The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Terry F. Davies - One of the best experts on this subject based on the ideXlab platform.
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Thyroid-Specific T Cells in the Wistar Rat: 3. Induction of Anergy by a Syngeneic Thyroid Cell Line
Autoimmunity, 1996Co-Authors: Hironori Kimura, Terry F. DaviesAbstract:Using a syngeneic Wistar rat model we have shown that the Wistar rat Thyroid (WRT) Cell Line causes significant and specific proliferation of lymph node T Cells from normal Wistar rats, and of splenic T Cells from a Thyroiditis prone Line of BB/W rats, when cultured in the presence of irradiated feeder Cells. These T Cell responses were associated with a marked increase in the number of CD8+ T Cells. However, using normal Wistar rat T Cells which had been previously exposed to WRT Cells, rested and then re-exposed to WRT Cells as antigen, we consistently found that the T Cell population had been rendered unreactive, or anergic, to further Thyroid Cell stimulation. However, if recombinant rat IL-2 was added to the cultures, then T Cell responsivity was seen on re-exposure to WRT Cells. The lymphopenic BB/W rat also had T Cells which showed a primary T Cell response to the WRT Cell Line accompanied by a marked increase in CD8 + T Cells. In contrast to the Wistar rat T Cells, the BB/W T Cells retained a prol...
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Thyroid-Specific T Cells in the Wistar Rat: 3. Induction of Anergy by a Syngeneic Thyroid Cell Line
Autoimmunity, 1996Co-Authors: Hironori Kimura, Terry F. DaviesAbstract:Using a syngeneic Wistar rat model we have shown that the Wistar rat Thyroid (WRT) Cell Line causes significant and specific proliferation of lymph node T Cells from normal Wistar rats, and of splenic T Cells from a Thyroiditis prone Line of BB/W rats, when cultured in the presence of irradiated feeder Cells. These T Cell responses were associated with a marked increase in the number of CD8+ T Cells. However, using normal Wistar rat T Cells which had been previously exposed to WRT Cells, rested and then re-exposed to WRT Cells as antigen, we consistently found that the T Cell population had been rendered unreactive, or anergic, to further Thyroid Cell stimulation. However, if recombinant rat IL-2 was added to the cultures, then T Cell responsivity was seen on re-exposure to WRT Cells. The lymphopenic BB/W rat also had T Cells which showed a primary T Cell response to the WRT Cell Line accompanied by a marked increase in CD8+ T Cells. In contrast to the Wistar rat T Cells, the BB/W T Cells retained a proliferative responsiveness to WRT Cells on re-exposure although such responsiveness could also be markedly enhanced with IL-2. These data suggested that antigen-mediated inhibitory signals were induced in normal Wistar rat T Cells by the syngeneic WRT Cell Line, independent of the presence of co-stimulatory molecules. Furthermore, the Thyroiditis prone BB/W rat T Cells appeared to be less responsive to such anergy induction, perhaps contributing to their susceptibility to autoimmune Thyroid disease.
Hironori Kimura - One of the best experts on this subject based on the ideXlab platform.
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Thyroid-Specific T Cells in the Wistar Rat: 3. Induction of Anergy by a Syngeneic Thyroid Cell Line
Autoimmunity, 1996Co-Authors: Hironori Kimura, Terry F. DaviesAbstract:Using a syngeneic Wistar rat model we have shown that the Wistar rat Thyroid (WRT) Cell Line causes significant and specific proliferation of lymph node T Cells from normal Wistar rats, and of splenic T Cells from a Thyroiditis prone Line of BB/W rats, when cultured in the presence of irradiated feeder Cells. These T Cell responses were associated with a marked increase in the number of CD8+ T Cells. However, using normal Wistar rat T Cells which had been previously exposed to WRT Cells, rested and then re-exposed to WRT Cells as antigen, we consistently found that the T Cell population had been rendered unreactive, or anergic, to further Thyroid Cell stimulation. However, if recombinant rat IL-2 was added to the cultures, then T Cell responsivity was seen on re-exposure to WRT Cells. The lymphopenic BB/W rat also had T Cells which showed a primary T Cell response to the WRT Cell Line accompanied by a marked increase in CD8 + T Cells. In contrast to the Wistar rat T Cells, the BB/W T Cells retained a prol...
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Thyroid-Specific T Cells in the Wistar Rat: 3. Induction of Anergy by a Syngeneic Thyroid Cell Line
Autoimmunity, 1996Co-Authors: Hironori Kimura, Terry F. DaviesAbstract:Using a syngeneic Wistar rat model we have shown that the Wistar rat Thyroid (WRT) Cell Line causes significant and specific proliferation of lymph node T Cells from normal Wistar rats, and of splenic T Cells from a Thyroiditis prone Line of BB/W rats, when cultured in the presence of irradiated feeder Cells. These T Cell responses were associated with a marked increase in the number of CD8+ T Cells. However, using normal Wistar rat T Cells which had been previously exposed to WRT Cells, rested and then re-exposed to WRT Cells as antigen, we consistently found that the T Cell population had been rendered unreactive, or anergic, to further Thyroid Cell stimulation. However, if recombinant rat IL-2 was added to the cultures, then T Cell responsivity was seen on re-exposure to WRT Cells. The lymphopenic BB/W rat also had T Cells which showed a primary T Cell response to the WRT Cell Line accompanied by a marked increase in CD8+ T Cells. In contrast to the Wistar rat T Cells, the BB/W T Cells retained a proliferative responsiveness to WRT Cells on re-exposure although such responsiveness could also be markedly enhanced with IL-2. These data suggested that antigen-mediated inhibitory signals were induced in normal Wistar rat T Cells by the syngeneic WRT Cell Line, independent of the presence of co-stimulatory molecules. Furthermore, the Thyroiditis prone BB/W rat T Cells appeared to be less responsive to such anergy induction, perhaps contributing to their susceptibility to autoimmune Thyroid disease.
Hisao Seo - One of the best experts on this subject based on the ideXlab platform.
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Thyrotropin modifies activation of nuclear factor kappaB by tumour necrosis factor alpha in rat Thyroid Cell Line.
Biochemical Journal, 2001Co-Authors: Toyone Kikumori, Fukushi Kambe, Takashi Nagaya, Hiroomi Funahashi, Hisao SeoAbstract:We have recently demonstrated that nuclear factor kappaB (NF-kappaB) mediates the tumour necrosis factor alpha (TNF-alpha)-dependent expression of the gene encoding interleukin 6 (IL-6) in rat Thyroid FRTL-5 Cells cultured in the presence of thyrotropin (TSH). In the present study we investigated how TSH is involved in the activation of NF-kappaB by TNF-alpha in the Cells. Electrophoretic mobility-shift assay revealed that, in the absence of TSH, TNF-alpha activated a single protein-DNA complex containing the p50 subunit but not other NF-kappaB subunits such as p65. In contrast, two distinct protein-DNA complexes were activated in the presence of TSH: the faster-migrating complex contained only p50 subunit; the slower-migrating complex consisted of p65-p50 heterodimer. This TSH effect was mimicked by forskolin and Thyroid-stimulating antibodies obtained from patients with Graves's disease, suggesting that an increase in intraCellular cAMP is responsible for the induction of different NF-kappaBs by TNF-alpha. A transient transfection study with a luciferase reporter gene driven by multimerized NF-kappaB sites demonstrated that TNF-alpha increased the luciferase activities only in the presence of TSH, and that this increase was inhibited by the co-transfection of mutant p65, which prevented the function of wild-type p65 in a dominant-negative manner. Accordingly, TNF-alpha activated the expression of the IL-6 gene in the presence of TSH but not in its absence. Although the expression of the p105 gene, another known target for NF-kappaB, was increased by TNF-alpha in the absence of TSH, the presence of TSH further increased the mRNA level. Taken together, these observations indicate that the presence of TSH is crucial for the NF-kappaB-mediated actions of TNF-alpha on Thyroid follicular Cells.
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Thyrotropin modifies activation of nuclear factor κB by tumour necrosis factor α in rat Thyroid Cell Line
Biochemical Journal, 2001Co-Authors: Toyone Kikumori, Fukushi Kambe, Takashi Nagaya, Hiroomi Funahashi, Hisao SeoAbstract:We have recently demonstrated that nuclear factor κB (NF-κB) mediates the tumour necrosis factor α (TNF-α)-dependent expression of the gene encoding interleukin 6 (IL-6) in rat Thyroid FRTL-5 Cells cultured in the presence of thyrotropin (TSH). In the present study we investigated how TSH is involved in the activation of NF-κB by TNF-α in the Cells. Electrophoretic mobility-shift assay revealed that, in the absence of TSH, TNF-α activated a single protein–DNA complex containing the p50 subunit but not other NF-κB subunits such as p65. In contrast, two distinct protein–DNA complexes were activated in the presence of TSH: the faster-migrating complex contained only p50 subunit; the slower-migrating complex consisted of p65–p50heterodimer. This TSH effect was mimicked by forskolin and Thyroid-stimulating antibodies obtained from patients with Graves's disease, suggesting that an increase in intraCellular cAMP is responsible for the induction of different NF-κBs by TNF-α. A transient transfection study with a luciferase reporter gene driven by multimerized NF-κB sites demonstrated that TNF-α increased the luciferase activities only in the presence of TSH, and that this increase was inhibited by the co-transfection of mutant p65, which prevented the function of wild-type p65 in a dominant-negative manner. Accordingly, TNF-α activated the expression of the IL-6 gene in the presence of TSH but not in its absence. Although the expression of the p105 gene, another known target for NF-κB, was increased by TNF-α in the absence of TSH, the presence of TSH further increased the mRNA level. Taken together, these observations indicate that the presence of TSH is crucial for the NF-κB-mediated actions of TNF-α on Thyroid follicular Cells.
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Differential induction of fos and jun family genes by thyrotropin in rat Thyroid FRTL-5 Cells.
Thyroid : official journal of the American Thyroid Association, 1996Co-Authors: Fukushi Kambe, Takashi Miyazaki, Hisao SeoAbstract:Effect of thyrotropin (TSH) on the expression of the members of fos and jun family genes in a rat Thyroid Cell Line (FRTL-5) was examined by the reverse transcription-polymerase chain reaction (RT-...
Jae Kyung Myung - One of the best experts on this subject based on the ideXlab platform.
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The Significance of TROP2 Expression in Predicting Mutations in Papillary Thyroid Carcinoma
Korean Society of Pathologists & the Korean Society for Cytopathology, 2018Co-Authors: Joon Seog Kong, Hyeon Jin Kim, Min-jung Kim, Areumnuri Kim, Dalnim Lee, Kanghee Han, Sunhoo Park, Jae Soo Koh, Jae Kyung MyungAbstract:Background Trophoblast antigen 2 (TROP2) is a human trophoblast Cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary Thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC. Methods First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor Cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three Thyroid cancer Cell Lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal Thyroid Cell Line. Additionally, we checked TROP2 protein levels in a normal Thyroid Cell Line after introduction of the BRAF V600E mutation. Results In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p
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The Significance of TROP2 Expression in Predicting BRAF Mutations in Papillary Thyroid Carcinoma.
Journal of pathology and translational medicine, 2017Co-Authors: Joon Seog Kong, Hyeon Jin Kim, Min-jung Kim, Areumnuri Kim, Dalnim Lee, Kanghee Han, Sunhoo Park, Jae Soo Koh, Jae Kyung MyungAbstract:BACKGROUND Trophoblast antigen 2 (TROP2) is a human trophoblast Cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary Thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC. METHODS First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor Cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three Thyroid cancer Cell Lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal Thyroid Cell Line. Additionally, we checked TROP2 protein levels in a normal Thyroid Cell Line after introduction of the BRAF V600E mutation. RESULTS In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p
Fulvio Basolo - One of the best experts on this subject based on the ideXlab platform.
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establishment of a non tumorigenic papillary Thyroid Cell Line fb 2 carrying the ret ptc1 rearrangement
International Journal of Cancer, 2002Co-Authors: Fulvio Basolo, Riccardo Giannini, Antonio Toniolo, R. Casalone, Marina N. Nikiforova, Furio Pacini, Rossella Elisei, Paolo Miccoli, Piero Berti, Pinuccia FavianaAbstract:A novel human Thyroid papillary carcinoma Cell Line (FB-2) has been established and characterized. FB-2 Cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 Cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to Thyroid Cell transformation, were abundantly expressed in FB-2 Cells but not in normal Thyroid Cells. FB-2 Cells only partially retained the differentiated Thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for Thyroid Cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 Cells produced high levels of interleukin (IL)-6 and IL-8. © 2001 Wiley-Liss, Inc.
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Establishment of a non-tumorigenic papillary Thyroid Cell Line (FB-2) carrying the RET/PTC1 rearrangement.
International journal of cancer, 2002Co-Authors: Fulvio Basolo, Riccardo Giannini, Antonio Toniolo, R. Casalone, Marina N. Nikiforova, Furio Pacini, Rossella Elisei, Paolo Miccoli, Piero Berti, Pinuccia FavianaAbstract:A novel human Thyroid papillary carcinoma Cell Line (FB-2) has been established and characterized. FB-2 Cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 Cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to Thyroid Cell transformation, were abundantly expressed in FB-2 Cells but not in normal Thyroid Cells. FB-2 Cells only partially retained the differentiated Thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for Thyroid Cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 Cells produced high levels of interleukin (IL)-6 and IL-8. © 2001 Wiley-Liss, Inc.
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Potentiation of the malignant phenotype of the undifferentiated ARO Thyroid Cell Line by insertion of the bcl-2 gene
International journal of cancer, 1999Co-Authors: Fulvio Basolo, Lisa Fiore, Alfredo Fusco, Riccardo Giannini, Adriana Albini, Giorgio R. Merlo, Gabriella Fontanini, Pier Giulio Conaldi, Antonio TonioloAbstract:We have reported that bcl-2 is expressed in normal human Thyroid epithelium and that its expression is down-regulated in undifferentiated Thyroid tumors. Production of IL-6 was concomitantly down-regulated in these forms. Based on these observations, we analyzed whether insertion of bcl-2 would reverse the highly malignant phenotype of a Thyroid Cell Line (ARO) derived from an undifferentiated carcinoma. This Cell Line fails to produce Bcl-2 and IL-6. By infection with a bcl-2 retroviral vector, ARO Cells expressing bcl-2 (ARObcl-2) were obtained. Compared with parental Cells, expression of bcl-2 was associated with enhancement of growth potential (DNA synthesis, in vitro proliferation rate, anchorage-independent growth in semi-solid media). Chemotaxis and invasive potential in Boyden chambers were also increased. bcl-2-expressing Cells showed a reduced response to apoptotic stimuli (low-serum conditions or anti-neoplastic drugs). Large branched colonies were formed in Matrigel from ARObcl-2 Cells but not from parental Cells. Finally, ARObcl-2 Cells showed a decreased latency of tumor appearance when injected into immunodeficient mice. Potentiation of the malignant phenotype of ARO Cells by bcl-2 was not ascribed to altered expression of (i) cytokine/growth factors (IL-4, IL-6, IL-8, IL-10, IL-12, TGF-α, TGF-β), (ii) Thyroid-specific transcripts (TG, TPO, TSH-R, PIGF, PAX-8) or (iii) genes influencing tumor aggressiveness [VEGF, HMGI (Y), HMGI-C]. Our data indicate that bcl-2 potentiates the malignant phenotype of ARO Cells not only by limiting the response to apoptotic stimuli but also by enhancing proliferation and tumor aggressiveness. Int. J. Cancer81:956–962, 1999. © 1999 Wiley-Liss, Inc.