Monitoring of Tumor Growth and Post-Irradiation Recurrence in a Diffuse Intrinsic Pontine Glioma Mouse Model
Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy because of its diffuse infiltrative growth pattern. Translational research suffers from the lack of a representative DIPG animal model. Hence, human E98 glioma cells were stereotactically injected into the pons of nude mice. The E98 DIPG...
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creator | Caretti, Viola Zondervan, Ilse Meijer, Dimphna H. Idema, Sander Vos, Wim Hamans, Bob Bugiani, Marianna Hulleman, Esther Wesseling, Pieter Vandertop, W. Peter Noske, David P. Kaspers, Gertjan Molthoff, Carla F.M. Wurdinger, Thomas |
description | Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy because of its diffuse infiltrative growth pattern. Translational research suffers from the lack of a representative DIPG animal model. Hence, human E98 glioma cells were stereotactically injected into the pons of nude mice. The E98 DIPG tumors presented a strikingly similar histhopathology to autopsy material of a DIPG patient, including diffuse and perivascular growth, brainstem‐ and supratentorial invasiveness and leptomeningeal growth. Magnetic resonance imaging (MRI) was effectively employed to image the E98 DIPG tumor. [18F] 3′‐deoxy‐3′‐[18F]fluorothymidine (FLT) positron emission tomography (PET) imaging was applied to assess the subcutaneous (s.c.) E98 tumor proliferation status but no orthotopic DIPG activity could be visualized. Next, E98 cells were cultured in vitro and engineered to express firefly luciferase and mCherry (E98‐Fluc‐mCherry). These cultured E98‐Fluc‐mCherry cells developed focal pontine glioma when injected into the pons directly. However, the diffuse E98 DIPG infiltrative phenotype was restored when cells were injected into the pons immediately after an intermediate s.c. passage. The diffuse E98‐Fluc‐mCherry model was subsequently used to test escalating doses of irradiation, applying the bioluminescent Fluc signal to monitor tumor recurrence over time. Altogether, we here describe an accurate DIPG mouse model that can be of clinical relevance for testing experimental therapeutics in vivo. |
doi_str_mv | 10.1111/j.1750-3639.2010.00468.x |
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Peter ; Noske, David P. ; Kaspers, Gertjan ; Molthoff, Carla F.M. ; Wurdinger, Thomas</creator><creatorcontrib>Caretti, Viola ; Zondervan, Ilse ; Meijer, Dimphna H. ; Idema, Sander ; Vos, Wim ; Hamans, Bob ; Bugiani, Marianna ; Hulleman, Esther ; Wesseling, Pieter ; Vandertop, W. Peter ; Noske, David P. ; Kaspers, Gertjan ; Molthoff, Carla F.M. ; Wurdinger, Thomas</creatorcontrib><description>Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy because of its diffuse infiltrative growth pattern. Translational research suffers from the lack of a representative DIPG animal model. Hence, human E98 glioma cells were stereotactically injected into the pons of nude mice. The E98 DIPG tumors presented a strikingly similar histhopathology to autopsy material of a DIPG patient, including diffuse and perivascular growth, brainstem‐ and supratentorial invasiveness and leptomeningeal growth. Magnetic resonance imaging (MRI) was effectively employed to image the E98 DIPG tumor. [18F] 3′‐deoxy‐3′‐[18F]fluorothymidine (FLT) positron emission tomography (PET) imaging was applied to assess the subcutaneous (s.c.) E98 tumor proliferation status but no orthotopic DIPG activity could be visualized. Next, E98 cells were cultured in vitro and engineered to express firefly luciferase and mCherry (E98‐Fluc‐mCherry). These cultured E98‐Fluc‐mCherry cells developed focal pontine glioma when injected into the pons directly. However, the diffuse E98 DIPG infiltrative phenotype was restored when cells were injected into the pons immediately after an intermediate s.c. passage. The diffuse E98‐Fluc‐mCherry model was subsequently used to test escalating doses of irradiation, applying the bioluminescent Fluc signal to monitor tumor recurrence over time. Altogether, we here describe an accurate DIPG mouse model that can be of clinical relevance for testing experimental therapeutics in vivo.</description><identifier>ISSN: 1015-6305</identifier><identifier>EISSN: 1750-3639</identifier><identifier>DOI: 10.1111/j.1750-3639.2010.00468.x</identifier><identifier>PMID: 21159008</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animal models ; Animals ; Autopsy ; Brain Stem Neoplasms - pathology ; Brain Stem Neoplasms - radiotherapy ; Brain tumors ; brainstem glioma ; Cell Line, Tumor ; DIPG ; Disease Models, Animal ; Female ; Glioma ; Glioma cells ; Growth patterns ; Humans ; imaging ; Immunohistochemistry ; Invasiveness ; luciferase ; Magnetic resonance imaging ; Malignancy ; Meninges ; Mice ; Mice, Nude ; Neoplasm Recurrence, Local - pathology ; Neoplasm Transplantation - methods ; Neuroimaging ; Pons ; Pons - pathology ; Pons - radiation effects ; Positron emission tomography ; Post-irradiation ; Radiation ; Radiotherapy ; Translation ; Tumors</subject><ispartof>Brain pathology (Zurich, Switzerland), 2011-07, Vol.21 (4), p.441-451</ispartof><rights>2010 The Authors; Brain Pathology © 2010 International Society of Neuropathology</rights><rights>2010 The Authors; Brain Pathology © 2010 International Society of Neuropathology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5428-21eab41b1fd57974e32fa568dd6668231b276a2dbc80fa5f28abaaef05a666e13</citedby><cites>FETCH-LOGICAL-c5428-21eab41b1fd57974e32fa568dd6668231b276a2dbc80fa5f28abaaef05a666e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094295/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094295/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,27924,27925,45574,45575,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21159008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caretti, Viola</creatorcontrib><creatorcontrib>Zondervan, Ilse</creatorcontrib><creatorcontrib>Meijer, Dimphna H.</creatorcontrib><creatorcontrib>Idema, Sander</creatorcontrib><creatorcontrib>Vos, Wim</creatorcontrib><creatorcontrib>Hamans, Bob</creatorcontrib><creatorcontrib>Bugiani, Marianna</creatorcontrib><creatorcontrib>Hulleman, Esther</creatorcontrib><creatorcontrib>Wesseling, Pieter</creatorcontrib><creatorcontrib>Vandertop, W. Peter</creatorcontrib><creatorcontrib>Noske, David P.</creatorcontrib><creatorcontrib>Kaspers, Gertjan</creatorcontrib><creatorcontrib>Molthoff, Carla F.M.</creatorcontrib><creatorcontrib>Wurdinger, Thomas</creatorcontrib><title>Monitoring of Tumor Growth and Post-Irradiation Recurrence in a Diffuse Intrinsic Pontine Glioma Mouse Model</title><title>Brain pathology (Zurich, Switzerland)</title><addtitle>Brain Pathol</addtitle><description>Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy because of its diffuse infiltrative growth pattern. Translational research suffers from the lack of a representative DIPG animal model. Hence, human E98 glioma cells were stereotactically injected into the pons of nude mice. The E98 DIPG tumors presented a strikingly similar histhopathology to autopsy material of a DIPG patient, including diffuse and perivascular growth, brainstem‐ and supratentorial invasiveness and leptomeningeal growth. Magnetic resonance imaging (MRI) was effectively employed to image the E98 DIPG tumor. [18F] 3′‐deoxy‐3′‐[18F]fluorothymidine (FLT) positron emission tomography (PET) imaging was applied to assess the subcutaneous (s.c.) E98 tumor proliferation status but no orthotopic DIPG activity could be visualized. Next, E98 cells were cultured in vitro and engineered to express firefly luciferase and mCherry (E98‐Fluc‐mCherry). These cultured E98‐Fluc‐mCherry cells developed focal pontine glioma when injected into the pons directly. However, the diffuse E98 DIPG infiltrative phenotype was restored when cells were injected into the pons immediately after an intermediate s.c. passage. The diffuse E98‐Fluc‐mCherry model was subsequently used to test escalating doses of irradiation, applying the bioluminescent Fluc signal to monitor tumor recurrence over time. Altogether, we here describe an accurate DIPG mouse model that can be of clinical relevance for testing experimental therapeutics in vivo.</description><subject>Animal models</subject><subject>Animals</subject><subject>Autopsy</subject><subject>Brain Stem Neoplasms - pathology</subject><subject>Brain Stem Neoplasms - radiotherapy</subject><subject>Brain tumors</subject><subject>brainstem glioma</subject><subject>Cell Line, Tumor</subject><subject>DIPG</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Glioma</subject><subject>Glioma cells</subject><subject>Growth patterns</subject><subject>Humans</subject><subject>imaging</subject><subject>Immunohistochemistry</subject><subject>Invasiveness</subject><subject>luciferase</subject><subject>Magnetic resonance imaging</subject><subject>Malignancy</subject><subject>Meninges</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasm Transplantation - methods</subject><subject>Neuroimaging</subject><subject>Pons</subject><subject>Pons - pathology</subject><subject>Pons - radiation effects</subject><subject>Positron emission tomography</subject><subject>Post-irradiation</subject><subject>Radiation</subject><subject>Radiotherapy</subject><subject>Translation</subject><subject>Tumors</subject><issn>1015-6305</issn><issn>1750-3639</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhSMEoj_wCsg7Vple27HjSAipFDqM1IEKirq8chKn9ZDYxU7o9O1xmDKCHd7Y8jnf8bVOlhEKC5rWyWZBSwE5l7xaMEi3AIVUi-2T7HAvPE1noCKXHMRBdhTjBoBWshLPswNGqagA1GHWr72zow_W3RDfkatp8IEsg78fb4l2Lbn0ccxXIejW6tF6R76YZgrBuMYQ64gm723XTdGQlRtTSLRNQtxonSHL3vpBk7Wf5bVvTf8ie9bpPpqXj_tx9u38w9XZx_zi83J1dnqRN6JgKmfU6LqgNe1aUVZlYTjrtJCqbaWUinFas1Jq1taNgiR0TOlaa9OB0MlgKD_O3u5y76Z6MG1j0my6x7tgBx0e0GuL_yrO3uKN_4kKqoJVIgW8fgwI_sdk4oiDjY3pe-1M-g4qxYGVHCA51c7ZBB9jMN3-FQo4d4UbnCvBuRKcu8LfXeE2oa_-nnIP_iknGd7sDPe2Nw__HYzvLk_TIeH5DrdxNNs9rsN3lCUvBV5_WuL1OYVKfl2j4L8AMKuzsg</recordid><startdate>201107</startdate><enddate>201107</enddate><creator>Caretti, Viola</creator><creator>Zondervan, Ilse</creator><creator>Meijer, Dimphna H.</creator><creator>Idema, Sander</creator><creator>Vos, Wim</creator><creator>Hamans, Bob</creator><creator>Bugiani, Marianna</creator><creator>Hulleman, Esther</creator><creator>Wesseling, Pieter</creator><creator>Vandertop, W. Peter</creator><creator>Noske, David P.</creator><creator>Kaspers, Gertjan</creator><creator>Molthoff, Carla F.M.</creator><creator>Wurdinger, Thomas</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7TK</scope><scope>5PM</scope></search><sort><creationdate>201107</creationdate><title>Monitoring of Tumor Growth and Post-Irradiation Recurrence in a Diffuse Intrinsic Pontine Glioma Mouse Model</title><author>Caretti, Viola ; Zondervan, Ilse ; Meijer, Dimphna H. ; Idema, Sander ; Vos, Wim ; Hamans, Bob ; Bugiani, Marianna ; Hulleman, Esther ; Wesseling, Pieter ; Vandertop, W. 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Peter</creatorcontrib><creatorcontrib>Noske, David P.</creatorcontrib><creatorcontrib>Kaspers, Gertjan</creatorcontrib><creatorcontrib>Molthoff, Carla F.M.</creatorcontrib><creatorcontrib>Wurdinger, Thomas</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Brain pathology (Zurich, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caretti, Viola</au><au>Zondervan, Ilse</au><au>Meijer, Dimphna H.</au><au>Idema, Sander</au><au>Vos, Wim</au><au>Hamans, Bob</au><au>Bugiani, Marianna</au><au>Hulleman, Esther</au><au>Wesseling, Pieter</au><au>Vandertop, W. Peter</au><au>Noske, David P.</au><au>Kaspers, Gertjan</au><au>Molthoff, Carla F.M.</au><au>Wurdinger, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monitoring of Tumor Growth and Post-Irradiation Recurrence in a Diffuse Intrinsic Pontine Glioma Mouse Model</atitle><jtitle>Brain pathology (Zurich, Switzerland)</jtitle><addtitle>Brain Pathol</addtitle><date>2011-07</date><risdate>2011</risdate><volume>21</volume><issue>4</issue><spage>441</spage><epage>451</epage><pages>441-451</pages><issn>1015-6305</issn><eissn>1750-3639</eissn><abstract>Diffuse intrinsic pontine glioma (DIPG) is a fatal malignancy because of its diffuse infiltrative growth pattern. Translational research suffers from the lack of a representative DIPG animal model. Hence, human E98 glioma cells were stereotactically injected into the pons of nude mice. The E98 DIPG tumors presented a strikingly similar histhopathology to autopsy material of a DIPG patient, including diffuse and perivascular growth, brainstem‐ and supratentorial invasiveness and leptomeningeal growth. Magnetic resonance imaging (MRI) was effectively employed to image the E98 DIPG tumor. [18F] 3′‐deoxy‐3′‐[18F]fluorothymidine (FLT) positron emission tomography (PET) imaging was applied to assess the subcutaneous (s.c.) E98 tumor proliferation status but no orthotopic DIPG activity could be visualized. Next, E98 cells were cultured in vitro and engineered to express firefly luciferase and mCherry (E98‐Fluc‐mCherry). These cultured E98‐Fluc‐mCherry cells developed focal pontine glioma when injected into the pons directly. However, the diffuse E98 DIPG infiltrative phenotype was restored when cells were injected into the pons immediately after an intermediate s.c. passage. The diffuse E98‐Fluc‐mCherry model was subsequently used to test escalating doses of irradiation, applying the bioluminescent Fluc signal to monitor tumor recurrence over time. Altogether, we here describe an accurate DIPG mouse model that can be of clinical relevance for testing experimental therapeutics in vivo.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21159008</pmid><doi>10.1111/j.1750-3639.2010.00468.x</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animal models Animals Autopsy Brain Stem Neoplasms - pathology Brain Stem Neoplasms - radiotherapy Brain tumors brainstem glioma Cell Line, Tumor DIPG Disease Models, Animal Female Glioma Glioma cells Growth patterns Humans imaging Immunohistochemistry Invasiveness luciferase Magnetic resonance imaging Malignancy Meninges Mice Mice, Nude Neoplasm Recurrence, Local - pathology Neoplasm Transplantation - methods Neuroimaging Pons Pons - pathology Pons - radiation effects Positron emission tomography Post-irradiation Radiation Radiotherapy Translation Tumors |
title | Monitoring of Tumor Growth and Post-Irradiation Recurrence in a Diffuse Intrinsic Pontine Glioma Mouse Model |
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