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[ { "id": "PMC-2736529-sec-09__text", "type": "sec", "text": [ "Assessment of various forms of bevavioural addictions\nA first approach for the comprehensive and standardized assessment of different forms of behavioural addictions (e.g., pathological gambling, workaholism, compulsive buying) is the German self-assessment questionnaire \"Fragebogen zur Differenzierten Anamnese exzessiver Verhaltensweisen\" (FDAV, Questionnaire on Differentiated Assessment of Excessive Behaviours) [96]. The FDAV is based on the criteria of substance-related addictions, pathological gambling and impulse control disorders of the ICD-10 [3] and the DSM-IV-TR [2].\nThe FDAV is a modified version of the \"Fragebogen zur Differenzierten Drogenanamnese\" (FDDA; Questionnaire on Differentiated Assessment of Addiction, QDAA) [97]. Its seven modules obtain \"sociodemographic information\" (e.g., age, profession, marital status), \"history of excessive behaviour\" (e.g., diagnostic criteria for addictions and impulse control disorder, individual patterns of behaviour, craving symptoms), \"critical life events\" (stress caused by traumatic events), \"legal situation\", \"medical history\", \"physical and psychological complaints\", and \"emotional state\" (triggering psychological conditions, or consequences of the addictive behaviour, respectively). Every module can be administered separately according to the suspected behavioural addiction, thereby making the FDAV an economical tool in assessing behavioural addictions. The FDAV is suitable for diagnostics, evaluation of therapy and follow-up in clinical practice and research. Currently, the FDAV is being validated in clinical and non-clinical samples.\n" ], "offsets": [ [ 0, 1618 ] ] } ]

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[ { "id": "PMID-19595081__text", "type": "abstract", "text": [ "[Quantitative analysis of regional cerebral blood flow in elderly with white matter lesions].\nOBJECTIVE:\nTo observe whether the severity of white matter lesions (WML) is related to ischemia in elderly.\nMETHODS:\nWML were divided into 2 categories (centrum semiovale and periventricular regions) and four grades (grade 0, grade 1, grade 2 and grade 3) according to the severity of WML showing on the FLAIR sequence of MRI using modified Fazekas scale. The values of regional cerebral blood flow (rCBF) within WML and other brain regions were measured using Xenon contrast CT.\nRESULTS:\nMean rCBF (ml x 100 g(-1) x min(-1)) within lesions around periventricular areas, in right and left centrum semiovale were 20.8 +/- 2.8, 22.3 +/- 1.9 and 22.2 +/- 2.1 in grade 0; 20.3 +/- 2.5, 21.3 +/- 1.0 and 21.0 +/- 1.8 in grade1; 16.3 +/- 2.0, 15.6 +/- 1.7 and 15.9 +/- 0.9 in grade 2; 14.1 +/- 2.6, 14.5 +/- 2.2 and 14.2 +/- 1.9 in grade 3 respectively. The severity of WML is associated significantly with reduction of rCBF within lesions both in centrum semiovale and periventricular regions (all P < 0.05). There was no significant difference in rCBF values between grade 0 and 1, but significant differences existed between grade 0 and grades 2 and 3, between grade 1 and grades 2 and 3 (all P < 0.05). Statistical significance also existed between the severity of white matter lesions and rCBF in bilateral temporal lobes and lentiform nucleases (P < 0.05).\nCONCLUSIONS:\nThe severity of WML both in centrum semiovale and periventricular regions is associated significantly with reduction of rCBF within lesions.\n" ], "offsets": [ [ 0, 1605 ] ] } ]

[ { "id": "PMID-19595081_T1", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 44, 49 ] ], "normalized": [] }, { "id": "PMID-19595081_T2", "type": "Pathological_formation", "text": [ "white matter lesions" ], "offsets": [ [ 140, 160 ] ], "normalized": [] }, { "id": "PMID-19595081_T3", "type": "Pathological_formation", "text": [ "WML" ], "offsets": [ [ 162, 165 ] ], "normalized": [] }, { "id": "PMID-19595081_T4", "type": "Pathological_formation", "text": [ "WML" ], "offsets": [ [ 211, 214 ] ], "normalized": [] }, { "id": "PMID-19595081_T5", "type": "Multi-tissue_structure", "text": [ "centrum semiovale" ], "offsets": [ [ 247, 264 ] ], "normalized": [] }, { "id": "PMID-19595081_T6", "type": "Multi-tissue_structure", "text": [ "periventricular regions" ], "offsets": [ [ 269, 292 ] ], "normalized": [] }, { "id": "PMID-19595081_T7", "type": "Pathological_formation", "text": [ "WML" ], "offsets": [ [ 379, 382 ] ], "normalized": [] }, { "id": "PMID-19595081_T8", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 482, 487 ] ], "normalized": [] }, { "id": "PMID-19595081_T9", "type": "Pathological_formation", "text": [ "WML" ], "offsets": [ [ 507, 510 ] ], "normalized": [] }, { "id": "PMID-19595081_T10", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 521, 526 ] ], "normalized": [] }, { "id": "PMID-19595081_T11", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 627, 634 ] ], "normalized": [] }, { "id": "PMID-19595081_T12", "type": "Multi-tissue_structure", "text": [ "periventricular areas" ], "offsets": [ [ 642, 663 ] ], "normalized": [] }, { "id": "PMID-19595081_T13", "type": "Multi-tissue_structure", "text": [ "left centrum semiovale" ], "offsets": [ [ 678, 700 ] ], "normalized": [] }, { "id": "PMID-19595081_T14", "type": "Pathological_formation", "text": [ "WML" ], "offsets": [ [ 958, 961 ] ], "normalized": [] }, { "id": "PMID-19595081_T15", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 1020, 1027 ] ], "normalized": [] }, { "id": "PMID-19595081_T16", "type": "Multi-tissue_structure", "text": [ "centrum semiovale" ], "offsets": [ [ 1036, 1053 ] ], "normalized": [] }, { "id": "PMID-19595081_T17", "type": "Multi-tissue_structure", "text": [ "periventricular regions" ], "offsets": [ [ 1058, 1081 ] ], "normalized": [] }, { "id": "PMID-19595081_T18", "type": "Pathological_formation", "text": [ "white matter lesions" ], "offsets": [ [ 1357, 1377 ] ], "normalized": [] }, { "id": "PMID-19595081_T19", "type": "Pathological_formation", "text": [ "WML" ], "offsets": [ [ 1480, 1483 ] ], "normalized": [] }, { "id": "PMID-19595081_T20", "type": "Multi-tissue_structure", "text": [ "centrum semiovale" ], "offsets": [ [ 1492, 1509 ] ], "normalized": [] }, { "id": "PMID-19595081_T21", "type": "Multi-tissue_structure", "text": [ "periventricular regions" ], "offsets": [ [ 1514, 1537 ] ], "normalized": [] }, { "id": "PMID-19595081_T22", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 1596, 1603 ] ], "normalized": [] }, { "id": "PMID-19595081_T23", "type": "Pathological_formation", "text": [ "white matter lesions" ], "offsets": [ [ 71, 91 ] ], "normalized": [] }, { "id": "PMID-19595081_T24", "type": "Organ", "text": [ "cerebral" ], "offsets": [ [ 35, 43 ] ], "normalized": [] }, { "id": "PMID-19595081_T25", "type": "Organ", "text": [ "cerebral" ], "offsets": [ [ 473, 481 ] ], "normalized": [] }, { "id": "PMID-19595081_T26", "type": "Multi-tissue_structure", "text": [ "temporal lobes" ], "offsets": [ [ 1400, 1414 ] ], "normalized": [] }, { "id": "PMID-19595081_T27", "type": "Multi-tissue_structure", "text": [ "right" ], "offsets": [ [ 668, 673 ] ], "normalized": [] } ]

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[ { "id": "PMID-198130__text", "type": "abstract", "text": [ "Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells.\nMeasurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle.\n" ], "offsets": [ [ 0, 1511 ] ] } ]

[ { "id": "PMID-198130_T2", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 109, 120 ] ], "normalized": [] }, { "id": "PMID-198130_T7", "type": "Cell", "text": [ "ascites tumor cells" ], "offsets": [ [ 322, 341 ] ], "normalized": [] }, { "id": "PMID-198130_T8", "type": "Cell", "text": [ "Ehrlich ascites tumor cells" ], "offsets": [ [ 358, 385 ] ], "normalized": [] }, { "id": "PMID-198130_T9", "type": "Cell", "text": [ "Krebs II carcinoma" ], "offsets": [ [ 387, 405 ] ], "normalized": [] }, { "id": "PMID-198130_T10", "type": "Cell", "text": [ "AS-30D carcinoma" ], "offsets": [ [ 407, 423 ] ], "normalized": [] }, { "id": "PMID-198130_T11", "type": "Cell", "text": [ "L1210 cells" ], "offsets": [ [ 429, 440 ] ], "normalized": [] }, { "id": "PMID-198130_T15", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 651, 656 ] ], "normalized": [] }, { "id": "PMID-198130_T18", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 869, 879 ] ], "normalized": [] }, { "id": "PMID-198130_T23", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1027, 1033 ] ], "normalized": [] }, { "id": "PMID-198130_T25", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1088, 1101 ] ], "normalized": [] }, { "id": "PMID-198130_T28", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1244, 1250 ] ], "normalized": [] }, { "id": "PMID-198130_T32", "type": "Organism_substance", "text": [ "cytosolic" ], "offsets": [ [ 1462, 1471 ] ], "normalized": [] }, { "id": "PMID-198130_T53", "type": "Organism_substance", "text": [ "cytosolic" ], "offsets": [ [ 1052, 1061 ] ], "normalized": [] }, { "id": "PMID-198130_T1", "type": "Cell", "text": [ "strains" ], "offsets": [ [ 347, 354 ] ], "normalized": [] } ]

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[ { "id": "PMC-1868914-caption-03__text", "type": "caption", "text": [ "Hypothetical distribution patterns of the meadow brown Maniola jurtina in Europe during the last glacial maximum (dark hatched areas). Postglacial expansions are indicated by solid arrows. The postulated actual hybrid zone is shown by the hatched area. Question marks indicate lack of information concerning ancient distribution patterns in the South and present distribution of hybrid populations in the North. Redrawn from Schmitt et. al. [36]; based on Thomson [37] and Schmitt et al. [36].\n" ], "offsets": [ [ 0, 494 ] ] } ]

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[ { "id": "PMID-1271119__text", "type": "abstract", "text": [ "Prenatal aspects of ascorbic acid metabolism in the albino rat.\nTransfer of ascorbic acid and/or its derivatives from maternal blood into the fetus was studied during the last week of gestation in the rat. Rats were injected intravenously with [1-14C]-ascorbic acid and the rate of transfer estimated by the concentration and content of label present in placentas and fetuses. At all times studied the concentration of label in the placenta was greater than in the fetus. The highest capacity of the placenta to concentrate label was found on day 15 decreasing to a low at day 19 and again increasing up to day 21. While in the fetuses, the concentration of label per gram of tissue remained remarkably constant throughout the study. The quantity of labeled compounds transferred into the fetus per gram of placental tissue increased between day 15 and day 21 of gestation.\n" ], "offsets": [ [ 0, 874 ] ] } ]

[ { "id": "PMID-1271119_T1", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 127, 132 ] ], "normalized": [] }, { "id": "PMID-1271119_T2", "type": "Developing_anatomical_structure", "text": [ "fetus" ], "offsets": [ [ 142, 147 ] ], "normalized": [] }, { "id": "PMID-1271119_T4", "type": "Organ", "text": [ "placentas" ], "offsets": [ [ 354, 363 ] ], "normalized": [] }, { "id": "PMID-1271119_T5", "type": "Developing_anatomical_structure", "text": [ "fetuses" ], "offsets": [ [ 368, 375 ] ], "normalized": [] }, { "id": "PMID-1271119_T3", "type": "Immaterial_anatomical_entity", "text": [ "intravenously" ], "offsets": [ [ 225, 238 ] ], "normalized": [] }, { "id": "PMID-1271119_T6", "type": "Organ", "text": [ "placenta" ], "offsets": [ [ 432, 440 ] ], "normalized": [] }, { "id": "PMID-1271119_T7", "type": "Developing_anatomical_structure", "text": [ "fetus" ], "offsets": [ [ 465, 470 ] ], "normalized": [] }, { "id": "PMID-1271119_T8", "type": "Organ", "text": [ "placenta" ], "offsets": [ [ 500, 508 ] ], "normalized": [] }, { "id": "PMID-1271119_T9", "type": "Developing_anatomical_structure", "text": [ "fetuses" ], "offsets": [ [ 628, 635 ] ], "normalized": [] }, { "id": "PMID-1271119_T10", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 676, 682 ] ], "normalized": [] }, { "id": "PMID-1271119_T11", "type": "Tissue", "text": [ "placental tissue" ], "offsets": [ [ 807, 823 ] ], "normalized": [] }, { "id": "PMID-1271119_T12", "type": "Developing_anatomical_structure", "text": [ "fetus" ], "offsets": [ [ 789, 794 ] ], "normalized": [] } ]

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[ { "id": "PMID-18245558__text", "type": "abstract", "text": [ "Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin.\nPURPOSE: Angiogenesis inhibitors have strong therapeutic potential as antitumor agents in suppressing tumor growth and metastatic progression. Vasostatin, the N-terminal domain of calreticulin, is a potent angiogenesis inhibitor. In this study, we determined the effectiveness of vasostatin delivered by recombinant pseudotype adeno-associated virus 2/5 (rAAV2/5-VAS) as a gene therapy approach for lung cancer treatment. EXPERIMENTAL DESIGN: We used rAAV2/5 to deliver vasostatin intratumorally or systemically in different mouse lung tumor models--subcutaneous, orthotopic xenograft, and spontaneous metastasis lung tumor models. The therapeutic efficacy of rAAV2/5-VAS was determined by monitoring tumor volume, survival rate, and degree of neovascularization after treatment in these models. RESULTS: Mice bearing subcutaneous tumor of rAAV2/5-VAS pretreated Lewis lung carcinoma cells showed >50% reduction in primary tumor volume and reduced spontaneous pulmonary metastases. The tumor-suppressive action of rAAV2/5-VAS in subcutaneous human lung tumor A549 xenograft correlated with a reduced number of capillary vessels in tumors. In the orthotopic xenograft model, rAAV2/5-VAS suppressed metastasis of A549 tumors to mediastinal lymph nodes and contralateral lung. Furthermore, treatment of immunocompetent mice in the spontaneous lung metastases model with rAAV2/5-VAS after primary tumor excision prolonged their median survival from 21 to 51.5 days. CONCLUSION: Our results show the effectiveness of rAAV2/5-VAS as an angiogenesis inhibitor in suppressing tumor growth during different stages of tumor progression, validating the application of rAAV2/5-VAS gene therapy in treatment against lung cancer.\n" ], "offsets": [ [ 0, 1833 ] ] } ]

[ { "id": "PMID-18245558_T1", "type": "Cancer", "text": [ "lung tumor" ], "offsets": [ [ 15, 25 ] ], "normalized": [] }, { "id": "PMID-18245558_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 191, 196 ] ], "normalized": [] }, { "id": "PMID-18245558_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 219, 224 ] ], "normalized": [] }, { "id": "PMID-18245558_T14", "type": "Cancer", "text": [ "lung cancer" ], "offsets": [ [ 516, 527 ] ], "normalized": [] }, { "id": "PMID-18245558_T18", "type": "Cancer", "text": [ "intratumorally" ], "offsets": [ [ 598, 612 ] ], "normalized": [] }, { "id": "PMID-18245558_T20", "type": "Cancer", "text": [ "lung tumor" ], "offsets": [ [ 648, 658 ] ], "normalized": [] }, { "id": "PMID-18245558_T21", "type": "Cancer", "text": [ "subcutaneous, orthotopic xenograft" ], "offsets": [ [ 667, 701 ] ], "normalized": [] }, { "id": "PMID-18245558_T22", "type": "Cancer", "text": [ "lung tumor" ], "offsets": [ [ 730, 740 ] ], "normalized": [] }, { "id": "PMID-18245558_T25", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 818, 823 ] ], "normalized": [] }, { "id": "PMID-18245558_T27", "type": "Cancer", "text": [ "subcutaneous tumor" ], "offsets": [ [ 935, 953 ] ], "normalized": [] }, { "id": "PMID-18245558_T30", "type": "Cell", "text": [ "Lewis lung carcinoma cells" ], "offsets": [ [ 980, 1006 ] ], "normalized": [] }, { "id": "PMID-18245558_T31", "type": "Cancer", "text": [ "primary tumor" ], "offsets": [ [ 1032, 1045 ] ], "normalized": [] }, { "id": "PMID-18245558_T32", "type": "Cancer", "text": [ "pulmonary metastases" ], "offsets": [ [ 1077, 1097 ] ], "normalized": [] }, { "id": "PMID-18245558_T33", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1103, 1108 ] ], "normalized": [] }, { "id": "PMID-18245558_T37", "type": "Cancer", "text": [ "subcutaneous human lung tumor A549 xenograft" ], "offsets": [ [ 1146, 1190 ] ], "normalized": [] }, { "id": "PMID-18245558_T38", "type": "Tissue", "text": [ "capillary vessels" ], "offsets": [ [ 1227, 1244 ] ], "normalized": [] }, { "id": "PMID-18245558_T39", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1248, 1254 ] ], "normalized": [] }, { "id": "PMID-18245558_T40", "type": "Cancer", "text": [ "xenograft" ], "offsets": [ [ 1274, 1283 ] ], "normalized": [] }, { "id": "PMID-18245558_T43", "type": "Cancer", "text": [ "A549 tumors" ], "offsets": [ [ 1328, 1339 ] ], "normalized": [] }, { "id": "PMID-18245558_T44", "type": "Multi-tissue_structure", "text": [ "lymph nodes" ], "offsets": [ [ 1355, 1366 ] ], "normalized": [] }, { "id": "PMID-18245558_T45", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 1385, 1389 ] ], "normalized": [] }, { "id": "PMID-18245558_T47", "type": "Cancer", "text": [ "lung metastases" ], "offsets": [ [ 1457, 1472 ] ], "normalized": [] }, { "id": "PMID-18245558_T50", "type": "Cancer", "text": [ "primary tumor" ], "offsets": [ [ 1502, 1515 ] ], "normalized": [] }, { "id": "PMID-18245558_T53", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1685, 1690 ] ], "normalized": [] }, { "id": "PMID-18245558_T54", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1725, 1730 ] ], "normalized": [] }, { "id": "PMID-18245558_T57", "type": "Cancer", "text": [ "lung cancer" ], "offsets": [ [ 1820, 1831 ] ], "normalized": [] } ]

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[ { "id": "PMID-9096095__text", "type": "abstract", "text": [ "Non-invasive grading of primary brain tumours: results of a comparative study between SPET with 123I-alpha-methyl tyrosine and PET with 18F-deoxyglucose.\nUse of iodine-123-alpha-methyl tyrosine (123I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of 123I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (18F-FDG); 123I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3. 18F-FDG and 123I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71, P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for 18F-FDG uptake and 1.8 for 123I-IMT uptake, the accuracy values of 18F-FDG PET and 123I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of 123I-IMT SPET on the therapeutic management of patients with brain tumours.\n" ], "offsets": [ [ 0, 1923 ] ] } ]

[ { "id": "PMID-9096095_T1", "type": "Cancer", "text": [ "primary brain tumours" ], "offsets": [ [ 24, 45 ] ], "normalized": [] }, { "id": "PMID-9096095_T7", "type": "Cancer", "text": [ "gliomas" ], "offsets": [ [ 262, 269 ] ], "normalized": [] }, { "id": "PMID-9096095_T10", "type": "Cancer", "text": [ "brain tumours" ], "offsets": [ [ 434, 447 ] ], "normalized": [] }, { "id": "PMID-9096095_T12", "type": "Cancer", "text": [ "primary brain tumours" ], "offsets": [ [ 524, 545 ] ], "normalized": [] }, { "id": "PMID-9096095_T13", "type": "Cancer", "text": [ "high-grade gliomas" ], "offsets": [ [ 554, 572 ] ], "normalized": [] }, { "id": "PMID-9096095_T14", "type": "Cancer", "text": [ "low-grade brain neoplasms" ], "offsets": [ [ 583, 608 ] ], "normalized": [] }, { "id": "PMID-9096095_T21", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 946, 952 ] ], "normalized": [] }, { "id": "PMID-9096095_T24", "type": "Cancer", "text": [ "brain tumours" ], "offsets": [ [ 1041, 1054 ] ], "normalized": [] }, { "id": "PMID-9096095_T25", "type": "Cancer", "text": [ "high-grade" ], "offsets": [ [ 1143, 1153 ] ], "normalized": [] }, { "id": "PMID-9096095_T26", "type": "Cancer", "text": [ "low-grade tumours" ], "offsets": [ [ 1158, 1175 ] ], "normalized": [] }, { "id": "PMID-9096095_T31", "type": "Cancer", "text": [ "high-grade" ], "offsets": [ [ 1312, 1322 ] ], "normalized": [] }, { "id": "PMID-9096095_T32", "type": "Cancer", "text": [ "low-grade tumours" ], "offsets": [ [ 1327, 1344 ] ], "normalized": [] }, { "id": "PMID-9096095_T35", "type": "Cancer", "text": [ "primary brain tumours" ], "offsets": [ [ 1738, 1759 ] ], "normalized": [] }, { "id": "PMID-9096095_T38", "type": "Cancer", "text": [ "brain tumours" ], "offsets": [ [ 1908, 1921 ] ], "normalized": [] } ]

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[ { "id": "PMC-2330176-sec-05__text", "type": "sec", "text": [ "3.\nResults and discussion\nAbsC was overexpressed and purified with a final yield of approximately 10 mg of protein from 1 l culture and was judged to be greater than 98% pure by SDS-PAGE analysis. The DLS analysis after gel filtration showed a monomodal distribution, with a polydispersity value of 18.9% and a molecular-size estimate of 39.6 kDa. This was comparable to the value of 36 kDa estimated from the calibrated gel-filtration column, strongly suggesting that AbsC exists as a homodimer in solution (calculated molecular weight of 41.0 kDa for the His-tagged dimer), in agreement with other characterized MarR homologues.\nPreliminary crystals grew within 24 h at 293 K from several different crystallization conditions. Improved crystals were subsequently obtained with a precipitant solution consisting of 1 M ammonium sulfate, 0.55 M potassium sodium tartrate in 100 mM citrate pH 5.6, giving crystals with approximate dimensions of 700 x 50 x 50 microm (Fig. 1 >).\nNative X-ray data were collected from a single AbsC crystal: a total of 214 x 0.4degrees oscillation images were recorded in a continuous sweep to a maximum resolution of 2.25 A. Indexing was consistent with a primitive orthorhombic lattice, with unit-cell parameters a = 43.53, b = 121.30, c = 143.75 A. After processing the data in space group P222, pseudo-precession plots were analysed using HKLVIEW (Collaborative Computational Project, Number 4, 1994 >) and the systematic absences were indicative of space group P212121. Reprocessing in this space group yielded a data set that was 95.6% complete to 2.25 A resolution. Data-collection statistics are summarized in Table 1 >.\nEstimation of the content of the asymmetric unit (ASU) suggested that three or four His-tagged AbsC subunits were most likely, giving solvent contents of 60.3% or 47.0% and crystal-packing parameters (V M) of 3.09 or 2.32 A3 Da-1, respectively. Given that both DLS and gel filtration suggest that AbsC is dimeric and that MarR homologues exist as homodimers (Wilkinson & Grove, 2006 >), an even number of subunits per ASU, i.e. four, would seem to be the most probable (Matthews, 1968 >).\nA Patterson function calculated on data in the resolution range 10.0-3.0 A revealed a significant peak (at 24% of the origin peak) with a vector of u = 0.0, v = 0.5, w = 0.014, indicating that one or more molecules in the ASU were similarly orientated. A self-rotation function calculated on data in the resolution range 10.0-5.0 A using MOLREP (Vagin & Teplyakov, 2000 >) did not show any clear noncrystallographic symmetry (NCS), perhaps suggesting that if NCS axes were present they were parallel (or almost parallel) to crystallographic axes.\nFold prediction, based on the amino-acid sequence of AbsC, was performed using the FUGUE server (http://www-cryst.bioc.cam.ac.uk/~fugue/prfsearch.html; Shi et al., 2001 >). This found eight 'certain' hits, with the top three being MarR (PDB code 1jgs; Z score 21.4; 18% sequence identity), SlyA (PDB code 1lj9; Z score 18.4; 16% sequence identity) and YusO (PDB code 1s3j; Z score 15.7; 16% sequence identity). All three hits were used as search models for molecular replacement in the program AMoRe (Navaza, 1994 >), but none yielded plausible solutions against the 2.25 A resolution native data set, although this is not too surprising given their very low sequence identities. Thus, we will need to solve the AbsC structure by isomorphous replacement methods. To this end, we are preparing selenomethionine-labelled protein; there are a total of seven methionine residues present in the 158-amino-acid sequence of AbsC.\n" ], "offsets": [ [ 0, 3618 ] ] } ]

[ { "id": "PMC-2330176-sec-05_T1", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1229, 1233 ] ], "normalized": [] } ]

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[ { "id": "PMC-1420288-sec-02__text", "type": "sec", "text": [ "Results\nThe set of E. coli expression vectors, encode for either a hexa-histidine tag or the three most commonly used solubility tags (GST, MBP, NusA) and all with an N-terminal hexa-histidine sequence. The result is two-fold: the His-tag facilitates purification by immobilised metal affinity chromatography, whilst the fusion domains act primarily as solubility aids during expression, in addition to providing an optional purification step. We have also incorporated a TEV recognition sequence following the solubility tag domain, which allows for highly specific cleavage (using TEV protease) of the fusion protein to yield native protein. These vectors are also designed for ligation-independent cloning and they possess a high-level expressing T7 promoter, which is suitable for auto-induction. To validate our vector system, we have cloned four different genes and also one gene into all four vectors and used small-scale expression and purification techniques. We demonstrate that the vectors are capable of high levels of expression and that efficient screening of new proteins can be readily achieved at the laboratory level.\n" ], "offsets": [ [ 0, 1136 ] ] } ]

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[ { "id": "PMID-20858762__text", "type": "abstract", "text": [ "Skin deep and deeper: multiple pathways in basal cell carcinogenesis. \nThis perspective places the report by Villani et al. that appears in this issue of the journal (beginning on page 1222) in the context of recent work showing an intersection between two important developmental pathways implicated in oncogenesis: the hedgehog and insulin-like growth factor (IGF) pathways. Villani et al. define a key role for the IGF regulatory protein Igfbp2 in a genetic model of basal cell carcinogenesis driven by targeted constitutive activation of hedgehog signaling. Placed in the framework of other recently published work, the observations of Villani et al. both raise questions about the cell of origin for basal cell cancers and define additional putative therapeutic and preventive targets for this disease.\n" ], "offsets": [ [ 0, 808 ] ] } ]

[ { "id": "PMID-20858762_T1", "type": "Organ", "text": [ "Skin" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-20858762_T2", "type": "Cell", "text": [ "basal cell" ], "offsets": [ [ 43, 53 ] ], "normalized": [] }, { "id": "PMID-20858762_T8", "type": "Cell", "text": [ "basal cell" ], "offsets": [ [ 470, 480 ] ], "normalized": [] }, { "id": "PMID-20858762_T10", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 686, 690 ] ], "normalized": [] }, { "id": "PMID-20858762_T11", "type": "Cancer", "text": [ "basal cell cancers" ], "offsets": [ [ 705, 723 ] ], "normalized": [] } ]

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[ { "id": "PMID-12686753__text", "type": "abstract", "text": [ "Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299. \nTo investigate whether bee venom (BV) induces apoptosis, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, terminal deoxynucleotidyl transferase- mediated dUTP nick end-labeling assay, 4,6-diamidino-2-phenylindole staining, flow cytometric analysis, and DNA fragmentation assay were performed on NCI-H1299 lung cancer cells treated with BV. Through morphological and biochemical analyses, it was demonstrated that NCI-H1299 cells treated with BV exhibit several features of apoptosis. In addition, reverse transcription-polymerase chain reaction and prostaglandin E(2) (PGE(2)) immunoassay were performed to verify whether BV possesses an inhibitory effect on the expression of cyclooxygenase (COX) and PGE(2 )synthesis. Expression of COX-2 mRNA and synthesis of PGE(2) were inhibited by BV. These results suggest the possibility that BV may exert an anti-tumor effect on human lung cancer.\n" ], "offsets": [ [ 0, 1033 ] ] } ]

[ { "id": "PMID-12686753_T2", "type": "Organism_substance", "text": [ "venom" ], "offsets": [ [ 4, 9 ] ], "normalized": [] }, { "id": "PMID-12686753_T5", "type": "Cell", "text": [ "lung cancer cell line NCI-H1299" ], "offsets": [ [ 86, 117 ] ], "normalized": [] }, { "id": "PMID-12686753_T7", "type": "Organism_substance", "text": [ "venom" ], "offsets": [ [ 147, 152 ] ], "normalized": [] }, { "id": "PMID-12686753_T8", "type": "Organism_substance", "text": [ "BV" ], "offsets": [ [ 154, 156 ] ], "normalized": [] }, { "id": "PMID-12686753_T14", "type": "Cell", "text": [ "NCI-H1299 lung cancer cells" ], "offsets": [ [ 438, 465 ] ], "normalized": [] }, { "id": "PMID-12686753_T15", "type": "Organism_substance", "text": [ "BV" ], "offsets": [ [ 479, 481 ] ], "normalized": [] }, { "id": "PMID-12686753_T16", "type": "Cell", "text": [ "NCI-H1299 cells" ], "offsets": [ [ 556, 571 ] ], "normalized": [] }, { "id": "PMID-12686753_T17", "type": "Organism_substance", "text": [ "BV" ], "offsets": [ [ 585, 587 ] ], "normalized": [] }, { "id": "PMID-12686753_T20", "type": "Organism_substance", "text": [ "BV" ], "offsets": [ [ 765, 767 ] ], "normalized": [] }, { "id": "PMID-12686753_T26", "type": "Organism_substance", "text": [ "BV" ], "offsets": [ [ 930, 932 ] ], "normalized": [] }, { "id": "PMID-12686753_T27", "type": "Organism_substance", "text": [ "BV" ], "offsets": [ [ 977, 979 ] ], "normalized": [] }, { "id": "PMID-12686753_T28", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 998, 1003 ] ], "normalized": [] }, { "id": "PMID-12686753_T30", "type": "Cancer", "text": [ "lung cancer" ], "offsets": [ [ 1020, 1031 ] ], "normalized": [] } ]

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[ { "id": "PMC-2759629-sec-03__text", "type": "sec", "text": [ "Results:\nAll fractures united. Individual movement of dorsiflexion, palmar flexion, supination, pronation and radial-ulnar deviation were all significantly better in the dorsiflexed-immobilized group as compared with the palmar flexed immobilized group. Grip strength recovery with subjective assessment was better in the dorsiflexed group (77%) as compared to the palmar flexed group (23%). Radiological parameters were markedly better in the dorsiflexed group. Ninety-one per cent of patients in the dorsiflexed group had excellent to good results as compared to 66% in the palmar flexed group.\n" ], "offsets": [ [ 0, 597 ] ] } ]

[ { "id": "PMC-2759629-sec-03_T1", "type": "Organism_subdivision", "text": [ "palmar" ], "offsets": [ [ 576, 582 ] ], "normalized": [] }, { "id": "PMC-2759629-sec-03_T2", "type": "Organism_subdivision", "text": [ "palmar" ], "offsets": [ [ 68, 74 ] ], "normalized": [] }, { "id": "PMC-2759629-sec-03_T3", "type": "Organ", "text": [ "radial" ], "offsets": [ [ 110, 116 ] ], "normalized": [] }, { "id": "PMC-2759629-sec-03_T4", "type": "Organ", "text": [ "ulnar" ], "offsets": [ [ 117, 122 ] ], "normalized": [] }, { "id": "PMC-2759629-sec-03_T5", "type": "Organism_subdivision", "text": [ "palmar" ], "offsets": [ [ 221, 227 ] ], "normalized": [] }, { "id": "PMC-2759629-sec-03_T6", "type": "Organism_subdivision", "text": [ "palmar" ], "offsets": [ [ 365, 371 ] ], "normalized": [] } ]

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[ { "id": "PMC-3032734-sec-23__text", "type": "sec", "text": [ "Statistical analysis\nAll statistical analyses were performed using SPSS13.0 software. The differences between groups were compared using Student's t-test, and data were expressed as mean +/- SD. Statistical difference was accepted at P<0.05.\n" ], "offsets": [ [ 0, 242 ] ] } ]

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[ { "id": "PMC-2171703-sec-06__text", "type": "sec", "text": [ "Immunocytochemistry\nC2C12 cells grown in 8-chamber slides (Nunc) were fixed in 4% PFA/PBS for 10 min and permeabilized in 0.1% Triton X-100 for 20 min. In some cases, they were fixed and permeabilized in methanol at -20degreesC for 2 min. The fixed and permeabilized cells were blocked in PBS containing 3% BSA (Jackson ImmunoResearch Laboratories) and incubated overnight at 4degreesC with primary antibodies in blocking solution. Immunoreactivity was detected with either Alexa-conjugated secondary antibody (Molecular Probes) or a combination of biotin-conjugated secondary antibody (Vector Laboratories) and Alexa-conjugated streptavidin (Molecular Probes).\n" ], "offsets": [ [ 0, 662 ] ] } ]

[ { "id": "PMC-2171703-sec-06_T1", "type": "Cell", "text": [ "C2C12 cells" ], "offsets": [ [ 20, 31 ] ], "normalized": [] }, { "id": "PMC-2171703-sec-06_T2", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 267, 272 ] ], "normalized": [] } ]

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[ { "id": "PMID-16540312__text", "type": "abstract", "text": [ "Inhibition of the mammalian target of rapamycin (mTOR) by rapamycin increases chemosensitivity of CaSki cells to paclitaxel. \nPaclitaxel, a potent anti-neoplastic agent, has been found to be effective against several tumours, including cervical cancer. However, the exact mechanism underlying the cytotoxic effects of pacitaxel, especially in the survival-signalling pathway, is poorly understood. The aim of this study was to investigate the molecular pathway of the cytotoxic effect of paclitaxel in human cervical cancer cell lines. Four human cervical cancer cell lines were treated for 24 h with various concentration of paclitaxel, and the sensitivity was analysed by an MTT assay. The cell cycle progression and sub-G1 population were analysed by flow cytometry. Apoptosis was further measured by DNA fragmentation and microscope examination. The protein expression was determined by Western blot analysis. Our results showed that HeLa cells demonstrated the highest sensitivity to paclitaxel, whereas CaSki cells showed the lowest. In cervical cancer cells, paclitaxel induced apoptosis through an intrinsic pathway with prior G2/M arrest. In addition, we showed that paclitaxel downregulated the phosphorylation of Akt in both HeLa and CaSki cells. Interestingly, in CaSki cells, which were more suggestive of a resistant phenotype, paclitaxel induced the activation of mTOR as a downstream target of Akt. Pre-treatment with rapamycin inhibited activation of mTOR signalling and significantly enhanced the sensitivity of CaSki cells to paclitaxel by increasing apoptotic cell death. This effect was mediated, at least partly, through caspase activation. Overall, paclitaxel exerts its anti-tumour effects on cervical cancer cells by inducing apoptosis through intrinsic pathway, and rapamycin targeted to mTOR can sensitise paclitaxel-resistant cervical cancer cells.\n" ], "offsets": [ [ 0, 1877 ] ] } ]

[ { "id": "PMID-16540312_T4", "type": "Cell", "text": [ "CaSki cells" ], "offsets": [ [ 98, 109 ] ], "normalized": [] }, { "id": "PMID-16540312_T7", "type": "Cancer", "text": [ "tumours" ], "offsets": [ [ 217, 224 ] ], "normalized": [] }, { "id": "PMID-16540312_T8", "type": "Cancer", "text": [ "cervical cancer" ], "offsets": [ [ 236, 251 ] ], "normalized": [] }, { "id": "PMID-16540312_T12", "type": "Cell", "text": [ "cervical cancer cell lines" ], "offsets": [ [ 508, 534 ] ], "normalized": [] }, { "id": "PMID-16540312_T14", "type": "Cell", "text": [ "cervical cancer cell lines" ], "offsets": [ [ 547, 573 ] ], "normalized": [] }, { "id": "PMID-16540312_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 692, 696 ] ], "normalized": [] }, { "id": "PMID-16540312_T18", "type": "Cell", "text": [ "HeLa cells" ], "offsets": [ [ 938, 948 ] ], "normalized": [] }, { "id": "PMID-16540312_T20", "type": "Cell", "text": [ "CaSki cells" ], "offsets": [ [ 1009, 1020 ] ], "normalized": [] }, { "id": "PMID-16540312_T21", "type": "Cell", "text": [ "cervical cancer cells" ], "offsets": [ [ 1043, 1064 ] ], "normalized": [] }, { "id": "PMID-16540312_T25", "type": "Cell", "text": [ "HeLa" ], "offsets": [ [ 1236, 1240 ] ], "normalized": [] }, { "id": "PMID-16540312_T26", "type": "Cell", "text": [ "CaSki cells" ], "offsets": [ [ 1245, 1256 ] ], "normalized": [] }, { "id": "PMID-16540312_T27", "type": "Cell", "text": [ "CaSki cells" ], "offsets": [ [ 1276, 1287 ] ], "normalized": [] }, { "id": "PMID-16540312_T33", "type": "Cell", "text": [ "CaSki cells" ], "offsets": [ [ 1530, 1541 ] ], "normalized": [] }, { "id": "PMID-16540312_T35", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "PMID-16540312_T38", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 1699, 1705 ] ], "normalized": [] }, { "id": "PMID-16540312_T39", "type": "Cell", "text": [ "cervical cancer cells" ], "offsets": [ [ 1717, 1738 ] ], "normalized": [] }, { "id": "PMID-16540312_T43", "type": "Cell", "text": [ "cervical cancer cells" ], "offsets": [ [ 1854, 1875 ] ], "normalized": [] }, { "id": "PMID-16540312_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 152, 162 ] ], "normalized": [] } ]

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[ { "id": "PMID-3830071__text", "type": "abstract", "text": [ "Clinical evaluation of radiotherapy for Graves' ophthalmopathy.\nSeventeen patients with moderately severe ophthalmopathy due to Graves' disease were treated by cobalt or supervoltage radiotherapy. All patients complained of diplopia. The mean proptosis value was 21.4 mm. Three patients (18%) showed good response, 7 (41%) moderate and 7 minimal or no response. Improvement was noted mainly in soft tissue changes and diplopia, while proptosis decreased in only 5 patients. All except one patient who had marked extraocular muscle involvement revealed by computed tomography responded to treatment. These data indicate that radiotherapy may be indicated in patients with progressive ophthalmopathy, especially in those who are associated with extraocular muscle enlargement.\n" ], "offsets": [ [ 0, 775 ] ] } ]

[ { "id": "PMID-3830071_T1", "type": "Tissue", "text": [ "soft tissue" ], "offsets": [ [ 394, 405 ] ], "normalized": [] }, { "id": "PMID-3830071_T2", "type": "Multi-tissue_structure", "text": [ "extraocular muscle" ], "offsets": [ [ 512, 530 ] ], "normalized": [] }, { "id": "PMID-3830071_T3", "type": "Multi-tissue_structure", "text": [ "extraocular muscle" ], "offsets": [ [ 743, 761 ] ], "normalized": [] } ]

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[ { "id": "PMID-6728933__text", "type": "abstract", "text": [ "Hippocampal afterdischarge interferes with storage of spatial information in a working memory test.\nIn an attempt to impair spatial working memory by reversible functional blockade rather than by irreversible lesion of the hippocampus, eight male hooded rats were trained to asymptotic performance of 1.2 to 1.4 errors per trial in the spatial 12-choice apparatus ( Bure s et al. 1982), formally similar to the radial maze. The rats were implanted with hippocampal stimulating and recording electrodes, which were used for eliciting and monitoring hippocampal afterdischarge (HAD) lasting for at least 20 s. In Experiment 1, HAD elicited 1 or 10 min before testing increased the incidence of errors to 2.75 or 2.50 per trial, respectively, but the performance still remained above chance level (4.18). In Experiment 2, interruption of the trial by 1, 10, 20 and 30 min intervals inserted between choices 6 and 7 increased the incidence of errors in choices 7 to 12 to 1.0, 1.5, 2.1 and 2.5, respectively. HAD elicited immediately after choice 6 increased error incidence in the subsequent 6 choices performed after 1-min or 10-min intervals to 3.1 or 2.75, respectively, i.e. to the chance level of 3 errors in 6 choices. It is concluded that HAD elicits transient shortening of the memory span for newly acquired spatial information (anterograde effect) and erases the current spatial working memory record (retrograde effect).\n" ], "offsets": [ [ 0, 1429 ] ] } ]

[ { "id": "PMID-6728933_T1", "type": "Multi-tissue_structure", "text": [ "Hippocampal" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-6728933_T2", "type": "Multi-tissue_structure", "text": [ "hippocampus" ], "offsets": [ [ 223, 234 ] ], "normalized": [] }, { "id": "PMID-6728933_T3", "type": "Multi-tissue_structure", "text": [ "hippocampal" ], "offsets": [ [ 453, 464 ] ], "normalized": [] }, { "id": "PMID-6728933_T4", "type": "Multi-tissue_structure", "text": [ "hippocampal" ], "offsets": [ [ 548, 559 ] ], "normalized": [] }, { "id": "PMID-6728933_T6", "type": "Pathological_formation", "text": [ "lesion" ], "offsets": [ [ 209, 215 ] ], "normalized": [] } ]

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[ { "id": "PMC-2961588-caption-01__text", "type": "caption", "text": [ "The molecular structure of (I), showing displacement ellipsoids at the 30% probability level for non-H atoms.\n" ], "offsets": [ [ 0, 110 ] ] } ]

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[ { "id": "PMID-9239276__text", "type": "abstract", "text": [ "[Treatment of acute liver failure in children].\nAmong the main causes of acute liver failure (ALF) in children, metabolic diseases (especially in infants), viral and toxin or drug induced hepatitis are the most frequent. The cause remains, however, undetermined in about 30% of the cases. Management must be conducted in a pediatric hepatology unit or intensive care unit in relation with a pediatric transplant team in order: 1) to perform urgent etiological diagnosis; 2) to initiate specific therapy and symptomatic treatment; 3) to evaluate the severity and prognosis of liver disease for selection of children for emergency liver transplantation; 4) to evaluate contraindications to liver transplantation. The overall survival of post-emergency liver transplantation for ALF in children averages 65%.\n" ], "offsets": [ [ 0, 806 ] ] } ]

[ { "id": "PMID-9239276_T1", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 79, 84 ] ], "normalized": [] }, { "id": "PMID-9239276_T2", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 575, 580 ] ], "normalized": [] }, { "id": "PMID-9239276_T3", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 629, 634 ] ], "normalized": [] }, { "id": "PMID-9239276_T4", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 688, 693 ] ], "normalized": [] }, { "id": "PMID-9239276_T5", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 750, 755 ] ], "normalized": [] }, { "id": "PMID-9239276_T6", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 20, 25 ] ], "normalized": [] } ]

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[ { "id": "PMID-19574426__text", "type": "abstract", "text": [ "Angiogenesis in platelet endothelial cell adhesion molecule-1-null mice.\nPlatelet endothelial cell adhesion molecule (PECAM)-1 has been previously implicated in endothelial cell migration; additionally, anti-PECAM-1 antibodies have been shown to inhibit in vivo angiogenesis. Studies were therefore performed with PECAM-1-null mice to further define the involvement of PECAM-1 in blood vessel formation. Vascularization of subcutaneous Matrigel implants as well as tumor angiogenesis were both inhibited in PECAM-1-null mice. Reciprocal bone marrow transplants that involved both wild-type and PECAM-1-deficient mice revealed that the impaired angiogenic response resulted from a loss of endothelial, but not leukocyte, PECAM-1. In vitro wound migration and single-cell motility by PECAM-1-null endothelial cells were also compromised. In addition, filopodia formation, a feature of motile cells, was inhibited in PECAM-1-null endothelial cells as well as in human endothelial cells treated with either anti-PECAM-1 antibody or PECAM-1 siRNA. Furthermore, the expression of PECAM-1 promoted filopodia formation and increased the protein expression levels of Cdc42, a Rho GTPase that is known to promote the formation of filopodia. In the developing retinal vasculature, numerous, long filamentous filopodia, emanating from endothelial cells at the tips of angiogenic sprouts, were observed in wild-type animals, but to a lesser extent in the PECAM-1-null mice. Together, these data further establish the involvement of endothelial PECAM-1 in angiogenesis and suggest that, in vivo, PECAM-1 may stimulate endothelial cell motility by promoting the formation of filopodia.\n" ], "offsets": [ [ 0, 1671 ] ] } ]

[ { "id": "PMID-19574426_T4", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 161, 177 ] ], "normalized": [] }, { "id": "PMID-19574426_T9", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 380, 392 ] ], "normalized": [] }, { "id": "PMID-19574426_T10", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 465, 470 ] ], "normalized": [] }, { "id": "PMID-19574426_T13", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 537, 548 ] ], "normalized": [] }, { "id": "PMID-19574426_T16", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 688, 699 ] ], "normalized": [] }, { "id": "PMID-19574426_T17", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 709, 718 ] ], "normalized": [] }, { "id": "PMID-19574426_T19", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 738, 743 ] ], "normalized": [] }, { "id": "PMID-19574426_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 765, 769 ] ], "normalized": [] }, { "id": "PMID-19574426_T21", "type": "Cell", "text": [ "PECAM-1-null endothelial cells" ], "offsets": [ [ 782, 812 ] ], "normalized": [] }, { "id": "PMID-19574426_T23", "type": "Cellular_component", "text": [ "filopodia" ], "offsets": [ [ 849, 858 ] ], "normalized": [] }, { "id": "PMID-19574426_T24", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 890, 895 ] ], "normalized": [] }, { "id": "PMID-19574426_T25", "type": "Cell", "text": [ "PECAM-1-null endothelial cells" ], "offsets": [ [ 914, 944 ] ], "normalized": [] }, { "id": "PMID-19574426_T28", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 965, 982 ] ], "normalized": [] }, { "id": "PMID-19574426_T32", "type": "Cellular_component", "text": [ "filopodia" ], "offsets": [ [ 1091, 1100 ] ], "normalized": [] }, { "id": "PMID-19574426_T35", "type": "Cellular_component", "text": [ "filopodia" ], "offsets": [ [ 1220, 1229 ] ], "normalized": [] }, { "id": "PMID-19574426_T36", "type": "Multi-tissue_structure", "text": [ "retinal vasculature" ], "offsets": [ [ 1249, 1268 ] ], "normalized": [] }, { "id": "PMID-19574426_T37", "type": "Cellular_component", "text": [ "long filamentous filopodia" ], "offsets": [ [ 1280, 1306 ] ], "normalized": [] }, { "id": "PMID-19574426_T38", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1323, 1340 ] ], "normalized": [] }, { "id": "PMID-19574426_T39", "type": "Tissue", "text": [ "sprouts" ], "offsets": [ [ 1367, 1374 ] ], "normalized": [] }, { "id": "PMID-19574426_T42", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 1519, 1530 ] ], "normalized": [] }, { "id": "PMID-19574426_T45", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1604, 1620 ] ], "normalized": [] }, { "id": "PMID-19574426_T46", "type": "Cellular_component", "text": [ "filopodia" ], "offsets": [ [ 1660, 1669 ] ], "normalized": [] }, { "id": "PMID-19574426_T1", "type": "Immaterial_anatomical_entity", "text": [ "subcutaneous" ], "offsets": [ [ 423, 435 ] ], "normalized": [] } ]

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[ { "id": "PMC-2958911-caption-05__text", "type": "caption", "text": [ "Additional file 2\nVideo S2 TTE apical 4-chamber view. The vegetation seems located just above the tricuspid septal valve without causing obstruction on it.\n" ], "offsets": [ [ 0, 156 ] ] } ]

[ { "id": "PMC-2958911-caption-05_T1", "type": "Multi-tissue_structure", "text": [ "tricuspid septal valve" ], "offsets": [ [ 98, 120 ] ], "normalized": [] } ]

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[ { "id": "PMID-18505892__text", "type": "abstract", "text": [ "Adenomatoid tumour of the liver.\nAn unusual primary adenomatoid tumour arising in the normal liver is described. Hepatectomy was performed, and the patient is alive and free of disease 1 year postsurgery. Grossly, the tumour showed a haemorrhagic cut surface with numerous microcystic structures. Histological examination revealed cystic or angiomatoid spaces of various sizes lined by cuboidal, low-columnar, or flattened epithelioid cells with vacuolated cytoplasm and round to oval nuclei. The epithelioid cells were entirely supported by proliferated capillaries and arteries together with collagenous stroma. Immunohistochemical studies showed that the epithelioid cells were strongly positive for a broad spectrum of cytokeratins (AE1/AE3, CAM5.2, epithelial membrane antigen and cytokeratin 7) and mesothelial markers (calretinin, Wilms' tumour 1 and D2-40). These cells were negative for Hep par-1, carcinoembryonic antigen, neural cell adhesion molecule, CD34, CD31 and HMB45. Atypically, abundant capillaries were observed; however, the cystic proliferation of epithelioid cells with vacuoles and immunohistochemical profile of the epithelioid element were consistent with hepatic adenomatoid tumour.\n" ], "offsets": [ [ 0, 1211 ] ] } ]

[ { "id": "PMID-18505892_T1", "type": "Cancer", "text": [ "Adenomatoid tumour" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "PMID-18505892_T2", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 26, 31 ] ], "normalized": [] }, { "id": "PMID-18505892_T3", "type": "Cancer", "text": [ "primary adenomatoid tumour" ], "offsets": [ [ 44, 70 ] ], "normalized": [] }, { "id": "PMID-18505892_T4", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 93, 98 ] ], "normalized": [] }, { "id": "PMID-18505892_T6", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 218, 224 ] ], "normalized": [] }, { "id": "PMID-18505892_T7", "type": "Pathological_formation", "text": [ "microcystic structures" ], "offsets": [ [ 273, 295 ] ], "normalized": [] }, { "id": "PMID-18505892_T8", "type": "Cell", "text": [ "epithelioid cells" ], "offsets": [ [ 423, 440 ] ], "normalized": [] }, { "id": "PMID-18505892_T9", "type": "Organism_substance", "text": [ "vacuolated cytoplasm" ], "offsets": [ [ 446, 466 ] ], "normalized": [] }, { "id": "PMID-18505892_T10", "type": "Cellular_component", "text": [ "nuclei" ], "offsets": [ [ 485, 491 ] ], "normalized": [] }, { "id": "PMID-18505892_T11", "type": "Cell", "text": [ "epithelioid cells" ], "offsets": [ [ 497, 514 ] ], "normalized": [] }, { "id": "PMID-18505892_T12", "type": "Tissue", "text": [ "capillaries" ], "offsets": [ [ 555, 566 ] ], "normalized": [] }, { "id": "PMID-18505892_T13", "type": "Multi-tissue_structure", "text": [ "arteries" ], "offsets": [ [ 571, 579 ] ], "normalized": [] }, { "id": "PMID-18505892_T14", "type": "Tissue", "text": [ "collagenous stroma" ], "offsets": [ [ 594, 612 ] ], "normalized": [] }, { "id": "PMID-18505892_T15", "type": "Cell", "text": [ "epithelioid cells" ], "offsets": [ [ 658, 675 ] ], "normalized": [] }, { "id": "PMID-18505892_T22", "type": "Tissue", "text": [ "mesothelial" ], "offsets": [ [ 805, 816 ] ], "normalized": [] }, { "id": "PMID-18505892_T26", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 872, 877 ] ], "normalized": [] }, { "id": "PMID-18505892_T33", "type": "Tissue", "text": [ "capillaries" ], "offsets": [ [ 1007, 1018 ] ], "normalized": [] }, { "id": "PMID-18505892_T34", "type": "Pathological_formation", "text": [ "cystic" ], "offsets": [ [ 1047, 1053 ] ], "normalized": [] }, { "id": "PMID-18505892_T35", "type": "Cell", "text": [ "epithelioid cells" ], "offsets": [ [ 1071, 1088 ] ], "normalized": [] }, { "id": "PMID-18505892_T36", "type": "Cellular_component", "text": [ "vacuoles" ], "offsets": [ [ 1094, 1102 ] ], "normalized": [] }, { "id": "PMID-18505892_T37", "type": "Tissue", "text": [ "epithelioid element" ], "offsets": [ [ 1142, 1161 ] ], "normalized": [] }, { "id": "PMID-18505892_T38", "type": "Cancer", "text": [ "hepatic adenomatoid tumour" ], "offsets": [ [ 1183, 1209 ] ], "normalized": [] }, { "id": "PMID-18505892_T43", "type": "Pathological_formation", "text": [ "cystic" ], "offsets": [ [ 331, 337 ] ], "normalized": [] }, { "id": "PMID-18505892_T5", "type": "Cancer", "text": [ "surface" ], "offsets": [ [ 251, 258 ] ], "normalized": [] } ]

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[ { "id": "PMID-15913739__text", "type": "abstract", "text": [ "Bcl-2 decreases cell proliferation and promotes accumulation of cells in S phase without affecting the rate of apoptosis in human ovarian carcinoma cells.\nOBJECTIVES:\nThe Bcl-2 protein is an important regulator of the apoptotic cascade and promotes cell survival. Bcl-2 can also delay entry into the cell cycle from quiescence. In the present study, we used two isogenic human ovarian carcinoma cell lines, which expressed differential levels of Bcl-2 proteins, to demonstrate that Bcl-2 may regulate the growth rates of adenocarcinoma cells.\nMETHODS:\nThe growth rates of two isogenic ovarian cancer cell lines were determined by XTT assays and flow cytometry combined with PI staining. Bcl-2-overexpressing SKOV3 cells were modified to express a doxycycline-inducible anti-Bcl-2 single-chain antibody and the effects of Bcl-2 protein inhibition on cell proliferation and apoptosis were assessed.\nRESULTS:\nWe demonstrate that Bcl-2 promotes the accumulation of proliferating carcinoma cells in S phase. The Bcl-2-overexpressing SKOV3 cell line proliferates markedly faster and shows delayed progression to G2M phase compared to its low Bcl-2-expressing counterpart SKOV3.ip1 cell line. Single-chain antibody-mediated inhibition of Bcl-2 in SKOV3 cells was associated with increased growth rates and more rapid cell cycle progression. Treatment with cisplatin resulted in more cells accumulating in S phase in Bcl-2-overexpressing SKOV3 cells, while the inhibition of Bcl-2 abolished delayed entry into G2M phase without affecting cisplatin-induced apoptosis.\nCONCLUSIONS:\nOur results suggest that, in ovarian cancer cells, Bcl-2 delays cell cycle progression by promoting accumulation of cells in S phase without affecting the rate of apoptosis. Thus, in addition to its known role at the G0/G1 checkpoint, we demonstrate for the first time that Bcl-2 also regulates the S phase.\n" ], "offsets": [ [ 0, 1880 ] ] } ]

[ { "id": "PMID-15913739_T1", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 16, 20 ] ], "normalized": [] }, { "id": "PMID-15913739_T2", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 64, 69 ] ], "normalized": [] }, { "id": "PMID-15913739_T3", "type": "Cell", "text": [ "ovarian carcinoma cells" ], "offsets": [ [ 130, 153 ] ], "normalized": [] }, { "id": "PMID-15913739_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 249, 253 ] ], "normalized": [] }, { "id": "PMID-15913739_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 300, 304 ] ], "normalized": [] }, { "id": "PMID-15913739_T6", "type": "Cell", "text": [ "ovarian carcinoma cell lines" ], "offsets": [ [ 377, 405 ] ], "normalized": [] }, { "id": "PMID-15913739_T7", "type": "Cell", "text": [ "adenocarcinoma cells" ], "offsets": [ [ 521, 541 ] ], "normalized": [] }, { "id": "PMID-15913739_T8", "type": "Cell", "text": [ "ovarian cancer cell lines" ], "offsets": [ [ 585, 610 ] ], "normalized": [] }, { "id": "PMID-15913739_T9", "type": "Cell", "text": [ "Bcl-2-overexpressing SKOV3 cells" ], "offsets": [ [ 687, 719 ] ], "normalized": [] }, { "id": "PMID-15913739_T10", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 849, 853 ] ], "normalized": [] }, { "id": "PMID-15913739_T11", "type": "Cell", "text": [ "carcinoma cells" ], "offsets": [ [ 975, 990 ] ], "normalized": [] }, { "id": "PMID-15913739_T12", "type": "Cell", "text": [ "Bcl-2-overexpressing SKOV3 cell line" ], "offsets": [ [ 1007, 1043 ] ], "normalized": [] }, { "id": "PMID-15913739_T13", "type": "Cell", "text": [ "Bcl-2-expressing counterpart SKOV3.ip1 cell line" ], "offsets": [ [ 1136, 1184 ] ], "normalized": [] }, { "id": "PMID-15913739_T14", "type": "Cell", "text": [ "SKOV3 cells" ], "offsets": [ [ 1240, 1251 ] ], "normalized": [] }, { "id": "PMID-15913739_T15", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1310, 1314 ] ], "normalized": [] }, { "id": "PMID-15913739_T16", "type": "Cell", "text": [ "Bcl-2-overexpressing SKOV3 cells" ], "offsets": [ [ 1409, 1441 ] ], "normalized": [] }, { "id": "PMID-15913739_T17", "type": "Cell", "text": [ "ovarian cancer cells" ], "offsets": [ [ 1601, 1621 ] ], "normalized": [] }, { "id": "PMID-15913739_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1636, 1640 ] ], "normalized": [] }, { "id": "PMID-15913739_T19", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1376, 1381 ] ], "normalized": [] }, { "id": "PMID-15913739_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1688, 1693 ] ], "normalized": [] } ]

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[ { "id": "PMID-17367752__text", "type": "abstract", "text": [ "SWAP-70 is required for oncogenic transformation by v-Src in mouse embryo fibroblasts. \nSWAP-70 is a phosphatidylinositol trisphosphate (PtdIns(3,4,5)P(3)) binding protein, which acts in F-actin rearrangement. The role of SWAP-70 in oncogenic transformation of mouse embryo fibroblasts (MEFs) by v-Src was examined by use of MEFs defective in SWAP-70. v-Src morphologically transformed MEFs lacking SWAP-70, but growth of the transformed cells in culture was slower than that of cells supplemented with exogenous SWAP-70. The v-Src-transformed MEFs deficient in SWAP-70 were unable to grow in soft agar while those expressing SWAP70 readily formed colonies, suggesting that SWAP-70 is required for anchorage independent growth of v-Src transformed MEFs. When transplanted in nude mice, tumors formed by the v-Src transformed SWAP-70(-/-) MEFs were smaller than those formed by cells expressing exogenous SWAP-70. These results suggest that SWAP-70 may be required for oncogenic transformation and contributes to cell growth in MEFs transformed by v-Src.\n" ], "offsets": [ [ 0, 1054 ] ] } ]

[ { "id": "PMID-17367752_T4", "type": "Cell", "text": [ "embryo fibroblasts" ], "offsets": [ [ 67, 85 ] ], "normalized": [] }, { "id": "PMID-17367752_T11", "type": "Cell", "text": [ "embryo fibroblasts" ], "offsets": [ [ 267, 285 ] ], "normalized": [] }, { "id": "PMID-17367752_T12", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 287, 291 ] ], "normalized": [] }, { "id": "PMID-17367752_T14", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 325, 329 ] ], "normalized": [] }, { "id": "PMID-17367752_T17", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 386, 390 ] ], "normalized": [] }, { "id": "PMID-17367752_T19", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 438, 443 ] ], "normalized": [] }, { "id": "PMID-17367752_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 479, 484 ] ], "normalized": [] }, { "id": "PMID-17367752_T23", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 544, 548 ] ], "normalized": [] }, { "id": "PMID-17367752_T29", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 748, 752 ] ], "normalized": [] }, { "id": "PMID-17367752_T31", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 786, 792 ] ], "normalized": [] }, { "id": "PMID-17367752_T34", "type": "Cell", "text": [ "SWAP-70(-/-) MEFs" ], "offsets": [ [ 825, 842 ] ], "normalized": [] }, { "id": "PMID-17367752_T35", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 877, 882 ] ], "normalized": [] }, { "id": "PMID-17367752_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1012, 1016 ] ], "normalized": [] }, { "id": "PMID-17367752_T39", "type": "Cell", "text": [ "MEFs" ], "offsets": [ [ 1027, 1031 ] ], "normalized": [] }, { "id": "PMID-17367752_T1", "type": "Cell", "text": [ "colonies" ], "offsets": [ [ 648, 656 ] ], "normalized": [] } ]

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[ { "id": "PMID-7586219__text", "type": "abstract", "text": [ "VEGF165 expressed by a replication-deficient recombinant adenovirus vector induces angiogenesis in vivo.\nTo evaluate the concept that localized delivery of angiogenic factors via virus-mediated gene transfer may be useful in the treatment of ischemic disorders, the replication-deficient adenovirus (Ad) vector AdCMV.VEGF165 (where CMV is cytomegalovirus and VEGF is vascular endothelial growth factor) containing the cDNA for human VEGF165, a secreted endothelial cell-specific angiogenic growth factor, was constructed. Human umbilical vein endothelial cells (HUVECs) and rat aorta smooth muscle cells (RASMCs) infected with AdCMV.VEGF165 (5 and 20 plaque-forming units [pfu] per cell) demonstrated VEGF mRNA expression and protein secretion into the supernatant. Furthermore, the conditioned medium from these cells enhanced vascular permeability in vivo. In contrast, neither VEGF mRNA nor secreted protein was found in uninfected HUVECs or RASMCs or in cells infected with the control vector AdCMV.beta gal (where beta gal is beta-galactosidase). Assessment of starved HUVECs at 14 days demonstrated sixfold more cells for AdCMV.VEGF165-infected HUVECs (20 pfu per cell) than for either infected or uninfected control cells. RASMC proliferation was unaffected by infection with AdCMV.VEGF165. When plated in 2% serum on dishes precoated with reconstituted basement membrane (Matrigel), HUVECs infected with AdCMV.VEGF165 (20 pfu per cell) differentiated into capillary-like structures. Under similar conditions, both uninfected HUVECs and HUVECs infected with AdCMV.beta gal did not differentiate. To evaluate the ability of AdCMV.VEGF165 to function in vivo, either AdCMV. VEGF165 or AdCMV.beta gal (2 x 10(10) pfu) was resuspended in 0.5 mL Matrigel and injected subcutaneously into mice. Immunohistochemical staining demonstrated VEGF in the tissues surrounding the Matrigel plugs containing AdCMV.VEGF165 up to 3 weeks after injection, whereas no VEGF was found in the control plugs with AdCMV.beta gal. Two weeks after injection, there was histological evidence of neovascularization in the tissues surrounding the Matrigel containing AdCMV.VEGF165, whereas no significant angiogenesis was observed in response to AdCMV.beta gal. Furthermore, the Matrigel plugs with AdCMV.VEGF165 demonstrated hemoglobin content fourfold higher than the plugs with AdCMV.beta gal. Together, these in vitro and in vivo studies are consistent with the concept that Ad vectors may provide a useful strategy for efficient local delivery of VEGF165 in the treatment of ischemic diseases.\n" ], "offsets": [ [ 0, 2577 ] ] } ]

[ { "id": "PMID-7586219_T14", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 453, 469 ] ], "normalized": [] }, { "id": "PMID-7586219_T15", "type": "Cell", "text": [ "Human umbilical vein endothelial cells" ], "offsets": [ [ 522, 560 ] ], "normalized": [] }, { "id": "PMID-7586219_T16", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 562, 568 ] ], "normalized": [] }, { "id": "PMID-7586219_T17", "type": "Cell", "text": [ "rat aorta smooth muscle cells" ], "offsets": [ [ 574, 603 ] ], "normalized": [] }, { "id": "PMID-7586219_T18", "type": "Cell", "text": [ "RASMCs" ], "offsets": [ [ 605, 611 ] ], "normalized": [] }, { "id": "PMID-7586219_T21", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 682, 686 ] ], "normalized": [] }, { "id": "PMID-7586219_T23", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 813, 818 ] ], "normalized": [] }, { "id": "PMID-7586219_T24", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "PMID-7586219_T26", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 935, 941 ] ], "normalized": [] }, { "id": "PMID-7586219_T27", "type": "Cell", "text": [ "RASMCs" ], "offsets": [ [ 945, 951 ] ], "normalized": [] }, { "id": "PMID-7586219_T28", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 958, 963 ] ], "normalized": [] }, { "id": "PMID-7586219_T33", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1074, 1080 ] ], "normalized": [] }, { "id": "PMID-7586219_T34", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1118, 1123 ] ], "normalized": [] }, { "id": "PMID-7586219_T37", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1151, 1157 ] ], "normalized": [] }, { "id": "PMID-7586219_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1170, 1174 ] ], "normalized": [] }, { "id": "PMID-7586219_T39", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1223, 1228 ] ], "normalized": [] }, { "id": "PMID-7586219_T40", "type": "Cell", "text": [ "RASMC" ], "offsets": [ [ 1230, 1235 ] ], "normalized": [] }, { "id": "PMID-7586219_T43", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1316, 1321 ] ], "normalized": [] }, { "id": "PMID-7586219_T44", "type": "Cellular_component", "text": [ "basement membrane" ], "offsets": [ [ 1361, 1378 ] ], "normalized": [] }, { "id": "PMID-7586219_T45", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1391, 1397 ] ], "normalized": [] }, { "id": "PMID-7586219_T48", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1438, 1442 ] ], "normalized": [] }, { "id": "PMID-7586219_T49", "type": "Tissue", "text": [ "capillary-like structures" ], "offsets": [ [ 1464, 1489 ] ], "normalized": [] }, { "id": "PMID-7586219_T50", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1533, 1539 ] ], "normalized": [] }, { "id": "PMID-7586219_T51", "type": "Cell", "text": [ "HUVECs" ], "offsets": [ [ 1544, 1550 ] ], "normalized": [] }, { "id": "PMID-7586219_T62", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1850, 1857 ] ], "normalized": [] }, { "id": "PMID-7586219_T68", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 2101, 2108 ] ], "normalized": [] }, { "id": "PMID-7586219_T113", "type": "Immaterial_anatomical_entity", "text": [ "subcutaneously" ], "offsets": [ [ 1770, 1784 ] ], "normalized": [] }, { "id": "PMID-7586219_T1", "type": "Organism_substance", "text": [ "supernatant" ], "offsets": [ [ 753, 764 ] ], "normalized": [] } ]

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[ { "id": "PMID-22279574__text", "type": "abstract", "text": [ "Mitochondrial apoptosis and FAK signaling disruption by a novel histone deacetylase inhibitor, HTPB, in antitumor and antimetastatic mouse models. \nBACKGROUND: Compound targeting histone deacetylase (HDAC) represents a new era in molecular cancer therapeutics. However, effective HDAC inhibitors for the treatment of solid tumors remain to be developed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we propose a novel HDAC inhibitor, N-Hydroxy-4-(4-phenylbutyryl-amino) benzamide (HTPB), as a potential chemotherapeutic drug for solid tumors. The HDAC inhibition of HTPB was confirmed using HDAC activity assay. The antiproliferative and anti-migratory mechanisms of HTPB were investigated by cell proliferation, flow cytometry, DNA ladder, caspase activity, Rho activity, F-actin polymerization, and gelatin-zymography for matrix metalloproteinases (MMPs). Mice with tumor xenograft and experimental metastasis model were used to evaluate effects on tumor growth and metastasis. Our results indicated that HTPB was a pan-HDAC inhibitor in suppressing cell viability specifically of lung cancer cells but not of the normal lung cells. Upon HTPB treatment, cell cycle arrest was induced and subsequently led to mitochondria-mediated apoptosis. HTPB disrupted F-actin dynamics via downregulating RhoA activity. Moreover, HTPB inhibited activity of MMP2 and MMP9, reduced integrin-beta1/focal adhesion complex formation and decreased pericellular poly-fibronectin assemblies. Finally, intraperitoneal injection or oral administration of HTPB efficiently inhibited A549 xenograft tumor growth in vivo without side effects. HTPB delayed lung metastasis of 4T1 mouse breast cancer cells. Acetylation of histone and non-histone proteins, induction of apoptotic-related proteins and de-phosphorylation of focal adhesion kinase were confirmed in treated mice. CONCLUSIONS/SIGNIFICANCE: These results suggested that intrinsic apoptotic pathway may involve in anti-tumor growth effects of HTPB in lung cancer cells. HTPB significantly suppresses tumor metastasis partly through inhibition of integrin-beta1/FAK/MMP/RhoA/F-actin pathways. We have provided convincing preclinical evidence that HTPB is a potent HDAC targeted inhibitor and is thus a promising candidate for lung cancer chemotherapy.\n" ], "offsets": [ [ 0, 2279 ] ] } ]

[ { "id": "PMID-22279574_T1", "type": "Cellular_component", "text": [ "Mitochondrial" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-22279574_T5", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 108, 113 ] ], "normalized": [] }, { "id": "PMID-22279574_T9", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 240, 246 ] ], "normalized": [] }, { "id": "PMID-22279574_T11", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 317, 329 ] ], "normalized": [] }, { "id": "PMID-22279574_T15", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 522, 534 ] ], "normalized": [] }, { "id": "PMID-22279574_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 686, 690 ] ], "normalized": [] }, { "id": "PMID-22279574_T28", "type": "Cancer", "text": [ "tumor xenograft" ], "offsets": [ [ 861, 876 ] ], "normalized": [] }, { "id": "PMID-22279574_T29", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 944, 949 ] ], "normalized": [] }, { "id": "PMID-22279574_T32", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1045, 1049 ] ], "normalized": [] }, { "id": "PMID-22279574_T33", "type": "Cell", "text": [ "lung cancer cells" ], "offsets": [ [ 1076, 1093 ] ], "normalized": [] }, { "id": "PMID-22279574_T34", "type": "Cell", "text": [ "lung cells" ], "offsets": [ [ 1116, 1126 ] ], "normalized": [] }, { "id": "PMID-22279574_T36", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1149, 1153 ] ], "normalized": [] }, { "id": "PMID-22279574_T37", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 1203, 1215 ] ], "normalized": [] }, { "id": "PMID-22279574_T47", "type": "Immaterial_anatomical_entity", "text": [ "intraperitoneal" ], "offsets": [ [ 1475, 1490 ] ], "normalized": [] }, { "id": "PMID-22279574_T48", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "PMID-22279574_T50", "type": "Cancer", "text": [ "A549 xenograft tumor" ], "offsets": [ [ 1554, 1574 ] ], "normalized": [] }, { "id": "PMID-22279574_T52", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 1625, 1629 ] ], "normalized": [] }, { "id": "PMID-22279574_T53", "type": "Cell", "text": [ "4T1 mouse breast cancer cells" ], "offsets": [ [ 1644, 1673 ] ], "normalized": [] }, { "id": "PMID-22279574_T59", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1947, 1952 ] ], "normalized": [] }, { "id": "PMID-22279574_T61", "type": "Cell", "text": [ "lung cancer cells" ], "offsets": [ [ 1979, 1996 ] ], "normalized": [] }, { "id": "PMID-22279574_T63", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 2028, 2033 ] ], "normalized": [] }, { "id": "PMID-22279574_T71", "type": "Cancer", "text": [ "lung cancer" ], "offsets": [ [ 2253, 2264 ] ], "normalized": [] }, { "id": "PMID-22279574_T2", "type": "Immaterial_anatomical_entity", "text": [ "pericellular" ], "offsets": [ [ 1424, 1436 ] ], "normalized": [] } ]

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[ { "id": "PMID-18814295__text", "type": "abstract", "text": [ "Thermostability and molecular encapsulation within an engineered caged protein scaffold.\nSelf-assembling biological complexes such as viral capsids have been manipulated to function in innovative nanotechnology applications. The E2 component of pyruvate dehydrogenase from Bacillus stearothermophilus forms a dodecahedral complex and potentially provides another platform for these purposes. In this investigation, we show that this protein assembly exhibits unusual stability and can be modified to encapsulate model drug molecules. To distill the E2 protein down to its structural scaffold core, we synthesized a truncated gene optimized for expression in Escherichia coli. The correct assembly and dodecahedral structure of the resulting scaffold was confirmed with dynamic light scattering and transmission electron microscopy. Using circular dichroism and differential scanning calorimetry, we found the thermostability of the complex to be unusually high, with an onset temperature of unfolding at 81.1 +/- 0.9 degrees C and an apparent midpoint unfolding temperature of 91.4 +/- 1.4 degrees C. To evaluate the potential of this scaffold for encapsulation of guest molecules, we made variants at residues 381 and 239 which altered the physicochemical properties of the hollow internal cavity. These mutants, yielding 60 and 120 mutations within this cavity, assembled into the correct architecture and exhibited high thermostability that was comparable to the wild-type scaffold. To show the applicability of this scaffold, two different fluorescent dye molecules were covalently coupled to the cysteine mutant at site 381. We demonstrate that these mutations can introduce non-native functionality and enable molecular encapsulation within the cavity while still retaining the dodecahedral structure. The unusually robust nature of this scaffold and its amenability to internal changes reveal its potential for nanoscale applications.\n" ], "offsets": [ [ 0, 1942 ] ] } ]

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[ { "id": "PMID-11387198__text", "type": "abstract", "text": [ "Thrombospondin-2 plays a protective role in multistep carcinogenesis: a novel host anti-tumor defense mechanism.\nThe angiogenic switch during tumorigenesis is thought to be induced by a change in the balance of pro- angiogenic and anti-angiogenic factors. To elucidate the biological role of the endogenous angiogenesis inhibitor thrombospondin-2 (TSP-2) during multistep carcinogenesis, we subjected TSP-2-deficient and wild-type mice to a chemical skin carcinogenesis regimen. Surprisingly, TSP-2 expression was strongly upregulated in the mesenchymal stroma of wild-type mice throughout the consecutive stages of tumorigenesis whereas the angiogenesis factor, vascular endothelial growth factor, was induced predominantly in tumor cells. TSP-2 deficiency dramatically enhanced susceptibility to skin carcinogenesis and resulted in accelerated and increased tumor formation. The angiogenic switch occurred in early stages of pre-malignant tumor formation, and tumor angiogenesis was significantly enhanced in TSP-2-deficient mice. While TSP-2 deficiency did not affect tumor differentiation or proliferation, tumor cell apoptosis was significantly reduced. These results reveal upregulation of an endogenous angiogenesis inhibitor during multi step tumorigenesis and identify enhanced stromal TSP-2 expression as a novel host anti-tumor defense mechanism.\n" ], "offsets": [ [ 0, 1358 ] ] } ]

[ { "id": "PMID-11387198_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 88, 93 ] ], "normalized": [] }, { "id": "PMID-11387198_T7", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 450, 454 ] ], "normalized": [] }, { "id": "PMID-11387198_T9", "type": "Tissue", "text": [ "mesenchymal stroma" ], "offsets": [ [ 542, 560 ] ], "normalized": [] }, { "id": "PMID-11387198_T12", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 728, 739 ] ], "normalized": [] }, { "id": "PMID-11387198_T14", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 798, 802 ] ], "normalized": [] }, { "id": "PMID-11387198_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 860, 865 ] ], "normalized": [] }, { "id": "PMID-11387198_T16", "type": "Pathological_formation", "text": [ "pre-malignant tumor" ], "offsets": [ [ 927, 946 ] ], "normalized": [] }, { "id": "PMID-11387198_T17", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 962, 967 ] ], "normalized": [] }, { "id": "PMID-11387198_T21", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1071, 1076 ] ], "normalized": [] }, { "id": "PMID-11387198_T22", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1111, 1121 ] ], "normalized": [] }, { "id": "PMID-11387198_T24", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1333, 1338 ] ], "normalized": [] }, { "id": "PMID-11387198_T67", "type": "Cell", "text": [ "stromal" ], "offsets": [ [ 1287, 1294 ] ], "normalized": [] } ]

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[ { "id": "PMC-2946569-sec-02__text", "type": "sec", "text": [ "2. Methods\n\n" ], "offsets": [ [ 0, 12 ] ] } ]

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[ { "id": "PMID-18942118__text", "type": "abstract", "text": [ "PI3K/Akt-dependent transcriptional regulation and activation of BMP-2-Smad signaling by NF-kappaB in metastatic prostate cancer cells. \nBACKGROUND: Bone morphogenetic proteins (BMPs) exert osteoinductive effects in prostate cancer (PC) via uncharacterized mechanisms. In this study, we investigated whether the nuclear transcription factor NF-kappaB, implicated in PC metastasis, is involved in transcriptional regulation and activation of BMP-2 or BMP-4/Smad signaling in PC cells. METHODS: NF-kappaB inhibition was achieved by IkappaBalpha super-repressor adenoviral vector and activation was monitored by EMSA and reporter assays. BMP expression and activation was measured by PCR and reporter assays. Promoter binding assay was performed by chromatin immunoprecipitation (ChIP) assay. Smad1/5/8 phosphorylation was measured by Western blot analysis. RESULTS: PCR and chimeric BMP-2 and BMP-4 luciferase assays demonstrate that NF-kappaB confers robust and selective activation of BMP-2 in p65 overexpressing or rhTNF-alpha-stimulated PC cells. Inhibition of NF-kappaB significantly reduced transcript levels and autocrine production of BMP-2 by rhTNF-alpha stimulated C4-2B cells and to a lesser extent by the parental LNCaP cells. Selective inhibition of PI3K/Akt suppressed the NF-kappaB-induced BMP-2 promoter activity. Furthermore, suppression of NF-kappaB activation decreased the transcript levels and BMP-2-induced phosphorylation of Smad1/5/8, critical downstream targets of BMP-2 signaling in PC cells. Notably, the activation of BMPRII by BMP-2 is required for modulation of Smad activation by NF-kappaB in PC cells. Based on ChIP analysis, the transcriptional regulation of BMP-2 gene by NF-kappaB may be partially attributed to binding to kappab site on the BMP-2 promoter. CONCLUSIONS: The data suggest that PI3K/Akt-NF-kappaB axis may promote PC bone metastasis in part by regulating transcription and activation of the BMP-2-Smad signaling cascade in osteotropic PC cells.\n" ], "offsets": [ [ 0, 1992 ] ] } ]

[ { "id": "PMID-18942118_T6", "type": "Cell", "text": [ "metastatic prostate cancer cells" ], "offsets": [ [ 101, 133 ] ], "normalized": [] }, { "id": "PMID-18942118_T7", "type": "Organ", "text": [ "Bone" ], "offsets": [ [ 148, 152 ] ], "normalized": [] }, { "id": "PMID-18942118_T8", "type": "Cancer", "text": [ "prostate cancer" ], "offsets": [ [ 215, 230 ] ], "normalized": [] }, { "id": "PMID-18942118_T9", "type": "Cancer", "text": [ "PC" ], "offsets": [ [ 232, 234 ] ], "normalized": [] }, { "id": "PMID-18942118_T10", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 311, 318 ] ], "normalized": [] }, { "id": "PMID-18942118_T12", "type": "Cancer", "text": [ "PC" ], "offsets": [ [ 365, 367 ] ], "normalized": [] }, { "id": "PMID-18942118_T16", "type": "Cell", "text": [ "PC cells" ], "offsets": [ [ 473, 481 ] ], "normalized": [] }, { "id": "PMID-18942118_T20", "type": "Cellular_component", "text": [ "chromatin" ], "offsets": [ [ 745, 754 ] ], "normalized": [] }, { "id": "PMID-18942118_T30", "type": "Cell", "text": [ "PC cells" ], "offsets": [ [ 1038, 1046 ] ], "normalized": [] }, { "id": "PMID-18942118_T34", "type": "Cell", "text": [ "C4-2B cells" ], "offsets": [ [ 1172, 1183 ] ], "normalized": [] }, { "id": "PMID-18942118_T35", "type": "Cell", "text": [ "LNCaP cells" ], "offsets": [ [ 1223, 1234 ] ], "normalized": [] }, { "id": "PMID-18942118_T46", "type": "Cell", "text": [ "PC cells" ], "offsets": [ [ 1506, 1514 ] ], "normalized": [] }, { "id": "PMID-18942118_T51", "type": "Cell", "text": [ "PC cells" ], "offsets": [ [ 1621, 1629 ] ], "normalized": [] }, { "id": "PMID-18942118_T59", "type": "Multi-tissue_structure", "text": [ "PC bone" ], "offsets": [ [ 1861, 1868 ] ], "normalized": [] }, { "id": "PMID-18942118_T62", "type": "Cell", "text": [ "osteotropic PC cells" ], "offsets": [ [ 1970, 1990 ] ], "normalized": [] } ]

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[ { "id": "PMID-18393343__text", "type": "abstract", "text": [ "A practical interface for microfluidics and nanoelectrospray mass spectrometry.\nWe report a new method for fabricating nanospray ionization tips for MS, formed from glass substrates and the inert polymer, parylene-C. Using a single photolithography step, the emitters are formed contiguously with microchannels, such that no dead volumes are observed. In addition, because the devices are very thin (approximately 0.3 mm) and the tips are formed at rectangular corners, the Taylor cone volumes are small, which makes the method attractive for future integration with microfluidic separations. Device performance was demonstrated by evaluating diverse analytes, ranging from synthetic polymers, to peptides, to nucleic acids. For all analytes, performance was similar to that of conventional emitters (pulled-glass capillaries and the Agilent HPLC Chip) with the advantage of rapid, batch fabrication of identical devices.\n" ], "offsets": [ [ 0, 922 ] ] } ]

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[ { "id": "PMID-18194650__text", "type": "abstract", "text": [ "Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia.\nVascular endothelial growth factor (VEGF) and Angiopoietin 1 (Ang1) are both potent proangiogenic factors, but, whereas VEGF causes vascular permeability, Ang1 stabilizes blood vessels and protects them from VEGF-induced plasma leakage. The antivascular permeability mechanisms deployed by Ang1 are still undefined. Here, we demonstrate that Ang1 halts the ability of VEGF to induce the phosphorylation-dependent redistribution of the adhesion molecule VE-cadherin, thereby rescuing the endothelial barrier function. Ang1 inhibits the activation of Src by VEGF, the most upstream component of the pathway linking VEGF receptors to VE-cadherin internalization. Indeed, Ang1 promotes the activation of mDia through RhoA, resulting in the association of mDia with Src. This ultimately deprives VEGF receptors of an essential molecule required for promoting the disruption of endothelial cell-cell contacts and paracellular permeability.\n" ], "offsets": [ [ 0, 1030 ] ] } ]

[ { "id": "PMID-18194650_T3", "type": "Tissue", "text": [ "endothelial" ], "offsets": [ [ 37, 48 ] ], "normalized": [] }, { "id": "PMID-18194650_T11", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 228, 236 ] ], "normalized": [] }, { "id": "PMID-18194650_T13", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 267, 280 ] ], "normalized": [] }, { "id": "PMID-18194650_T15", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 317, 323 ] ], "normalized": [] }, { "id": "PMID-18194650_T16", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 341, 349 ] ], "normalized": [] }, { "id": "PMID-18194650_T21", "type": "Tissue", "text": [ "endothelial barrier" ], "offsets": [ [ 583, 602 ] ], "normalized": [] }, { "id": "PMID-18194650_T34", "type": "Immaterial_anatomical_entity", "text": [ "paracellular" ], "offsets": [ [ 1003, 1015 ] ], "normalized": [] }, { "id": "PMID-18194650_T1", "type": "Cellular_component", "text": [ "endothelial cell-cell contacts" ], "offsets": [ [ 968, 998 ] ], "normalized": [] } ]

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[ { "id": "PMID-17608264__text", "type": "abstract", "text": [ "An assay to measure angiogenesis in human fat tissue.\nBACKGROUND: Inhibition of angiogenesis reverses rodent obesity. A validated assay in human fat tissue is needed to study the role of angiogenesis in human obesity. METHODS: Human fat tissue fragments from surgery were placed in 96-well plates, embedded in fibrin thrombin clot and overlaid with cell culture media containing 20% fetal bovine serum. After 15 days, the clots were examined by histology and electron microscopy. The effect of taxol, cobalt chloride and a heparin-steroid combination was tested in the fat tissue assay and compared to the validated human placental vein angiogenesis model (HPVAM). RESULTS: Blood vessels initiated growth and elongated from the fat tissue fragments over 15 days. Presence of blood vessels was confirmed with histology and electron microscopy. Taxol at 10(-6) and 10(-7) M completely inhibited angiogenesis, while Taxol 10(-8) and 10(-9) M and the heparin-steroid partially inhibited angiogenesis. The response to taxol and heparin-steroid was similar to that of the HPVAM, a validated angiogenesis assay. Cobalt chloride, a stimulator of vascular endothelial growth factor (VEGF) stimulated angiogenesis initiation at 10(-9) M in fat tissue and the HPVAM, but at 10(-10) M blood vessel growth was stimulated only in the fat assay. CONCLUSION: This angiogenesis assay based on human fat tissue uses three-dimensionally intact human tissue. The vessels are derived from quiescient vessels within the fat. These properties allow the angiogenic switch to be evaluated in an in vitro setting. The angiogenic response of fat tissue is not identical to placental tissue. This assay allows exploration of angiogenesis in fat tissue.\n" ], "offsets": [ [ 0, 1725 ] ] } ]

[ { "id": "PMID-17608264_T2", "type": "Tissue", "text": [ "fat tissue" ], "offsets": [ [ 42, 52 ] ], "normalized": [] }, { "id": "PMID-17608264_T4", "type": "Tissue", "text": [ "fat tissue" ], "offsets": [ [ 145, 155 ] ], "normalized": [] }, { "id": "PMID-17608264_T7", "type": "Tissue", "text": [ "fat tissue fragments" ], "offsets": [ [ 233, 253 ] ], "normalized": [] }, { "id": "PMID-17608264_T10", "type": "Organism_substance", "text": [ "clot" ], "offsets": [ [ 326, 330 ] ], "normalized": [] }, { "id": "PMID-17608264_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 349, 353 ] ], "normalized": [] }, { "id": "PMID-17608264_T13", "type": "Organism_substance", "text": [ "fetal bovine serum" ], "offsets": [ [ 383, 401 ] ], "normalized": [] }, { "id": "PMID-17608264_T14", "type": "Organism_substance", "text": [ "clots" ], "offsets": [ [ 422, 427 ] ], "normalized": [] }, { "id": "PMID-17608264_T18", "type": "Tissue", "text": [ "fat tissue" ], "offsets": [ [ 569, 579 ] ], "normalized": [] }, { "id": "PMID-17608264_T20", "type": "Multi-tissue_structure", "text": [ "placental vein" ], "offsets": [ [ 622, 636 ] ], "normalized": [] }, { "id": "PMID-17608264_T21", "type": "Multi-tissue_structure", "text": [ "Blood vessels" ], "offsets": [ [ 674, 687 ] ], "normalized": [] }, { "id": "PMID-17608264_T22", "type": "Tissue", "text": [ "fat tissue fragments" ], "offsets": [ [ 728, 748 ] ], "normalized": [] }, { "id": "PMID-17608264_T23", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 775, 788 ] ], "normalized": [] }, { "id": "PMID-17608264_T32", "type": "Tissue", "text": [ "fat tissue" ], "offsets": [ [ 1230, 1240 ] ], "normalized": [] }, { "id": "PMID-17608264_T33", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 1273, 1285 ] ], "normalized": [] }, { "id": "PMID-17608264_T34", "type": "Tissue", "text": [ "fat" ], "offsets": [ [ 1320, 1323 ] ], "normalized": [] }, { "id": "PMID-17608264_T36", "type": "Tissue", "text": [ "fat tissue" ], "offsets": [ [ 1382, 1392 ] ], "normalized": [] }, { "id": "PMID-17608264_T38", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1431, 1437 ] ], "normalized": [] }, { "id": "PMID-17608264_T39", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 1443, 1450 ] ], "normalized": [] }, { "id": "PMID-17608264_T40", "type": "Multi-tissue_structure", "text": [ "quiescient vessels" ], "offsets": [ [ 1468, 1486 ] ], "normalized": [] }, { "id": "PMID-17608264_T41", "type": "Tissue", "text": [ "fat" ], "offsets": [ [ 1498, 1501 ] ], "normalized": [] }, { "id": "PMID-17608264_T42", "type": "Tissue", "text": [ "fat tissue" ], "offsets": [ [ 1615, 1625 ] ], "normalized": [] }, { "id": "PMID-17608264_T43", "type": "Tissue", "text": [ "placental tissue" ], "offsets": [ [ 1646, 1662 ] ], "normalized": [] }, { "id": "PMID-17608264_T44", "type": "Tissue", "text": [ "fat tissue" ], "offsets": [ [ 1713, 1723 ] ], "normalized": [] } ]

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[ { "id": "PMID-1945393__text", "type": "abstract", "text": [ "[Incidence of fungal infection in surgical diseases of the pancreas].\nRecently the number of mycotic infections has increased significantly. Authors have observed 13 mycotic infections on operated patients suffering pancreatic diseases between 1984 and 1990. 9 of 13 patients had pancreatic abscesses as well. The risk factors of fungal infections are analysed. It is important to take differentiation between fungal colonisation and septicaemia caused by yeasts. Repeated microbiological examinations can promote recognising of the fungal invasion. The base of the therapy is to avoid risk factors of infections and to use antifungal medication in time.\n" ], "offsets": [ [ 0, 655 ] ] } ]

[ { "id": "PMID-1945393_T1", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 59, 67 ] ], "normalized": [] }, { "id": "PMID-1945393_T2", "type": "Organ", "text": [ "pancreatic" ], "offsets": [ [ 216, 226 ] ], "normalized": [] }, { "id": "PMID-1945393_T3", "type": "Pathological_formation", "text": [ "pancreatic abscesses" ], "offsets": [ [ 280, 300 ] ], "normalized": [] } ]

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[ { "id": "PMID-9931156__text", "type": "abstract", "text": [ "Selective inhibition of the renal dopamine subtype D1A receptor induces antinatriuresis in conscious rats.\nBoth dopamine D1-like (D1A and D1B) and D2-like (D2, D3, and D4) receptor subfamilies are present in the kidney. Blockade of the intrarenal D1-like receptor family is associated with natriuresis and diuresis. Because the D1A and D1B receptor subtypes are not distinguishable by currently available dopaminergic agents, their functional role remains undefined. In the present study, the effect of selective inhibition of the renal D1A receptor with phosphorothioated antisense oligodeoxynucleotide (AS-ODN) was investigated in conscious uninephrectomized rats. After renal interstitial administration of Texas red-labeled D1A receptor AS-ODN, intense fluorescent signal was localized in the renal tubular epithelium and vasculature. In rats on normal salt intake, AS-ODN injected interstitially into the kidney reduced daily urinary sodium excretion (1.4+/-0.04 versus 0.8+/-0.2 mEq/d, n=5, P<0.05) and urine output (16.9+/-3.8 versus 12.5+/-3.6 mL/d, n=5, P<0.05). In rats on high sodium intake, continuous renal interstitial administration of D1A receptor AS-ODN transiently decreased daily urinary sodium excretion (5.4+/-0.5 versus 4.2+/-0.3 mEq/d, n=7, P<0.01) and urine output (27.6+/-4.5 versus 18.1+/-1.8 mL/d, n=7, P<0.01). Neither vehicle nor sense oligodeoxynucleotide had significant effects. Systolic blood pressure remained unchanged. The renal D1A receptor protein was significantly decreased by 35% and 46% at the end of the study in AS-ODN-treated rats on normal and high salt intake, respectively, whereas the D1B receptor and beta-actin were not affected. These results provide the first direct evidence that the renal D1A receptor subtype plays an important role in the control of sodium excretion.\n" ], "offsets": [ [ 0, 1825 ] ] } ]

[ { "id": "PMID-9931156_T1", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 28, 33 ] ], "normalized": [] }, { "id": "PMID-9931156_T2", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 212, 218 ] ], "normalized": [] }, { "id": "PMID-9931156_T3", "type": "Immaterial_anatomical_entity", "text": [ "renal interstitial" ], "offsets": [ [ 673, 691 ] ], "normalized": [] }, { "id": "PMID-9931156_T4", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 531, 536 ] ], "normalized": [] }, { "id": "PMID-9931156_T5", "type": "Tissue", "text": [ "renal tubular epithelium" ], "offsets": [ [ 797, 821 ] ], "normalized": [] }, { "id": "PMID-9931156_T6", "type": "Multi-tissue_structure", "text": [ "vasculature" ], "offsets": [ [ 826, 837 ] ], "normalized": [] }, { "id": "PMID-9931156_T7", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 910, 916 ] ], "normalized": [] }, { "id": "PMID-9931156_T8", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 931, 938 ] ], "normalized": [] }, { "id": "PMID-9931156_T9", "type": "Organism_substance", "text": [ "urine" ], "offsets": [ [ 1009, 1014 ] ], "normalized": [] }, { "id": "PMID-9931156_T10", "type": "Immaterial_anatomical_entity", "text": [ "renal interstitial" ], "offsets": [ [ 1114, 1132 ] ], "normalized": [] }, { "id": "PMID-9931156_T11", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 1199, 1206 ] ], "normalized": [] }, { "id": "PMID-9931156_T12", "type": "Organism_substance", "text": [ "urine" ], "offsets": [ [ 1276, 1281 ] ], "normalized": [] }, { "id": "PMID-9931156_T13", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 1420, 1425 ] ], "normalized": [] }, { "id": "PMID-9931156_T14", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 1459, 1464 ] ], "normalized": [] }, { "id": "PMID-9931156_T15", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 1738, 1743 ] ], "normalized": [] } ]

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[ { "id": "PMID-10417401__text", "type": "abstract", "text": [ "Bradycardia-induced coronary angiogenesis is dependent on vascular endothelial growth factor.\nA marked coronary angiogenesis is known to occur with chronic bradycardia. We tested the hypothesis that vascular endothelial growth factor (VEGF), an endothelial cell mitogen and a major regulator of angiogenesis, is upregulated in response to low heart rate and consequential increased stroke volume. Bradycardia was induced in rats by administering the bradycardic drug alinidine (3 mg/kg body weight) twice daily. Heart rate decreased by 32% for 20 to 40 minutes after injection and was chronically reduced by 10%, 14%, and 18.5% after 1, 2, and 3 weeks of treatment, respectively. Arterial pressure and cardiac output were unchanged. Left ventricular capillary length density (mm/mm(3)) increased gradually with alinidine administration; a 15% increase after 2 weeks and a 40% increase after 3 weeks of alinidine treatment were documented. Left ventricular weight, body weight, and their ratio were not significantly altered by alinidine treatment. After 1 week of treatment, before an increase in capillary length density, VEGF mRNA increased greater than 2-fold and then declined to control levels after 3 weeks of treatment. VEGF protein was higher in alinidine-treated rats than in controls after 2 weeks and increased further after 3 weeks of treatment. Injection of VEGF-neutralizing antibodies over a 2-week period completely blocked alinidine-stimulated angiogenesis. In contrast, bFGF mRNA was not altered by alinidine treatment. These data suggest that VEGF plays a key role in the angiogenic response that occurs with chronic bradycardia. The mechanism underlying this VEGF-associated angiogenesis may be an increase in stretch due to enhanced diastolic filling.\n" ], "offsets": [ [ 0, 1774 ] ] } ]

[ { "id": "PMID-10417401_T1", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 20, 28 ] ], "normalized": [] }, { "id": "PMID-10417401_T3", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 103, 111 ] ], "normalized": [] }, { "id": "PMID-10417401_T6", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 245, 261 ] ], "normalized": [] }, { "id": "PMID-10417401_T7", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 343, 348 ] ], "normalized": [] }, { "id": "PMID-10417401_T10", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "PMID-10417401_T11", "type": "Organ", "text": [ "Heart" ], "offsets": [ [ 512, 517 ] ], "normalized": [] }, { "id": "PMID-10417401_T12", "type": "Multi-tissue_structure", "text": [ "Arterial" ], "offsets": [ [ 680, 688 ] ], "normalized": [] }, { "id": "PMID-10417401_T13", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 702, 709 ] ], "normalized": [] }, { "id": "PMID-10417401_T14", "type": "Tissue", "text": [ "Left ventricular capillary" ], "offsets": [ [ 733, 759 ] ], "normalized": [] }, { "id": "PMID-10417401_T17", "type": "Multi-tissue_structure", "text": [ "Left ventricular" ], "offsets": [ [ 939, 955 ] ], "normalized": [] }, { "id": "PMID-10417401_T18", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 964, 968 ] ], "normalized": [] }, { "id": "PMID-10417401_T20", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 1097, 1106 ] ], "normalized": [] } ]

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[ { "id": "PMID-19575421__text", "type": "abstract", "text": [ "Desipramine inhibits the growth of a mouse skin squamous cell carcinoma cell line and affects glucocorticoid receptor-mediated transcription. \nThe purpose of this study was to examine the effect of tricyclic antidepressant desipramine (DMI) on the growth inhibition and translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus in cancerous and noncancerous cell lines and the effect of DMI on GR-mediated transcription. Nontumorigenic, immortalized keratinocytes cell line (3PC), papilloma (MT1/2), and squamous cell carcinoma (Ca3/7) cell lines were initially used to study the cell growth inhibition by DMI. Although, the growth of all three cell lines was suppressed by DMI, it was more effective in Ca3/7 cells. Therefore, we next examined the effect of DMI on Ca3/7 cells, resistant to growth inhibition by the synthetic glucocorticoid fluocinolone acetonide (FA). DMI inhibited cell proliferation in a time-dependent manner. The translocation of GR was induced by FA alone, DMI alone, and combination of both agents. FA induced GR-mediated transcription in Ca3/7 cells transfected with a luciferase reporter gene under the control of glucocorticoid response element (GRE), but DMI alone did not affect GR-mediated transcription. However, DMI inhibited FA-induced, GR-mediated transcription when both agents were given together. Pretreatment with DMI followed by combination of DMI and FA decreased GR-mediated transcription more than pretreatment with FA. The expression of metallothionein-1 (Mt-1) gene, which is regulated by GR, was induced significantly by the combination of DMI and FA, and enhanced significantly by pretreatment with FA but not DMI. DMI is suggested to inhibit the growth of Ca3/7 cells and to affect GR-mediated transcription.\n" ], "offsets": [ [ 0, 1783 ] ] } ]

[ { "id": "PMID-19575421_T3", "type": "Cell", "text": [ "skin squamous cell carcinoma cell line" ], "offsets": [ [ 43, 81 ] ], "normalized": [] }, { "id": "PMID-19575421_T9", "type": "Organism_substance", "text": [ "cytoplasm" ], "offsets": [ [ 329, 338 ] ], "normalized": [] }, { "id": "PMID-19575421_T10", "type": "Cellular_component", "text": [ "nucleus" ], "offsets": [ [ 346, 353 ] ], "normalized": [] }, { "id": "PMID-19575421_T11", "type": "Cell", "text": [ "cancerous" ], "offsets": [ [ 357, 366 ] ], "normalized": [] }, { "id": "PMID-19575421_T12", "type": "Cell", "text": [ "noncancerous cell lines" ], "offsets": [ [ 371, 394 ] ], "normalized": [] }, { "id": "PMID-19575421_T15", "type": "Cell", "text": [ "keratinocytes cell line" ], "offsets": [ [ 476, 499 ] ], "normalized": [] }, { "id": "PMID-19575421_T16", "type": "Cell", "text": [ "3PC" ], "offsets": [ [ 501, 504 ] ], "normalized": [] }, { "id": "PMID-19575421_T17", "type": "Cell", "text": [ "papilloma" ], "offsets": [ [ 507, 516 ] ], "normalized": [] }, { "id": "PMID-19575421_T18", "type": "Cell", "text": [ "MT1/2" ], "offsets": [ [ 518, 523 ] ], "normalized": [] }, { "id": "PMID-19575421_T21", "type": "Cell", "text": [ "squamous cell carcinoma (Ca3/7) cell lines" ], "offsets": [ [ 530, 572 ] ], "normalized": [] }, { "id": "PMID-19575421_T22", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 606, 610 ] ], "normalized": [] }, { "id": "PMID-19575421_T24", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 671, 681 ] ], "normalized": [] }, { "id": "PMID-19575421_T26", "type": "Cell", "text": [ "Ca3/7 cells" ], "offsets": [ [ 730, 741 ] ], "normalized": [] }, { "id": "PMID-19575421_T28", "type": "Cell", "text": [ "Ca3/7 cells" ], "offsets": [ [ 792, 803 ] ], "normalized": [] }, { "id": "PMID-19575421_T32", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 911, 915 ] ], "normalized": [] }, { "id": "PMID-19575421_T38", "type": "Cell", "text": [ "Ca3/7 cells" ], "offsets": [ [ 1090, 1101 ] ], "normalized": [] }, { "id": "PMID-19575421_T58", "type": "Cell", "text": [ "Ca3/7 cells" ], "offsets": [ [ 1730, 1741 ] ], "normalized": [] } ]

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[ { "id": "PMID-18188789__text", "type": "abstract", "text": [ "[Photodynamic therapy in severe chronic central serous chorioretinopaty]\nOBJECTIVE: To determine the efficacy of Photodynamic Therapy (PDT) in chronic Central Serous Chorioretinopathy (CSC). METHODS: Patients diagnosed with chronic CSC, with clinical evidence of activity and treated with Photodynamic Therapy, are included in this report. All were assessed by a complete ophthalmological examination, including assessment of the best corrected visual acuity (BCVA) using an ETDRS chart, fluorescein and indocyanine angiography and optical coherence tomography (OCT). The main objective of the study was to determine the mean visual acuity change. RESULTS: 11 eyes of 11 patients were included in the study, which had a mean follow-up period of 11 months. The mean BCVA increased from 20/76 to 20/64. 35% of eyes improved their BCVA by 2 lines or more, 45% remained stable and 18% lost 2 lines or more. Choroidal hyperpermeability was reduced in every case. Neurosensorial retinal detachment decreased in 80% of cases. Only one eye received a second PDT treatment due to choroidal neovascularization. An increase of atrophy over the Retinal Pigment Epithelium (RPE) was observed in another patient. CONCLUSIONS: PDT can reduce the clinical signs of activity, such as choroidal hyperpermeability or neurosensorial retinal detachment, in patients affected by chronic CSC. However, the increase in visual acuity is variable, probably due to the extent of RPE damage.\n" ], "offsets": [ [ 0, 1464 ] ] } ]

[ { "id": "PMID-18188789_T1", "type": "Organism_substance", "text": [ "serous" ], "offsets": [ [ 48, 54 ] ], "normalized": [] }, { "id": "PMID-18188789_T2", "type": "Organism_substance", "text": [ "Serous" ], "offsets": [ [ 159, 165 ] ], "normalized": [] }, { "id": "PMID-18188789_T6", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 660, 664 ] ], "normalized": [] }, { "id": "PMID-18188789_T8", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 808, 812 ] ], "normalized": [] }, { "id": "PMID-18188789_T9", "type": "Multi-tissue_structure", "text": [ "Choroidal" ], "offsets": [ [ 903, 912 ] ], "normalized": [] }, { "id": "PMID-18188789_T10", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 973, 980 ] ], "normalized": [] }, { "id": "PMID-18188789_T11", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 1028, 1031 ] ], "normalized": [] }, { "id": "PMID-18188789_T12", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 1071, 1080 ] ], "normalized": [] }, { "id": "PMID-18188789_T13", "type": "Tissue", "text": [ "Retinal Pigment Epithelium" ], "offsets": [ [ 1133, 1159 ] ], "normalized": [] }, { "id": "PMID-18188789_T14", "type": "Tissue", "text": [ "RPE" ], "offsets": [ [ 1161, 1164 ] ], "normalized": [] }, { "id": "PMID-18188789_T16", "type": "Multi-tissue_structure", "text": [ "choroidal" ], "offsets": [ [ 1267, 1276 ] ], "normalized": [] }, { "id": "PMID-18188789_T17", "type": "Multi-tissue_structure", "text": [ "retinal" ], "offsets": [ [ 1313, 1320 ] ], "normalized": [] }, { "id": "PMID-18188789_T19", "type": "Tissue", "text": [ "RPE" ], "offsets": [ [ 1452, 1455 ] ], "normalized": [] } ]

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[ { "id": "PMID-4066990__text", "type": "abstract", "text": [ "Rapid enzyme analysis of amniotic fluid phospholipids containing choline: a comparison with the lecithin to sphingomyelin ratio in prenatal assessment of fetal lung maturity.\nThe relation between the choline containing surfactant phospholipids lecithin and sphingomyelin in amniotic fluid and fetal lung maturity is well established. An enzymatic method that had been automated and optimised for use on a centrifugal analyser was used to measure the total choline containing phospholipids in amniotic fluid. The total time taken for this assay was 10 minutes. The results obtained from 100 patient samples, using this procedure, compared favourably with the results obtained by the thin layer chromatography procedure used to determine the lecithin to sphingomyelin ratio (r = 0.93). A clinical study of 60 patients showed that this assay predicted prenatal respiratory distress syndrome as well as the lecithin to sphingomyelin ratios. The advantage of this assay over existing procedures is that it requires minimum preparation of the specimen and no extraction, is quick, and shows a high degree of precision.\n" ], "offsets": [ [ 0, 1113 ] ] } ]

[ { "id": "PMID-4066990_T1", "type": "Organism_substance", "text": [ "amniotic fluid" ], "offsets": [ [ 25, 39 ] ], "normalized": [] }, { "id": "PMID-4066990_T2", "type": "Organism_substance", "text": [ "amniotic fluid" ], "offsets": [ [ 274, 288 ] ], "normalized": [] }, { "id": "PMID-4066990_T3", "type": "Organ", "text": [ "fetal lung" ], "offsets": [ [ 293, 303 ] ], "normalized": [] }, { "id": "PMID-4066990_T4", "type": "Organ", "text": [ "fetal lung" ], "offsets": [ [ 154, 164 ] ], "normalized": [] }, { "id": "PMID-4066990_T5", "type": "Organism_substance", "text": [ "amniotic fluid" ], "offsets": [ [ 492, 506 ] ], "normalized": [] }, { "id": "PMID-4066990_T6", "type": "Organism_substance", "text": [ "specimen" ], "offsets": [ [ 1037, 1045 ] ], "normalized": [] }, { "id": "PMID-4066990_T7", "type": "Anatomical_system", "text": [ "respiratory" ], "offsets": [ [ 858, 869 ] ], "normalized": [] }, { "id": "PMID-4066990_T8", "type": "Organism_substance", "text": [ "samples" ], "offsets": [ [ 598, 605 ] ], "normalized": [] } ]

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[ { "id": "PMID-10645002__text", "type": "abstract", "text": [ "Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. \nAutotaxin (ATX), an exo-nucleotide pyrophosphatase and phosphodiesterase, was originally isolated as a potent stimulator of tumor cell motility. In order to study whether ATX expression affects motility-dependent processes such as invasion and metastasis, we stably transfected full-length ATX cDNA into two non-expressing cell lines, parental and ras-transformed NIH3T3 (clone7) cells. The effect of ATX secretion on in vitro cell motility was variable. The ras-transformed, ATX-secreting subclones had enhanced motility to ATX as chemoattractant, but there was little difference in the motility responses of NIH3T3 cells transfected with atx, an inactive mutant gene, or empty vector. In MatrigelTM invasion assays, all subclones, which secreted enzymatically active ATX, demonstrated greater spontaneous and ATX-stimulated invasion than appropriate controls. This difference in invasiveness was not caused by differences in gelatinase production, which was constant within each group of transfectants. In vivo studies with athymic nude mice demonstrated that injection of atx-transfected NIH3T3 cells resulted in a weak tumorigenic capacity with few experimental metastases. Combination of ATX expression with ras transformation produced cells with greatly amplified tumorigenesis and metastatic potential compared to ras-transformed controls. Thus, ATX appears to augment cellular characteristics necessary for tumor aggressiveness.\n" ], "offsets": [ [ 0, 1548 ] ] } ]

[ { "id": "PMID-10645002_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 26, 31 ] ], "normalized": [] }, { "id": "PMID-10645002_T5", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 103, 108 ] ], "normalized": [] }, { "id": "PMID-10645002_T8", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 235, 245 ] ], "normalized": [] }, { "id": "PMID-10645002_T11", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 434, 444 ] ], "normalized": [] }, { "id": "PMID-10645002_T13", "type": "Cell", "text": [ "NIH3T3 (clone7) cells" ], "offsets": [ [ 475, 496 ] ], "normalized": [] }, { "id": "PMID-10645002_T15", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 538, 542 ] ], "normalized": [] }, { "id": "PMID-10645002_T18", "type": "Cell", "text": [ "subclones" ], "offsets": [ [ 601, 610 ] ], "normalized": [] }, { "id": "PMID-10645002_T20", "type": "Cell", "text": [ "NIH3T3 cells" ], "offsets": [ [ 721, 733 ] ], "normalized": [] }, { "id": "PMID-10645002_T22", "type": "Cell", "text": [ "subclones" ], "offsets": [ [ 833, 842 ] ], "normalized": [] }, { "id": "PMID-10645002_T26", "type": "Cell", "text": [ "transfectants" ], "offsets": [ [ 1101, 1114 ] ], "normalized": [] }, { "id": "PMID-10645002_T29", "type": "Cell", "text": [ "NIH3T3 cells" ], "offsets": [ [ 1202, 1214 ] ], "normalized": [] }, { "id": "PMID-10645002_T32", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1352, 1357 ] ], "normalized": [] }, { "id": "PMID-10645002_T34", "type": "Cell", "text": [ "controls" ], "offsets": [ [ 1448, 1456 ] ], "normalized": [] }, { "id": "PMID-10645002_T36", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1487, 1495 ] ], "normalized": [] }, { "id": "PMID-10645002_T37", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1526, 1531 ] ], "normalized": [] }, { "id": "PMID-10645002_T1", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 1277, 1287 ] ], "normalized": [] } ]

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[ { "id": "PMID-16771309__text", "type": "abstract", "text": [ "Dendrimer-templated Fe nanoparticles for the growth of single-wall carbon nanotubes by plasma-enhanced CVD.\nA fourth-generation (G4) poly(amidoamine) (PAMAM) dendrimer (G4-NH2) has been used as a template to deliver nearly monodispersed catalyst nanoparticles to SiO2/Si, Ti/Si, sapphire, and porous anodic alumina (PAA) substrates. Fe2O3 nanoparticles obtained after calcination of the immobilized Fe3+/G4-NH2 composite served as catalytic \"seeds\" for the growth of single-wall carbon nanotubes (SWNTs) by microwave plasma-enhanced CVD (PECVD). To surmount the difficulty associated with SWNT growth via PECVD, reaction conditions that promote the stabilization of Fe nanoparticles, resulting in enhanced SWNT selectivity and quality, have been identified. In particular, in situ annealing of Fe catalyst in an N2 atmosphere was found to improve SWNT selectivity and quality. H2 prereduction at 900 degrees C for 5 min was also found to enhance SWNT selectivity and quality for SiO2/Si supported catalyst, albeit of lower quality for sapphire supported catalyst. The application of positive dc bias voltage (+200 V) during SWNT growth was shown to be very effective in removing amorphous carbon impurities while enhancing graphitization, SWNT selectivity, and vertical alignment. The results of this study should promote the use of exposed Fe nanoparticles supported on different substrates for the growth of high-quality SWNTs by PECVD.\n" ], "offsets": [ [ 0, 1439 ] ] } ]

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[ { "id": "PMID-18852899__text", "type": "abstract", "text": [ "M-CSF signals through the MAPK/ERK pathway via Sp1 to induce VEGF production and induces angiogenesis in vivo.\nBACKGROUND: M-CSF recruits mononuclear phagocytes which regulate processes such as angiogenesis and metastases in tumors. VEGF is a potent activator of angiogenesis as it promotes endothelial cell proliferation and new blood vessel formation. Previously, we reported that in vitro M-CSF induces the expression of biologically-active VEGF from human monocytes. METHODOLOGY AND RESULTS: In this study, we demonstrate the molecular mechanism of M-CSF-induced VEGF production. Using a construct containing the VEGF promoter linked to a luciferase reporter, we found that a mutation reducing HIF binding to the VEGF promoter had no significant effect on luciferase production induced by M-CSF stimulation. Further analysis revealed that M-CSF induced VEGF through the MAPK/ERK signaling pathway via the transcription factor, Sp1. Thus, inhibition of either ERK or Sp1 suppressed M-CSF-induced VEGF at the mRNA and protein level. M-CSF also induced the nuclear localization of Sp1, which was blocked by ERK inhibition. Finally, mutating the Sp1 binding sites within the VEGF promoter or inhibiting ERK decreased VEGF promoter activity in M-CSF-treated human monocytes. To evaluate the biological significance of M-CSF induced VEGF production, we used an in vivo angiogenesis model to illustrate the ability of M-CSF to recruit mononuclear phagocytes, increase VEGF levels, and enhance angiogenesis. Importantly, the addition of a neutralizing VEGF antibody abolished M-CSF-induced blood vessel formation. CONCLUSION: These data delineate an ERK- and Sp1-dependent mechanism of M-CSF induced VEGF production and demonstrate for the first time the ability of M-CSF to induce angiogenesis via VEGF in vivo.\n" ], "offsets": [ [ 0, 1809 ] ] } ]

[ { "id": "PMID-18852899_T7", "type": "Cell", "text": [ "mononuclear phagocytes" ], "offsets": [ [ 138, 160 ] ], "normalized": [] }, { "id": "PMID-18852899_T8", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 225, 231 ] ], "normalized": [] }, { "id": "PMID-18852899_T10", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 291, 307 ] ], "normalized": [] }, { "id": "PMID-18852899_T11", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 330, 342 ] ], "normalized": [] }, { "id": "PMID-18852899_T15", "type": "Cell", "text": [ "monocytes" ], "offsets": [ [ 460, 469 ] ], "normalized": [] }, { "id": "PMID-18852899_T34", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1058, 1065 ] ], "normalized": [] }, { "id": "PMID-18852899_T43", "type": "Cell", "text": [ "monocytes" ], "offsets": [ [ 1263, 1272 ] ], "normalized": [] }, { "id": "PMID-18852899_T47", "type": "Cell", "text": [ "mononuclear phagocytes" ], "offsets": [ [ 1432, 1454 ] ], "normalized": [] }, { "id": "PMID-18852899_T51", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 1586, 1598 ] ], "normalized": [] }, { "id": "PMID-18852899_T1", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 211, 221 ] ], "normalized": [] } ]

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[ { "id": "PMID-15029197__text", "type": "abstract", "text": [ "The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis.\nGliomas are the most common primary tumours of the central nervous system, with nearly 15,000 diagnosed annually in the United States and a lethality approaching 80% within the first year of glioblastoma diagnosis. The marked induction of angiogenesis in glioblastomas suggests that it is a necessary part of malignant progression; however, the precise molecular mechanisms underlying the regulation of brain tumour growth and angiogenesis remain unresolved. Here we report that a candidate tumour suppressor gene, ING4, is involved in regulating brain tumour growth and angiogenesis. Expression of ING4 is significantly reduced in gliomas as compared with normal human brain tissue, and the extent of reduction correlates with the progression from lower to higher grades of tumours. In mice, xenografts of human glioblastoma U87MG, which has decreased expression of ING4, grow significantly faster and have higher vascular volume fractions than control tumours. We show that ING4 physically interacts with p65 (RelA) subunit of nuclear factor NF-kappaB, and that ING4 regulates brain tumour angiogenesis through transcriptional repression of NF-kappaB-responsive genes. These results indicate that ING4 has an important role in brain tumour pathogenesis.\n" ], "offsets": [ [ 0, 1349 ] ] } ]

[ { "id": "PMID-15029197_T1", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 14, 20 ] ], "normalized": [] }, { "id": "PMID-15029197_T3", "type": "Cancer", "text": [ "brain tumour" ], "offsets": [ [ 55, 67 ] ], "normalized": [] }, { "id": "PMID-15029197_T4", "type": "Cancer", "text": [ "Gliomas" ], "offsets": [ [ 93, 100 ] ], "normalized": [] }, { "id": "PMID-15029197_T5", "type": "Cancer", "text": [ "primary tumours" ], "offsets": [ [ 121, 136 ] ], "normalized": [] }, { "id": "PMID-15029197_T6", "type": "Anatomical_system", "text": [ "central nervous system" ], "offsets": [ [ 144, 166 ] ], "normalized": [] }, { "id": "PMID-15029197_T7", "type": "Cancer", "text": [ "glioblastoma" ], "offsets": [ [ 284, 296 ] ], "normalized": [] }, { "id": "PMID-15029197_T8", "type": "Cancer", "text": [ "glioblastomas" ], "offsets": [ [ 348, 361 ] ], "normalized": [] }, { "id": "PMID-15029197_T9", "type": "Cancer", "text": [ "brain tumour" ], "offsets": [ [ 496, 508 ] ], "normalized": [] }, { "id": "PMID-15029197_T10", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 584, 590 ] ], "normalized": [] }, { "id": "PMID-15029197_T12", "type": "Cancer", "text": [ "brain tumour" ], "offsets": [ [ 640, 652 ] ], "normalized": [] }, { "id": "PMID-15029197_T14", "type": "Cancer", "text": [ "gliomas" ], "offsets": [ [ 725, 732 ] ], "normalized": [] }, { "id": "PMID-15029197_T16", "type": "Tissue", "text": [ "brain tissue" ], "offsets": [ [ 763, 775 ] ], "normalized": [] }, { "id": "PMID-15029197_T17", "type": "Cancer", "text": [ "tumours" ], "offsets": [ [ 868, 875 ] ], "normalized": [] }, { "id": "PMID-15029197_T19", "type": "Cancer", "text": [ "xenografts" ], "offsets": [ [ 886, 896 ] ], "normalized": [] }, { "id": "PMID-15029197_T21", "type": "Cancer", "text": [ "glioblastoma U87MG" ], "offsets": [ [ 906, 924 ] ], "normalized": [] }, { "id": "PMID-15029197_T23", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1008, 1016 ] ], "normalized": [] }, { "id": "PMID-15029197_T24", "type": "Cancer", "text": [ "tumours" ], "offsets": [ [ 1047, 1054 ] ], "normalized": [] }, { "id": "PMID-15029197_T30", "type": "Cancer", "text": [ "brain tumour" ], "offsets": [ [ 1172, 1184 ] ], "normalized": [] }, { "id": "PMID-15029197_T33", "type": "Cancer", "text": [ "brain tumour" ], "offsets": [ [ 1322, 1334 ] ], "normalized": [] } ]

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[ { "id": "PMID-7088434__text", "type": "abstract", "text": [ "Verrucous carcinoma of the endometrium--a unique neoplasm with long survival.\nA case of verrucous carcinoma of the endometrium with long survival is described. It represents the first of its type to be recorded in this site. The literature on verrucous carcinoma and on other cases of squamous carcinoma of the endometrium is briefly reviewed.\n" ], "offsets": [ [ 0, 344 ] ] } ]

[ { "id": "PMID-7088434_T1", "type": "Cancer", "text": [ "Verrucous carcinoma" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "PMID-7088434_T2", "type": "Multi-tissue_structure", "text": [ "endometrium" ], "offsets": [ [ 27, 38 ] ], "normalized": [] }, { "id": "PMID-7088434_T3", "type": "Cancer", "text": [ "neoplasm" ], "offsets": [ [ 49, 57 ] ], "normalized": [] }, { "id": "PMID-7088434_T4", "type": "Cancer", "text": [ "verrucous carcinoma" ], "offsets": [ [ 88, 107 ] ], "normalized": [] }, { "id": "PMID-7088434_T5", "type": "Multi-tissue_structure", "text": [ "endometrium" ], "offsets": [ [ 115, 126 ] ], "normalized": [] }, { "id": "PMID-7088434_T6", "type": "Cancer", "text": [ "verrucous carcinoma" ], "offsets": [ [ 243, 262 ] ], "normalized": [] }, { "id": "PMID-7088434_T7", "type": "Cancer", "text": [ "squamous carcinoma" ], "offsets": [ [ 285, 303 ] ], "normalized": [] }, { "id": "PMID-7088434_T8", "type": "Multi-tissue_structure", "text": [ "endometrium" ], "offsets": [ [ 311, 322 ] ], "normalized": [] }, { "id": "PMID-7088434_T9", "type": "Multi-tissue_structure", "text": [ "site" ], "offsets": [ [ 219, 223 ] ], "normalized": [] } ]

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[ { "id": "PMID-20563198__text", "type": "abstract", "text": [ "Yellow-green 52.3W laser at 556nm based on frequency doubling of a diode side-pumped Q-switched Nd:YAG laser.\nWe demonstrate a high-power 556nm yellow-green laser generated by intracavity frequency doubling of a diode side-pumped Nd:YAG laser at 1112nm. A symmetrical L-shaped flat-flat cavity was employed to implement efficient operation of the low-gain 1112nm transition and to achieve good power scalability. The coatings of the cavity mirrors were carefully designed to optimize the performance of the laser, and a 92W continuous wave laser output at 1112nm was achieved when the pumping power of the laser diodes reached 960W. By intracavity frequency doubling of the fundamental laser in a lithium triborate crystal, the maximum power of the frequency-doubled output at 556nm was found to be as high as 52.3W with a pulse repetition frequency of 10kHz. This corresponds to an optical-to-optical conversion efficiency of about 5.4%.\n" ], "offsets": [ [ 0, 939 ] ] } ]

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[ { "id": "PMID-14981920__text", "type": "abstract", "text": [ "Effect of antitumor agents on cytotoxicity induction by sodium fluoride.\nWe have recently found that sodium fluoride (NaF) induced apoptotic cell death in tumor cell lines. We investigated here whether 6 popular antitumor compounds modify the cytotoxic activity of NaF against human squamous cell carcinoma (HSC-2) and human promyelocytic leukemia (HL-60) cell lines. Cytotoxic concentrations of cisplatin, etoposide, doxorubicin or peplomycin (tentatively termed as Group I compounds), but not methotrexate and 5-FU (tentatively termed as Group II compounds), enhanced the cytotoxic activity of NaF. NaF and Group I compounds induced internucleosomal DNA fragmentation in HL-60 cells, whereas Group II compounds were inactive even in the presence of NaF. Most Group I compounds except doxorubicin (which induced DNA fragmentation less effectively than others) activated caspase 3 more efficiently than Group II compounds. Caspase 8 (involved in non-mitochondrial extrinsic pathway) and caspase 9 (involved in mitochondrial intrinsic pathway) were also activated, but to a much lesser extent. NaF reduced the glucose consumption at early stage, possibly by inhibition of glycolysis, whereas cisplatin and etoposide reduced the glucose consumption at later stage, suggesting that early decline of glucose consumption is rather specific to NaF.\n" ], "offsets": [ [ 0, 1343 ] ] } ]

[ { "id": "PMID-14981920_T1", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-14981920_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 141, 145 ] ], "normalized": [] }, { "id": "PMID-14981920_T6", "type": "Cell", "text": [ "tumor cell lines" ], "offsets": [ [ 155, 171 ] ], "normalized": [] }, { "id": "PMID-14981920_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 216, 221 ] ], "normalized": [] }, { "id": "PMID-14981920_T10", "type": "Cancer", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 283, 306 ] ], "normalized": [] }, { "id": "PMID-14981920_T11", "type": "Cell", "text": [ "HSC-2)" ], "offsets": [ [ 308, 314 ] ], "normalized": [] }, { "id": "PMID-14981920_T14", "type": "Cell", "text": [ "promyelocytic leukemia (HL-60) cell lines" ], "offsets": [ [ 325, 366 ] ], "normalized": [] }, { "id": "PMID-14981920_T24", "type": "Cell", "text": [ "HL-60 cells" ], "offsets": [ [ 673, 684 ] ], "normalized": [] }, { "id": "PMID-14981920_T30", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 950, 963 ] ], "normalized": [] }, { "id": "PMID-14981920_T32", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1010, 1023 ] ], "normalized": [] } ]

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[ { "id": "PMID-15673543__text", "type": "abstract", "text": [ "Reduced prognostic power of ventricular late potentials in post-infarction patients of the reperfusion era.\nAIMS:\nTo test the prognostic value of ventricular late potentials (LPs) in a large cohort of post-infarction patients in the modern reperfusion era.\nMETHODS AND RESULTS:\n1800 consecutive survivors of acute myocardial infarction in sinus rhythm and under 76 years of age were enrolled. Many (99%) of the patients received reperfusion/revascularization therapy (91% percutaneous coronary intervention) and up-to-date pharmacological treatment (99% aspirin, 93% beta-blockers, 90% ACE-inhibitors, and 85% statins). LPs were calculated in 968 patients and found to be present in 90 (9.3%). The primary endpoint was the composite of cardiac death and serious arrhythmic events. The secondary endpoint was the composite of sudden cardiac death and serious arrhythmic events. During follow-up (median 34 months), 26 patients reached the primary endpoint. The presence of LPs was not significantly associated with the primary endpoint in univariable or multivariable analysis. In contrast, low (< or = 30%) left ventricular ejection fraction (hazard ratio 9.6, 95% confidence interval 4.1-22.4), heart rate turbulence category 2 (7.5, 2.4-23.9) and category 1 (5.3, 1.9-14.9) were significant predictors in both univariable and multivariable analysis.\nCONCLUSION:\nVentricular LPs are of limited use for risk stratification in unselected post-infarction patients in the modern reperfusion era.\n" ], "offsets": [ [ 0, 1493 ] ] } ]

[ { "id": "PMID-15673543_T1", "type": "Multi-tissue_structure", "text": [ "ventricular" ], "offsets": [ [ 28, 39 ] ], "normalized": [] }, { "id": "PMID-15673543_T2", "type": "Multi-tissue_structure", "text": [ "ventricular" ], "offsets": [ [ 146, 157 ] ], "normalized": [] }, { "id": "PMID-15673543_T3", "type": "Multi-tissue_structure", "text": [ "myocardial" ], "offsets": [ [ 314, 324 ] ], "normalized": [] }, { "id": "PMID-15673543_T4", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 736, 743 ] ], "normalized": [] }, { "id": "PMID-15673543_T5", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 832, 839 ] ], "normalized": [] }, { "id": "PMID-15673543_T6", "type": "Multi-tissue_structure", "text": [ "left ventricular" ], "offsets": [ [ 1107, 1123 ] ], "normalized": [] }, { "id": "PMID-15673543_T7", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 1196, 1201 ] ], "normalized": [] }, { "id": "PMID-15673543_T8", "type": "Multi-tissue_structure", "text": [ "Ventricular" ], "offsets": [ [ 1364, 1375 ] ], "normalized": [] }, { "id": "PMID-15673543_T9", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 485, 493 ] ], "normalized": [] }, { "id": "PMID-15673543_T11", "type": "Immaterial_anatomical_entity", "text": [ "percutaneous" ], "offsets": [ [ 472, 484 ] ], "normalized": [] } ]

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[ { "id": "PMID-15723619__text", "type": "abstract", "text": [ "Novel biological agents for the treatment of hormone-refractory prostate cancer (HRPC).\nHormone-refractory prostate cancer (HRPC) is an inevitable evolution of prostate carcinogenesis, through which the normal dependence on hormones for growth and survival is bypassed. Although advances in terms of symptoms palliation and quality of life improvement have been addressed with current treatment options, innovative approaches are needed to improve survival rates. A thorough understanding of HRPC-associated molecular pathways and mechanisms of resistance are a prerequisite for novel potential therapeutic interventions. Preclinical and early clinical studies are ongoing to evaluate new therapies that target specific molecular entities. Agents under development include growth factor receptor inhibitors, small molecules targeting signal transduction pathways, apoptosis and cell-cycle regulators, angiogenesis and metastasis inhibitors, differentiation agents, telomerase inactivators, and epigenetic therapeutics. Incorporation of these agents into existing treatment regimens will guide us in the development of a multidisciplinary treatment strategy of HRPC. This article critically reviews published data on new biological agents that are being tested in HRPC clinical trials, highlights ongoing research and considers the future perspectives of this new class of agents.\n" ], "offsets": [ [ 0, 1380 ] ] } ]

[ { "id": "PMID-15723619_T1", "type": "Cancer", "text": [ "hormone-refractory prostate cancer" ], "offsets": [ [ 45, 79 ] ], "normalized": [] }, { "id": "PMID-15723619_T3", "type": "Cancer", "text": [ "HRPC" ], "offsets": [ [ 81, 85 ] ], "normalized": [] }, { "id": "PMID-15723619_T4", "type": "Cancer", "text": [ "Hormone-refractory prostate cancer" ], "offsets": [ [ 88, 122 ] ], "normalized": [] }, { "id": "PMID-15723619_T6", "type": "Cancer", "text": [ "HRPC" ], "offsets": [ [ 124, 128 ] ], "normalized": [] }, { "id": "PMID-15723619_T7", "type": "Organ", "text": [ "prostate" ], "offsets": [ [ 160, 168 ] ], "normalized": [] }, { "id": "PMID-15723619_T8", "type": "Cancer", "text": [ "HRPC" ], "offsets": [ [ 492, 496 ] ], "normalized": [] }, { "id": "PMID-15723619_T11", "type": "Cancer", "text": [ "HRPC" ], "offsets": [ [ 1160, 1164 ] ], "normalized": [] }, { "id": "PMID-15723619_T12", "type": "Cancer", "text": [ "HRPC" ], "offsets": [ [ 1263, 1267 ] ], "normalized": [] }, { "id": "PMID-15723619_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 878, 882 ] ], "normalized": [] } ]

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[ { "id": "PMID-20631994__text", "type": "abstract", "text": [ "Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions.\nUNLABELLED:\nRATIONAL: Exposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability.\nOBJECTIVE:\nThis study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine.\nMETHODS:\nAdult NVHL vs. SHAM-operated rats underwent a 5-day injection series of cocaine (15 mg/kg/day) vs. saline. One week later, rats were cannulated in nucleus accumbens SHELL, CORE, or caudate-putamen. Another week later, in vivo microdialysis sampled DA during locomotor testing in which a single cocaine injection (15 mg/kg) was delivered.\nRESULTS:\nNVHLs and cocaine history significantly increased behavioral activation approximately 2-fold over SHAM-saline history rats. DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient. However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.\nCONCLUSION:\nDifferences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history. These findings suggest other neurotransmitter systems, and alterations in striatal network function post-synaptic to DA transmission are more important to understanding the interactive effects of addictive drugs and mental illness.\n" ], "offsets": [ [ 0, 2041 ] ] } ]

[ { "id": "PMID-20631994_T1", "type": "Multi-tissue_structure", "text": [ "Ventral" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-20631994_T2", "type": "Multi-tissue_structure", "text": [ "dorsal striatal" ], "offsets": [ [ 12, 27 ] ], "normalized": [] }, { "id": "PMID-20631994_T3", "type": "Pathological_formation", "text": [ "neonatal ventral hippocampal lesions" ], "offsets": [ [ 130, 166 ] ], "normalized": [] }, { "id": "PMID-20631994_T4", "type": "Pathological_formation", "text": [ "neonatal ventral hippocampal lesions" ], "offsets": [ [ 370, 406 ] ], "normalized": [] }, { "id": "PMID-20631994_T5", "type": "Pathological_formation", "text": [ "NVHL" ], "offsets": [ [ 408, 412 ] ], "normalized": [] }, { "id": "PMID-20631994_T6", "type": "Pathological_formation", "text": [ "NVHL" ], "offsets": [ [ 577, 581 ] ], "normalized": [] }, { "id": "PMID-20631994_T7", "type": "Pathological_formation", "text": [ "NVHL" ], "offsets": [ [ 653, 657 ] ], "normalized": [] }, { "id": "PMID-20631994_T8", "type": "Multi-tissue_structure", "text": [ "nucleus accumbens" ], "offsets": [ [ 794, 811 ] ], "normalized": [] }, { "id": "PMID-20631994_T9", "type": "Multi-tissue_structure", "text": [ "caudate-putamen" ], "offsets": [ [ 828, 843 ] ], "normalized": [] }, { "id": "PMID-20631994_T10", "type": "Pathological_formation", "text": [ "NVHLs" ], "offsets": [ [ 994, 999 ] ], "normalized": [] }, { "id": "PMID-20631994_T11", "type": "Multi-tissue_structure", "text": [ "striatal region" ], "offsets": [ [ 1241, 1256 ] ], "normalized": [] }, { "id": "PMID-20631994_T12", "type": "Pathological_formation", "text": [ "NVHLs" ], "offsets": [ [ 1402, 1407 ] ], "normalized": [] }, { "id": "PMID-20631994_T13", "type": "Multi-tissue_structure", "text": [ "striatal region" ], "offsets": [ [ 1540, 1555 ] ], "normalized": [] }, { "id": "PMID-20631994_T14", "type": "Multi-tissue_structure", "text": [ "ventral" ], "offsets": [ [ 1584, 1591 ] ], "normalized": [] }, { "id": "PMID-20631994_T15", "type": "Multi-tissue_structure", "text": [ "dorsal striatal" ], "offsets": [ [ 1592, 1607 ] ], "normalized": [] }, { "id": "PMID-20631994_T16", "type": "Multi-tissue_structure", "text": [ "striatal network" ], "offsets": [ [ 1883, 1899 ] ], "normalized": [] }, { "id": "PMID-20631994_T17", "type": "Multi-tissue_structure", "text": [ "ventral" ], "offsets": [ [ 525, 532 ] ], "normalized": [] }, { "id": "PMID-20631994_T18", "type": "Multi-tissue_structure", "text": [ "dorsal striatal" ], "offsets": [ [ 537, 552 ] ], "normalized": [] }, { "id": "PMID-20631994_T19", "type": "Multi-tissue_structure", "text": [ "ventral" ], "offsets": [ [ 1356, 1363 ] ], "normalized": [] }, { "id": "PMID-20631994_T20", "type": "Multi-tissue_structure", "text": [ "dorsal striatal" ], "offsets": [ [ 1367, 1382 ] ], "normalized": [] }, { "id": "PMID-20631994_T21", "type": "Multi-tissue_structure", "text": [ "neural" ], "offsets": [ [ 292, 298 ] ], "normalized": [] }, { "id": "PMID-20631994_T22", "type": "Pathological_formation", "text": [ "NVHLs" ], "offsets": [ [ 1742, 1747 ] ], "normalized": [] } ]

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[ { "id": "PMID-22468084__text", "type": "abstract", "text": [ "Expression of HER2 and bradykinin B1 receptors in precursor lesions of gallbladder carcinoma. \nAIM: To determine the expression of HER2 and bradykinin B(1) receptors (B(1)R) in the two pathogenic models of gallbladder cancer: the metaplasia-dysplasia-carcinoma and the adenoma-carcinoma pathways. METHODS: Receptor proteins were visualized by immunohistochemistry on 5-mum sections of paraffin-embedded tissue. Expression of both receptors was studied in biopsy samples from 92 patients (6 males and 86 females; age ranging from 28 to 86 years, mean 56 years). High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridization. Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker. RESULTS: HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium. On the contrary, there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia (22/24; 91.7%) and carcinoma in situ (9/10; 90%), the lesions that displayed a significantly high proliferation index. Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene amplification. A similar result was observed in invasive carcinomas (0/12). The B(1)R distribution pattern mirrored that of HER2 except that B(1)R was additionally observed in the adenomas. The B(1)R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia (24/24; 100%) and carcinoma in situ (10/10; 100%) and in the epithelial cells of adenomas. In contrast, both HER2 (4/12; 33%) and B(1)R (1/12; 8.3%) showed a low expression in invasive gallbladder carcinomas. CONCLUSION: The up-regulation of HER2 and B(1)R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis.\n" ], "offsets": [ [ 0, 1995 ] ] } ]

[ { "id": "PMID-22468084_T3", "type": "Pathological_formation", "text": [ "precursor lesions" ], "offsets": [ [ 50, 67 ] ], "normalized": [] }, { "id": "PMID-22468084_T4", "type": "Cancer", "text": [ "gallbladder carcinoma" ], "offsets": [ [ 71, 92 ] ], "normalized": [] }, { "id": "PMID-22468084_T8", "type": "Cancer", "text": [ "gallbladder cancer" ], "offsets": [ [ 206, 224 ] ], "normalized": [] }, { "id": "PMID-22468084_T9", "type": "Cancer", "text": [ "metaplasia-dysplasia-carcinoma" ], "offsets": [ [ 230, 260 ] ], "normalized": [] }, { "id": "PMID-22468084_T10", "type": "Cancer", "text": [ "adenoma-carcinoma" ], "offsets": [ [ 269, 286 ] ], "normalized": [] }, { "id": "PMID-22468084_T11", "type": "Multi-tissue_structure", "text": [ "sections" ], "offsets": [ [ 373, 381 ] ], "normalized": [] }, { "id": "PMID-22468084_T12", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 403, 409 ] ], "normalized": [] }, { "id": "PMID-22468084_T13", "type": "Cancer", "text": [ "biopsy samples" ], "offsets": [ [ 455, 469 ] ], "normalized": [] }, { "id": "PMID-22468084_T16", "type": "Cancer", "text": [ "specimens" ], "offsets": [ [ 585, 594 ] ], "normalized": [] }, { "id": "PMID-22468084_T17", "type": "Cell", "text": [ "Cell" ], "offsets": [ [ 664, 668 ] ], "normalized": [] }, { "id": "PMID-22468084_T19", "type": "Cancer", "text": [ "adenomas" ], "offsets": [ [ 797, 805 ] ], "normalized": [] }, { "id": "PMID-22468084_T20", "type": "Tissue", "text": [ "gallbladder epithelium" ], "offsets": [ [ 820, 842 ] ], "normalized": [] }, { "id": "PMID-22468084_T22", "type": "Cellular_component", "text": [ "basolateral membrane" ], "offsets": [ [ 904, 924 ] ], "normalized": [] }, { "id": "PMID-22468084_T23", "type": "Cell", "text": [ "epithelial cells" ], "offsets": [ [ 928, 944 ] ], "normalized": [] }, { "id": "PMID-22468084_T24", "type": "Pathological_formation", "text": [ "intestinal metaplasia" ], "offsets": [ [ 948, 969 ] ], "normalized": [] }, { "id": "PMID-22468084_T26", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 1024, 1031 ] ], "normalized": [] }, { "id": "PMID-22468084_T28", "type": "Tissue", "text": [ "epithelium" ], "offsets": [ [ 1126, 1136 ] ], "normalized": [] }, { "id": "PMID-22468084_T29", "type": "Pathological_formation", "text": [ "metaplasia" ], "offsets": [ [ 1142, 1152 ] ], "normalized": [] }, { "id": "PMID-22468084_T30", "type": "Cancer", "text": [ "carcinoma in situ" ], "offsets": [ [ 1156, 1173 ] ], "normalized": [] }, { "id": "PMID-22468084_T32", "type": "Cancer", "text": [ "invasive carcinomas" ], "offsets": [ [ 1255, 1274 ] ], "normalized": [] }, { "id": "PMID-22468084_T36", "type": "Cancer", "text": [ "adenomas" ], "offsets": [ [ 1387, 1395 ] ], "normalized": [] }, { "id": "PMID-22468084_T38", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 1426, 1437 ] ], "normalized": [] }, { "id": "PMID-22468084_T39", "type": "Cellular_component", "text": [ "apical cell membrane" ], "offsets": [ [ 1462, 1482 ] ], "normalized": [] }, { "id": "PMID-22468084_T40", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1490, 1495 ] ], "normalized": [] }, { "id": "PMID-22468084_T41", "type": "Tissue", "text": [ "epithelia" ], "offsets": [ [ 1510, 1519 ] ], "normalized": [] }, { "id": "PMID-22468084_T42", "type": "Pathological_formation", "text": [ "intestinal metaplasia" ], "offsets": [ [ 1525, 1546 ] ], "normalized": [] }, { "id": "PMID-22468084_T43", "type": "Cancer", "text": [ "carcinoma in situ" ], "offsets": [ [ 989, 1006 ] ], "normalized": [] }, { "id": "PMID-22468084_T44", "type": "Cell", "text": [ "epithelial cells" ], "offsets": [ [ 1608, 1624 ] ], "normalized": [] }, { "id": "PMID-22468084_T45", "type": "Cancer", "text": [ "adenomas" ], "offsets": [ [ 1628, 1636 ] ], "normalized": [] }, { "id": "PMID-22468084_T48", "type": "Cancer", "text": [ "invasive gallbladder carcinomas" ], "offsets": [ [ 1723, 1754 ] ], "normalized": [] }, { "id": "PMID-22468084_T51", "type": "Pathological_formation", "text": [ "precursor lesions" ], "offsets": [ [ 1807, 1824 ] ], "normalized": [] }, { "id": "PMID-22468084_T52", "type": "Cancer", "text": [ "gallbladder carcinoma" ], "offsets": [ [ 1828, 1849 ] ], "normalized": [] }, { "id": "PMID-22468084_T53", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1945, 1949 ] ], "normalized": [] }, { "id": "PMID-22468084_T54", "type": "Organ", "text": [ "gallbladder" ], "offsets": [ [ 1967, 1978 ] ], "normalized": [] }, { "id": "PMID-22468084_T71", "type": "Cancer", "text": [ "carcinoma in situ" ], "offsets": [ [ 1565, 1582 ] ], "normalized": [] }, { "id": "PMID-22468084_T1", "type": "Cancer", "text": [ "sample" ], "offsets": [ [ 691, 697 ] ], "normalized": [] } ]

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[ { "id": "PMID-19760065__text", "type": "abstract", "text": [ "Targeting TNF for Treatment of Cancer and Autoimmunity.\nTumor necrosis factor-alpha (TNF-alpha) was first isolated two decades ago as a macrophageproduced protein that can effectively kill tumor cells. TNF-alpha is also an essential component of the immune system and is required for hematopoiesis, for protection from bacterial infection and for immune cell-mediated cytotoxicity. Extensive research, however, has revealed that TNF-alpha is one of the major players in tumor initiation, proliferation, invasion, angiogenesis and metastasis. The proinflammatory activities link TNF-alpha with a wide variety of autoimmune diseases, including psoriasis, inflammatory bowel disease, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, diabetes and ankylosing spondylitis. Systemic inhibitors of TNF such as etanercept (Enbrel) (a soluble TNF receptor) and infliximab (Remicade) and adalimumab (Humira) (anti-TNF antibodies) have been approved for the treatment inflammatory bowel disease, psoriasis and rheumatoid arthritis. These drugs, however, exhibit severe side effects and are expensive. Hence orally active blockers of TNF-alpha that are safe, efficacious and inexpensive are urgently needed. Numerous products from fruits, vegetable and traditional medicinal plants have been described which can suppress TNF expression and TNF signaling but their clinical potential is yet uncertain.\n" ], "offsets": [ [ 0, 1431 ] ] } ]

[ { "id": "PMID-19760065_T2", "type": "Cancer", "text": [ "Cancer" ], "offsets": [ [ 31, 37 ] ], "normalized": [] }, { "id": "PMID-19760065_T5", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 189, 200 ] ], "normalized": [] }, { "id": "PMID-19760065_T7", "type": "Cell", "text": [ "immune cell" ], "offsets": [ [ 347, 358 ] ], "normalized": [] }, { "id": "PMID-19760065_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 470, 475 ] ], "normalized": [] }, { "id": "PMID-19760065_T11", "type": "Organ", "text": [ "bowel" ], "offsets": [ [ 666, 671 ] ], "normalized": [] }, { "id": "PMID-19760065_T21", "type": "Organ", "text": [ "bowel" ], "offsets": [ [ 1012, 1017 ] ], "normalized": [] }, { "id": "PMID-19760065_T23", "type": "Organism_subdivision", "text": [ "fruits" ], "offsets": [ [ 1261, 1267 ] ], "normalized": [] }, { "id": "PMID-19760065_T24", "type": "Organism_subdivision", "text": [ "vegetable" ], "offsets": [ [ 1269, 1278 ] ], "normalized": [] }, { "id": "PMID-19760065_T43", "type": "Anatomical_system", "text": [ "immune system" ], "offsets": [ [ 250, 263 ] ], "normalized": [] }, { "id": "PMID-19760065_T44", "type": "Organism_subdivision", "text": [ "orally" ], "offsets": [ [ 1138, 1144 ] ], "normalized": [] } ]

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[ { "id": "PMC-3124045-caption-01__text", "type": "caption", "text": [ "Parkin regulates the proteasomal degradation of PARIS and PGC-1alpha-dependent mitochondrial biogenesis. (A) Normal physiological conditions that maintain mitochondrial homeostasis: PINK1 recruits parkin to the mitochondria, where these two proteins interact to eliminate abnormal mitochondria through mitophagy. Alterations in mitochondrial membrane potential (DeltaPsim; a key indicator of mitochondrial physiology and cell viability) initiate the PINK1-parkin cascade of events that lead to mitophagy. Furthermore, parkin ubiquitylates and thereby promotes proteasomal degradation of PARIS. Because PARIS represses the expression of PGC-1alpha, degradation of PARIS by parkin allows PGC-1alpha-dependent gene expression and enables mitochondrial biogenesis. Parkin seems to be an integral regulator of mitochondrial homeostasis, controlling both degradation and biogenesis. (B) Loss of parkin function as a result of familial mutations (in the case of AR-PD) or aging, environmental or cellular stress (in the case of sporadic PD) leads to the accumulation of abnormal mitochondria, owing to faulty mitophagy. In addition, PARIS accumulates and represses PGC-1alpha, preventing mitochondrial biogenesis. Loss of parkin function does not tip the balance between mitochondrial biogenesis and degradation to either side, but leads to a general breakdown of mitochondrial homeostasis that can ultimately lead to PD.\n" ], "offsets": [ [ 0, 1415 ] ] } ]

[ { "id": "PMC-3124045-caption-01_T1", "type": "Cellular_component", "text": [ "proteasomal" ], "offsets": [ [ 21, 32 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T2", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 79, 92 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T3", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 155, 168 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T4", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 211, 223 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T5", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 281, 293 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T6", "type": "Cellular_component", "text": [ "mitochondrial membrane" ], "offsets": [ [ 328, 350 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T7", "type": "Cellular_component", "text": [ "proteasomal" ], "offsets": [ [ 560, 571 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T8", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 735, 748 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T9", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 805, 818 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T10", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 989, 997 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T11", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 1072, 1084 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T12", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1181, 1194 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T13", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1264, 1277 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T14", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1357, 1370 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T15", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 392, 405 ] ], "normalized": [] }, { "id": "PMC-3124045-caption-01_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 421, 425 ] ], "normalized": [] } ]

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[ { "id": "PMID-2902221__text", "type": "abstract", "text": [ "Time course of transmitter action at the sympathetic neuroeffector junction in rodent vascular and non-vascular smooth muscle.\n1. Transmitter release from sympathetic postganglionic nerve terminals innervating the guinea-pig and mouse vas deferens and the rat tail artery has been studied in vitro by focal extracellular recording with particular emphasis on the time course of transmitter action underlying the intracellular potential changes. 2. In the absence of stimulation, spontaneous excitatory junction currents (SEJCs) were recorded with amplitudes up to 500 microV and durations between 40 and 100 ms. SEJCs were unaffected by the competitive alpha-adrenoceptor antagonist prazosin but blocked by alpha, beta-methylene ATP which desensitizes P2-purinoceptors. 3. During trains of supramaximal stimuli at 0.1-4 Hz stimulus locked excitatory junction currents (EJCs) were evoked intermittently from the population of varicosities located under the suction electrode. 4. SEJCs were similar in amplitude and time course to EJCs evoked by low-frequency stimulation in the same attachment in all three tissues. 5. SEJCs recorded using either a conventional AC amplifier or a patch clamp amplifier had the same time course. 6. These studies show that the time course of the current underlying the excitatory junction potential is brief and essentially the same in three different tissues. The prolonged time course of the excitatory junction potential in different tissues can be accounted for by the passive membrane properties.\n" ], "offsets": [ [ 0, 1533 ] ] } ]

[ { "id": "PMID-2902221_T1", "type": "Organ", "text": [ "vascular" ], "offsets": [ [ 86, 94 ] ], "normalized": [] }, { "id": "PMID-2902221_T2", "type": "Organ", "text": [ "non-vascular smooth muscle" ], "offsets": [ [ 99, 125 ] ], "normalized": [] }, { "id": "PMID-2902221_T5", "type": "Multi-tissue_structure", "text": [ "vas deferens" ], "offsets": [ [ 235, 247 ] ], "normalized": [] }, { "id": "PMID-2902221_T6", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1106, 1113 ] ], "normalized": [] }, { "id": "PMID-2902221_T7", "type": "Tissue", "text": [ "excitatory junction" ], "offsets": [ [ 491, 510 ] ], "normalized": [] }, { "id": "PMID-2902221_T8", "type": "Tissue", "text": [ "excitatory junction" ], "offsets": [ [ 839, 858 ] ], "normalized": [] }, { "id": "PMID-2902221_T9", "type": "Tissue", "text": [ "excitatory junction" ], "offsets": [ [ 1300, 1319 ] ], "normalized": [] }, { "id": "PMID-2902221_T10", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1383, 1390 ] ], "normalized": [] }, { "id": "PMID-2902221_T11", "type": "Tissue", "text": [ "excitatory junction" ], "offsets": [ [ 1425, 1444 ] ], "normalized": [] }, { "id": "PMID-2902221_T12", "type": "Tissue", "text": [ "sympathetic neuroeffector junction" ], "offsets": [ [ 41, 75 ] ], "normalized": [] }, { "id": "PMID-2902221_T13", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 307, 320 ] ], "normalized": [] }, { "id": "PMID-2902221_T14", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 412, 425 ] ], "normalized": [] }, { "id": "PMID-2902221_T4", "type": "Multi-tissue_structure", "text": [ "tail artery" ], "offsets": [ [ 260, 271 ] ], "normalized": [] }, { "id": "PMID-2902221_T15", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1468, 1475 ] ], "normalized": [] }, { "id": "PMID-2902221_T16", "type": "Multi-tissue_structure", "text": [ "membrane" ], "offsets": [ [ 1512, 1520 ] ], "normalized": [] }, { "id": "PMID-2902221_T3", "type": "Cellular_component", "text": [ "sympathetic postganglionic nerve terminals" ], "offsets": [ [ 155, 197 ] ], "normalized": [] } ]

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[ { "id": "PMC-2255579-caption-01__text", "type": "caption", "text": [ "Loss of both apical pathways (bottom) allows astral microtubules (arrows) to form apically and basally in neuroblasts.\n" ], "offsets": [ [ 0, 119 ] ] } ]

[ { "id": "PMC-2255579-caption-01_T1", "type": "Cellular_component", "text": [ "apical pathways" ], "offsets": [ [ 13, 28 ] ], "normalized": [] }, { "id": "PMC-2255579-caption-01_T2", "type": "Cellular_component", "text": [ "astral microtubules" ], "offsets": [ [ 45, 64 ] ], "normalized": [] }, { "id": "PMC-2255579-caption-01_T3", "type": "Cell", "text": [ "neuroblasts" ], "offsets": [ [ 106, 117 ] ], "normalized": [] } ]

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[ { "id": "PMID-17311993__text", "type": "abstract", "text": [ "Inhibition of Dll4-mediated signaling induces proliferation of immature vessels and results in poor tissue perfusion.\nVascular development is dependent on various growth factors and certain modifiers critical for providing arterial or venous identity, interaction with the surrounding stroma and tissues, hierarchic network formation, and recruitment of pericytes. Notch receptors and ligands (Jagged and Delta-like) play a critical role in this process in addition to VEGF. Dll4 is one of the Notch ligands that regulates arterial specification and maturation events. In the current study, we have shown that loss of function by either targeted allele deletion or use of a soluble form of Dll4 extracellular domain leads to inhibition of Notch signaling, resulting in increased vascular proliferation but defective maturation. Newly forming vessels have thin caliber, a markedly reduced vessel lumen, markedly reduced pericyte recruitment, and deficient vascular perfusion. sDll4 similarly induced defective vascular response in tumor implants leading to reduced tumor growth. Interference with Dll4-Notch signaling may be particularly desirable in tumors that have highly induced Dll4-Notch pathway.\n" ], "offsets": [ [ 0, 1202 ] ] } ]

[ { "id": "PMID-17311993_T2", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 72, 79 ] ], "normalized": [] }, { "id": "PMID-17311993_T3", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 100, 106 ] ], "normalized": [] }, { "id": "PMID-17311993_T4", "type": "Multi-tissue_structure", "text": [ "Vascular" ], "offsets": [ [ 118, 126 ] ], "normalized": [] }, { "id": "PMID-17311993_T5", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 223, 231 ] ], "normalized": [] }, { "id": "PMID-17311993_T6", "type": "Multi-tissue_structure", "text": [ "venous" ], "offsets": [ [ 235, 241 ] ], "normalized": [] }, { "id": "PMID-17311993_T7", "type": "Tissue", "text": [ "stroma" ], "offsets": [ [ 285, 291 ] ], "normalized": [] }, { "id": "PMID-17311993_T8", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 296, 303 ] ], "normalized": [] }, { "id": "PMID-17311993_T9", "type": "Tissue", "text": [ "hierarchic network" ], "offsets": [ [ 305, 323 ] ], "normalized": [] }, { "id": "PMID-17311993_T10", "type": "Cell", "text": [ "pericytes" ], "offsets": [ [ 354, 363 ] ], "normalized": [] }, { "id": "PMID-17311993_T17", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 523, 531 ] ], "normalized": [] }, { "id": "PMID-17311993_T19", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 695, 708 ] ], "normalized": [] }, { "id": "PMID-17311993_T21", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 779, 787 ] ], "normalized": [] }, { "id": "PMID-17311993_T22", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 842, 849 ] ], "normalized": [] }, { "id": "PMID-17311993_T23", "type": "Immaterial_anatomical_entity", "text": [ "caliber" ], "offsets": [ [ 860, 867 ] ], "normalized": [] }, { "id": "PMID-17311993_T24", "type": "Immaterial_anatomical_entity", "text": [ "vessel lumen" ], "offsets": [ [ 888, 900 ] ], "normalized": [] }, { "id": "PMID-17311993_T25", "type": "Cell", "text": [ "pericyte" ], "offsets": [ [ 919, 927 ] ], "normalized": [] }, { "id": "PMID-17311993_T26", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 955, 963 ] ], "normalized": [] }, { "id": "PMID-17311993_T28", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1009, 1017 ] ], "normalized": [] }, { "id": "PMID-17311993_T29", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [] }, { "id": "PMID-17311993_T30", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1064, 1069 ] ], "normalized": [] }, { "id": "PMID-17311993_T33", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1150, 1156 ] ], "normalized": [] } ]

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[ { "id": "PMID-15034302__text", "type": "abstract", "text": [ "TGFbeta1, back to the future: revisiting its role as a transforming growth factor.\nTGFbeta1 was initially identified in culture media from transformed cells as part of a factor that could produce a transformed phenotype in a nontransformed cell line. Subsequently this activity was separated into TGFbeta and TGFalpha an EGF receptor ligand. With the discovery that TGFbeta1 was a potent growth inhibitor of epithelial cells, and the identification of inactivating mutations within the TGFbeta1 signaling pathway in cancers it became clear that TGFbeta1 signaling is a tumor suppressor pathway for early stages of cancer. However many human carcinomas overexpress TGFbeta1 and this is associated with poor patient prognosis and increased frequency of metastasis. Similar results have been obtained with tumor cell lines and experimental animal models. Thus stage specific duality of function is the emerging paradigm for the role of TGFbeta1 in cancer. This review will focus on the evidence for TGFbeta1 as a tumor promoting and metastasis factor and examine the biological and molecular basis for these effects. It is proposed that the switch from tumor suppressor to oncogene reflects genetic or epigenetic alterations in signaling pathways in tumor cells that alter the readout from the TGFbeta1 pathway.\n" ], "offsets": [ [ 0, 1309 ] ] } ]

[ { "id": "PMID-15034302_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 151, 156 ] ], "normalized": [] }, { "id": "PMID-15034302_T4", "type": "Cell", "text": [ "cell line" ], "offsets": [ [ 240, 249 ] ], "normalized": [] }, { "id": "PMID-15034302_T9", "type": "Cell", "text": [ "epithelial cells" ], "offsets": [ [ 408, 424 ] ], "normalized": [] }, { "id": "PMID-15034302_T11", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 516, 523 ] ], "normalized": [] }, { "id": "PMID-15034302_T13", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 569, 574 ] ], "normalized": [] }, { "id": "PMID-15034302_T14", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 614, 620 ] ], "normalized": [] }, { "id": "PMID-15034302_T16", "type": "Cancer", "text": [ "carcinomas" ], "offsets": [ [ 641, 651 ] ], "normalized": [] }, { "id": "PMID-15034302_T19", "type": "Cell", "text": [ "tumor cell lines" ], "offsets": [ [ 803, 819 ] ], "normalized": [] }, { "id": "PMID-15034302_T21", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 945, 951 ] ], "normalized": [] }, { "id": "PMID-15034302_T23", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1010, 1015 ] ], "normalized": [] }, { "id": "PMID-15034302_T24", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1150, 1155 ] ], "normalized": [] }, { "id": "PMID-15034302_T25", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1247, 1258 ] ], "normalized": [] } ]

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[ { "id": "PMID-21939640__text", "type": "abstract", "text": [ "IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice. \nIL-17 plays an important role in gut homeostasis. However, the role of IL-17F in intestinal tumorigenesis has not been addressed. Here we demonstrate that ablation of IL-17F significantly inhibits spontaneous intestinal tumorigenesis in the small intestine of Apc(Min/+) mice. IL-17F ablation decreased IL-1beta and Cox-2 expression as well as IL-17 receptor C (IL-17RC) expression, which were increased in tumors from Apc(Min/+) mice. Lack of IL-17F did not reverse the splenomegaly but partially restored thymic atrophy, suggesting a local effect of IL-17F in the intestine. IL-17F deficient Apc(Min/+) mice showed a significant decrease in immune cell infiltration in the lamina propria. Interestingly, the expression of IL-17A from CD4 T cells in the lamina propria remains unchanged in the absence of IL-17F. Collectively, our results suggest the proinflammatory and essential role of IL-17F to develop spontaneous intestinal tumorigenesis in Apc(Min/+) mice in the presence of IL-17A.\n" ], "offsets": [ [ 0, 1068 ] ] } ]

[ { "id": "PMID-21939640_T2", "type": "Organ", "text": [ "small intestinal" ], "offsets": [ [ 27, 43 ] ], "normalized": [] }, { "id": "PMID-21939640_T6", "type": "Organism_subdivision", "text": [ "gut" ], "offsets": [ [ 110, 113 ] ], "normalized": [] }, { "id": "PMID-21939640_T8", "type": "Multi-tissue_structure", "text": [ "intestinal" ], "offsets": [ [ 158, 168 ] ], "normalized": [] }, { "id": "PMID-21939640_T10", "type": "Multi-tissue_structure", "text": [ "intestinal" ], "offsets": [ [ 286, 296 ] ], "normalized": [] }, { "id": "PMID-21939640_T11", "type": "Organ", "text": [ "small intestine" ], "offsets": [ [ 318, 333 ] ], "normalized": [] }, { "id": "PMID-21939640_T19", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 484, 490 ] ], "normalized": [] }, { "id": "PMID-21939640_T23", "type": "Pathological_formation", "text": [ "splenomegaly" ], "offsets": [ [ 548, 560 ] ], "normalized": [] }, { "id": "PMID-21939640_T24", "type": "Organ", "text": [ "thymic" ], "offsets": [ [ 584, 590 ] ], "normalized": [] }, { "id": "PMID-21939640_T26", "type": "Organ", "text": [ "intestine" ], "offsets": [ [ 643, 652 ] ], "normalized": [] }, { "id": "PMID-21939640_T30", "type": "Cell", "text": [ "immune cell" ], "offsets": [ [ 720, 731 ] ], "normalized": [] }, { "id": "PMID-21939640_T31", "type": "Tissue", "text": [ "lamina propria" ], "offsets": [ [ 752, 766 ] ], "normalized": [] }, { "id": "PMID-21939640_T34", "type": "Cell", "text": [ "CD4 T cells" ], "offsets": [ [ 813, 824 ] ], "normalized": [] }, { "id": "PMID-21939640_T35", "type": "Tissue", "text": [ "lamina propria" ], "offsets": [ [ 832, 846 ] ], "normalized": [] }, { "id": "PMID-21939640_T38", "type": "Multi-tissue_structure", "text": [ "intestinal" ], "offsets": [ [ 997, 1007 ] ], "normalized": [] } ]

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[ { "id": "PMID-537829__text", "type": "abstract", "text": [ "Differences between the arterial and the venous pathomorphology in Buerger's disease.\nMorphological lesions were found to be different in arteries and in veins, in 9 cases of Buerger's disease. The arterial lesions were not characteristic and consisted of non-specific inflammation, thrombosis and obliteration which also occur in many other disease. In contrast, in addition to wall infiltration and thrombosis, the veins showed microabscesses and giant cell granulomas, which we believe to be absent in all other known diseases. The affected venous segment exhibited a variety of lesions. In the earliest period, the morphological aspect of inflammation in arteries and veins was fairly similar. In a late periods, that is those of vascular obliteration, the arteries and veins did not show any distinguishing morphological differences.\n" ], "offsets": [ [ 0, 839 ] ] } ]

[ { "id": "PMID-537829_T1", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 24, 32 ] ], "normalized": [] }, { "id": "PMID-537829_T2", "type": "Multi-tissue_structure", "text": [ "venous" ], "offsets": [ [ 41, 47 ] ], "normalized": [] }, { "id": "PMID-537829_T3", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 100, 107 ] ], "normalized": [] }, { "id": "PMID-537829_T4", "type": "Multi-tissue_structure", "text": [ "arteries" ], "offsets": [ [ 138, 146 ] ], "normalized": [] }, { "id": "PMID-537829_T5", "type": "Multi-tissue_structure", "text": [ "veins" ], "offsets": [ [ 154, 159 ] ], "normalized": [] }, { "id": "PMID-537829_T6", "type": "Pathological_formation", "text": [ "arterial lesions" ], "offsets": [ [ 198, 214 ] ], "normalized": [] }, { "id": "PMID-537829_T7", "type": "Multi-tissue_structure", "text": [ "veins" ], "offsets": [ [ 417, 422 ] ], "normalized": [] }, { "id": "PMID-537829_T8", "type": "Pathological_formation", "text": [ "microabscesses" ], "offsets": [ [ 430, 444 ] ], "normalized": [] }, { "id": "PMID-537829_T9", "type": "Pathological_formation", "text": [ "giant cell granulomas" ], "offsets": [ [ 449, 470 ] ], "normalized": [] }, { "id": "PMID-537829_T10", "type": "Multi-tissue_structure", "text": [ "venous" ], "offsets": [ [ 544, 550 ] ], "normalized": [] }, { "id": "PMID-537829_T11", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 582, 589 ] ], "normalized": [] }, { "id": "PMID-537829_T12", "type": "Multi-tissue_structure", "text": [ "arteries" ], "offsets": [ [ 659, 667 ] ], "normalized": [] }, { "id": "PMID-537829_T13", "type": "Multi-tissue_structure", "text": [ "veins" ], "offsets": [ [ 672, 677 ] ], "normalized": [] }, { "id": "PMID-537829_T14", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 734, 742 ] ], "normalized": [] }, { "id": "PMID-537829_T15", "type": "Multi-tissue_structure", "text": [ "arteries" ], "offsets": [ [ 761, 769 ] ], "normalized": [] }, { "id": "PMID-537829_T16", "type": "Multi-tissue_structure", "text": [ "veins" ], "offsets": [ [ 774, 779 ] ], "normalized": [] }, { "id": "PMID-537829_T17", "type": "Multi-tissue_structure", "text": [ "wall" ], "offsets": [ [ 379, 383 ] ], "normalized": [] } ]

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[ { "id": "PMID-8388511__text", "type": "abstract", "text": [ "Transformation-associated cytokine 9E3/CEF4 is chemotactic for chicken peripheral blood mononuclear cells. \n9E3/CEF4, which is released from transformed chicken embryo fibroblasts (CEF), is a member of the platelet factor 4 family of inflammatory proteins and may be the avian homolog of interleukin-8. Since the function of 9E3/CEF4 is unknown, we examined the effect of the protein on mitogenicity and chemotaxis, as well as its expression, in fibroblasts and peripheral blood cells. 9E3/CEF4 mRNA was expressed in chicken peripheral blood monocytes, and its expression was stimulated by incubation of the monocytes with lipopolysaccharide or phorbol myristic acetate. Boyden double-membrane analysis of chemotaxis showed that 9E3/CEF4 was chemotactic for chicken peripheral blood mononuclear cells, as well as for heterophils. Untransformed CEF and CEF transformed with Rous sarcoma virus also migrated to 9E3/CEF4 protein, as measured by Boyden single-membrane analysis. 9E3/CEF4 was slightly mitogenic for CEF, causing a doubling of [3H]thymidine uptake when added to serum-starved CEF.9E3/CEF4 was found associated not only with the cell and in the culture medium of Rous sarcoma virus-transformed CEF but also with the extracellular matrix. The in vivo role of 9E3/CEF4 may be involved with chemotaxis and metastasis, rather than with direct stimulation of mitogenicity.\n" ], "offsets": [ [ 0, 1378 ] ] } ]

[ { "id": "PMID-8388511_T4", "type": "Cell", "text": [ "peripheral blood mononuclear cells" ], "offsets": [ [ 71, 105 ] ], "normalized": [] }, { "id": "PMID-8388511_T8", "type": "Cell", "text": [ "embryo fibroblasts" ], "offsets": [ [ 161, 179 ] ], "normalized": [] }, { "id": "PMID-8388511_T9", "type": "Cell", "text": [ "CEF" ], "offsets": [ [ 181, 184 ] ], "normalized": [] }, { "id": "PMID-8388511_T14", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 446, 457 ] ], "normalized": [] }, { "id": "PMID-8388511_T15", "type": "Cell", "text": [ "peripheral blood cells" ], "offsets": [ [ 462, 484 ] ], "normalized": [] }, { "id": "PMID-8388511_T19", "type": "Organism_substance", "text": [ "peripheral blood monocytes" ], "offsets": [ [ 525, 551 ] ], "normalized": [] }, { "id": "PMID-8388511_T20", "type": "Cell", "text": [ "monocytes" ], "offsets": [ [ 608, 617 ] ], "normalized": [] }, { "id": "PMID-8388511_T26", "type": "Cell", "text": [ "peripheral blood mononuclear cells" ], "offsets": [ [ 766, 800 ] ], "normalized": [] }, { "id": "PMID-8388511_T27", "type": "Cell", "text": [ "heterophils" ], "offsets": [ [ 817, 828 ] ], "normalized": [] }, { "id": "PMID-8388511_T28", "type": "Cell", "text": [ "CEF" ], "offsets": [ [ 844, 847 ] ], "normalized": [] }, { "id": "PMID-8388511_T29", "type": "Cell", "text": [ "CEF" ], "offsets": [ [ 852, 855 ] ], "normalized": [] }, { "id": "PMID-8388511_T35", "type": "Cell", "text": [ "CEF" ], "offsets": [ [ 1011, 1014 ] ], "normalized": [] }, { "id": "PMID-8388511_T37", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1073, 1078 ] ], "normalized": [] }, { "id": "PMID-8388511_T38", "type": "Cell", "text": [ "CEF" ], "offsets": [ [ 1087, 1090 ] ], "normalized": [] }, { "id": "PMID-8388511_T41", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1139, 1143 ] ], "normalized": [] }, { "id": "PMID-8388511_T43", "type": "Cell", "text": [ "CEF" ], "offsets": [ [ 1204, 1207 ] ], "normalized": [] }, { "id": "PMID-8388511_T44", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 1226, 1246 ] ], "normalized": [] } ]

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[ { "id": "PMID-16485028__text", "type": "abstract", "text": [ "NF-kappaB and IKK as therapeutic targets in cancer.\nThe transcription factor NF-kappaB and associated regulatory factors (including IkappaB kinase subunits and the IkappaB family member Bcl-3) are strongly implicated in a variety of hematologic and solid tumor malignancies. A role for NF-kappaB in cancer cells appears to involve regulation of cell proliferation, control of apoptosis, promotion of angiogenesis, and stimulation of invasion/metastasis. Consistent with a role for NF-kappaB in oncogenesis are observations that inhibition of NF-kappaB alone or in combination with cancer therapies leads to tumor cell death or growth inhibition. However, other experimental data indicate that NF-kappaB can play a tumor suppressor role in certain settings and that it can be important in promoting an apoptotic signal downstream of certain cancer therapy regimens. In order to appropriately move NF-kappaB inhibitors in the clinic, thorough approaches must be initiated to determine the molecular mechanisms that dictate the complexity of oncologic and therapeutic outcomes that are controlled by NF-kappaB.\n" ], "offsets": [ [ 0, 1108 ] ] } ]

[ { "id": "PMID-16485028_T3", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 44, 50 ] ], "normalized": [] }, { "id": "PMID-16485028_T8", "type": "Cancer", "text": [ "hematologic" ], "offsets": [ [ 233, 244 ] ], "normalized": [] }, { "id": "PMID-16485028_T9", "type": "Cancer", "text": [ "solid tumor malignancies" ], "offsets": [ [ 249, 273 ] ], "normalized": [] }, { "id": "PMID-16485028_T11", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 299, 311 ] ], "normalized": [] }, { "id": "PMID-16485028_T12", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 345, 349 ] ], "normalized": [] }, { "id": "PMID-16485028_T15", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 581, 587 ] ], "normalized": [] }, { "id": "PMID-16485028_T16", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 607, 617 ] ], "normalized": [] }, { "id": "PMID-16485028_T18", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 714, 719 ] ], "normalized": [] }, { "id": "PMID-16485028_T19", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 840, 846 ] ], "normalized": [] } ]

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[ { "id": "PMC-3239939-sec-01__text", "type": "sec", "text": [ "Background\nEucalyptus globulus is the most widely planted species for pulpwood production in temperate regions of the world and there are breeding programs in numerous countries. There is interest in molecular approaches to breeding, particularly marker assisted selection of wood properties. QTL analysis has an important role in identifying positional candidate genes responsible for variation in wood properties. This is one approach to targeting genes which may harbour functional allelic variants (SNPs). The objective of this study was to detect and validate QTL across multiple sites and pedigrees, in order to identify genomic regions and genes affecting growth and wood properties with wide applicability in the species. We also aimed to determine the proportion of QTL which were stable in their expression across sites of contrasting productivity. Such information will be important to exploit the full potential of the impending Eucalyptus genome sequences.\n" ], "offsets": [ [ 0, 970 ] ] } ]

[ { "id": "PMC-3239939-sec-01_T1", "type": "Multi-tissue_structure", "text": [ "pulpwood" ], "offsets": [ [ 70, 78 ] ], "normalized": [] }, { "id": "PMC-3239939-sec-01_T2", "type": "Multi-tissue_structure", "text": [ "wood" ], "offsets": [ [ 276, 280 ] ], "normalized": [] }, { "id": "PMC-3239939-sec-01_T3", "type": "Multi-tissue_structure", "text": [ "wood" ], "offsets": [ [ 399, 403 ] ], "normalized": [] }, { "id": "PMC-3239939-sec-01_T4", "type": "Multi-tissue_structure", "text": [ "wood" ], "offsets": [ [ 674, 678 ] ], "normalized": [] } ]

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[ { "id": "PMID-19542562__text", "type": "abstract", "text": [ "Mechanical regulation of the proangiogenic factor CCN1/CYR61 gene requires the combined activities of MRTF-A and CREB-binding protein histone acetyltransferase.\nSmooth muscle-rich tissues respond to mechanical overload by an adaptive hypertrophic growth combined with activation of angiogenesis, which potentiates their mechanical overload-bearing capabilities. Neovascularization is associated with mechanical strain-dependent induction of angiogenic factors such as CCN1, an immediate-early gene-encoded matricellular molecule critical for vascular development and repair. Here we have demonstrated that mechanical strain-dependent induction of the CCN1 gene involves signaling cascades through RhoA-mediated actin remodeling and the p38 stress-activated protein kinase (SAPK). Actin signaling controls serum response factor (SRF) activity via SRF interaction with the myocardin-related transcriptional activator (MRTF)-A and tethering to a single CArG box sequence within the CCN1 promoter. Such activity was abolished in mechanically stimulated mouse MRTF-A(-/-) cells or upon inhibition of CREB-binding protein (CBP) histone acetyltransferase (HAT) either pharmacologically or by siRNAs. Mechanical strain induced CBP-mediated acetylation of histones 3 and 4 at the SRF-binding site and within the CCN1 gene coding region. Inhibition of p38 SAPK reduced CBP HAT activity and its recruitment to the SRF.MRTF-A complex, whereas enforced induction of p38 by upstream activators (e.g. MKK3 and MKK6) enhanced both CBP HAT and CCN1 promoter activities. Similarly, mechanical overload-induced CCN1 gene expression in vivo was associated with nuclear localization of MRTF-A and enrichment of the CCN1 promoter with both MRTF-A and acetylated histone H3. Taken together, these data suggest that signal-controlled activation of SRF, MRTF-A, and CBP provides a novel connection between mechanical stimuli and angiogenic gene expression.\n" ], "offsets": [ [ 0, 1932 ] ] } ]

[ { "id": "PMID-19542562_T5", "type": "Tissue", "text": [ "Smooth muscle-rich tissues" ], "offsets": [ [ 161, 187 ] ], "normalized": [] }, { "id": "PMID-19542562_T7", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 542, 550 ] ], "normalized": [] }, { "id": "PMID-19542562_T10", "type": "Cellular_component", "text": [ "actin" ], "offsets": [ [ 711, 716 ] ], "normalized": [] }, { "id": "PMID-19542562_T20", "type": "Cell", "text": [ "MRTF-A(-/-) cells" ], "offsets": [ [ 1055, 1072 ] ], "normalized": [] }, { "id": "PMID-19542562_T84", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1641, 1648 ] ], "normalized": [] } ]

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[ { "id": "PMID-9728053__text", "type": "abstract", "text": [ "Store-operated calcium entry promotes shape change in pulmonary endothelial cells expressing Trp1.\nActivation of Ca2+ entry is known to produce endothelial cell shape change, leading to increased permeability, leukocyte migration, and initiation of angiogenesis in conduit-vessel endothelial cells. The mode of Ca2+ entry regulating cell shape is unknown. We hypothesized that activation of store-operated Ca2+ channels (SOCs) is sufficient to promote cell shape change necessary for these processes. SOC activation in rat pulmonary arterial endothelial cells increased free cytosolic Ca2+ that was dependent on a membrane current having a net inward component of 5.45 +/- 0.90 pA/pF at -80 mV. Changes in endothelial cell shape accompanied SOC activation and were dependent on Ca2+ entry-induced reconfiguration of peripheral (cortical) filamentous actin (F-actin). Because the identity of pulmonary endothelial SOCs is unknown, but mammalian homologues of the Drosophila melanogaster transient receptor potential (trp) gene have been proposed to form Ca2+ entry channels in nonexcitable cells, we performed RT-PCR using Trp oligonucleotide primers in both rat and human pulmonary arterial endothelial cells. Both cell types were found to express Trp1, but neither expressed Trp3 nor Trp6. Our study indicates that 1) Ca2+ entry in pulmonary endothelial cells through SOCs produces cell shape change that is dependent on site-specific rearrangement of the microfilamentous cytoskeleton and 2) Trp1 may be a component of pulmonary endothelial SOCs.\n" ], "offsets": [ [ 0, 1549 ] ] } ]

[ { "id": "PMID-9728053_T2", "type": "Cell", "text": [ "pulmonary endothelial cells" ], "offsets": [ [ 54, 81 ] ], "normalized": [] }, { "id": "PMID-9728053_T5", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 144, 160 ] ], "normalized": [] }, { "id": "PMID-9728053_T6", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 210, 219 ] ], "normalized": [] }, { "id": "PMID-9728053_T7", "type": "Cell", "text": [ "conduit-vessel endothelial cells" ], "offsets": [ [ 265, 297 ] ], "normalized": [] }, { "id": "PMID-9728053_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 333, 337 ] ], "normalized": [] }, { "id": "PMID-9728053_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 452, 456 ] ], "normalized": [] }, { "id": "PMID-9728053_T13", "type": "Cell", "text": [ "pulmonary arterial endothelial cells" ], "offsets": [ [ 523, 559 ] ], "normalized": [] }, { "id": "PMID-9728053_T14", "type": "Organism_substance", "text": [ "cytosolic" ], "offsets": [ [ 575, 584 ] ], "normalized": [] }, { "id": "PMID-9728053_T16", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 614, 622 ] ], "normalized": [] }, { "id": "PMID-9728053_T17", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 706, 722 ] ], "normalized": [] }, { "id": "PMID-9728053_T19", "type": "Multi-tissue_structure", "text": [ "cortical" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "PMID-9728053_T22", "type": "Cell", "text": [ "pulmonary endothelial" ], "offsets": [ [ 891, 912 ] ], "normalized": [] }, { "id": "PMID-9728053_T27", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1089, 1094 ] ], "normalized": [] }, { "id": "PMID-9728053_T31", "type": "Cell", "text": [ "pulmonary arterial endothelial cells" ], "offsets": [ [ 1172, 1208 ] ], "normalized": [] }, { "id": "PMID-9728053_T32", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1215, 1219 ] ], "normalized": [] }, { "id": "PMID-9728053_T37", "type": "Cell", "text": [ "pulmonary endothelial cells" ], "offsets": [ [ 1333, 1360 ] ], "normalized": [] }, { "id": "PMID-9728053_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1383, 1387 ] ], "normalized": [] }, { "id": "PMID-9728053_T39", "type": "Cellular_component", "text": [ "microfilamentous cytoskeleton" ], "offsets": [ [ 1457, 1486 ] ], "normalized": [] }, { "id": "PMID-9728053_T41", "type": "Cell", "text": [ "pulmonary endothelial" ], "offsets": [ [ 1521, 1542 ] ], "normalized": [] }, { "id": "PMID-9728053_T1", "type": "Cellular_component", "text": [ "filamentous" ], "offsets": [ [ 838, 849 ] ], "normalized": [] } ]

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[ { "id": "PMC-1281265-sec-06__text", "type": "sec", "text": [ "Conclusions\nOnly after careful consideration of the biological underpinnings of a truly beneficial response can an exposure be considered for the general population, such as the addition of folic acid to cereals. If a toxic or hazardous pollutant were found to have truly beneficial effects at low dose, then that agent should be tested clinically, go through the U.S. Food and Drug Administration (FDA) approval process, and be regulated as a pharmaceutical for those who might benefit from its use. Certainly, the general population should not be exposed to chemotherapeutic agents that benefit cancer patients. For pharmaceuticals, it is understood that there are trade offs between benefits and risks. For example, although aspirin is a generally well-tolerated pain reliever and is increasingly advocated as a preventative tool for heart attacks and colorectal cancer (Vainio and Miller 2003; Werner et al. 2004), it is also linked to increased risk of gastrointestinal bleeding, cerebral hemorrhage (Werner et al. 2004), and asthma attacks (Jenkins et al. 2004). In addition, aspirin is not recommended for children or teenagers who have or are recovering from chicken pox or flulike symptoms because it can cause debilitating and sometimes lethal Reyes syndrome (U.S. FDA 2003). Individual risks to pharmaceutical agents can be controlled with proper usage; however, increased exposure to environmental toxins presents additional involuntary risks for the general population. Under the latter condition, exposure is inadequately controlled, and there is no mechanism to correct for individual circumstances (e.g., medical condition or age) that may result in harm.\nAlthough hormetic effects may occur in some instances, it is indeed rare that exposures to toxic, mutagenic, teratogenic, and carcinogenic chemicals, even at low exposure levels, would be risk free and provide health benefits for the general public. Portraying chemicals with numerous adverse effects as having benefits while ignoring their hazards is irresponsible and does not provide full and objective disclosure. In the 1950s doctors prescribed DES to pregnant women to prevent miscarriage and premature births and to produce \"bigger and stronger babies\" even though DES had been shown to cause damage to reproductive tissues in animals (Dinusson et al. 1948; Dunn and Green 1963; Takasugi and Bern 1964). Human use of DES was banned in the United States in 1971 after the discovery of high rates of rare, clear-cell adenocarcinomas of the vagina and cervix in DES-exposed daughters (Herbst 1981), and later studies showed elevated breast cancer risk in women who took DES during pregnancy (Titus-Ernstoff et al. 2001). Certainly, health policy decisions should be based on scientific evidence and not on speculation of health benefits in order for the general population to avoid repeating the mistakes of the past similar to that of the DES tragedy.\nThe claims and projections of health benefits from exposures to environmental toxicants and carcinogens are based on untested assumptions and disregard numerous well-established scientific principles that underpin a public health-protective approach to regulating exposure to toxic substances. If hormesis were used in the decision-making process to allow higher exposures to toxic and carcinogenic agents, this would substantially increase health risks for many, if not most, segments of the general population.\n" ], "offsets": [ [ 0, 3442 ] ] } ]

[ { "id": "PMC-1281265-sec-06_T1", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 597, 603 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T2", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 837, 842 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T3", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 855, 872 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T4", "type": "Organism_subdivision", "text": [ "gastrointestinal" ], "offsets": [ [ 958, 974 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T5", "type": "Organ", "text": [ "cerebral" ], "offsets": [ [ 985, 993 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T6", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 2295, 2302 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T8", "type": "Cancer", "text": [ "adenocarcinomas" ], "offsets": [ [ 2494, 2509 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T9", "type": "Multi-tissue_structure", "text": [ "vagina" ], "offsets": [ [ 2517, 2523 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T10", "type": "Multi-tissue_structure", "text": [ "cervix" ], "offsets": [ [ 2528, 2534 ] ], "normalized": [] }, { "id": "PMC-1281265-sec-06_T11", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 2609, 2622 ] ], "normalized": [] } ]

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[ { "id": "PMC-3132469-sec-12__text", "type": "sec", "text": [ "3.1. Glucose Tolerance Test at Various Times following Dosing\nDIO mice were treated with a single IV dose of CNTO 530 (0.3 mg/kg), and glucose metabolism was monitored using an intraperitoneal glucose tolerance test (IPGTT) at various times following dosing (day 1 to 35). CNTO 530 did not influence glucose tolerance 24 hours after dosing. However, a significant improvement was observed in both fasting glucose (179 +/- 29 versus 133 +/- 19 mg/dL for untreated versus treated) and overall glucose tolerance seven days after a single dose of CNTO 530 (Figure 2(b)). In a separate study, the activity of CNTO 530 was compared to a control protein that lacked the EMP-1 peptides to ensure that the observed effects were due to the peptide and not the Fc. The glucose lowering effect was not observed in the mice treated with the protein lacking the EMP-1 peptides (data not shown). Fasting blood glucose remained improved in the treated animals 14 and 21 days after CNTO530 treatment, but was similar to the untreated group after 35 days (data not shown). The area under the curve (AUC) for the glucose tolerance tests showed a significant improvement with CNTO 530 treatment on days 7, 14, 20, and 28 (Figure 2(b)). The most dramatic effect on glucose tolerance following CNTO 530-treatment was observed on day 14 where glucose was cleared from circulation by the 15-minute time point (Figure 2(a)). CNTO 530-mediated acceleration of glucose utilization was diminished but still significant by day 28 and not seen by day 35 (Figure 2(b)). Hemoglobin levels followed a similar time-dependent change, showing an increase that peaked on day 22 and returned to normal levels by day 29 (Figure 2(c)).\nSimilar studies were completed in lean littermate mice fed a normal chow diet. Mice (n = 7) were given a single administration of CNTO 530 (0.01-0.3 mg/kg), and glucose tolerance tests were completed after 1 and 14 days. As we observed in the diabetic rodents, no significant changes were seen in glucose clearance 24 hours after dosing. However, there were significant improvements in the area under the curve in the glucose tolerance test in animals dosed with 0.3 and 0.1 mg/kg CNTO 530 as compared to PBS (22865.4 +/- 1900.2, 24478.9 +/- 1093.4, and 28773.2 +/- 1368.3, resp., mean +/- SEM). There were no dose-dependent changes in the fasting blood glucose.\n" ], "offsets": [ [ 0, 2359 ] ] } ]

[ { "id": "PMC-3132469-sec-12_T1", "type": "Immaterial_anatomical_entity", "text": [ "intraperitoneal" ], "offsets": [ [ 177, 192 ] ], "normalized": [] }, { "id": "PMC-3132469-sec-12_T2", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 889, 894 ] ], "normalized": [] }, { "id": "PMC-3132469-sec-12_T3", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 2344, 2349 ] ], "normalized": [] } ]

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[ { "id": "PMID-19000097__text", "type": "abstract", "text": [ "Are former female elite athletes more likely to experience urinary incontinence later in life than non-athletes?\nThe aim of the present study was to investigate whether former female elite athletes are more likely to experience urinary incontinence (UI) later in life than non-athletes and to assess possible risk factors for UI in athletes. Three hundred and thirty-one former elite athletes (response rate 81%) and 640 controls replied to a postal questionnaire including validated questions on UI. While competing in sport, 10.9% and 2.7% of the former elite athletes reported stress urinary incontinence (SUI) and urge incontinence, respectively. Presently, 36.5% of the former elite athletes and 36.9% of the controls reported SUI. 9.1% and 9.4% reported urge incontinence. Among former elite athletes, those with two or three children were more likely than nulliparous women to have UI now. Also, among former athletes, UI was more common in women with vs those without UI while competing (odds ratio 8.57, 95% confidence interval: 3.55-20.71). Age, menopause and being regularly physically active now were not associated with UI in either group. Based on this study, the prevalence of UI does not seem to be higher in former athletes than in controls. However, the results indicate that UI early in life, as reported during elite sport, is a strong predictor of UI later in life.\n" ], "offsets": [ [ 0, 1387 ] ] } ]

[ { "id": "PMID-19000097_T1", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 59, 66 ] ], "normalized": [] }, { "id": "PMID-19000097_T2", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 228, 235 ] ], "normalized": [] }, { "id": "PMID-19000097_T3", "type": "Organism_substance", "text": [ "urinary" ], "offsets": [ [ 587, 594 ] ], "normalized": [] } ]

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[ { "id": "PMID-18657078__text", "type": "abstract", "text": [ "Investigation of the effect of kaolin and tissue-factor-activated citrated whole blood, on clot-forming variables, as evaluated by thromboelastography.\nBACKGROUND:\nThe Thrombelastograph (TEG; Haemoscope Corp.) analyzes clot formation in whole blood (WB) and treatment based on this analysis has been shown to reduce transfusion requirements in liver and cardiac surgery when compared to conventional coagulation analysis. Implementing TEG as a routine laboratory-based analysis, however, requires validation of the activators employed and the effect of storage of the WB sample in citrate before analysis.\nSTUDY DESIGN AND METHODS:\nThe effect of kaolin, tissue factor (TF) 1:17,000, or TF 1:42,500 on TEG clotting time (R), Angle (velocity of clot formation), and maximum clot strength (amplitude [MA]) were evaluated, together with day-to-day variation, the coefficient of variance (CV%), and the effect of citrate storage time.\nRESULTS:\nClot formation variables were equally affected by TF 1:17,000 and kaolin activation, whereas R was significantly longer when TF 1:42,500 was used. The CV for the different variables varied from 3 to 13 percent with no significant differences between assays. Storage of citrated WB significantly affected the TEG variables in a hypercoagulable direction. Only the R, however, was significantly affected (12%) when samples rested for 0 and 30 minutes were evaluated with kaolin as the activator.\nCONCLUSION:\nThe TEG assays evaluated were reproducible and present with an acceptable CV% for routine clinical practice. Kaolin and TF 1:17,000 equally affected the clot formation variables. Storage of WB for up to 30 minutes in citrate did not, except for R, affect clot formation variables when kaolin was used as activator allowing for immediate analysis when the sample arrives in the laboratory.\n" ], "offsets": [ [ 0, 1834 ] ] } ]

[ { "id": "PMID-18657078_T2", "type": "Organism_substance", "text": [ "whole blood" ], "offsets": [ [ 75, 86 ] ], "normalized": [] }, { "id": "PMID-18657078_T3", "type": "Organism_substance", "text": [ "clot" ], "offsets": [ [ 91, 95 ] ], "normalized": [] }, { "id": "PMID-18657078_T4", "type": "Organism_substance", "text": [ "clot" ], "offsets": [ [ 219, 223 ] ], "normalized": [] }, { "id": "PMID-18657078_T5", "type": "Organism_substance", "text": [ "whole blood" ], "offsets": [ [ 237, 248 ] ], "normalized": [] }, { "id": "PMID-18657078_T6", "type": "Organism_substance", "text": [ "WB" ], "offsets": [ [ 250, 252 ] ], "normalized": [] }, { "id": "PMID-18657078_T7", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 344, 349 ] ], "normalized": [] }, { "id": "PMID-18657078_T8", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 354, 361 ] ], "normalized": [] }, { "id": "PMID-18657078_T9", "type": "Organism_substance", "text": [ "WB sample" ], "offsets": [ [ 568, 577 ] ], "normalized": [] }, { "id": "PMID-18657078_T10", "type": "Organism_substance", "text": [ "clot" ], "offsets": [ [ 743, 747 ] ], "normalized": [] }, { "id": "PMID-18657078_T11", "type": "Organism_substance", "text": [ "clot" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-18657078_T12", "type": "Organism_substance", "text": [ "Clot" ], "offsets": [ [ 939, 943 ] ], "normalized": [] }, { "id": "PMID-18657078_T13", "type": "Organism_substance", "text": [ "WB" ], "offsets": [ [ 1217, 1219 ] ], "normalized": [] }, { "id": "PMID-18657078_T14", "type": "Organism_substance", "text": [ "clot" ], "offsets": [ [ 1598, 1602 ] ], "normalized": [] }, { "id": "PMID-18657078_T15", "type": "Organism_substance", "text": [ "WB" ], "offsets": [ [ 1635, 1637 ] ], "normalized": [] }, { "id": "PMID-18657078_T16", "type": "Organism_substance", "text": [ "clot" ], "offsets": [ [ 1700, 1704 ] ], "normalized": [] }, { "id": "PMID-18657078_T18", "type": "Organism_substance", "text": [ "sample" ], "offsets": [ [ 1800, 1806 ] ], "normalized": [] }, { "id": "PMID-18657078_T1", "type": "Organism_substance", "text": [ "samples" ], "offsets": [ [ 1352, 1359 ] ], "normalized": [] } ]

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[ { "id": "PMID-15975645__text", "type": "abstract", "text": [ "Thalidomide and angiostatin inhibit tumor growth in a murine xenograft model of human cervical cancer.\nOBJECTIVE: To determine the impact of thalidomide and angiostatin on tumor growth, angiogenesis, and apoptosis in a xenograft model of cervical cancer. METHODS: Human umbilical endothelial cells were treated with angiostatin or thalidomide and bFGF-induced proliferation was assessed with the MTT assay. Human cervical cancer cells (CaSki and SiHa) were injected into the flanks of nude mice. After tumors developed, mice were treated with angiostatin 20 mg/kg/day or thalidomide 200 mg/kg/day for 30 days. Fractional tumor growth was determined and immunohistochemical analysis of tumors was used to determine degree of angiogenesis. TUNEL assay was used to assess apoptosis. RESULTS: Angiostatin inhibited endothelial cell proliferation by 50-60%. Thalidomide had no direct effect on endothelial cells. Angiostatin and thalidomide both inhibited tumor growth by about 55%. We found no additive or synergistic effect when the two agents were combined. Both agents inhibited angiogenesis and induced apoptosis when compared to tumors from control animals. CONCLUSIONS: Angiostatin and thalidomide inhibit tumor growth, angiogenesis, and induce apoptosis in this xenograft model of cervical cancer.\n" ], "offsets": [ [ 0, 1301 ] ] } ]

[ { "id": "PMID-15975645_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 36, 41 ] ], "normalized": [] }, { "id": "PMID-15975645_T5", "type": "Cancer", "text": [ "xenograft" ], "offsets": [ [ 61, 70 ] ], "normalized": [] }, { "id": "PMID-15975645_T7", "type": "Cancer", "text": [ "cervical cancer" ], "offsets": [ [ 86, 101 ] ], "normalized": [] }, { "id": "PMID-15975645_T10", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "PMID-15975645_T11", "type": "Cancer", "text": [ "xenograft" ], "offsets": [ [ 219, 228 ] ], "normalized": [] }, { "id": "PMID-15975645_T12", "type": "Cancer", "text": [ "cervical cancer" ], "offsets": [ [ 238, 253 ] ], "normalized": [] }, { "id": "PMID-15975645_T14", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 280, 297 ] ], "normalized": [] }, { "id": "PMID-15975645_T19", "type": "Cell", "text": [ "cervical cancer cells" ], "offsets": [ [ 413, 434 ] ], "normalized": [] }, { "id": "PMID-15975645_T20", "type": "Cell", "text": [ "CaSki" ], "offsets": [ [ 436, 441 ] ], "normalized": [] }, { "id": "PMID-15975645_T21", "type": "Cell", "text": [ "SiHa" ], "offsets": [ [ 446, 450 ] ], "normalized": [] }, { "id": "PMID-15975645_T22", "type": "Organism_subdivision", "text": [ "flanks" ], "offsets": [ [ 475, 481 ] ], "normalized": [] }, { "id": "PMID-15975645_T24", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 502, 508 ] ], "normalized": [] }, { "id": "PMID-15975645_T28", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 621, 626 ] ], "normalized": [] }, { "id": "PMID-15975645_T29", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 685, 691 ] ], "normalized": [] }, { "id": "PMID-15975645_T31", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 811, 827 ] ], "normalized": [] }, { "id": "PMID-15975645_T33", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 889, 906 ] ], "normalized": [] }, { "id": "PMID-15975645_T36", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 951, 956 ] ], "normalized": [] }, { "id": "PMID-15975645_T37", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1130, 1136 ] ], "normalized": [] }, { "id": "PMID-15975645_T40", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1208, 1213 ] ], "normalized": [] }, { "id": "PMID-15975645_T41", "type": "Cancer", "text": [ "xenograft" ], "offsets": [ [ 1265, 1274 ] ], "normalized": [] }, { "id": "PMID-15975645_T42", "type": "Cancer", "text": [ "cervical cancer" ], "offsets": [ [ 1284, 1299 ] ], "normalized": [] } ]

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[ { "id": "PMC-3150795-sec-01__text", "type": "sec", "text": [ "Introduction\nDuring the weaning period and transition to solid foods in the first year of life, infants take a critical step in their eating behavior and need to meet high nutrient requirements [1, 2]. They are exposed to new foods and food combinations, which should ensure a smooth transition to the family diet later in life. At this stage, either homemade or commercially prepared foods may be fed. It is worth noting that in prosperous countries the modern diet differs considerably from that of previous generations, now dominated by products that have been processed, stored, and transported over great distances. Traditional, cold-pressed vegetable oils of the highest nutritional quality, e.g. extra virgin olive oil, may therefore constitute an important part of the modern diet [3, 4].\nIn Poland, many infants do not receive any traditional homemade foods and even fruits come from purchased jars. Commercial baby foods are regarded by some parents and medical professionals to be more appropriate for several reasons: they undergo intense screening for contaminants in comparison to foods sold for the general population, contain no additives of certain types, and are thought to be designed to help infants meet nutrient requirements [5]. The process of peeling, however, was identified as the most effective, and simple, procedure in reducing residues, e.g. pesticides, in fruits and vegetables [6]. Moreover, contrary to homemade food, which does not contain furan, the highest average content of this chemical was found in ready-to-eat baby foods with pasta meals, followed by vegetable meals and meals with meat [7]. Furan is considered to be potentially hazardous chemical and is classified as a possible carcinogen. The problem of this chemical in homemade food may only arise if meals with potatoes are stored and then hardly re-heated [7].\nThere is a growing body of evidence that flavor experiences and dietary patterns in childhood influence these patterns later in life [1, 8, 9]. It is most likely early in life that culture-specific flavor preferences are initiated [10, 11]. Consequently, exposure to flavors and smells of transitory foods may serve to heighten preferences for \"known tastes\" in the family diet later in adulthood. Moreover, adopting elements of childhood dinner patterns was recognized to be an important part of the social reproduction of family identities across generations [12].\nProcessing industries have been successful in manufacturing and marketing jarred baby foods on a commercial scale. Available products contain different ingredients and depend on the manufacturer, country, traditional cuisine, income rate, and lastly, personal beliefs and values of parents [9, 11]. Jarred foods with vegetables, meats, and desserts may contain added fat from a variety of sources: vegetable oils, cow milk butter, or cream. Manufacturer advertising makes the majority of consumers feel safe, causing them to believe that they are doing the best possible in buying given products [11]. A noteworthy fact is that many types of baby foods produced by international manufacturers are, in essence, the same mixtures with different names; this procedure aims to exploit the specifics of local markets without delivering any new, real value [11].\nIn the book, How to Eat Well and Stay Well the Mediterranean Way by Keys [13] first used the term \"good Mediterranean diet\" to describe the eating patterns of populations dwelling in southern Europe, where the olive tree (Olea europaea) is an emblematic species [4, 14]. There is variation between the exact diet in different parts of the Mediterranean region. However, generalized and distinctive dietary patterns do exist, including olive oil as the main source of visible fat, employed both in cooking and as a dressing, moderate fish and poultry but low red meat consumption, high intake of vegetables, fruits, legumes, nuts, and whole-grain cereals [4, 14-16]. When dietary fats are added, in accordance with the traditional Mediterranean diet, olive oil is the choice for children [17]. It has been repeatedly observed that individuals applying the Mediterranean diet have reduced risks of type 2 diabetes and other diseases associated with the metabolic syndrome, autoimmunological diseases, and certain forms of cancer [18]. Moreover, considerable evidence exists that the Mediterranean diet increases quality of life in the course of ageing, as well as longevity [13, 19]. The health benefits of olive oil have been attributed to two main constituents: a high oleic acid (monounsaturated fatty acid, 18:1n-9) content (70-85%) and a large amount of antioxidant compounds, which also possess antiviral, antibacterial, and immunomodulating effects [3, 4, 14, 16]. Polyphenols found in virgin olive oil are linked to both its flavor and its remarkable stability [3].\nThe introduction of solid foods in infancy is one of the primary matters often discussed by parents with their child's pediatrician. However, many parents do not feel that the diet of their child may be linked to poor health outcomes in the future. Parents should be educated about the interplay of environmental and genetic influences on children, specifically during the early years of development when the child is maturing and taking control of its own diet [11]. Nutrition educators should increase the critical awareness of parents in relation to their child's solid food choices. It is important to emphasize to parents the fundamental role that the Mediterranean diet and consumption of foods with olive oil play in a healthy life style [14, 20]. Parental management of the family food environment may be complicated by numerous mitigating factors, e.g. health literacy, time availability, and financial resources. Considering the role baby food manufacturers play in the infant's contextual environment, their products, as well as the manufacturers themselves, should also be viewed as key players and central agents in establishing dietary habits. Consequently, we attempted to survey manufacturer claims concerning added fat in jarred infant foods supplied to the Polish market.\n" ], "offsets": [ [ 0, 6147 ] ] } ]

[ { "id": "PMC-3150795-sec-01_T1", "type": "Organism_substance", "text": [ "vegetable oils" ], "offsets": [ [ 647, 661 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T2", "type": "Organism_substance", "text": [ "olive oil" ], "offsets": [ [ 716, 725 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T3", "type": "Organism_subdivision", "text": [ "fruits" ], "offsets": [ [ 876, 882 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T4", "type": "Organism_subdivision", "text": [ "fruits" ], "offsets": [ [ 1387, 1393 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T5", "type": "Organism_subdivision", "text": [ "fruits" ], "offsets": [ [ 3892, 3898 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T6", "type": "Organism_subdivision", "text": [ "vegetables" ], "offsets": [ [ 1398, 1408 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T7", "type": "Organism_subdivision", "text": [ "vegetable" ], "offsets": [ [ 1593, 1602 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T8", "type": "Organism_subdivision", "text": [ "meat" ], "offsets": [ [ 1624, 1628 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T9", "type": "Organism_subdivision", "text": [ "vegetables" ], "offsets": [ [ 2745, 2755 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T10", "type": "Organism_subdivision", "text": [ "meats" ], "offsets": [ [ 2757, 2762 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T11", "type": "Organism_substance", "text": [ "vegetable oils" ], "offsets": [ [ 2826, 2840 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T12", "type": "Organism_substance", "text": [ "milk" ], "offsets": [ [ 2846, 2850 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T13", "type": "Organism_subdivision", "text": [ "red meat" ], "offsets": [ [ 3843, 3851 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T14", "type": "Organism_subdivision", "text": [ "vegetables" ], "offsets": [ [ 3880, 3890 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T15", "type": "Organism_subdivision", "text": [ "nuts" ], "offsets": [ [ 3909, 3913 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T16", "type": "Organism_substance", "text": [ "dietary fats" ], "offsets": [ [ 3956, 3968 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T17", "type": "Organism_substance", "text": [ "olive oil" ], "offsets": [ [ 4035, 4044 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T18", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 4305, 4311 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T19", "type": "Organism_substance", "text": [ "olive oil" ], "offsets": [ [ 4490, 4499 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T20", "type": "Organism_substance", "text": [ "olive oil" ], "offsets": [ [ 4783, 4792 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T21", "type": "Organism_substance", "text": [ "olive oil" ], "offsets": [ [ 5563, 5572 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T22", "type": "Organism_substance", "text": [ "olive oil" ], "offsets": [ [ 3720, 3729 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T23", "type": "Organism_subdivision", "text": [ "legumes" ], "offsets": [ [ 3900, 3907 ] ], "normalized": [] }, { "id": "PMC-3150795-sec-01_T24", "type": "Organism_substance", "text": [ "fat" ], "offsets": [ [ 3760, 3763 ] ], "normalized": [] } ]

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[ { "id": "PMID-10969782__text", "type": "abstract", "text": [ "Caspase-3 is essential for procaspase-9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells. \nIn this study, we sought to investigate in more detail the role of caspase-3 in apoptotic processes in cultured cells and in cell-free extracts of breast cancer cells. We present evidence that apoptosis of caspase-3-deficient MCF-7 breast cancer cells is defective in response to cisplatin treatment, as determined by chromatin condensation, nuclear fragmentation, DNA fragmentation, and release of cytochrome c from the mitochondria. Reconstitution of MCF-7 cells by stable transfection of CASP-3 cDNA restores all these defects and results in an extensive apoptosis after cisplatin treatment. We further show that in extracts from caspase-3-deficient MCF-7 cells, procaspase-9 processing is strongly impaired after stimulation with either cytochrome c or recombinant caspase-8. Reconstitution of MCF-7 cell extracts with procaspase-3 corrects this defect, resulting in an efficient and complete processing of procaspase-9. Together, our data define caspase-3 as an important integrator of the apoptotic process in MCF-7 breast cancer cells and reveal an essential function of caspase-3 for procaspase-9 processing.\n" ], "offsets": [ [ 0, 1231 ] ] } ]

[ { "id": "PMID-10969782_T4", "type": "Cell", "text": [ "MCF-7 breast cancer cells" ], "offsets": [ [ 86, 111 ] ], "normalized": [] }, { "id": "PMID-10969782_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 226, 231 ] ], "normalized": [] }, { "id": "PMID-10969782_T7", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 239, 243 ] ], "normalized": [] }, { "id": "PMID-10969782_T8", "type": "Organism_substance", "text": [ "extracts" ], "offsets": [ [ 249, 257 ] ], "normalized": [] }, { "id": "PMID-10969782_T9", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 261, 280 ] ], "normalized": [] }, { "id": "PMID-10969782_T11", "type": "Cell", "text": [ "caspase-3-deficient MCF-7 breast cancer cells" ], "offsets": [ [ 320, 365 ] ], "normalized": [] }, { "id": "PMID-10969782_T13", "type": "Cellular_component", "text": [ "chromatin" ], "offsets": [ [ 432, 441 ] ], "normalized": [] }, { "id": "PMID-10969782_T14", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 456, 463 ] ], "normalized": [] }, { "id": "PMID-10969782_T17", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 535, 547 ] ], "normalized": [] }, { "id": "PMID-10969782_T18", "type": "Cell", "text": [ "MCF-7 cells" ], "offsets": [ [ 567, 578 ] ], "normalized": [] }, { "id": "PMID-10969782_T21", "type": "Organism_substance", "text": [ "extracts" ], "offsets": [ [ 733, 741 ] ], "normalized": [] }, { "id": "PMID-10969782_T23", "type": "Cell", "text": [ "caspase-3-deficient MCF-7 cells" ], "offsets": [ [ 747, 778 ] ], "normalized": [] }, { "id": "PMID-10969782_T27", "type": "Organism_substance", "text": [ "MCF-7 cell extracts" ], "offsets": [ [ 912, 931 ] ], "normalized": [] }, { "id": "PMID-10969782_T31", "type": "Cell", "text": [ "MCF-7 breast cancer cells" ], "offsets": [ [ 1130, 1155 ] ], "normalized": [] } ]

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[ { "id": "PMID-17289834__text", "type": "abstract", "text": [ "Hyperforin blocks neutrophil activation of matrix metalloproteinase-9, motility and recruitment, and restrains inflammation-triggered angiogenesis and lung fibrosis.\nHyperforin (Hyp), a polyphenol-derivative of St. John's wort (Hypericum perforatum), has emerged as key player not only in the antidepressant activity of the plant but also as an inhibitor of bacteria lymphocyte and tumor cell proliferation, and matrix proteinases. We tested whether as well as inhibiting leukocyte elastase (LE) activity, Hyp might be effective in containing both polymorphonuclear neutrophil (PMN) leukocyte recruitment and unfavorable eventual tissue responses. The results show that, without affecting in vitro human PMN viability and chemokine-receptor expression, Hyp (as stable dicyclohexylammonium salt) was able to inhibit in a dose-dependent manner their chemotaxis and chemoinvasion (IC50=1 microM for both); this effect was associated with a reduced expression of the adhesion molecule CD11b by formyl-Met-Leu-Phe-stimulated neutrophils and block of LE-triggered activation of the gelatinase matrix metalloproteinase-9. PMN-triggered angiogenesis is also blocked by both local injection and daily i.p. administration of the Hyp salt in an interleukin-8-induced murine model. Furthermore, i.p. treatment with Hyp reduces acute PMN recruitment and enhances resolution in a pulmonary bleomycin-induced inflammation model, significantly reducing consequent fibrosis. These results indicate that Hyp is a powerful anti-inflammatory compound with therapeutic potential, and they elucidate mechanistic keys.\n" ], "offsets": [ [ 0, 1596 ] ] } ]

[ { "id": "PMID-17289834_T2", "type": "Cell", "text": [ "neutrophil" ], "offsets": [ [ 18, 28 ] ], "normalized": [] }, { "id": "PMID-17289834_T4", "type": "Organ", "text": [ "lung" ], "offsets": [ [ 151, 155 ] ], "normalized": [] }, { "id": "PMID-17289834_T10", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 367, 377 ] ], "normalized": [] }, { "id": "PMID-17289834_T11", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 382, 392 ] ], "normalized": [] }, { "id": "PMID-17289834_T16", "type": "Cell", "text": [ "polymorphonuclear neutrophil (PMN) leukocyte" ], "offsets": [ [ 548, 592 ] ], "normalized": [] }, { "id": "PMID-17289834_T17", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 630, 636 ] ], "normalized": [] }, { "id": "PMID-17289834_T19", "type": "Cell", "text": [ "PMN" ], "offsets": [ [ 704, 707 ] ], "normalized": [] }, { "id": "PMID-17289834_T24", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 1020, 1031 ] ], "normalized": [] }, { "id": "PMID-17289834_T27", "type": "Cell", "text": [ "PMN" ], "offsets": [ [ 1115, 1118 ] ], "normalized": [] }, { "id": "PMID-17289834_T32", "type": "Cell", "text": [ "PMN" ], "offsets": [ [ 1321, 1324 ] ], "normalized": [] }, { "id": "PMID-17289834_T33", "type": "Organ", "text": [ "pulmonary" ], "offsets": [ [ 1366, 1375 ] ], "normalized": [] } ]

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[ { "id": "PMID-16045802__text", "type": "abstract", "text": [ "Therapeutic Electromagnetic Field (TEMF) and gamma irradiation on human breast cancer xenograft growth, angiogenesis and metastasis.\nBACKGROUND: The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the end of IR. TEMF treatment continued for 3 additional weeks. Tumor sections were stained for: endothelial cells with CD31 and PAS or hypoxia inducible factor 1alpha (HIF). RESULTS: Most tumors less than 35 mm3 were white but tumors greater than 35 mm3 were pink and had a vascularized capsule. The cortex within 100 microns of the capsule had little vascularization. Blood vessels, capillaries, and endothelial pseudopods were found at greater than 100 microns from the capsule (subcortex). Tumors greater than 35 mm3 treated with IR 24 hours previously or with TEMF had decreased blood vessels in the subcortex and more endothelial pseudopods projecting into hypoxic, HIF positive areas than tumors from the control group. Mice that received either IR or TEMF had significantly fewer lung metastatic sites and slower tumor growth than did untreated mice. No harmful side effects were attributed to TEMF. CONCLUSION: TEMF therapy provided a safe means for retarding tumor vascularization, growth and metastasis.\n" ], "offsets": [ [ 0, 1770 ] ] } ]

[ { "id": "PMID-16045802_T2", "type": "Cancer", "text": [ "breast cancer xenograft" ], "offsets": [ [ 72, 95 ] ], "normalized": [] }, { "id": "PMID-16045802_T5", "type": "Cancer", "text": [ "MDA MB231 breast cancer xenograft" ], "offsets": [ [ 355, 388 ] ], "normalized": [] }, { "id": "PMID-16045802_T7", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 441, 453 ] ], "normalized": [] }, { "id": "PMID-16045802_T8", "type": "Tissue", "text": [ "mammary fat pad" ], "offsets": [ [ 477, 492 ] ], "normalized": [] }, { "id": "PMID-16045802_T12", "type": "Cancer", "text": [ "Tumor sections" ], "offsets": [ [ 815, 829 ] ], "normalized": [] }, { "id": "PMID-16045802_T13", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 848, 865 ] ], "normalized": [] }, { "id": "PMID-16045802_T18", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 940, 946 ] ], "normalized": [] }, { "id": "PMID-16045802_T19", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 980, 986 ] ], "normalized": [] }, { "id": "PMID-16045802_T20", "type": "Cancer", "text": [ "capsule" ], "offsets": [ [ 1041, 1048 ] ], "normalized": [] }, { "id": "PMID-16045802_T21", "type": "Cancer", "text": [ "cortex" ], "offsets": [ [ 1054, 1060 ] ], "normalized": [] }, { "id": "PMID-16045802_T22", "type": "Cancer", "text": [ "capsule" ], "offsets": [ [ 1087, 1094 ] ], "normalized": [] }, { "id": "PMID-16045802_T23", "type": "Multi-tissue_structure", "text": [ "Blood vessels" ], "offsets": [ [ 1123, 1136 ] ], "normalized": [] }, { "id": "PMID-16045802_T24", "type": "Tissue", "text": [ "capillaries" ], "offsets": [ [ 1138, 1149 ] ], "normalized": [] }, { "id": "PMID-16045802_T25", "type": "Cellular_component", "text": [ "endothelial pseudopods" ], "offsets": [ [ 1155, 1177 ] ], "normalized": [] }, { "id": "PMID-16045802_T26", "type": "Cancer", "text": [ "capsule" ], "offsets": [ [ 1227, 1234 ] ], "normalized": [] }, { "id": "PMID-16045802_T27", "type": "Cancer", "text": [ "subcortex" ], "offsets": [ [ 1236, 1245 ] ], "normalized": [] }, { "id": "PMID-16045802_T28", "type": "Cancer", "text": [ "Tumors" ], "offsets": [ [ 1248, 1254 ] ], "normalized": [] }, { "id": "PMID-16045802_T29", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 1339, 1352 ] ], "normalized": [] }, { "id": "PMID-16045802_T30", "type": "Cancer", "text": [ "subcortex" ], "offsets": [ [ 1360, 1369 ] ], "normalized": [] }, { "id": "PMID-16045802_T31", "type": "Cellular_component", "text": [ "endothelial pseudopods" ], "offsets": [ [ 1379, 1401 ] ], "normalized": [] }, { "id": "PMID-16045802_T33", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1451, 1457 ] ], "normalized": [] }, { "id": "PMID-16045802_T36", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1576, 1581 ] ], "normalized": [] }, { "id": "PMID-16045802_T38", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1724, 1729 ] ], "normalized": [] }, { "id": "PMID-16045802_T1", "type": "Cancer", "text": [ "lung metastatic sites" ], "offsets": [ [ 1543, 1564 ] ], "normalized": [] } ]

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[ { "id": "PMC-2703643-sec-15__text", "type": "sec", "text": [ "Sex and age distributions of confirmed cases\nOf 480 confirmed cases, 56% (269/480) were male patients and 44% (211/480) were female, respectively. The percentage of male cases was higher than that of females in all groups except for the group aged 31-40 (chi2 = 42.4, P < 0.001). 278 (57.9%) cases were in the group aged 21-50, followed by 102 (21.3%), 79 (16.5%) and 21 (4.4%) cases in the group aged 51-70, 0-20, and >= 71, respectively. The youngest and oldest cases were 1.5 and 81 years old, respectively (Table 2).\nTable 2\nAge and occupational distributions and activities (1-3 weeks prior to symptom appearance) of confirmed cases\nCases (%) (Male: Female, %)\nAge (Years)\n0-10 46 (9.6) (76:24)\n11-20 33 (6.9) (79:21)\n21-30 78 (16.3) (51:49)\n31-40 99 (20.6) (46:54)\n41-50 101 (21.0) (56:44)\n51-60 47 (9.8) (55:45)\n61-70 55 (11.5) (53:47)\n>= 71 21 (4.4) (52:48)\nOccupation\nChildren at preschool age 20 (4.2) (75:25)\nPupils 50 (10.4) (78:22)\nFarmers 408 (85.0) (52:48)\nOthers 2 (0.4) (50:50)\nActivities\nFarm work 325 (67.7) (53:47)\nPlay on grassland 65 (13.5) (75:25)\nRecreation 20 (4.2) (65:35)\nHousework 25 (5.2) (8:92)\nUnknown 45 (9.4) (71:29)\n" ], "offsets": [ [ 0, 1150 ] ] } ]

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[ { "id": "PMID-20955597__text", "type": "abstract", "text": [ "Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis. \nBACKGROUND: The Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. METHODS: Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. RESULTS: In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. CONCLUSION: Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.\n" ], "offsets": [ [ 0, 1898 ] ] } ]

[ { "id": "PMID-20955597_T2", "type": "Cell", "text": [ "breast cancer cell" ], "offsets": [ [ 50, 68 ] ], "normalized": [] }, { "id": "PMID-20955597_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 324, 329 ] ], "normalized": [] }, { "id": "PMID-20955597_T11", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 438, 443 ] ], "normalized": [] }, { "id": "PMID-20955597_T14", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 550, 569 ] ], "normalized": [] }, { "id": "PMID-20955597_T15", "type": "Cell", "text": [ "T47D cells" ], "offsets": [ [ 622, 632 ] ], "normalized": [] }, { "id": "PMID-20955597_T18", "type": "Cell", "text": [ "Cell" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-20955597_T21", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 916, 935 ] ], "normalized": [] }, { "id": "PMID-20955597_T23", "type": "Cell", "text": [ "breast cancer cell lines" ], "offsets": [ [ 977, 1001 ] ], "normalized": [] }, { "id": "PMID-20955597_T24", "type": "Cell", "text": [ "MDA-MB231" ], "offsets": [ [ 1003, 1012 ] ], "normalized": [] }, { "id": "PMID-20955597_T25", "type": "Cell", "text": [ "T47D" ], "offsets": [ [ 1017, 1021 ] ], "normalized": [] }, { "id": "PMID-20955597_T26", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1066, 1070 ] ], "normalized": [] }, { "id": "PMID-20955597_T28", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 1138, 1157 ] ], "normalized": [] }, { "id": "PMID-20955597_T29", "type": "Cell", "text": [ "MDA-MB231" ], "offsets": [ [ 1159, 1168 ] ], "normalized": [] }, { "id": "PMID-20955597_T30", "type": "Cell", "text": [ "T47D" ], "offsets": [ [ 1173, 1177 ] ], "normalized": [] }, { "id": "PMID-20955597_T31", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1211, 1215 ] ], "normalized": [] }, { "id": "PMID-20955597_T34", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1348, 1353 ] ], "normalized": [] }, { "id": "PMID-20955597_T35", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 1422, 1441 ] ], "normalized": [] }, { "id": "PMID-20955597_T38", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 1531, 1550 ] ], "normalized": [] }, { "id": "PMID-20955597_T41", "type": "Cell", "text": [ "T47D cell" ], "offsets": [ [ 1668, 1677 ] ], "normalized": [] }, { "id": "PMID-20955597_T44", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1789, 1794 ] ], "normalized": [] }, { "id": "PMID-20955597_T45", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 1877, 1896 ] ], "normalized": [] } ]

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[ { "id": "PMC-529442-sec-05__text", "type": "sec", "text": [ "Results\n\n" ], "offsets": [ [ 0, 9 ] ] } ]

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[ { "id": "PMID-7897308__text", "type": "abstract", "text": [ "Effects of doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells.\nMetastatic disease is one of the major causes of death from cancer in human beings. Several enzyme systems have been implicated in the metastatic process, but the metalloproteinases (MPs) appear to be the major group involved in most instances of neoplastic invasion. Increased MP activity has been correlated with the metastatic potential of many cancers, including breast cancer. MPs also play a role in tumor angiogenesis. Tetracyclines are antimicrobial agents that can suppress MP activity in a variety of tissues, including gingiva, bone, and cartilage. Several reports have indicated that tetracyclines can suppress tumor MPs as well. A synthetic tetracycline, doxycycline, inhibits migration of human MDA-MB-435 breast adenocarcinoma cells through a reconstituted basement membrane (Matrigel), an assay used as an in vitro surrogate for the in vivo process of tumor invasion through basement membranes. Additionally, doxycycline diminishes the proliferation of this breast cancer cell line and also decreases its gelatinolytic activity, as determined by gel zymography.\n" ], "offsets": [ [ 0, 1183 ] ] } ]

[ { "id": "PMID-7897308_T2", "type": "Cell", "text": [ "breast carcinoma cells" ], "offsets": [ [ 81, 103 ] ], "normalized": [] }, { "id": "PMID-7897308_T3", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 165, 171 ] ], "normalized": [] }, { "id": "PMID-7897308_T8", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 453, 460 ] ], "normalized": [] }, { "id": "PMID-7897308_T9", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 472, 485 ] ], "normalized": [] }, { "id": "PMID-7897308_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 511, 516 ] ], "normalized": [] }, { "id": "PMID-7897308_T14", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 616, 623 ] ], "normalized": [] }, { "id": "PMID-7897308_T15", "type": "Multi-tissue_structure", "text": [ "gingiva" ], "offsets": [ [ 635, 642 ] ], "normalized": [] }, { "id": "PMID-7897308_T16", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 644, 648 ] ], "normalized": [] }, { "id": "PMID-7897308_T17", "type": "Tissue", "text": [ "cartilage" ], "offsets": [ [ 654, 663 ] ], "normalized": [] }, { "id": "PMID-7897308_T19", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 728, 733 ] ], "normalized": [] }, { "id": "PMID-7897308_T24", "type": "Cell", "text": [ "MDA-MB-435 breast adenocarcinoma cells" ], "offsets": [ [ 814, 852 ] ], "normalized": [] }, { "id": "PMID-7897308_T25", "type": "Cellular_component", "text": [ "basement membrane" ], "offsets": [ [ 877, 894 ] ], "normalized": [] }, { "id": "PMID-7897308_T26", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 973, 978 ] ], "normalized": [] }, { "id": "PMID-7897308_T27", "type": "Cellular_component", "text": [ "basement membranes" ], "offsets": [ [ 996, 1014 ] ], "normalized": [] }, { "id": "PMID-7897308_T29", "type": "Cell", "text": [ "breast cancer cell line" ], "offsets": [ [ 1079, 1102 ] ], "normalized": [] }, { "id": "PMID-7897308_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 352, 362 ] ], "normalized": [] } ]

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[ { "id": "PMID-8097963__text", "type": "abstract", "text": [ "Increased expression of specific protein tyrosine phosphatases in human breast epithelial cells neoplastically transformed by the neu oncogene. \nProtein tyrosine phosphorylation/dephosphorylation is a fundamental mechanism in the regulation of cell proliferation and neoplastic transformation; this metabolic process is modulated by the opposing activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPases). While the role of protein tyrosine kinases has been examined extensively in human breast tumorigenesis, the role of PTPases in this process is virtually unknown. To address this issue, an activated neu oncogene was introduced into an immortalized nontumorigenic human breast epithelial cell line (184B5). This resulted in a substantial increase in P185neu expression, which led to the formation of progressively growing carcinomas after such cells were inoculated into athymic nude mice. Importantly, a striking increase in the expression of specific PTPases, LAR and PTP1B, was observed in 3 independently neu transformed cell lines and their derived tumors. This elevation was verified at both the mRNA and protein levels. TC-PTP PTPase expression was only slightly increased in these neu transformed cells, and no expression of CD45 PTPase was observed. The level of neu expression, as well as the differential expression between P185neu and LAR/PTP1B, directly correlated with tumorigenicity. Furthermore, rat mammary carcinomas with elevated neu expression (neu-induced) also had sharply elevated LAR-PTPase expression when compared to rat mammary carcinomas with little or no neu expression (7,12-dimethylbenzanthracene induced); the level of expression of LAR PTPase was directly correlated with the level of neu expression. Thus, our results provide the first evidence that, in human breast carcinoma cells and in rat mammary carcinomas that have an induced increase in neu expression, a consistent and substantial increase in the expression of specific PTPases occurs. The relationship between P185neu-protein tyrosine kinase expression and specific PTPase expression may play a critical role in human breast tumorigenesis.\n" ], "offsets": [ [ 0, 2163 ] ] } ]

[ { "id": "PMID-8097963_T3", "type": "Cell", "text": [ "breast epithelial cells" ], "offsets": [ [ 72, 95 ] ], "normalized": [] }, { "id": "PMID-8097963_T6", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 244, 248 ] ], "normalized": [] }, { "id": "PMID-8097963_T12", "type": "Organism_subdivision", "text": [ "breast" ], "offsets": [ [ 512, 518 ] ], "normalized": [] }, { "id": "PMID-8097963_T16", "type": "Cell", "text": [ "breast epithelial cell line" ], "offsets": [ [ 698, 725 ] ], "normalized": [] }, { "id": "PMID-8097963_T17", "type": "Cell", "text": [ "184B5" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "PMID-8097963_T19", "type": "Cancer", "text": [ "carcinomas" ], "offsets": [ [ 850, 860 ] ], "normalized": [] }, { "id": "PMID-8097963_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 872, 877 ] ], "normalized": [] }, { "id": "PMID-8097963_T26", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1053, 1063 ] ], "normalized": [] }, { "id": "PMID-8097963_T27", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1082, 1088 ] ], "normalized": [] }, { "id": "PMID-8097963_T30", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [] }, { "id": "PMID-8097963_T37", "type": "Cancer", "text": [ "mammary carcinomas" ], "offsets": [ [ 1444, 1462 ] ], "normalized": [] }, { "id": "PMID-8097963_T42", "type": "Cancer", "text": [ "mammary carcinomas" ], "offsets": [ [ 1575, 1593 ] ], "normalized": [] }, { "id": "PMID-8097963_T48", "type": "Cell", "text": [ "breast carcinoma cells" ], "offsets": [ [ 1822, 1844 ] ], "normalized": [] }, { "id": "PMID-8097963_T50", "type": "Cancer", "text": [ "mammary carcinomas" ], "offsets": [ [ 1856, 1874 ] ], "normalized": [] }, { "id": "PMID-8097963_T57", "type": "Organism_subdivision", "text": [ "breast" ], "offsets": [ [ 2141, 2147 ] ], "normalized": [] }, { "id": "PMID-8097963_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 267, 277 ] ], "normalized": [] } ]

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[ { "id": "PMID-17369844__text", "type": "abstract", "text": [ "Tsg101 is upregulated in a subset of invasive human breast cancers and its targeted overexpression in transgenic mice reveals weak oncogenic properties for mammary cancer initiation. \nPrevious studies reported that the Tumor Susceptibility Gene 101 (TSG101) is upregulated in selected human malignancies, and the expression of exogenous Tsg101 was suggested to transform immortalized fibroblasts in culture. To date, the potential oncogenic properties of Tsg101 have not been examined in vivo owing to the lack of appropriate model systems. In this study, we show that Tsg101 is highly expressed in a subset of invasive human breast cancers. Based on this observation, we generated the first transgenic mouse model with a targeted overexpression of Tsg101 in the developing mammary gland to test whether exogenous Tsg101 is capable of initiating tumorigenesis. Normal functionality of exogenous Tsg101 was tested by rescuing the survival of Tsg101-deficient mammary epithelial cells in conditional knockout mice. The overexpression of Tsg101 resulted in increased phosphorylation of the epidermal growth factor receptor and downstream activation of MAP kinases. Despite an increase in the activation of these signal transducers, the mammary gland of females expressing exogenous Tsg101 developed normally throughout the reproductive cycle. In aging females, the overexpression of Tsg101 seemed to increase the susceptibility of mammary epithelia toward malignant transformation. However, owing to the long latency of tumor formation and the sporadic occurrence of bona fide mammary cancers, we conclude that the Tsg101 protein has only weak oncogenic properties. Instead of cancer initiation, it is therefore likely that Tsg101 plays a more predominant role in the progression of a subset of spontaneously arising breast cancers.\n" ], "offsets": [ [ 0, 1830 ] ] } ]

[ { "id": "PMID-17369844_T3", "type": "Cancer", "text": [ "invasive human breast cancers" ], "offsets": [ [ 37, 66 ] ], "normalized": [] }, { "id": "PMID-17369844_T5", "type": "Cancer", "text": [ "mammary cancer" ], "offsets": [ [ 156, 170 ] ], "normalized": [] }, { "id": "PMID-17369844_T9", "type": "Cancer", "text": [ "malignancies" ], "offsets": [ [ 291, 303 ] ], "normalized": [] }, { "id": "PMID-17369844_T11", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 384, 395 ] ], "normalized": [] }, { "id": "PMID-17369844_T15", "type": "Cancer", "text": [ "invasive human breast cancers" ], "offsets": [ [ 611, 640 ] ], "normalized": [] }, { "id": "PMID-17369844_T18", "type": "Organ", "text": [ "mammary gland" ], "offsets": [ [ 774, 787 ] ], "normalized": [] }, { "id": "PMID-17369844_T22", "type": "Cell", "text": [ "mammary epithelial cells" ], "offsets": [ [ 958, 982 ] ], "normalized": [] }, { "id": "PMID-17369844_T27", "type": "Organ", "text": [ "mammary gland" ], "offsets": [ [ 1233, 1246 ] ], "normalized": [] }, { "id": "PMID-17369844_T30", "type": "Tissue", "text": [ "mammary epithelia" ], "offsets": [ [ 1428, 1445 ] ], "normalized": [] }, { "id": "PMID-17369844_T31", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1517, 1522 ] ], "normalized": [] }, { "id": "PMID-17369844_T32", "type": "Cancer", "text": [ "mammary cancers" ], "offsets": [ [ 1574, 1589 ] ], "normalized": [] }, { "id": "PMID-17369844_T34", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1674, 1680 ] ], "normalized": [] }, { "id": "PMID-17369844_T36", "type": "Cancer", "text": [ "breast cancers" ], "offsets": [ [ 1814, 1828 ] ], "normalized": [] } ]

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[ { "id": "PMID-18451223__text", "type": "abstract", "text": [ "Hematogenous metastasis in gastric cancer requires isolated tumor cells and expression of vascular endothelial growth factor receptor-1. \nPURPOSE: Recent studies of cancer metastasis have focused on the role of premetastatic gene expression and circulating tumor cells. We did a blind prospective study in gastric cancer to assess the significance of isolated tumor cells (ITC) and to test the hypothesis that vascular endothelial growth factor receptor-1 (VEGFR-1) is expressed within the bone marrow at tumor-specific, premetastatic sites. EXPERIMENTAL DESIGN: Both bone marrow and peripheral blood samples from 810 gastric cancer patients were collected at the Central Hospital, National Cancer Center (Tokyo, Japan). The samples were transferred to Kyushu University Hospital (Beppu, Japan) where they were analyzed by quantitative real-time reverse transcription-PCR for three epithelial cell markers, carcinoembryonic antigen, cytokeratin-19, and cytokeratin-7, as well as VEGFR-1. RESULTS: ITCs were observed in peripheral blood and bone marrow even in early stages of gastric cancer. The frequency of ITC in bone marrow was significantly associated with the stage of disease by ANOVA (P < 0.01). Gastric cancer metastasized when ITCs were observed in the presence of VEGFR-1. In the 380 patients who were ITC negative and showed low VEGFR-1 expression, synchronous (at the time of surgery) and heterochronous (recurrent) metastases were not observed. CONCLUSIONS: ITCs circulate even in early stages of disease. Furthermore, elevated expression of VEGFR-1 facilitates the establishment of hematogenous metastases in gastric cancer. This study indicates that the simultaneous presence of ITC and VEGFR-1 expression at premetastatic sites is clinically significant for disease progression.\n" ], "offsets": [ [ 0, 1796 ] ] } ]

[ { "id": "PMID-18451223_T1", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 27, 41 ] ], "normalized": [] }, { "id": "PMID-18451223_T2", "type": "Cell", "text": [ "isolated tumor cells" ], "offsets": [ [ 51, 71 ] ], "normalized": [] }, { "id": "PMID-18451223_T4", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 165, 171 ] ], "normalized": [] }, { "id": "PMID-18451223_T5", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 257, 268 ] ], "normalized": [] }, { "id": "PMID-18451223_T6", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 306, 320 ] ], "normalized": [] }, { "id": "PMID-18451223_T7", "type": "Cell", "text": [ "isolated tumor cells" ], "offsets": [ [ 351, 371 ] ], "normalized": [] }, { "id": "PMID-18451223_T8", "type": "Cell", "text": [ "ITC" ], "offsets": [ [ 373, 376 ] ], "normalized": [] }, { "id": "PMID-18451223_T11", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 490, 501 ] ], "normalized": [] }, { "id": "PMID-18451223_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 505, 510 ] ], "normalized": [] }, { "id": "PMID-18451223_T13", "type": "Multi-tissue_structure", "text": [ "premetastatic sites" ], "offsets": [ [ 521, 540 ] ], "normalized": [] }, { "id": "PMID-18451223_T14", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 568, 579 ] ], "normalized": [] }, { "id": "PMID-18451223_T15", "type": "Organism_substance", "text": [ "peripheral blood samples" ], "offsets": [ [ 584, 608 ] ], "normalized": [] }, { "id": "PMID-18451223_T16", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 618, 632 ] ], "normalized": [] }, { "id": "PMID-18451223_T18", "type": "Cell", "text": [ "epithelial cell" ], "offsets": [ [ 882, 897 ] ], "normalized": [] }, { "id": "PMID-18451223_T23", "type": "Cell", "text": [ "ITCs" ], "offsets": [ [ 997, 1001 ] ], "normalized": [] }, { "id": "PMID-18451223_T24", "type": "Organism_substance", "text": [ "peripheral blood" ], "offsets": [ [ 1019, 1035 ] ], "normalized": [] }, { "id": "PMID-18451223_T25", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 1040, 1051 ] ], "normalized": [] }, { "id": "PMID-18451223_T26", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 1076, 1090 ] ], "normalized": [] }, { "id": "PMID-18451223_T27", "type": "Cell", "text": [ "ITC" ], "offsets": [ [ 1109, 1112 ] ], "normalized": [] }, { "id": "PMID-18451223_T28", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 1116, 1127 ] ], "normalized": [] }, { "id": "PMID-18451223_T29", "type": "Cancer", "text": [ "Gastric cancer" ], "offsets": [ [ 1204, 1218 ] ], "normalized": [] }, { "id": "PMID-18451223_T30", "type": "Cell", "text": [ "ITCs" ], "offsets": [ [ 1237, 1241 ] ], "normalized": [] }, { "id": "PMID-18451223_T33", "type": "Cell", "text": [ "ITC" ], "offsets": [ [ 1313, 1316 ] ], "normalized": [] }, { "id": "PMID-18451223_T35", "type": "Cell", "text": [ "ITCs" ], "offsets": [ [ 1472, 1476 ] ], "normalized": [] }, { "id": "PMID-18451223_T37", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 1624, 1638 ] ], "normalized": [] }, { "id": "PMID-18451223_T38", "type": "Cell", "text": [ "ITC" ], "offsets": [ [ 1695, 1698 ] ], "normalized": [] }, { "id": "PMID-18451223_T40", "type": "Multi-tissue_structure", "text": [ "premetastatic sites" ], "offsets": [ [ 1725, 1744 ] ], "normalized": [] }, { "id": "PMID-18451223_T60", "type": "Organism_substance", "text": [ "samples" ], "offsets": [ [ 725, 732 ] ], "normalized": [] }, { "id": "PMID-18451223_T3", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 1429, 1439 ] ], "normalized": [] }, { "id": "PMID-18451223_T9", "type": "Cancer", "text": [ "hematogenous metastases" ], "offsets": [ [ 1597, 1620 ] ], "normalized": [] } ]

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[ { "id": "PMID-8083968__text", "type": "abstract", "text": [ "Identification of latency-associated transcripts that map antisense to the ICP4 homolog gene of Marek's disease virus. \nTwo small RNAs (0.9 and 0.75 kb), named Marek's disease virus (MDV) small RNAs (MSRs) and a 10-kb RNA, all of which map antisense to the MDV ICP4 homolog gene, have been readily detected in MDCC-MSB1 MDV-transformed T-lymphoblastoid cells. These RNAs were not detectable in reticuloendotheliosis virus-transformed T cells. When MDV was reactivated by treatment of lymphoblastoid cells with 25 micrograms of iododeoxyuridine per ml, the relative levels of the transcripts decreased. These RNAs were not detected by Northern (RNA) hybridization in productively infected chicken embryo fibroblasts 48 h postinfection; however, they were apparent 140 h postinfection. By using Northern hybridization, RNase protection assays, and primer extension analysis, the MSRs were determined to map antisense to the predicted translational start site of the ICP4 homolog gene. The conclusion most consistent with the data is that the two MSRs are overlapping, spliced RNAs. Both small RNAs contain a latency promoter binding factor consensus recognition sequence located toward their 5' ends as well as two potential ICP4 recognition consensus sequences, one in each orientation. The region contains a number of small open reading frames on each side and within the MSRs. Although the exact endpoints are unknown, the large 10-kb species spans the entire ICP4 homolog region. We believe that this group of RNAs, which map antisense to the ICP4 homolog gene, are latency-associated transcripts of MDV.\n" ], "offsets": [ [ 0, 1607 ] ] } ]

[ { "id": "PMID-8083968_T7", "type": "Cell", "text": [ "MDCC-MSB1" ], "offsets": [ [ 310, 319 ] ], "normalized": [] }, { "id": "PMID-8083968_T9", "type": "Cell", "text": [ "T-lymphoblastoid cells" ], "offsets": [ [ 336, 358 ] ], "normalized": [] }, { "id": "PMID-8083968_T11", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 434, 441 ] ], "normalized": [] }, { "id": "PMID-8083968_T13", "type": "Cell", "text": [ "lymphoblastoid cells" ], "offsets": [ [ 484, 504 ] ], "normalized": [] }, { "id": "PMID-8083968_T16", "type": "Cell", "text": [ "embryo fibroblasts" ], "offsets": [ [ 696, 714 ] ], "normalized": [] } ]

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[ { "id": "PMID-12485499__text", "type": "abstract", "text": [ "[Expression and mutation of c-kit gene in gastrointestinal stromal tumor]. \nOBJECTIVE: To investigate the effect of the expression and mutation of c-kit gene and its relationship with clinical pathology and prognosis of gastrointestinal stromal tumor (GIST). METHODS: Immunohistochemical and PCR-SSCP techniques were used to detect c-kit protein expression and c-kit gene exon 11 mutation in 82 patients with GIST. RESULTS: The positive c-kit protein expression and c-kit gene mutation rates were 97.6% (80/82) and 41.5% (34/82). Correlating the results of these two methods and clinicopathological factors, the c-kit expression and c-kit gene mutation rates were 95.0% (19/20) and 0 in benign GIST, and were 98.4% (61/62), 54.8% (34/62) in malignant GIST. Mutation positive GIST showed higher frequency of adjacent tissue invasion, metastasis and recurrence as compared with mutation negative ones. CONCLUSION: c-kit protein is an important diagnostic marker of gastrointestinal stromal tumor. c-kit gene mutation may play a significant role in the pathogenesis of GIST and also may be a prognostic marker.\n" ], "offsets": [ [ 0, 1108 ] ] } ]

[ { "id": "PMID-12485499_T2", "type": "Cancer", "text": [ "gastrointestinal stromal tumor" ], "offsets": [ [ 42, 72 ] ], "normalized": [] }, { "id": "PMID-12485499_T4", "type": "Cancer", "text": [ "gastrointestinal stromal tumor" ], "offsets": [ [ 220, 250 ] ], "normalized": [] }, { "id": "PMID-12485499_T5", "type": "Cancer", "text": [ "GIST" ], "offsets": [ [ 252, 256 ] ], "normalized": [] }, { "id": "PMID-12485499_T9", "type": "Cancer", "text": [ "GIST" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "PMID-12485499_T14", "type": "Cancer", "text": [ "benign GIST" ], "offsets": [ [ 687, 698 ] ], "normalized": [] }, { "id": "PMID-12485499_T15", "type": "Cancer", "text": [ "malignant GIST" ], "offsets": [ [ 741, 755 ] ], "normalized": [] }, { "id": "PMID-12485499_T16", "type": "Cancer", "text": [ "GIST" ], "offsets": [ [ 775, 779 ] ], "normalized": [] }, { "id": "PMID-12485499_T17", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 816, 822 ] ], "normalized": [] }, { "id": "PMID-12485499_T19", "type": "Cancer", "text": [ "gastrointestinal stromal tumor" ], "offsets": [ [ 963, 993 ] ], "normalized": [] }, { "id": "PMID-12485499_T21", "type": "Cancer", "text": [ "GIST" ], "offsets": [ [ 1066, 1070 ] ], "normalized": [] } ]

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[ { "id": "PMID-20385008__text", "type": "abstract", "text": [ "Lactate-dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1.\nAIMS: As one of the five lactate dehydrogenase (LDH) isoenzymes, LDH5 has the highest efficiency to catalyze pyruvate transformation to lactate. LDH5 overexpression in cancer cells induces an upregulated glycolytic metabolism and reduced dependence on the presence of oxygen. Here we analyzed LDH5 protein expression in a well characterized large cohort of primary lung cancers in correlation to clinico-pathological data and its possible impact on patient survival. METHODS: Primary lung cancers (n = 269) and non neoplastic lung tissue (n = 35) were tested for LDH5 expression by immunohistochemistry using a polyclonal LDH5 antibody (ab53010). The results of LDH5 expression were correlated to clinico-pathological data as well as to patient's survival. In addition, the results of the previously tested transketolase like 1 protein (TKTL1) expression were correlated to LDH5 expression. RESULTS: 89.5% (n = 238) of NSCLC revealed LDH5 expression whereas LDH5 expression was not detected in non neoplastic lung tissues (n = 34) (p < 0.0001). LDH5 overexpression was associated with histological type (adenocarcinoma = 57%, squamous cell carcinoma = 45%, large cell carcinoma = 46%, p = 0.006). No significant correlation could be detected with regard to TNM-stage, grading or survival. A two sided correlation between the expression of TKTL1 and LDH5 could be shown (p = 0.002) within the overall cohort as well as for each grading and pN group. A significant correlation between LDH5 and TKTL1 within each histologic tumortype could not be revealed. CONCLUSIONS: LDH5 is overexpressed in NSCLC and could hence serve as an additional marker for malignancy. Furthermore, LDH5 correlates positively with the prognostic marker TKTL1. Our results confirm a close link between the two metabolic enzymes and indicate an alteration in the glucose metabolism in the process of malignant transformation.\n" ], "offsets": [ [ 0, 2041 ] ] } ]

[ { "id": "PMID-20385008_T2", "type": "Cancer", "text": [ "non-small cell lung cancer" ], "offsets": [ [ 44, 70 ] ], "normalized": [] }, { "id": "PMID-20385008_T10", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 311, 323 ] ], "normalized": [] }, { "id": "PMID-20385008_T13", "type": "Cancer", "text": [ "primary lung cancers" ], "offsets": [ [ 500, 520 ] ], "normalized": [] }, { "id": "PMID-20385008_T15", "type": "Cancer", "text": [ "Primary lung cancers" ], "offsets": [ [ 619, 639 ] ], "normalized": [] }, { "id": "PMID-20385008_T16", "type": "Tissue", "text": [ "non neoplastic lung tissue" ], "offsets": [ [ 654, 680 ] ], "normalized": [] }, { "id": "PMID-20385008_T24", "type": "Cancer", "text": [ "NSCLC" ], "offsets": [ [ 1062, 1067 ] ], "normalized": [] }, { "id": "PMID-20385008_T27", "type": "Tissue", "text": [ "non neoplastic lung tissues" ], "offsets": [ [ 1137, 1164 ] ], "normalized": [] }, { "id": "PMID-20385008_T29", "type": "Cancer", "text": [ "adenocarcinoma" ], "offsets": [ [ 1247, 1261 ] ], "normalized": [] }, { "id": "PMID-20385008_T30", "type": "Cancer", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 1269, 1292 ] ], "normalized": [] }, { "id": "PMID-20385008_T31", "type": "Cancer", "text": [ "large cell carcinoma" ], "offsets": [ [ 1300, 1320 ] ], "normalized": [] }, { "id": "PMID-20385008_T36", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1664, 1669 ] ], "normalized": [] }, { "id": "PMID-20385008_T38", "type": "Cancer", "text": [ "NSCLC" ], "offsets": [ [ 1735, 1740 ] ], "normalized": [] } ]

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[ { "id": "PMID-19742300__text", "type": "abstract", "text": [ "Islet endothelial activation and oxidative stress gene expression is reduced by IL-1Ra treatment in the type 2 diabetic GK rat.\nBACKGROUND: Inflammation followed by fibrosis is a component of islet dysfunction in both rodent and human type 2 diabetes. Because islet inflammation may originate from endothelial cells, we assessed the expression of selected genes involved in endothelial cell activation in islets from a spontaneous model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet vascularization and fibrosis after treatment with the interleukin-1 (IL-1) receptor antagonist (IL-1Ra). METHODOLOGY/PRINCIPAL FINDINGS: Gene expression was analyzed by quantitative RT-PCR on islets isolated from 10-week-old diabetic GK and control Wistar rats. Furthermore, GK rats were treated s.c twice daily with IL-1Ra (Kineret, Amgen, 100 mg/kg/day) or saline, from 4 weeks of age onwards (onset of diabetes). Four weeks later, islet gene analysis and pancreas immunochemistry were performed. Thirty-two genes were selected encoding molecules involved in endothelial cell activation, particularly fibrinolysis, vascular tone, OS, angiogenesis and also inflammation. All genes except those encoding angiotensinogen and epoxide hydrolase (that were decreased), and 12-lipoxygenase and vascular endothelial growth factor (that showed no change), were significantly up-regulated in GK islets. After IL-1Ra treatment of GK rats in vivo, most selected genes implied in endothelium/OS/immune cells/fibrosis were significantly down-regulated. IL-1Ra also improved islet vascularization, reduced fibrosis and ameliorated glycemia. CONCLUSIONS/SIGNIFICANCE: GK rat islets have increased mRNA expression of markers of early islet endothelial cell activation, possibly triggered by several metabolic factors, and also some defense mechanisms. The beneficial effect of IL-1Ra on most islet endothelial/OS/immune cells/fibrosis parameters analyzed highlights a major endothelial-related role for IL-1 in GK islet alterations. Thus, metabolically-altered islet endothelium might affect the beta-cell microenvironment and contribute to progressive type 2 diabetic beta-cell dysfunction in GK rats. Counteracting islet endothelial cell inflammation might be one way to ameliorate/prevent beta-cell dysfunction in type 2 diabetes.\n" ], "offsets": [ [ 0, 2406 ] ] } ]

[ { "id": "PMID-19742300_T1", "type": "Cell", "text": [ "Islet endothelial" ], "offsets": [ [ 0, 17 ] ], "normalized": [] }, { "id": "PMID-19742300_T4", "type": "Multi-tissue_structure", "text": [ "islet" ], "offsets": [ [ 192, 197 ] ], "normalized": [] }, { "id": "PMID-19742300_T6", "type": "Multi-tissue_structure", "text": [ "islet" ], "offsets": [ [ 260, 265 ] ], "normalized": [] }, { "id": "PMID-19742300_T7", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 298, 315 ] ], "normalized": [] }, { "id": "PMID-19742300_T8", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 374, 390 ] ], "normalized": [] }, { "id": "PMID-19742300_T9", "type": "Multi-tissue_structure", "text": [ "islets" ], "offsets": [ [ 405, 411 ] ], "normalized": [] }, { "id": "PMID-19742300_T11", "type": "Tissue", "text": [ "islet endotheliuml" ], "offsets": [ [ 502, 520 ] ], "normalized": [] }, { "id": "PMID-19742300_T12", "type": "Multi-tissue_structure", "text": [ "islet" ], "offsets": [ [ 581, 586 ] ], "normalized": [] }, { "id": "PMID-19742300_T15", "type": "Multi-tissue_structure", "text": [ "islets" ], "offsets": [ [ 779, 785 ] ], "normalized": [] }, { "id": "PMID-19742300_T22", "type": "Multi-tissue_structure", "text": [ "islet" ], "offsets": [ [ 1021, 1026 ] ], "normalized": [] }, { "id": "PMID-19742300_T23", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 1045, 1053 ] ], "normalized": [] }, { "id": "PMID-19742300_T24", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1148, 1164 ] ], "normalized": [] }, { "id": "PMID-19742300_T25", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1204, 1212 ] ], "normalized": [] }, { "id": "PMID-19742300_T31", "type": "Multi-tissue_structure", "text": [ "islets" ], "offsets": [ [ 1474, 1480 ] ], "normalized": [] }, { "id": "PMID-19742300_T34", "type": "Tissue", "text": [ "endothelium" ], "offsets": [ [ 1556, 1567 ] ], "normalized": [] }, { "id": "PMID-19742300_T35", "type": "Cell", "text": [ "immune cells" ], "offsets": [ [ 1571, 1583 ] ], "normalized": [] }, { "id": "PMID-19742300_T37", "type": "Multi-tissue_structure", "text": [ "islet" ], "offsets": [ [ 1649, 1654 ] ], "normalized": [] }, { "id": "PMID-19742300_T39", "type": "Multi-tissue_structure", "text": [ "islets" ], "offsets": [ [ 1748, 1754 ] ], "normalized": [] }, { "id": "PMID-19742300_T40", "type": "Cell", "text": [ "islet endothelial cell" ], "offsets": [ [ 1806, 1828 ] ], "normalized": [] }, { "id": "PMID-19742300_T42", "type": "Cell", "text": [ "islet endothelial" ], "offsets": [ [ 1964, 1981 ] ], "normalized": [] }, { "id": "PMID-19742300_T43", "type": "Cell", "text": [ "immune cells" ], "offsets": [ [ 1985, 1997 ] ], "normalized": [] }, { "id": "PMID-19742300_T44", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 2046, 2057 ] ], "normalized": [] }, { "id": "PMID-19742300_T47", "type": "Multi-tissue_structure", "text": [ "islet" ], "offsets": [ [ 2086, 2091 ] ], "normalized": [] }, { "id": "PMID-19742300_T48", "type": "Tissue", "text": [ "islet endothelium" ], "offsets": [ [ 2133, 2150 ] ], "normalized": [] }, { "id": "PMID-19742300_T49", "type": "Cell", "text": [ "beta-cell" ], "offsets": [ [ 2168, 2177 ] ], "normalized": [] }, { "id": "PMID-19742300_T50", "type": "Cell", "text": [ "beta-cell" ], "offsets": [ [ 2241, 2250 ] ], "normalized": [] }, { "id": "PMID-19742300_T52", "type": "Cell", "text": [ "islet endothelial cell" ], "offsets": [ [ 2289, 2311 ] ], "normalized": [] }, { "id": "PMID-19742300_T53", "type": "Cell", "text": [ "beta-cell" ], "offsets": [ [ 2364, 2373 ] ], "normalized": [] } ]

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[ { "id": "PMC-2064791-sec-02__text", "type": "sec", "text": [ "Results\n\n" ], "offsets": [ [ 0, 9 ] ] } ]

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[ { "id": "PMID-11410793__text", "type": "abstract", "text": [ "Relationship of p53 and Helicobacter pylori to clinicopathological features of human remnant stomach cancer after gastric surgery for primary gastric cancer. \nThe purpose of this study was to evaluate the biological features of gastric cancer of the remnant stomach (RSC). Twenty-one patients underwent resection of the remnant stomach for RSC and were divided into two groups: the RSCB group consisted of 11 patients who underwent distal gastrectomy for benign disease and the RSCM group consisted of 10 patients who underwent gastrectomy for primary gastric cancer. The interval between primary surgery and the appearance of gastric cancer in the remnant stomach was significantly shorter in the RSCM group than in the RSCB group. Invasion of adjacent organs was more frequent in the RSCM group than in the RSCB group and the Ki-67 labeling index of the tumors was significantly higher in the former group. Furthermore, p53 overexpression by tumors was almost twice as common in the RSCM group as in the RSCB group. Although there was no significant difference of the H. pylori positivity between the two groups, the rate for both groups was higher than reported in previous studies. Mutation of p53 may play an important role in the high proliferative activity of tumors in the RSCM group and H. pylori infection may be closely related to carcinogenesis in patients with RSC.\n" ], "offsets": [ [ 0, 1379 ] ] } ]

[ { "id": "PMID-11410793_T4", "type": "Cancer", "text": [ "remnant stomach cancer" ], "offsets": [ [ 85, 107 ] ], "normalized": [] }, { "id": "PMID-11410793_T5", "type": "Organ", "text": [ "gastric" ], "offsets": [ [ 114, 121 ] ], "normalized": [] }, { "id": "PMID-11410793_T6", "type": "Cancer", "text": [ "primary gastric cancer" ], "offsets": [ [ 134, 156 ] ], "normalized": [] }, { "id": "PMID-11410793_T7", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 228, 242 ] ], "normalized": [] }, { "id": "PMID-11410793_T8", "type": "Organ", "text": [ "remnant stomach" ], "offsets": [ [ 250, 265 ] ], "normalized": [] }, { "id": "PMID-11410793_T9", "type": "Cancer", "text": [ "RSC" ], "offsets": [ [ 267, 270 ] ], "normalized": [] }, { "id": "PMID-11410793_T11", "type": "Organ", "text": [ "remnant stomach" ], "offsets": [ [ 320, 335 ] ], "normalized": [] }, { "id": "PMID-11410793_T12", "type": "Cancer", "text": [ "RSC" ], "offsets": [ [ 340, 343 ] ], "normalized": [] }, { "id": "PMID-11410793_T13", "type": "Cancer", "text": [ "RSCB" ], "offsets": [ [ 382, 386 ] ], "normalized": [] }, { "id": "PMID-11410793_T15", "type": "Cancer", "text": [ "RSCM" ], "offsets": [ [ 478, 482 ] ], "normalized": [] }, { "id": "PMID-11410793_T17", "type": "Cancer", "text": [ "primary gastric cancer" ], "offsets": [ [ 544, 566 ] ], "normalized": [] }, { "id": "PMID-11410793_T18", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 627, 641 ] ], "normalized": [] }, { "id": "PMID-11410793_T19", "type": "Organ", "text": [ "remnant stomach" ], "offsets": [ [ 649, 664 ] ], "normalized": [] }, { "id": "PMID-11410793_T20", "type": "Cancer", "text": [ "RSCM" ], "offsets": [ [ 698, 702 ] ], "normalized": [] }, { "id": "PMID-11410793_T21", "type": "Cancer", "text": [ "RSCB" ], "offsets": [ [ 721, 725 ] ], "normalized": [] }, { "id": "PMID-11410793_T22", "type": "Organ", "text": [ "organs" ], "offsets": [ [ 754, 760 ] ], "normalized": [] }, { "id": "PMID-11410793_T23", "type": "Cancer", "text": [ "RSCM" ], "offsets": [ [ 786, 790 ] ], "normalized": [] }, { "id": "PMID-11410793_T24", "type": "Cancer", "text": [ "RSCB" ], "offsets": [ [ 809, 813 ] ], "normalized": [] }, { "id": "PMID-11410793_T26", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 856, 862 ] ], "normalized": [] }, { "id": "PMID-11410793_T28", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 944, 950 ] ], "normalized": [] }, { "id": "PMID-11410793_T29", "type": "Cancer", "text": [ "RSCM" ], "offsets": [ [ 985, 989 ] ], "normalized": [] }, { "id": "PMID-11410793_T30", "type": "Cancer", "text": [ "RSCB" ], "offsets": [ [ 1006, 1010 ] ], "normalized": [] }, { "id": "PMID-11410793_T33", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1267, 1273 ] ], "normalized": [] }, { "id": "PMID-11410793_T34", "type": "Cancer", "text": [ "RSCM" ], "offsets": [ [ 1281, 1285 ] ], "normalized": [] }, { "id": "PMID-11410793_T37", "type": "Cancer", "text": [ "RSC" ], "offsets": [ [ 1374, 1377 ] ], "normalized": [] }, { "id": "PMID-11410793_T1", "type": "Pathological_formation", "text": [ "benign disease" ], "offsets": [ [ 455, 469 ] ], "normalized": [] } ]

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[ { "id": "PMC-2938106-sec-02__text", "type": "sec", "text": [ "Study Population\nThis prospective longitudinal study was conducted at the University of British Columbia and was approved by the human research ethics board at that institution. All subjects who received a renal transplant from January 2005 to December 2007 were invited to participate, and those who agreed and signed consent forms were enrolled in the study. Patients were followed routinely at the transplant center, and blood and urine samples were obtained prior to and serially post-transplant at 0.5, 1, 2, 3, 4, 8, 12, and 26 weeks; then every 6 months through year 3; and also at the time of suspected rejection. Graft biopsy tissue was obtained pretransplant and at the time of all biopsies performed post-transplant. Blood samples from normal healthy controls served as reference samples. Samples from cases, controls, and comparators were treated identically.\nAll rejection episodes were diagnosed by conventional clinical and laboratory parameters, confirmed by biopsy, and graded according to the Banff 97 working classification of renal allograft pathology (28). Banff categories 2 and 4 (antibody-mediated or acute/active cellular rejection) were considered significant. Category 3 (borderline change) was only considered significant if associated with graft dysfunction and treated for rejection. All baseline demographic and follow-up data were recorded in the transplant program electronic database, and there was no loss to follow-up during the period of study.\n" ], "offsets": [ [ 0, 1482 ] ] } ]

[ { "id": "PMC-2938106-sec-02_T1", "type": "Organ", "text": [ "renal transplant" ], "offsets": [ [ 206, 222 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T2", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 424, 429 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T3", "type": "Organism_substance", "text": [ "urine samples" ], "offsets": [ [ 434, 447 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T4", "type": "Tissue", "text": [ "Graft biopsy tissue" ], "offsets": [ [ 622, 641 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T5", "type": "Organism_substance", "text": [ "Blood samples" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T6", "type": "Organism_substance", "text": [ "samples" ], "offsets": [ [ 791, 798 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T7", "type": "Organism_substance", "text": [ "Samples" ], "offsets": [ [ 800, 807 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T8", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1138, 1146 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T9", "type": "Organ", "text": [ "renal allograft" ], "offsets": [ [ 1046, 1061 ] ], "normalized": [] }, { "id": "PMC-2938106-sec-02_T11", "type": "Organ", "text": [ "graft" ], "offsets": [ [ 1269, 1274 ] ], "normalized": [] } ]

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[ { "id": "PMID-19101635__text", "type": "abstract", "text": [ "Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense.\nThe p53 tumor suppressor plays pivotal role in the organism by supervising strict compliance of individual cells to needs of the whole organisms. It has been widely accepted that p53 acts in response to stresses and abnormalities in cell physiology by mobilizing the repair processes or by removing the diseased cells through initiating the cell death programs. Recent studies, however, indicate that even under normal physiological conditions certain activities of p53 participate in homeostatic regulation of metabolic processes and that these activities are important for prevention of cancer. These novel functions of p53 help to align metabolic processes with the proliferation and energy status, to maintain optimal mode of glucose metabolism and to boost the energy efficient mitochondrial respiration in response to ATP deficiency. Additional activities of p53 in non-stressed cells tune up the antioxidant defense mechanisms reducing the probability of mutations caused by DNA oxidation under conditions of daily stresses. The deficiency in the p53-mediated regulation of glycolysis and mitochondrial respiration greatly accounts for the deficient respiration of the predominance of aerobic glycolysis in cancer cells (the Warburg effect), while the deficiency in the p53-modulated antioxidant defense mechanisms contributes to mutagenesis and additionally boosts the carcinogenesis process.\n" ], "offsets": [ [ 0, 1509 ] ] } ]

[ { "id": "PMID-19101635_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 33, 38 ] ], "normalized": [] }, { "id": "PMID-19101635_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 116, 121 ] ], "normalized": [] }, { "id": "PMID-19101635_T5", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 215, 220 ] ], "normalized": [] }, { "id": "PMID-19101635_T7", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "PMID-19101635_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "PMID-19101635_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 449, 453 ] ], "normalized": [] }, { "id": "PMID-19101635_T11", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 697, 703 ] ], "normalized": [] }, { "id": "PMID-19101635_T14", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 891, 904 ] ], "normalized": [] }, { "id": "PMID-19101635_T17", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 993, 998 ] ], "normalized": [] }, { "id": "PMID-19101635_T20", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 1204, 1217 ] ], "normalized": [] }, { "id": "PMID-19101635_T21", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 1322, 1334 ] ], "normalized": [] } ]

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[ { "id": "PMID-15715968__text", "type": "abstract", "text": [ "Expression and purification of the catalytic domain of human vascular endothelial growth factor receptor 2 for inhibitor screening.\nVascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, can act in tumor-induced angiogenesis by binding to specific receptors on the surface of endothelial cells. One such receptor, VEGFR-2/KDR, plays a key role in VEGF-induced angiogenesis. Here, we expressed the catalytic domain of VEGFR-2 as a soluble active kinase using Bac-to-Bac expression system, and investigated correlations between VEGFR-2 activity and enzyme concentration, ATP concentration, substrate concentration and divalent cation type. We used these data to establish a convenient, effective and non-radioactive ELISA screening technique for the identification and evaluation of potential inhibitors for VEGFR-2 kinase. We screened 200 RTK target-based compounds and identified one (TKI-31) that potently inhibited VEGFR-2 kinase activity (IC50=0.596 microM). Treatment of NIH3T3/KDR cells with TKI-31 blocked VEGF-induced phosphorylation of KDR in a dose-dependent manner. Moreover, TKI-31 dose-dependently suppressed HUVEC tube formation. Thus, we herein report a novel, efficient method for identifying VEGFR-2 kinase inhibitors and introduce one, TKI-31, that may prove to be a useful new angiogenesis inhibitor.\n" ], "offsets": [ [ 0, 1345 ] ] } ]

[ { "id": "PMID-15715968_T5", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 178, 194 ] ], "normalized": [] }, { "id": "PMID-15715968_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 224, 229 ] ], "normalized": [] }, { "id": "PMID-15715968_T7", "type": "Cellular_component", "text": [ "surface" ], "offsets": [ [ 291, 298 ] ], "normalized": [] }, { "id": "PMID-15715968_T8", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 302, 319 ] ], "normalized": [] }, { "id": "PMID-15715968_T18", "type": "Cell", "text": [ "NIH3T3/KDR cells" ], "offsets": [ [ 1001, 1017 ] ], "normalized": [] }, { "id": "PMID-15715968_T23", "type": "Tissue", "text": [ "HUVEC tube" ], "offsets": [ [ 1147, 1157 ] ], "normalized": [] } ]

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[ { "id": "PMC-2715888-caption-05__text", "type": "caption", "text": [ "Duplicated HGT candidates in K. thermotolerans.\n(A) Part of the conserved synteny block surrounding KLTH0C07700g and KLTH0C07722g tandem genes. Same legend as Figure 3A. (B) Part of the conserved synteny block surrounding KLTH0F12276g gene. Same legend as Figure 3A. (C) Sequence alignment of proteins from K. thermotolerans and K. waltii. (D) Phylogenetic tree reconstructed from sequence alignment of 100 sites of K. thermotolerans protein family members, K. waltii gene, bacterial (green) and amoebal (blue) proteins. Bootstrap values are indicated next to the nodes and branch length scale is shown at bottom left.\n" ], "offsets": [ [ 0, 619 ] ] } ]

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[ { "id": "PMID-12167423__text", "type": "abstract", "text": [ "Molecular characterization of angiogenic properties of human oral squamous cell carcinoma cells.\nLittle is known about the specificity of angiogenic properties of oral cancer cells and the possible mechanisms. Stimulatory effects on proliferation and migration of human umbilical vein endothelial cells (HUVEC) characterized the angiogenic properties of oral cancer cells but not normal oral keratinocytes (NOK). ELISA found the presence of vascular endothelial growth factors (VEGF) both in the tested oral cancer cells and NOK. Attenuation of the proangiogenic effects by neutralizing VEGF antibodies suggests VEGF play a key role in the acquisition of the angiogenic phenotype in oral cancer cells. Western blotting of p53 and murine double mutant 2 (Mdm2) together with p53 DNA sequencing analysis indicate that p53 function loss by mutation or overexpression of Mdm2 occurred in all tested oral cancer cells regardless of their etiology. In summary, the angiogenic property of oral cancer cells is mediated by many factors in addition to VEGF and the functional status of p53.\n" ], "offsets": [ [ 0, 1082 ] ] } ]

[ { "id": "PMID-12167423_T2", "type": "Cell", "text": [ "oral squamous cell carcinoma cells" ], "offsets": [ [ 61, 95 ] ], "normalized": [] }, { "id": "PMID-12167423_T3", "type": "Cell", "text": [ "oral cancer cells" ], "offsets": [ [ 163, 180 ] ], "normalized": [] }, { "id": "PMID-12167423_T4", "type": "Cell", "text": [ "human umbilical vein endothelial cells" ], "offsets": [ [ 264, 302 ] ], "normalized": [] }, { "id": "PMID-12167423_T5", "type": "Cell", "text": [ "HUVEC" ], "offsets": [ [ 304, 309 ] ], "normalized": [] }, { "id": "PMID-12167423_T6", "type": "Cell", "text": [ "oral cancer cells" ], "offsets": [ [ 354, 371 ] ], "normalized": [] }, { "id": "PMID-12167423_T7", "type": "Cell", "text": [ "normal oral keratinocytes" ], "offsets": [ [ 380, 405 ] ], "normalized": [] }, { "id": "PMID-12167423_T8", "type": "Cell", "text": [ "NOK" ], "offsets": [ [ 407, 410 ] ], "normalized": [] }, { "id": "PMID-12167423_T11", "type": "Cell", "text": [ "oral cancer cells" ], "offsets": [ [ 503, 520 ] ], "normalized": [] }, { "id": "PMID-12167423_T12", "type": "Cell", "text": [ "NOK" ], "offsets": [ [ 525, 528 ] ], "normalized": [] }, { "id": "PMID-12167423_T15", "type": "Cell", "text": [ "oral cancer cells" ], "offsets": [ [ 683, 700 ] ], "normalized": [] }, { "id": "PMID-12167423_T23", "type": "Cell", "text": [ "oral cancer cells" ], "offsets": [ [ 895, 912 ] ], "normalized": [] }, { "id": "PMID-12167423_T24", "type": "Cell", "text": [ "oral cancer cells" ], "offsets": [ [ 982, 999 ] ], "normalized": [] } ]

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[ { "id": "PMID-1196405__text", "type": "abstract", "text": [ "Stimulation of beta-adrenergic receptors in the pineal gland increases the noradrenaline stores of its sympathetic nerves.\nThe administration of isoproterenol decreases the level of serotonin in the rat pineal gland and at the same time it increases pineal noradrenaline. These effects depend on the stimulation of a beta-adrenergic receptor because they are blocked by pretreatment of the animals with propranolol; this drug by itself does not modify either serotonin or noradrenaline levels in the pineal. The elevation of noradrenaline produced by isoproterenol is selective for the pineal because it is not observed in the salivary gland innervated by postganglionic adrenergic fibers from the same origin as pineal nerves. Pineal serotonin is stored in equilibrium in two compartments, i.e., the parenchymal cells and the adrenergic nerves and thus is most probably reduced in both sites. Since noradrenaline and serotonin are detected in pineal nerve vesicles and may coexist in them, the diminution of intravesicular serotonin, by making more storage sites available, probably determines the selective increase of pineal noradrenaline. A similar modification in the ratio of intravesicular amines as a result of the physiological stimulation of pineal beta-adrenergic receptors by the adrenergic neurotransmitter may explain some of the changes observed in the content of pineal amines.\n" ], "offsets": [ [ 0, 1394 ] ] } ]

[ { "id": "PMID-1196405_T1", "type": "Multi-tissue_structure", "text": [ "pineal gland" ], "offsets": [ [ 48, 60 ] ], "normalized": [] }, { "id": "PMID-1196405_T2", "type": "Multi-tissue_structure", "text": [ "sympathetic nerves" ], "offsets": [ [ 103, 121 ] ], "normalized": [] }, { "id": "PMID-1196405_T3", "type": "Multi-tissue_structure", "text": [ "pineal gland" ], "offsets": [ [ 203, 215 ] ], "normalized": [] }, { "id": "PMID-1196405_T4", "type": "Multi-tissue_structure", "text": [ "pineal" ], "offsets": [ [ 250, 256 ] ], "normalized": [] }, { "id": "PMID-1196405_T5", "type": "Multi-tissue_structure", "text": [ "pineal" ], "offsets": [ [ 500, 506 ] ], "normalized": [] }, { "id": "PMID-1196405_T6", "type": "Multi-tissue_structure", "text": [ "pineal" ], "offsets": [ [ 586, 592 ] ], "normalized": [] }, { "id": "PMID-1196405_T7", "type": "Multi-tissue_structure", "text": [ "salivary gland" ], "offsets": [ [ 627, 641 ] ], "normalized": [] }, { "id": "PMID-1196405_T9", "type": "Multi-tissue_structure", "text": [ "pineal nerves" ], "offsets": [ [ 713, 726 ] ], "normalized": [] }, { "id": "PMID-1196405_T10", "type": "Multi-tissue_structure", "text": [ "Pineal" ], "offsets": [ [ 728, 734 ] ], "normalized": [] }, { "id": "PMID-1196405_T12", "type": "Cell", "text": [ "parenchymal cells" ], "offsets": [ [ 801, 818 ] ], "normalized": [] }, { "id": "PMID-1196405_T13", "type": "Multi-tissue_structure", "text": [ "adrenergic nerves" ], "offsets": [ [ 827, 844 ] ], "normalized": [] }, { "id": "PMID-1196405_T14", "type": "Cellular_component", "text": [ "pineal nerve vesicles" ], "offsets": [ [ 944, 965 ] ], "normalized": [] }, { "id": "PMID-1196405_T15", "type": "Immaterial_anatomical_entity", "text": [ "intravesicular" ], "offsets": [ [ 1009, 1023 ] ], "normalized": [] }, { "id": "PMID-1196405_T16", "type": "Multi-tissue_structure", "text": [ "pineal" ], "offsets": [ [ 1121, 1127 ] ], "normalized": [] }, { "id": "PMID-1196405_T17", "type": "Immaterial_anatomical_entity", "text": [ "intravesicular" ], "offsets": [ [ 1182, 1196 ] ], "normalized": [] }, { "id": "PMID-1196405_T18", "type": "Multi-tissue_structure", "text": [ "pineal" ], "offsets": [ [ 1252, 1258 ] ], "normalized": [] }, { "id": "PMID-1196405_T19", "type": "Multi-tissue_structure", "text": [ "pineal" ], "offsets": [ [ 1379, 1385 ] ], "normalized": [] }, { "id": "PMID-1196405_T20", "type": "Cell", "text": [ "postganglionic adrenergic fibers" ], "offsets": [ [ 656, 688 ] ], "normalized": [] }, { "id": "PMID-1196405_T8", "type": "Multi-tissue_structure", "text": [ "compartments" ], "offsets": [ [ 777, 789 ] ], "normalized": [] }, { "id": "PMID-1196405_T11", "type": "Multi-tissue_structure", "text": [ "sites" ], "offsets": [ [ 887, 892 ] ], "normalized": [] }, { "id": "PMID-1196405_T21", "type": "Multi-tissue_structure", "text": [ "sites" ], "offsets": [ [ 1058, 1063 ] ], "normalized": [] } ]

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[ { "id": "PMID-22136381__text", "type": "abstract", "text": [ "Selective inhibition of nuclear factor-kappaB by nuclear factor-kappaB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma. \nNuclear factor-kappaB (NF-kappaB) activation contributes to the development of metastasis, thus leading to a poor prognosis in many cancers, including OSCC. However, little in vivo experimental data are available about the effects of NF-kappaB inhibition on OSCC metastasis. OSCC sublines were established from a GFP-expressing parental cell line, GSAS, and designated GSAS/N3 and N5 according to the in vivo passage number after cervical lymph node metastasis by a serial orthotopic transplantation model. In vitro migration and invasion were assessed in these cells, and the NF-kappaB activities and expression of NF-kappaB-regulated metastasis-related molecules were also examined. In in vivo experiments, the metastasis and survival of tumor-engrafted mice were monitored. Furthermore, the effects of a selective NF-kappaB inhibitor, NEMO-binding domain (NBD) peptide, on metastasis in GSAS/N5-engrafted mice were assessed, and engrafted tongue tumors were immunohistochemically examined. Highly metastatic GSAS/N3 and N5 cells showed an enhanced NF-kappaB activity, thus contributing to increased migration, invasion, and a poor prognosis compared with the parent cells. Furthermore, the expression levels of NF-kappaB-regulated metastasis-related molecules, such as fibronectin, beta1 integrin, MMP-1, -2, -9, and -14, and VEGF-C, were upregulated in the highly metastatic cells. The NBD peptide suppressed metastasis and tongue tumor growth in GSAS/N5-inoculated mice, and was accompanied by the downregulation of the NF-kappaB-regulated metastasis-related molecules in engrafted tongue tumors. Our results suggest that the selective inhibition of NF-kappaB activation by NBD peptide may provide an effective approach for the treatment of highly metastatic OSCC.\n" ], "offsets": [ [ 0, 1962 ] ] } ]

[ { "id": "PMID-22136381_T3", "type": "Cancer", "text": [ "metastatic oral squamous cell carcinoma" ], "offsets": [ [ 150, 189 ] ], "normalized": [] }, { "id": "PMID-22136381_T6", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 324, 331 ] ], "normalized": [] }, { "id": "PMID-22136381_T7", "type": "Cancer", "text": [ "OSCC" ], "offsets": [ [ 343, 347 ] ], "normalized": [] }, { "id": "PMID-22136381_T9", "type": "Cancer", "text": [ "OSCC" ], "offsets": [ [ 450, 454 ] ], "normalized": [] }, { "id": "PMID-22136381_T10", "type": "Cell", "text": [ "OSCC sublines" ], "offsets": [ [ 467, 480 ] ], "normalized": [] }, { "id": "PMID-22136381_T12", "type": "Cell", "text": [ "parental cell line" ], "offsets": [ [ 520, 538 ] ], "normalized": [] }, { "id": "PMID-22136381_T13", "type": "Cell", "text": [ "GSAS" ], "offsets": [ [ 540, 544 ] ], "normalized": [] }, { "id": "PMID-22136381_T14", "type": "Cell", "text": [ "GSAS/N3" ], "offsets": [ [ 561, 568 ] ], "normalized": [] }, { "id": "PMID-22136381_T15", "type": "Cell", "text": [ "N5" ], "offsets": [ [ 573, 575 ] ], "normalized": [] }, { "id": "PMID-22136381_T16", "type": "Multi-tissue_structure", "text": [ "cervical lymph node" ], "offsets": [ [ 622, 641 ] ], "normalized": [] }, { "id": "PMID-22136381_T17", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 754, 759 ] ], "normalized": [] }, { "id": "PMID-22136381_T20", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 932, 937 ] ], "normalized": [] }, { "id": "PMID-22136381_T24", "type": "Cell", "text": [ "GSAS/N5" ], "offsets": [ [ 1082, 1089 ] ], "normalized": [] }, { "id": "PMID-22136381_T26", "type": "Cancer", "text": [ "tongue tumors" ], "offsets": [ [ 1134, 1147 ] ], "normalized": [] }, { "id": "PMID-22136381_T27", "type": "Cell", "text": [ "metastatic GSAS/N3" ], "offsets": [ [ 1192, 1210 ] ], "normalized": [] }, { "id": "PMID-22136381_T28", "type": "Cell", "text": [ "N5 cells" ], "offsets": [ [ 1215, 1223 ] ], "normalized": [] }, { "id": "PMID-22136381_T30", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1361, 1366 ] ], "normalized": [] }, { "id": "PMID-22136381_T39", "type": "Cell", "text": [ "metastatic cells" ], "offsets": [ [ 1560, 1576 ] ], "normalized": [] }, { "id": "PMID-22136381_T41", "type": "Cancer", "text": [ "tongue tumor" ], "offsets": [ [ 1620, 1632 ] ], "normalized": [] }, { "id": "PMID-22136381_T42", "type": "Cell", "text": [ "GSAS/N5" ], "offsets": [ [ 1643, 1650 ] ], "normalized": [] }, { "id": "PMID-22136381_T45", "type": "Cancer", "text": [ "tongue tumors" ], "offsets": [ [ 1779, 1792 ] ], "normalized": [] }, { "id": "PMID-22136381_T48", "type": "Cancer", "text": [ "metastatic OSCC" ], "offsets": [ [ 1945, 1960 ] ], "normalized": [] } ]

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[ { "id": "PMID-12975002__text", "type": "abstract", "text": [ "[Community intervention on hypertension and stroke].\nOBJECTIVE:\nTo evaluate the community-based intervention on reduction of hypertension and stroke in different age groups and subtypes hypertension.\nMETHODS:\nIn 6 cities, 2 geographically separated communities with a registered population about 10 000 of each were selected as either intervention or control communities. A cohort containing 2 700 subjects, 35 years or older, and free of stroke were sampled from each community. The baseline survey was conducted to screen the subjects for intervention. In each city, a program for control of hypertension, heart diseases and diabetes was initiated in the intervention cohort and health education was provided to the whole intervention community. A follow-up survey was conducted 3 years later.\nRESULTS:\nWithin 3 years, the prevalence of hypertension increased in both intervention and control cohorts, as well as in the middle and elderly cohorts, especially in the middle aged in control group. Among hypertensives in the intervention cohort, the rates of awareness, treatment and control of hypertension got improved. The incidence of stroke was 29% lower (HR = 0.71, 95% CI: 0.58 - 0.87) and mortality of stroke was 40% lower (HR = 0.60, 95% CI: 0.42 - 0.86) in the intervention cohort than the control cohort. The intervention was most effective in reduction of stroke for those with isolated systolic hypertension and combined systolic and diastolic hypertension (All P < 0.05). Meanwhile, all-cause mortality was 11% lower (HR = 0.89, 95% CI: 0.78 - 0.99) in the intervention cohort than in the control cohort.\nCONCLUSION:\nThe community-based intervention was effective in controlling the development of hypertension and stroke, while the elderly people benefit more than the middle aged people from the intervention.\n" ], "offsets": [ [ 0, 1826 ] ] } ]

[ { "id": "PMID-12975002_T1", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 608, 613 ] ], "normalized": [] } ]

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[ { "id": "PMID-7954458__text", "type": "abstract", "text": [ "Transforming growth factor beta 1 promotes spontaneous transformation of cultured rat liver epithelial cells. \nThe neoplastic transformation of cultured rat liver epithelial cells by various means has consistently been associated with the development of resistance to the mito-inhibitory effect of transforming growth factor beta (TGF-beta), suggesting that such phenotype plays a mechanistic role during the transformation of these cells. We have studied the induction of the \"TGF-beta-resistant\" phenotype in a clonal strain of early passage WB-F344 normal cultured rat liver epithelial cells, the proliferation of which was markedly inhibited by TGF-beta. The control WB cells in continuous culture slowly developed TGF-beta resistance. However, when the same cells were exposed to step-wise increases of TGF-beta concentration in their culture medium, the development of TGF-beta resistance was accelerated. Cells which had been grown in medium containing 1 ng/ml TGF-beta developed colony-forming capacity in soft agar containing epidermal growth factor. Cells which were grown in media containing 5 and 10 ng/ml TGF-beta demonstrated a low level of colony-forming efficiency in soft agar medium without added epidermal growth factor and tumorigenicity in isogeneic rats. These TGF-beta-resistant cells also exhibited progressively increasing levels of expression of the c-fos and and myc mRNA, and increased resistance to the cytotoxicity of Adriamycin and melphalan. The latter phenomenon was accompanied by an increase in the mdr-1 mRNA expression, cellular glutathione level, and glutathione S-transferase activity. The results suggest that chronic exposure to high concentration of TGF-beta promotes the spontaneous neoplastic transformation of cultured rat liver epithelial cells, and that this process may represent one of the mechanisms of cellular adaptation for induction of the multidrug-resistant phenotype during the carcinogenesis of epithelial cells.\n" ], "offsets": [ [ 0, 1971 ] ] } ]

[ { "id": "PMID-7954458_T3", "type": "Cell", "text": [ "liver epithelial cells" ], "offsets": [ [ 86, 108 ] ], "normalized": [] }, { "id": "PMID-7954458_T5", "type": "Cell", "text": [ "liver epithelial cells" ], "offsets": [ [ 157, 179 ] ], "normalized": [] }, { "id": "PMID-7954458_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 433, 438 ] ], "normalized": [] }, { "id": "PMID-7954458_T10", "type": "Cell", "text": [ "WB-F344" ], "offsets": [ [ 544, 551 ] ], "normalized": [] }, { "id": "PMID-7954458_T12", "type": "Cell", "text": [ "liver epithelial cells" ], "offsets": [ [ 572, 594 ] ], "normalized": [] }, { "id": "PMID-7954458_T14", "type": "Cell", "text": [ "WB cells" ], "offsets": [ [ 671, 679 ] ], "normalized": [] }, { "id": "PMID-7954458_T16", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 763, 768 ] ], "normalized": [] }, { "id": "PMID-7954458_T19", "type": "Cell", "text": [ "Cells" ], "offsets": [ [ 912, 917 ] ], "normalized": [] }, { "id": "PMID-7954458_T22", "type": "Cell", "text": [ "Cells" ], "offsets": [ [ 1060, 1065 ] ], "normalized": [] }, { "id": "PMID-7954458_T27", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1302, 1307 ] ], "normalized": [] }, { "id": "PMID-7954458_T33", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1557, 1565 ] ], "normalized": [] }, { "id": "PMID-7954458_T38", "type": "Cell", "text": [ "liver epithelial cells" ], "offsets": [ [ 1768, 1790 ] ], "normalized": [] }, { "id": "PMID-7954458_T39", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1853, 1861 ] ], "normalized": [] }, { "id": "PMID-7954458_T40", "type": "Cell", "text": [ "epithelial cells" ], "offsets": [ [ 1953, 1969 ] ], "normalized": [] }, { "id": "PMID-7954458_T71", "type": "Cell", "text": [ "clonal strain" ], "offsets": [ [ 513, 526 ] ], "normalized": [] }, { "id": "PMID-7954458_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 115, 125 ] ], "normalized": [] }, { "id": "PMID-7954458_T2", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 1726, 1736 ] ], "normalized": [] }, { "id": "PMID-7954458_T4", "type": "Cell", "text": [ "colony" ], "offsets": [ [ 987, 993 ] ], "normalized": [] }, { "id": "PMID-7954458_T6", "type": "Cell", "text": [ "colony" ], "offsets": [ [ 1155, 1161 ] ], "normalized": [] } ]

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[ { "id": "PMID-20346999__text", "type": "abstract", "text": [ "Dose- and time-dependent effects of doxorubicin on cytotoxicity, cell cycle and apoptotic cell death in human colon cancer cells. \nThe cytostatic drug doxorubicin is a well-known chemotherapeutic agent which is used in treatment of a wide variety of cancers. A key factor in the response of cancer cells to chemotherapeutic drugs is the activation of the apoptotic pathway, a pathway that is often impaired in chemoresistant colon cancer cells. The aim of the present study was to investigate the effects of doxorubicin in Hct-116 human colon carcinoma cells in order to clarify if a time/concentration range for optimal doxorubicin-induced apoptosis exists. We compared a treatment schedule were cells were bolus incubated for 3h with doxorubicin followed by 24h in drug-free medium, with a continuous doxorubicin treatment schedule for 24h. Bolus incubation was carried out to determine effects of doxorubicin accumulated during the first 3h, whereas continuous incubation allowed further (continuous) exposure to doxorubicin. We found that bolus (3h) treatment with doxorubicin resulted in a dose-dependent decrease of viable cells and concomitant increase of apoptosis. Additionally, bolus (3h) doxorubicin incubation led to phosphorylation of p53 at serine 392, induction of p21, G2 arrest and increase of proapoptotic protein Bax. In contrast, continuous (24h) treatment with doxorubicin reduced the number of living cells with no parallel raise in the amount of dead cells. Continuous (24h) treatment with 5 microM doxorubicin resulted in cell cycle arrest in G0/G1 phase that was neither accompanied by phosphorylation and activation of p53 nor enhanced expression of p21. These results suggest that doxorubicin is able to induce cell death by apoptosis only at particular dose and treatment conditions and imply a completely different cellular response following bolus or continuous exposure to doxorubicin.\n" ], "offsets": [ [ 0, 1917 ] ] } ]

[ { "id": "PMID-20346999_T2", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 65, 69 ] ], "normalized": [] }, { "id": "PMID-20346999_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 90, 94 ] ], "normalized": [] }, { "id": "PMID-20346999_T5", "type": "Cell", "text": [ "colon cancer cells" ], "offsets": [ [ 110, 128 ] ], "normalized": [] }, { "id": "PMID-20346999_T7", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 250, 257 ] ], "normalized": [] }, { "id": "PMID-20346999_T8", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 291, 303 ] ], "normalized": [] }, { "id": "PMID-20346999_T9", "type": "Cell", "text": [ "colon cancer cells" ], "offsets": [ [ 425, 443 ] ], "normalized": [] }, { "id": "PMID-20346999_T11", "type": "Cell", "text": [ "Hct-116 human colon carcinoma cells" ], "offsets": [ [ 523, 558 ] ], "normalized": [] }, { "id": "PMID-20346999_T13", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 697, 702 ] ], "normalized": [] }, { "id": "PMID-20346999_T19", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1129, 1134 ] ], "normalized": [] }, { "id": "PMID-20346999_T26", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1423, 1428 ] ], "normalized": [] }, { "id": "PMID-20346999_T27", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1474, 1479 ] ], "normalized": [] }, { "id": "PMID-20346999_T29", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1546, 1550 ] ], "normalized": [] }, { "id": "PMID-20346999_T33", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1738, 1742 ] ], "normalized": [] }, { "id": "PMID-20346999_T34", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1844, 1852 ] ], "normalized": [] } ]

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[ { "id": "PMID-21752900__text", "type": "abstract", "text": [ "The members of an Epstein-Barr virus microRNA cluster cooperate to transform B lymphocytes. \nEpstein-Barr virus (EBV) transforms B lymphocytes through the expression of the latent viral proteins EBNA and latent membrane protein (LMP). Recently, it has become apparent that microRNAs (miRNAs) also contribute to EBV's oncogenic properties; recombinant EBVs that lack the BHRF1 miRNA cluster display a reduced ability to transform B lymphocytes in vitro. Furthermore, infected cells evince a marked upregulation of the EBNA genes. Using recombinant viruses that lack only one member of the cluster, we now show that all three BHRF1 miRNAs contribute to B-cell transformation. Recombinants that lacked miR-BHRF1-2 or miR-BHRF1-3 displayed enhanced EBNA expression initiated at the Cp and Wp promoters. Interestingly, we find that the deletion of miR-BHRF1-2 reduced the expression level of miR-BHRF1-3 and possibly that of miR-BHRF1-1, demonstrating that the expression of one miRNA can potentiate the expression of other miRNAs located in the same cluster. Therefore, the phenotypic traits of the miR-BHRF1-2 null mutant could result partly from reduced miR-BHRF1-1 and miR-BHRF1-3 expression levels. Nevertheless, using an miR-BHRF1-1 and miR-BHRF1-3 double mutant, we could directly assess and confirm the contribution of miR-BHRF1-2 to B-cell transformation. Furthermore, we found that the potentiating effect of miR-BHRF1-2 on miR-BHRF1-3 synthesis can be reproduced with simple expression plasmids, provided that both miRNAs are processed from the same transcript. Therefore, this enhancing effect does not result from an idiosyncrasy of the EBV genome but rather reflects a general property of these miRNAs. This study highlights the advantages of arranging the BHRF1 miRNAs in clusters: it allows the synchronous and synergistic expression of genetic elements that cooperate to transform their target cells.\n" ], "offsets": [ [ 0, 1913 ] ] } ]

[ { "id": "PMID-21752900_T2", "type": "Cell", "text": [ "B lymphocytes" ], "offsets": [ [ 77, 90 ] ], "normalized": [] }, { "id": "PMID-21752900_T5", "type": "Cell", "text": [ "B lymphocytes" ], "offsets": [ [ 129, 142 ] ], "normalized": [] }, { "id": "PMID-21752900_T12", "type": "Cell", "text": [ "B lymphocytes" ], "offsets": [ [ 429, 442 ] ], "normalized": [] }, { "id": "PMID-21752900_T13", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 475, 480 ] ], "normalized": [] }, { "id": "PMID-21752900_T16", "type": "Cell", "text": [ "B-cell" ], "offsets": [ [ 651, 657 ] ], "normalized": [] }, { "id": "PMID-21752900_T31", "type": "Cell", "text": [ "B-cell" ], "offsets": [ [ 1337, 1343 ] ], "normalized": [] }, { "id": "PMID-21752900_T36", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1906, 1911 ] ], "normalized": [] }, { "id": "PMID-21752900_T1", "type": "Cellular_component", "text": [ "plasmids" ], "offsets": [ [ 1492, 1500 ] ], "normalized": [] } ]

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[ { "id": "PMID-10644902__text", "type": "abstract", "text": [ "Obstructive nephropathy: lessons from cystic kidney disease.\nObstructive nephropathy is one of the most important causes of renal failure in infants and children, while polycystic kidney disease (PKD) is a major cause of renal failure in the adult population. This review summarizes the evidence that there may be a number of mechanisms common to the pathophysiology of both conditions. In animal models of obstructive nephropathy and PKD, the renal tubular expression of epidermal growth factor is suppressed, and expression of clusterin is increased, both of which suggest arrested maturation or dedifferentiation of the tubular cell. There is a marked increase in apoptosis of epithelial cells in dilated tubules, associated with an increase in apoptotic stimuli. The renin-angiotensin system is activated in both obstructive nephropathy and PKD, which may contribute to tubular atrophy and interstitial fibrosis, which characterize the progression of both conditions. Focal cystic dilatation of the tubule is found in obstructive nephropathy, while tubular obstruction is present in cystic kidney disease. It is therefore likely that elucidation of the effects of mechanical stretch on renal tubular epithelial cells will contribute to our understanding of both conditions.\n" ], "offsets": [ [ 0, 1278 ] ] } ]

[ { "id": "PMID-10644902_T1", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 45, 51 ] ], "normalized": [] }, { "id": "PMID-10644902_T2", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 180, 186 ] ], "normalized": [] }, { "id": "PMID-10644902_T3", "type": "Multi-tissue_structure", "text": [ "renal tubular" ], "offsets": [ [ 444, 457 ] ], "normalized": [] }, { "id": "PMID-10644902_T4", "type": "Cell", "text": [ "tubular cell" ], "offsets": [ [ 623, 635 ] ], "normalized": [] }, { "id": "PMID-10644902_T5", "type": "Cell", "text": [ "epithelial cells" ], "offsets": [ [ 680, 696 ] ], "normalized": [] }, { "id": "PMID-10644902_T6", "type": "Multi-tissue_structure", "text": [ "tubules" ], "offsets": [ [ 708, 715 ] ], "normalized": [] }, { "id": "PMID-10644902_T7", "type": "Multi-tissue_structure", "text": [ "tubule" ], "offsets": [ [ 1003, 1009 ] ], "normalized": [] }, { "id": "PMID-10644902_T8", "type": "Multi-tissue_structure", "text": [ "tubular" ], "offsets": [ [ 1053, 1060 ] ], "normalized": [] }, { "id": "PMID-10644902_T9", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 1094, 1100 ] ], "normalized": [] }, { "id": "PMID-10644902_T10", "type": "Cell", "text": [ "renal tubular epithelial cells" ], "offsets": [ [ 1190, 1220 ] ], "normalized": [] }, { "id": "PMID-10644902_T11", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 124, 129 ] ], "normalized": [] }, { "id": "PMID-10644902_T12", "type": "Organ", "text": [ "renal" ], "offsets": [ [ 221, 226 ] ], "normalized": [] }, { "id": "PMID-10644902_T13", "type": "Multi-tissue_structure", "text": [ "tubular" ], "offsets": [ [ 874, 881 ] ], "normalized": [] }, { "id": "PMID-10644902_T14", "type": "Immaterial_anatomical_entity", "text": [ "interstitial" ], "offsets": [ [ 894, 906 ] ], "normalized": [] }, { "id": "PMID-10644902_T15", "type": "Pathological_formation", "text": [ "cystic" ], "offsets": [ [ 38, 44 ] ], "normalized": [] }, { "id": "PMID-10644902_T16", "type": "Pathological_formation", "text": [ "cystic" ], "offsets": [ [ 173, 179 ] ], "normalized": [] }, { "id": "PMID-10644902_T17", "type": "Pathological_formation", "text": [ "cystic" ], "offsets": [ [ 978, 984 ] ], "normalized": [] }, { "id": "PMID-10644902_T18", "type": "Pathological_formation", "text": [ "cystic" ], "offsets": [ [ 1087, 1093 ] ], "normalized": [] } ]

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[ { "id": "PMC-2900753-caption-02__text", "type": "caption", "text": [ "Water emerging from the yoke adapter of the nitrous oxide hose\n" ], "offsets": [ [ 0, 63 ] ] } ]

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[ { "id": "PMC-2994753-caption-05__text", "type": "caption", "text": [ "Sensitivity of intervention cost-effectiveness to rates of decay in intervention effectiveness between 0% (life-long health benefits from one-off intervention) and 100% (no health benefits beyond the end of intervention).\n" ], "offsets": [ [ 0, 222 ] ] } ]

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[ { "id": "PMID-8111717__text", "type": "abstract", "text": [ "In vivo effects of insulin on tumor and skeletal muscle glucose metabolism in patients with lymphoma. \nBACKGROUND: The anabolic properties of insulin have been suggested for use to reverse malnutrition associated with cancer. The host and tumor sensitivities to insulin are critical for such treatments, which aim to improve patient nutrition. The authors studied insulin effects on tumor and skeletal muscle metabolism with 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). METHODS: Six patients with lymphoma twice underwent [18F]FDG-PET imaging: once after fasting overnight and once during euglycemic hyperinsulinemic clamp. The dynamic uptake of the glucose analogue [18F]FDG was measured in diseased nodes and upper arm skeletal muscle in both metabolic states. The [18F]FDG uptake in muscle and the whole body glucose use during euglycemic hyperinsulinemic clamp were compared with those of weight-matched healthy subjects studied under similar circumstances. RESULTS: In lymphomatous tissue, [18F]FDG uptake rates were similar in overnight fasting and euglycemic hyperinsulinemic clamp (38 +/- 10 versus 41 +/- 9 mumol/100 g/minute, not significant), whereas glucose uptake in skeletal muscle was increased by insulin (1.7 +/- 0.2 versus 3.8 +/- 0.5 mumol/100 g/minute, P = 0.012). Both basal (2.3 +/- 0.2 mumol/100 g/minute, P = 0.061) and insulin-stimulated (8.5 +/- 1.9 mumol/100 g/minute, P = 0.055) skeletal arm muscle glucose uptake rates were higher in control subjects than in patients. Whole body glucose use was 55% lower in patients than in control subjects (17 +/- 3 mumol/kg/minute versus 38 +/- 3 mumol/kg/minute, P = 0.002), consistent with insulin resistance in cancer. CONCLUSIONS: We found that insulin does not induce major changes in glucose uptake of lymphomatous tissue. Although insulin sensitivity of skeletal muscle was also reduced in patients with lymphoma, the net insulin effect may counteract imbalance between glucose uptake of tumor and muscle, offering a potential means to circumvent at least some metabolic abnormalities found in cancer.\n" ], "offsets": [ [ 0, 2115 ] ] } ]

[ { "id": "PMID-8111717_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "PMID-8111717_T3", "type": "Organ", "text": [ "skeletal muscle" ], "offsets": [ [ 40, 55 ] ], "normalized": [] }, { "id": "PMID-8111717_T6", "type": "Cancer", "text": [ "lymphoma" ], "offsets": [ [ 92, 100 ] ], "normalized": [] }, { "id": "PMID-8111717_T8", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 218, 224 ] ], "normalized": [] }, { "id": "PMID-8111717_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 239, 244 ] ], "normalized": [] }, { "id": "PMID-8111717_T13", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 383, 388 ] ], "normalized": [] }, { "id": "PMID-8111717_T14", "type": "Organ", "text": [ "skeletal muscle" ], "offsets": [ [ 393, 408 ] ], "normalized": [] }, { "id": "PMID-8111717_T18", "type": "Cancer", "text": [ "lymphoma" ], "offsets": [ [ 536, 544 ] ], "normalized": [] }, { "id": "PMID-8111717_T22", "type": "Multi-tissue_structure", "text": [ "diseased nodes" ], "offsets": [ [ 731, 745 ] ], "normalized": [] }, { "id": "PMID-8111717_T24", "type": "Organ", "text": [ "upper arm skeletal muscle" ], "offsets": [ [ 750, 775 ] ], "normalized": [] }, { "id": "PMID-8111717_T26", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 825, 831 ] ], "normalized": [] }, { "id": "PMID-8111717_T27", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "PMID-8111717_T29", "type": "Tissue", "text": [ "lymphomatous tissue" ], "offsets": [ [ 1013, 1032 ] ], "normalized": [] }, { "id": "PMID-8111717_T32", "type": "Organ", "text": [ "skeletal muscle" ], "offsets": [ [ 1219, 1234 ] ], "normalized": [] }, { "id": "PMID-8111717_T35", "type": "Multi-tissue_structure", "text": [ "skeletal arm muscle" ], "offsets": [ [ 1446, 1465 ] ], "normalized": [] }, { "id": "PMID-8111717_T38", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 1543, 1547 ] ], "normalized": [] }, { "id": "PMID-8111717_T43", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1720, 1726 ] ], "normalized": [] }, { "id": "PMID-8111717_T46", "type": "Tissue", "text": [ "lymphomatous tissue" ], "offsets": [ [ 1814, 1833 ] ], "normalized": [] }, { "id": "PMID-8111717_T48", "type": "Organ", "text": [ "skeletal muscle" ], "offsets": [ [ 1867, 1882 ] ], "normalized": [] }, { "id": "PMID-8111717_T50", "type": "Cancer", "text": [ "lymphoma" ], "offsets": [ [ 1917, 1925 ] ], "normalized": [] }, { "id": "PMID-8111717_T53", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 2001, 2006 ] ], "normalized": [] }, { "id": "PMID-8111717_T54", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 2011, 2017 ] ], "normalized": [] }, { "id": "PMID-8111717_T55", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 2107, 2113 ] ], "normalized": [] } ]

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