Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33233 http://dx.doi.org/10.3233/ACP-2011-0010 |
Resumo: | Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 x 10(6) human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). the experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. in the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. the recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001). the PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase in SERPINB5, a tumor suppressor gene, and a 10-fold higher expression of KISS I, a metastasis suppressor gene, in the treated group. Proangiogenic genes such as VEGFA, PDGFA and PDGFB were downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM. |
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Fernandes, Bruno F.Di Cesare, SebastianBelfort Neto, Rubens [UNIFESP]Maloney, ShawnMartins, ClaudiaCastiglione, EnzoIsenberg, JordanAbourbih, DanielAntecka, EmiliaBurnier Júnior, Miguel Nascente [UNIFESP]McGill UnivHenry C Witelson Ocular Pathol LabUniversidade Federal de São Paulo (UNIFESP)2016-01-24T14:05:54Z2016-01-24T14:05:54Z2011-01-01Analytical Cellular Pathology. Amsterdam: Ios Press, v. 34, n. 3, p. 123-130, 2011.2210-7177http://repositorio.unifesp.br/handle/11600/33233http://dx.doi.org/10.3233/ACP-2011-0010WOS000293107200004.pdf10.3233/ACP-2011-0010WOS:000293107200004Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 x 10(6) human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). the experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. in the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. the recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001). the PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase in SERPINB5, a tumor suppressor gene, and a 10-fold higher expression of KISS I, a metastasis suppressor gene, in the treated group. Proangiogenic genes such as VEGFA, PDGFA and PDGFB were downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM.McGill Univ, Ctr Hlth, Dept Ophthalmol & Pathol, Montreal, PQ, CanadaHenry C Witelson Ocular Pathol Lab, Montreal, PQ, CanadaUniversidade Federal de São Paulo UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilWeb of Science123-130engIos PressAnalytical Cellular Pathologyhttp://www.iospress.nl/service/authors/author-copyright-agreement/info:eu-repo/semantics/openAccessImatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000293107200004.pdfapplication/pdf1567094${dspace.ui.url}/bitstream/11600/33233/1/WOS000293107200004.pdf1202faaa606132bac2ad0da9d5eb32d7MD51open accessTEXTWOS000293107200004.pdf.txtWOS000293107200004.pdf.txtExtracted texttext/plain34932${dspace.ui.url}/bitstream/11600/33233/2/WOS000293107200004.pdf.txtc719fd0d4ae277f6897bdb8c6cea9fdcMD52open access11600/332332022-02-07 21:51:36.066open accessoai:repositorio.unifesp.br:11600/33233Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-02-08T00:51:36Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma |
title |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma |
spellingShingle |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma Fernandes, Bruno F. |
title_short |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma |
title_full |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma |
title_fullStr |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma |
title_full_unstemmed |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma |
title_sort |
Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma |
author |
Fernandes, Bruno F. |
author_facet |
Fernandes, Bruno F. Di Cesare, Sebastian Belfort Neto, Rubens [UNIFESP] Maloney, Shawn Martins, Claudia Castiglione, Enzo Isenberg, Jordan Abourbih, Daniel Antecka, Emilia Burnier Júnior, Miguel Nascente [UNIFESP] |
author_role |
author |
author2 |
Di Cesare, Sebastian Belfort Neto, Rubens [UNIFESP] Maloney, Shawn Martins, Claudia Castiglione, Enzo Isenberg, Jordan Abourbih, Daniel Antecka, Emilia Burnier Júnior, Miguel Nascente [UNIFESP] |
author2_role |
author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
McGill Univ Henry C Witelson Ocular Pathol Lab Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Fernandes, Bruno F. Di Cesare, Sebastian Belfort Neto, Rubens [UNIFESP] Maloney, Shawn Martins, Claudia Castiglione, Enzo Isenberg, Jordan Abourbih, Daniel Antecka, Emilia Burnier Júnior, Miguel Nascente [UNIFESP] |
description |
Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 x 10(6) human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). the experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. in the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. the recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001). the PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase in SERPINB5, a tumor suppressor gene, and a 10-fold higher expression of KISS I, a metastasis suppressor gene, in the treated group. Proangiogenic genes such as VEGFA, PDGFA and PDGFB were downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-01-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:05:54Z |
dc.date.available.fl_str_mv |
2016-01-24T14:05:54Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Analytical Cellular Pathology. Amsterdam: Ios Press, v. 34, n. 3, p. 123-130, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33233 http://dx.doi.org/10.3233/ACP-2011-0010 |
dc.identifier.issn.none.fl_str_mv |
2210-7177 |
dc.identifier.file.none.fl_str_mv |
WOS000293107200004.pdf |
dc.identifier.doi.none.fl_str_mv |
10.3233/ACP-2011-0010 |
dc.identifier.wos.none.fl_str_mv |
WOS:000293107200004 |
identifier_str_mv |
Analytical Cellular Pathology. Amsterdam: Ios Press, v. 34, n. 3, p. 123-130, 2011. 2210-7177 WOS000293107200004.pdf 10.3233/ACP-2011-0010 WOS:000293107200004 |
url |
http://repositorio.unifesp.br/handle/11600/33233 http://dx.doi.org/10.3233/ACP-2011-0010 |
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eng |
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Analytical Cellular Pathology |
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123-130 |
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Ios Press |
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