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Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea
We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capaci...
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Published in: | PloS one 2017-06, Vol.12 (6), p.e0179444-e0179444 |
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description | We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p |
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An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0179444</identifier><identifier>PMID: 28594929</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiogenesis ; Animal models ; Animal models in research ; Animals ; Anoxia ; Apnea ; Biology and Life Sciences ; Cancer ; Carcinoma, Renal Cell - blood supply ; Carcinoma, Renal Cell - complications ; Carcinoma, Renal Cell - pathology ; Care and treatment ; Càncer de ronyó ; Disease Models, Animal ; Endothelial cells ; Exposure ; Gene expression ; Genotype & phenotype ; Hospitals ; Hypoxia ; Hypoxia - complications ; Hypoxia - genetics ; Hypoxia - pathology ; Immune response ; Immune system ; In vitro methods and tests ; Kidney ; Kidney cancer ; Kidney Neoplasms - blood supply ; Kidney Neoplasms - complications ; Kidney Neoplasms - genetics ; Kidney Neoplasms - pathology ; Macrophages ; Macrophages - pathology ; Male ; Medicine and Health Sciences ; Melanoma ; Metastases ; Metastasis ; Mice, Inbred BALB C ; Models animals en la investigació ; Mortality ; Neoplasm Metastasis ; Neovascularization, Pathologic - genetics ; Neovascularization, Pathologic - pathology ; Obesity ; Renal cancer ; Renal cell carcinoma ; Research and Analysis Methods ; Rodents ; Sleep ; Sleep apnea ; Sleep apnea syndromes ; Sleep Apnea Syndromes - complications ; Sleep Apnea Syndromes - genetics ; Sleep Apnea Syndromes - pathology ; Sleep disorders ; Subcutaneous Tissue - pathology ; Surgery ; Síndromes d'apnea del son ; Urology ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; Vascularization</subject><ispartof>PloS one, 2017-06, Vol.12 (6), p.e0179444-e0179444</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Vilaseca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>cc-by (c) Vilaseca, Antoni et al., 2017 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a></rights><rights>2017 Vilaseca et al 2017 Vilaseca et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c734t-5324def60c21712c54b0165e9d3a38afc5c0cedf92bbaf45edc32e11d111b91c3</citedby><cites>FETCH-LOGICAL-c734t-5324def60c21712c54b0165e9d3a38afc5c0cedf92bbaf45edc32e11d111b91c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1907553407/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1907553407?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28594929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Vinci, Maria Cristina</contributor><creatorcontrib>Vilaseca, Antoni</creatorcontrib><creatorcontrib>Campillo, Noelia</creatorcontrib><creatorcontrib>Torres, Marta</creatorcontrib><creatorcontrib>Musquera, Mireia</creatorcontrib><creatorcontrib>Gozal, David</creatorcontrib><creatorcontrib>Montserrat, Josep M</creatorcontrib><creatorcontrib>Alcaraz, Antonio</creatorcontrib><creatorcontrib>Touijer, Karim A</creatorcontrib><creatorcontrib>Farré, Ramon</creatorcontrib><creatorcontrib>Almendros, Isaac</creatorcontrib><title>Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.</description><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animal models in research</subject><subject>Animals</subject><subject>Anoxia</subject><subject>Apnea</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>Carcinoma, Renal Cell - blood supply</subject><subject>Carcinoma, Renal Cell - complications</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Care and treatment</subject><subject>Càncer de ronyó</subject><subject>Disease Models, Animal</subject><subject>Endothelial cells</subject><subject>Exposure</subject><subject>Gene expression</subject><subject>Genotype & phenotype</subject><subject>Hospitals</subject><subject>Hypoxia</subject><subject>Hypoxia - complications</subject><subject>Hypoxia - genetics</subject><subject>Hypoxia - pathology</subject><subject>Immune response</subject><subject>Immune system</subject><subject>In vitro methods and tests</subject><subject>Kidney</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - blood supply</subject><subject>Kidney Neoplasms - complications</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - pathology</subject><subject>Macrophages</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Melanoma</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice, Inbred BALB C</subject><subject>Models animals en la investigació</subject><subject>Mortality</subject><subject>Neoplasm Metastasis</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Obesity</subject><subject>Renal cancer</subject><subject>Renal cell carcinoma</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>Sleep</subject><subject>Sleep apnea</subject><subject>Sleep apnea syndromes</subject><subject>Sleep Apnea Syndromes - complications</subject><subject>Sleep Apnea Syndromes - genetics</subject><subject>Sleep Apnea Syndromes - pathology</subject><subject>Sleep disorders</subject><subject>Subcutaneous Tissue - pathology</subject><subject>Surgery</subject><subject>Síndromes d'apnea del son</subject><subject>Urology</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vascularization</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjPlsmxthWfwYWFjw60oIaXo6k7VtapIuO_5605nuMJW9kFLaps_7npyTc5LkOUZLTHP87toOrlPNsrcdLBHOBWPsQXKKBSWLjCD68Oj9JHni_TVCnBZZ9jg5IQUXTBBxmvxcdQFca0KALqSbbW9vjUpNpx0oDz79ZaoOtmkYWuvSG-X10Chn_qhgbBexVKXt4EwHaWsraFJbp74B6FPVd6CeJo9q1Xh4Nj3Pku8fP3y7-Ly4vPq0uji_XOicsrDglLAK6gxpgnNMNGclwhkHUVFFC1VrrpGGqhakLFXNOFSaEsC4whiXAmt6lrzc-_aN9XIqjJdYoJxzylAeidWeqKy6lr0zrXJbaZWRuwXr1lK5YHQDkuWloCpGLTQwXiOBeF0UGHCZVQRKGr3eT9GGso17iYVzqpmZzv90ZiPX9kZylrE8Gw3w3kD7QUsHGpxWYSc8fIw3QTmRlOOiIFHzZgrq7O8BfJCt8RqaRnVgh12uBaOZKMZcX_2D3l-RiVqrmLTpahv3qkdTec4EKxiLPRWp5T1UvCpojY6dV5u4PhO8nQkiE-A2rNXgvVx9_fL_7NWPOfv6iN2AasLG22YY-9DPQTYV11nvHdSHg8FIjoNzVw05Do6cBifKXhwf6kF0Nyn0L1XRFGc</recordid><startdate>20170608</startdate><enddate>20170608</enddate><creator>Vilaseca, Antoni</creator><creator>Campillo, Noelia</creator><creator>Torres, Marta</creator><creator>Musquera, Mireia</creator><creator>Gozal, David</creator><creator>Montserrat, Josep M</creator><creator>Alcaraz, Antonio</creator><creator>Touijer, Karim A</creator><creator>Farré, Ramon</creator><creator>Almendros, Isaac</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>XX2</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20170608</creationdate><title>Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea</title><author>Vilaseca, Antoni ; Campillo, Noelia ; Torres, Marta ; Musquera, Mireia ; Gozal, David ; Montserrat, Josep M ; Alcaraz, Antonio ; Touijer, Karim A ; Farré, Ramon ; Almendros, Isaac</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c734t-5324def60c21712c54b0165e9d3a38afc5c0cedf92bbaf45edc32e11d111b91c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animal models in research</topic><topic>Animals</topic><topic>Anoxia</topic><topic>Apnea</topic><topic>Biology and Life Sciences</topic><topic>Cancer</topic><topic>Carcinoma, Renal Cell - blood supply</topic><topic>Carcinoma, Renal Cell - complications</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>Care and treatment</topic><topic>Càncer de ronyó</topic><topic>Disease Models, Animal</topic><topic>Endothelial cells</topic><topic>Exposure</topic><topic>Gene expression</topic><topic>Genotype & phenotype</topic><topic>Hospitals</topic><topic>Hypoxia</topic><topic>Hypoxia - complications</topic><topic>Hypoxia - genetics</topic><topic>Hypoxia - pathology</topic><topic>Immune response</topic><topic>Immune system</topic><topic>In vitro methods and tests</topic><topic>Kidney</topic><topic>Kidney cancer</topic><topic>Kidney Neoplasms - blood supply</topic><topic>Kidney Neoplasms - complications</topic><topic>Kidney Neoplasms - genetics</topic><topic>Kidney Neoplasms - pathology</topic><topic>Macrophages</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Melanoma</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice, Inbred BALB C</topic><topic>Models animals en la investigació</topic><topic>Mortality</topic><topic>Neoplasm Metastasis</topic><topic>Neovascularization, Pathologic - 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Academic</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vilaseca, Antoni</au><au>Campillo, Noelia</au><au>Torres, Marta</au><au>Musquera, Mireia</au><au>Gozal, David</au><au>Montserrat, Josep M</au><au>Alcaraz, Antonio</au><au>Touijer, Karim A</au><au>Farré, Ramon</au><au>Almendros, Isaac</au><au>Vinci, Maria Cristina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-06-08</date><risdate>2017</risdate><volume>12</volume><issue>6</issue><spage>e0179444</spage><epage>e0179444</epage><pages>e0179444-e0179444</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28594929</pmid><doi>10.1371/journal.pone.0179444</doi><tpages>e0179444</tpages><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_1907553407 |
source | Publicly Available Content Database; PubMed Central |
subjects | Angiogenesis Animal models Animal models in research Animals Anoxia Apnea Biology and Life Sciences Cancer Carcinoma, Renal Cell - blood supply Carcinoma, Renal Cell - complications Carcinoma, Renal Cell - pathology Care and treatment Càncer de ronyó Disease Models, Animal Endothelial cells Exposure Gene expression Genotype & phenotype Hospitals Hypoxia Hypoxia - complications Hypoxia - genetics Hypoxia - pathology Immune response Immune system In vitro methods and tests Kidney Kidney cancer Kidney Neoplasms - blood supply Kidney Neoplasms - complications Kidney Neoplasms - genetics Kidney Neoplasms - pathology Macrophages Macrophages - pathology Male Medicine and Health Sciences Melanoma Metastases Metastasis Mice, Inbred BALB C Models animals en la investigació Mortality Neoplasm Metastasis Neovascularization, Pathologic - genetics Neovascularization, Pathologic - pathology Obesity Renal cancer Renal cell carcinoma Research and Analysis Methods Rodents Sleep Sleep apnea Sleep apnea syndromes Sleep Apnea Syndromes - complications Sleep Apnea Syndromes - genetics Sleep Apnea Syndromes - pathology Sleep disorders Subcutaneous Tissue - pathology Surgery Síndromes d'apnea del son Urology Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism Vascularization |
title | Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea |
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