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36 results on '"Eskandarpour, Malihe"'

4. Therapeutic Validation of GEF-H1 Using a De Novo Designed Inhibitor in Models of Retinal Disease

Author

Mills, Clare, primary, Hemkemeyer, Sandra A., additional, Alimajstorovic, Zerin, additional, Bowers, Chantelle, additional, Eskandarpour, Malihe, additional, Greenwood, John, additional, Calder, Virginia, additional, Chan, A. W. Edith, additional, Gane, Paul J., additional, Selwood, David L., additional, Matter, Karl, additional, and Balda, Maria S., additional

Published
2022
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12. Allergic eye disease: Blocking LTB4/C5 in vivo suppressed disease and Th2 & Th9 cells.

Author

Eskandarpour, Malihe, Zhang, Xiaozhe, Micera, Alessandra, Zaher, Sarah, Larkin, Frank D. P., Nunn, Miles, Bonini, Stefano, Weston‐Davies, Wynne, and Calder, Virginia L.

Subjects
*TH2 cells, *EYE diseases, *ALLERGIES, *TRYPTASE, *CELL receptors, *ALLERGIC conjunctivitis
Abstract

Within the infiltrating CD4 SP + sp T cells in EAC, Th9 cells (IL-9 SP + sp PU.1 SP + sp ) and IL-9-expressing Th2 cells (GATA3 SP + sp IL-4 SP + sp IL-9 SP + sp ) cells were increased in OVA-challenged mice compared with controls (Figure S1H-J). Recent studies have demonstrated that IL-9 can be produced by Th9 and Th2 cells.5,6 To determine which CD4 SP + sp T cell subset was producing IL-9, transcription factor expression was investigated. [Extracted from the article]

Published
2022
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15. Functionally distinct IFN‐γ+IL‐17A+ Th cells in experimental autoimmune uveitis: T‐cell heterogeneity, migration, and steroid response.

Author

Chen, Yi‐Hsing, Eskandarpour, Malihe, Gondrand, Aurelia, Zhang, Xiaozhe, Gu, Renyang, Galatowicz, Grazyna, Lightman, Sue L., and Calder, Virginia L.

Subjects
T helper cells, TH1 cells, STEROID drugs, UVEITIS, CHEMOKINE receptors
Abstract

Immunopathogenic roles for both Th1 (CD4+IFN‐γ+) and Th17 (CD4+IL‐17A+) cells have been demonstrated in experimental autoimmune uveitis (EAU). However, the role for Th17/Th1 (CD4+ T cells co‐expressing IFN‐γ and IL‐17A) cells in EAU is not yet understood. Using interphotoreceptor retinoid‐binding protein peptide‐induced EAU in mice, we found increased levels of Th17/Th1 cells in EAU retinae (mean 9.6 ± 4.2%) and draining LNs (mean 8.4 ± 3.9%; p = 0.01) relative to controls. Topical dexamethasone treatment effectively reduced EAU severity and decreased retinal Th1 cells (p = 0.01), but had no impact on retinal Th17/Th1 or Th17 cells compared to saline controls. Using in vitro migration assays with mouse CNS endothelium, we demonstrated that Th17/Th1 cells were significantly increased within the migrated population relative to controls (mean 15.6 ± 9.5% vs. 1.9 ± 1.5%; p = 0.01). Chemokine receptor profiles of Th17/Th1 cells (CXCR3 and CCR6) did not change throughout the transendothelial migration process and were unaffected by dexamethasone treatment. These findings support a role for Th17/Th1 cells in EAU and their resistance to steroid inhibition suggests the importance of targeting both Th17 and Th17/Th1 cells for improving therapy. [ABSTRACT FROM AUTHOR]

Published
2020
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16. Leukotriene B4and Its Receptor in Experimental Autoimmune Uveitis and in Human Retinal Tissues

Author

Eskandarpour, Malihe, Chen, Yi-Hsing, Nunn, Miles A., Coupland, Sarah E., Weston-Davies, Wynne, and Calder, Virginia L.

Abstract

Nomacopan, a drug originally derived from tick saliva, has dual functions of sequestering leukotriene B4(LTB4) and inhibiting complement component 5 (C5) activation. Nomacopan has been shown to provide therapeutic benefit in experimental autoimmune uveitis (EAU). Longer acting forms of nomacopan were more efficacious in mouse EAU models, and the long-acting variant that inhibited only LTB4was at least as effective as the long-acting variant that inhibited both C5 and LTB4, preventing structural damage to the retina and a significantly reducing effector T helper 17 cells and inflammatory macrophages. Increased levels of LTB4and C5a (produced upon C5 activation) were detected during disease progression. Activated retinal lymphocytes were shown to express LTB4receptors (R) in vitroand in inflamed draining lymph nodes. Levels of LTB4R-expressing active/inflammatory retinal macrophages were also increased. Within the draining lymph node CD4+T-cell population, 30% expressed LTB4R+ following activation in vitro, whereas retinal infiltrating cells expressed LTB4R and C5aR. Validation of expression of those receptors in human uveitis and healthy tissues suggests that infiltrating cells could be targeted by inhibitors of the LTB4-LTB4 receptor 1 (BLT1) pathway as a novel therapeutic approach. This study provides novel data on intraocular LTB4and C5a in EAU, their associated receptor expression by retinal infiltrating cells in mouse and human tissues, and in attenuating EAU via the dual inhibitor nomacopan.

Published
2021
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19. T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex

Author

Hertweck, Arnulf, primary, Evans, Catherine M., additional, Eskandarpour, Malihe, additional, Lau, Jonathan C.H., additional, Oleinika, Kristine, additional, Jackson, Ian, additional, Kelly, Audrey, additional, Ambrose, John, additional, Adamson, Peter, additional, Cousins, David J., additional, Lavender, Paul, additional, Calder, Virginia L., additional, Lord, Graham M., additional, and Jenner, Richard G., additional

Published
2016
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20. Species-specific in vivo engraftment of the human BL melanoma cell line results in an invasive dedifferentiated phenotype not present in xenografts

Author

Cedervall, Jessica, Jamil, Seema, Prasmickaite, Lina, Cheng, YenFu, Eskandarpour, Malihe, Hansson, Johan, Maelandsmo, Gunhild M., Ringborg, Ulrik, Gulyas, Miklos, Zhen, He Suo, Kanter, Lena, Ahrlund-Richter, Lars, Cedervall, Jessica, Jamil, Seema, Prasmickaite, Lina, Cheng, YenFu, Eskandarpour, Malihe, Hansson, Johan, Maelandsmo, Gunhild M., Ringborg, Ulrik, Gulyas, Miklos, Zhen, He Suo, Kanter, Lena, and Ahrlund-Richter, Lars

Abstract

For clinically relevant studies on melanoma progression and invasiveness, in vivo experimental systems with a human cellular microenvironment would be advantageous. We have compared tumor formation from a human cutaneous malignant melanoma cell line (BL), after injection as conventional xenografts in the mouse, or when injected into a predominantly species-specific environment of human embryonic stem cell-derived teratoma induced in the mouse (the hEST model). The resulting melanoma histology was generally analogous, both systems showing delimited densely packed areas with pleomorphic cells of malignant appearance. A specificity of the integration process into the human embryonic teratoma tissues was indicated by the melanoma exclusively being found in areas compatible with condensed mesenchyme, similar to neural crest development. Here, also enhanced neovascularization was seen within the human mesenchymal tissues facing the BL melanoma growth. Furthermore, in the hEST model an additional melanoma cell phenotype occurred, located at the border of, or infiltrating into, the surrounding human loose mesenchymal fibrous stroma. This BL population had a desmoplastic spindle-like appearance, with markers indicative of dedifferentiation and migration. The appearance of this apparently more aggressive phenotype, as well as the induction of human angiogenesis, shows specific interactions with the human embryonic microenvironment in the hEST model. In conclusion, these data provide exciting options for using the hEST model in molecular in vivo studies on differentiation, invasiveness, and malignancy of human melanoma, while analyzing species-specific reactions in vivo.

Published
2009
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21. Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2

Author

Guilhamon, Paul, primary, Eskandarpour, Malihe, additional, Halai, Dina, additional, Wilson, Gareth A., additional, Feber, Andrew, additional, Teschendorff, Andrew E., additional, Gomez, Valenti, additional, Hergovich, Alexander, additional, Tirabosco, Roberto, additional, Fernanda Amary, M., additional, Baumhoer, Daniel, additional, Jundt, Gernot, additional, Ross, Mark T., additional, Flanagan, Adrienne M., additional, and Beck, Stephan, additional

Published
2013
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22. Molecular genetics of cutaneous malignant melanoma

Author

Eskandarpour, Malihe and Eskandarpour, Malihe

Abstract

Cutaneous malignant melanoma is an aggressive tumor of melanocytes in the skin with rapidly increasing incidence. Patients with advanced disease have a poor prognosis since the tumor is usually resistant to current therapies. Therefore, the development of novel strategies for preventing and treating melanoma is important. To explore novel therapies we need to find appropriate targets and for that knowledge about the biology of melanoma is important. There is growing evidence suggesting that NRAS has an important role in tumorigenesis and tumor maintenance in malignant melanoma and that the RAS-RAF-ERK signaling pathway is constitutively activated through multiple mechanisms, one of which is activating mutations in NRAS gene. In an initial study, we investigated the occurrence of activating mutation in the NRAS gene in a subset of patients with hereditary melanoma carrying germ line CDKN2A alterations. From this study we found differences in the frequency of NRAS mutations between hereditary and sporadic melanomas. Activating mutations in NRAS codon 61 were found in 95% (20/21) of primary hereditary melanomas but in only 10% (1/10) of sporadic melanomas. We also detected multiple activating NRAS mutations in tumor cells from different regions of individual primary hereditary melanomas. We concluded that the high frequency of NRAS codon 61 mutations detected in these hereditary melanomas may be the result of a hypermutability phenotype associated with the hereditary predisposition for melanoma development in patients with germline CDKN2A mutations. The presence of a mutant NRAS oncogene in sporadic and familial melanomas implies that the NRAS oncogene may be an important target for prevention and treatment of melanomas. Therefore, to better define the role of this oncogene in melanoma development, we specifically targeted this mutant oncogene using RNAi techniques and studied the effect of suppression of mutant NRAS on melanoma cell lines. Suppression of oncogenic NRA

Published
2007

23. Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2

Author

Amary, M Fernanda, primary, Damato, Stephen, additional, Halai, Dina, additional, Eskandarpour, Malihe, additional, Berisha, Fitim, additional, Bonar, Fiona, additional, McCarthy, Stan, additional, Fantin, Valeria R, additional, Straley, Kimberly S, additional, Lobo, Samira, additional, Aston, Will, additional, Green, Claire L, additional, Gale, Rosemary E, additional, Tirabosco, Roberto, additional, Futreal, Andrew, additional, Campbell, Peter, additional, Presneau, Nadège, additional, and Flanagan, Adrienne M, additional

Published
2011
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27. Species-Specific In vivo Engraftment of the Human BL Melanoma Cell Line Results in an Invasive Dedifferentiated Phenotype Not Present in Xenografts

Author

Cedervall, Jessica, primary, Jamil, Seema, additional, Prasmickaite, Lina, additional, Cheng, YenFu, additional, Eskandarpour, Malihe, additional, Hansson, Johan, additional, Mælandsmo, Gunhild M., additional, Ringborg, Ulrik, additional, Gulyas, Miklos, additional, Zhen, He Suo, additional, Kanter, Lena, additional, and Ährlund-Richter, Lars, additional

Published
2009
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35. T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex

Author

Hertweck, Arnulf, Evans, Catherine M., Eskandarpour, Malihe, Lau, Jonathan C.H., Oleinika, Kristine, Jackson, Ian, Kelly, Audrey, Ambrose, John, Adamson, Peter, Cousins, David J., Lavender, Paul, Calder, Virginia L., Lord, Graham M., and Jenner, Richard G.

Subjects
lcsh:Biology (General), Biochemistry, Genetics and Molecular Biology(all), chemical and pharmacologic phenomena, hemic and immune systems, lcsh:QH301-705.5
Abstract

The transcription factor T-bet directs Th1 cell differentiation, but the molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood. Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the form of the super elongation complex (SEC). Th1 genes are occupied by H3K4me3 and RNA polymerase II in Th2 cells, while T-bet-mediated recruitment of P-TEFb in Th1 cells activates transcriptional elongation. P-TEFb is recruited to both genes and enhancers, where it activates enhancer RNA transcription. P-TEFb inhibition and Mediator and SEC knockdown selectively block activation of T-bet target genes, and P-TEFb inhibition abrogates Th1-associated experimental autoimmune uveitis. T-bet activity is independent of changes in NF-κB RelA and Brd4 binding, with T-bet- and NF-κB-mediated pathways instead converging to allow P-TEFb recruitment. These data provide insight into the mechanism through which lineage-specifying factors promote differentiation of alternative T cell fates.

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36. Functionally distinct IFN-γ + IL-17A + Th cells in experimental autoimmune uveitis: T-cell heterogeneity, migration, and steroid response.

Author

Chen YH, Eskandarpour M, Gondrand A, Zhang X, Gu R, Galatowicz G, Lightman SL, and Calder VL

Subjects
Animals, CD4-Positive T-Lymphocytes immunology, Cells, Cultured, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred C57BL, Autoimmune Diseases immunology, Cell Movement immunology, Interferon-gamma immunology, Interleukin-17 immunology, Th1 Cells immunology, Th17 Cells immunology
Abstract

Immunopathogenic roles for both Th1 (CD4 + IFN-γ + ) and Th17 (CD4 + IL-17A + ) cells have been demonstrated in experimental autoimmune uveitis (EAU). However, the role for Th17/Th1 (CD4 + T cells co-expressing IFN-γ and IL-17A) cells in EAU is not yet understood. Using interphotoreceptor retinoid-binding protein peptide-induced EAU in mice, we found increased levels of Th17/Th1 cells in EAU retinae (mean 9.6 ± 4.2%) and draining LNs (mean 8.4 ± 3.9%; p = 0.01) relative to controls. Topical dexamethasone treatment effectively reduced EAU severity and decreased retinal Th1 cells (p = 0.01), but had no impact on retinal Th17/Th1 or Th17 cells compared to saline controls. Using in vitro migration assays with mouse CNS endothelium, we demonstrated that Th17/Th1 cells were significantly increased within the migrated population relative to controls (mean 15.6 ± 9.5% vs. 1.9 ± 1.5%; p = 0.01). Chemokine receptor profiles of Th17/Th1 cells (CXCR3 and CCR6) did not change throughout the transendothelial migration process and were unaffected by dexamethasone treatment. These findings support a role for Th17/Th1 cells in EAU and their resistance to steroid inhibition suggests the importance of targeting both Th17 and Th17/Th1 cells for improving therapy., (© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Published
2020
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