High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma
Purpose To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials The vascular effects of radiation ther...
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| Veröffentlicht in: | International journal of radiation oncology, biology, physics biology, physics, 2016-04, Vol.94 (5), p.1173-1180 |
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| creator | Jani, Ashish, MD Shaikh, Fauzia, MD Barton, Sunjay, BA Willis, Callen, BA Banerjee, Debarshi, PhD Mitchell, Jason, BA Hernandez, Sonia L., PhD Hei, Tom, PhD Kadenhe-Chiweshe, Angela, MD Yamashiro, Darrell J., MD, PhD Connolly, Eileen P., MD, PhD |
| description | Purpose To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes. |
| doi_str_mv | 10.1016/j.ijrobp.2015.12.367 |
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Methods and Materials The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2015.12.367</identifier><identifier>PMID: 26907918</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Angiography - methods ; Animals ; Apoptosis ; BIOMEDICAL RADIOGRAPHY ; BLOOD VESSELS ; Cell Communication ; Cell Line, Tumor ; Endothelium, Vascular - cytology ; Endothelium, Vascular - radiation effects ; GY RANGE 01-10 ; Hematology, Oncology and Palliative Medicine ; Heterografts ; Humans ; IN VIVO ; IRRADIATION ; Lectins ; Mice, Nude ; NEOPLASMS ; Neuroblastoma - blood supply ; Neuroblastoma - diagnostic imaging ; Neuroblastoma - radiotherapy ; Pericytes - cytology ; Pericytes - radiation effects ; RADIATION DOSES ; RADIATION HAZARDS ; Radiology ; RADIOLOGY AND NUCLEAR MEDICINE ; RADIOTHERAPY ; Radiotherapy Dosage ; Random Allocation ; Regional Blood Flow - radiation effects ; Time Factors ; Ultrasonography</subject><ispartof>International journal of radiation oncology, biology, physics, 2016-04, Vol.94 (5), p.1173-1180</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-20a75063efae4ed3693c0c049fa8ceb8515425122b495a8a17937db2524a71eb3</citedby><cites>FETCH-LOGICAL-c445t-20a75063efae4ed3693c0c049fa8ceb8515425122b495a8a17937db2524a71eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0360301615272215$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26907918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22645160$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Jani, Ashish, MD</creatorcontrib><creatorcontrib>Shaikh, Fauzia, MD</creatorcontrib><creatorcontrib>Barton, Sunjay, BA</creatorcontrib><creatorcontrib>Willis, Callen, BA</creatorcontrib><creatorcontrib>Banerjee, Debarshi, PhD</creatorcontrib><creatorcontrib>Mitchell, Jason, BA</creatorcontrib><creatorcontrib>Hernandez, Sonia L., PhD</creatorcontrib><creatorcontrib>Hei, Tom, PhD</creatorcontrib><creatorcontrib>Kadenhe-Chiweshe, Angela, MD</creatorcontrib><creatorcontrib>Yamashiro, Darrell J., MD, PhD</creatorcontrib><creatorcontrib>Connolly, Eileen P., MD, PhD</creatorcontrib><title>High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Purpose To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.</description><subject>Angiography - methods</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>BIOMEDICAL RADIOGRAPHY</subject><subject>BLOOD VESSELS</subject><subject>Cell Communication</subject><subject>Cell Line, Tumor</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - radiation effects</subject><subject>GY RANGE 01-10</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Heterografts</subject><subject>Humans</subject><subject>IN VIVO</subject><subject>IRRADIATION</subject><subject>Lectins</subject><subject>Mice, Nude</subject><subject>NEOPLASMS</subject><subject>Neuroblastoma - blood supply</subject><subject>Neuroblastoma - diagnostic imaging</subject><subject>Neuroblastoma - radiotherapy</subject><subject>Pericytes - cytology</subject><subject>Pericytes - radiation effects</subject><subject>RADIATION DOSES</subject><subject>RADIATION HAZARDS</subject><subject>Radiology</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>RADIOTHERAPY</subject><subject>Radiotherapy Dosage</subject><subject>Random Allocation</subject><subject>Regional Blood Flow - radiation effects</subject><subject>Time Factors</subject><subject>Ultrasonography</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9v1DAQxSMEokvhGyBkiQsHEmzHjpMLEiqUVip_1BbUmzWxJ1uHxF7sBGklPjwJWzhw4TRz-M3M03uTZU8ZLRhl1au-cH0M7a7glMmC8aKs1L1sw2rV5KWUN_ezDS0rmpcLfJQ9SqmnlDKmxMPsiFcNVQ2rN9nPM7e9zd-GhC_JlfPbAfPTCGZywZPzGME6-N1fws7ZYU8u0c4GE7mexxDJV0hmHmCaIxLwlnzG2M1p5Z0nQG7Qh22EbiIfgsWBhI58xHkRPUCawgiPswcdDAmf3NXj7Mvpu-uTs_zi0_vzkzcXuRFCTjmnoCStSuwABdqyakpDDRVNB7XBtpZMCi4Z561oJNTAVFMq23LJBSiGbXmcPT_sDWlyOhk3obk1wXs0k-a8EpJVdKFeHKhdDN9nTJMeXTI4DOAxzEkzpZRY3OV8QcUBNTGkFLHTu-hGiHvNqF7T0b0-pKPXdDTjeklnGXt2d2FuR7R_h_7EsQCvDwAubvxwGFex6A1aF1etNrj_Xfh3gRmcdwaGb7jH1Ic5-sVpzXTimuqr9UPWB2GSK86ZLH8BK8q3cQ</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Jani, Ashish, MD</creator><creator>Shaikh, Fauzia, MD</creator><creator>Barton, Sunjay, BA</creator><creator>Willis, Callen, BA</creator><creator>Banerjee, Debarshi, PhD</creator><creator>Mitchell, Jason, BA</creator><creator>Hernandez, Sonia L., PhD</creator><creator>Hei, Tom, PhD</creator><creator>Kadenhe-Chiweshe, Angela, MD</creator><creator>Yamashiro, Darrell J., MD, PhD</creator><creator>Connolly, Eileen P., MD, PhD</creator><general>Elsevier Inc</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>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20160401</creationdate><title>High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma</title><author>Jani, Ashish, MD ; Shaikh, Fauzia, MD ; Barton, Sunjay, BA ; Willis, Callen, BA ; Banerjee, Debarshi, PhD ; Mitchell, Jason, BA ; Hernandez, Sonia L., PhD ; Hei, Tom, PhD ; Kadenhe-Chiweshe, Angela, MD ; Yamashiro, Darrell J., MD, PhD ; Connolly, Eileen P., MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-20a75063efae4ed3693c0c049fa8ceb8515425122b495a8a17937db2524a71eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Angiography - methods</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>BIOMEDICAL RADIOGRAPHY</topic><topic>BLOOD VESSELS</topic><topic>Cell Communication</topic><topic>Cell Line, Tumor</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - radiation effects</topic><topic>GY RANGE 01-10</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Heterografts</topic><topic>Humans</topic><topic>IN VIVO</topic><topic>IRRADIATION</topic><topic>Lectins</topic><topic>Mice, Nude</topic><topic>NEOPLASMS</topic><topic>Neuroblastoma - blood supply</topic><topic>Neuroblastoma - diagnostic imaging</topic><topic>Neuroblastoma - radiotherapy</topic><topic>Pericytes - cytology</topic><topic>Pericytes - radiation effects</topic><topic>RADIATION DOSES</topic><topic>RADIATION HAZARDS</topic><topic>Radiology</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>RADIOTHERAPY</topic><topic>Radiotherapy Dosage</topic><topic>Random Allocation</topic><topic>Regional Blood Flow - radiation effects</topic><topic>Time Factors</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jani, Ashish, MD</creatorcontrib><creatorcontrib>Shaikh, Fauzia, MD</creatorcontrib><creatorcontrib>Barton, Sunjay, BA</creatorcontrib><creatorcontrib>Willis, Callen, BA</creatorcontrib><creatorcontrib>Banerjee, Debarshi, PhD</creatorcontrib><creatorcontrib>Mitchell, Jason, BA</creatorcontrib><creatorcontrib>Hernandez, Sonia L., PhD</creatorcontrib><creatorcontrib>Hei, Tom, PhD</creatorcontrib><creatorcontrib>Kadenhe-Chiweshe, Angela, MD</creatorcontrib><creatorcontrib>Yamashiro, Darrell J., MD, PhD</creatorcontrib><creatorcontrib>Connolly, Eileen P., MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jani, Ashish, MD</au><au>Shaikh, Fauzia, MD</au><au>Barton, Sunjay, BA</au><au>Willis, Callen, BA</au><au>Banerjee, Debarshi, PhD</au><au>Mitchell, Jason, BA</au><au>Hernandez, Sonia L., PhD</au><au>Hei, Tom, PhD</au><au>Kadenhe-Chiweshe, Angela, MD</au><au>Yamashiro, Darrell J., MD, PhD</au><au>Connolly, Eileen P., MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>94</volume><issue>5</issue><spage>1173</spage><epage>1180</epage><pages>1173-1180</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract>Purpose To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26907918</pmid><doi>10.1016/j.ijrobp.2015.12.367</doi><tpages>8</tpages></addata></record> |
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| subjects | Angiography - methods Animals Apoptosis BIOMEDICAL RADIOGRAPHY BLOOD VESSELS Cell Communication Cell Line, Tumor Endothelium, Vascular - cytology Endothelium, Vascular - radiation effects GY RANGE 01-10 Hematology, Oncology and Palliative Medicine Heterografts Humans IN VIVO IRRADIATION Lectins Mice, Nude NEOPLASMS Neuroblastoma - blood supply Neuroblastoma - diagnostic imaging Neuroblastoma - radiotherapy Pericytes - cytology Pericytes - radiation effects RADIATION DOSES RADIATION HAZARDS Radiology RADIOLOGY AND NUCLEAR MEDICINE RADIOTHERAPY Radiotherapy Dosage Random Allocation Regional Blood Flow - radiation effects Time Factors Ultrasonography |
| title | High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma |
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