[ { "instruction": "Given a text, identify and extract specified relations between anatomical entities mentioned within it. The specified relation types are [frag, Part-of]. Relation explanation: frag: Frag relation marking coordination with ellipsis; Part-of: Part-of relation marking entity mention spanning a prepositional phrase. Present each relation in format as follows: [ ].", "input": "A pancreatic beta -cell-specific enhancer in the human PDX-1 gene is regulated by hepatocyte nuclear factor 3beta (HNF-3beta ), HNF-1alpha, and SPs transcription factors.\nThe PDX-1 transcription factor plays a key role in pancreas development. Although expressed in all cells at the early stages, in the adult it is mainly restricted to the beta-cell. To characterize the regulatory elements and potential transcription factors necessary for human PDX-1 gene expression in beta-cells, we constructed a series of 5' and 3' deletion fragments of the 5'-flanking region of the gene, fused to the luciferase reporter gene. In this report, we identify by transient transfections in beta- and non-beta-cells a novel beta-cell-specific distal enhancer element located between -3.7 and -3.45 kilobases. DNase I footprinting analysis revealed two protected regions, one binding the transcription factors SP1 and SP3 and the other hepatocyte nuclear factor 3beta (HNF-3beta) and HNF-1alpha. Cotransfection experiments suggest that HNF-3beta, HNF-1alpha, and SP1 are positive regulators of the herein-described human PDX-1 enhancer element. Furthermore, mutations within each motif abolished the binding of the corresponding factor(s) and dramatically impaired the enhancer activity, therefore suggesting cooperativity between these factors.\n", "output": "[ ]" }, { "instruction": "Given a text, identify and extract specified relations between anatomical entities mentioned within it. The specified relation types are [frag, Part-of]. Relation explanation: frag: Frag relation marking coordination with ellipsis; Part-of: Part-of relation marking entity mention spanning a prepositional phrase. Present each relation in format as follows: [ ].", "input": "Dynorphin is contained within hippocampal mossy fibers: immunochemical alterations after kainic acid administration and colchicine-induced neurotoxicity.\nAntisera raised against synthetic dynorphin or [Leu5]enkephalin demonstrate immunostaining in hippocampal mossy fibers and in dentate granule cells. However, dynorphin immunoreactivity (ir) appears to be denser in immunocytochemical preparations and is quantitatively greater by radioimmunoassay than enkephalin-ir. Immunostaining with dynorphin antisera is eliminated by adsorption with 1-100 microM dynorphin-17 whereas immunostaining with enkephalin antisera is eliminated by adsorption with 1-100 microM [Leu5]enkephalin, dynorphin-17, dynorphin-(1-13), or alpha-neo-endorphin. Intrahippocampal colchicine injections, which selectively destroy dentate granule cells, significantly decrease the dynorphin-ir and enkephalin-ir levels in rat hippocampus. Intraventricularly administered kainic acid, which selectively destroys CA3-4 pyramidal cells, results in an increase of enkephalin immunostaining in mossy fibers and a significant increase in enkephalin-ir by radioimmunoassay in whole hippocampus. The enkephalin-ir cells and fibers in entorhinal/perirhinal cortex, which innervate rat hippocampus and dentate gyrus, do not contain dynorphin-ir.\n", "output": "[ ]" }, { "instruction": "Given a text, identify and extract specified relations between anatomical entities mentioned within it. The specified relation types are [frag, Part-of]. Relation explanation: frag: Frag relation marking coordination with ellipsis; Part-of: Part-of relation marking entity mention spanning a prepositional phrase. Present each relation in format as follows: [ ].", "input": "Prognostic significance of TRAIL signaling molecules in stage II and III colorectal cancer.\nPURPOSE:\nWe previously found that cellular FLICE-inhibitory protein (c-FLIP), caspase 8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (DR5) are major regulators of cell viability and chemotherapy-induced apoptosis in colorectal cancer. In this study, we determined the prognostic significance of c-FLIP, caspase 8, TRAIL and DR5 expression in tissues from patients with stage II and III colorectal cancer.\nEXPERIMENTAL DESIGN:\nTissue microarrays were constructed from matched normal and tumor tissue derived from patients (n = 253) enrolled in a phase III trial of adjuvant 5-fluorouracil-based chemotherapy versus postoperative observation alone. TRAIL, DR5, caspase 8, and c-FLIP expression levels were determined by immunohistochemistry.\nRESULTS:\nColorectal tumors displayed significantly higher expression levels of c-FLIP (P < 0.001), caspase 8 (P = 0.01), and DR5 (P < 0.001), but lower levels of TRAIL (P < 0.001) compared with matched normal tissue. In univariate analysis, higher TRAIL expression in the tumor was associated with worse overall survival (P = 0.026), with a trend to decreased relapse-free survival (RFS; P = 0.06), and higher tumor c-FLIP expression was associated with a significantly decreased RFS (P = 0.015). Using multivariate predictive modeling for RFS in all patients and including all biomarkers, age, treatment, and stage, we found that the model was significant when the mean tumor c-FLIP expression score and disease stage were included (P < 0.001). As regards overall survival, the overall model was predictive when both TRAIL expression and disease stage were included (P < 0.001).\nCONCLUSIONS:\nHigh c-FLIP and TRAIL expression may be independent adverse prognostic markers in stage II and III colorectal cancer and might identify patients most at risk of relapse.\n", "output": "[ ]" }, { "instruction": "Given a text, identify and extract specified relations between anatomical entities mentioned within it. The specified relation types are [frag, Part-of]. Relation explanation: frag: Frag relation marking coordination with ellipsis; Part-of: Part-of relation marking entity mention spanning a prepositional phrase. Present each relation in format as follows: [ ].", "input": "Introduction\nTea (Camellia sinensis L.) is one of the most widely consumed beverages in the world. (-)-Epigallocatechin-3-O-gallate (EGCG), which is the major green tea catechin present in the leaves, is believed to the compound most responsible for the health benefits attributed to tea. EGCG was reported to have antioxidative [1], [2], antimutagenic [3], anti-inflammatory [4], and anticarcinogenic activities [5].\nAlthough the EGCG concentrations required to elicit the anticancer activity have been shown to be more than 1 microM, the blood level of EGCG after consuming the equivalent of 2-3 cups of green tea was 0.1-0.6 microM and for an equivalent of 7-9 cups was still lower than 1 microM [6], [7]. In a cohort study, daily consumption of ten cups of green tea was required for the cancer preventive effect [8]. Moreover, adverse effects of green tea, mainly hepatitis, by consumption of high doses of green tea have been reported [9]. Therefore, it is important to enhance the pharmacologic effect of EGCG to obtain the health benefit in reasonable concentration in daily life.\nWe have reported that the cell-surface binding of EGCG and its derivatives is involved in their biological activities [10]-[15]. We have identified the 67-kDa laminin receptor (67LR) as a cell surface receptor for EGCG that mediates the anticancer activity of EGCG [16]. 67LR has been shown to be overexpressed on the cell surface of various tumor cells [17]. It was postulated that 67LR plays a significant role in the tumor progression and speculated that studies conducted to define the function of 67LR could provide a new approach to cancer prevention. Indeed, expression of 67 LR confers EGCG responsiveness to tumor cells in vivo [18].\nVitamin A, also known as retinol, participates in physiological activities related to the immune system, maintenance of epithelial and mucosa tissues, growth, reproduction, and bone development. It comes from animal sources, such as eggs, meat, milk, cheese, cream, liver, kidney, cod and halibut fish oil. In vitro and in animal models, it has been demonstrated that vitamin A is involved in the regulation and promotion of growth and differentiation of many cells [19]. The visual function of vitamin A depends on its natural and synthetic derivatives, retinoids [20]. All-trans-retinoic acid (ATRA), the active derivative of vitamin A, has been well documented as a growth and differentiation factor in many tissues and cells, and proved to be an effective treatment to many diseases including cancers [21], [22].\nRetinoids exert their physiological activities through retinoid receptor nuclear proteins that belong to the superfamily of steroid/thyroid hormone receptors, of which there are two classes, retinoic acid receptors (RARs) and the retinoic-X receptors (RXRs), each of which has three subtypes, alpha, beta, and gamma [23], [24]. The natural ligands for the RARs are ATRA and its stereoisomers 9-cis-RA and 13-cis-RA, whereas RXRs are activated by 9-cis-RA only. ATRA acts through RAR to transcriptionally activate target genes, such as cytochrome P450 and CRABI [24].\nThis study was designed to identify a food component that could be effectively used in combination with EGCG and to investigate the mechanism of action of this combination. By using in vitro and in vivo systems involving a highly metastatic mouse B16 melanoma cell line [25], we found that ATRA enhances the antitumor activity of EGCG by upregulating the 67 LR expression through RAR.\n", "output": "[ ] [ ]" }, { "instruction": "Given a text, identify and extract specified relations between anatomical entities mentioned within it. The specified relation types are [frag, Part-of]. Relation explanation: frag: Frag relation marking coordination with ellipsis; Part-of: Part-of relation marking entity mention spanning a prepositional phrase. Present each relation in format as follows: [ ].", "input": "[Histophysiology and histopathology of the adrenals in experimental hypokinesia].\nIn experiments on male rats in the course of 3-month hypokinesia phasic changes were observed in the relative adrenal gland weight, in the volume of the cell nuclei of the glomerular, fasicular zones and the medulla, in the activity of the succinic dehydrogenase, alkaline and acid phosphatases, in the RNA and catecholamine content. These changes are associated with variations in the secretion and biosynthesis of the hormones of the cortical and the medullary layer of the adrenal glands during the hypokinetic stress development.\n", "output": "[ ] [ ] [ ] [ ] [ ] [ ]" } ]