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PMID-9006118 | PMID-9006118 | [
{
"id": "PMID-9006118__text",
"type": "abstract",
"text": [
"Comparison of transformation by manganese sulfate and 5-azacytidine in Rat 6 cells overexpressing the c-myc oncogene. \nRat 6 cells are not transformed by treatment with the well-known carcinogens benzo[a]pyrene (BP) or N-methyl-N-nitro-N'-nitrosoguanidine (MNNG). Upon retroviral transduction of the mouse c-myc gene, Rat 6 cells showed mildly altered morphology and formed microcolonies in soft agar; furthermore, they could be transformed by BP and MNNG to form large colonies in agar (Hsiao et al. (1992) Mol. Carcinogenesis, 5, 140-154). In the current report, we tested the sensitivity of the c-myc-overexpressing cells (Rat 6/c-myc) to two additional chemicals: 5-azacytidine and MnSO4. These chemicals differ from the direct-acting mutagens tested previously. 5-Azacytidine, a potent DNA methylation inhibitor, induced growth of large colonies in soft agar cultures of Rat 6 or Rat 6/c-myc cells. On the other hand, MnSO4 only induced transformation in Rat 6/c-myc cells, but not the parental Rat 6 cells. Transformants induced by 5-azacytidine lost c-myc-induced apoptotic cell death, whereas MnSO4-induced transformants showed a higher degree of apoptosis than the parental Rat 6/c-myc cells. These results suggest that MnSO4 co-operates with overexpressed c-myc in inducing transformation, while 5-azacytidine transformation is independent of c-myc overexpression and may involve alterations in the regulation of apoptosis.\n"
],
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"Rat 6 cells"
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"Rat 6 cells"
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"id": "PMID-9006118_T13",
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"Rat 6 cells"
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"id": "PMID-9006118_T17",
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"c-myc-overexpressing cells"
],
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"id": "PMID-9006118_T18",
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"Rat 6/c-myc"
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"Rat 6"
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"Rat 6/c-myc cells"
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"id": "PMID-9006118_T28",
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"Rat 6/c-myc cells"
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"Rat 6 cells"
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"text": [
"Transformants"
],
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"cell"
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"transformants"
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"Rat 6/c-myc cells"
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},
{
"id": "PMID-9006118_T1",
"type": "Cell",
"text": [
"colonies"
],
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{
"id": "PMID-9006118_T4",
"type": "Cell",
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"microcolonies"
],
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"id": "PMID-9006118_T6",
"type": "Cell",
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"colonies"
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{
"id": "PMID-9006118_T2",
"type": "Cell",
"text": [
"cultures"
],
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864,
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}
] | [] | [] | [] |
PMID-17873348 | PMID-17873348 | [
{
"id": "PMID-17873348__text",
"type": "abstract",
"text": [
"Wnt signaling, stem cells, and the cellular origin of breast cancer. \nThe breast epithelium comprises cells at different stages of differentiation, including stem cells, progenitor cells, and more differentiated epithelial and myoepithelial cells. Wnt signaling plays a critical role in regulating stem/progenitor cells in the mammary gland as well as other tissue compartments. Furthermore, there is strong evidence suggesting that aberrant activation of Wnt signaling induces mammary tumors from stem/progenitor cells, and that Wnt exerts its oncogenic effects through LRP5/6-mediated activation of beta-catenin and mTOR pathways. Recent studies using avian retrovirus-mediated introduction of oncogenes into a small subset of somatic mammary cells suggest that polyoma middle T antigen (PyMT) may also preferentially transform stem/progenitor cells. These observations suggest that stem/progenitor cells in the mammary gland may be especially susceptible to oncogenic transformation. Whether more differentiated cells may also be transformed by particular oncogenes is actively debated; it is presently unclear whether stem cells or differentiated mammary cells are more susceptible to transformation by individual oncogenes. Better stem cell and progenitor cell markers as well as the ability to specifically target oncogenes into different mammary cell types will be needed to determine the spectrum of oncogene transformation for stem cells versus more differentiated cells.\n"
],
"offsets": [
[
0,
1481
]
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] | [
{
"id": "PMID-17873348_T2",
"type": "Cell",
"text": [
"stem cells"
],
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15,
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"id": "PMID-17873348_T3",
"type": "Cell",
"text": [
"cellular"
],
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35,
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{
"id": "PMID-17873348_T4",
"type": "Cancer",
"text": [
"breast cancer"
],
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[
54,
67
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"normalized": []
},
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"id": "PMID-17873348_T5",
"type": "Tissue",
"text": [
"breast epithelium"
],
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74,
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"id": "PMID-17873348_T6",
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"cells"
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102,
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"id": "PMID-17873348_T7",
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"text": [
"stem cells"
],
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158,
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"id": "PMID-17873348_T8",
"type": "Cell",
"text": [
"progenitor cells"
],
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{
"id": "PMID-17873348_T9",
"type": "Cell",
"text": [
"epithelial"
],
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[
212,
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],
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"id": "PMID-17873348_T10",
"type": "Cell",
"text": [
"myoepithelial cells"
],
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[
227,
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]
],
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"id": "PMID-17873348_T13",
"type": "Cell",
"text": [
"stem/progenitor cells"
],
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[
298,
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],
"normalized": []
},
{
"id": "PMID-17873348_T14",
"type": "Organ",
"text": [
"mammary gland"
],
"offsets": [
[
327,
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]
],
"normalized": []
},
{
"id": "PMID-17873348_T15",
"type": "Multi-tissue_structure",
"text": [
"tissue compartments"
],
"offsets": [
[
358,
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]
],
"normalized": []
},
{
"id": "PMID-17873348_T17",
"type": "Cancer",
"text": [
"mammary tumors"
],
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[
478,
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]
],
"normalized": []
},
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"id": "PMID-17873348_T19",
"type": "Cell",
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"stem/progenitor cells"
],
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[
498,
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],
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},
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"id": "PMID-17873348_T26",
"type": "Cell",
"text": [
"somatic mammary cells"
],
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[
729,
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"stem/progenitor cells"
],
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"stem/progenitor cells"
],
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"mammary gland"
],
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"cells"
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"stem cells"
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"mammary cells"
],
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"stem cell"
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"progenitor cell"
],
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"id": "PMID-17873348_T40",
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"mammary cell"
],
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1345,
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"id": "PMID-17873348_T41",
"type": "Cell",
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"stem cells"
],
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"type": "Cell",
"text": [
"cells"
],
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}
] | [] | [] | [] |
PMID-2512762 | PMID-2512762 | [
{
"id": "PMID-2512762__text",
"type": "abstract",
"text": [
"Gastric microcirculatory change and development of acute gastric mucosal lesions (stress ulcer).\nConcerning the pathogenesis of acute gastric mucosal lesions, gastric microcirculatory change has drawn attention as an important factor. In view of this fact, gastric mucosal blood flow and microvascular structure were investigated in normal and in burn stressed rats. Moreover, alterations in acid and pepsin activities in by morphological and biochemical procedures in order to evaluate the relationship between defensive and aggressive factors of the gastric mucosa. Gastric mucosal blood flow decreased significantly in early period after induction of stress (p less than 0.01). The incidence of ulceration showed a correlative relation with the decrease of mucosal blood flow. Reduction of blood flow in burn was due to opening of arteriovenular shunt and it appeared that this was responsible for mucosal ischemia and congestion. Following the decrease of blood flow, acid output was lower in stress than that in control. Finally, the results of these studies demonstrated the importance of defensive factors. The reduction of mucosal blood flow resulted in the sequence of events that led to formation of acute gastric mucosal lesion.\n"
],
"offsets": [
[
0,
1240
]
]
}
] | [
{
"id": "PMID-2512762_T1",
"type": "Organ",
"text": [
"Gastric"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "PMID-2512762_T2",
"type": "Pathological_formation",
"text": [
"gastric mucosal lesions"
],
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[
57,
80
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],
"normalized": []
},
{
"id": "PMID-2512762_T3",
"type": "Pathological_formation",
"text": [
"stress ulcer"
],
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[
82,
94
]
],
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},
{
"id": "PMID-2512762_T4",
"type": "Pathological_formation",
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"gastric mucosal lesions"
],
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134,
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"id": "PMID-2512762_T5",
"type": "Organ",
"text": [
"gastric"
],
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[
159,
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},
{
"id": "PMID-2512762_T6",
"type": "Multi-tissue_structure",
"text": [
"gastric mucosal"
],
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257,
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"id": "PMID-2512762_T7",
"type": "Organism_substance",
"text": [
"blood"
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"id": "PMID-2512762_T8",
"type": "Tissue",
"text": [
"microvascular"
],
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"id": "PMID-2512762_T9",
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"gastric mucosa"
],
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"Gastric mucosal"
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"blood"
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"mucosal"
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"blood"
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"blood"
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},
{
"id": "PMID-2512762_T15",
"type": "Multi-tissue_structure",
"text": [
"arteriovenular"
],
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"id": "PMID-2512762_T16",
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"mucosal"
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"blood"
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"id": "PMID-2512762_T18",
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"mucosal"
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"blood"
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"text": [
"gastric mucosal lesion"
],
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1216,
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}
] | [] | [] | [] |
PMID-10623751 | PMID-10623751 | [
{
"id": "PMID-10623751__text",
"type": "abstract",
"text": [
"LMP1 of Epstein-Barr virus induces proliferation of primary mouse embryonic fibroblasts and cooperatively transforms the cells with a p16-insensitive CDK4 oncogene. \nThe latent membrane protein LMP1 of Epstein-Barr virus (EBV) is often present in EBV-associated malignancies including nasopharyngeal carcinoma and Hodgkin's lymphoma. Previous work demonstrates that the LMP1 gene of EBV is sufficient to transform certain established rodent fibroblast cell lines and to induce the tumorigenicity of some human epithelial cell lines. In addition, LMP1 plays pleiotropic roles in cell growth arrest, differentiation, and apoptosis, depending on the background of the target cells. To examine the roles of LMP1 in cell proliferation and growth regulation in primary culture cells, we constructed a recombinant retrovirus containing an LMP1 gene. With this retrovirus, LMP1 was shown to stimulate the proliferation of primary mouse embryonic fibroblasts (MEF cells). It has a mitogenic activity for MEF cells, as demonstrated by an immediate induction of cell doubling time. In addition, it significantly extends the passage number of MEF cells to more than 30 after retroviral infection, compared with less than 5 for uninfected MEF cells. Furthermore, LMP1 cooperates with a p16-insensitive CDK4(R24C) oncogene in transforming MEF cells. Our results provide the first evidence of the abilities of the LMP1 gene, acting alone, to effectively induce the proliferation of primary MEF cells and of its cooperativity with another cellular oncogene in transforming primary cells.\n"
],
"offsets": [
[
0,
1572
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]
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] | [
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"id": "PMID-10623751_T4",
"type": "Cell",
"text": [
"embryonic fibroblasts"
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[
66,
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"cells"
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[
121,
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},
{
"id": "PMID-10623751_T12",
"type": "Cancer",
"text": [
"malignancies"
],
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[
262,
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},
{
"id": "PMID-10623751_T13",
"type": "Cancer",
"text": [
"nasopharyngeal carcinoma"
],
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[
285,
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]
],
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},
{
"id": "PMID-10623751_T14",
"type": "Cancer",
"text": [
"Hodgkin's lymphoma"
],
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[
314,
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],
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},
{
"id": "PMID-10623751_T17",
"type": "Cell",
"text": [
"fibroblast cell lines"
],
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441,
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},
{
"id": "PMID-10623751_T19",
"type": "Cell",
"text": [
"epithelial cell lines"
],
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"cell"
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"cells"
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"cell"
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"culture cells"
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"MEF cells"
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"MEF cells"
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"MEF cells"
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"MEF cells"
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"MEF cells"
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"MEF cells"
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"cellular"
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"type": "Cell",
"text": [
"cells"
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] | [] | [] | [] |
PMC-2909993-sec-05 | PMC-2909993-sec-05 | [
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"Histological analysis\nA cross-section of the distal colon (2 cm) was fixed in 10% paraformaldehyde solution. Afterwards, it was cut into small fragments, dehydrated through an ethanol series (70%-100%), cleared in xylol and embedded in paraffin. The fragments were sliced into 5 mum thick sections and stained with hematoxylin-eosin. Histological evaluation was done by a pathologist who was blinded to the experimental groups, and it was based on the intensity of mononuclear and polymorphonuclear infiltrates in the lamina propria, crypt dilation, cellular destruction and mucosal ulceration. Histopathological changes were graded according to the degree of inflammation using the following scale: absent (0), light (1), moderate (2) and intense (3), and the numbers represented the inflammation score (IS). Results were expressed as mean values of IS +/- standard error of the mean (SEM) for each experimental group.\n"
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PMC-3088328-sec-10 | PMC-3088328-sec-10 | [
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"Etymology.\nProfessor Stephen Lane Wood worked extensively on collections of Scolytinae preserved in Indian museums, and described a number of new Scolytinae species from India. In this paper we describe one more new bark-beetle species from India kept in the Natural History Museum in Vienna (NHMW) and dedicate this species to the late Professor Stephen Lane Wood.\n"
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PMC-2193592-sec-11 | PMC-2193592-sec-11 | [
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"Stimulation/Inhibition of iDC Functions by Activated NK Cells.\nTwo previous studies have shown that both resting and activated NK cells partially kill autologous DCs, as measured by 3-4-h chromium release assays using high NK/DC ratios (11, 12). However, in our long-term cultures (24-48 h) the NK cells stimulated the iDCs rather than lysing them. Based on these conflicting results, we examined in more detail the apparent stimulation of iDCs after contact with NK cells. We reasoned that activated NK cells would be more useful for these experiments because (i) an encounter in vivo between NK cells that normally traffic in the blood (4) and iDCs which reside in the tissues (1, 3), should only occur when both cells are activated; (ii) activated NK cells mediate more potent lysis of iDCs (11-13), thereby allowing for a more rigorous examination of a potential cytotoxic effect; and (iii) the number of NK cells obtained after short-term in vitro culture would be far greater providing more cells for analysis (9).\nThe DC maturation induced by resting NK cells we observed was dependent on endogenous TNF-alpha production. Furthermore, TNF-alpha and other proinflammatory cytokines are important amplifiers of immune responses (14). Therefore, we used TNF-alpha production as a readout for DC stimulation in our culture system. Culturing activated NK cells with DCs at low NK/DC ratios (1:5) led to increases in TNF-alpha production, which were augmented dramatically by the addition of suboptimal doses (10 ng/ml) of LPS (Fig. 2 A). The increased TNF-alpha production was dependent on cell-to-cell contact because when the two cell types were separated in trans-wells, no stimulation was observed (Fig. 2 B). In separate experiments we observed this NK-stimulatory effect on TNF-alpha production at NK/DC ratios as low as 1:20 and 1:40 (data not shown). Raising the NK/DC ratio to 5:1 changes the interaction from one of potent DC stimulation to that of complete inhibition in the presence or absence of LPS (Fig. 2 C). An identical pattern is seen for IL-12 p40 production (Fig. 2 D). No IL-10 production in the cultures was detected under any of the conditions tested (data not shown). The massive production of TNF-alpha in the cultures at the lowest ratios was mediated primarily by DCs in the culture due to the low number of NK cells (2 x 104 cells per well) used in these experiments. In addition, efforts to stimulate NK cells directly with optimal doses of anti-CD16, rIL-2, rIL-12, and PMA/ionomycin alone or in combination induced only moderate (<500 pg/ml) TNF-alpha production by the NK cells alone which were present at 2 x 105 cells per well (data not shown).\nFigure 2.\nActivated/cultured NK cell-mediated amplification/inhibition of DC cytokine production. Results are presented on log scales. Cultured iDCs were incubated alone or with cultured/purified NK cells for 24 h (A and B) or 48 h (C-E) in the presence or absence of the indicated concentrations of LPS. After culture the supernatants were removed and analyzed by ELISA for TNF-alpha or IL-12 p40. (A) TNF-alpha production was measured in the supernatants from cultures of: DCs alone (gray bars); NK+DC (1:5) (black bars). LPS concentrations used were: 0, 10, and 1,000 ng/ml (DCs alone only). (B) Contact-dependent stimulation of iDC TNF-alpha production by NK cells was tested under the following conditions: DCs alone (gray bars); NK+DC (1:5) (black bars); NK/DC (1:5) trans-wells (striped bars). LPS concentrations used were: 10 ng/ml (donor 1) and 20 ng/ml (donor 2). (C and D) Effect of increasing the NK/DC ratio (DCs alone; NK:DC-1:5; 1:1; 5:1) on (C) TNF-alpha and (D) IL-12 p40 production. LPS concentrations used were: 0 ng/ml (*); 20 ng/ml (*); 50 ng/ml (^); and 1,000 ng/ml-LPS (*) (DCs alone only). (E) The effect of neutralizing IFN-gamma production was tested under the following conditions: DCs alone (gray bars); NK+DC (1:5) (black bars); NK+DC (1:5) and 10 mug/ml of blocking anti-IFN-gamma mAb (stippled bars). LPS concentrations used were: 0 ng/ml (NO LPS) and 20 ng/ml (LPS 20).\nBlocking reagents for CD80, CD86, CD154, CD95, CD11a, CD50, or IL-12, had no effect on the NK cell-induced TNF-alpha or IL-12 p40 production, whereas a neutralizing antibody for IFN-gamma while not affecting TNF-alpha production partially blocked (<20%) IL-12 p40 production induced by the NK cells (Fig. 2 E). This partial inhibition is consistent with numerous previous reports demonstrating a central role for an IL-12/IFN-gamma positive feedback loop active between NK cells and IL-12-producing cells (15-17). Clearly, however, this well-described cytokine cross-talk mechanism is secondary to the contact-dependent activation of DCs by NK cells described here. Taken together these results indicate that novel mechanisms control cognate interactions between NK cells and DCs and that NK-DC contact has the potential to serve as an important control switch for both amplifying and attenuating innate immune responses in vivo.\nWe next tested directly whether NK cell killing was active in our system using both short-term (4-h) chromium release assays (data not shown) and a flow cytometric assay which allowed us to follow the survival of the autologous iDCs in the presence of NK cells over longer periods (Fig. 3). The results demonstrate that NK cells kill autologous iDCs (Fig. 3 A) at all NK/DC ratios tested after 4 h and the level of killing is similar to the lysis of K562 cells over the same time (Fig. 3 B). After 24 h, however, the presence of NK cells led to completely divergent effects on the DCs. At the 5:1 (NK/DC) ratio, NK cell-mediated destruction of the iDCs was the dominant feature, whereas at the low ratio (1:5) the same NK cells promoted iDCs survival compared with iDCs alone over the same period (Fig. 3 A). The equal ratio of NK/DC (1:1) fell between these two extremes. The NK cell-mediated lysis of the K562 targets increased at all ratios tested after the 24-h incubation. These striking differences between death and survival of DCs upon encountering NK cells correlate precisely with our previous results on TNF-alpha and IL-12 p40 production where increasing numbers of NK cells in the culture shifts the NK effect from potent stimulation to complete inhibition (Fig. 2).\nFigure 3.\nActivated/cultured NK cell-mediated death/survival of DCs and NK-DC conjugate formation. NK cell mediated killing/survival of CFDA.SE-loaded iDCs (A) and K562 cells (B) was measured by flow cytometry over 4 h (*) or 24 h (*) at the indicated NK/DC ratios as described in Materials and Methods. Results are presented as percentage of specific lysis +/- SEM (n = 3 independent experiments). NK-DC (C-E) or NK-K562 (F-H) conjugate formation was measured by flow cytometry, at the following ratios (NK/DC or NK/K562): 1:5 (C and F); 1:1 (D and G); and 5:1 (E and H). Snarf-1 (FL3)-labeled iDCs or K562 cells were incubated (30 min) with CFDA.SE (FL1)-labeled NK cells at the different ratios. The percentage of conjugates formed (top right quadrant) was calculated by determining the percentage of FL3+ (Snarf-1) events which were also positive for FL1 (CFDA.SE). The results are representative of four experiments performed with activated NK cells. Resting NK cells also readily formed conjugates with autologous iDCs (data not shown).\nNK cells can both efficiently kill and potently stimulate DCs in our model system and each of these opposing effects appear dependent on cell-to-cell contact. To quantify these apparent cognate interactions we measured the formation of NK-DC conjugates and compared them to conjugates formed by NK cells and tumor targets. Our analysis revealed that NK cells bound DC (Fig. 3 C-E) with an efficiency almost equal to that of NK cell binding to the classical NK-target, K562 (Fig. 3 F-H). Binding was detectable even at the lowest NK/DC ratio tested (1:5) indicating that NK-DC conjugates are formed in our other experiments measuring cytokine production and cell killing.\nOur initial experiments using resting NK cells (Fig. 1) demonstrated a contact-dependent NK effect driving iDCs to mature. Therefore, we tested what effects activated NK cells mediated on DC maturation (Fig. 4). Similar to our previous results with activated NK cells (Figs. 2 and 3), addition of NK cells to the culture leads to opposing effects on the iDC population depending on the NK/DC ratio. Compared with the untreated DCs (Fig. 4 A-C), low NK/DC ratios (1:5 or 1:1) consistently augmented expression of the maturation markers: CD86 (Fig. 4 D-I), CD83, and HLA-DR (data not shown). At a 5:1 ratio (NK/DC) most of the DCs are nonviable (Fig. 4 J-L). Addition of suboptimal doses of LPS (Fig. 4 C, F, I, and L) augmented the NK-induced maturation at NK/DC ratios of 1:5 and 1:1, but had no effect at the 5:1 ratio. Again, DC maturation was dependent on NK cell contact and endogenously produced TNF-alpha, because it did not occur when the two cell types were separated in trans-wells or upon the addition of a neutralizing antibody for TNF-alpha (Fig. 5). Moreover, addition of blocking reagents for CD80, CD86, CD154, CD95, CD11a, CD50, IL-12, IFN-gamma, IFN-alpha, or IFN-beta had no effect on the NK-induced maturation (data not shown).\nFigure 4.\nActivated/cultured NK cell-mediated maturation/death of DCs. Cultured iDCs were incubated for 48 h, alone (A-C), or with NK cells at the following ratios (NK/DC), 1:5 (D-F), 1:1 (G-I), and 5:1 (J-L). Forward versus side scatter plots (A, D, G, and J) show the gating on the DC subset and demonstrate its disappearance at the 5:1 (NK/DC) ratio (J). Propidium iodide staining of the NK/DC (5:1) cultures confirmed the almost complete absence of viable DCs (data not shown). Staining for CD86 expression was performed as described in Fig. 1 and the histograms are shown for DCs cultured in the presence (C, F, I, and L) or absence (B, E, H, and K) of 1 ng/ml of LPS. Results are representative of six experiments performed.\nFigure 5.\nActivated/cultured NK cell-induced DC maturation is dependent on cell-to-cell contact and endogenous TNF-alpha production. Cultured iDCs were incubated alone (A, D, and G); with activated NK cells at an NK/DC ratio of 1:5 (B, E, and H); with activated NK cells (NK/DC; 1:5) separated in trans-wells (C and F); or with activated NK cells and 10 mug/ml of a neutralizing antibody for TNF-alpha (I). LPS concentrations used were: 0 ng/ml (A-C); 10 ng/ml (D-F) and 50 ng/ml (G-I). CD86 staining of the DC subset was performed as in Figs. 1 and 4. Results are representative of four experiments performed.\n"
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},
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"id": "PMC-2193592-sec-11_T188",
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"tissues"
],
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},
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},
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"tumor"
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7645,
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],
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},
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"id": "PMC-2193592-sec-11_T195",
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"supernatants"
],
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]
],
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},
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"supernatants"
],
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],
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},
{
"id": "PMC-2193592-sec-11_T197",
"type": "Cell",
"text": [
"cultures"
],
"offsets": [
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3144,
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]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2989791-sec-04 | PMC-2989791-sec-04 | [
{
"id": "PMC-2989791-sec-04__text",
"type": "sec",
"text": [
"Measurement of IgA1 content\nIgA1 content in the supernatant from each culture well was measured in duplicate using enzyme-linked immunosorbent assay (ELISA). All incubations were performed at room temperature except for capture antibody coating. Briefly, 96-well immunoplates (Thermo Fisher Scientific, Waltham, MA, USA) were coated with 5 microg/mL of F(ab')2 fragment goat anti-human IgA antibody (Jackson ImmunoResearch Laboratories, West Grove, PA, USA), in phosphate-buffered saline (PBS) at 4degreesC overnight. After three washes with PBS containing 0.05% Tween-20 (PBST), plates were blocked by adding PBS containing 1% bovine serum albumin (BSA) to the wells for 90 min. Next, 50 microL of supernatant sample or standard human IgA1 (CALBIOCHEM, La Jolla, CA, USA) was added to the reaction wells and then incubated for 90 min. After three washes, 0.75 microg/mL alkaline phosphatase conjugated goat anti-human IgA (Southern Biotechnology Associates, Birmingham, AL, USA) in 1% BSA/PBS was added to the reaction wells and then incubated for 90 min. Plates were washed three times and developed with a substrate solution of 1 mg/mL p-nitrophenyl phosphate disodium salt (SIGMA, St. Louis, MO, USA) in 0.1 M glycine buffer containing 1 mM MgCl2, 1 mM ZnCl2, pH 10.4. The optical density at 405 nm was determined in a microplate reader (Benchmark PlusTM Bio-Rad Laboratories, Hercules, CA, USA). IgA1 concentration in unknown duplicate samples was determined by interpolation of the respective optical density into the appropriate standard curve. IgG and IgM contents in the supernatant were measured using sandwich ELISA (IMMUNOtek(R), ZeptoMetrix Corporation, Buffalo, NY, USA) according to the manufacturer's instructions.\n"
],
"offsets": [
[
0,
1731
]
]
}
] | [
{
"id": "PMC-2989791-sec-04_T1",
"type": "Organism_substance",
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"supernatant"
],
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[
48,
59
]
],
"normalized": []
},
{
"id": "PMC-2989791-sec-04_T2",
"type": "Organism_substance",
"text": [
"serum"
],
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[
635,
640
]
],
"normalized": []
},
{
"id": "PMC-2989791-sec-04_T4",
"type": "Organism_substance",
"text": [
"supernatant sample"
],
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[
699,
717
]
],
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},
{
"id": "PMC-2989791-sec-04_T5",
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"supernatant"
],
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1580,
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]
],
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},
{
"id": "PMC-2989791-sec-04_T3",
"type": "Cell",
"text": [
"culture"
],
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[
70,
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]
],
"normalized": []
},
{
"id": "PMC-2989791-sec-04_T6",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
1441,
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]
],
"normalized": []
}
] | [] | [] | [] |
PMC-3252742-sec-08 | PMC-3252742-sec-08 | [
{
"id": "PMC-3252742-sec-08__text",
"type": "sec",
"text": [
"Mitochondria in Cardiac Myocyte Apoptosis\nIt has been suggested that activation of the mitochondrial apoptotic pathway leading to executioner casp activation is relevant in heart injury.1 The notion of participation of casp activation in adult cardiac myocyte apoptosis emerged from studies using immunofluorescence microscopy16 and casp inhibitors.37 Bahi et al.38 demonstrated that cardiomyocyte levels of all casps decrease with age, and they are very low in adult cardiac cells. Recently, Bae et al.39 reported that apoptosis can be induced in the heart lacking casp activation via casp-independent pathways, probably through apoptosis-inducing factor (AIF). Both the intrinsic and extrinsic pathways can be inhibited by the cytoprotective protein apoptosis repressor with caspase recruitment domain (ARC). ARC inhibits the extrinsic pathway by interacting with casp 8 and components of the death-inducing signaling complex, such as FADD, whereas inhibition of the intrinsic pathway is mediated by blocking BAX activation and mitochondria translocation.40\nAIF is anchored by its N terminus to the mitochondrial inner membrane, with its C terminus oriented toward the intermembrane space. AIF is required for oxidative phosphorylation and for the assembly and/or stabilization of respiratory complex I.41 Upon induction of apoptosis, AIF is cleaved and released into the cytosol, where it translocates to the nucleus and mediates chromatin condensation and large-scale DNA fragmentation.41 However, this well-known pro-apoptotic action of AIF is in conflict with the observation that AIF is essential for the maintenance of normal heart function and its inactivation results in dilated C.42 Moreover, cardiac myocytes isolated from a mouse model with 80% reduction in AIF levels manifested increased cell death induced by oxidative stress, and the hearts of these mice displayed enhanced ischemic damage after in vivo I/R.43 Although it has been described that AIF is released from cardiac myocyte mitochondria during I/R, its contribution to I/R-induced apoptosis was discounted.38 However, AIF has been implicated in cardiac myocyte death induced by oxidative stress and HF.44\nEndonuclease G (Endo G) is a nuclear-encoded endonuclease localized to the intermembrane space of mitochondria. In cardiac myocyte apoptosis, Endo G translocates to the nucleus, where it cleaves DNA. In heart and cultured cardiac myocytes, Endo G has a role in I/R-mediated cell death.38 Activation of the intrinsic pathway by the extrinsic apoptotic pathway can take place through casp-8-dependent cleavage of BCL2-interacting protein (BID) to truncated BID (t-BID). The C-terminal fragment of t-BID subsequently translocates to the mitochondrial outer membrane, where it presumably activates the intrinsic pathway. This pathway is operative in the heart.1\n"
],
"offsets": [
[
0,
2840
]
]
}
] | [
{
"id": "PMC-3252742-sec-08_T1",
"type": "Cellular_component",
"text": [
"Mitochondria"
],
"offsets": [
[
0,
12
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T2",
"type": "Cell",
"text": [
"Cardiac Myocyte"
],
"offsets": [
[
16,
31
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T3",
"type": "Cellular_component",
"text": [
"mitochondrial"
],
"offsets": [
[
87,
100
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T4",
"type": "Organ",
"text": [
"heart"
],
"offsets": [
[
173,
178
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T5",
"type": "Cell",
"text": [
"adult cardiac myocyte"
],
"offsets": [
[
238,
259
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T6",
"type": "Cell",
"text": [
"cardiomyocyte"
],
"offsets": [
[
384,
397
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T7",
"type": "Cell",
"text": [
"adult cardiac cells"
],
"offsets": [
[
462,
481
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T8",
"type": "Organ",
"text": [
"heart"
],
"offsets": [
[
552,
557
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T9",
"type": "Cellular_component",
"text": [
"mitochondria"
],
"offsets": [
[
1030,
1042
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T10",
"type": "Cellular_component",
"text": [
"mitochondrial inner membrane"
],
"offsets": [
[
1101,
1129
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T11",
"type": "Immaterial_anatomical_entity",
"text": [
"intermembrane space"
],
"offsets": [
[
1171,
1190
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T12",
"type": "Organism_substance",
"text": [
"cytosol"
],
"offsets": [
[
1374,
1381
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T13",
"type": "Cellular_component",
"text": [
"nucleus"
],
"offsets": [
[
1412,
1419
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T14",
"type": "Cellular_component",
"text": [
"chromatin"
],
"offsets": [
[
1433,
1442
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T15",
"type": "Organ",
"text": [
"heart"
],
"offsets": [
[
1634,
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]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T16",
"type": "Cell",
"text": [
"cardiac myocytes"
],
"offsets": [
[
1704,
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]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T17",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1803,
1807
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T18",
"type": "Organ",
"text": [
"hearts"
],
"offsets": [
[
1851,
1857
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T19",
"type": "Cellular_component",
"text": [
"cardiac myocyte mitochondria"
],
"offsets": [
[
1985,
2013
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T20",
"type": "Cell",
"text": [
"cardiac myocyte"
],
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[
2122,
2137
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T21",
"type": "Cellular_component",
"text": [
"nuclear"
],
"offsets": [
[
2211,
2218
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T22",
"type": "Immaterial_anatomical_entity",
"text": [
"intermembrane space"
],
"offsets": [
[
2257,
2276
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T23",
"type": "Cellular_component",
"text": [
"mitochondria"
],
"offsets": [
[
2280,
2292
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T24",
"type": "Cell",
"text": [
"cardiac myocyte"
],
"offsets": [
[
2297,
2312
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T25",
"type": "Cellular_component",
"text": [
"nucleus"
],
"offsets": [
[
2351,
2358
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T26",
"type": "Organ",
"text": [
"heart"
],
"offsets": [
[
2385,
2390
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T27",
"type": "Cell",
"text": [
"cardiac myocytes"
],
"offsets": [
[
2404,
2420
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T28",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
2456,
2460
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T29",
"type": "Cellular_component",
"text": [
"mitochondrial outer membrane"
],
"offsets": [
[
2716,
2744
]
],
"normalized": []
},
{
"id": "PMC-3252742-sec-08_T30",
"type": "Organ",
"text": [
"heart"
],
"offsets": [
[
2832,
2837
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-12604762 | PMID-12604762 | [
{
"id": "PMID-12604762__text",
"type": "abstract",
"text": [
"Rural/urban differences in access to and utilization of services among people in Alabama with sickle cell disease.\nOBJECTIVE:\nThis study examined relationships between socioeconomic factors and the geographic distribution of 662 cases of sickle cell disease in Alabama in 1999-2001.\nMETHODS:\nMeasures of community distress, physical functioning, and medical problems were used in analyzing utilization differences between individuals with sickle cell disease living in urban and rural areas.\nRESULTS:\nUtilization of comprehensive sickle cells disease services was lower for individuals with sickle cell disease living in rural areas than for those living in urban areas. Rural clients reported significantly more limitations than urban clients on several measures of physical functioning. The results also suggest that utilization of services was higher for those with more medical problems and those who lived in high distress areas, although these findings did not meet the criterion for statistical significance.\nCONCLUSIONS:\nConclusions based on statistical evidence that geographic location and socioeconomic factors relate to significantly different health care service experience bear important implications for medical and health care support systems, especially on the community level.\n"
],
"offsets": [
[
0,
1295
]
]
}
] | [
{
"id": "PMID-12604762_T1",
"type": "Cell",
"text": [
"sickle cell"
],
"offsets": [
[
94,
105
]
],
"normalized": []
},
{
"id": "PMID-12604762_T2",
"type": "Cell",
"text": [
"sickle cell"
],
"offsets": [
[
238,
249
]
],
"normalized": []
},
{
"id": "PMID-12604762_T3",
"type": "Cell",
"text": [
"sickle cell"
],
"offsets": [
[
439,
450
]
],
"normalized": []
},
{
"id": "PMID-12604762_T4",
"type": "Cell",
"text": [
"sickle cells"
],
"offsets": [
[
530,
542
]
],
"normalized": []
},
{
"id": "PMID-12604762_T5",
"type": "Cell",
"text": [
"sickle cell"
],
"offsets": [
[
591,
602
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17855765 | PMID-17855765 | [
{
"id": "PMID-17855765__text",
"type": "abstract",
"text": [
"Transporters, enzymes, and enalapril removal in a rat (CC531-induced) liver metastatic model. \nTemporal changes in physiological spaces, protein expression of transporters and enzymes, and enalapril removal were appraised in the metastatic liver tumor model developed from male Wag/Rij rats after the intraportal injection of CC531 colon adenocarcinoma cells; sham-operated preparations received PBS. Liver tissue spaces, investigated with multiple indicator dilution technique in liver perfusion studies, were unchanged at week 3 after tumor induction. At week 4, however, the sinusoidal blood volume and albumin Disse space in tumor-bearing livers were slightly lower compared with those of shams. Increased levels of the canalicular ATP transporters, P-glycoprotein, multidrug resistance-associated protein 2 (Mrp2), and bile salt export pump (Bsep) at week 2 (P < 0.05), unchanged levels of Ntcp, Oatp1a1, Oatp1a4, and Mct2, but decreased levels of cytochrome P450 3a2 (Cyp3a2) and glutathione S-transferase (Gst4-4) at week 4 (P < 0.05) were observed in peritumor vs. sham-operated liver tissues with Western blotting. The steady-state extraction ratio of enalapril, a substrate that enters the liver rapidly via Oatp1a1 and primarily undergoes metabolism by the carboxylesterases, was unaffected by liver metastasis at week 4 regardless of its delivery via the portal vein or hepatic artery into the perfused liver preparations.\n"
],
"offsets": [
[
0,
1435
]
]
}
] | [
{
"id": "PMID-17855765_T3",
"type": "Cell",
"text": [
"CC531"
],
"offsets": [
[
55,
60
]
],
"normalized": []
},
{
"id": "PMID-17855765_T4",
"type": "Organ",
"text": [
"liver"
],
"offsets": [
[
70,
75
]
],
"normalized": []
},
{
"id": "PMID-17855765_T6",
"type": "Cancer",
"text": [
"metastatic liver tumor"
],
"offsets": [
[
229,
251
]
],
"normalized": []
},
{
"id": "PMID-17855765_T8",
"type": "Cell",
"text": [
"CC531 colon adenocarcinoma cells"
],
"offsets": [
[
326,
358
]
],
"normalized": []
},
{
"id": "PMID-17855765_T9",
"type": "Tissue",
"text": [
"Liver tissue"
],
"offsets": [
[
401,
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]
],
"normalized": []
},
{
"id": "PMID-17855765_T10",
"type": "Organ",
"text": [
"liver"
],
"offsets": [
[
481,
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]
],
"normalized": []
},
{
"id": "PMID-17855765_T11",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
537,
542
]
],
"normalized": []
},
{
"id": "PMID-17855765_T12",
"type": "Multi-tissue_structure",
"text": [
"sinusoidal blood"
],
"offsets": [
[
578,
594
]
],
"normalized": []
},
{
"id": "PMID-17855765_T14",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
629,
634
]
],
"normalized": []
},
{
"id": "PMID-17855765_T15",
"type": "Organ",
"text": [
"livers"
],
"offsets": [
[
643,
649
]
],
"normalized": []
},
{
"id": "PMID-17855765_T16",
"type": "Multi-tissue_structure",
"text": [
"canalicular"
],
"offsets": [
[
724,
735
]
],
"normalized": []
},
{
"id": "PMID-17855765_T29",
"type": "Cell",
"text": [
"peritumor"
],
"offsets": [
[
1059,
1068
]
],
"normalized": []
},
{
"id": "PMID-17855765_T30",
"type": "Tissue",
"text": [
"liver tissues"
],
"offsets": [
[
1087,
1100
]
],
"normalized": []
},
{
"id": "PMID-17855765_T32",
"type": "Organ",
"text": [
"liver"
],
"offsets": [
[
1200,
1205
]
],
"normalized": []
},
{
"id": "PMID-17855765_T34",
"type": "Organ",
"text": [
"liver"
],
"offsets": [
[
1305,
1310
]
],
"normalized": []
},
{
"id": "PMID-17855765_T35",
"type": "Multi-tissue_structure",
"text": [
"portal vein"
],
"offsets": [
[
1367,
1378
]
],
"normalized": []
},
{
"id": "PMID-17855765_T36",
"type": "Multi-tissue_structure",
"text": [
"hepatic artery"
],
"offsets": [
[
1382,
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]
],
"normalized": []
},
{
"id": "PMID-17855765_T37",
"type": "Organ",
"text": [
"liver"
],
"offsets": [
[
1415,
1420
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-18600526 | PMID-18600526 | [
{
"id": "PMID-18600526__text",
"type": "abstract",
"text": [
"The role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in tumor behavior.\nPlatelet-derived endothelial cell growth-factor (PD-ECGF) is similar to the pyrimidine enzyme thymidine phosphorylase (TP). A high TP expression at tumor sites is correlated with tumor growth, induction of angiogenesis, and metastasis. Therefore, high TP is most likely associated with a poor prognosis. TP is not only expressed in tumor cells but also in tumor surrounding tissues, such as tumor infiltrating macrophages. TP catalyzes the conversion of thymidine to thymine and doxyribose-1-phosphate (dR-1-P). The latter in its parent form or in its sugar form, deoxyribose (dR) may play a role in the induction of angiogenesis. It may modulate cellular energy metabolism or be a substrate in a chemical reaction generating reactive oxygen species. L-deoxyribose (L-dR) and thymidine phosphorylase inhibitor (TPI) can reverse these effects. The mechanism of TP induction is not yet completely clear, but TNF, IL10 and other cytokines have been clearly shown to induce its expression. The various complex interactions of TP give it an essential role in cellular functioning and, hence, it is an ideal target in cancer therapy.\n"
],
"offsets": [
[
0,
1231
]
]
}
] | [
{
"id": "PMID-18600526_T3",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
87,
92
]
],
"normalized": []
},
{
"id": "PMID-18600526_T9",
"type": "Cancer",
"text": [
"tumor sites"
],
"offsets": [
[
251,
262
]
],
"normalized": []
},
{
"id": "PMID-18600526_T10",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
282,
287
]
],
"normalized": []
},
{
"id": "PMID-18600526_T13",
"type": "Cell",
"text": [
"tumor cells"
],
"offsets": [
[
435,
446
]
],
"normalized": []
},
{
"id": "PMID-18600526_T14",
"type": "Tissue",
"text": [
"tumor surrounding tissues"
],
"offsets": [
[
459,
484
]
],
"normalized": []
},
{
"id": "PMID-18600526_T15",
"type": "Cell",
"text": [
"tumor infiltrating macrophages"
],
"offsets": [
[
494,
524
]
],
"normalized": []
},
{
"id": "PMID-18600526_T24",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
750,
758
]
],
"normalized": []
},
{
"id": "PMID-18600526_T34",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
1157,
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]
],
"normalized": []
},
{
"id": "PMID-18600526_T35",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
1215,
1221
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-14714614 | PMID-14714614 | [
{
"id": "PMID-14714614__text",
"type": "abstract",
"text": [
"Prognostic significance and correlation with survival of bcl-2 and TGF-beta RII in colon cancer.\nBcl-2 and TGF-beta receptors type II (RII) in colon carcinomas were studied in a series of 113 patients, to determine their prognostic significance and to correlate their expression with other prognostic indicators. Bcl-2 expression in the tumor cells showed a reverse relation with tumor size (P = 0.018), histological grade (P = 0.04), and stage (P = 0.013). Univariate survival analysis using the log rank test showed that the survival of patients with bcl-2-positive tumors was significantly better than the survival of patients with bcl-2-negative tumors (P = 0.02). However, when entered into a multivariate analysis model, it was not found to be of independent prognostic significance. TGF-beta RII expression was correlated with stage (P = 0.03), while no statistically significant correlation was found between TGF-beta RII expression and histological grade or survival. In conclusion, these results provide additional evidence for the role of bcl-2 and TGF-beta RII in carcinogenesis of the colon, while they do not support the use of these factors as prognostic markers in patients with colon cancer.\n"
],
"offsets": [
[
0,
1209
]
]
}
] | [
{
"id": "PMID-14714614_T1",
"type": "Cancer",
"text": [
"colon cancer"
],
"offsets": [
[
83,
95
]
],
"normalized": []
},
{
"id": "PMID-14714614_T2",
"type": "Cancer",
"text": [
"colon carcinomas"
],
"offsets": [
[
143,
159
]
],
"normalized": []
},
{
"id": "PMID-14714614_T3",
"type": "Cell",
"text": [
"tumor cells"
],
"offsets": [
[
337,
348
]
],
"normalized": []
},
{
"id": "PMID-14714614_T4",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
380,
385
]
],
"normalized": []
},
{
"id": "PMID-14714614_T5",
"type": "Cancer",
"text": [
"bcl-2-positive tumors"
],
"offsets": [
[
553,
574
]
],
"normalized": []
},
{
"id": "PMID-14714614_T6",
"type": "Cancer",
"text": [
"bcl-2-negative tumors"
],
"offsets": [
[
635,
656
]
],
"normalized": []
},
{
"id": "PMID-14714614_T7",
"type": "Organ",
"text": [
"colon"
],
"offsets": [
[
1098,
1103
]
],
"normalized": []
},
{
"id": "PMID-14714614_T8",
"type": "Cancer",
"text": [
"colon cancer"
],
"offsets": [
[
1195,
1207
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2660343-sec-18 | PMC-2660343-sec-18 | [
{
"id": "PMC-2660343-sec-18__text",
"type": "sec",
"text": [
"Peptide-BSA conjugates as diagnostic antigens\nTo analyse the potential of the peptides to behave as antigen mimics, their ability to react with IgM antibodies from individuals infected with EBV was assessed. In our previous study, we demonstrated that the sensitivity of detection was greatly improved when the peptides were coupled to a carrier molecule such as BSA prior to immobilisation onto a solid surface (Casey et al., 2006). This strategy was adopted to test peptides Eb1-4 and H1. A set of 40 clinical samples that were classified as EBV seropositive (n = 16), seronegative (n = 16) or potentially cross-reactive sera (n = 8) were assessed for reactivity with Eb1-4 and H1 peptides individually. The cut-off level was defined as the mean optical density of the seronegative samples plus 3 standard deviations shown as a line on the graphs in Fig. 5. Readings above this level were defined as positive and below this level negative. The same set of samples were analysed on BSA alone and these values were subtracted from the peptide-BSA conjugate readings and the corrected absorbance readings were plotted individually for our new peptides Eb1-4 and H1 in Fig. 5. There was a clear difference in the detection of seropositive antibodies by all the peptides (Fig. 5A-E) compared with the analysis of BSA alone (Fig. 5F), with the majority of absorbance readings above the cut-off level. We compared the ability of our panel of peptide mimotopes to be recognised by antibodies in the same set of seropositive samples in Fig. 6A and the sensitivity of detection is shown in Fig. 6B. We also included F1 and Gp125 mimotopes specific for two mAbs in our previous study (Casey et al., 2006). Of the peptides identified from polyclonal sera Eb1, Gp125 and F1 had the highest sensitivity (94%). Slightly lower sensitivity was observed for Eb2, 3 and 4 (88%) and H1 peptide had the lowest sensitivity (81%) as summarised in Fig. 6B. The sensitivity of F1 and Gp125 was similar to that produced by the mimotopes selected in our previous study, 95% for F1 and 92% for Gp125.\nFig. 5\nEvaluation of peptides Eb1-4 and H1 coupled to BSA as EBV diagnostic reagents. Human serum (n = 40) previously analysed using a diagnostic test for VCA IgM was allowed to react with the peptides and the bound IgM antibodies were detected using anti-human IgM HRP. The absorbance readings for 1 (positive), 2 (negative) and putative cross-reactive sera for 3 (Parvo), 4 (HSV), 5 (CMV) and 6 (RF) are plotted for (A) Eb1, (B) Eb2, (C) Eb3, (D) Eb4, (E) H1 and (F) BSA, respectively. The cut-off value is defined as the mean of the negative population +3SD indicated by a solid horizontal line; since there were no false positives, the specificity for each mimotope was 100%.\nFig. 6\nComparison of the reactivities of our panel of mimotopes Eb1-4, H1, F1 and Gp125 conjugated to BSA with EBV IgM-positive sera (n = 16) absorbance values are plotted and the cut-off levels are depicted by a horizontal line in (A). (B) Summary of the false-negative results from the 5/16 serum samples seropositive for IgM EBV and the overall sensitivity for each mimotope for diagnosis of EBV IgM antibodies.\nWe also considered which seropositive EBV samples contained antibodies that did not recognise the panel of peptides, i.e. false-negative readings, listed in Fig. 6B. The antibodies in serum 1 (s1) were unreactive with all of the peptides identified in this study, s2 was not reactive with Eb3, Eb4 and H1 and s3 was unreactive with H1. Gp125 and F1 that were selected in our previous study were recognised by s1, 2 and 3; however, two different serum samples (s4 and 5) did not recognise F1 or Gp125, respectively. This demonstrates that individual peptides are not recognised by all EBV antibodies and confirms that different peptides are required to represent different epitopes. Therefore, a combination of Eb1 peptide F1 and Gp125 peptides could be recognised by antibodies present in all this set of EBV clinical samples resulting in 100% sensitivity.\nFor the samples defined as EBV-seronegative, there were no readings above the cut-off level and therefore no false positives, resulting in 100% specificity. In addition, there were no absorbance readings above the cut-off levels for the potentially cross-reactive serum samples, inferring that the peptides identified in this study have high specificity for EBV antibodies.\n"
],
"offsets": [
[
0,
4401
]
]
}
] | [
{
"id": "PMC-2660343-sec-18_T1",
"type": "Organism_substance",
"text": [
"sera"
],
"offsets": [
[
1740,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T2",
"type": "Organism_substance",
"text": [
"serum"
],
"offsets": [
[
2167,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T3",
"type": "Organism_substance",
"text": [
"sera"
],
"offsets": [
[
2429,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T4",
"type": "Organism_substance",
"text": [
"sera"
],
"offsets": [
[
2883,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T5",
"type": "Organism_substance",
"text": [
"serum samples"
],
"offsets": [
[
3048,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T6",
"type": "Organism_substance",
"text": [
"serum"
],
"offsets": [
[
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T7",
"type": "Organism_substance",
"text": [
"serum samples"
],
"offsets": [
[
3615,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T8",
"type": "Organism_substance",
"text": [
"serum samples"
],
"offsets": [
[
4291,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T9",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
3212,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T14",
"type": "Organism_substance",
"text": [
"sera"
],
"offsets": [
[
623,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T10",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
512,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T11",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
784,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T12",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
958,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T13",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
1518,
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T15",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
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]
],
"normalized": []
},
{
"id": "PMC-2660343-sec-18_T16",
"type": "Organism_substance",
"text": [
"samples"
],
"offsets": [
[
4035,
4042
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-21340684 | PMID-21340684 | [
{
"id": "PMID-21340684__text",
"type": "abstract",
"text": [
"Metabolic regulation by p53.\nWe are increasingly aware that cellular metabolism plays a vital role in diseases such as cancer, and that p53 is an important regulator of metabolic pathways. By transcriptional activation and other means, p53 is able to contribute to the regulation of glycolysis, oxidative phosphorylation, glutaminolysis, insulin sensitivity, nucleotide biosynthesis, mitochondrial integrity, fatty acid oxidation, antioxidant response, autophagy and mTOR signalling. The ability to positively and negatively regulate many of these pathways, combined with feedback signalling from these pathways to p53, demonstrates the reciprocal and flexible nature of the regulation, facilitating a diverse range of responses to metabolic stress. Intriguingly, metabolic stress triggers primarily an adaptive (rather than pro-apoptotic) p53 response, and p53 is emerging as an important regulator of metabolic homeostasis. A better understanding of how p53 coordinates metabolic adaptation will facilitate the identification of novel therapeutic targets and will also illuminate the wider role of p53 in human biology.\n"
],
"offsets": [
[
0,
1122
]
]
}
] | [
{
"id": "PMID-21340684_T2",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
60,
68
]
],
"normalized": []
},
{
"id": "PMID-21340684_T3",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
119,
125
]
],
"normalized": []
},
{
"id": "PMID-21340684_T8",
"type": "Cellular_component",
"text": [
"mitochondrial"
],
"offsets": [
[
384,
397
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-1557851-sec-01 | PMC-1557851-sec-01 | [
{
"id": "PMC-1557851-sec-01__text",
"type": "sec",
"text": [
"Background\nHallucinations may occur in any sensory modalities. Formed musical hallucinations (i.e. Perception of either vocal or instrumental melodies) reported in English literature to date have typically been associated with marked hearing loss, advanced age, female sex (71%), lack of response to treatment and associated psychopathology [1] but has been concluded that hearing loss is neither a necessary nor sufficient condition for the occurrence of musical hallucinations [1]. Tumor like Astrocytoma, Temporal lobe epilepsy, raised intra cranial tension, drug induced (tricyclics, Propronolol etc ;), meningitis and psychotic illness were shown to cause palinacousis and musical hallucinations [2,3].\nMusical hallucinations are pseudo hallucinations that originate in memory representations and they may undergo a transition to true hallucination. In musical hallucination spatial projection is less definite. Sometimes they are perceived like the tinnitus in patient's own head. The quality is usually very intense and distinct often very loud. They vary from elementary sounds to instrumental music, vocal music, bird songs, bells, pieces of melodies or sentences, religious music etc:- We report an unusual presentation of an elderly lady who had experienced musical hallucinations whilst being treated with Electro Convulsive Therapy. Though this has never been reported earlier, there seemed to have a good association between the initiation of Electro convulsive therapy and musical hallucination in our patient.\n"
],
"offsets": [
[
0,
1526
]
]
}
] | [
{
"id": "PMC-1557851-sec-01_T1",
"type": "Cancer",
"text": [
"Tumor"
],
"offsets": [
[
484,
489
]
],
"normalized": []
},
{
"id": "PMC-1557851-sec-01_T2",
"type": "Cancer",
"text": [
"Astrocytoma"
],
"offsets": [
[
495,
506
]
],
"normalized": []
},
{
"id": "PMC-1557851-sec-01_T3",
"type": "Multi-tissue_structure",
"text": [
"Temporal lobe"
],
"offsets": [
[
508,
521
]
],
"normalized": []
},
{
"id": "PMC-1557851-sec-01_T4",
"type": "Organism_subdivision",
"text": [
"cranial"
],
"offsets": [
[
545,
552
]
],
"normalized": []
},
{
"id": "PMC-1557851-sec-01_T5",
"type": "Organism_subdivision",
"text": [
"head"
],
"offsets": [
[
981,
985
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-16470244 | PMID-16470244 | [
{
"id": "PMID-16470244__text",
"type": "abstract",
"text": [
"Pericytes limit tumor cell metastasis.\nPreviously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role for pericytes in limiting tumor cell metastasis. These data support a new model for how tumor cells trigger metastasis by perturbing pericyte-endothelial cell-cell interactions.\n"
],
"offsets": [
[
0,
1135
]
]
}
] | [
{
"id": "PMID-16470244_T1",
"type": "Cell",
"text": [
"Pericytes"
],
"offsets": [
[
0,
9
]
],
"normalized": []
},
{
"id": "PMID-16470244_T2",
"type": "Cell",
"text": [
"tumor cell"
],
"offsets": [
[
16,
26
]
],
"normalized": []
},
{
"id": "PMID-16470244_T5",
"type": "Cell",
"text": [
"beta tumor cells"
],
"offsets": [
[
118,
134
]
],
"normalized": []
},
{
"id": "PMID-16470244_T6",
"type": "Organ",
"text": [
"organs"
],
"offsets": [
[
171,
177
]
],
"normalized": []
},
{
"id": "PMID-16470244_T7",
"type": "Multi-tissue_structure",
"text": [
"lymph nodes"
],
"offsets": [
[
188,
199
]
],
"normalized": []
},
{
"id": "PMID-16470244_T8",
"type": "Cancer",
"text": [
"NCAM-deficient beta cell tumors"
],
"offsets": [
[
220,
251
]
],
"normalized": []
},
{
"id": "PMID-16470244_T10",
"type": "Multi-tissue_structure",
"text": [
"blood vessels"
],
"offsets": [
[
263,
276
]
],
"normalized": []
},
{
"id": "PMID-16470244_T11",
"type": "Cell",
"text": [
"pericyte"
],
"offsets": [
[
292,
300
]
],
"normalized": []
},
{
"id": "PMID-16470244_T12",
"type": "Cell",
"text": [
"endothelial"
],
"offsets": [
[
301,
312
]
],
"normalized": []
},
{
"id": "PMID-16470244_T13",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
313,
317
]
],
"normalized": []
},
{
"id": "PMID-16470244_T14",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
318,
322
]
],
"normalized": []
},
{
"id": "PMID-16470244_T15",
"type": "Immaterial_anatomical_entity",
"text": [
"perivascular"
],
"offsets": [
[
350,
362
]
],
"normalized": []
},
{
"id": "PMID-16470244_T16",
"type": "Cellular_component",
"text": [
"ECM components"
],
"offsets": [
[
377,
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]
],
"normalized": []
},
{
"id": "PMID-16470244_T17",
"type": "Cell",
"text": [
"tumor cell"
],
"offsets": [
[
405,
415
]
],
"normalized": []
},
{
"id": "PMID-16470244_T19",
"type": "Cancer",
"text": [
"fibrosarcoma"
],
"offsets": [
[
440,
452
]
],
"normalized": []
},
{
"id": "PMID-16470244_T20",
"type": "Cancer",
"text": [
"T241"
],
"offsets": [
[
460,
464
]
],
"normalized": []
},
{
"id": "PMID-16470244_T21",
"type": "Cell",
"text": [
"pericyte"
],
"offsets": [
[
475,
483
]
],
"normalized": []
},
{
"id": "PMID-16470244_T22",
"type": "Immaterial_anatomical_entity",
"text": [
"perivascular"
],
"offsets": [
[
510,
522
]
],
"normalized": []
},
{
"id": "PMID-16470244_T23",
"type": "Cellular_component",
"text": [
"ECM molecules"
],
"offsets": [
[
537,
550
]
],
"normalized": []
},
{
"id": "PMID-16470244_T25",
"type": "Cell",
"text": [
"tumor cell"
],
"offsets": [
[
605,
615
]
],
"normalized": []
},
{
"id": "PMID-16470244_T26",
"type": "Tissue",
"text": [
"microvessel wall"
],
"offsets": [
[
646,
662
]
],
"normalized": []
},
{
"id": "PMID-16470244_T27",
"type": "Cell",
"text": [
"pericyte"
],
"offsets": [
[
692,
700
]
],
"normalized": []
},
{
"id": "PMID-16470244_T28",
"type": "Cancer",
"text": [
"solid tumors"
],
"offsets": [
[
751,
763
]
],
"normalized": []
},
{
"id": "PMID-16470244_T29",
"type": "Cell",
"text": [
"beta cell"
],
"offsets": [
[
776,
785
]
],
"normalized": []
},
{
"id": "PMID-16470244_T30",
"type": "Cell",
"text": [
"pericyte"
],
"offsets": [
[
811,
819
]
],
"normalized": []
},
{
"id": "PMID-16470244_T33",
"type": "Cancer",
"text": [
"beta tumor cell metastases"
],
"offsets": [
[
868,
894
]
],
"normalized": []
},
{
"id": "PMID-16470244_T34",
"type": "Organ",
"text": [
"organs"
],
"offsets": [
[
906,
912
]
],
"normalized": []
},
{
"id": "PMID-16470244_T35",
"type": "Multi-tissue_structure",
"text": [
"lymph nodes"
],
"offsets": [
[
923,
934
]
],
"normalized": []
},
{
"id": "PMID-16470244_T36",
"type": "Cell",
"text": [
"pericytes"
],
"offsets": [
[
961,
970
]
],
"normalized": []
},
{
"id": "PMID-16470244_T37",
"type": "Cell",
"text": [
"tumor cell"
],
"offsets": [
[
983,
993
]
],
"normalized": []
},
{
"id": "PMID-16470244_T38",
"type": "Cell",
"text": [
"tumor cells"
],
"offsets": [
[
1045,
1056
]
],
"normalized": []
},
{
"id": "PMID-16470244_T39",
"type": "Cell",
"text": [
"pericyte"
],
"offsets": [
[
1090,
1098
]
],
"normalized": []
},
{
"id": "PMID-16470244_T40",
"type": "Cell",
"text": [
"endothelial"
],
"offsets": [
[
1099,
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]
],
"normalized": []
},
{
"id": "PMID-16470244_T41",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1111,
1115
]
],
"normalized": []
},
{
"id": "PMID-16470244_T42",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1116,
1120
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-1281295-caption-02 | PMC-1281295-caption-02 | [
{
"id": "PMC-1281295-caption-02__text",
"type": "caption",
"text": [
"Measured analytes in five biologic sample matrices.a\n"
],
"offsets": [
[
0,
53
]
]
}
] | [] | [] | [] | [] |
PMID-17305525 | PMID-17305525 | [
{
"id": "PMID-17305525__text",
"type": "abstract",
"text": [
"New vectors and strategies for cardiovascular gene therapy.\nCardiovascular diseases are the major cause of morbidity and mortality in both men and women in industrially developed countries. These disorders may result from impaired angiogenesis, particularly in response to hypoxia. Despite many limitations, gene therapy is still emerging as a potential alternative for patients who are not candidates for traditional revascularization procedures, like angioplasty or vein grafts. This review focuses on recent approaches in the development of new gene delivery vectors, with great respect to newly discovered AAV serotypes and their modified forms. Moreover, some new cardiovascular gene therapy strategies have been highlighted, such as combination of different angiogenic growth factors or simultaneous application of genes and progenitor cells in order to obtain stable and functional blood vessels in ischemic tissue.\n"
],
"offsets": [
[
0,
923
]
]
}
] | [
{
"id": "PMID-17305525_T8",
"type": "Multi-tissue_structure",
"text": [
"vein grafts"
],
"offsets": [
[
468,
479
]
],
"normalized": []
},
{
"id": "PMID-17305525_T12",
"type": "Cell",
"text": [
"progenitor cells"
],
"offsets": [
[
831,
847
]
],
"normalized": []
},
{
"id": "PMID-17305525_T14",
"type": "Multi-tissue_structure",
"text": [
"blood vessels"
],
"offsets": [
[
889,
902
]
],
"normalized": []
},
{
"id": "PMID-17305525_T15",
"type": "Tissue",
"text": [
"tissue"
],
"offsets": [
[
915,
921
]
],
"normalized": []
},
{
"id": "PMID-17305525_T4",
"type": "Anatomical_system",
"text": [
"cardiovascular"
],
"offsets": [
[
31,
45
]
],
"normalized": []
},
{
"id": "PMID-17305525_T5",
"type": "Anatomical_system",
"text": [
"Cardiovascular"
],
"offsets": [
[
60,
74
]
],
"normalized": []
},
{
"id": "PMID-17305525_T6",
"type": "Anatomical_system",
"text": [
"cardiovascular"
],
"offsets": [
[
669,
683
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-19269647 | PMID-19269647 | [
{
"id": "PMID-19269647__text",
"type": "abstract",
"text": [
"Handling within run retention time shifts in two-dimensional chromatography data using shift correction and modeling.\nThe use of PARAFAC for modeling GC x GC-TOFMS peaks is well documented. This success is due to the trilinear structure of these data under ideal, or sufficiently close to ideal, chromatographic conditions. However, using temperature programming to cope with the general elution problem, deviations from trilinearity within a run are more likely to be seen for the following three cases: (1) compounds (i.e., analytes) severely broadened on the first column hence defined by many modulation periods, (2) analytes with a very high retention factor on the second column and likely wrapped around in that dimension, or (3) with fast temperature program rates. This deviation from trilinearity is seen as retention time-shifted peak profiles in subsequent modulation periods (first column fractions). In this report, a relaxed yet powerful version of PARAFAC, known as PARAFAC2 has been applied to handle this shift within the model step by allowing generation of individual peak profiles in subsequent first column fractions. An alternative approach was also studied, utilizing a standard retention time shift correction to restore the data trilinearity structure followed by PARAFAC. These two approaches are compared when identifying and quantifying a known analyte over a large concentration series where a certain shift is simulated in the successive first column fractions. Finally, the methods are applied to real chromatographic data showing severely shifted peak profiles. The pros and cons of the presented approaches are discussed in relation to the model parameters, the signal-to-noise ratio and the degree of shift.\n"
],
"offsets": [
[
0,
1743
]
]
}
] | [] | [] | [] | [] |
PMC-2578989-sec-01 | PMC-2578989-sec-01 | [
{
"id": "PMC-2578989-sec-01__text",
"type": "sec",
"text": [
"Images\nFigure 1\nFigure 5\nFigure 6\n"
],
"offsets": [
[
0,
34
]
]
}
] | [] | [] | [] | [] |
PMID-17005546 | PMID-17005546 | [
{
"id": "PMID-17005546__text",
"type": "abstract",
"text": [
"Neoplastic transformation of ciliary body epithelium is associated with loss of opticin expression. \nBACKGROUND: Opticin is a recently discovered glycoprotein present predominantly in the vitreous humour. It is synthesised and secreted by the ciliary body epithelium (CBE) from the initiation of CBE development in the embryo, and production continues throughout life. AIM: To determine whether a variety of ciliary body tumours synthesise opticin to characterise further its role in ciliary body health and disease. METHODS: Immunohistochemistry was used to determine the distribution of opticin in normal human CBE, and in hyperplastic and neoplastic CBE lesions. RESULTS: Opticin was immunolocalised to the basal cell surface and basement membrane material of the non-pigmented CBE in nine donor eyes as well as four hyperplastic lesions of the CBE (Fuchs's adenoma). By contrast, none of eight neoplastic lesions (two adenoma and six adenocarcinoma) of CBE stained for opticin. CONCLUSION: The present series supports the theory that opticin is produced by the non-pigmented CBE throughout adult life. Loss of opticin expression by this tissue is associated with and could contribute towards neoplastic transformation.\n"
],
"offsets": [
[
0,
1223
]
]
}
] | [
{
"id": "PMID-17005546_T1",
"type": "Tissue",
"text": [
"ciliary body epithelium"
],
"offsets": [
[
29,
52
]
],
"normalized": []
},
{
"id": "PMID-17005546_T4",
"type": "Organism_substance",
"text": [
"vitreous humour"
],
"offsets": [
[
188,
203
]
],
"normalized": []
},
{
"id": "PMID-17005546_T5",
"type": "Tissue",
"text": [
"ciliary body epithelium"
],
"offsets": [
[
243,
266
]
],
"normalized": []
},
{
"id": "PMID-17005546_T6",
"type": "Tissue",
"text": [
"CBE"
],
"offsets": [
[
268,
271
]
],
"normalized": []
},
{
"id": "PMID-17005546_T7",
"type": "Tissue",
"text": [
"CBE"
],
"offsets": [
[
296,
299
]
],
"normalized": []
},
{
"id": "PMID-17005546_T8",
"type": "Developing_anatomical_structure",
"text": [
"embryo"
],
"offsets": [
[
319,
325
]
],
"normalized": []
},
{
"id": "PMID-17005546_T9",
"type": "Cancer",
"text": [
"ciliary body tumours"
],
"offsets": [
[
408,
428
]
],
"normalized": []
},
{
"id": "PMID-17005546_T11",
"type": "Multi-tissue_structure",
"text": [
"ciliary body"
],
"offsets": [
[
484,
496
]
],
"normalized": []
},
{
"id": "PMID-17005546_T14",
"type": "Tissue",
"text": [
"CBE"
],
"offsets": [
[
613,
616
]
],
"normalized": []
},
{
"id": "PMID-17005546_T15",
"type": "Cancer",
"text": [
"hyperplastic"
],
"offsets": [
[
625,
637
]
],
"normalized": []
},
{
"id": "PMID-17005546_T16",
"type": "Cancer",
"text": [
"neoplastic CBE lesions"
],
"offsets": [
[
642,
664
]
],
"normalized": []
},
{
"id": "PMID-17005546_T18",
"type": "Cellular_component",
"text": [
"basal cell surface"
],
"offsets": [
[
710,
728
]
],
"normalized": []
},
{
"id": "PMID-17005546_T19",
"type": "Cellular_component",
"text": [
"basement membrane material"
],
"offsets": [
[
733,
759
]
],
"normalized": []
},
{
"id": "PMID-17005546_T20",
"type": "Tissue",
"text": [
"non-pigmented CBE"
],
"offsets": [
[
767,
784
]
],
"normalized": []
},
{
"id": "PMID-17005546_T21",
"type": "Organ",
"text": [
"eyes"
],
"offsets": [
[
799,
803
]
],
"normalized": []
},
{
"id": "PMID-17005546_T22",
"type": "Cancer",
"text": [
"hyperplastic lesions"
],
"offsets": [
[
820,
840
]
],
"normalized": []
},
{
"id": "PMID-17005546_T23",
"type": "Tissue",
"text": [
"CBE"
],
"offsets": [
[
848,
851
]
],
"normalized": []
},
{
"id": "PMID-17005546_T24",
"type": "Cancer",
"text": [
"Fuchs's adenoma"
],
"offsets": [
[
853,
868
]
],
"normalized": []
},
{
"id": "PMID-17005546_T25",
"type": "Cancer",
"text": [
"neoplastic lesions"
],
"offsets": [
[
898,
916
]
],
"normalized": []
},
{
"id": "PMID-17005546_T26",
"type": "Pathological_formation",
"text": [
"adenoma"
],
"offsets": [
[
922,
929
]
],
"normalized": []
},
{
"id": "PMID-17005546_T27",
"type": "Cancer",
"text": [
"adenocarcinoma"
],
"offsets": [
[
938,
952
]
],
"normalized": []
},
{
"id": "PMID-17005546_T28",
"type": "Tissue",
"text": [
"CBE"
],
"offsets": [
[
957,
960
]
],
"normalized": []
},
{
"id": "PMID-17005546_T31",
"type": "Tissue",
"text": [
"non-pigmented CBE"
],
"offsets": [
[
1065,
1082
]
],
"normalized": []
},
{
"id": "PMID-17005546_T33",
"type": "Tissue",
"text": [
"tissue"
],
"offsets": [
[
1141,
1147
]
],
"normalized": []
},
{
"id": "PMID-17005546_T2",
"type": "Cancer",
"text": [
"Neoplastic"
],
"offsets": [
[
0,
10
]
],
"normalized": []
},
{
"id": "PMID-17005546_T3",
"type": "Cancer",
"text": [
"neoplastic"
],
"offsets": [
[
1196,
1206
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-15776477 | PMID-15776477 | [
{
"id": "PMID-15776477__text",
"type": "abstract",
"text": [
"Angiogenin is up-regulated in the nucleus and cytoplasm in human primary breast carcinoma and is associated with markers of hypoxia but not survival. \nAngiogenin, a 14.2 kD polypeptide that was originally noted for its angiogenic activity, is now increasingly recognized to have a multiplicity of biological roles in both physiological and pathological conditions. In breast cancer, there are conflicting studies questioning the role of angiogenin. Here, the pattern of expression of angiogenin during the transition from normal breast tissue to ductal carcinoma in situ and invasive carcinoma is reported together with the correlates between the level of angiogenin in 239 invasive carcinomas and standard clinicopathological parameters, hypoxia-inducible factor (HIF)-1 alpha and the HIF-1 alpha target gene DEC-1. This study shows that angiogenin expression is up-regulated in the cytoplasmic and nuclear compartments in in situ carcinoma and invasive carcinoma compared with normal breast tissue and that angiogenin expression in invasive carcinomas is significantly positively associated with high tumour grade (p = 0.03), positive oestrogen receptor (ER) status (p = 0.01), HIF-1 alpha (p = 0.001) and DEC 1 (p = 0.001), but not with patient age (p = 0.8), tumour size (p = 0.25), lymph node status (p = 0.69), epidermal growth factor receptor (p = 0.56) or microvessel density (p = 0.32). No difference in relapse-free (p = 0.26) or overall (p = 0.63) survival was observed in patients stratified by angiogenin expression. This study suggests that angiogenin may be important in breast cancer progression and that, through its relationship with ER, it may be a target for tamoxifen.\n"
],
"offsets": [
[
0,
1690
]
]
}
] | [
{
"id": "PMID-15776477_T2",
"type": "Cellular_component",
"text": [
"nucleus"
],
"offsets": [
[
34,
41
]
],
"normalized": []
},
{
"id": "PMID-15776477_T3",
"type": "Organism_substance",
"text": [
"cytoplasm"
],
"offsets": [
[
46,
55
]
],
"normalized": []
},
{
"id": "PMID-15776477_T5",
"type": "Cancer",
"text": [
"primary breast carcinoma"
],
"offsets": [
[
65,
89
]
],
"normalized": []
},
{
"id": "PMID-15776477_T7",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
368,
381
]
],
"normalized": []
},
{
"id": "PMID-15776477_T10",
"type": "Tissue",
"text": [
"breast tissue"
],
"offsets": [
[
529,
542
]
],
"normalized": []
},
{
"id": "PMID-15776477_T11",
"type": "Cancer",
"text": [
"ductal carcinoma in situ"
],
"offsets": [
[
546,
570
]
],
"normalized": []
},
{
"id": "PMID-15776477_T12",
"type": "Cancer",
"text": [
"invasive carcinoma"
],
"offsets": [
[
575,
593
]
],
"normalized": []
},
{
"id": "PMID-15776477_T14",
"type": "Cancer",
"text": [
"invasive carcinomas"
],
"offsets": [
[
674,
693
]
],
"normalized": []
},
{
"id": "PMID-15776477_T19",
"type": "Cellular_component",
"text": [
"cytoplasmic"
],
"offsets": [
[
884,
895
]
],
"normalized": []
},
{
"id": "PMID-15776477_T20",
"type": "Cellular_component",
"text": [
"nuclear compartments"
],
"offsets": [
[
900,
920
]
],
"normalized": []
},
{
"id": "PMID-15776477_T21",
"type": "Cancer",
"text": [
"in situ carcinoma"
],
"offsets": [
[
924,
941
]
],
"normalized": []
},
{
"id": "PMID-15776477_T22",
"type": "Cancer",
"text": [
"invasive carcinoma"
],
"offsets": [
[
946,
964
]
],
"normalized": []
},
{
"id": "PMID-15776477_T23",
"type": "Tissue",
"text": [
"breast tissue"
],
"offsets": [
[
986,
999
]
],
"normalized": []
},
{
"id": "PMID-15776477_T25",
"type": "Cancer",
"text": [
"invasive carcinomas"
],
"offsets": [
[
1034,
1053
]
],
"normalized": []
},
{
"id": "PMID-15776477_T26",
"type": "Cancer",
"text": [
"tumour"
],
"offsets": [
[
1103,
1109
]
],
"normalized": []
},
{
"id": "PMID-15776477_T32",
"type": "Cancer",
"text": [
"tumour"
],
"offsets": [
[
1263,
1269
]
],
"normalized": []
},
{
"id": "PMID-15776477_T33",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1287,
1297
]
],
"normalized": []
},
{
"id": "PMID-15776477_T35",
"type": "Tissue",
"text": [
"microvessel"
],
"offsets": [
[
1364,
1375
]
],
"normalized": []
},
{
"id": "PMID-15776477_T39",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
1586,
1599
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-15876269 | PMID-15876269 | [
{
"id": "PMID-15876269__text",
"type": "abstract",
"text": [
"Rofecoxib as adjunctive therapy for haemophilic arthropathy.\nJoint haemorrhage and subsequent haemophilic arthropathy are significant complications in haemophilia. The pathophysiology involves inflammation and angiogenesis. Cyclooxygenase-2 (COX-2) inhibitors are anti-inflammatory agents, which have potent anti-inflammatory, anti-angiogenic and analgesic properties yet do not affect platelet function in the manner of traditional non-steroidal anti-inflammatory drugs. These properties make such agents potentially useful as adjunctive therapy in haemophilia. There is only one prior report describing rofecoxib treatment in a single haemophilia patient. Our objectives were to determine the safety and efficacy of rofecoxib in treating acute haemarthrosis, chronic synovitis, target joints and pain. We conducted a retrospective medical record review of patients treated with rofecoxib for acute haemarthrosis, chronic synovitis, target joint or pain. The safety and efficacy of rofecoxib treatment were determined based on subjective patient reports and physical examinations during follow-up clinic visits. A total of 28 patients between 3 and 37 years of age were treated for a total of 42 courses of rofecoxib treatment. All courses were evaluated for safety and 31 for efficacy. Rofecoxib was used for eight acute haemarthrosis, four target joints, seven cases of synovitis and 12 episodes of pain. Efficacy was demonstrated particularly for chronic synovitis and pain and no serious adverse events occurred. This is the largest study to date evaluating COX-2 inhibitors as adjunctive therapy in haemophilia and suggests that these agents may be an important adjunctive therapy in the management of haemophilia.\n"
],
"offsets": [
[
0,
1721
]
]
}
] | [
{
"id": "PMID-15876269_T2",
"type": "Multi-tissue_structure",
"text": [
"Joint"
],
"offsets": [
[
61,
66
]
],
"normalized": []
},
{
"id": "PMID-15876269_T5",
"type": "Cell",
"text": [
"platelet"
],
"offsets": [
[
386,
394
]
],
"normalized": []
},
{
"id": "PMID-15876269_T10",
"type": "Multi-tissue_structure",
"text": [
"joints"
],
"offsets": [
[
787,
793
]
],
"normalized": []
},
{
"id": "PMID-15876269_T13",
"type": "Multi-tissue_structure",
"text": [
"joint"
],
"offsets": [
[
941,
946
]
],
"normalized": []
},
{
"id": "PMID-15876269_T19",
"type": "Multi-tissue_structure",
"text": [
"joints"
],
"offsets": [
[
1350,
1356
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17016553 | PMID-17016553 | [
{
"id": "PMID-17016553__text",
"type": "abstract",
"text": [
"Imaging tumor angiogenesis.\nSince the discovery of vascular-specific growth factors with angiogenic activity, there has been a significant effort to develop cancer drugs that restrict tumorigenesis by targeting the blood supply. In this issue of the JCI, Mancuso et al. use mouse models to better understand the plasticity of the tumor vasculature in the face of antiangiogenic therapy (see the related article beginning on page 2610). They describe a rapid regrowth of the tumor vasculature following withdrawal of VEGFR inhibitors, emphasizing the importance of fully understanding the function of these and similar treatments used in the clinic at the cellular and molecular level.\n"
],
"offsets": [
[
0,
685
]
]
}
] | [
{
"id": "PMID-17016553_T1",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
8,
13
]
],
"normalized": []
},
{
"id": "PMID-17016553_T4",
"type": "Organism_substance",
"text": [
"blood"
],
"offsets": [
[
215,
220
]
],
"normalized": []
},
{
"id": "PMID-17016553_T6",
"type": "Multi-tissue_structure",
"text": [
"tumor vasculature"
],
"offsets": [
[
330,
347
]
],
"normalized": []
},
{
"id": "PMID-17016553_T9",
"type": "Multi-tissue_structure",
"text": [
"tumor vasculature"
],
"offsets": [
[
474,
491
]
],
"normalized": []
},
{
"id": "PMID-17016553_T5",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
157,
163
]
],
"normalized": []
},
{
"id": "PMID-17016553_T8",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
655,
663
]
],
"normalized": []
},
{
"id": "PMID-17016553_T15",
"type": "Multi-tissue_structure",
"text": [
"vascular"
],
"offsets": [
[
51,
59
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-12171358 | PMID-12171358 | [
{
"id": "PMID-12171358__text",
"type": "abstract",
"text": [
"Impacts of water management options on flows in the Condamine River in Southern Queensland.\nThis paper examines the implications for river flows of a number of water practices and potential management options in the alluvial plains of the Upper Condamine River. It is an intensively cultivated area where irrigation is limited by the availability of water resources. The practice of capturing overland flows was investigated by the development of a model that simulates the performance of clusters of offstream storages up to sub-catchment scale. Management options examined included improvement to on-farm water use efficiency, the suppression of evaporation from open water storages, increasing the depth of those storages, decreasing their number, and improved tailwater return from irrigated land. Impacts of management options were analysed using a catchment scale water allocation model.\n"
],
"offsets": [
[
0,
894
]
]
}
] | [] | [] | [] | [] |
PMID-8686754 | PMID-8686754 | [
{
"id": "PMID-8686754__text",
"type": "abstract",
"text": [
"Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin.\nWe have identified several mechanisms by which the angiogenic cytokine vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) likely regulates endothelial cells (EC) migration. VPF/VEGF induced dermal microvascular EC expression of mRNAs encoding the alphav and beta3 integrin subunits resulting in increased levels of the alphavbeta3 heterodimer at the cell surface, and VPF/VEGF also induced mRNA encoding osteopontin (OPN), an alphavbeta3 ligand. OPN promoted EC migration in vitro; and VPF/VEGF induction of alphavbeta3 was accompanied by increased EC migration toward OPN. Because thrombin cleavage of OPN results in substantial enhancement of OPN's adhesive properties, and because VPF/VEGF promotes increased microvascular permeability leading to activation of the extrinsic coagulation pathway, we also investigated whether VPF/VEGF facilitates thrombin cleavage of OPN in vivo. Consistent with this hypothesis, co-injection of VPF/VEGF together with OPN resulted in rapid cleavage of OPN by endogenous thrombin. Furthermore, in comparison with native OPN, thrombin-cleaved OPN stimulated a greater rate of EC migration in vitro, which was additive to the increased migration associated with induction of alpha v beta 3. Thus, these data demonstrate cooperative mechanisms for VPF/VEGF regulation of EC migration involving the alphavbeta3 integrin, the alphavbeta3 ligand OPN, and thrombin cleavage of OPN. These findings also illustrate an operational link between VPF/VEGF induction of EC gene expression and VPF/VEGF enhancement of microvascular permeability, suggesting that these distinct biological activities may act accordingly to stimulate EC migration during angiogenesis.\n"
],
"offsets": [
[
0,
1914
]
]
}
] | [
{
"id": "PMID-8686754_T1",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
15,
31
]
],
"normalized": []
},
{
"id": "PMID-8686754_T11",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
366,
383
]
],
"normalized": []
},
{
"id": "PMID-8686754_T12",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
385,
387
]
],
"normalized": []
},
{
"id": "PMID-8686754_T15",
"type": "Cell",
"text": [
"dermal microvascular EC"
],
"offsets": [
[
417,
440
]
],
"normalized": []
},
{
"id": "PMID-8686754_T19",
"type": "Cellular_component",
"text": [
"cell surface"
],
"offsets": [
[
577,
589
]
],
"normalized": []
},
{
"id": "PMID-8686754_T26",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
686,
688
]
],
"normalized": []
},
{
"id": "PMID-8686754_T30",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
776,
778
]
],
"normalized": []
},
{
"id": "PMID-8686754_T37",
"type": "Tissue",
"text": [
"microvascular"
],
"offsets": [
[
939,
952
]
],
"normalized": []
},
{
"id": "PMID-8686754_T50",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1338,
1340
]
],
"normalized": []
},
{
"id": "PMID-8686754_T54",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1531,
1533
]
],
"normalized": []
},
{
"id": "PMID-8686754_T62",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1719,
1721
]
],
"normalized": []
},
{
"id": "PMID-8686754_T65",
"type": "Tissue",
"text": [
"microvascular"
],
"offsets": [
[
1766,
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]
],
"normalized": []
},
{
"id": "PMID-8686754_T66",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1880,
1882
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-18578357 | PMID-18578357 | [
{
"id": "PMID-18578357__text",
"type": "abstract",
"text": [
"Intraoperative handling and wound healing of arthroscopic portal wounds: a clinical study comparing nylon suture with wound closure strips.\nThis prospective, single-centre study compared wound closure methods in patients undergoing arthroscopy. Closure of arthroscopic portal wounds with sterile adhesive strips is effective and convenient for wound management. The method was associated with a reduced potential for infection, faster renewal of tensile strength, greater cost effectiveness, and better cosmetic effects comparing with suture closure. This method of wound closure may also reduce the incidence of needle stick injury in the theatre environment. Thereby the incidence of percutaneous exposure following a surgical procedure may not facilitate transmission of blood borne pathogens such as human immunodeficiency virus (HIV), hepatitis C virus and hepatitis B virus. As a result it may reduce litigation in today's changing healthcare climate.\n"
],
"offsets": [
[
0,
958
]
]
}
] | [
{
"id": "PMID-18578357_T1",
"type": "Pathological_formation",
"text": [
"wound"
],
"offsets": [
[
28,
33
]
],
"normalized": []
},
{
"id": "PMID-18578357_T2",
"type": "Pathological_formation",
"text": [
"wounds"
],
"offsets": [
[
65,
71
]
],
"normalized": []
},
{
"id": "PMID-18578357_T3",
"type": "Pathological_formation",
"text": [
"wound"
],
"offsets": [
[
118,
123
]
],
"normalized": []
},
{
"id": "PMID-18578357_T4",
"type": "Pathological_formation",
"text": [
"wound"
],
"offsets": [
[
187,
192
]
],
"normalized": []
},
{
"id": "PMID-18578357_T5",
"type": "Pathological_formation",
"text": [
"wounds"
],
"offsets": [
[
276,
282
]
],
"normalized": []
},
{
"id": "PMID-18578357_T6",
"type": "Pathological_formation",
"text": [
"wound"
],
"offsets": [
[
344,
349
]
],
"normalized": []
},
{
"id": "PMID-18578357_T7",
"type": "Pathological_formation",
"text": [
"wound"
],
"offsets": [
[
566,
571
]
],
"normalized": []
},
{
"id": "PMID-18578357_T8",
"type": "Organism_substance",
"text": [
"blood"
],
"offsets": [
[
774,
779
]
],
"normalized": []
},
{
"id": "PMID-18578357_T9",
"type": "Immaterial_anatomical_entity",
"text": [
"percutaneous"
],
"offsets": [
[
686,
698
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-12476350 | PMID-12476350 | [
{
"id": "PMID-12476350__text",
"type": "abstract",
"text": [
"CXC chemokine receptors in the central nervous system: Role in cerebellar neuromodulation and development.\nChemokines and their receptors are constitutively present in the central nervous system (CNS), expressed in neurons and glial cells. Much evidence suggests that, beyond their involvement in neuroinflammation, these proteins play a role in neurodevelopment and neurophysiological signaling. The goal of this review is to summarize recent information concerning expression, signaling, and function of CXC chemokine receptor in the CNS, with the main focus on the developmental and neuromodulatory actions of chemokines in the cerebellum.\n"
],
"offsets": [
[
0,
643
]
]
}
] | [
{
"id": "PMID-12476350_T1",
"type": "Anatomical_system",
"text": [
"central nervous system"
],
"offsets": [
[
31,
53
]
],
"normalized": []
},
{
"id": "PMID-12476350_T2",
"type": "Multi-tissue_structure",
"text": [
"cerebellar"
],
"offsets": [
[
63,
73
]
],
"normalized": []
},
{
"id": "PMID-12476350_T3",
"type": "Anatomical_system",
"text": [
"central nervous system"
],
"offsets": [
[
172,
194
]
],
"normalized": []
},
{
"id": "PMID-12476350_T4",
"type": "Anatomical_system",
"text": [
"CNS"
],
"offsets": [
[
196,
199
]
],
"normalized": []
},
{
"id": "PMID-12476350_T5",
"type": "Cell",
"text": [
"neurons"
],
"offsets": [
[
215,
222
]
],
"normalized": []
},
{
"id": "PMID-12476350_T6",
"type": "Cell",
"text": [
"glial cells"
],
"offsets": [
[
227,
238
]
],
"normalized": []
},
{
"id": "PMID-12476350_T7",
"type": "Multi-tissue_structure",
"text": [
"cerebellum"
],
"offsets": [
[
631,
641
]
],
"normalized": []
},
{
"id": "PMID-12476350_T8",
"type": "Anatomical_system",
"text": [
"CNS"
],
"offsets": [
[
536,
539
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-6294124 | PMID-6294124 | [
{
"id": "PMID-6294124__text",
"type": "abstract",
"text": [
"Cells transformed by Rous sarcoma virus release transforming growth factors. \nChicken embryo fibroblasts and hamster BHK cells transformed by Rous sarcoma virus (RSV) release in their culture media growth factors which enhance markedly anchorage-independent colony formation in gelified medium, at the restrictive temperature (41 degrees 5 C), of chicken embryo fibroblasts (CEF) infected by RSV mutants with a ts mutation of the src gene. This action is not observed with uninfected CEF, and, therefore, appears to require some expression of the viral src gene in the target cells. The enhancing factors are proteins related to the family of the transforming growth factors (TGFs) by their molecular weight (about 20 kd), their heat and acid resistance, and their sensitivity to dithiothreitol. They do not compete with 125I EGF for binding on the EGF receptors of the membrane of A431 cells. As chicken embryo fibroblasts are devoid of EGF receptors, their activity is not potentiated by EGF.\n"
],
"offsets": [
[
0,
995
]
]
}
] | [
{
"id": "PMID-6294124_T1",
"type": "Cell",
"text": [
"Cells"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "PMID-6294124_T5",
"type": "Cell",
"text": [
"embryo fibroblasts"
],
"offsets": [
[
86,
104
]
],
"normalized": []
},
{
"id": "PMID-6294124_T6",
"type": "Cell",
"text": [
"hamster BHK cells"
],
"offsets": [
[
109,
126
]
],
"normalized": []
},
{
"id": "PMID-6294124_T10",
"type": "Cell",
"text": [
"embryo fibroblasts"
],
"offsets": [
[
355,
373
]
],
"normalized": []
},
{
"id": "PMID-6294124_T11",
"type": "Cell",
"text": [
"CEF"
],
"offsets": [
[
375,
378
]
],
"normalized": []
},
{
"id": "PMID-6294124_T14",
"type": "Cell",
"text": [
"CEF"
],
"offsets": [
[
484,
487
]
],
"normalized": []
},
{
"id": "PMID-6294124_T16",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
576,
581
]
],
"normalized": []
},
{
"id": "PMID-6294124_T22",
"type": "Cellular_component",
"text": [
"membrane"
],
"offsets": [
[
870,
878
]
],
"normalized": []
},
{
"id": "PMID-6294124_T23",
"type": "Cell",
"text": [
"A431 cells"
],
"offsets": [
[
882,
892
]
],
"normalized": []
},
{
"id": "PMID-6294124_T25",
"type": "Cell",
"text": [
"embryo fibroblasts"
],
"offsets": [
[
905,
923
]
],
"normalized": []
},
{
"id": "PMID-6294124_T42",
"type": "Cell",
"text": [
"colony"
],
"offsets": [
[
258,
264
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-22105864 | PMID-22105864 | [
{
"id": "PMID-22105864__text",
"type": "abstract",
"text": [
"Aquaporins in human breast cancer: identification and involvement in carcinogenesis of breast cancer. \nBACKGROUND AND OBJECTIVES: Aquaporins (AQPs) play important roles in water and glycerol transport. Recently, the role of AQPs in human carcinogenesis has become an area of great interest. However, little is known about the function of AQPs in human breast cancer. The aim of this study was to investigate the expression profile of AQPs in human breast cancer and its significance. METHODS: In this study, we screened the expression profile of AQP0-12 in breast cancer tissues and corresponding normal tissues by RT-PCR, Western blotting and immunohistochemistry. RESULTS: AQP1, 3-5, and 10-12 were expressed in human breast cancer and/or normal breast tissues, and AQP1 and 3-5 exhibited differential expression. AQP1 was expressed in cell membranes and its expression was higher in cancer than that in normal tissues. AQP4 was expressed in the cell membrane and cytoplasm and was detected markedly stronger in normal than in cancer tissues. AQP5 was expressed mainly in cell membranes in carcinoma tissues, but was almost absent in normal breast tissues. Expression of AQP5 was associated with cellular differentiation, lymph node invasion, and clinicopathological staging. CONCLUSIONS: These observations suggested that several subtypes of the AQP family play a role in human breast carcinogenesis.\n"
],
"offsets": [
[
0,
1404
]
]
}
] | [
{
"id": "PMID-22105864_T3",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
20,
33
]
],
"normalized": []
},
{
"id": "PMID-22105864_T4",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
87,
100
]
],
"normalized": []
},
{
"id": "PMID-22105864_T13",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
352,
365
]
],
"normalized": []
},
{
"id": "PMID-22105864_T16",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
448,
461
]
],
"normalized": []
},
{
"id": "PMID-22105864_T18",
"type": "Tissue",
"text": [
"breast cancer tissues"
],
"offsets": [
[
557,
578
]
],
"normalized": []
},
{
"id": "PMID-22105864_T19",
"type": "Tissue",
"text": [
"tissues"
],
"offsets": [
[
604,
611
]
],
"normalized": []
},
{
"id": "PMID-22105864_T26",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
720,
733
]
],
"normalized": []
},
{
"id": "PMID-22105864_T27",
"type": "Tissue",
"text": [
"breast tissues"
],
"offsets": [
[
748,
762
]
],
"normalized": []
},
{
"id": "PMID-22105864_T32",
"type": "Cellular_component",
"text": [
"cell membranes"
],
"offsets": [
[
838,
852
]
],
"normalized": []
},
{
"id": "PMID-22105864_T33",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
886,
892
]
],
"normalized": []
},
{
"id": "PMID-22105864_T34",
"type": "Tissue",
"text": [
"tissues"
],
"offsets": [
[
913,
920
]
],
"normalized": []
},
{
"id": "PMID-22105864_T36",
"type": "Cellular_component",
"text": [
"cell membrane"
],
"offsets": [
[
948,
961
]
],
"normalized": []
},
{
"id": "PMID-22105864_T37",
"type": "Organism_substance",
"text": [
"cytoplasm"
],
"offsets": [
[
966,
975
]
],
"normalized": []
},
{
"id": "PMID-22105864_T38",
"type": "Tissue",
"text": [
"cancer tissues"
],
"offsets": [
[
1029,
1043
]
],
"normalized": []
},
{
"id": "PMID-22105864_T40",
"type": "Cellular_component",
"text": [
"cell membranes"
],
"offsets": [
[
1074,
1088
]
],
"normalized": []
},
{
"id": "PMID-22105864_T41",
"type": "Tissue",
"text": [
"carcinoma tissues"
],
"offsets": [
[
1092,
1109
]
],
"normalized": []
},
{
"id": "PMID-22105864_T42",
"type": "Tissue",
"text": [
"breast tissues"
],
"offsets": [
[
1143,
1157
]
],
"normalized": []
},
{
"id": "PMID-22105864_T44",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
1198,
1206
]
],
"normalized": []
},
{
"id": "PMID-22105864_T45",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1224,
1234
]
],
"normalized": []
},
{
"id": "PMID-22105864_T48",
"type": "Organism_subdivision",
"text": [
"breast"
],
"offsets": [
[
1381,
1387
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-8418304 | PMID-8418304 | [
{
"id": "PMID-8418304__text",
"type": "abstract",
"text": [
"Increased nm23-H1 and nm23-H2 messenger RNA expression and absence of mutations in colon carcinomas of low and high metastatic potential. \nBACKGROUND: The murine nm23 gene suppresses the metastatic behavior of malignant rodent tumor lines, and reduced nm23 expression correlates with increased likelihood of lymph node metastases in human breast cancers. More recent data have demonstrated the existence of two human nm23 gene homologues, nm23-H1 and nm23-H2, and have shown that deletion of nm23-H1 alleles occurs in some colon carcinomas associated with poor prognosis. These findings suggest that nm23-H1 encodes for suppression of colon carcinoma metastasis. In contrast, we have previously reported that total nm23 messenger RNA (mRNA) expression is increased to similar levels in colon tumors of both high and low metastatic potential. PURPOSE: This study was designed to reconcile our previous findings with the recent report of nm23-H1 allelic deletion in human colon cancers associated with poor prognosis. Our purpose was to examine human colon cancers for inactivation of two candidate metastasis suppressor genes, nm23-H1 and nm23-H2, either by mutation or by loss of gene transcription. METHODS: We used ribonuclease protection assays to analyze human colon tumors for the level of nm23-H1 (43 samples) and nm23-H2 (41 samples) transcript (mRNA) expression and the presence of mutations that could inactivate potential suppressor function. RESULTS: We detected only wild-type nm23-H1 and nm23-H2 mRNA. Expression of nm23-H1 mRNA increased in 33 of 41 colon tumors, and expression of nm23-H2 mRNA was elevated in 28 of 41 colon tumors relative to that in matched normal mucosa. Increases in these mRNA levels were similar in tumors of both low and high metastatic potential. CONCLUSIONS: These results suggest that, despite correlation of nm23-H1 allelic deletions with colon cancers associated with poor prognosis, nm23-H1 and nm23-H2 alleles do not directly mediate metastasis suppression in colon carcinoma. Our results leave unexplained the observation that nm23-H1 allelic deletion correlates with metastatic potential of colon carcinomas. IMPLICATIONS: These findings also contrast with the demonstration of nm23 metastasis suppressor activity in murine melanoma and with the correlation of loss of nm23 expression in breast cancer with poor prognosis. It may be that metastasis suppression by the nm23 gene is a tissue-specific phenomenon.\n"
],
"offsets": [
[
0,
2459
]
]
}
] | [
{
"id": "PMID-8418304_T3",
"type": "Cancer",
"text": [
"colon carcinomas"
],
"offsets": [
[
83,
99
]
],
"normalized": []
},
{
"id": "PMID-8418304_T6",
"type": "Cell",
"text": [
"malignant rodent tumor lines"
],
"offsets": [
[
210,
238
]
],
"normalized": []
},
{
"id": "PMID-8418304_T10",
"type": "Cancer",
"text": [
"breast cancers"
],
"offsets": [
[
339,
353
]
],
"normalized": []
},
{
"id": "PMID-8418304_T16",
"type": "Cancer",
"text": [
"colon carcinomas"
],
"offsets": [
[
523,
539
]
],
"normalized": []
},
{
"id": "PMID-8418304_T18",
"type": "Cancer",
"text": [
"colon carcinoma"
],
"offsets": [
[
635,
650
]
],
"normalized": []
},
{
"id": "PMID-8418304_T20",
"type": "Cancer",
"text": [
"colon tumors"
],
"offsets": [
[
786,
798
]
],
"normalized": []
},
{
"id": "PMID-8418304_T23",
"type": "Cancer",
"text": [
"colon cancers"
],
"offsets": [
[
970,
983
]
],
"normalized": []
},
{
"id": "PMID-8418304_T25",
"type": "Cancer",
"text": [
"colon cancers"
],
"offsets": [
[
1049,
1062
]
],
"normalized": []
},
{
"id": "PMID-8418304_T30",
"type": "Cancer",
"text": [
"colon tumors"
],
"offsets": [
[
1265,
1277
]
],
"normalized": []
},
{
"id": "PMID-8418304_T32",
"type": "Cancer",
"text": [
"samples"
],
"offsets": [
[
1307,
1314
]
],
"normalized": []
},
{
"id": "PMID-8418304_T34",
"type": "Cancer",
"text": [
"samples"
],
"offsets": [
[
1332,
1339
]
],
"normalized": []
},
{
"id": "PMID-8418304_T38",
"type": "Cancer",
"text": [
"colon tumors"
],
"offsets": [
[
1564,
1576
]
],
"normalized": []
},
{
"id": "PMID-8418304_T40",
"type": "Cancer",
"text": [
"colon tumors"
],
"offsets": [
[
1634,
1646
]
],
"normalized": []
},
{
"id": "PMID-8418304_T41",
"type": "Multi-tissue_structure",
"text": [
"mucosa"
],
"offsets": [
[
1682,
1688
]
],
"normalized": []
},
{
"id": "PMID-8418304_T42",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
1737,
1743
]
],
"normalized": []
},
{
"id": "PMID-8418304_T44",
"type": "Cancer",
"text": [
"colon cancers"
],
"offsets": [
[
1882,
1895
]
],
"normalized": []
},
{
"id": "PMID-8418304_T47",
"type": "Cancer",
"text": [
"colon carcinoma"
],
"offsets": [
[
2006,
2021
]
],
"normalized": []
},
{
"id": "PMID-8418304_T49",
"type": "Cancer",
"text": [
"colon carcinomas"
],
"offsets": [
[
2139,
2155
]
],
"normalized": []
},
{
"id": "PMID-8418304_T52",
"type": "Cancer",
"text": [
"melanoma"
],
"offsets": [
[
2272,
2280
]
],
"normalized": []
},
{
"id": "PMID-8418304_T54",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
2336,
2349
]
],
"normalized": []
},
{
"id": "PMID-8418304_T56",
"type": "Tissue",
"text": [
"tissue"
],
"offsets": [
[
2431,
2437
]
],
"normalized": []
},
{
"id": "PMID-8418304_T1",
"type": "Cancer",
"text": [
"lymph node metastases"
],
"offsets": [
[
308,
329
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-9380745 | PMID-9380745 | [
{
"id": "PMID-9380745__text",
"type": "abstract",
"text": [
"Blind separation of auditory event-related brain responses into independent components.\nAveraged event-related potential (ERP) data recorded from the human scalp reveal electroencephalographic (EEG) activity that is reliably time-locked and phase-locked to experimental events. We report here the application of a method based on information theory that decomposes one or more ERPs recorded at multiple scalp sensors into a sum of components with fixed scalp distributions and sparsely activated, maximally independent time courses. Independent component analysis (ICA) decomposes ERP data into a number of components equal to the number of sensors. The derived components have distinct but not necessarily orthogonal scalp projections. Unlike dipole-fitting methods, the algorithm does not model the locations of their generators in the head. Unlike methods that remove second-order correlations, such as principal component analysis (PCA), ICA also minimizes higher-order dependencies. Applied to detected-and undetected-target ERPs from an auditory vigilance experiment, the algorithm derived ten components that decomposed each of the major response peaks into one or more ICA components with relatively simple scalp distributions. Three of these components were active only when the subject detected the targets, three other components only when the target went undetected, and one in both cases. Three additional components accounted for the steady-state brain response to a 39-Hz background click train. Major features of the decomposition proved robust across sessions and changes in sensor number and placement. This method of ERP analysis can be used to compare responses from multiple stimuli, task conditions, and subject states.\n"
],
"offsets": [
[
0,
1742
]
]
}
] | [
{
"id": "PMID-9380745_T1",
"type": "Organ",
"text": [
"brain"
],
"offsets": [
[
43,
48
]
],
"normalized": []
},
{
"id": "PMID-9380745_T2",
"type": "Multi-tissue_structure",
"text": [
"scalp"
],
"offsets": [
[
156,
161
]
],
"normalized": []
},
{
"id": "PMID-9380745_T3",
"type": "Multi-tissue_structure",
"text": [
"scalp"
],
"offsets": [
[
403,
408
]
],
"normalized": []
},
{
"id": "PMID-9380745_T4",
"type": "Multi-tissue_structure",
"text": [
"scalp"
],
"offsets": [
[
453,
458
]
],
"normalized": []
},
{
"id": "PMID-9380745_T5",
"type": "Multi-tissue_structure",
"text": [
"scalp"
],
"offsets": [
[
718,
723
]
],
"normalized": []
},
{
"id": "PMID-9380745_T6",
"type": "Organism_subdivision",
"text": [
"head"
],
"offsets": [
[
838,
842
]
],
"normalized": []
},
{
"id": "PMID-9380745_T7",
"type": "Multi-tissue_structure",
"text": [
"scalp"
],
"offsets": [
[
1215,
1220
]
],
"normalized": []
},
{
"id": "PMID-9380745_T8",
"type": "Organ",
"text": [
"brain"
],
"offsets": [
[
1461,
1466
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-8102531 | PMID-8102531 | [
{
"id": "PMID-8102531__text",
"type": "abstract",
"text": [
"Epilepsy in Down syndrome: clinical aspects and possible mechanisms.\nAlthough epilepsy is more common in persons with trisomy 21 (Down syndrome) than in the general population, the mechanisms by which seizures are generated in this population have received little attention. It is likely that this increased seizure susceptibility is due to a combination of medical risk factors and inherent neurologic abnormalities characteristic of Down syndrome. In this review clinical aspects of seizures among individuals with Down syndrome were described and possible mechanisms by which the trisomy 21 brain may generate seizures were explored.\n"
],
"offsets": [
[
0,
637
]
]
}
] | [
{
"id": "PMID-8102531_T1",
"type": "Anatomical_system",
"text": [
"neurologic"
],
"offsets": [
[
392,
402
]
],
"normalized": []
},
{
"id": "PMID-8102531_T2",
"type": "Organ",
"text": [
"brain"
],
"offsets": [
[
594,
599
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17157465 | PMID-17157465 | [
{
"id": "PMID-17157465__text",
"type": "abstract",
"text": [
"Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer.\nThe last 7 years have seen over seven times as many publications indexed by Medline dealing with pomegranate and Punica granatum than in all the years preceding them. Because of this, and the virtual explosion of interest in pomegranate as a medicinal and nutritional product that has followed, this review is accordingly launched. The pomegranate tree, Punica granatum, especially its fruit, possesses a vast ethnomedical history and represents a phytochemical reservoir of heuristic medicinal value. The tree/fruit can be divided into several anatomical compartments: (1) seed, (2) juice, (3) peel, (4) leaf, (5) flower, (6) bark, and (7) roots, each of which has interesting pharmacologic activity. Juice and peels, for example, possess potent antioxidant properties, while juice, peel and oil are all weakly estrogenic and heuristically of interest for the treatment of menopausal symptoms and sequellae. The use of juice, peel and oil have also been shown to possess anticancer activities, including interference with tumor cell proliferation, cell cycle, invasion and angiogenesis. These may be associated with plant based anti-inflammatory effects, The phytochemistry and pharmacological actions of all Punica granatum components suggest a wide range of clinical applications for the treatment and prevention of cancer, as well as other diseases where chronic inflammation is believed to play an essential etiologic role.\n"
],
"offsets": [
[
0,
1534
]
]
}
] | [
{
"id": "PMID-17157465_T3",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
97,
103
]
],
"normalized": []
},
{
"id": "PMID-17157465_T10",
"type": "Developing_anatomical_structure",
"text": [
"seed"
],
"offsets": [
[
679,
683
]
],
"normalized": []
},
{
"id": "PMID-17157465_T11",
"type": "Organism_substance",
"text": [
"juice"
],
"offsets": [
[
689,
694
]
],
"normalized": []
},
{
"id": "PMID-17157465_T12",
"type": "Tissue",
"text": [
"peel"
],
"offsets": [
[
700,
704
]
],
"normalized": []
},
{
"id": "PMID-17157465_T13",
"type": "Organ",
"text": [
"leaf"
],
"offsets": [
[
710,
714
]
],
"normalized": []
},
{
"id": "PMID-17157465_T14",
"type": "Organism_subdivision",
"text": [
"flower"
],
"offsets": [
[
720,
726
]
],
"normalized": []
},
{
"id": "PMID-17157465_T15",
"type": "Tissue",
"text": [
"bark"
],
"offsets": [
[
732,
736
]
],
"normalized": []
},
{
"id": "PMID-17157465_T16",
"type": "Organ",
"text": [
"roots"
],
"offsets": [
[
746,
751
]
],
"normalized": []
},
{
"id": "PMID-17157465_T17",
"type": "Organism_substance",
"text": [
"Juice"
],
"offsets": [
[
807,
812
]
],
"normalized": []
},
{
"id": "PMID-17157465_T18",
"type": "Tissue",
"text": [
"peels"
],
"offsets": [
[
817,
822
]
],
"normalized": []
},
{
"id": "PMID-17157465_T19",
"type": "Organism_substance",
"text": [
"juice"
],
"offsets": [
[
882,
887
]
],
"normalized": []
},
{
"id": "PMID-17157465_T20",
"type": "Tissue",
"text": [
"peel"
],
"offsets": [
[
889,
893
]
],
"normalized": []
},
{
"id": "PMID-17157465_T21",
"type": "Organism_substance",
"text": [
"oil"
],
"offsets": [
[
898,
901
]
],
"normalized": []
},
{
"id": "PMID-17157465_T22",
"type": "Organism_substance",
"text": [
"juice"
],
"offsets": [
[
1025,
1030
]
],
"normalized": []
},
{
"id": "PMID-17157465_T23",
"type": "Tissue",
"text": [
"peel"
],
"offsets": [
[
1032,
1036
]
],
"normalized": []
},
{
"id": "PMID-17157465_T24",
"type": "Organism_substance",
"text": [
"oil"
],
"offsets": [
[
1041,
1044
]
],
"normalized": []
},
{
"id": "PMID-17157465_T25",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
1081,
1087
]
],
"normalized": []
},
{
"id": "PMID-17157465_T26",
"type": "Cell",
"text": [
"tumor cell"
],
"offsets": [
[
1128,
1138
]
],
"normalized": []
},
{
"id": "PMID-17157465_T27",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1154,
1158
]
],
"normalized": []
},
{
"id": "PMID-17157465_T29",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
1424,
1430
]
],
"normalized": []
},
{
"id": "PMID-17157465_T1",
"type": "Organism_subdivision",
"text": [
"fruit"
],
"offsets": [
[
616,
621
]
],
"normalized": []
},
{
"id": "PMID-17157465_T2",
"type": "Organism_subdivision",
"text": [
"compartments"
],
"offsets": [
[
661,
673
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-1834974 | PMID-1834974 | [
{
"id": "PMID-1834974__text",
"type": "abstract",
"text": [
"A novel putative tyrosine kinase receptor with oncogenic potential. \nWe have detected transforming activity by a tumorigenicity assay using NIH3T3 cells transfected with DNA from a chronic myeloproliferative disorder patient. Here, we report the cDNA cloning of the corresponding oncogene, designated UFO, in allusion to the as yet unidentified function of its protein. Nucleotide sequence analysis of a 3116bp cDNA clone revealed a 2682-bp-long open reading frame capable of directing the synthesis of a 894 amino acid polypeptide. The predicted UFO protein exhibits characteristic features of a transmembrane receptor with associated tyrosine kinase activity. The UFO proto-oncogene maps to human chromosome 19q13.1 and is transcribed into two 5.0 kb and 3.2 kb mRNAs in human bone marrow and human tumor cell lines. The UFO locus is evolutionarily conserved between vertebrate species. A 4.0 kb mRNA of the murine UFO homolog is expressed in a variety of different mouse tissues. We thus have identified a novel element of the complex signaling network involved in the control of cell proliferation and differentiation.\n"
],
"offsets": [
[
0,
1123
]
]
}
] | [
{
"id": "PMID-1834974_T2",
"type": "Cell",
"text": [
"NIH3T3 cells"
],
"offsets": [
[
140,
152
]
],
"normalized": []
},
{
"id": "PMID-1834974_T7",
"type": "Cellular_component",
"text": [
"transmembrane"
],
"offsets": [
[
597,
610
]
],
"normalized": []
},
{
"id": "PMID-1834974_T12",
"type": "Multi-tissue_structure",
"text": [
"bone marrow"
],
"offsets": [
[
779,
790
]
],
"normalized": []
},
{
"id": "PMID-1834974_T14",
"type": "Cell",
"text": [
"tumor cell lines"
],
"offsets": [
[
801,
817
]
],
"normalized": []
},
{
"id": "PMID-1834974_T19",
"type": "Tissue",
"text": [
"tissues"
],
"offsets": [
[
974,
981
]
],
"normalized": []
},
{
"id": "PMID-1834974_T20",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1083,
1087
]
],
"normalized": []
},
{
"id": "PMID-1834974_T30",
"type": "Cellular_component",
"text": [
"chromosome 19q13.1"
],
"offsets": [
[
699,
717
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-16252749 | PMID-16252749 | [
{
"id": "PMID-16252749__text",
"type": "abstract",
"text": [
"Sensitivity variation in two-center holographic recording.\nAn experimental study of variation of sensitivity with recording and sensitizing intensities in two-center recording is presented. The experimental results are in good agreement with the theoretical predictions. It is shown experimentally, for what is to our knowledge the first time, that the sensitivity is a function of the ratio of recording to sensitizing intensities and not the absolute intensities. Also, the ratio of recording to sensitizing intensities should be small to obtain high sensitivity values. We also report the highest sensitivity (S=0.15 cm/J) that has been achieved to date for a LiNbO3:Fe:Mn crystal.\n"
],
"offsets": [
[
0,
685
]
]
}
] | [] | [] | [] | [] |
PMID-16250015 | PMID-16250015 | [
{
"id": "PMID-16250015__text",
"type": "abstract",
"text": [
"Normal and transforming functions of RUNX1: a perspective. \nConverging studies from many investigators indicate that RUNX1 has a critical role in the correct maintenance of essential cellular functions during embryonic development and after birth. The discovery that this gene is also frequently mutated in human leukemia has increased the interest in the role that RUNX1 plays in both normal and transforming pathways. Here, we provide an overview of the many roles of RUNX1 in hematopoietic self-renewal and differentiation and summarize the information that is currently available on the many mechanisms of RUNX1 deregulation in human leukemia.\n"
],
"offsets": [
[
0,
648
]
]
}
] | [
{
"id": "PMID-16250015_T3",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
183,
191
]
],
"normalized": []
},
{
"id": "PMID-16250015_T4",
"type": "Developing_anatomical_structure",
"text": [
"embryonic"
],
"offsets": [
[
209,
218
]
],
"normalized": []
},
{
"id": "PMID-16250015_T6",
"type": "Cancer",
"text": [
"leukemia"
],
"offsets": [
[
313,
321
]
],
"normalized": []
},
{
"id": "PMID-16250015_T9",
"type": "Cell",
"text": [
"hematopoietic"
],
"offsets": [
[
479,
492
]
],
"normalized": []
},
{
"id": "PMID-16250015_T12",
"type": "Cancer",
"text": [
"leukemia"
],
"offsets": [
[
638,
646
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-21196269 | PMID-21196269 | [
{
"id": "PMID-21196269__text",
"type": "abstract",
"text": [
"Emerging metabolic targets in cancer therapy.\nCancer cells are different from normal cells in their metabolic properties. Normal cells mostly rely on mitochondrial oxidative phosphorylation to produce energy. In contrast, cancer cells depend mostly on glycolysis, the aerobic breakdown of glucose into ATP. This altered energy dependency is known as the \"Warburg effect\" and is a hallmark of cancer cells. In recent years, investigating the metabolic changes within cancer cells has been a rapidly growing area. Emerging evidence shows that oncogenes that drive the cancer-promoting signals also drive the altered metabolism. Although the exact mechanisms underlying the Warburg effect are unclear, the existing evidence suggests that increased glycolysis plays an important role in support malignant behavior of cancer cells. A thorough understanding of the unique metabolism of cancer cells will help to design of more effective drugs targeting metabolic pathways, which will greatly impact the capacity to effectively treat cancer patients. Here we provide an overview of the current understanding of the Warburg effect upon tumor cell growth and survival, and discussion on the potential metabolic targets for cancer therapy.\n"
],
"offsets": [
[
0,
1230
]
]
}
] | [
{
"id": "PMID-21196269_T1",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
30,
36
]
],
"normalized": []
},
{
"id": "PMID-21196269_T2",
"type": "Cell",
"text": [
"Cancer cells"
],
"offsets": [
[
46,
58
]
],
"normalized": []
},
{
"id": "PMID-21196269_T3",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
85,
90
]
],
"normalized": []
},
{
"id": "PMID-21196269_T4",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
129,
134
]
],
"normalized": []
},
{
"id": "PMID-21196269_T5",
"type": "Cellular_component",
"text": [
"mitochondrial"
],
"offsets": [
[
150,
163
]
],
"normalized": []
},
{
"id": "PMID-21196269_T6",
"type": "Cell",
"text": [
"cancer cells"
],
"offsets": [
[
222,
234
]
],
"normalized": []
},
{
"id": "PMID-21196269_T9",
"type": "Cell",
"text": [
"cancer cells"
],
"offsets": [
[
392,
404
]
],
"normalized": []
},
{
"id": "PMID-21196269_T10",
"type": "Cell",
"text": [
"cancer cells"
],
"offsets": [
[
466,
478
]
],
"normalized": []
},
{
"id": "PMID-21196269_T12",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
566,
572
]
],
"normalized": []
},
{
"id": "PMID-21196269_T13",
"type": "Cell",
"text": [
"cancer cells"
],
"offsets": [
[
813,
825
]
],
"normalized": []
},
{
"id": "PMID-21196269_T14",
"type": "Cell",
"text": [
"cancer cells"
],
"offsets": [
[
880,
892
]
],
"normalized": []
},
{
"id": "PMID-21196269_T15",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
1027,
1033
]
],
"normalized": []
},
{
"id": "PMID-21196269_T17",
"type": "Cell",
"text": [
"tumor cell"
],
"offsets": [
[
1128,
1138
]
],
"normalized": []
},
{
"id": "PMID-21196269_T18",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
1214,
1220
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-10823420 | PMID-10823420 | [
{
"id": "PMID-10823420__text",
"type": "abstract",
"text": [
"CD40 expression on human lung cancer correlates with metastatic spread. \nPURPOSE: The poor prognosis associated with lung cancer is related to the high incidence of regional and distant metastasis. There is a crucial need to identify parameters that can predict a tendancy to metastatic spread to allow better prognostic evaluation and therapeutic approach. METHODS: Using flow cytometry we evaluated 18 human lung cancer cell lines for the expression of different surface markers on lung cancers suggested to be possible prognostic parameters, including epidermal growth factor receptor (EGFR), intercellular adhesion molecule 1 (ICAM-1), Fas and CD40. RESULTS: No correlation was found between tumor prognosis and EGFR, ICAM-1 or Fas. However, a statistically significant correlation was found between the surface expression of CD40 and the metastatic spread of the tumor. In this study, 14 of 18 lung cancer cell lines (78%) expressed CD40 on their surface. All of the 4 tumors that were CD40-negative, were stage I tumors, without any evidence of regional or distant metastasis. Of the 14 tumors that expressed CD40, all but 1 (93%) had either nodal or systemic metastasis at the time of diagnosis. Patients whose tumors were CD40-negative showed a significantly better N stage, overall stage at presentation and survival than those patients with CD40-positive patients. No significant differences between the two groups were observed in tumor size, gender, age, histology, differentiation or preoperative therapy. CONCLUSIONS: These results suggest that CD40 expression on lung cancer may play a role in metastatic spread, and also may serve as a prognostic marker and an indicator of advanced disease.\n"
],
"offsets": [
[
0,
1708
]
]
}
] | [
{
"id": "PMID-10823420_T3",
"type": "Cancer",
"text": [
"lung cancer"
],
"offsets": [
[
25,
36
]
],
"normalized": []
},
{
"id": "PMID-10823420_T4",
"type": "Cancer",
"text": [
"lung cancer"
],
"offsets": [
[
117,
128
]
],
"normalized": []
},
{
"id": "PMID-10823420_T6",
"type": "Cell",
"text": [
"lung cancer cell lines"
],
"offsets": [
[
410,
432
]
],
"normalized": []
},
{
"id": "PMID-10823420_T7",
"type": "Cancer",
"text": [
"lung cancers"
],
"offsets": [
[
484,
496
]
],
"normalized": []
},
{
"id": "PMID-10823420_T14",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
696,
701
]
],
"normalized": []
},
{
"id": "PMID-10823420_T18",
"type": "Cellular_component",
"text": [
"surface"
],
"offsets": [
[
808,
815
]
],
"normalized": []
},
{
"id": "PMID-10823420_T20",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
868,
873
]
],
"normalized": []
},
{
"id": "PMID-10823420_T21",
"type": "Cell",
"text": [
"lung cancer cell lines"
],
"offsets": [
[
899,
921
]
],
"normalized": []
},
{
"id": "PMID-10823420_T23",
"type": "Cellular_component",
"text": [
"surface"
],
"offsets": [
[
952,
959
]
],
"normalized": []
},
{
"id": "PMID-10823420_T24",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
974,
980
]
],
"normalized": []
},
{
"id": "PMID-10823420_T26",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
1019,
1025
]
],
"normalized": []
},
{
"id": "PMID-10823420_T27",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
1093,
1099
]
],
"normalized": []
},
{
"id": "PMID-10823420_T29",
"type": "Multi-tissue_structure",
"text": [
"nodal"
],
"offsets": [
[
1148,
1153
]
],
"normalized": []
},
{
"id": "PMID-10823420_T31",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
1218,
1224
]
],
"normalized": []
},
{
"id": "PMID-10823420_T36",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
1442,
1447
]
],
"normalized": []
},
{
"id": "PMID-10823420_T38",
"type": "Cancer",
"text": [
"lung cancer"
],
"offsets": [
[
1578,
1589
]
],
"normalized": []
},
{
"id": "PMID-10823420_T57",
"type": "Cellular_component",
"text": [
"surface"
],
"offsets": [
[
465,
472
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-1072800-sec-07 | PMC-1072800-sec-07 | [
{
"id": "PMC-1072800-sec-07__text",
"type": "sec",
"text": [
"Immunostaining and confocal analysis\nDNA labelling and staining with 5-bromo-2'-deoxyuridine (BrdU labelling and detection kit I; Boehringer Mannheim, Germany) was performed according to the manufacturer's instructions. The nucleoli were detected with an anti-nucleolin antibody (clone 3G4B2; Upstate biotechnology, Lake Placid, NY) on cells fixed in 2% formalin for 10 min followed by permeabilization with ice-cold methanol for 30 min. The secondary antibody used for both BrdU and nucleoli staining was a rhodamine (tetra-methyl)-conjugated goat anti-mouse antibody (T-2762) from Molecular Probe (Eugene, OR). The cells were examined in a Zeiss LSM 510 laser scanning microscope equipped with a Plan-Apochromate 63x/1.4 oil immersion objective. We used the 488 nm laser line for excitation of EGFP (detected at 505 nm < lambdaEGFP < 530 nm) and the 543 nm laser line for rhodamine (tetra-methyl) (detected at lambdaRhodamine > 560 nm). ECFP fusion protein was excited with a 458 nm laser line (detected at 480 nm < lambdaECFP < 520 nm), EYFP fusion protein was excited with a 514 nm laser line (lambdaEGFP > 560 nm) and HcRed fusion protein was excited with a 543 nm laser line and detected at >585 or 650 nm. The images were from 1 mum thick slices of the cells. The images were exported into Adobe Photoshop (Adobe Systems Inc., San Jose, CA).\n"
],
"offsets": [
[
0,
1349
]
]
}
] | [
{
"id": "PMC-1072800-sec-07_T1",
"type": "Cellular_component",
"text": [
"nucleoli"
],
"offsets": [
[
224,
232
]
],
"normalized": []
},
{
"id": "PMC-1072800-sec-07_T2",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
336,
341
]
],
"normalized": []
},
{
"id": "PMC-1072800-sec-07_T3",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
617,
622
]
],
"normalized": []
},
{
"id": "PMC-1072800-sec-07_T4",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
1260,
1265
]
],
"normalized": []
},
{
"id": "PMC-1072800-sec-07_T6",
"type": "Cellular_component",
"text": [
"nucleoli"
],
"offsets": [
[
484,
492
]
],
"normalized": []
},
{
"id": "PMC-1072800-sec-07_T7",
"type": "Cellular_component",
"text": [
"slices"
],
"offsets": [
[
1246,
1252
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17500304 | PMID-17500304 | [
{
"id": "PMID-17500304__text",
"type": "abstract",
"text": [
"Stress and psychological distress among SARS survivors 1 year after the outbreak.\nOBJECTIVE:\nOur study examined the stress level and psychological distress of severe acute respiratory syndrome (SARS) survivors 1 year after the outbreak.\nMETHOD:\nDuring the SARS outbreak in 2003, we used the 10-item Perceived Stress Scale (PSS-10) to assess SARS survivors treated in 2 major hospitals (non-health care workers, n = 49; health care workers, n = 30). We invited SARS survivors from the same hospitals (non-health care workers, n = 63; health care workers, n = 33) to complete the PSS-10 again in 2004. At that time, they were also asked to complete the General Health Questionnaire (GHQ-12) and measures of depression, anxiety, and posttraumatic symptoms. PSS-10 scores were also obtained from matched community control subjects during the outbreak (n = 145) and again in 2004 (n = 112).\nRESULTS:\nSARS survivors had higher stress levels during the outbreak, compared with control subjects (PSS-10 scores = 19.8 and 17.9, respectively; P < 0.01), and this persisted 1 year later (PSS-10 scores = 19.9 and 17.3, respectively; P < 0.01) without signs of decrease. In 2004, SARS survivors also showed worrying levels of depression, anxiety, and posttraumatic symptoms. An alarming proportion (64%) scored above the GHQ-12 cut-off that suggests psychiatric morbidity. During the outbreak, health care worker SARS survivors had stress levels similar to those of non-health care workers, but health care workers showed significantly higher stress levels in 2004 (PSS-10 score = 22.8, compared with PSS-10 score = 18.4; P < 0.05) and had higher depression, anxiety, posttraumatic symptoms, and GHQ-12 scores.\nCONCLUSIONS:\nOne year after the outbreak, SARS survivors still had elevated stress levels and worrying levels of psychological distress. The situation of health care worker SARS survivors is particularly worrying. The long-term psychological implications of infectious diseases should not be ignored. Mental health services could play an important role in rehabilitation.\n"
],
"offsets": [
[
0,
2071
]
]
}
] | [] | [] | [] | [] |
PMID-12405260 | PMID-12405260 | [
{
"id": "PMID-12405260__text",
"type": "abstract",
"text": [
"Brn-3a, a neuronal transcription factor of the POU gene family: indications for its involvement in cancer and angiogenesis.\nBrn-3a, a member of the POU gene family (so-called because of the similarity with the group of transcription factors Pit, Oct, and Unc), was found in neuronal cells engaged in the transcription activity of the p1 and p2 promoters of the most powerful antiapoptotic gene, namely, Bcl-2. The alternative splicing of Brn-3a mRNA produces two molecular forms: a longer, Bcl-2 transactivating form, and a shorter inactive form, lacking 84 AA in the aminoterminus. In neuronal cells, following Brn-3a gene transfection and superexpression, an increase of 30 fold of the Bcl-2 protein occurs, leading to apoptosis protection. However, recent works demonstrate that Brn-3a expression is not restricted to neuronal cells, as its activity was detected also in cancer cells of non-neuronal nature. Looking for mechanisms linking Brn-3a to carcinogenesis, we discuss the role of this transcription factor in influencing Bcl-2/p53 antagonism and Bcl-2/VEGF induction of tumor angiogenesis, concluding this review with a proposal for the oncogenic nature of Brn-3a.\n"
],
"offsets": [
[
0,
1176
]
]
}
] | [
{
"id": "PMID-12405260_T2",
"type": "Cell",
"text": [
"neuronal"
],
"offsets": [
[
10,
18
]
],
"normalized": []
},
{
"id": "PMID-12405260_T3",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
99,
105
]
],
"normalized": []
},
{
"id": "PMID-12405260_T8",
"type": "Cell",
"text": [
"neuronal cells"
],
"offsets": [
[
274,
288
]
],
"normalized": []
},
{
"id": "PMID-12405260_T12",
"type": "Cell",
"text": [
"neuronal cells"
],
"offsets": [
[
586,
600
]
],
"normalized": []
},
{
"id": "PMID-12405260_T16",
"type": "Cell",
"text": [
"neuronal cells"
],
"offsets": [
[
821,
835
]
],
"normalized": []
},
{
"id": "PMID-12405260_T17",
"type": "Cell",
"text": [
"cancer cells"
],
"offsets": [
[
874,
886
]
],
"normalized": []
},
{
"id": "PMID-12405260_T18",
"type": "Cell",
"text": [
"neuronal"
],
"offsets": [
[
894,
902
]
],
"normalized": []
},
{
"id": "PMID-12405260_T24",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
1081,
1086
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-18384219 | PMID-18384219 | [
{
"id": "PMID-18384219__text",
"type": "abstract",
"text": [
"Proteomic comparison of nasopharyngeal cancer cell lines C666-1 and NP69 identifies down-regulation of annexin II and beta2-tubulin for nasopharyngeal carcinoma. \nCONTEXT: Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management. OBJECTIVES: To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens. DESIGN: Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia. RESULTS: Proteomic findings indicated that adenosine triphosphate synthase alpha chain was up-regulated, whereas annexin II, annexin V, beta(2)-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and beta(2)-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC. CONCLUSIONS: The results suggest that annexin II and beta(2)-tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.\n"
],
"offsets": [
[
0,
1928
]
]
}
] | [
{
"id": "PMID-18384219_T1",
"type": "Cell",
"text": [
"nasopharyngeal cancer cell lines C666-1"
],
"offsets": [
[
24,
63
]
],
"normalized": []
},
{
"id": "PMID-18384219_T2",
"type": "Cell",
"text": [
"NP69"
],
"offsets": [
[
68,
72
]
],
"normalized": []
},
{
"id": "PMID-18384219_T5",
"type": "Cancer",
"text": [
"nasopharyngeal carcinoma"
],
"offsets": [
[
136,
160
]
],
"normalized": []
},
{
"id": "PMID-18384219_T6",
"type": "Cancer",
"text": [
"Nasopharyngeal carcinoma"
],
"offsets": [
[
172,
196
]
],
"normalized": []
},
{
"id": "PMID-18384219_T7",
"type": "Cancer",
"text": [
"NPC"
],
"offsets": [
[
198,
201
]
],
"normalized": []
},
{
"id": "PMID-18384219_T9",
"type": "Cancer",
"text": [
"NPC"
],
"offsets": [
[
528,
531
]
],
"normalized": []
},
{
"id": "PMID-18384219_T12",
"type": "Cell",
"text": [
"NPC cell line"
],
"offsets": [
[
704,
717
]
],
"normalized": []
},
{
"id": "PMID-18384219_T13",
"type": "Cell",
"text": [
"C666-1"
],
"offsets": [
[
719,
725
]
],
"normalized": []
},
{
"id": "PMID-18384219_T14",
"type": "Cell",
"text": [
"NP cell line"
],
"offsets": [
[
740,
752
]
],
"normalized": []
},
{
"id": "PMID-18384219_T15",
"type": "Cell",
"text": [
"NP69"
],
"offsets": [
[
754,
758
]
],
"normalized": []
},
{
"id": "PMID-18384219_T16",
"type": "Cancer",
"text": [
"NPC"
],
"offsets": [
[
840,
843
]
],
"normalized": []
},
{
"id": "PMID-18384219_T17",
"type": "Tissue",
"text": [
"specimens"
],
"offsets": [
[
862,
871
]
],
"normalized": []
},
{
"id": "PMID-18384219_T18",
"type": "Cell",
"text": [
"cell lines"
],
"offsets": [
[
942,
952
]
],
"normalized": []
},
{
"id": "PMID-18384219_T19",
"type": "Tissue",
"text": [
"samples"
],
"offsets": [
[
1070,
1077
]
],
"normalized": []
},
{
"id": "PMID-18384219_T20",
"type": "Cell",
"text": [
"NPCs"
],
"offsets": [
[
1126,
1130
]
],
"normalized": []
},
{
"id": "PMID-18384219_T21",
"type": "Tissue",
"text": [
"epithelia"
],
"offsets": [
[
1167,
1176
]
],
"normalized": []
},
{
"id": "PMID-18384219_T27",
"type": "Cell",
"text": [
"cell lines"
],
"offsets": [
[
1414,
1424
]
],
"normalized": []
},
{
"id": "PMID-18384219_T30",
"type": "Cell",
"text": [
"tumor cells"
],
"offsets": [
[
1494,
1505
]
],
"normalized": []
},
{
"id": "PMID-18384219_T31",
"type": "Cell",
"text": [
"epithelial cells"
],
"offsets": [
[
1530,
1546
]
],
"normalized": []
},
{
"id": "PMID-18384219_T33",
"type": "Tissue",
"text": [
"specimens"
],
"offsets": [
[
1580,
1589
]
],
"normalized": []
},
{
"id": "PMID-18384219_T35",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1672,
1682
]
],
"normalized": []
},
{
"id": "PMID-18384219_T36",
"type": "Cancer",
"text": [
"NPC"
],
"offsets": [
[
1744,
1747
]
],
"normalized": []
},
{
"id": "PMID-18384219_T39",
"type": "Cancer",
"text": [
"NPC"
],
"offsets": [
[
1850,
1853
]
],
"normalized": []
},
{
"id": "PMID-18384219_T3",
"type": "Cancer",
"text": [
"metastatic diseases"
],
"offsets": [
[
452,
471
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-19700757 | PMID-19700757 | [
{
"id": "PMID-19700757__text",
"type": "abstract",
"text": [
"A key role for the integrin alpha2beta1 in experimental and developmental angiogenesis.\nThe alpha2beta1 integrin receptor plays a key role in angiogenesis. Here we investigated the effects of small molecule inhibitors (SMIs) designed to disrupt integrin alpha2 I or beta1 I-like domain function on angiogenesis. In unchallenged endothelial cells, fibrillar collagen induced robust capillary morphogenesis. In contrast, tube formation was significantly reduced by SMI496, a beta1 I-like domain inhibitor and by function-blocking anti-alpha2beta1 but not -alpha1beta1 antibodies. Endothelial cells bound fluorescein-labeled collagen I fibrils, an interaction specifically inhibited by SMI496. Moreover, SMI496 caused cell retraction and cytoskeletal collapse of endothelial cells as well as delayed endothelial cell wound healing. SMI activities were examined in vivo by supplementing the growth medium of zebrafish embryos expressing green fluorescent protein under the control of the vascular endothelial growth factor receptor-2 promoter. SMI496, but not a control compound, interfered with angiogenesis in vivo by reversibly inhibiting sprouting from the axial vessels. We further characterized zebrafish alpha2 integrin and discovered that this integrin is highly conserved, especially the I domain. Notably, a similar vascular phenotype was induced by morpholino-mediated knockdown of the integrin alpha2 subunit. By live videomicroscopy, we confirmed that the vessels were largely nonfunctional in the absence of alpha2beta1 integrin. Collectively, our results provide strong biochemical and genetic evidence of a central role for alpha2beta1 integrin in experimental and developmental angiogenesis.\n"
],
"offsets": [
[
0,
1705
]
]
}
] | [
{
"id": "PMID-19700757_T5",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
328,
345
]
],
"normalized": []
},
{
"id": "PMID-19700757_T7",
"type": "Tissue",
"text": [
"capillary"
],
"offsets": [
[
381,
390
]
],
"normalized": []
},
{
"id": "PMID-19700757_T8",
"type": "Tissue",
"text": [
"tube"
],
"offsets": [
[
419,
423
]
],
"normalized": []
},
{
"id": "PMID-19700757_T13",
"type": "Cell",
"text": [
"Endothelial cells"
],
"offsets": [
[
578,
595
]
],
"normalized": []
},
{
"id": "PMID-19700757_T18",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
715,
719
]
],
"normalized": []
},
{
"id": "PMID-19700757_T19",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
760,
777
]
],
"normalized": []
},
{
"id": "PMID-19700757_T20",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
797,
813
]
],
"normalized": []
},
{
"id": "PMID-19700757_T21",
"type": "Pathological_formation",
"text": [
"wound"
],
"offsets": [
[
814,
819
]
],
"normalized": []
},
{
"id": "PMID-19700757_T23",
"type": "Developing_anatomical_structure",
"text": [
"embryos"
],
"offsets": [
[
914,
921
]
],
"normalized": []
},
{
"id": "PMID-19700757_T27",
"type": "Multi-tissue_structure",
"text": [
"axial vessels"
],
"offsets": [
[
1157,
1170
]
],
"normalized": []
},
{
"id": "PMID-19700757_T31",
"type": "Multi-tissue_structure",
"text": [
"vascular"
],
"offsets": [
[
1322,
1330
]
],
"normalized": []
},
{
"id": "PMID-19700757_T33",
"type": "Multi-tissue_structure",
"text": [
"vessels"
],
"offsets": [
[
1465,
1472
]
],
"normalized": []
},
{
"id": "PMID-19700757_T1",
"type": "Cellular_component",
"text": [
"cytoskeletal"
],
"offsets": [
[
735,
747
]
],
"normalized": []
},
{
"id": "PMID-19700757_T2",
"type": "Cellular_component",
"text": [
"fibrillar"
],
"offsets": [
[
347,
356
]
],
"normalized": []
},
{
"id": "PMID-19700757_T3",
"type": "Cellular_component",
"text": [
"fibrils"
],
"offsets": [
[
633,
640
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-12134045 | PMID-12134045 | [
{
"id": "PMID-12134045__text",
"type": "abstract",
"text": [
"Simian virus 40 large T antigen and two independent T-antigen segments sensitize cells to apoptosis following genotoxic damage. \nThe simian virus 40 (SV40) large tumor (T) antigen is sufficient to transform cells in cultures and induce tumors in experimental animals. Transformation of primary cells in cultures requires both overcoming growth arrest by stimulating the cell cycle and blocking cell death activities presumably activated by oncogene-mediated hyperproliferation signals. The study presented here examined the ability of specific regions and activities of T antigen to modulate apoptosis in cells treated with the genotoxic agent 5-fluorouracil (5-FU). The results showed that the expression of full-length T antigen rendered rat embryo fibroblasts (REF) sensitive to 5-FU-induced apoptosis. Thus, neither the p53-binding region nor the Bcl-2 homology region of T antigen was sufficient to prevent cell death induced by the DNA-damaging agent. T-antigen-mediated sensitization occurred independently of retinoblastoma protein or p53 and p300 binding. An N-terminal segment containing the first 127 T-antigen amino acids (T1-127) was sufficient to sensitize cells. A C-terminal segment consisting of T-antigen amino acids 251 to 708 (T251-708) also sensitized cells to 5-FU-induced apoptosis. This sensitization did not occur when T251-708 was targeted to the nucleus by inclusion of the SV40 nuclear localization signal. The introduction of mutations into the T-antigen J domain resulted in mutation-specific and variable inhibition of apoptosis. This result suggested that either the structural or the functional integrity of the J domain is required to sensitize cells to apoptosis. Treatment of REF or REF expressing full-length T antigen, an N-terminal segment, or T251-708 resulted in increased expression of the p53-responsive MDM2 gene; apoptosis occurred through a p53-dependent pathway, as p53-null cells expressing these T antigens were resistant to 5-FU-induced apoptosis. Possible mechanisms involved in sensitizing cells to a p53-dependent apoptosis pathway in spite of the ability of T antigen to bind and inactivate the transcriptional transactivating activity of p53 are discussed.\n"
],
"offsets": [
[
0,
2212
]
]
}
] | [
{
"id": "PMID-12134045_T4",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
81,
86
]
],
"normalized": []
},
{
"id": "PMID-12134045_T8",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
207,
212
]
],
"normalized": []
},
{
"id": "PMID-12134045_T9",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
236,
242
]
],
"normalized": []
},
{
"id": "PMID-12134045_T10",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
294,
299
]
],
"normalized": []
},
{
"id": "PMID-12134045_T11",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
370,
374
]
],
"normalized": []
},
{
"id": "PMID-12134045_T12",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
394,
398
]
],
"normalized": []
},
{
"id": "PMID-12134045_T14",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
605,
610
]
],
"normalized": []
},
{
"id": "PMID-12134045_T19",
"type": "Cell",
"text": [
"embryo fibroblasts"
],
"offsets": [
[
744,
762
]
],
"normalized": []
},
{
"id": "PMID-12134045_T20",
"type": "Cell",
"text": [
"REF"
],
"offsets": [
[
764,
767
]
],
"normalized": []
},
{
"id": "PMID-12134045_T25",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
912,
916
]
],
"normalized": []
},
{
"id": "PMID-12134045_T33",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
1171,
1176
]
],
"normalized": []
},
{
"id": "PMID-12134045_T36",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
1273,
1278
]
],
"normalized": []
},
{
"id": "PMID-12134045_T38",
"type": "Cellular_component",
"text": [
"nucleus"
],
"offsets": [
[
1373,
1380
]
],
"normalized": []
},
{
"id": "PMID-12134045_T41",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
1679,
1684
]
],
"normalized": []
},
{
"id": "PMID-12134045_T42",
"type": "Cell",
"text": [
"REF"
],
"offsets": [
[
1712,
1715
]
],
"normalized": []
},
{
"id": "PMID-12134045_T43",
"type": "Cell",
"text": [
"REF"
],
"offsets": [
[
1719,
1722
]
],
"normalized": []
},
{
"id": "PMID-12134045_T49",
"type": "Cell",
"text": [
"p53-null cells"
],
"offsets": [
[
1913,
1927
]
],
"normalized": []
},
{
"id": "PMID-12134045_T52",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
2042,
2047
]
],
"normalized": []
},
{
"id": "PMID-12134045_T120",
"type": "Cellular_component",
"text": [
"nuclear"
],
"offsets": [
[
1406,
1413
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-22127321 | PMID-22127321 | [
{
"id": "PMID-22127321__text",
"type": "abstract",
"text": [
"Research and discovery of the first human cancer virus, HTLV-1. \nHuman T-cell lymphoma virus (HTLV)-1 was the first human retrovirus to be discovered. It has been recognized as the cause of adult T-cell leukemia (ATL). In addition to giving a historical perspective on HTLV-1 and other retrovirus research, this paper discusses the origin of HTLV-1; the modes of transmission and global epidemiology of HTLV-1 infection; the genome of HTLV-1 and the mechanism of HTLV-1-induced leukemogenesis; the role of HTLV-1 in other diseases, and recent breakthroughs in ATL therapy.\n"
],
"offsets": [
[
0,
573
]
]
}
] | [
{
"id": "PMID-22127321_T2",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
42,
48
]
],
"normalized": []
},
{
"id": "PMID-22127321_T6",
"type": "Cancer",
"text": [
"adult T-cell leukemia"
],
"offsets": [
[
190,
211
]
],
"normalized": []
},
{
"id": "PMID-22127321_T7",
"type": "Cancer",
"text": [
"ATL"
],
"offsets": [
[
213,
216
]
],
"normalized": []
},
{
"id": "PMID-22127321_T14",
"type": "Cancer",
"text": [
"ATL"
],
"offsets": [
[
560,
563
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-7875243 | PMID-7875243 | [
{
"id": "PMID-7875243__text",
"type": "abstract",
"text": [
"Modulation of apoptosis in human myeloid leukemic cells by GM-CSF. \nApoptosis (programmed cell death) regulates cell population size. To determine the mechanisms whereby hematopoietic growth factors (HGFs) modulate apoptosis in human myeloid leukemic cells, we evaluated the roles of protein and mRNA synthesis for altering apoptosis in growth factor-stimulated vs. quiescent leukemic TF1 cells. Lysates of cells from the granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent myeloid leukemic cell line TF1 were separated into high molecular weight (HMW) pellets of intact DNA and supernatants of fragmented low MW (LMW) DNA, and the DNA purified from these fractions was quantified. In the absence of both GM-CSF and fetal bovine serum (FBS), 70% of the DNA was fragmented after 3 days in culture, with a characteristic apoptotic ladder-like pattern on agarose gel electrophoresis, whereas this proportion had initially been < 5%. In contrast, less than 5% of the DNA was fragmented in cells incubated with GM-CSF plus FBS or GM-CSF alone. Delayed addition of GM-CSF, but not FBS, permitted partial rescue of the cells, inhibiting increasing rates of accumulation of fragmented DNA. When the macro-molecular synthesis inhibitor cycloheximide (CHX) or actinomycin D (Act D) was present for 26 hours in the absence of GM-CSF and FBS, apoptosis was inhibited. In contrast, in the presence of GM-CSF or FBS, apoptosis was enhanced upon addition of CHX or Act D. The latter effect persisted even with the late addition of CHX. These findings indicate that disparate mechanisms of enhancing or inhibiting apoptosis exist in myeloid leukemic cells related to environmental conditions, including HGF-regulated cellular synthesis of distinct proteins and mRNA.\n"
],
"offsets": [
[
0,
1767
]
]
}
] | [
{
"id": "PMID-7875243_T2",
"type": "Cell",
"text": [
"myeloid leukemic cells"
],
"offsets": [
[
33,
55
]
],
"normalized": []
},
{
"id": "PMID-7875243_T4",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
90,
94
]
],
"normalized": []
},
{
"id": "PMID-7875243_T5",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
112,
116
]
],
"normalized": []
},
{
"id": "PMID-7875243_T9",
"type": "Cell",
"text": [
"myeloid leukemic cells"
],
"offsets": [
[
234,
256
]
],
"normalized": []
},
{
"id": "PMID-7875243_T10",
"type": "Cell",
"text": [
"leukemic TF1 cells"
],
"offsets": [
[
376,
394
]
],
"normalized": []
},
{
"id": "PMID-7875243_T11",
"type": "Organism_substance",
"text": [
"Lysates"
],
"offsets": [
[
396,
403
]
],
"normalized": []
},
{
"id": "PMID-7875243_T12",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
407,
412
]
],
"normalized": []
},
{
"id": "PMID-7875243_T15",
"type": "Cell",
"text": [
"myeloid leukemic cell line TF1"
],
"offsets": [
[
490,
520
]
],
"normalized": []
},
{
"id": "PMID-7875243_T20",
"type": "Organism_substance",
"text": [
"fetal bovine serum"
],
"offsets": [
[
732,
750
]
],
"normalized": []
},
{
"id": "PMID-7875243_T21",
"type": "Organism_substance",
"text": [
"FBS"
],
"offsets": [
[
752,
755
]
],
"normalized": []
},
{
"id": "PMID-7875243_T25",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
1001,
1006
]
],
"normalized": []
},
{
"id": "PMID-7875243_T27",
"type": "Organism_substance",
"text": [
"FBS"
],
"offsets": [
[
1034,
1037
]
],
"normalized": []
},
{
"id": "PMID-7875243_T30",
"type": "Organism_substance",
"text": [
"FBS"
],
"offsets": [
[
1091,
1094
]
],
"normalized": []
},
{
"id": "PMID-7875243_T31",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
1128,
1133
]
],
"normalized": []
},
{
"id": "PMID-7875243_T38",
"type": "Organism_substance",
"text": [
"FBS"
],
"offsets": [
[
1342,
1345
]
],
"normalized": []
},
{
"id": "PMID-7875243_T40",
"type": "Organism_substance",
"text": [
"FBS"
],
"offsets": [
[
1414,
1417
]
],
"normalized": []
},
{
"id": "PMID-7875243_T44",
"type": "Cell",
"text": [
"myeloid leukemic cells"
],
"offsets": [
[
1633,
1655
]
],
"normalized": []
},
{
"id": "PMID-7875243_T46",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
1717,
1725
]
],
"normalized": []
},
{
"id": "PMID-7875243_T1",
"type": "Organism_substance",
"text": [
"supernatants"
],
"offsets": [
[
595,
607
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-9094635 | PMID-9094635 | [
{
"id": "PMID-9094635__text",
"type": "abstract",
"text": [
"Regulation of p53-dependent apoptosis, transcriptional repression, and cell transformation by phosphorylation of the 55-kilodalton E1B protein of human adenovirus type 5. \nThe adenovirus type 5 55-kDa E1B protein (E1B-55kDa) cooperates with E1A gene products to induce cell transformation. E1A proteins stimulate DNA synthesis and cell proliferation; however, they also cause rapid cell death by p53-dependent and p53-independent apoptosis. It is believed that the role of the E1B-55kDa protein in transformation is to protect against p53-dependent apoptosis by binding to and inactivating p53. It has been shown previously that the 55-kDa polypeptide abrogates p53-mediated transactivation and that mutants defective in p53 binding are unable to cooperate with E1A in transformation. We have previously mapped phosphorylation sites near the carboxy terminus of the E1B-55kDa protein at Ser-490 and Ser-491, which lie within casein kinase II consensus sequences. Conversion of these sites to alanine residues greatly reduced transforming activity, and although the mutant 55-kDa protein was found to interact with p53 at normal levels, it was somewhat defective for suppression of p53 transactivation activity. We now report that a nearby residue, Thr-495, also appears to be phosphorylated. We demonstrate directly that the wild-type 55-kDa protein is able to block E1A-induced p53-dependent apoptosis, whereas cells infected by mutant pm490/1/5A, which contains alanine residues at all three phosphorylation sites, exhibited extensive DNA fragmentation and classic apoptotic cell death. The E1B-55kDa product has been shown to exhibit intrinsic transcriptional repression activity when localized to promoters, such as by fusion with the GAL4 DNA-binding domain, even in the absence of p53. Such repression activity was totally absent with mutant pm490/1/5A. These data suggested that inhibition of p53-dependent apoptosis may depend on the transcriptional repression function of the 55-kDa protein, which appears to be regulated be phosphorylation at the carboxy terminus.\n"
],
"offsets": [
[
0,
2075
]
]
}
] | [
{
"id": "PMID-9094635_T2",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
71,
75
]
],
"normalized": []
},
{
"id": "PMID-9094635_T9",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
269,
273
]
],
"normalized": []
},
{
"id": "PMID-9094635_T12",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
331,
335
]
],
"normalized": []
},
{
"id": "PMID-9094635_T13",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
382,
386
]
],
"normalized": []
},
{
"id": "PMID-9094635_T35",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
1412,
1417
]
],
"normalized": []
},
{
"id": "PMID-9094635_T39",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1577,
1581
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-11716301 | PMID-11716301 | [
{
"id": "PMID-11716301__text",
"type": "abstract",
"text": [
"Assembly strategies and GTPase regulation of the eukaryotic and Escherichia coil translocons.\nThe translocation of most proteins across the endoplasmic reticulum or bacterial inner membrane occurs through an aqueous pore that spans the membrane. Substrates that are translocated co-translationally across the membrane are directed to the translocation pore via an interaction between the cytosolic signal recognition particle and its membrane-bound receptor. Together the translocation pore and the receptor are referred to as a translocon. By studying the biogenesis of the translocon a number of alternate targeting and membrane-integration pathways have been discovered that operate independently of the signal recognition particle (SRP) pathway. The novel assembly strategies of the translocon and the ways in which these components interact to ensure the fidelity and unidirectionality of the targeting and translocation process are reviewed here.\n"
],
"offsets": [
[
0,
953
]
]
}
] | [
{
"id": "PMID-11716301_T1",
"type": "Cellular_component",
"text": [
"endoplasmic reticulum"
],
"offsets": [
[
140,
161
]
],
"normalized": []
},
{
"id": "PMID-11716301_T2",
"type": "Cellular_component",
"text": [
"inner membrane"
],
"offsets": [
[
175,
189
]
],
"normalized": []
},
{
"id": "PMID-11716301_T4",
"type": "Cellular_component",
"text": [
"membrane"
],
"offsets": [
[
236,
244
]
],
"normalized": []
},
{
"id": "PMID-11716301_T5",
"type": "Cellular_component",
"text": [
"membrane"
],
"offsets": [
[
309,
317
]
],
"normalized": []
},
{
"id": "PMID-11716301_T6",
"type": "Cellular_component",
"text": [
"membrane"
],
"offsets": [
[
434,
442
]
],
"normalized": []
},
{
"id": "PMID-11716301_T7",
"type": "Cellular_component",
"text": [
"translocation pore"
],
"offsets": [
[
472,
490
]
],
"normalized": []
},
{
"id": "PMID-11716301_T8",
"type": "Cellular_component",
"text": [
"translocation pore"
],
"offsets": [
[
338,
356
]
],
"normalized": []
},
{
"id": "PMID-11716301_T9",
"type": "Cellular_component",
"text": [
"aqueous pore"
],
"offsets": [
[
208,
220
]
],
"normalized": []
},
{
"id": "PMID-11716301_T10",
"type": "Cellular_component",
"text": [
"membrane"
],
"offsets": [
[
622,
630
]
],
"normalized": []
},
{
"id": "PMID-11716301_T3",
"type": "Organism_substance",
"text": [
"cytosolic"
],
"offsets": [
[
388,
397
]
],
"normalized": []
},
{
"id": "PMID-11716301_T11",
"type": "Cellular_component",
"text": [
"translocon"
],
"offsets": [
[
529,
539
]
],
"normalized": []
},
{
"id": "PMID-11716301_T12",
"type": "Cellular_component",
"text": [
"translocon"
],
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[
575,
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]
],
"normalized": []
},
{
"id": "PMID-11716301_T13",
"type": "Cellular_component",
"text": [
"translocon"
],
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787,
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]
],
"normalized": []
},
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"id": "PMID-11716301_T14",
"type": "Cellular_component",
"text": [
"translocons"
],
"offsets": [
[
81,
92
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-1388088 | PMID-1388088 | [
{
"id": "PMID-1388088__text",
"type": "abstract",
"text": [
"Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat.\nInterleukin-1 (IL-1) synthesis in the brain is stimulated by mechanical injury and IL-1 mimics some effects of injury, such as gliosis and neovascularization. We report that neuronal death resulting from focal cerebral ischaemia (middle cerebral artery occlusion, 24 h) is significantly inhibited (by 50%) in rats injected with a recombinant IL-1 receptor antagonist (IL-1ra, 10 micrograms, icv 30 min before and 10 min after ischaemia). Excitotoxic damage due to striatal infusion of an NMDA-receptor agonist (cis-2,4-methanoglutamate) was also markedly inhibited (71%) by injection of the IL-1ra. These data indicate that endogenous IL-1 is a mediator of ischaemic and excitotoxic brain damage, and that inhibitors of IL-1 action may be of therapeutic value in the treatment of acute or chronic neuronal death.\n"
],
"offsets": [
[
0,
910
]
]
}
] | [
{
"id": "PMID-1388088_T2",
"type": "Cell",
"text": [
"neuronal"
],
"offsets": [
[
69,
77
]
],
"normalized": []
},
{
"id": "PMID-1388088_T6",
"type": "Organ",
"text": [
"brain"
],
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[
135,
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]
],
"normalized": []
},
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"id": "PMID-1388088_T8",
"type": "Cell",
"text": [
"neuronal"
],
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[
271,
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]
],
"normalized": []
},
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"id": "PMID-1388088_T9",
"type": "Organ",
"text": [
"cerebral"
],
"offsets": [
[
307,
315
]
],
"normalized": []
},
{
"id": "PMID-1388088_T10",
"type": "Multi-tissue_structure",
"text": [
"middle cerebral artery"
],
"offsets": [
[
327,
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]
],
"normalized": []
},
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"id": "PMID-1388088_T14",
"type": "Multi-tissue_structure",
"text": [
"striatal"
],
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561,
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]
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"normalized": []
},
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"id": "PMID-1388088_T19",
"type": "Organ",
"text": [
"brain"
],
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[
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]
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},
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"id": "PMID-1388088_T21",
"type": "Cell",
"text": [
"neuronal"
],
"offsets": [
[
894,
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]
],
"normalized": []
}
] | [] | [] | [] |
PMC-3003518-sec-05 | PMC-3003518-sec-05 | [
{
"id": "PMC-3003518-sec-05__text",
"type": "sec",
"text": [
"Introduction\nAdipose tissue, once viewed as simply a storage and release depot for lipids, is now considered an endocrine tissue [1,2] that secretes various substances (adipokines), including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, leptin, adiponectin, resistin, visfatin, and omenetin [3,4]. Among these adipokines, much attention has been paid to adiponectin's relationship with insulin sensitivity and glucose and lipid metabolism in the past 10 years. In addition, adiponectin is known to exhibit potent anti-inflammatory [5], atheroprotective [6], and antidiabetic [7] effects.\nRecent findings suggest that adiponectin may be involved in the pathogenesis of rheumatoid arthritis (RA). Levels of adiponectin in synovial fluid and sera were elevated in patients with RA [8,9]. Adiponectin also induces the production of proinflammatory cytokines, IL-6, matrix metalloproteinase (MMP)-1, and IL-8 from RA synovial fibroblasts in vitro [10,11]. Thus, it was suggested that adiponectin can also exert significant proinflammatory and matrix-degrading effects. However, the role of adiponectin in the pathogenesis of RA is still controversial because of conflicting reports about its function [10,12-15]. In particular, adiponectin seems to play an anti-inflammatory role because it significantly inhibited IL-1beta-stimulated synovial cell proliferation in collagen-induced arthritic mice, despite increased IL-6 expression [16]. In contrast, high-grade inflammation in RA patients was negatively correlated with circulating adiponectin concentrations [17]. Rather, it was suggested that circulating adiponectin may be involved in cardiovascular disease in RA patients. Although this contradiction was partly explained by the induction of tolerance to inflammatory stimuli by adiponectin [18], the pro- or anti-inflammatory effects of adiponectin on the pathogenesis of RA remain unknown.\nWith regard to adiponectin's proinflammatory effects, we wondered whether adiponectin might stimulate the production of vascular endothelial growth factor (VEGF) and MMPs as well as proinflammatory mediators like IL-1beta and TNF-alpha do. In this study, we investigated the stimulatory effect of adiponectin on the production of IL-6, IL-8, prostaglandin E2 (PGE2), VEGF, and MMPs. In addition, the correlation between adiponectin and VEGF or MMPs was investigated by measuring the levels of these three proteins in the joint fluid of patients with RA or osteoarthritis (OA).\n"
],
"offsets": [
[
0,
2486
]
]
}
] | [
{
"id": "PMC-3003518-sec-05_T1",
"type": "Tissue",
"text": [
"Adipose tissue"
],
"offsets": [
[
13,
27
]
],
"normalized": []
},
{
"id": "PMC-3003518-sec-05_T2",
"type": "Tissue",
"text": [
"endocrine tissue"
],
"offsets": [
[
112,
128
]
],
"normalized": []
},
{
"id": "PMC-3003518-sec-05_T4",
"type": "Organism_substance",
"text": [
"synovial fluid"
],
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[
736,
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]
],
"normalized": []
},
{
"id": "PMC-3003518-sec-05_T5",
"type": "Organism_substance",
"text": [
"sera"
],
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[
755,
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]
],
"normalized": []
},
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"id": "PMC-3003518-sec-05_T6",
"type": "Cell",
"text": [
"synovial fibroblasts"
],
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928,
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]
],
"normalized": []
},
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"id": "PMC-3003518-sec-05_T7",
"type": "Cell",
"text": [
"synovial cell"
],
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]
],
"normalized": []
},
{
"id": "PMC-3003518-sec-05_T8",
"type": "Anatomical_system",
"text": [
"cardiovascular"
],
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1651,
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]
],
"normalized": []
},
{
"id": "PMC-3003518-sec-05_T10",
"type": "Organism_substance",
"text": [
"joint fluid"
],
"offsets": [
[
2430,
2441
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-16210037 | PMID-16210037 | [
{
"id": "PMID-16210037__text",
"type": "abstract",
"text": [
"Pathogenesis of thrombosis in essential thrombocythemia and polycythemia vera: the role of neutrophils.\nThrombotic complications are frequently observed in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Abnormalities of red blood cells and platelets arising from the clonal rearrangement of hematopoietic cells have been considered, although causal relationships between any of these specific abnormalities and thrombosis have not been clearly established. The involvement of neutrophils and macrophages, which participate in thrombosis and hemostasis, has been insufficiently explored in PV and ET. Persistent activation of circulating neutrophils was recently demonstrated in ET and PV patients, in parallel with an increase in plasma concentrations of endothelial damage-derived and prothrombotic substances. Other studies have explored whether the augmentation of adhesion of neutrophils may affect neutrophil/platelet interaction since a significant increase in circulating neutrophil/platelet aggregates is found in ET and PV. This review summarizes the current knowledge of the pathogenesis of thrombosis in PV and ET, with emphasis on the role of neutrophils in hemostasis and their possible involvement in the mechanisms of the acquired thrombophilia of these patients. Available data suggest that these hemostatic markers deserve to be included in prospective clinical studies aimed at identifying their predictive role in the vascular complications of patients with ET and PV.\n"
],
"offsets": [
[
0,
1514
]
]
}
] | [
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"id": "PMID-16210037_T1",
"type": "Cell",
"text": [
"neutrophils"
],
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[
91,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T2",
"type": "Cell",
"text": [
"red blood cells"
],
"offsets": [
[
246,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T3",
"type": "Cell",
"text": [
"platelets"
],
"offsets": [
[
266,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T4",
"type": "Cell",
"text": [
"hematopoietic cells"
],
"offsets": [
[
317,
336
]
],
"normalized": []
},
{
"id": "PMID-16210037_T5",
"type": "Cell",
"text": [
"neutrophils"
],
"offsets": [
[
502,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T6",
"type": "Cell",
"text": [
"macrophages"
],
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[
518,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T7",
"type": "Cell",
"text": [
"neutrophils"
],
"offsets": [
[
663,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T8",
"type": "Organism_substance",
"text": [
"plasma"
],
"offsets": [
[
756,
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]
],
"normalized": []
},
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"id": "PMID-16210037_T9",
"type": "Tissue",
"text": [
"endothelial"
],
"offsets": [
[
781,
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]
],
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},
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"id": "PMID-16210037_T10",
"type": "Cell",
"text": [
"neutrophils"
],
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906,
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]
],
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},
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"id": "PMID-16210037_T11",
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"text": [
"neutrophil"
],
"offsets": [
[
929,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T12",
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"text": [
"platelet"
],
"offsets": [
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940,
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]
],
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},
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"id": "PMID-16210037_T13",
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"neutrophil"
],
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1005,
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]
],
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},
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"id": "PMID-16210037_T14",
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"text": [
"platelet"
],
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1016,
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]
],
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},
{
"id": "PMID-16210037_T15",
"type": "Cell",
"text": [
"neutrophils"
],
"offsets": [
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1181,
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]
],
"normalized": []
},
{
"id": "PMID-16210037_T16",
"type": "Multi-tissue_structure",
"text": [
"vascular"
],
"offsets": [
[
1463,
1471
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-19416474 | PMID-19416474 | [
{
"id": "PMID-19416474__text",
"type": "abstract",
"text": [
"The EGFR-GEP100-Arf6-AMAP1 signaling pathway specific to breast cancer invasion and metastasis. \nTumors are tissue-specific diseases, and their mechanisms of invasion and metastasis are highly diverse. In breast cancer, biomarkers that specifically correlate with the invasive phenotypes have not been clearly identified. A small GTPase Arf6 primarily regulates recycling of plasma membrane components. We have shown that Arf6 and its effector AMAP1 (DDEF1, DEF1, ASAP1 and centaurin beta4) are abnormally overexpressed in some breast cancers and used for their invasion and metastasis. Overexpression of these proteins is independent of the transcriptional upregulation of their genes, and occurs only in highly malignant breast cancer cells. We recently identified GEP100 (BRAG2) to be responsible for the Arf6 activation to induce invasion and metastasis, by directly binding to ligand-activated epidermal growth factor receptor (EGFR). A series of our studies revealed that for activation of the invasion pathway of EGFR, it is prerequisite that Arf6 and AMAP1 both are highly overexpressed, and that EGFR is activated by ligands. Pathological analyses indicate that a significant large population of human ductal cancers may utilize the EGFR-GEP100-Arf6-AMAP1 pathway for their malignancy. Microenvironments have been highly implicated in the malignancy of mammary tumors. Our results reveal an aspect of the precise molecular mechanisms of some breast cancers, in which full invasiveness is not acquired just by intracellular alterations of cancer cells, but extracellular factors from microenvironments may also be necessary. Possible translation of our knowledge to cancer therapeutics will also be discussed.\n"
],
"offsets": [
[
0,
1718
]
]
}
] | [
{
"id": "PMID-19416474_T5",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
57,
70
]
],
"normalized": []
},
{
"id": "PMID-19416474_T6",
"type": "Cancer",
"text": [
"Tumors"
],
"offsets": [
[
97,
103
]
],
"normalized": []
},
{
"id": "PMID-19416474_T7",
"type": "Tissue",
"text": [
"tissue"
],
"offsets": [
[
108,
114
]
],
"normalized": []
},
{
"id": "PMID-19416474_T8",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
205,
218
]
],
"normalized": []
},
{
"id": "PMID-19416474_T11",
"type": "Cellular_component",
"text": [
"plasma membrane components"
],
"offsets": [
[
375,
401
]
],
"normalized": []
},
{
"id": "PMID-19416474_T18",
"type": "Cancer",
"text": [
"breast cancers"
],
"offsets": [
[
528,
542
]
],
"normalized": []
},
{
"id": "PMID-19416474_T19",
"type": "Cell",
"text": [
"malignant breast cancer cells"
],
"offsets": [
[
713,
742
]
],
"normalized": []
},
{
"id": "PMID-19416474_T30",
"type": "Cancer",
"text": [
"ductal cancers"
],
"offsets": [
[
1211,
1225
]
],
"normalized": []
},
{
"id": "PMID-19416474_T35",
"type": "Cancer",
"text": [
"mammary tumors"
],
"offsets": [
[
1362,
1376
]
],
"normalized": []
},
{
"id": "PMID-19416474_T36",
"type": "Cancer",
"text": [
"breast cancers"
],
"offsets": [
[
1451,
1465
]
],
"normalized": []
},
{
"id": "PMID-19416474_T37",
"type": "Immaterial_anatomical_entity",
"text": [
"intracellular"
],
"offsets": [
[
1518,
1531
]
],
"normalized": []
},
{
"id": "PMID-19416474_T38",
"type": "Cell",
"text": [
"cancer cells"
],
"offsets": [
[
1547,
1559
]
],
"normalized": []
},
{
"id": "PMID-19416474_T39",
"type": "Immaterial_anatomical_entity",
"text": [
"extracellular"
],
"offsets": [
[
1565,
1578
]
],
"normalized": []
},
{
"id": "PMID-19416474_T40",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
1674,
1680
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2474682-caption-05 | PMC-2474682-caption-05 | [
{
"id": "PMC-2474682-caption-05__text",
"type": "caption",
"text": [
"Summary of studies reporting comorbidities with diabetes.\n"
],
"offsets": [
[
0,
58
]
]
}
] | [] | [] | [] | [] |
PMID-17210799 | PMID-17210799 | [
{
"id": "PMID-17210799__text",
"type": "abstract",
"text": [
"Activation of vascular endothelial growth factor through reactive oxygen species mediates 20-hydroxyeicosatetraenoic acid-induced endothelial cell proliferation.\n20-Hydroxyeicosatetraenoic acid (20-HETE) is formed by the omega-hydroxylation of arachidonic acid by cytochrome P450 4A and 4F enzymes, and it induces angiogenic responses in vivo. To test the hypothesis that 20-HETE increases endothelial cell (EC) proliferation via vascular endothelial growth factor (VEGF), we studied the effects of WIT003 [20-hydroxyeicosa-5(Z),14(Z)-dienoic acid], a 20-HETE analog on human macrovascular or microvascular EC. WIT003, as well as pure 20-HETE, stimulated EC proliferation by approximately 40%. These proliferative effects were accompanied by increased VEGF expression and release that were observed as early as 4 h after 20-HETE agonist addition. This was accompanied by increased phosphorylation of the VEGF receptor 2. The proliferative effects of 20-HETE were markedly inhibited by a VEGF-neutralizing antibody. Polyethylene glycol-superoxide dismutase (PEG-SOD) markedly inhibited both the increases in VEGF expression and the proliferative effects of 20-HETE. In contrast, administration of the NAD(P)H oxidase inhibitor apocynin had no effect to the proliferative response to 20-HETE. The 20-HETE agonist markedly increased superoxide formation as reflected by an increase in dihydroethidium staining of EC, and this increase was inhibited by PEG-SOD but not by apocynin. 20-HETE also increased the phosphorylation of p42/p44 mitogen-activated protein kinase (MAPK) in EC, whereas an inhibitor of MAPK [U0126, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] suppressed the proliferative and the VEGF changes but not the pro-oxidant effects of 20-HETE. These data suggest that 20-HETE stimulates superoxide formation by pathways other than apocynin-sensitive NAD(P)H oxidase, thereby activating MAPK and then enhancing VEGF synthesis that drives EC proliferation. Thus, 20-HETE may be involved in the regulation of EC functions, such as angiogenesis.\n"
],
"offsets": [
[
0,
2069
]
]
}
] | [
{
"id": "PMID-17210799_T4",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
130,
146
]
],
"normalized": []
},
{
"id": "PMID-17210799_T11",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
390,
406
]
],
"normalized": []
},
{
"id": "PMID-17210799_T12",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
408,
410
]
],
"normalized": []
},
{
"id": "PMID-17210799_T19",
"type": "Cell",
"text": [
"macrovascular"
],
"offsets": [
[
576,
589
]
],
"normalized": []
},
{
"id": "PMID-17210799_T20",
"type": "Cell",
"text": [
"microvascular EC"
],
"offsets": [
[
593,
609
]
],
"normalized": []
},
{
"id": "PMID-17210799_T23",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
655,
657
]
],
"normalized": []
},
{
"id": "PMID-17210799_T39",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1410,
1412
]
],
"normalized": []
},
{
"id": "PMID-17210799_T45",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1575,
1577
]
],
"normalized": []
},
{
"id": "PMID-17210799_T57",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1964,
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]
],
"normalized": []
},
{
"id": "PMID-17210799_T59",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
2033,
2035
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-14638851 | PMID-14638851 | [
{
"id": "PMID-14638851__text",
"type": "abstract",
"text": [
"Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. \nMalignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.\n"
],
"offsets": [
[
0,
1345
]
]
}
] | [
{
"id": "PMID-14638851_T2",
"type": "Cell",
"text": [
"Malignant cells"
],
"offsets": [
[
87,
102
]
],
"normalized": []
},
{
"id": "PMID-14638851_T3",
"type": "Cellular_component",
"text": [
"cytoplasmic organelles"
],
"offsets": [
[
213,
235
]
],
"normalized": []
},
{
"id": "PMID-14638851_T4",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
316,
321
]
],
"normalized": []
},
{
"id": "PMID-14638851_T7",
"type": "Cancer",
"text": [
"breast"
],
"offsets": [
[
427,
433
]
],
"normalized": []
},
{
"id": "PMID-14638851_T8",
"type": "Cancer",
"text": [
"ovarian"
],
"offsets": [
[
435,
442
]
],
"normalized": []
},
{
"id": "PMID-14638851_T9",
"type": "Cancer",
"text": [
"prostate cancer"
],
"offsets": [
[
448,
463
]
],
"normalized": []
},
{
"id": "PMID-14638851_T13",
"type": "Cancer",
"text": [
"malignancies"
],
"offsets": [
[
692,
704
]
],
"normalized": []
},
{
"id": "PMID-14638851_T15",
"type": "Pathological_formation",
"text": [
"premalignant lesions"
],
"offsets": [
[
766,
786
]
],
"normalized": []
},
{
"id": "PMID-14638851_T16",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
810,
816
]
],
"normalized": []
},
{
"id": "PMID-14638851_T20",
"type": "Cell",
"text": [
"cellular"
],
"offsets": [
[
988,
996
]
],
"normalized": []
},
{
"id": "PMID-14638851_T22",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
1107,
1112
]
],
"normalized": []
},
{
"id": "PMID-14638851_T23",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1197,
1201
]
],
"normalized": []
},
{
"id": "PMID-14638851_T24",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
1221,
1226
]
],
"normalized": []
},
{
"id": "PMID-14638851_T27",
"type": "Cancer",
"text": [
"cancers"
],
"offsets": [
[
1336,
1343
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2790131-sec-02 | PMC-2790131-sec-02 | [
{
"id": "PMC-2790131-sec-02__text",
"type": "sec",
"text": [
"Subjects and Methods\nABPM was conducted for 60 selected patients who had visited Sunlin Hospital between January 2008 and August 2008. Patients were classified into 3 groups; an obese group whose body mass index (BMI) was > the 95th percentile, an overweight group whose BMI was > the 85th percentile but less than the 95th percentile, and a normal group whose BMI was below the 85th percentile. Overall mean BP, day and night BP and BP load were measured by ABPM.\n"
],
"offsets": [
[
0,
465
]
]
}
] | [
{
"id": "PMC-2790131-sec-02_T1",
"type": "Organism_subdivision",
"text": [
"body"
],
"offsets": [
[
196,
200
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-10620704 | PMID-10620704 | [
{
"id": "PMID-10620704__text",
"type": "abstract",
"text": [
"Phosphatidyl serine exposure during apoptosis precedes release of cytochrome c and decrease in mitochondrial transmembrane potential.\nTime kinetics of phosphatidyl serine (PS) exposure were compared to other apoptotic parameters following different apoptotic stimuli. Our data indicate that anti-Fas treatment of L929sAhFas cells results in rapid exposure of PS, which precedes decrease in mitochondrial transmembrane potential (DeltaPsi(m)) and release of cytochrome c, indicating that PS exposure occurs independently of these mitochondrial events. Also during TNF-, etoposide- or staurosporine-mediated apoptosis in PC60 RI/RII cells, PS-positive cells were observed before they had a decreased DeltaPsi(m). However, during growth factor depletion-induced death of 32D cells, both phenomena seemed to occur at the same time.\n"
],
"offsets": [
[
0,
828
]
]
}
] | [
{
"id": "PMID-10620704_T1",
"type": "Cellular_component",
"text": [
"mitochondrial transmembrane"
],
"offsets": [
[
95,
122
]
],
"normalized": []
},
{
"id": "PMID-10620704_T2",
"type": "Cell",
"text": [
"L929sAhFas cells"
],
"offsets": [
[
313,
329
]
],
"normalized": []
},
{
"id": "PMID-10620704_T3",
"type": "Cellular_component",
"text": [
"mitochondrial transmembrane"
],
"offsets": [
[
390,
417
]
],
"normalized": []
},
{
"id": "PMID-10620704_T4",
"type": "Cellular_component",
"text": [
"mitochondrial"
],
"offsets": [
[
529,
542
]
],
"normalized": []
},
{
"id": "PMID-10620704_T5",
"type": "Cell",
"text": [
"PC60 RI/RII cells"
],
"offsets": [
[
619,
636
]
],
"normalized": []
},
{
"id": "PMID-10620704_T6",
"type": "Cell",
"text": [
"PS-positive cells"
],
"offsets": [
[
638,
655
]
],
"normalized": []
},
{
"id": "PMID-10620704_T7",
"type": "Cell",
"text": [
"32D cells"
],
"offsets": [
[
768,
777
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17617824 | PMID-17617824 | [
{
"id": "PMID-17617824__text",
"type": "abstract",
"text": [
"Rapid mixing between old and new C pools in the canopy of mature forest trees.\nStable C isotope signals in plant tissues became a key tool in explaining growth responses to the environment. The technique is based on the fundamental assumption that the isotopic composition of a given unit of tissue (e.g. a tree ring) reflects the specific C uptake conditions in the leaf at a given time. Beyond the methodological implications of any deviation from this assumption, it is of physiological interest whether new C is transferred directly from sources (a photosynthesizing leaf) to structural sinks (e.g. adjacent stem tissue), or inherently passes through existing (mobile) C pools, which may be of variable (older) age. Here, we explore the fate of (13)C-labelled photosynthates in the crowns of a 30-35 m tall, mixed forest using a canopy crane. In all nine study species labelled C reached woody tissue within 2-9 h after labelling. Four months later, very small signals were left in branch wood of Tilia suggesting that low mixing of new, labelled C with old C had taken place. In contrast, signals in Fagus and Quercus had increased, indicating more intense mixing. This species-specific mixing of new with old C pools is likely to mask year- or season-specific linkages between tree ring formation and climate and has considerable implications for climate reconstruction using stable isotopes as proxies for past climatic conditions.\n"
],
"offsets": [
[
0,
1439
]
]
}
] | [
{
"id": "PMID-17617824_T1",
"type": "Tissue",
"text": [
"tissues"
],
"offsets": [
[
113,
120
]
],
"normalized": []
},
{
"id": "PMID-17617824_T2",
"type": "Tissue",
"text": [
"tissue"
],
"offsets": [
[
292,
298
]
],
"normalized": []
},
{
"id": "PMID-17617824_T3",
"type": "Tissue",
"text": [
"tree ring"
],
"offsets": [
[
307,
316
]
],
"normalized": []
},
{
"id": "PMID-17617824_T4",
"type": "Organ",
"text": [
"leaf"
],
"offsets": [
[
367,
371
]
],
"normalized": []
},
{
"id": "PMID-17617824_T5",
"type": "Organ",
"text": [
"leaf"
],
"offsets": [
[
571,
575
]
],
"normalized": []
},
{
"id": "PMID-17617824_T6",
"type": "Tissue",
"text": [
"stem tissue"
],
"offsets": [
[
612,
623
]
],
"normalized": []
},
{
"id": "PMID-17617824_T7",
"type": "Organism_subdivision",
"text": [
"crowns"
],
"offsets": [
[
786,
792
]
],
"normalized": []
},
{
"id": "PMID-17617824_T8",
"type": "Tissue",
"text": [
"woody tissue"
],
"offsets": [
[
892,
904
]
],
"normalized": []
},
{
"id": "PMID-17617824_T9",
"type": "Tissue",
"text": [
"tree ring"
],
"offsets": [
[
1283,
1292
]
],
"normalized": []
},
{
"id": "PMID-17617824_T10",
"type": "Multi-tissue_structure",
"text": [
"branch wood"
],
"offsets": [
[
986,
997
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-3274927-sec-07 | PMC-3274927-sec-07 | [
{
"id": "PMC-3274927-sec-07__text",
"type": "sec",
"text": [
"Supplementary Material\nCrystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812002796/hg5166sup1.cif\nStructure factors: contains datablock(s) I. DOI: 10.1107/S1600536812002796/hg5166Isup2.hkl\nAdditional supplementary materials: crystallographic information; 3D view; checkCIF report\n"
],
"offsets": [
[
0,
303
]
]
}
] | [] | [] | [] | [] |
PMID-8182638 | PMID-8182638 | [
{
"id": "PMID-8182638__text",
"type": "abstract",
"text": [
"Distribution and predictors of depressive symptoms in osteoarthritis.\nOBJECTIVE:\nTo determine the prevalence and correlates of depressive symptoms in a sample of elderly persons with osteoarthritis (OA).\nMETHODS:\nSecondary analysis of cross sectional interview data from 108 community living persons age 50 or over who met American College of Rheumatology clinical criteria for OA of the hip and/or knee.\nRESULTS:\nThe prevalence of substantial depressive symptomatology appeared to be no greater than would be expected in the general population for this age group. However, persons currently under a physician's care for OA were significantly more depressed than those not under care, and, with the exception of those who had post-high school education, depression was a better predictor of being under care than OA symptoms. The direct and interactive effects of 3 variables--education, age and self-perceived impact of the OA problem--were found to explain 40% of variance in depression scores in the total sample and 50% among those currently receiving care. Younger and less educated subjects had relatively more depressive symptoms and, furthermore, in this subgroup the correlation between OA impact and depression was high.\nCONCLUSIONS:\nThe importance of assessing depression in persons who seek care for OA is supported. Furthermore, our results suggest that the observed relationship between education and arthritis outcomes could be mediated, at least in part, by depression.\n"
],
"offsets": [
[
0,
1486
]
]
}
] | [
{
"id": "PMID-8182638_T1",
"type": "Organism_subdivision",
"text": [
"hip"
],
"offsets": [
[
388,
391
]
],
"normalized": []
},
{
"id": "PMID-8182638_T2",
"type": "Organism_subdivision",
"text": [
"knee"
],
"offsets": [
[
399,
403
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2858094-sec-14 | PMC-2858094-sec-14 | [
{
"id": "PMC-2858094-sec-14__text",
"type": "sec",
"text": [
"Calcium intake and effects on QUS T-score\nFigure 5 shows the amounts of dietary calcium intake according to menopausal status. Calcium consumption in most groups, like that in the study population as a whole, was inadequate. Fewer than one third of premenopausal and postmenopausal women received more than 800 mg calcium daily, and fewer than 16% of premenopausal women in the 50-59 age decade (n = 38) consumed more than 800 mg calcium daily.\nFigure 5\nDaily calcium intake in premenopausal and postmenopausal women. This figure depicts the daily amounts of dietary calcium intake (and percent) according to menopausal status using 800 mg daily as cut off point.\nQUS T-score were then calculated according to daily calcium intake in all premenopausal and postmenopausal activity groups using 800 mg daily calcium as cutoff point. As shown in Tables 3 and 4 and Figure 6, premenopausal women who were systematically active and consumed more than 800 mg calcium daily had significantly higher QUS T-scores compared with all other activity groups (p < 0.05). Among systematically active premenopausal women who received more than 800 mg calcium per day, this difference was separately significant verses sedentary (p = 0.028) and moderately active (p = 0.04) women. In contrast, postmenopausal women showed no difference in QUS T-scores regardless of the amount of daily calcium intake.\nFigure 6\nSynergy between physical activity and dietary calcium intake in women consuming calcium amounts greater than 800 mg/day. This graphic depicts mean QUS T-score values calculated according to daily calcium intake in all premenopausal and postmenopausal activity groups using 800 mg daily as cut off point (for statistical significant values see text).\n"
],
"offsets": [
[
0,
1744
]
]
}
] | [] | [] | [] | [] |
PMID-19318806 | PMID-19318806 | [
{
"id": "PMID-19318806__text",
"type": "abstract",
"text": [
"The semaphorin 7A receptor Plexin C1 is lost during melanoma metastasis.\nThe transformation of normal melanocytes, or melanocyte stem cells, to melanoma, is a complex process involving multiple mechanisms. Loss of tumor suppressor proteins, which function as brakes on cell growth, migration, or cell survival, was recognized early on as an important mechanism for initiation and progression of melanoma. Semaphorins and their cognate receptors, Plexins and neuropilins, are involved in neuronal pathfinding, immune function, and tumor progression through effects on blood vessel growth and cell migration. Semaphorin 7A (Sema7A) is a membrane-linked semaphorin that is expressed by human keratinocytes, and we have shown that Sema7A binds to human melanocytes through beta1-integrins and the Plexin C1 receptor. Functional studies showed that Sema7A stimulates cytoskeletal reorganization in human melanocytes, resulting in adhesion and dendrite formation. Downstream targets of Plexin C1 signaling in human melanocytes include cofilin and LIM kinase II, both of which are critical mediators of cell adhesion and migration. In this report, we analyzed the expression of Plexin C1 using immunohistochemistry on sections of primary and matched metastatic lesions from 19 subjects and in a large melanoma tumor microarray. Our data show a significant loss of Plexin C1 in metastatic melanoma compared with primary melanoma, suggesting the possibility that the Plexin C1 receptor is a tumor suppressor protein for melanoma.\n"
],
"offsets": [
[
0,
1521
]
]
}
] | [
{
"id": "PMID-19318806_T3",
"type": "Cancer",
"text": [
"melanoma"
],
"offsets": [
[
52,
60
]
],
"normalized": []
},
{
"id": "PMID-19318806_T4",
"type": "Cell",
"text": [
"melanocytes"
],
"offsets": [
[
102,
113
]
],
"normalized": []
},
{
"id": "PMID-19318806_T5",
"type": "Cell",
"text": [
"melanocyte stem cells"
],
"offsets": [
[
118,
139
]
],
"normalized": []
},
{
"id": "PMID-19318806_T6",
"type": "Cancer",
"text": [
"melanoma"
],
"offsets": [
[
144,
152
]
],
"normalized": []
},
{
"id": "PMID-19318806_T7",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
214,
219
]
],
"normalized": []
},
{
"id": "PMID-19318806_T8",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
269,
273
]
],
"normalized": []
},
{
"id": "PMID-19318806_T9",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
296,
300
]
],
"normalized": []
},
{
"id": "PMID-19318806_T10",
"type": "Cancer",
"text": [
"melanoma"
],
"offsets": [
[
395,
403
]
],
"normalized": []
},
{
"id": "PMID-19318806_T14",
"type": "Cell",
"text": [
"neuronal"
],
"offsets": [
[
487,
495
]
],
"normalized": []
},
{
"id": "PMID-19318806_T15",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
530,
535
]
],
"normalized": []
},
{
"id": "PMID-19318806_T16",
"type": "Multi-tissue_structure",
"text": [
"blood vessel"
],
"offsets": [
[
567,
579
]
],
"normalized": []
},
{
"id": "PMID-19318806_T17",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
591,
595
]
],
"normalized": []
},
{
"id": "PMID-19318806_T20",
"type": "Cellular_component",
"text": [
"membrane"
],
"offsets": [
[
635,
643
]
],
"normalized": []
},
{
"id": "PMID-19318806_T23",
"type": "Cell",
"text": [
"keratinocytes"
],
"offsets": [
[
689,
702
]
],
"normalized": []
},
{
"id": "PMID-19318806_T26",
"type": "Cell",
"text": [
"melanocytes"
],
"offsets": [
[
749,
760
]
],
"normalized": []
},
{
"id": "PMID-19318806_T30",
"type": "Cellular_component",
"text": [
"cytoskeletal"
],
"offsets": [
[
862,
874
]
],
"normalized": []
},
{
"id": "PMID-19318806_T32",
"type": "Cell",
"text": [
"melanocytes"
],
"offsets": [
[
899,
910
]
],
"normalized": []
},
{
"id": "PMID-19318806_T33",
"type": "Cellular_component",
"text": [
"dendrite"
],
"offsets": [
[
938,
946
]
],
"normalized": []
},
{
"id": "PMID-19318806_T36",
"type": "Cell",
"text": [
"melanocytes"
],
"offsets": [
[
1009,
1020
]
],
"normalized": []
},
{
"id": "PMID-19318806_T39",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1096,
1100
]
],
"normalized": []
},
{
"id": "PMID-19318806_T41",
"type": "Cancer",
"text": [
"metastatic lesions"
],
"offsets": [
[
1243,
1261
]
],
"normalized": []
},
{
"id": "PMID-19318806_T42",
"type": "Cancer",
"text": [
"melanoma tumor"
],
"offsets": [
[
1294,
1308
]
],
"normalized": []
},
{
"id": "PMID-19318806_T44",
"type": "Cancer",
"text": [
"metastatic melanoma"
],
"offsets": [
[
1370,
1389
]
],
"normalized": []
},
{
"id": "PMID-19318806_T45",
"type": "Cancer",
"text": [
"primary melanoma"
],
"offsets": [
[
1404,
1420
]
],
"normalized": []
},
{
"id": "PMID-19318806_T47",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
1482,
1487
]
],
"normalized": []
},
{
"id": "PMID-19318806_T48",
"type": "Cancer",
"text": [
"melanoma"
],
"offsets": [
[
1511,
1519
]
],
"normalized": []
},
{
"id": "PMID-19318806_T77",
"type": "Cancer",
"text": [
"sections"
],
"offsets": [
[
1211,
1219
]
],
"normalized": []
},
{
"id": "PMID-19318806_T1",
"type": "Cancer",
"text": [
"primary"
],
"offsets": [
[
1223,
1230
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-1877751 | PMID-1877751 | [
{
"id": "PMID-1877751__text",
"type": "abstract",
"text": [
"Quantitative retention-biological activity relationship study by micellar liquid chromatography.\nIn a previous paper, the usefulness of micellar liquid chromatography (MLC) in predicting octanol-water partition coefficients of organic compounds was reported. This paper is the first successful report of a quantitative retention-activity relationship study using the retention factor in MLC for predicting the biological activity of a group of phenolic compounds. Excellent correlation was obtained between the capacity factor in MLC and the bioactivity (measured as log 1/C, where C is the 50% inhibitory growth concentration) of 26 para-substituted phenols. A single MLC retention parameter is capable of describing the bioactivity of phenols, while three conventional molecular descriptors (log P(ow), pKa, and R) are needed to achieve a similar correlation. This indicates that both hydrophobic and electronic interactions are incorporated in a single MLC retention parameter, which is due to the amphiphilic nature of surfactants in the system. In situations like this, QRAR is a suitable alternative to QSAR since measuring MLC retention is much easier than measuring different molecular descriptors needed to build the QSAR model. Addition of 10% 2-propanol to a micellar system (hybrid system) proved to be the best chromatographic system for the best estimation of the phenols bioactivity. Other chromatographic factors such as pH and stationary phase also showed significant effect on the correlation between capacity factor k' and log 1/C.\n"
],
"offsets": [
[
0,
1551
]
]
}
] | [] | [] | [] | [] |
PMID-6229539 | PMID-6229539 | [
{
"id": "PMID-6229539__text",
"type": "abstract",
"text": [
"Phosphorylation-induced mobility shift in phospholamban in sodium dodecyl sulfate-polyacrylamide gels. Evidence for a protein structure consisting of multiple identical phosphorylatable subunits.\nPhosphorylation of purified phospholamban isolated from canine cardiac sarcoplasmic reticulum vesicles decreased the electrophoretic mobility of the protein in sodium dodecyl sulfate (SDS)-polyacrylamide gels. Different mobility forms of phospholamban in SDS gels were visualized both by direct protein staining and by autoradiography. Unphosphorylated phospholamban migrated with an apparent Mr = 25,000 in SDS gels; maximal phosphorylation of phospholamban by cAMP- or Ca2+-calmodulin-dependent protein kinase increased the apparent Mr to 27,000. Partial phosphorylation of phospholamban by either protein kinase gave intermediate mobility forms of molecular weights between 25,000 and 27,000, suggesting that more than one phosphorylation site was present on the holoprotein for each activity. Boiling of phospholamban in SDS dissociated the holoprotein into an apparently homogeneous class of low molecular weight \"monomers.\" Only two mobility forms of monomeric phospholamban were observed in SDS gels after phosphorylation by cAMP-dependent protein kinase, corresponding to 9-kDa dephospho- and 11-kDa phosphoproteins. All of the 9-kDa protein could be phosphorylated and converted into the 11-kDa mobility form, suggesting the presence of only one site of phosphorylation on a single type of monomer for cAMP-dependent protein kinase. Simultaneous phosphorylation of monomeric phospholamban by cAMP-dependent protein kinase and Ca2+-calmodulin-dependent protein kinase gave an additional mobility form of the protein, suggesting that different sites of phosphorylation were present for each activity on each monomer. Incomplete dissociation of the holoprotein by boiling it in a relatively low concentration of SDS facilitated the detection of five major mobility forms of the protein in SDS gels, and the mobilities of all of these forms were decreased by phosphorylation. We propose that the high molecular weight form of phospholamban is a multimer of electrophoretically indistinguishable monomers, each of which contains a different phosphorylation site for cAMP-dependent protein kinase activity and Ca2+-calmodulin-dependent protein kinase activity. Phosphorylation of phospholamban at multiple sites is responsible for the various mobility forms of the holoprotein detected in SDS-polyacrylamide gels.\n"
],
"offsets": [
[
0,
2513
]
]
}
] | [
{
"id": "PMID-6229539_T1",
"type": "Cellular_component",
"text": [
"cardiac sarcoplasmic reticulum vesicles"
],
"offsets": [
[
259,
298
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-16406676 | PMID-16406676 | [
{
"id": "PMID-16406676__text",
"type": "abstract",
"text": [
"Regulation of tumor angiogenesis by thrombospondin-1.\nAngiogenesis plays a critical role in the growth and metastasis of tumors. Thrombospondin-1 (TSP-1) is a potent angiogenesis inhibitor, and down-regulation of TSP-1 has been suggested to alter tumor growth by modulating angiogenesis in a variety of tumor types. Expression of TSP-1 is up-regulated by the tumor suppressor gene, p53, and down-regulated by oncogenes such as Myc and Ras. TSP-1 inhibits angiogenesis by inhibiting endothelial cell migration and proliferation and by inducing apoptosis. In addition, activation of transforming growth factor beta (TGF-beta) by TSP-1 plays a crucial role in the regulation of tumor progression. An understanding of the molecular basis of TSP-1-mediated inhibition of angiogenesis and tumor progression will aid in the development of novel therapeutics for the treatment of cancer.\n"
],
"offsets": [
[
0,
880
]
]
}
] | [
{
"id": "PMID-16406676_T1",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
14,
19
]
],
"normalized": []
},
{
"id": "PMID-16406676_T3",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
121,
127
]
],
"normalized": []
},
{
"id": "PMID-16406676_T7",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
247,
252
]
],
"normalized": []
},
{
"id": "PMID-16406676_T8",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
303,
308
]
],
"normalized": []
},
{
"id": "PMID-16406676_T10",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
359,
364
]
],
"normalized": []
},
{
"id": "PMID-16406676_T15",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
482,
498
]
],
"normalized": []
},
{
"id": "PMID-16406676_T19",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
675,
680
]
],
"normalized": []
},
{
"id": "PMID-16406676_T21",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
783,
788
]
],
"normalized": []
},
{
"id": "PMID-16406676_T22",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
872,
878
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-1274342-sec-02 | PMC-1274342-sec-02 | [
{
"id": "PMC-1274342-sec-02__text",
"type": "sec",
"text": [
"Results\nOFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG >= 150 [MetS+TG, (n = 22)] or <150 mg/dl [MetS-TG (n = 11)], and into those with or without hypertension [MetS+HTN (n = 24), MetS-HTN (n = 9), respectively]. TG concentrations were measured before and at 4, 6 and 8 h after OFTT and the postprandial response was quantified using the area under the curve (AUC) for TG.\nThe postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 +/- 1016 vs. 1620 +/- 494 and 1019 +/- 280, respectively, p <= 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001).\n"
],
"offsets": [
[
0,
1106
]
]
}
] | [] | [] | [] | [] |
PMID-765945 | PMID-765945 | [
{
"id": "PMID-765945__text",
"type": "abstract",
"text": [
"Central nervous system infection with Eikenella corrodens: report of two cases.\nTwo cases of central nervous system infections from which E. corrodens has been isolated are reported. The portals of entry, clinical course, and antimicrobial responses conform to other reports in the literature. The importance of obtaining careful anaerobic cultures is emphasized.\n"
],
"offsets": [
[
0,
364
]
]
}
] | [
{
"id": "PMID-765945_T1",
"type": "Anatomical_system",
"text": [
"Central nervous system"
],
"offsets": [
[
0,
22
]
],
"normalized": []
},
{
"id": "PMID-765945_T2",
"type": "Anatomical_system",
"text": [
"central nervous system"
],
"offsets": [
[
93,
115
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2908855-caption-01 | PMC-2908855-caption-01 | [
{
"id": "PMC-2908855-caption-01__text",
"type": "caption",
"text": [
"The pedigree of a Korean family with macular dystrophy demonstrating the characteristics of an autosomal dominant inheritance trait.\n"
],
"offsets": [
[
0,
133
]
]
}
] | [
{
"id": "PMC-2908855-caption-01_T1",
"type": "Tissue",
"text": [
"macular"
],
"offsets": [
[
37,
44
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-20460116 | PMID-20460116 | [
{
"id": "PMID-20460116__text",
"type": "abstract",
"text": [
"Pain assessment by continuous EEG: association between subjective perception of tonic pain and peak frequency of alpha oscillations during stimulation and at rest.\nRecordings of neurophysiological brain responses to noxious stimuli have been traditionally based on short stimuli, in the order of milliseconds, which induce distinct event-related potentials (ERPs). However, using such stimuli in the experimental setting is disadvantageous as they are too brief to faithfully simulate clinical pain. We aimed at utilizing continuous EEG to investigate the properties of peak alpha frequency (PAF) as an objective cortical measure associated with subjective perception of tonic pain. Five minute long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with peak frequencies of alpha power-curves derived from central, temporal and frontal electrodes. NPSs and PAFs remained stable throughout the recording conditions (RM-ANOVAs; Ps>0.51). In the noxious condition, PAFs obtained at the bilateral temporal scalp were correlated with NPSs (Ps<0.001). Moreover, resting-state PAFs recorded at the bilateral temporal scalp were correlated with NPSs reported during the noxious condition (Ps<0.01). These psychophysical-neurophysiological relations attest to the properties of PAF as a novel cortical objective measure of subjective perception of tonic pain. Moreover, resting-state PAFs might hold inherent pain modulation attributes, possibly enabling the prediction of individual responsiveness to prolonged pain. The relevance of PAF to the neural processing of tonic pain may indicate its potential to advance pain research as well as clinical pain characterization.\n"
],
"offsets": [
[
0,
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]
]
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] | [
{
"id": "PMID-20460116_T1",
"type": "Organ",
"text": [
"brain"
],
"offsets": [
[
197,
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]
],
"normalized": []
},
{
"id": "PMID-20460116_T2",
"type": "Multi-tissue_structure",
"text": [
"cortical"
],
"offsets": [
[
613,
621
]
],
"normalized": []
},
{
"id": "PMID-20460116_T3",
"type": "Multi-tissue_structure",
"text": [
"cortical"
],
"offsets": [
[
1514,
1522
]
],
"normalized": []
},
{
"id": "PMID-20460116_T4",
"type": "Multi-tissue_structure",
"text": [
"neural"
],
"offsets": [
[
1767,
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]
],
"normalized": []
},
{
"id": "PMID-20460116_T5",
"type": "Multi-tissue_structure",
"text": [
"temporal scalp"
],
"offsets": [
[
1223,
1237
]
],
"normalized": []
},
{
"id": "PMID-20460116_T6",
"type": "Multi-tissue_structure",
"text": [
"temporal scalp"
],
"offsets": [
[
1331,
1345
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-3210127-sec-05 | PMC-3210127-sec-05 | [
{
"id": "PMC-3210127-sec-05__text",
"type": "sec",
"text": [
"Discussion\nIn our previous work, we considered in CD families the risk to develop the disease according to a specific HLA haplotypes, obtaining a risk range from 0.01 to >=0.20 [1]. In the present study we evaluated the role of 3 non-HLA genetic markers to influence the CD risk in first relatives of CD affected children.\nWe collected data on families with at least one CD-affected among offspring. This family set helped to evaluate the association between SNPs and CD (TDT on parents-offspring trios) and to estimate the risk of CD in the other sibs. The TDT design provides robustness to population stratification and mitigation of the possible confounding effect of environmental factors, because all family members share the same environment [16].\nTen SNPs, selected from those previously found to be associated with CD by GWAS [13], were successfully genotyped. In our population three SNPs resulted significantly associated with CD (those in LPP, RGS1 and REL genes) and the other seven investigated SNPs, even if not statistically associated with CD, showed always an higher frequency of the previously reported risk alleles [13] in affected subjects than in controls.\nThe three genes selected appear to be appealing for the pathogenesis of CD. LPP (OR = 2.36; p<0.001) was reported to be highly expressed in small intestinal mucosa and may have a structural role at sites of cell adhesion in maintaining cell shape and motility [7]. RGS1 (OR = 1.75; p = 0.025) belongs to a family of RGS genes. It attenuates the signaling activity of G-proteins, blocking the homing of Intra Epithelial Lymphocytes (IELs), and it is specifically expressed both in human small intestinal mucosa and in murine IELs, key players in the development of human CD villous atrophy [7], [17]. REL (OR = 1.66; p = 0.034) is a subunit of NF-kB complex, implicated in T cell differentiation [18] and it appears to be a key molecule regulating inflammation and the switch from tolerance to autoimmunity [19]. It is interesting to note that our data confirm previous pathogenetic implications reported in literature of these SNPs with CD as well as with other autoimmune diseases [20].\nBy the Bayesian approach we calculated a ranking score (BS) among the sibs. However, it should be considered that BS is not a plain disease risk, rather a method to rank different genotypes according to their contribution to make an individual susceptible to CD. For instance, some of our BS are very near to 1, nevertheless none of the considered genotypes could give a 100% risk to develop the disease. In other terms, we considered the BS as a ranking measure, only stating that a given genotype could assign a higher risk than another genotype but does not allow a quantitative measure of the risk difference (2-fold, 3-fold, etc). However, even if the addition of only 3 SNPs to HLA could be considered at \"minor effect\" [13], we demonstrated that they could significantly improve the prediction of CD risk in sibs, in terms of diagnostic sensitivity and negative predictive value. So, in a cohort of CD families, our data confirm that non-HLA SNPs evaluation is an usefull diagnostic tool in CD risk evaluation as a previous study showed in CD unrelated subjects [14].\nCD, on the basis of the actual knowledge, cannot be exactly predicted by genetic testing, but a reliable probabilistic method might be associated to careful surveillance of infants carrying the higher risk. This will help to significantly reduce the heavy load of anxiety and pain associated with the appearance of symptoms of CD, by anticipating, with simple serological tests, the clinical appearance of the disease.\nTo improve the possibility to identify high risk patients in CD families we propose in alternative to the classical HLA classification (Fig. 4, panel A) a slight improved flow-chart (Fig. 4, panel B): 1) HLA genotyping: subjects belonging to the HLA risk groups 1 and 2 will be classified as at high CD risk; 2) subjects belonging to the HLA risk groups 3 and 4, will be further investigated for our SNPs combination (LPP, REL, RGS1) in order to calculate their BS (Fig. 4, panel B). Among these latter subjects those with a BS >= the median value will be classified at high risk; 3) subjects belonging to the HLA risk group 5 will be considered at low CD risk. All CD familials belonging to the above high risk groups (HLA group 1-2 and HLA group 3-4 with BS >= median) will be undergo a strict surveillance.\n10.1371/journal.pone.0026920.g004 Figure 4\nClassification flow-chart.\nIn panel A the classical HLA-based classification. In panel B the proposed BS-based classification considering the genotypes of HLA plus LPP, RGS1 and REL SNPs.\nOne of the limitation of our cohort family study could be the sample size, which may have not allowed to explore genes at smaller effect, so explaining the lack of association between SNPs in TAGAP, IL2/IL21, OLIG3, CCR, SH2B3, IL12A and IL12A/SCHIP1 genes with CD although the trend observed in previous studies in unrelated CD patients was confirmed [13]. In the main time the homogeneity of the genetic and environmental domains in the tested families allows to explore risk factors within a controlled cohort. A second limit of the study is the relatively short (6 years) follow up of the sibship, which could cause an underestimation of the disease development at later ages. Our aim is to go on with the monitoring of these families in the next years.\nIn conclusion, the estimate of the CD risk by HLA+SNPs approach, even if not applicable to prevention, could be a precious tool improving CD diagnosis respect to the only HLA (NPV: 95% vs 91%, and DS: 79% vs 45%), in the cohort of first degree relatives. In fact in clinical practice the absence of HLA risk groups 1 or 2, allows to exclude the disease with high probability, while testing the three SNPs in HLA groups 3 or 4 could represent a further tool to identify less frequent CD cases. So, an infant with high HLA+SNPs score even if belonging to HLA low risk groups, shall undergo a simple surveillance system to allow proper diagnosis and treatment before the full blow disease appears.\n"
],
"offsets": [
[
0,
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]
]
}
] | [
{
"id": "PMC-3210127-sec-05_T1",
"type": "Multi-tissue_structure",
"text": [
"small intestinal mucosa"
],
"offsets": [
[
1318,
1341
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T2",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1414,
1418
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T3",
"type": "Cell",
"text": [
"Intra Epithelial Lymphocytes"
],
"offsets": [
[
1580,
1608
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T4",
"type": "Multi-tissue_structure",
"text": [
"small intestinal mucosa"
],
"offsets": [
[
1664,
1687
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T5",
"type": "Cell",
"text": [
"T cell"
],
"offsets": [
[
1850,
1856
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T6",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1385,
1389
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T7",
"type": "Cellular_component",
"text": [
"sites"
],
"offsets": [
[
1376,
1381
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T8",
"type": "Cell",
"text": [
"IELs"
],
"offsets": [
[
1610,
1614
]
],
"normalized": []
},
{
"id": "PMC-3210127-sec-05_T9",
"type": "Cell",
"text": [
"IELs"
],
"offsets": [
[
1702,
1706
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2959025-sec-14 | PMC-2959025-sec-14 | [
{
"id": "PMC-2959025-sec-14__text",
"type": "sec",
"text": [
"Histology of the lung\nThe left lung was fixed by gentle infusion of fixative (4% paraformaldehyde) through the tracheal cannula [24]. After excision, the lung was immersed in a fresh fixative for 2 h. The lung lobe was embedded in paraffin and cut into 3 mum transverse sections, followed by immunohistochemical and chemical staining. Photomicrographs were captured using KS400 image analyze platform (Zeiss, Oberkochen, Germany) and analyzed quantitatively.\n"
],
"offsets": [
[
0,
459
]
]
}
] | [
{
"id": "PMC-2959025-sec-14_T1",
"type": "Organ",
"text": [
"lung"
],
"offsets": [
[
17,
21
]
],
"normalized": []
},
{
"id": "PMC-2959025-sec-14_T2",
"type": "Organ",
"text": [
"left lung"
],
"offsets": [
[
26,
35
]
],
"normalized": []
},
{
"id": "PMC-2959025-sec-14_T3",
"type": "Multi-tissue_structure",
"text": [
"tracheal"
],
"offsets": [
[
111,
119
]
],
"normalized": []
},
{
"id": "PMC-2959025-sec-14_T4",
"type": "Organ",
"text": [
"lung"
],
"offsets": [
[
154,
158
]
],
"normalized": []
},
{
"id": "PMC-2959025-sec-14_T5",
"type": "Multi-tissue_structure",
"text": [
"lung lobe"
],
"offsets": [
[
205,
214
]
],
"normalized": []
},
{
"id": "PMC-2959025-sec-14_T6",
"type": "Multi-tissue_structure",
"text": [
"sections"
],
"offsets": [
[
270,
278
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-911696 | PMID-911696 | [
{
"id": "PMID-911696__text",
"type": "abstract",
"text": [
"Some findings concerning beliefs about alcoholism.\nThe beliefs that alcoholics hold about alcoholism and themselves, and the beliefs that hospital staff and other personnel hold about alcoholism, were investigated using methods derived from the repertory grid, with anonymous facial photographs as elements. Data are presented as to the degree of association of various characteristics with alcoholism for the various groups. Differences between groups, and overall changes during group psychotherapy for patients were small. The relative contribution of personal and shared aspects of belief was measured. It was found that the agreement between groups was high and closely similar to that predictable from consistencies within groups. It is concluded that there may be a very general stereotype of alcoholism, consistent with a personality disorder concept which is implicitly held even in the face of nominal acceptance of other concepts. The self constructs of alcoholics were found to be complex. In a small follow-up study of patients, there was found to be a relationship of poor outcome with tightness of construing for key constructs after psychotherapy. The implications of the findings are discussed briefly.\n"
],
"offsets": [
[
0,
1220
]
]
}
] | [
{
"id": "PMID-911696_T1",
"type": "Organism_subdivision",
"text": [
"facial"
],
"offsets": [
[
276,
282
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-6776697 | PMID-6776697 | [
{
"id": "PMID-6776697__text",
"type": "abstract",
"text": [
"[In vitro studies of the thyroid gland regulation principles and their evaluation].\nThe free fractions of the thyroid hormone further the metabolism of the body cells and regulate the synthesis of the thyroid hormone. Once the level of FT3 and FT4 decreases. With the help of a liberation of the hormone stimulating the thyroid gland from the anterior lobe of the pituitary gland the lack of thyroid hormone is corrected. The synthesis and secretion of the thyroid gland stimulating hormone is induced by the thyreotropin releasing hormone which is given by the hypothalamus. Moreover, the organism is able as needed to carry out the monodiodation of LT4 to biologically active LT3 or biologically inactive so-called revers T3 (RT3). The estimation of thyroid gland stimulating hormone before and 30 minutes after intravenous application of thyreotropin releasing hormone has its main importance for the early recognition of a disturbance of the regulating circle hypophysis-thyroid gland, above all in the diagnosis of clinically not yet manifest clinical pictures, such as the latent hypothyreosis and the latent hyperthyreosis, respectively (Basedow hyperthyreosis and thyroidal autonomy). According to the questioning the estimations of the levels of the thyroid hormones and of the thyroid gland stimulating hormone should be used stepwise.\n"
],
"offsets": [
[
0,
1346
]
]
}
] | [
{
"id": "PMID-6776697_T1",
"type": "Organ",
"text": [
"thyroid gland"
],
"offsets": [
[
25,
38
]
],
"normalized": []
},
{
"id": "PMID-6776697_T3",
"type": "Cell",
"text": [
"body cells"
],
"offsets": [
[
156,
166
]
],
"normalized": []
},
{
"id": "PMID-6776697_T5",
"type": "Organ",
"text": [
"thyroid gland"
],
"offsets": [
[
320,
333
]
],
"normalized": []
},
{
"id": "PMID-6776697_T6",
"type": "Multi-tissue_structure",
"text": [
"anterior lobe"
],
"offsets": [
[
343,
356
]
],
"normalized": []
},
{
"id": "PMID-6776697_T7",
"type": "Organ",
"text": [
"pituitary gland"
],
"offsets": [
[
364,
379
]
],
"normalized": []
},
{
"id": "PMID-6776697_T9",
"type": "Organ",
"text": [
"thyroid gland"
],
"offsets": [
[
457,
470
]
],
"normalized": []
},
{
"id": "PMID-6776697_T10",
"type": "Multi-tissue_structure",
"text": [
"hypothalamus"
],
"offsets": [
[
562,
574
]
],
"normalized": []
},
{
"id": "PMID-6776697_T11",
"type": "Organ",
"text": [
"thyroid gland"
],
"offsets": [
[
752,
765
]
],
"normalized": []
},
{
"id": "PMID-6776697_T12",
"type": "Immaterial_anatomical_entity",
"text": [
"intravenous"
],
"offsets": [
[
814,
825
]
],
"normalized": []
},
{
"id": "PMID-6776697_T13",
"type": "Organ",
"text": [
"thyroid gland"
],
"offsets": [
[
975,
988
]
],
"normalized": []
},
{
"id": "PMID-6776697_T15",
"type": "Organ",
"text": [
"thyroid gland"
],
"offsets": [
[
1287,
1300
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-12753707 | PMID-12753707 | [
{
"id": "PMID-12753707__text",
"type": "abstract",
"text": [
"[Effects of Epstein-Barr virus latent membrane protein 1(EBV-LMP1) on related factors of metastasis of nasopharyngeal carcinoma cell line CNE1]. \nBACKGROUND & OBJECTIVE: It has been proved that Epstein- Barr virus (EBV) latent membrane protein 1 (EBV-LMP1) can induce the expression of matrix metalloproteinase-9 (MMP-9). This study was designed to investigate the effect of EBV-LMP1 on related factors of metastasis of nasopharyngeal carcinoma cell line CNE1. METHODS: Expression of MMP-9 was studied in human NPC cell lines cultured in vitro: CNE1 (well differentiated cell line of NPC) and CNE1-GL (CNE1 cell line transfected with an eukaryotic LMP1-expression plasmid) by SP immunohistochemistry and Western blot analysis. Cell-matrix adhesion assay was used to study the adhesive ability of CNE1-GL cells. The effects of LMP1 on the invasion and migration of CNE1 cells were investigated by transwell methods. RESULTS: MMP-9 was expressed in both cell lines but the intensity of the staining was different. The positive rates of expression of MMP-9 in CNE1 and CNE1-GL cells were 30.2% and 98.2%, respectively (P< 0.05). The increased expression of MMP-9 was also shown in CNE1-GL cells by Western blot analysis. Cell-matrix adhesion assay showed that the adhesive ability of CNE1-GL with the matrix (mean A value: 1.2508+/-0.0711) was higher than that of CNE1 cell (mean A value: 0.9519+/-0.068) (P< 0.001). Invasion assay and migration assay showed that the invasion and migration of CNE1-GL cell were higher than those of CNE1 cells (P< 0.01). CONCLUSION: The transfection of LMP1 can increase the expression of MMP-9 in CNE1 cells. Abilities of adhesion, migration, and invasion of CNE1 cell were induced by LMP1. It is suggested that MMP-9 may have a role in the LMP1-induced acceleration of invasion and metastasis of NPC cells.\n"
],
"offsets": [
[
0,
1844
]
]
}
] | [
{
"id": "PMID-12753707_T5",
"type": "Cell",
"text": [
"nasopharyngeal carcinoma cell line CNE1"
],
"offsets": [
[
103,
142
]
],
"normalized": []
},
{
"id": "PMID-12753707_T15",
"type": "Cell",
"text": [
"nasopharyngeal carcinoma cell line CNE1"
],
"offsets": [
[
424,
463
]
],
"normalized": []
},
{
"id": "PMID-12753707_T18",
"type": "Cell",
"text": [
"NPC cell lines"
],
"offsets": [
[
515,
529
]
],
"normalized": []
},
{
"id": "PMID-12753707_T19",
"type": "Cell",
"text": [
"CNE1"
],
"offsets": [
[
549,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T20",
"type": "Cell",
"text": [
"cell line"
],
"offsets": [
[
575,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T21",
"type": "Cell",
"text": [
"NPC"
],
"offsets": [
[
588,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T22",
"type": "Cell",
"text": [
"CNE1-GL"
],
"offsets": [
[
597,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T23",
"type": "Cell",
"text": [
"CNE1 cell line"
],
"offsets": [
[
606,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T25",
"type": "Cell",
"text": [
"Cell"
],
"offsets": [
[
731,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T26",
"type": "Cellular_component",
"text": [
"matrix"
],
"offsets": [
[
736,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T27",
"type": "Cell",
"text": [
"CNE1-GL cells"
],
"offsets": [
[
800,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T29",
"type": "Cell",
"text": [
"CNE1 cells"
],
"offsets": [
[
868,
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]
],
"normalized": []
},
{
"id": "PMID-12753707_T31",
"type": "Cell",
"text": [
"cell lines"
],
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[
956,
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]
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"normalized": []
},
{
"id": "PMID-12753707_T33",
"type": "Cell",
"text": [
"CNE1"
],
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[
1061,
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]
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"id": "PMID-12753707_T34",
"type": "Cell",
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"CNE1-GL cells"
],
"offsets": [
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1070,
1083
]
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"id": "PMID-12753707_T36",
"type": "Cell",
"text": [
"CNE1-GL cells"
],
"offsets": [
[
1182,
1195
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"normalized": []
},
{
"id": "PMID-12753707_T37",
"type": "Cell",
"text": [
"Cell"
],
"offsets": [
[
1222,
1226
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"id": "PMID-12753707_T38",
"type": "Cellular_component",
"text": [
"matrix"
],
"offsets": [
[
1227,
1233
]
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"id": "PMID-12753707_T39",
"type": "Cell",
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"CNE1-GL"
],
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1285,
1292
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"id": "PMID-12753707_T40",
"type": "Cellular_component",
"text": [
"matrix"
],
"offsets": [
[
1302,
1308
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],
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"id": "PMID-12753707_T41",
"type": "Cell",
"text": [
"CNE1 cell"
],
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[
1365,
1374
]
],
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"id": "PMID-12753707_T42",
"type": "Cell",
"text": [
"CNE1-GL cell"
],
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1495,
1507
]
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"id": "PMID-12753707_T43",
"type": "Cell",
"text": [
"CNE1 cells"
],
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1534,
1544
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"normalized": []
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"id": "PMID-12753707_T46",
"type": "Cell",
"text": [
"CNE1 cells"
],
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[
1633,
1643
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"id": "PMID-12753707_T47",
"type": "Cell",
"text": [
"CNE1 cell"
],
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[
1695,
1704
]
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"normalized": []
},
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"id": "PMID-12753707_T51",
"type": "Cell",
"text": [
"NPC cells"
],
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[
1833,
1842
]
],
"normalized": []
},
{
"id": "PMID-12753707_T1",
"type": "Cellular_component",
"text": [
"plasmid"
],
"offsets": [
[
668,
675
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-20433031 | PMID-20433031 | [
{
"id": "PMID-20433031__text",
"type": "abstract",
"text": [
"Is the elimination of HIV infection within reach in the United States? Lessons from an epidemiologic transmission model.\nRecent estimates show that the transmission rate of human immunodeficiency virus (HIV) in the U.S. has substantially decreased. This raises the question, is elimination of HIV infection in the nation feasible in the foreseeable future? We demonstrate that if the HIV transmission rate were reduced by 50%, then the reproductive rate of HIV infection would drop below unity and lead to eventual elimination of infection. In recent congressional testimony, the director of the Centers for Disease Control and Prevention and others asserted that the HIV transmission rate can be halved by 2020, if not earlier, provided sufficient investment is made toward achieving this goal. We assert that if adequate investment is made and the transmission rate is in fact lowered by 50%, then the HIV reproductive rate would fall below unity, setting the stage for eventual elimination of HIV infection in the U.S.\n"
],
"offsets": [
[
0,
1022
]
]
}
] | [] | [] | [] | [] |
PMID-9503276 | PMID-9503276 | [
{
"id": "PMID-9503276__text",
"type": "abstract",
"text": [
"Clozapine-induced agranulocytosis and thrombopenia in a patient with dopaminergic psychosis.\nIn patients with Parkinson' disease and dopaminergic psychosis, clozapine treatment is recommended as the drug is free from extrapyramidal side effects and does not worsen motor symptoms of the underlying disease. The use of clozapine, however, is limited due to its hematotoxic side effects. For treatment of clozapine-induced agranulocytosis, granulocyte colony-stimulating factors (G-CSF) are recommended. We report the case of a 72-years-old male patient with clozapine-induced agranulocytosis and thrombopenia. Neutropenia was successfully treated with G-CSF, but thrombopenia persisted and resolved spontaneously after 14 days. Bone marrow toxicity of clozapine is not restricted to white cell maturation, but may also impair thrombocytopoesis.\n"
],
"offsets": [
[
0,
844
]
]
}
] | [
{
"id": "PMID-9503276_T1",
"type": "Multi-tissue_structure",
"text": [
"Bone marrow"
],
"offsets": [
[
727,
738
]
],
"normalized": []
},
{
"id": "PMID-9503276_T2",
"type": "Cell",
"text": [
"white cell"
],
"offsets": [
[
782,
792
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-21308684 | PMID-21308684 | [
{
"id": "PMID-21308684__text",
"type": "abstract",
"text": [
"Serum soluble vascular adhesion protein-1 is a valuable prognostic marker in gastric cancer. \nBACKGROUND: Vascular adhesion protein-1 (VAP-1) regulates leukocyte tissue infiltration. Elevated serum soluble VAP-1 (sVAP-1) levels occur in certain diseases having an inflammatory component. We previously showed in colorectal cancer that sVAP-1 expression is significantly higher relative to controls, and this decreased expression is associated with poor prognosis and lymph node and liver metastasis. However, sVAP-1 expression has not been described for gastric cancer. This study determines the relationship between preoperative serum sVAP-1 levels and clinicopathological features and prognosis in gastric cancer. METHODS: Preoperative serum was collected from 107 gastric cancer patients and 33 normal controls. sVAP-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: The mean sVAP-1 level for cancer patients was significantly higher relative to controls, and decreased with disease progression. Tumor size, serosal invasion, lymph node metastasis, peritoneal dissemination, and TNM classification was significantly correlated with sVAP-1 level. sVAP-1 is also an independent predictive marker for lymph node metastasis. Patients having low sVAP-1 levels had significantly poorer prognosis relative to patients having elevated sVAP-1 in all or stages I-III gastric cancer patients, respectively. CONCLUSIONS: Low sVAP-1 levels are associated with poor prognosis in gastric cancer. Determining sVAP-1 levels may be valuable for predicting prognosis and lymph node metastasis.\n"
],
"offsets": [
[
0,
1597
]
]
}
] | [
{
"id": "PMID-21308684_T1",
"type": "Organism_substance",
"text": [
"Serum"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "PMID-21308684_T3",
"type": "Cancer",
"text": [
"gastric cancer"
],
"offsets": [
[
77,
91
]
],
"normalized": []
},
{
"id": "PMID-21308684_T6",
"type": "Cell",
"text": [
"leukocyte tissue"
],
"offsets": [
[
152,
168
]
],
"normalized": []
},
{
"id": "PMID-21308684_T7",
"type": "Organism_substance",
"text": [
"serum"
],
"offsets": [
[
192,
197
]
],
"normalized": []
},
{
"id": "PMID-21308684_T10",
"type": "Cancer",
"text": [
"colorectal cancer"
],
"offsets": [
[
312,
329
]
],
"normalized": []
},
{
"id": "PMID-21308684_T12",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
467,
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]
],
"normalized": []
},
{
"id": "PMID-21308684_T13",
"type": "Organ",
"text": [
"liver"
],
"offsets": [
[
482,
487
]
],
"normalized": []
},
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"id": "PMID-21308684_T15",
"type": "Cancer",
"text": [
"gastric cancer"
],
"offsets": [
[
554,
568
]
],
"normalized": []
},
{
"id": "PMID-21308684_T16",
"type": "Organism_substance",
"text": [
"serum"
],
"offsets": [
[
630,
635
]
],
"normalized": []
},
{
"id": "PMID-21308684_T18",
"type": "Cancer",
"text": [
"gastric cancer"
],
"offsets": [
[
700,
714
]
],
"normalized": []
},
{
"id": "PMID-21308684_T19",
"type": "Organism_substance",
"text": [
"serum"
],
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[
738,
743
]
],
"normalized": []
},
{
"id": "PMID-21308684_T20",
"type": "Cancer",
"text": [
"gastric cancer"
],
"offsets": [
[
767,
781
]
],
"normalized": []
},
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"id": "PMID-21308684_T24",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
915,
921
]
],
"normalized": []
},
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"id": "PMID-21308684_T27",
"type": "Cancer",
"text": [
"Tumor"
],
"offsets": [
[
1018,
1023
]
],
"normalized": []
},
{
"id": "PMID-21308684_T28",
"type": "Multi-tissue_structure",
"text": [
"serosal"
],
"offsets": [
[
1030,
1037
]
],
"normalized": []
},
{
"id": "PMID-21308684_T29",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1048,
1058
]
],
"normalized": []
},
{
"id": "PMID-21308684_T30",
"type": "Multi-tissue_structure",
"text": [
"peritoneal"
],
"offsets": [
[
1071,
1081
]
],
"normalized": []
},
{
"id": "PMID-21308684_T33",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1220,
1230
]
],
"normalized": []
},
{
"id": "PMID-21308684_T38",
"type": "Cancer",
"text": [
"gastric cancer"
],
"offsets": [
[
1379,
1393
]
],
"normalized": []
},
{
"id": "PMID-21308684_T41",
"type": "Cancer",
"text": [
"gastric cancer"
],
"offsets": [
[
1487,
1501
]
],
"normalized": []
},
{
"id": "PMID-21308684_T43",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1574,
1584
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-7969665 | PMID-7969665 | [
{
"id": "PMID-7969665__text",
"type": "abstract",
"text": [
"Appetite regulation by serotoninergic mechanisms and effects of d-fenfluramine.\nIn this literature review, evidence is presented for the theory that the neurotransmitter, serotonin (5-hydroxytryptamine, 5HT), in medial hypothalamic centres is an important regulator for appetite and for the selection of major food constituents. High local levels of 5HT cause a reduction of appetite and a preference for protein, low levels the opposite. The main antagonistic system is noradrenergic. The drug d-fenfluramine mimics the effects of 5HT by releasing 5HT from serotoninergic nerve endings and inhibiting its neuronal re-uptake. Further experimental data prove that a high-carbohydrate, low-protein diet promotes uptake of serum tryptophan in the brain and its conversion into 5HT. Hence, this serotoninergic system may function as a self-regulatory mechanism. In patients with decreased peripheral insulin sensitivity, the system may be disturbed, causing overconsumption of carbohydrates. This is sometimes compulsive (\"carbohydrate craving\"). It may be presumed that in the treatment of obesity, in addition to the use of serotoninergic drugs, successes with reducing diets may be enhanced by including periods of high-carbohydrate, low-protein intake. It would be worthwhile to explore whether similar alimentary self-regulatory mechanisms of neurotransmitter function exist in other regulatory systems.\n"
],
"offsets": [
[
0,
1405
]
]
}
] | [
{
"id": "PMID-7969665_T1",
"type": "Multi-tissue_structure",
"text": [
"medial hypothalamic centres"
],
"offsets": [
[
212,
239
]
],
"normalized": []
},
{
"id": "PMID-7969665_T3",
"type": "Cell",
"text": [
"neuronal"
],
"offsets": [
[
606,
614
]
],
"normalized": []
},
{
"id": "PMID-7969665_T4",
"type": "Organism_substance",
"text": [
"serum"
],
"offsets": [
[
720,
725
]
],
"normalized": []
},
{
"id": "PMID-7969665_T5",
"type": "Organ",
"text": [
"brain"
],
"offsets": [
[
744,
749
]
],
"normalized": []
},
{
"id": "PMID-7969665_T2",
"type": "Cellular_component",
"text": [
"nerve endings"
],
"offsets": [
[
573,
586
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-7541555 | PMID-7541555 | [
{
"id": "PMID-7541555__text",
"type": "abstract",
"text": [
"Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. \nCytokines and growth factors induce tyrosine phosphorylation of signal transducers and activators of transcription (STATs) that directly activate gene expression. Cells stably transformed by the Src oncogene tyrosine kinase were examined for STAT protein activation. Assays of electrophoretic mobility, DNA-binding specificity, and antigenicity indicated that Stat3 or a closely related STAT family member was constitutively activated by the Src oncoprotein. Induction of this DNA-binding activity was accompanied by tyrosine phosphorylation of Stat3 and correlated with Src transformation. These findings demonstrate that Src can activate STAT signaling pathways and raise the possibility that Stat3 contributes to oncogenesis by Src.\n"
],
"offsets": [
[
0,
839
]
]
}
] | [
{
"id": "PMID-7541555_T3",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
60,
65
]
],
"normalized": []
},
{
"id": "PMID-7541555_T10",
"type": "Cell",
"text": [
"Cells"
],
"offsets": [
[
266,
271
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-21910784 | PMID-21910784 | [
{
"id": "PMID-21910784__text",
"type": "abstract",
"text": [
"Development of a mouse model for lymph node metastasis with endometrial cancer. \nControlling lymph node metastasis is currently a key issue in cancer therapy. Lymph node metastasis is one of the most important prognostic factors in various types of cancers, including endometrial cancer. Vascular endothelial growth factor-C (VEGF-C) plays a crucial role in lymphangiogenesis, and is implicated to play an important role in lymph node metastasis. To evaluate the role of VEGF-C in lymph node metastasis, we developed an animal model by using an endometrial cancer cell line, HEC1A. This cell line is not invasive by nature and secretes moderate amounts of VEGF-C; intrauterine injection of HEC1A cells into Balb/c nude mice resulted in uterine cancer with lymph node metastasis after 8 weeks. To analyze the contribution of VEGF-C to lymph node metastasis, its corresponding gene was stably introduced into HEC1A cells (HEC1A/VEGF-C), which then produced more than 10 times the amount of VEGF-C. The number of lymph node metastases was significantly higher in HEC1A/VEGF-C cells than in HEC1A cells (3.2 vs 1.1 nodes/animal, respectively). Augmented lymphangiogenesis was observed within tumors when HEC1A/VEGF-C cells were inoculated. These results indicate that VEGF-C plays a critical role in lymph node metastasis, in addition to serving as a platform to test the efficacy of various therapeutic modalities against lymph node metastasis.\n"
],
"offsets": [
[
0,
1442
]
]
}
] | [
{
"id": "PMID-21910784_T2",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
33,
43
]
],
"normalized": []
},
{
"id": "PMID-21910784_T3",
"type": "Cancer",
"text": [
"endometrial cancer"
],
"offsets": [
[
60,
78
]
],
"normalized": []
},
{
"id": "PMID-21910784_T4",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
93,
103
]
],
"normalized": []
},
{
"id": "PMID-21910784_T5",
"type": "Cancer",
"text": [
"cancer"
],
"offsets": [
[
143,
149
]
],
"normalized": []
},
{
"id": "PMID-21910784_T6",
"type": "Multi-tissue_structure",
"text": [
"Lymph node"
],
"offsets": [
[
159,
169
]
],
"normalized": []
},
{
"id": "PMID-21910784_T7",
"type": "Cancer",
"text": [
"cancers"
],
"offsets": [
[
249,
256
]
],
"normalized": []
},
{
"id": "PMID-21910784_T8",
"type": "Cancer",
"text": [
"endometrial cancer"
],
"offsets": [
[
268,
286
]
],
"normalized": []
},
{
"id": "PMID-21910784_T11",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
424,
434
]
],
"normalized": []
},
{
"id": "PMID-21910784_T13",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
481,
491
]
],
"normalized": []
},
{
"id": "PMID-21910784_T14",
"type": "Cell",
"text": [
"endometrial cancer cell line"
],
"offsets": [
[
545,
573
]
],
"normalized": []
},
{
"id": "PMID-21910784_T15",
"type": "Cell",
"text": [
"HEC1A"
],
"offsets": [
[
575,
580
]
],
"normalized": []
},
{
"id": "PMID-21910784_T16",
"type": "Cell",
"text": [
"cell line"
],
"offsets": [
[
587,
596
]
],
"normalized": []
},
{
"id": "PMID-21910784_T18",
"type": "Immaterial_anatomical_entity",
"text": [
"intrauterine"
],
"offsets": [
[
664,
676
]
],
"normalized": []
},
{
"id": "PMID-21910784_T19",
"type": "Cell",
"text": [
"HEC1A cells"
],
"offsets": [
[
690,
701
]
],
"normalized": []
},
{
"id": "PMID-21910784_T21",
"type": "Cancer",
"text": [
"uterine cancer"
],
"offsets": [
[
736,
750
]
],
"normalized": []
},
{
"id": "PMID-21910784_T22",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
756,
766
]
],
"normalized": []
},
{
"id": "PMID-21910784_T24",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
834,
844
]
],
"normalized": []
},
{
"id": "PMID-21910784_T25",
"type": "Cell",
"text": [
"HEC1A cells"
],
"offsets": [
[
907,
918
]
],
"normalized": []
},
{
"id": "PMID-21910784_T26",
"type": "Cell",
"text": [
"HEC1A"
],
"offsets": [
[
920,
925
]
],
"normalized": []
},
{
"id": "PMID-21910784_T29",
"type": "Cancer",
"text": [
"lymph node metastases"
],
"offsets": [
[
1010,
1031
]
],
"normalized": []
},
{
"id": "PMID-21910784_T30",
"type": "Cell",
"text": [
"HEC1A/VEGF-C cells"
],
"offsets": [
[
1060,
1078
]
],
"normalized": []
},
{
"id": "PMID-21910784_T32",
"type": "Cell",
"text": [
"HEC1A cells"
],
"offsets": [
[
1087,
1098
]
],
"normalized": []
},
{
"id": "PMID-21910784_T33",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
1188,
1194
]
],
"normalized": []
},
{
"id": "PMID-21910784_T34",
"type": "Cell",
"text": [
"HEC1A/VEGF-C cells"
],
"offsets": [
[
1200,
1218
]
],
"normalized": []
},
{
"id": "PMID-21910784_T37",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1296,
1306
]
],
"normalized": []
},
{
"id": "PMID-21910784_T38",
"type": "Multi-tissue_structure",
"text": [
"lymph node"
],
"offsets": [
[
1419,
1429
]
],
"normalized": []
},
{
"id": "PMID-21910784_T1",
"type": "Multi-tissue_structure",
"text": [
"nodes"
],
"offsets": [
[
1111,
1116
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17227832 | PMID-17227832 | [
{
"id": "PMID-17227832__text",
"type": "abstract",
"text": [
"Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis. \nCooperative activation of Meis1 and Hoxa9 perturbs myeloid differentiation and eventually leads myeloid progenitors to leukemia, yet it remains to be clarified what kinds of subsequent molecular processes are required for development of overt leukemia. To understand the molecular pathway in Hoxa9/Meis1-induced leukemogenesis, retroviral insertional mutagenesis was applied using retrovirus-mediated gene transfer. The mice that received Hoxa9/Meis1-transduced bone marrow cells developed acute myeloid leukemia (AML), and Trib1, Evi1, Ahi1, Raralpha, Pitpnb, and AK039950 were identified as candidate cooperative genes located near common retroviral integration sites. Trib1 and Evi1 were up-regulated due to retroviral insertions, and coexpression of these genes significantly accelerated the onset of Hoxa9/Meis1-induced AML, suggesting that Trib1 and Evi1 are the key collaborators. Furthermore, Trib1 by itself is a novel myeloid oncogene, enhancing phosphorylation of ERK, resulting in inhibition of apoptosis. These results demonstrate the importance of specific oncogene interaction in myeloid leukemogenesis.\n"
],
"offsets": [
[
0,
1192
]
]
}
] | [
{
"id": "PMID-17227832_T5",
"type": "Cell",
"text": [
"myeloid"
],
"offsets": [
[
48,
55
]
],
"normalized": []
},
{
"id": "PMID-17227832_T8",
"type": "Cell",
"text": [
"myeloid"
],
"offsets": [
[
124,
131
]
],
"normalized": []
},
{
"id": "PMID-17227832_T9",
"type": "Cell",
"text": [
"myeloid progenitors"
],
"offsets": [
[
169,
188
]
],
"normalized": []
},
{
"id": "PMID-17227832_T10",
"type": "Cancer",
"text": [
"leukemia"
],
"offsets": [
[
192,
200
]
],
"normalized": []
},
{
"id": "PMID-17227832_T11",
"type": "Cancer",
"text": [
"overt leukemia"
],
"offsets": [
[
310,
324
]
],
"normalized": []
},
{
"id": "PMID-17227832_T19",
"type": "Cell",
"text": [
"bone marrow cells"
],
"offsets": [
[
535,
552
]
],
"normalized": []
},
{
"id": "PMID-17227832_T20",
"type": "Cancer",
"text": [
"acute myeloid leukemia"
],
"offsets": [
[
563,
585
]
],
"normalized": []
},
{
"id": "PMID-17227832_T21",
"type": "Cancer",
"text": [
"AML"
],
"offsets": [
[
587,
590
]
],
"normalized": []
},
{
"id": "PMID-17227832_T33",
"type": "Cancer",
"text": [
"AML"
],
"offsets": [
[
898,
901
]
],
"normalized": []
},
{
"id": "PMID-17227832_T37",
"type": "Cell",
"text": [
"myeloid"
],
"offsets": [
[
1001,
1008
]
],
"normalized": []
},
{
"id": "PMID-17227832_T39",
"type": "Cell",
"text": [
"myeloid"
],
"offsets": [
[
1168,
1175
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-21913457 | PMID-21913457 | [
{
"id": "PMID-21913457__text",
"type": "abstract",
"text": [
"[Rubella in Poland in 2009].\nIn Poland, 7,587 cases of rubella were registered in 2009 (incidence 19.9 per 100,000 population). According to a new rubella case definition, introduced in 2009, 7 (0.1%) cases were classified as confirmed cases, 30 (0.4%) as probable. One case of congenital rubella syndrome was reported. The incidence in men (26.6) was 1.9-times higher than in women (13.6). The highest incidence was observed in children aged 7 and 8 years (180.3 and 175.6, respectively). No rubella deaths were registered. An improvement of laboratory diagnosis of reported cases is necessary to assess the impact of 2-dose immunization implemented in 2003 on rubella epidemiology in Poland.\n"
],
"offsets": [
[
0,
694
]
]
}
] | [] | [] | [] | [] |
PMID-22056386 | PMID-22056386 | [
{
"id": "PMID-22056386__text",
"type": "abstract",
"text": [
"PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target. \nParathyroid hormone-related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer - it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention.\n"
],
"offsets": [
[
0,
1670
]
]
}
] | [
{
"id": "PMID-22056386_T2",
"type": "Cancer",
"text": [
"breast tumor"
],
"offsets": [
[
13,
25
]
],
"normalized": []
},
{
"id": "PMID-22056386_T6",
"type": "Tissue",
"text": [
"fetal"
],
"offsets": [
[
206,
211
]
],
"normalized": []
},
{
"id": "PMID-22056386_T7",
"type": "Tissue",
"text": [
"adult tissues"
],
"offsets": [
[
216,
229
]
],
"normalized": []
},
{
"id": "PMID-22056386_T8",
"type": "Organism_substance",
"text": [
"serum"
],
"offsets": [
[
318,
323
]
],
"normalized": []
},
{
"id": "PMID-22056386_T11",
"type": "Cancer",
"text": [
"skeletal metastases"
],
"offsets": [
[
393,
412
]
],
"normalized": []
},
{
"id": "PMID-22056386_T12",
"type": "Cancer",
"text": [
"cancers"
],
"offsets": [
[
458,
465
]
],
"normalized": []
},
{
"id": "PMID-22056386_T14",
"type": "Cancer",
"text": [
"breast tumors"
],
"offsets": [
[
552,
565
]
],
"normalized": []
},
{
"id": "PMID-22056386_T15",
"type": "Cancer",
"text": [
"solid cancers"
],
"offsets": [
[
576,
589
]
],
"normalized": []
},
{
"id": "PMID-22056386_T16",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
606,
611
]
],
"normalized": []
},
{
"id": "PMID-22056386_T19",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
715,
728
]
],
"normalized": []
},
{
"id": "PMID-22056386_T20",
"type": "Cancer",
"text": [
"primary tumors"
],
"offsets": [
[
779,
793
]
],
"normalized": []
},
{
"id": "PMID-22056386_T22",
"type": "Tissue",
"text": [
"mammary epithelium"
],
"offsets": [
[
832,
850
]
],
"normalized": []
},
{
"id": "PMID-22056386_T25",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
868,
881
]
],
"normalized": []
},
{
"id": "PMID-22056386_T27",
"type": "Cancer",
"text": [
"primary tumor"
],
"offsets": [
[
912,
925
]
],
"normalized": []
},
{
"id": "PMID-22056386_T28",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
948,
953
]
],
"normalized": []
},
{
"id": "PMID-22056386_T29",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1070,
1074
]
],
"normalized": []
},
{
"id": "PMID-22056386_T33",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1156,
1160
]
],
"normalized": []
},
{
"id": "PMID-22056386_T42",
"type": "Cancer",
"text": [
"breast cancer xenografts"
],
"offsets": [
[
1459,
1483
]
],
"normalized": []
},
{
"id": "PMID-22056386_T44",
"type": "Cancer",
"text": [
"breast cancer"
],
"offsets": [
[
1573,
1586
]
],
"normalized": []
},
{
"id": "PMID-22056386_T1",
"type": "Cancer",
"text": [
"metastases"
],
"offsets": [
[
798,
808
]
],
"normalized": []
},
{
"id": "PMID-22056386_T3",
"type": "Multi-tissue_structure",
"text": [
"distal sites"
],
"offsets": [
[
993,
1005
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-205979 | PMID-205979 | [
{
"id": "PMID-205979__text",
"type": "abstract",
"text": [
"Structure of human hemoglobin messenger RNA and its relation to hemoglobinopathies.\n1. One-fifth to 1/4 of globin mRNA is untranslated sequence other than polyadenylic acid. 2. The untranslated sequences of mRNA vary markedly in their sequence and in their length. 3. Globin mRNAs demonstrate a marked bias in codon selection. 4. Viral mRNA shows a quite different pattern of codon selection; therefore, the selection of codons is not uniform for all mRNAs functioning in animal cells. 5. Elongated hemoglobin chains can be accounted for by frame-shift mutations, or point mutations within the normal termination codon. The additional amino acids are then coded for by sequences that are normally untranslated. 6. Certain hemoglobin deletion mutants occur at sites where there are partially reiterated sequences within the heomoglobin messenger RNA.\n"
],
"offsets": [
[
0,
850
]
]
}
] | [
{
"id": "PMID-205979_T1",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
479,
484
]
],
"normalized": []
}
] | [] | [] | [] |
PMC-2774332-sec-09 | PMC-2774332-sec-09 | [
{
"id": "PMC-2774332-sec-09__text",
"type": "sec",
"text": [
"Target volumes' coverage\nThe mean PTV1 and PTV2 volumes were 452 cm3 (range 276-1074 cm3) and 300 cm3 (range 137-567 cm3) respectively. A mean of >98% (range 92-100%) of the PTV1 received 100% of the prescribed dose in all planning methods. A mean of 95.5% and 95.7% of the PTV2 received 100% of the prescribed dose with TOMO and IMRT plans respectively. A mean of 94% and 92% of the PTV2 received 100% of the prescribed dose with IB and 3D treatment plans, respectively. The mean IB and 3D plans PTV2 coverage was significantly inferior then the IMRT and TOMO plans (p < 0.02, for all comparisons).\nThe mean Inhomogeneity Coefficient (IC) was significantly lower (better) with the TOMO plans, compared to all other plans for both PTV1 and PTV2 (p < 0.0003 for all comparisons) (figure 3). The mean IC of the IMRT plans was significantly higher (worse) than the mean IC of the 3D plans regarding PTV 1 (p < 0.02) and higher (worse) then the mean IC of the IB plans regarding PTV2 (p < 0.03) (figure 3). No significant difference was found between the means of the IC of the 3D and IB plans.\nFigure 3\nThe mean Inhomogeneity Coefficient (IC) achieved by the different planning methods. The mean of the Inhomogeneity Coefficient is a measure of dose inhomogeneity in the target volumes. The closer the IC to zero, the more homogenous the dose is.\n"
],
"offsets": [
[
0,
1344
]
]
}
] | [] | [] | [] | [] |
PMC-3112138-sec-20 | PMC-3112138-sec-20 | [
{
"id": "PMC-3112138-sec-20__text",
"type": "sec",
"text": [
"Acknowledgements\nThe authors gratefully acknowledge the support of DRUID study participants, study staff, members of the Indigenous Steering Group, and partner organisations. The DRUID Study was funded by the National Health and Medical Research Council (NHMRC Project Grant #236207), with additional support from the Australian Government Department of Employment and Workplace Relations, the Clive and Vera Ramaciotti Foundation, the Vincent Fairfax Family Foundation, the International Diabetes Institute (AusDiab Partnership), and Bayer HealthCare. The DRUID Study is an in-kind project of the Cooperative Research Centre for Aboriginal Health. LMB had a NHMRC Scholarship 2003-5 and is supported by NHMRC Training Fellowship (#605837), NHMRC #320860 and the Centre of Clinical Research Excellence in Clinical Science in Diabetes, University of Melbourne. JC was supported by a NHMRC Career Development Award (#283310) and a NHMRC Research Fellowship (#545200). AH is supported by NHMRC Fellowship (#520316). Thank you to Dr Jaquelyne Hughes for comments on the manuscript. Funding sources played no role in the study design, in the collection, analysis and interpretation of the data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.\n"
],
"offsets": [
[
0,
1285
]
]
}
] | [] | [] | [] | [] |
PMID-19514363 | PMID-19514363 | [
{
"id": "PMID-19514363__text",
"type": "abstract",
"text": [
"[Role of the tumor suppressor ARF in oncogenesis]\nThe paper reviews the data available in the literature on a role of the tumor suppressor ARF in oncogenesis and considers the structure of a gene encoding ARF protein. The p53-dependent and p-53-independent functions of this protein are under many studies. There is evidence for the implication of ARF in angiogenesis. There is more and more information on the role of ARF in the regulation of a cell cycle, apoptosis, and autophagy. The importance of this tumor suppressor in the mechanisms of carcinogenesis is beyond question as the inactivation of ARF suppressor activity leads to the rapid growth of neoplasia. However, the exact mechanisms of ARF action yet remain unclear and require further studies by different specialists at both the molecular genetic and other levels of investigation.\n"
],
"offsets": [
[
0,
847
]
]
}
] | [
{
"id": "PMID-19514363_T1",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
13,
18
]
],
"normalized": []
},
{
"id": "PMID-19514363_T3",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
122,
127
]
],
"normalized": []
},
{
"id": "PMID-19514363_T10",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
446,
450
]
],
"normalized": []
},
{
"id": "PMID-19514363_T11",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
507,
512
]
],
"normalized": []
},
{
"id": "PMID-19514363_T13",
"type": "Cancer",
"text": [
"neoplasia"
],
"offsets": [
[
655,
664
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-21468425 | PMID-21468425 | [
{
"id": "PMID-21468425__text",
"type": "abstract",
"text": [
"Systematic proteomic analysis of human hepotacellular carcinoma cells reveals molecular pathways and networks involved in metastasis. \nSystematic proteomic studying of the mechanism of hepatocellular carcinoma (HCC) metastasis remains challenging. We performed comparative proteomic and pathway analysis of four human metastatic HCC cell lines to identify metastasis-associated proteins. These HCC cell lines had a similar genetic background but with an increasing potential of metastasis. Using a combination of two dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry, a total of 125 proteins and their post-translational modification forms or isoforms were found to be differentially expressed in the cell lines. Among them, 29 were gradually up-regulated whereas 17 were down-regulated with increasing metastatic potential. Instead of a traditional single-gene readout, global bioinformatics analysis was carried out, which revealed that the glycolysis pathway was the most significantly enriched pathway. The heat shock proteins (HSPs) centered and NF-kappaB centered networks were also enriched in the result, which may imply the key function of inflaming on metastasis. Meanwhile, knockdown of HDGF, an up-regulated protein and a target of NF-kappaB, induced cell apoptosis in the metastatic HCC cells. This work provides a demonstration that a combination of bioinformatics and comparative proteomics can help in finding out potential biomarkers associated with HCC metastasis on the level of pathways.\n"
],
"offsets": [
[
0,
1525
]
]
}
] | [
{
"id": "PMID-21468425_T2",
"type": "Cell",
"text": [
"hepotacellular carcinoma cells"
],
"offsets": [
[
39,
69
]
],
"normalized": []
},
{
"id": "PMID-21468425_T3",
"type": "Cancer",
"text": [
"hepatocellular carcinoma"
],
"offsets": [
[
185,
209
]
],
"normalized": []
},
{
"id": "PMID-21468425_T4",
"type": "Cancer",
"text": [
"HCC"
],
"offsets": [
[
211,
214
]
],
"normalized": []
},
{
"id": "PMID-21468425_T6",
"type": "Cell",
"text": [
"metastatic HCC cell lines"
],
"offsets": [
[
318,
343
]
],
"normalized": []
},
{
"id": "PMID-21468425_T7",
"type": "Cell",
"text": [
"HCC cell lines"
],
"offsets": [
[
394,
408
]
],
"normalized": []
},
{
"id": "PMID-21468425_T8",
"type": "Cell",
"text": [
"cell lines"
],
"offsets": [
[
718,
728
]
],
"normalized": []
},
{
"id": "PMID-21468425_T14",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1280,
1284
]
],
"normalized": []
},
{
"id": "PMID-21468425_T15",
"type": "Cell",
"text": [
"metastatic HCC cells"
],
"offsets": [
[
1302,
1322
]
],
"normalized": []
},
{
"id": "PMID-21468425_T16",
"type": "Cancer",
"text": [
"HCC"
],
"offsets": [
[
1484,
1487
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-6089351 | PMID-6089351 | [
{
"id": "PMID-6089351__text",
"type": "abstract",
"text": [
"Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. \nThe human T-cell leukemia viruses HTLV-I and HTLV-II are unique among the transforming retroviruses of vertebrates in their ability to transform human T cells in vitro and in their close association with human malignancies (T-cell lymphomas and leukemia). Their genomes are relatively simple, containing the genes gag, pol, env, and a 3' region termed \"X.\" This 3' region may be responsible for the transforming potential of the viruses. The existence of proteins encoded by the 3' region has been postulated on the basis of multiple open reading frames. In the present study this region is shown to contain a gene encoding a protein of 40 kilodaltons in HTLV-I and 37 kilodaltons in HTLV-II. It is proposed that these proteins be called, respectively, p40xI and p37xII.\n"
],
"offsets": [
[
0,
881
]
]
}
] | [
{
"id": "PMID-6089351_T7",
"type": "Cell",
"text": [
"T cells"
],
"offsets": [
[
261,
268
]
],
"normalized": []
},
{
"id": "PMID-6089351_T9",
"type": "Cancer",
"text": [
"malignancies"
],
"offsets": [
[
320,
332
]
],
"normalized": []
},
{
"id": "PMID-6089351_T10",
"type": "Cancer",
"text": [
"T-cell lymphomas"
],
"offsets": [
[
334,
350
]
],
"normalized": []
},
{
"id": "PMID-6089351_T11",
"type": "Cancer",
"text": [
"leukemia"
],
"offsets": [
[
355,
363
]
],
"normalized": []
},
{
"id": "PMID-6089351_T15",
"type": "Cellular_component",
"text": [
"3' region"
],
"offsets": [
[
445,
454
]
],
"normalized": []
},
{
"id": "PMID-6089351_T16",
"type": "Cellular_component",
"text": [
"X"
],
"offsets": [
[
463,
464
]
],
"normalized": []
},
{
"id": "PMID-6089351_T17",
"type": "Cellular_component",
"text": [
"3' region"
],
"offsets": [
[
472,
481
]
],
"normalized": []
},
{
"id": "PMID-6089351_T18",
"type": "Cellular_component",
"text": [
"3' region"
],
"offsets": [
[
589,
598
]
],
"normalized": []
},
{
"id": "PMID-6089351_T1",
"type": "Cancer",
"text": [
"T-cell leukemia"
],
"offsets": [
[
65,
80
]
],
"normalized": []
},
{
"id": "PMID-6089351_T2",
"type": "Cancer",
"text": [
"T-cell leukemia"
],
"offsets": [
[
120,
135
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-12414659 | PMID-12414659 | [
{
"id": "PMID-12414659__text",
"type": "abstract",
"text": [
"Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats.\nRoles of cell adhesion molecules mediating the interaction of cancer and endothelial cells in tumor angiogenesis were investigated using new in vitro and in vivo model systems with a cultured murine endothelial cell line (F-2) and human cultured epidermoid cancer cells (A431). The A431 cells exhibited typical in vitro cell adhesion to the endothelial F-2 cells. The initial step of adhesion was mediated by sialyl Lewis(x) (Le(x)) and sialyl Le(a), the carbohydrate determinants expressed on the cancer cells, and E-selectin expressed constitutively on F-2 cells. Prolonged culture led to the implantation of cancer cells into the monolayer of the F-2 cells, which was mediated mainly by alpha(3)beta(1)-integrin. F-2 cells cultured on Matrigel showed evident tube formation, and coculture of F-2 cells with A431 cells led to the formation of A431 cell nests constantly surrounded by tube-like networks consisting of F-2 cells. This in vitro morphogenesis was inhibited by the addition of anti-sialyl Le(x)/Le(a) or anti-beta(1)-integrin antibodies, which led to the formation of cancer cell aggregates that were independent from the F-2 cell networks. This in vitro morphological appearance was exactly reproduced in the in vivo tumors, which were formed when the mixture of A431 and F-2 cells at the ratio of 10:1 were cotransplanted s.c. into the back of nude rats. The tumors of A431 supplemented with F-2 cells were profoundly vascularized throughout by the tubular structures formed by F-2 cells, the lumen of which contained the host rat blood cells. The tumor mass thus formed was an average 5.8-fold as large as control A431 tumors that were grown without F-2 cells. The co-injection of anti-Le(x)/Le(a) or anti-beta(1)-integrin antibodies produced a marked reduction in the size of A431 tumors, which were not vascularized and accompanied an independent tiny remnant clump of F-2 cells. The size of these A431 tumors did not differ significantly from those of control A431 tumors raised without F-2 cells. These results indicate that the interaction of tumor cells and endothelial cells in orderly tumor angiomorphogenesis is highly dependent on the action of cell adhesion molecules mediating the adhesion of cancer cells to endothelial cells, inhibition of which remarkably retards tumor growth and angiogenesis.\n"
],
"offsets": [
[
0,
2457
]
]
}
] | [
{
"id": "PMID-12414659_T1",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
9,
13
]
],
"normalized": []
},
{
"id": "PMID-12414659_T2",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
36,
41
]
],
"normalized": []
},
{
"id": "PMID-12414659_T3",
"type": "Cell",
"text": [
"cancer"
],
"offsets": [
[
87,
93
]
],
"normalized": []
},
{
"id": "PMID-12414659_T4",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
98,
115
]
],
"normalized": []
},
{
"id": "PMID-12414659_T6",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
139,
143
]
],
"normalized": []
},
{
"id": "PMID-12414659_T7",
"type": "Cell",
"text": [
"cancer"
],
"offsets": [
[
192,
198
]
],
"normalized": []
},
{
"id": "PMID-12414659_T8",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
203,
220
]
],
"normalized": []
},
{
"id": "PMID-12414659_T9",
"type": "Cancer",
"text": [
"tumor"
],
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[
224,
229
]
],
"normalized": []
},
{
"id": "PMID-12414659_T11",
"type": "Cell",
"text": [
"endothelial cell line"
],
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329,
350
]
],
"normalized": []
},
{
"id": "PMID-12414659_T12",
"type": "Cell",
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"F-2"
],
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352,
355
]
],
"normalized": []
},
{
"id": "PMID-12414659_T14",
"type": "Cell",
"text": [
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],
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376,
399
]
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"normalized": []
},
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"id": "PMID-12414659_T15",
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],
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401,
405
]
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},
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"id": "PMID-12414659_T16",
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412,
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"id": "PMID-12414659_T17",
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450,
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]
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},
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"id": "PMID-12414659_T18",
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471,
492
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"normalized": []
},
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"id": "PMID-12414659_T22",
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628,
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]
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},
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],
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685,
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]
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},
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"id": "PMID-12414659_T25",
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],
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741,
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]
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},
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],
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763,
772
]
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780,
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846,
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]
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},
{
"id": "PMID-12414659_T30",
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"tube"
],
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892,
896
]
],
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},
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"id": "PMID-12414659_T31",
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"F-2 cells"
],
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]
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},
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"id": "PMID-12414659_T32",
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"A431 cells"
],
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940,
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]
],
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},
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"id": "PMID-12414659_T33",
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],
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975,
984
]
],
"normalized": []
},
{
"id": "PMID-12414659_T34",
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"tube-like networks"
],
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1016,
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]
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},
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"id": "PMID-12414659_T35",
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"F-2 cells"
],
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1049,
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]
],
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},
{
"id": "PMID-12414659_T39",
"type": "Cell",
"text": [
"cancer cell aggregates"
],
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1212,
1234
]
],
"normalized": []
},
{
"id": "PMID-12414659_T40",
"type": "Cell",
"text": [
"F-2 cell"
],
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[
1266,
1274
]
],
"normalized": []
},
{
"id": "PMID-12414659_T41",
"type": "Cancer",
"text": [
"tumors"
],
"offsets": [
[
1362,
1368
]
],
"normalized": []
},
{
"id": "PMID-12414659_T42",
"type": "Cell",
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"A431"
],
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1408,
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]
],
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},
{
"id": "PMID-12414659_T43",
"type": "Cell",
"text": [
"F-2 cells"
],
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1417,
1426
]
],
"normalized": []
},
{
"id": "PMID-12414659_T44",
"type": "Organism_subdivision",
"text": [
"back"
],
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[
1482,
1486
]
],
"normalized": []
},
{
"id": "PMID-12414659_T46",
"type": "Cancer",
"text": [
"tumors"
],
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1505,
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]
],
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},
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"id": "PMID-12414659_T47",
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"A431"
],
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1515,
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]
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},
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"id": "PMID-12414659_T48",
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"F-2 cells"
],
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1538,
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]
],
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},
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"id": "PMID-12414659_T49",
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"text": [
"tubular structures"
],
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1595,
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]
],
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},
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"id": "PMID-12414659_T50",
"type": "Cell",
"text": [
"F-2 cells"
],
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1624,
1633
]
],
"normalized": []
},
{
"id": "PMID-12414659_T51",
"type": "Immaterial_anatomical_entity",
"text": [
"lumen"
],
"offsets": [
[
1639,
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]
],
"normalized": []
},
{
"id": "PMID-12414659_T53",
"type": "Cell",
"text": [
"blood cells"
],
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[
1677,
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]
],
"normalized": []
},
{
"id": "PMID-12414659_T54",
"type": "Cancer",
"text": [
"tumor mass"
],
"offsets": [
[
1694,
1704
]
],
"normalized": []
},
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"id": "PMID-12414659_T55",
"type": "Cancer",
"text": [
"A431 tumors"
],
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]
],
"normalized": []
},
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"id": "PMID-12414659_T56",
"type": "Cell",
"text": [
"F-2 cells"
],
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1797,
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]
],
"normalized": []
},
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"id": "PMID-12414659_T60",
"type": "Cancer",
"text": [
"A431 tumors"
],
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1924,
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]
],
"normalized": []
},
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"id": "PMID-12414659_T61",
"type": "Cell",
"text": [
"F-2 cells"
],
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[
2018,
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]
],
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},
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"id": "PMID-12414659_T62",
"type": "Cancer",
"text": [
"A431 tumors"
],
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2047,
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]
],
"normalized": []
},
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"id": "PMID-12414659_T63",
"type": "Cancer",
"text": [
"A431 tumors"
],
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[
2110,
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]
],
"normalized": []
},
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"id": "PMID-12414659_T64",
"type": "Cell",
"text": [
"F-2 cells"
],
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[
2137,
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]
],
"normalized": []
},
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"id": "PMID-12414659_T65",
"type": "Cell",
"text": [
"tumor cells"
],
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[
2195,
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]
],
"normalized": []
},
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"id": "PMID-12414659_T66",
"type": "Cell",
"text": [
"endothelial cells"
],
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[
2211,
2228
]
],
"normalized": []
},
{
"id": "PMID-12414659_T67",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
2240,
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]
],
"normalized": []
},
{
"id": "PMID-12414659_T68",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
2302,
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]
],
"normalized": []
},
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"id": "PMID-12414659_T69",
"type": "Cell",
"text": [
"cancer cells"
],
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[
2352,
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]
],
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},
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"id": "PMID-12414659_T70",
"type": "Cell",
"text": [
"endothelial cells"
],
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[
2368,
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]
],
"normalized": []
},
{
"id": "PMID-12414659_T71",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
2426,
2431
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17384243 | PMID-17384243 | [
{
"id": "PMID-17384243__text",
"type": "abstract",
"text": [
"Expression of Bcl-xL, Bax, and p53 in primary tumors and lymph node metastases in oral squamous cell carcinoma. \nDisturbances in expression of apoptosis-associated proteins take part in the development and progression of many human malignancies. The aim of this study was the assessment of correlations among proteins involved in apoptosis-Bcl-xL, Bax, and p53-as well as relationships of these proteins with selected clinicopathological features in oral squamous cell carcinoma. Consequently, we examined by immunohistochemistry, using the avidin-biotin-peroxidase method, Bcl-xL, Bax, and p53 expression in 56 samples of primary oral squamous cell carcinoma and in 22 matched pairs of primary and metastatic tumors. The evaluation of immunostaining of Bcl-xL, Bax, and p53 was analyzed in 10 different tumor fields, and the mean percentage of tumor cells with positive staining was evaluated. The significance of the associations was determined using Spearman correlation analysis and the chi-square test. We found positive Bcl-xL, Bax, and p53 immunostaining in 44.6%, 28.6%, and 58.9% of the studied primary tumors and in 63.6%, 45.5%, and 72.7% of lymph node metastases, respectively. Analysis of associations among studied proteins revealed positive correlation between Bcl-xL and Bax in primary tumors (P<0.03, r=0.307). Statistically significant relationship between p53 expression in primary oral cancers and its expression in lymph node metastases (P<0.02) as well as increased expression of Bcl-xL, Bax, and p53 in metastatic sites compared with primary tumors could indicate an association of these proteins with oral cancer progression and development of metastases. Moreover, we suppose that knowledge about heterogeneity between primary and metastatic tumor might help to understand mechanisms of oral cancer progression.\n"
],
"offsets": [
[
0,
1837
]
]
}
] | [
{
"id": "PMID-17384243_T4",
"type": "Cancer",
"text": [
"primary tumors"
],
"offsets": [
[
38,
52
]
],
"normalized": []
},
{
"id": "PMID-17384243_T5",
"type": "Cancer",
"text": [
"lymph node metastases"
],
"offsets": [
[
57,
78
]
],
"normalized": []
},
{
"id": "PMID-17384243_T6",
"type": "Cancer",
"text": [
"oral squamous cell carcinoma"
],
"offsets": [
[
82,
110
]
],
"normalized": []
},
{
"id": "PMID-17384243_T8",
"type": "Cancer",
"text": [
"malignancies"
],
"offsets": [
[
232,
244
]
],
"normalized": []
},
{
"id": "PMID-17384243_T12",
"type": "Cancer",
"text": [
"oral squamous cell carcinoma"
],
"offsets": [
[
450,
478
]
],
"normalized": []
},
{
"id": "PMID-17384243_T19",
"type": "Cancer",
"text": [
"primary oral squamous cell carcinoma"
],
"offsets": [
[
623,
659
]
],
"normalized": []
},
{
"id": "PMID-17384243_T20",
"type": "Cancer",
"text": [
"metastatic tumors"
],
"offsets": [
[
699,
716
]
],
"normalized": []
},
{
"id": "PMID-17384243_T24",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
804,
809
]
],
"normalized": []
},
{
"id": "PMID-17384243_T25",
"type": "Cell",
"text": [
"tumor cells"
],
"offsets": [
[
845,
856
]
],
"normalized": []
},
{
"id": "PMID-17384243_T29",
"type": "Cancer",
"text": [
"primary tumors"
],
"offsets": [
[
1104,
1118
]
],
"normalized": []
},
{
"id": "PMID-17384243_T30",
"type": "Cancer",
"text": [
"lymph node metastases"
],
"offsets": [
[
1153,
1174
]
],
"normalized": []
},
{
"id": "PMID-17384243_T33",
"type": "Cancer",
"text": [
"primary tumors"
],
"offsets": [
[
1294,
1308
]
],
"normalized": []
},
{
"id": "PMID-17384243_T36",
"type": "Cancer",
"text": [
"primary oral cancers"
],
"offsets": [
[
1393,
1413
]
],
"normalized": []
},
{
"id": "PMID-17384243_T37",
"type": "Cancer",
"text": [
"lymph node metastases"
],
"offsets": [
[
1436,
1457
]
],
"normalized": []
},
{
"id": "PMID-17384243_T41",
"type": "Cancer",
"text": [
"primary tumors"
],
"offsets": [
[
1557,
1571
]
],
"normalized": []
},
{
"id": "PMID-17384243_T42",
"type": "Cancer",
"text": [
"oral cancer"
],
"offsets": [
[
1625,
1636
]
],
"normalized": []
},
{
"id": "PMID-17384243_T43",
"type": "Cancer",
"text": [
"metastatic tumor"
],
"offsets": [
[
1756,
1772
]
],
"normalized": []
},
{
"id": "PMID-17384243_T44",
"type": "Cancer",
"text": [
"oral cancer"
],
"offsets": [
[
1812,
1823
]
],
"normalized": []
},
{
"id": "PMID-17384243_T64",
"type": "Cancer",
"text": [
"samples"
],
"offsets": [
[
612,
619
]
],
"normalized": []
},
{
"id": "PMID-17384243_T1",
"type": "Cancer",
"text": [
"metastases"
],
"offsets": [
[
1668,
1678
]
],
"normalized": []
},
{
"id": "PMID-17384243_T2",
"type": "Cancer",
"text": [
"metastatic sites"
],
"offsets": [
[
1526,
1542
]
],
"normalized": []
},
{
"id": "PMID-17384243_T3",
"type": "Cancer",
"text": [
"primary"
],
"offsets": [
[
687,
694
]
],
"normalized": []
},
{
"id": "PMID-17384243_T7",
"type": "Cancer",
"text": [
"primary"
],
"offsets": [
[
1744,
1751
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-16221381 | PMID-16221381 | [
{
"id": "PMID-16221381__text",
"type": "abstract",
"text": [
"The merits of vascular targeting for gynecologic malignancies.\nNeovascularization is an early and critical step in tumor development and progression. Tumor vessels are distinct from their normal counterparts morphologically as well as at a molecular level. Recent studies on factors involved in tumor vascular development have identified new therapeutic targets for inhibiting tumor neovascularization and thus tumor progression. However, the process of tumor blood vessel formation is complex, and each tumor exhibits unique features in its vasculature. An understanding of the relative contribution of various pathways in the development of tumor vasculature is critical for developing effective and selective therapeutic approaches. Several such agents are currently in clinical trials, and many others are under development. In this review, the mechanisms and factors involved in tumor blood vessel formation are discussed. In addition, selected novel classes of antivascular therapies, including those targeting tumor endothelial cells and other components of the tumor vasculature, are summarized.\n"
],
"offsets": [
[
0,
1104
]
]
}
] | [
{
"id": "PMID-16221381_T1",
"type": "Multi-tissue_structure",
"text": [
"vascular"
],
"offsets": [
[
14,
22
]
],
"normalized": []
},
{
"id": "PMID-16221381_T2",
"type": "Cancer",
"text": [
"malignancies"
],
"offsets": [
[
49,
61
]
],
"normalized": []
},
{
"id": "PMID-16221381_T3",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
115,
120
]
],
"normalized": []
},
{
"id": "PMID-16221381_T4",
"type": "Multi-tissue_structure",
"text": [
"Tumor vessels"
],
"offsets": [
[
150,
163
]
],
"normalized": []
},
{
"id": "PMID-16221381_T5",
"type": "Multi-tissue_structure",
"text": [
"tumor vascular"
],
"offsets": [
[
295,
309
]
],
"normalized": []
},
{
"id": "PMID-16221381_T6",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
377,
382
]
],
"normalized": []
},
{
"id": "PMID-16221381_T7",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
411,
416
]
],
"normalized": []
},
{
"id": "PMID-16221381_T8",
"type": "Multi-tissue_structure",
"text": [
"tumor blood vessel"
],
"offsets": [
[
454,
472
]
],
"normalized": []
},
{
"id": "PMID-16221381_T9",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
504,
509
]
],
"normalized": []
},
{
"id": "PMID-16221381_T10",
"type": "Multi-tissue_structure",
"text": [
"vasculature"
],
"offsets": [
[
542,
553
]
],
"normalized": []
},
{
"id": "PMID-16221381_T11",
"type": "Multi-tissue_structure",
"text": [
"tumor vasculature"
],
"offsets": [
[
643,
660
]
],
"normalized": []
},
{
"id": "PMID-16221381_T12",
"type": "Multi-tissue_structure",
"text": [
"tumor blood vessel"
],
"offsets": [
[
884,
902
]
],
"normalized": []
},
{
"id": "PMID-16221381_T13",
"type": "Multi-tissue_structure",
"text": [
"vascular"
],
"offsets": [
[
971,
979
]
],
"normalized": []
},
{
"id": "PMID-16221381_T14",
"type": "Cell",
"text": [
"tumor endothelial cells"
],
"offsets": [
[
1017,
1040
]
],
"normalized": []
},
{
"id": "PMID-16221381_T15",
"type": "Multi-tissue_structure",
"text": [
"tumor vasculature"
],
"offsets": [
[
1069,
1086
]
],
"normalized": []
}
] | [] | [] | [] |
PMID-17488804 | PMID-17488804 | [
{
"id": "PMID-17488804__text",
"type": "abstract",
"text": [
"Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells.\nFrequent coffee consumption has been associated with a reduced risk of colorectal cancer in a number of case-control studies. Coffee is a leading source of methylxanthines, such as caffeine. The induction of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) is an essential feature of tumor angiogenesis, and the hypoxia-inducible factor-1 (HIF-1) transcription factor is known to be a key regulator of this process. In this study, we investigated the effects of caffeine on HIF-1 protein accumulation and on VEGF and IL-8 expression in the human colon cancer cell line HT29 under hypoxic conditions. Our results show that caffeine significantly inhibits adenosine-induced HIF-1alpha protein accumulation in cancer cells. We show that HIF-1alpha and VEGF are increased through A3 adenosine receptor stimulation, whereas the effects on IL-8 are mediated via the A2B subtype. Pretreatment of cells with caffeine significantly reduces adenosine-induced VEGF promoter activity and VEGF and IL-8 expression. The mechanism of caffeine seems to involve the inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and Akt, leading to a marked decrease in adenosine-induced HIF-1alpha accumulation, VEGF transcriptional activation, and VEGF and IL-8 protein accumulation. From a functional perspective, we observe that caffeine also significantly inhibits the A3 receptor-stimulated cell migration of colon cancer cells. Conditioned media prepared from colon cells treated with an adenosine analog increased human umbilical vein endothelial cell migration. These data provide evidence that adenosine could modulate the migration of colon cancer cells by an HIF-1alpha/VEGF/IL-8-dependent mechanism and that caffeine has the potential to inhibit colon cancer cell growth.\n"
],
"offsets": [
[
0,
1985
]
]
}
] | [
{
"id": "PMID-17488804_T7",
"type": "Cell",
"text": [
"colon cancer cells"
],
"offsets": [
[
167,
185
]
],
"normalized": []
},
{
"id": "PMID-17488804_T8",
"type": "Cancer",
"text": [
"colorectal cancer"
],
"offsets": [
[
258,
275
]
],
"normalized": []
},
{
"id": "PMID-17488804_T15",
"type": "Cancer",
"text": [
"tumor"
],
"offsets": [
[
489,
494
]
],
"normalized": []
},
{
"id": "PMID-17488804_T23",
"type": "Cell",
"text": [
"colon cancer cell line HT29"
],
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"cancer cells"
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"cells"
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"cell"
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"id": "PMID-17488804_T54",
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"colon cancer cells"
],
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"id": "PMID-17488804_T55",
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"colon cells"
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"id": "PMID-17488804_T57",
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"human umbilical vein endothelial cell"
],
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"id": "PMID-17488804_T59",
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"colon cancer cells"
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"id": "PMID-17488804_T64",
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"colon cancer cell"
],
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}
] | [] | [] | [] |
PMC-2998423-sec-17 | PMC-2998423-sec-17 | [
{
"id": "PMC-2998423-sec-17__text",
"type": "sec",
"text": [
"Real time RT-PCR\nRNA extraction and real-time RT-PCR were performed as we described previously [22]. The sequences of ABCG2 primers are 5'-GGCTTTCTACCTGCACGAAAACCAGTTGAG-3' (forward) and 5'-ATGGCGTTGAGACCAG-3' (reverse). The sequences of GAPDH primers are 5'-AAGGACTCATGACCACAGTCCAT-3' (forward) and 5'-CCATCACGCCACAGTTTCC-3' (reverse). The relative ABCG2 RNA level (2DeltaCT) treated with inhibitors was expressed as percentage of the control (in the presence of 0.1% DMSO) where DeltaCT (threshold cycle) = (CTABCG2-CTGAPDH).\n"
],
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0,
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]
}
] | [] | [] | [] | [] |
PMC-3131097-caption-02 | PMC-3131097-caption-02 | [
{
"id": "PMC-3131097-caption-02__text",
"type": "caption",
"text": [
"Scheme of the activity of 5-HT (A) and norepinephrine (NE) (B) neurotransmission during treatment with milnacipran. A) 5-HT system. Acute treatment with milnacipran results in a decreased firing of 5-HT neurons from the raphe nucleus possibly due in part to increased stimulation of somatodendritic autoreceptors. Long-term treatment with milnacipran results in a full recovery in the firing rate of 5-HT neurons in the presence of milnacipran thereby leading to a net increase in 5-HT neurotransmission. Contributing to this enhancement are: 1) the normalized firing rate of 5-HT neurons in the presence of milnacipran 2) the desensitization of the terminal 5-HT1B autoreceptor, and 3) the desensitization of the alpha2-adrenergic heteroreceptors on 5-HT terminals. B) NE system. Acute treatment with milnacipran results in increased synaptic concentrations of NE but decreased firing of the NE neurons of the locus coeruleus due to increased stimulation of the somatodendritic alpha2-adrenergic autoreceptors. Long-term treatment with milnacipran results in a further increase in synaptic concentrations of NE due to desensitization of presynaptic autoreceptors. The somatodendritic alpha2-adrenergic autoreceptors do not desensitize.\n"
],
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[
0,
1237
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]
}
] | [
{
"id": "PMC-3131097-caption-02_T1",
"type": "Cell",
"text": [
"5-HT neurons"
],
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198,
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]
],
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},
{
"id": "PMC-3131097-caption-02_T2",
"type": "Tissue",
"text": [
"raphe nucleus"
],
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[
220,
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]
],
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},
{
"id": "PMC-3131097-caption-02_T3",
"type": "Cell",
"text": [
"somatodendritic"
],
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283,
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]
],
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},
{
"id": "PMC-3131097-caption-02_T4",
"type": "Cell",
"text": [
"5-HT neurons"
],
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[
400,
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]
],
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},
{
"id": "PMC-3131097-caption-02_T5",
"type": "Cell",
"text": [
"5-HT neurons"
],
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[
576,
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]
],
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},
{
"id": "PMC-3131097-caption-02_T6",
"type": "Cell",
"text": [
"NE neurons"
],
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893,
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]
],
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},
{
"id": "PMC-3131097-caption-02_T7",
"type": "Tissue",
"text": [
"locus coeruleus"
],
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911,
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]
],
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},
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"id": "PMC-3131097-caption-02_T8",
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"somatodendritic"
],
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963,
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],
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},
{
"id": "PMC-3131097-caption-02_T9",
"type": "Cellular_component",
"text": [
"synaptic"
],
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]
],
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},
{
"id": "PMC-3131097-caption-02_T10",
"type": "Cellular_component",
"text": [
"presynaptic"
],
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1138,
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]
],
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},
{
"id": "PMC-3131097-caption-02_T11",
"type": "Cell",
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"somatodendritic"
],
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],
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},
{
"id": "PMC-3131097-caption-02_T12",
"type": "Cellular_component",
"text": [
"synaptic"
],
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[
835,
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]
],
"normalized": []
}
] | [] | [] | [] |
PMID-18537682 | PMID-18537682 | [
{
"id": "PMID-18537682__text",
"type": "abstract",
"text": [
"Research advances of endostatin and its short internal fragments.\nEndostatin, the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, there are a large number of research papers on endostatin. However, the action mechanism of endostatin is still a matter of ongoing discussion. The objective of this review is to elucidate its origin and elementary structure, and to discuss its structure basis of activity and action mechanisms based on the latest research. Furthermore, some published studies reporting the antiangiogenic effects of endostatin-derived peptides were also reviewed. It is proposed that the amino acid sequence of endostatin contains both angiosuppressive and angiostimulatory domains. Short endostatin fragments may be exploited as a new angiogenesis inhibitor for therapeutic applications, in substitution of the full length endostatin. These studies on endostatin fragments also shed light on our understanding of the molecular action mechanisms of endostatin.\n"
],
"offsets": [
[
0,
1015
]
]
}
] | [] | [] | [] | [] |
PMC-1896192-sec-09 | PMC-1896192-sec-09 | [
{
"id": "PMC-1896192-sec-09__text",
"type": "sec",
"text": [
"Supporting Information\nAlternate Language Article S1\nTranslation of the manuscript into French by EL\n(201 KB DOC).\nClick here for additional data file.\n"
],
"offsets": [
[
0,
152
]
]
}
] | [] | [] | [] | [] |
PMID-9695407 | PMID-9695407 | [
{
"id": "PMID-9695407__text",
"type": "abstract",
"text": [
"Homeobox genes in hematopoiesis and leukemogenesis. \nHomeobox genes have a strikingly conserved 61-amino acid sequence, encoding DNA-binding domain. Some homeobox genes, located in four clusters are designated HOX A through D, while others are known as divergent homeobox genes. Many researchers have demonstrated that hematopoietic cells express many homeobox genes. Induced over- and under-expression of these genes has been used to demonstrate their affect on some aspects of hematopoiesis and leukemogenesis. Recently, knock-out mice of homeobox genes by targeted disruption have also been used to examine their hematological effect. There are examples of the aberrant expression of a homeobox gene causing leukemias in humans. In pre-B acute lymphoblastic leukemia (ALL) with t(1;19) translocation, a fusion protein is created between E2A and a homeobox gene PBX. In T-cell ALL with t(10;14) translocation, the HOX 11 gene is deregulated. In acute myeloid leukemia (AML) with t(7;11) translocation, the HOX A9 gene is rearranged. In this review article, many functions of homeobox genes both at the early stem cell level as well as at the later stages of hematopoietic differentiation, and the leukemogenic effect of altered homeobox genes are discussed.\n"
],
"offsets": [
[
0,
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]
]
}
] | [
{
"id": "PMID-9695407_T9",
"type": "Cell",
"text": [
"hematopoietic cells"
],
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[
319,
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]
],
"normalized": []
},
{
"id": "PMID-9695407_T14",
"type": "Cancer",
"text": [
"leukemias"
],
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[
711,
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],
"normalized": []
},
{
"id": "PMID-9695407_T16",
"type": "Cancer",
"text": [
"pre-B acute lymphoblastic leukemia"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-9695407_T17",
"type": "Cancer",
"text": [
"ALL"
],
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[
771,
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]
],
"normalized": []
},
{
"id": "PMID-9695407_T21",
"type": "Cancer",
"text": [
"T-cell ALL"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-9695407_T23",
"type": "Cancer",
"text": [
"acute myeloid leukemia"
],
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[
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]
],
"normalized": []
},
{
"id": "PMID-9695407_T24",
"type": "Cancer",
"text": [
"AML"
],
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[
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"normalized": []
},
{
"id": "PMID-9695407_T27",
"type": "Cell",
"text": [
"stem cell"
],
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[
1110,
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]
],
"normalized": []
},
{
"id": "PMID-9695407_T47",
"type": "Cell",
"text": [
"hematopoietic"
],
"offsets": [
[
1160,
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],
"normalized": []
}
] | [] | [] | [] |