Homo sapiens
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PROVIDER: PRJNA113709 | ENA |
REPOSITORIES: ENA
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Project description:A Microarray Search for Effects of Thyrotropin and Iodide on Angiogenesis Factors Objective: Excess iodide has been administered to hyperthyroid patients before thyroid surgery to reduce intraoperative bleeding and oozing. The purpose of this study was to elucidate the mechanism by which iodide reduces blood flow in the hypervascular thyroid gland. Design: Human thyroid follicles were cultured in the presence or absence of thyrotropin (TSH), or in medium containing various concentrations of iodide, and TSH- or iodide-regulated gene expression was analyzed by cDNA microarray. Main outcome: TSH stimulated the expression of thyroglobulin, peroxidase, sodium-iodide symporter, vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PGF) but decreased that of VEGF-C by half. When thyroid follicles were cultured in high-iodide (10-5M) medium, TSH-induced expression of VEGF-A, VEGF-B and PGF was decreased, accompanied by a reduction of VEGF-A release into the medium. Furthermore, expression of putative angiogenesis inhibitors such as urokinase-type plasminogen activator (PLAU) was increased. These findings were confirmed by real-time polymerase chain reaction (PCR) and Northern blot hybridization. Conclusions: We have demonstrated for the first time that iodide at high concentration decreases the expression of the angiogenic factors VEGF-A, VEGF-B, and PGF, accompanied by an increase in the expression of possible anti-angiogenic factors such as PLAU. These proangiogenic and antiangiogenic factors may at least partly account for the iodide-induced decrease in thyroid blood flow.
2008-08-01 | GSE12244 | GEO
Project description:We are going to submit a paper entitled “Iodide-induced Chemokines and Genes Related to Immunological Function in Cultured Human Thyroid Follicles” to THYROID
2009-07-14 | GSE16957 | GEO
Project description:Amiodarone reversibly decreases sodium-iodide symporter mRNA expression at therapeutic concentrations and induces antioxidant responses at supraphysiological concentrations in cultured human thyroid follicles Amiodarone, a potent antiarrhythmic agent, is a highly active oxidant, exerting cytotoxic effects on thyrocytes at pharmacological concentrations. Patients receiving amiodarone usually remain euthyroid, but occasionally develop thyroid dysfunction, such as amiodarone-associated hypothyroidism or amiodarone-induced thyrotoxicosis. To elucidate the mechanism by which amiodarone elicits thyroid dysfunction, human thyroid follicles were cultured with TSH and amiodarone at therapeutic (1-2 microM) and pharmacological (10-20microM) concentrations, and the drug-induced effect on whole human gene expression was analyzed by cDNA microarray. Amiodarone at 1-2microM decreased the expression level of the sodium-iodide symporter (NIS) to nearly half, but did not affect genes participating in thyroid hormonogenesis (thyroid peroxidase, thyroglobulin, pendrin, NADPH oxidase). Higher concentrations (10-20 microM) decreased the expression of all these genes, accompanied by increased expression of antioxidant proteins such as heme oxygenase 1 and ferritin. When thyroid follicles obtained from a patient with Graves’ disease who had been treated with amiodarone for 2 months before thyroidectomy were cultured in amiodarone-free medium, TSH-induced thyroid function was intact, suggesting that amiodarone at a maintenance dose did not elicit any cytotoxic effect on thyrocytes. The ultrastructural features of cultured thyroid follicles were compatible with these in vitro findings. These in vitro and ex vivo findings suggest that patients taking maintenance doses of amiodarone usually remain euthyroid, probably due to escape from the Wolff-Chaikoff effect mediated by decreased expression of NIS mRNA. Furthermore, amiodarone is not cytotoxic for thyrocytes at therapeutic concentrations but elicits cytotoxicity through oxidant activity at supra-physiological concentrations. Keywords: Cultured human thyroid follicles
2008-07-19 | GSE12164 | GEO
Project description:Graves’ disease is characterized by goiter, palpitation and exophthalmos (Merseburg’s trias). However, a few patients develop exophthalmos even though their thyroid function is normal, a condition known as euthyroid Graves’ disease (EGD). It remains unknown why these patients remain euthyroid, even though they have potent thyroid-stimulating antibody (TSAb). To investigate whether the immunoglobulins (IgGs) obtained from EGD patients elicit thyroid hormone-releasing activity (THRA), thyroid follicles obtained from Graves’ patients were cultured in agarose-coated culture dishes, and 125I incorporated into the thyroid follicles and organic 125I (mainly de novo-synthesized 125I-T3+125I-T4) released into the culture medium by TSH or purified IgGs were determined as thyroid hormone-releasing activity (THRA). This thyroid follicle culture system allows maintenance of the Wolff-Chaikoff effect, and the expression of mRNA for the sodium-iodide symporter is decreased by high concentrations of iodide (10-6-10-4M) and therapeutic concentrations of amiodarone (1-2microM). hTSH elicited THRA most efficiently at 0.4-10 microU/ml, suggesting that thyroid function is controlled within the normal range of TSH concentration (0.4-4.0 microU/ml). All IgGs obtained from hyperthyroid Graves’ patients elicited THRA equivalent to more than 4.6 microU/ml hTSH. IgGs obtained from EGD patients also had potent THRA, whereas IgGs obtained from normal subjects and Graves’ patients in complete remission had no significant THRA. When thyroid follicles from Graves’ thyroid, into which a number of lymphocytes had infiltrated, were used, only slight THRA was elicited by bTSH or Graves’ IgGs, probably due to inflammatory cytokines produced by immunocompetent cells that could not be separated during gentle centrifugation. Indeed, when thyroid follicles were cultured with autologous intrathyroidal lymphocytes, interleukin-2 completely abolished TSH-induced THRA. When thyroid follicles were cultured with inflammatory cytokines (interleukin-1, tumor-necrosis factor-alpha, or interferon-gamma), each cytokine inhibited TSH-induced THRA in a concentration-dependent manner. These cytokines at lower concentrations synergistically and completely inhibited TSH-induced THRA. Microarray analyses of thyroid follicles cultured with IL-1alpha, TNF-alpha, or INF-gamma revealed decreased expression of mRNAs for TSHR, NIS, TPO and thyroglobulin, accompanied by increased expression of mRNAs for chemokines and cytokines. These findings suggest that IgGs obtained from patients with EGD have potent THRA in vitro, whereas in vivo, these IgGs are unable to elicit biological activity in the thyroid gland. Presumably, immunocompetent cells that infiltrate the thyroid gland produce inflammatory cytokines that synergistically inhibit thyroid function. Since a similar phenomenon may occur in the retroorbital tissues, these patients may develop exophthalmos despite having a normal serum level of TSH. This data will be published in Hyperthyroidism: Etiology, Diagnosis and Treatment (editor-in-chief;Dr.Frank Clumbus,Nova Science Publishers, Inc, New York, USA) Experiment Overall Design: One conditioned experiments: control vs. IL-1 alpha 5ng/ml, cultured for 24 hours; control vs. TNF alpha 20ng/ml, cultured for 24 hours; control vs. IFN gamma 1000U/ml, cultured for 48 hours.
2009-05-01 | E-GEOD-15838 | biostudies-arrayexpress
Project description:Fruquintinib (HMPL-013) is a novel oral small molecule that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts. Combined with hepatic arterial infusion chemotherapy (HAIC), this study is conducted to assess the efficacy and safety of this regimen in patients with unresectable colorectal cancer liver metastases as the third-line therapy.
| 2733287 | ecrin-mdr-crc
Project description:Graves’ disease is characterized by goiter, palpitation and exophthalmos (Merseburg’s trias). However, a few patients develop exophthalmos even though their thyroid function is normal, a condition known as euthyroid Graves’ disease (EGD). It remains unknown why these patients remain euthyroid, even though they have potent thyroid-stimulating antibody (TSAb). To investigate whether the immunoglobulins (IgGs) obtained from EGD patients elicit thyroid hormone-releasing activity (THRA), thyroid follicles obtained from Graves’ patients were cultured in agarose-coated culture dishes, and 125I incorporated into the thyroid follicles and organic 125I (mainly de novo-synthesized 125I-T3+125I-T4) released into the culture medium by TSH or purified IgGs were determined as thyroid hormone-releasing activity (THRA). This thyroid follicle culture system allows maintenance of the Wolff-Chaikoff effect, and the expression of mRNA for the sodium-iodide symporter is decreased by high concentrations of iodide (10-6-10-4M) and therapeutic concentrations of amiodarone (1-2microM). hTSH elicited THRA most efficiently at 0.4-10 microU/ml, suggesting that thyroid function is controlled within the normal range of TSH concentration (0.4-4.0 microU/ml). All IgGs obtained from hyperthyroid Graves’ patients elicited THRA equivalent to more than 4.6 microU/ml hTSH. IgGs obtained from EGD patients also had potent THRA, whereas IgGs obtained from normal subjects and Graves’ patients in complete remission had no significant THRA. When thyroid follicles from Graves’ thyroid, into which a number of lymphocytes had infiltrated, were used, only slight THRA was elicited by bTSH or Graves’ IgGs, probably due to inflammatory cytokines produced by immunocompetent cells that could not be separated during gentle centrifugation. Indeed, when thyroid follicles were cultured with autologous intrathyroidal lymphocytes, interleukin-2 completely abolished TSH-induced THRA. When thyroid follicles were cultured with inflammatory cytokines (interleukin-1, tumor-necrosis factor-alpha, or interferon-gamma), each cytokine inhibited TSH-induced THRA in a concentration-dependent manner. These cytokines at lower concentrations synergistically and completely inhibited TSH-induced THRA. Microarray analyses of thyroid follicles cultured with IL-1alpha, TNF-alpha, or INF-gamma revealed decreased expression of mRNAs for TSHR, NIS, TPO and thyroglobulin, accompanied by increased expression of mRNAs for chemokines and cytokines. These findings suggest that IgGs obtained from patients with EGD have potent THRA in vitro, whereas in vivo, these IgGs are unable to elicit biological activity in the thyroid gland. Presumably, immunocompetent cells that infiltrate the thyroid gland produce inflammatory cytokines that synergistically inhibit thyroid function. Since a similar phenomenon may occur in the retroorbital tissues, these patients may develop exophthalmos despite having a normal serum level of TSH. This data will be published in Hyperthyroidism: Etiology, Diagnosis and Treatment (editor-in-chief;Dr.Frank Clumbus,Nova Science Publishers, Inc, New York, USA)
2009-04-28 | GSE15838 | GEO
Project description:Fruquintinib is a novel oral small molecule compound discovered and developed by Hutchison MediPharma that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts.Based on first-in-human study, both 4mg QD and 5mg 3wks on/1wk off are safety and efficacy, this phase Ib study is to evaluable the safety, tolerability and efficacy of these 2 regimens with mCRC failed 2nd therapy or more and to determine the recommended dose and regimen in phase II/III study.
| 2154098 | ecrin-mdr-crc
Project description:Amiodarone effects on cultured human thyroid follicles
| PRJNA113455 | ENA
Project description:The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial post-wound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage prior to progression of wound healing toward tissue homeostasis. Due to its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 hours of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment.
2014-04-15 | PXD000462 | Pride
Project description:We are going to submit a paper entitled âIodide-induced Chemokines and Genes Related to Immunological Function in Cultured Human Thyroid Folliclesâ to THYROID One conditioned experiments, control NaI 10-8M vs. NaI 10-5M , cultured for 3 hours or 48 hours.
2010-08-18 | E-GEOD-16957 | biostudies-arrayexpress