets": [ [ 875, 891 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T9", "type": "Cancer", "text": [ "KS" ], "offsets": [ [ 775, 777 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T10", "type": "Cancer", "text": [ "KS" ], "offsets": [ [ 897, 899 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T13", "type": "Cancer", "text": [ "Kaposi's sarcoma" ], "offsets": [ [ 1710, 1726 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T14", "type": "Organism_subdivision", "text": [ "lower limbs" ], "offsets": [ [ 1776, 1787 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T15", "type": "Cancer", "text": [ "Kaposi's Sarcoma" ], "offsets": [ [ 1817, 1833 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T16", "type": "Pathological_formation", "text": [ "anasarca" ], "offsets": [ [ 2049, 2057 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T17", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 2080, 2085 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T11", "type": "Cell", "text": [ "WBC" ], "offsets": [ [ 2309, 2312 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T12", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 2528, 2532 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T18", "type": "Cancer", "text": [ "Kaposi's Sarcoma" ], "offsets": [ [ 2631, 2647 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T19", "type": "Cancer", "text": [ "KS" ], "offsets": [ [ 2896, 2898 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T20", "type": "Cancer", "text": [ "basal cell carcinoma" ], "offsets": [ [ 2957, 2977 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T21", "type": "Cancer", "text": [ "KS lesions" ], "offsets": [ [ 3167, 3177 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T22", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 3194, 3199 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T23", "type": "Cancer", "text": [ "Kaposi Sarcoma" ], "offsets": [ [ 3323, 3337 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T24", "type": "Organism_subdivision", "text": [ "knee" ], "offsets": [ [ 3444, 3448 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T25", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 3457, 3461 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T26", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1568, 1573 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T27", "type": "Pathological_formation", "text": [ "anasarca" ], "offsets": [ [ 2596, 2604 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T28", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 1427, 1431 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T29", "type": "Cancer", "text": [ "KS" ], "offsets": [ [ 572, 574 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T30", "type": "Cancer", "text": [ "KS" ], "offsets": [ [ 1321, 1323 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T31", "type": "Cancer", "text": [ "KS" ], "offsets": [ [ 2072, 2074 ] ], "normalized": [] }, { "id": "PMC-1852096-sec-05_T32", "type": "Organ", "text": [ "visceral" ], "offsets": [ [ 907, 915 ] ], "normalized": [] } ]

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[ { "id": "PMID-14652292__text", "type": "abstract", "text": [ "Effects of dietary folate on ulcerative colitis-associated colorectal carcinogenesis in the interleukin 2- and beta(2)-microglobulin-deficient mice. \nFolate supplementation may reduce the risk of colorectal dysplasia and cancer in subjects with chronic ulcerative colitis (UC). The interleukin (IL) 2- and beta(2)-microglobulin (beta(2)m)-deficient (IL-2(null) x beta(2)m(null)) mice spontaneously develop colon cancer in the setting of chronic UC. This study investigated the effects of dietary folate on the development of UC-associated colon cancer in the IL-2(null) x beta(2)m(null) mice. Weaning IL-2(null) x beta(2)m(null) mice were randomized to receive 0 (deficient; n = 40), 2 (basal requirement; control; n = 46), or 8 (supplemented; n = 36) mg folate/kg diet for 32 weeks. At necropsy, all macroscopic colonic tumors were identified and histologically classified as dysplasia or adenocarcinoma. The incidence of high-grade lesions (high-grade dysplasia/carcinoma in situ and invasive adenocarcinoma) in the folate-supplemented group was 46% lower than that in the control group (35.3% versus 65.1%, P = 0.009). The incidence of high-grade lesions in the folate-deficient group was also 49% lower than that in the control group (33.3% versus 65.1%, P = 0.007). The higher mortality rate in the folate-deficient group compared with the other two groups (25% versus 6.5% and 5.6%, P < 0.02) partially accounted for the low incidence of high-grade lesions in this group. These data indicate that dietary folate supplementation at 4x the basal dietary requirement significantly suppresses UC-associated colorectal carcinogenesis in the IL-2(null) x beta(2)m(null) mice. These data also suggest that folate deficiency may inhibit colorectal carcinogenesis in chronic UC. However, the high mortality observed in the folate-deficient group precludes a definitive conclusion concerning the effect of folate deficiency on UC-associated colorectal carcinogenesis in this model.\n" ], "offsets": [ [ 0, 1978 ] ] } ]

[ { "id": "PMID-14652292_T2", "type": "Pathological_formation", "text": [ "ulcerative" ], "offsets": [ [ 29, 39 ] ], "normalized": [] }, { "id": "PMID-14652292_T3", "type": "Multi-tissue_structure", "text": [ "colorectal" ], "offsets": [ [ 59, 69 ] ], "normalized": [] }, { "id": "PMID-14652292_T8", "type": "Pathological_formation", "text": [ "colorectal dysplasia" ], "offsets": [ [ 196, 216 ] ], "normalized": [] }, { "id": "PMID-14652292_T9", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 221, 227 ] ], "normalized": [] }, { "id": "PMID-14652292_T10", "type": "Pathological_formation", "text": [ "ulcerative" ], "offsets": [ [ 253, 263 ] ], "normalized": [] }, { "id": "PMID-14652292_T18", "type": "Cancer", "text": [ "colon cancer" ], "offsets": [ [ 406, 418 ] ], "normalized": [] }, { "id": "PMID-14652292_T22", "type": "Cancer", "text": [ "colon cancer" ], "offsets": [ [ 539, 551 ] ], "normalized": [] }, { "id": "PMID-14652292_T30", "type": "Cancer", "text": [ "colonic tumors" ], "offsets": [ [ 813, 827 ] ], "normalized": [] }, { "id": "PMID-14652292_T31", "type": "Pathological_formation", "text": [ "dysplasia" ], "offsets": [ [ 877, 886 ] ], "normalized": [] }, { "id": "PMID-14652292_T32", "type": "Cancer", "text": [ "adenocarcinoma" ], "offsets": [ [ 890, 904 ] ], "normalized": [] }, { "id": "PMID-14652292_T33", "type": "Pathological_formation", "text": [ "high-grade lesions" ], "offsets": [ [ 923, 941 ] ], "normalized": [] }, { "id": "PMID-14652292_T34", "type": "Pathological_formation", "text": [ "high-grade dysplasia" ], "offsets": [ [ 943, 963 ] ], "normalized": [] }, { "id": "PMID-14652292_T35", "type": "Cancer", "text": [ "carcinoma in situ" ], "offsets": [ [ 964, 981 ] ], "normalized": [] }, { "id": "PMID-14652292_T36", "type": "Cancer", "text": [ "invasive adenocarcinoma" ], "offsets": [ [ 986, 1009 ] ], "normalized": [] }, { "id": "PMID-14652292_T38", "type": "Pathological_formation", "text": [ "high-grade lesions" ], "offsets": [ [ 1139, 1157 ] ], "normalized": [] }, { "id": "PMID-14652292_T41", "type": "Pathological_formation", "text": [ "high-grade lesions" ], "offsets": [ [ 1444, 1462 ] ], "normalized": [] }, { "id": "PMID-14652292_T44", "type": "Multi-tissue_structure", "text": [ "colorectal" ], "offsets": [ [ 1609, 1619 ] ], "normalized": [] }, { "id": "PMID-14652292_T49", "type": "Multi-tissue_structure", "text": [ "colorectal" ], "offsets": [ [ 1735, 1745 ] ], "normalized": [] }, { "id": "PMID-14652292_T54", "type": "Multi-tissue_structure", "text": [ "colorectal" ], "offsets": [ [ 1937, 1947 ] ], "normalized": [] } ]

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[ { "id": "PMID-16489021__text", "type": "abstract", "text": [ "Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. \nMembers of the Runx and MYC families have been implicated as collaborating oncogenes. The mechanism of this potent collaboration is elucidated in this study of Runx2/MYC mice. As shown previously, ectopic expression of Runx2 in the thymus leads to a preneoplastic state defined by an accumulation of cells with an immature phenotype and a low proliferative rate. We now show that c-MYC overexpression is sufficient to rescue proliferation and to release the differentiation block imposed by Runx2. Analysis of Runx2-expressing lymphomas reveals a consistently low rate of apoptosis, in contrast to lymphomas of MYC mice which are often highly apoptotic. The low apoptosis phenotype is dominant in Runx2/MYC tumors, indicating that Runx2 confers a potent survival advantage to MYC-expressing tumor cells. The role of the p53 pathway in Runx2/MYC tumors was explored on a p53 heterozygote background. Surprisingly, functional p53 was retained in vivo, even after transplantation, whereas explanted tumor cells displayed rapid allele loss in vitro. Our results show that Runx2 and MYC overcome distinct \"fail-safe\" responses and that their selection as collaborating genes is due to their ability to neutralize each other's negative growth effect. Furthermore, the Runx2/MYC combination overcomes the requirement for genetic inactivation of the p53 pathway in vivo.\n" ], "offsets": [ [ 0, 1475 ] ] } ]

[ { "id": "PMID-16489021_T3", "type": "Cancer", "text": [ "lymphoma" ], "offsets": [ [ 29, 37 ] ], "normalized": [] }, { "id": "PMID-16489021_T10", "type": "Organ", "text": [ "thymus" ], "offsets": [ [ 344, 350 ] ], "normalized": [] }, { "id": "PMID-16489021_T11", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 412, 417 ] ], "normalized": [] }, { "id": "PMID-16489021_T15", "type": "Cancer", "text": [ "lymphomas" ], "offsets": [ [ 639, 648 ] ], "normalized": [] }, { "id": "PMID-16489021_T16", "type": "Cancer", "text": [ "lymphomas" ], "offsets": [ [ 710, 719 ] ], "normalized": [] }, { "id": "PMID-16489021_T20", "type": "Cancer", "text": [ "Runx2/MYC tumors" ], "offsets": [ [ 809, 825 ] ], "normalized": [] }, { "id": "PMID-16489021_T24", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 903, 914 ] ], "normalized": [] }, { "id": "PMID-16489021_T27", "type": "Cancer", "text": [ "Runx2/MYC tumors" ], "offsets": [ [ 947, 963 ] ], "normalized": [] }, { "id": "PMID-16489021_T30", "type": "Cell", "text": [ "p53 heterozygote" ], "offsets": [ [ 982, 998 ] ], "normalized": [] }, { "id": "PMID-16489021_T32", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1108, 1119 ] ], "normalized": [] }, { "id": "PMID-16489021_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 365, 375 ] ], "normalized": [] } ]

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[ { "id": "PMID-12454816__text", "type": "abstract", "text": [ "Topoisomerase I protein expression in primary colorectal cancer and lymph node metastases. \nTopoisomerase I (topo I) is an important target for the treatment of malignant disease, especially colorectal cancer. Because there is little information on the expression of topo I in colorectal tumors, this study evaluated and characterized topo I protein expression in primary colorectal cancer and lymph node metastases and studied the association between topo I protein expression and clinicopathologic data, p53 status, and proliferating cell nuclear antigen (PCNA) status. Immunohistochemistry assay was performed for topo I protein expression in 249 primary human colorectal cancer and 42 paired lymph node metastasis samples. Topo I expression was described as the percentage of cells staining positive for topo I, along with the intensity and localization of the staining. Clinicopathologic data (sex, age, Dukes' stage, differentiation grade, survival status), p53 status, and PCNA status were statistically analyzed for association with topo I protein expression. Topo I expression in paired primary lymph node metastases were studied for concordance. Topo I protein expression was detected in 127 (51%) samples, including 24.4% with >50% positive tumor cells. The majority had nuclear (70.1%) or nuclear and cytoplasmic staining (17.3%). A higher percentage of cells expressing topo I in primary colorectal cancer was significantly associated with advanced age (P =.040). Patients with rectal cancer had greater topo I expression than those with colon tumors (P =.029). No significant correlation was found between topo I protein expression and sex, Dukes' stage, differentiation grade, survival status, p53 status, and PCNA status. Concordance in topo I staining between primary and lymph node metastases was observed in 33 of 42 cases (P =.029). This suggests that the activity of topo I inhibitors will not differ across various tumor stages, pathology, and patient gender. p53 and PCNA status do not appear to influence topo I expression, and topo I has no apparent association with the acquisition of a metastatic phenotype. Topo I expression now needs to be evaluated in patients undergoing topo I-inhibitor therapy, to better define the role of this protein as a predictive marker.\n" ], "offsets": [ [ 0, 2294 ] ] } ]

[ { "id": "PMID-12454816_T2", "type": "Cancer", "text": [ "primary colorectal cancer" ], "offsets": [ [ 38, 63 ] ], "normalized": [] }, { "id": "PMID-12454816_T6", "type": "Cancer", "text": [ "malignant disease" ], "offsets": [ [ 161, 178 ] ], "normalized": [] }, { "id": "PMID-12454816_T7", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 191, 208 ] ], "normalized": [] }, { "id": "PMID-12454816_T9", "type": "Cancer", "text": [ "colorectal tumors" ], "offsets": [ [ 277, 294 ] ], "normalized": [] }, { "id": "PMID-12454816_T11", "type": "Cancer", "text": [ "primary colorectal cancer" ], "offsets": [ [ 364, 389 ] ], "normalized": [] }, { "id": "PMID-12454816_T19", "type": "Cancer", "text": [ "primary human colorectal cancer" ], "offsets": [ [ 650, 681 ] ], "normalized": [] }, { "id": "PMID-12454816_T20", "type": "Cancer", "text": [ "lymph node metastasis samples" ], "offsets": [ [ 696, 725 ] ], "normalized": [] }, { "id": "PMID-12454816_T22", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 780, 785 ] ], "normalized": [] }, { "id": "PMID-12454816_T30", "type": "Cancer", "text": [ "samples" ], "offsets": [ [ 1208, 1215 ] ], "normalized": [] }, { "id": "PMID-12454816_T31", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1252, 1263 ] ], "normalized": [] }, { "id": "PMID-12454816_T32", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1282, 1289 ] ], "normalized": [] }, { "id": "PMID-12454816_T33", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1301, 1308 ] ], "normalized": [] }, { "id": "PMID-12454816_T34", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1313, 1324 ] ], "normalized": [] }, { "id": "PMID-12454816_T35", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1366, 1371 ] ], "normalized": [] }, { "id": "PMID-12454816_T37", "type": "Cancer", "text": [ "primary colorectal cancer" ], "offsets": [ [ 1393, 1418 ] ], "normalized": [] }, { "id": "PMID-12454816_T39", "type": "Cancer", "text": [ "rectal cancer" ], "offsets": [ [ 1491, 1504 ] ], "normalized": [] }, { "id": "PMID-12454816_T41", "type": "Cancer", "text": [ "colon tumors" ], "offsets": [ [ 1551, 1563 ] ], "normalized": [] }, { "id": "PMID-12454816_T46", "type": "Cancer", "text": [ "primary" ], "offsets": [ [ 1777, 1784 ] ], "normalized": [] }, { "id": "PMID-12454816_T49", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1937, 1942 ] ], "normalized": [] }, { "id": "PMID-12454816_T80", "type": "Cancer", "text": [ "lymph node metastases" ], "offsets": [ [ 394, 415 ] ], "normalized": [] }, { "id": "PMID-12454816_T3", "type": "Cancer", "text": [ "lymph node metastases" ], "offsets": [ [ 68, 89 ] ], "normalized": [] }, { "id": "PMID-12454816_T12", "type": "Cancer", "text": [ "lymph node metastases" ], "offsets": [ [ 1789, 1810 ] ], "normalized": [] }, { "id": "PMID-12454816_T47", "type": "Cancer", "text": [ "primary lymph node metastases" ], "offsets": [ [ 1096, 1125 ] ], "normalized": [] } ]

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[ { "id": "PMID-3365266__text", "type": "abstract", "text": [ "Glutamine and glucose as energy substrates for Ehrlich ascites tumour cells.\nEnergy metabolism of freshly harvested Ehrlich ascites tumour cells in the presence of 5 mM glucose and/or 0.5 mM glutamine was studied. The rate of oxygen utilization was not altered by the addition of 0.5 mM glutamine; 5 mM glucose induced an inhibition of respiration. In the presence of both glucose and glutamine, the Crabtree effect decreased. In these conditions, the rates of oxygen uptake, the CO2 evolution and the changes in the redox states of cytochromes indicate that glucose is preferred by Ehrlich ascites tumour cells as energy substrate. Glucose decreased the rate of glutamine utilization by 34%. On the other hand, glutaminolysis did not inhibit glycolysis.\n" ], "offsets": [ [ 0, 755 ] ] } ]

[ { "id": "PMID-3365266_T3", "type": "Cell", "text": [ "Ehrlich ascites tumour cells" ], "offsets": [ [ 47, 75 ] ], "normalized": [] }, { "id": "PMID-3365266_T4", "type": "Cell", "text": [ "Ehrlich ascites tumour cells" ], "offsets": [ [ 116, 144 ] ], "normalized": [] }, { "id": "PMID-3365266_T16", "type": "Cell", "text": [ "Ehrlich ascites tumour cells" ], "offsets": [ [ 583, 611 ] ], "normalized": [] } ]

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[ { "id": "PMID-10403689__text", "type": "abstract", "text": [ "Immunohistochemical analysis of nm23-H1 gene product in node-positive lung cancer and lymph nodes. \nThe nm23-H1 gene product has been considered as an anti-metastatic protein and the level of its expression has been reported to correlate inversely with metastatic potential in some cancers. However, the expression of nm23-H1 gene product in the metastatic sites have not been studied in detail. We examined the expression of nm23-H1 gene product in surgically resected 46 pairs of primary lung cancers and metastatic lymph nodes by immunohistochemistry. The positive staining of nm23-H1 gene product in primary cancers and metastatic lymph nodes were observed in 56.5 and 67.4%, respectively. The heterogeneity of nm23-H1 gene product expression between primary cancers and metastatic lymph nodes was observed in 41.3%. No correlations were found between the nm23-H1 gene product expression in lung cancers and the patients survival. No significant association was also observed between nm23-H1 gene product expression in lymph nodes and the patients survival. There was, furthermore, no correlation between the heterogeneity of nm23-H1 gene product expression and the patients survival. In conclusion, the level of nm23-H1 gene product expression does not significantly reveal prognostic value in node-positive lung cancers. Expression of nm23-H1 gene product in metastatic lymph nodes was also unrelated to patients survival.\n" ], "offsets": [ [ 0, 1429 ] ] } ]

[ { "id": "PMID-10403689_T2", "type": "Multi-tissue_structure", "text": [ "node" ], "offsets": [ [ 56, 60 ] ], "normalized": [] }, { "id": "PMID-10403689_T3", "type": "Cancer", "text": [ "lung cancer" ], "offsets": [ [ 70, 81 ] ], "normalized": [] }, { "id": "PMID-10403689_T4", "type": "Multi-tissue_structure", "text": [ "lymph nodes" ], "offsets": [ [ 86, 97 ] ], "normalized": [] }, { "id": "PMID-10403689_T6", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 282, 289 ] ], "normalized": [] }, { "id": "PMID-10403689_T10", "type": "Cancer", "text": [ "primary lung cancers" ], "offsets": [ [ 482, 502 ] ], "normalized": [] }, { "id": "PMID-10403689_T11", "type": "Multi-tissue_structure", "text": [ "metastatic lymph nodes" ], "offsets": [ [ 507, 529 ] ], "normalized": [] }, { "id": "PMID-10403689_T13", "type": "Cancer", "text": [ "primary cancers" ], "offsets": [ [ 604, 619 ] ], "normalized": [] }, { "id": "PMID-10403689_T14", "type": "Multi-tissue_structure", "text": [ "metastatic lymph nodes" ], "offsets": [ [ 624, 646 ] ], "normalized": [] }, { "id": "PMID-10403689_T16", "type": "Cancer", "text": [ "primary cancers" ], "offsets": [ [ 755, 770 ] ], "normalized": [] }, { "id": "PMID-10403689_T17", "type": "Multi-tissue_structure", "text": [ "metastatic lymph nodes" ], "offsets": [ [ 775, 797 ] ], "normalized": [] }, { "id": "PMID-10403689_T19", "type": "Cancer", "text": [ "lung cancers" ], "offsets": [ [ 895, 907 ] ], "normalized": [] }, { "id": "PMID-10403689_T22", "type": "Multi-tissue_structure", "text": [ "lymph nodes" ], "offsets": [ [ 1023, 1034 ] ], "normalized": [] }, { "id": "PMID-10403689_T27", "type": "Cancer", "text": [ "lung cancers" ], "offsets": [ [ 1313, 1325 ] ], "normalized": [] }, { "id": "PMID-10403689_T29", "type": "Multi-tissue_structure", "text": [ "metastatic lymph nodes" ], "offsets": [ [ 1365, 1387 ] ], "normalized": [] }, { "id": "PMID-10403689_T1", "type": "Cancer", "text": [ "metastatic sites" ], "offsets": [ [ 346, 362 ] ], "normalized": [] }, { "id": "PMID-10403689_T5", "type": "Multi-tissue_structure", "text": [ "node" ], "offsets": [ [ 1299, 1303 ] ], "normalized": [] } ]

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[ { "id": "PMID-3985123__text", "type": "abstract", "text": [ "Mast cells and tumors. The specific enhancement of tumor proliferation in vitro.\nMast cells were found to be unique among the peritoneal leukocytes by virtue of their capacity to enhance profoundly the proliferation of a variety of tumors in vitro. This phenomenon occurs at mast cell/tumor ratios which reflect the stoichiometry of host cell/tumor relationships in vivo. The growth factor was found to reside in mast cell granules and was identified as heparin by sequential purification and enzymatic degradation. This cellular interaction was tumor-specific, although isolated granules could enhance fibroblast proliferation. The findings are discussed in relation to previous morphologic studies, reports of in vitro mast-cell-mediated tumor cytotoxicity, and the role of mast cells in angiogenesis and connective tissue proliferation.\n" ], "offsets": [ [ 0, 840 ] ] } ]

[ { "id": "PMID-3985123_T1", "type": "Cell", "text": [ "Mast cells" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "PMID-3985123_T2", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 15, 21 ] ], "normalized": [] }, { "id": "PMID-3985123_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMID-3985123_T4", "type": "Cell", "text": [ "Mast cells" ], "offsets": [ [ 81, 91 ] ], "normalized": [] }, { "id": "PMID-3985123_T5", "type": "Cell", "text": [ "peritoneal leukocytes" ], "offsets": [ [ 126, 147 ] ], "normalized": [] }, { "id": "PMID-3985123_T6", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 232, 238 ] ], "normalized": [] }, { "id": "PMID-3985123_T7", "type": "Cell", "text": [ "mast cell" ], "offsets": [ [ 275, 284 ] ], "normalized": [] }, { "id": "PMID-3985123_T8", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 285, 290 ] ], "normalized": [] }, { "id": "PMID-3985123_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 338, 342 ] ], "normalized": [] }, { "id": "PMID-3985123_T10", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 343, 348 ] ], "normalized": [] }, { "id": "PMID-3985123_T11", "type": "Cell", "text": [ "mast cell" ], "offsets": [ [ 413, 422 ] ], "normalized": [] }, { "id": "PMID-3985123_T12", "type": "Organism_substance", "text": [ "granules" ], "offsets": [ [ 423, 431 ] ], "normalized": [] }, { "id": "PMID-3985123_T14", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 521, 529 ] ], "normalized": [] }, { "id": "PMID-3985123_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 546, 551 ] ], "normalized": [] }, { "id": "PMID-3985123_T16", "type": "Organism_substance", "text": [ "granules" ], "offsets": [ [ 580, 588 ] ], "normalized": [] }, { "id": "PMID-3985123_T17", "type": "Cell", "text": [ "fibroblast" ], "offsets": [ [ 603, 613 ] ], "normalized": [] }, { "id": "PMID-3985123_T18", "type": "Cell", "text": [ "mast-cell" ], "offsets": [ [ 721, 730 ] ], "normalized": [] }, { "id": "PMID-3985123_T19", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 740, 745 ] ], "normalized": [] }, { "id": "PMID-3985123_T20", "type": "Cell", "text": [ "mast cells" ], "offsets": [ [ 776, 786 ] ], "normalized": [] }, { "id": "PMID-3985123_T21", "type": "Tissue", "text": [ "connective tissue" ], "offsets": [ [ 807, 824 ] ], "normalized": [] } ]

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[ { "id": "PMC-137449-sec-08__text", "type": "sec", "text": [ "Competing interests\nNone declared.\nThis article is the third in an ongoing, educational review series on medical statistics in critical care. Previous articles have covered 'presenting and summarising data' [3] and 'samples and populations' [4]. Future topics to be covered include power calculations, comparison of means, comparison of proportions, and analysis of survival data to name but a few. If there is a medical statistics topic you would like explained contact us on editorial@ccforum.com .\n" ], "offsets": [ [ 0, 501 ] ] } ]

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