Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation
Background Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown. Methods Establ...
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| Veröffentlicht in: | Pediatric blood & cancer 2010-10, Vol.55 (4), p.644-651 |
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| creator | Panosyan, Eduard H. Laks, Dan R. Masterman-Smith, Michael Mottahedeh, Jack Yong, William H. Cloughesy, Timothy F. Lazareff, Jorge A. Mischel, Paul S. Moore, Theodore B. Kornblum, Harley I. |
| description | Background
Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown.
Methods
Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients. Potential associations between neurosphere formation and clinical outcome were analyzed retrospectively.
Results
Thirty‐seven percent of all samples formed renewable neurospheres. Analysis of available clinical outcome data from 51 patients demonstrated significantly increased hazard ratios (HR) for both disease progression (HR = 9.9, P |
| doi_str_mv | 10.1002/pbc.22627 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4017922</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>749015890</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4857-239433635754e2c2d88dd192e28c580b492a980faf0cdc6ae1f49be6f47d49ad3</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhSNERUthwQsg74BFWsex43iDVKZQCiN-BIil5Tg3MwbHTm2nZVa8Oi7TjmABq2vrfufIPqcoHlX4qMKYHE-dPiKkIfxOcVAxykqGK353d8Ziv7gf47eMNpi194p9kodomDgofi6scUYri_yctB8BGYcm6I1KwWi0siavlOsRjF3YeJdvXVCZSfPoQ0TahwBWJYjoyqT1tfrSpODRONtkyknFqFagOgvIwRx8nNYQAA0-jCoZ7x4Ue4OyER7ezMPiy6uXnxevy-X7s_PFybLUtGW8JLWgdd3UjDMKRJO-bfu-EgRIq1mLOyqIEi0e1IB1rxsF1UBFB81AeU-F6uvD4vnWd5q7EXoNLgVl5RTMqMJGemXk3xtn1nLlLyXNUQpCssGTG4PgL2aISY4marBWOfBzlJwKXOVUcSaf_pes6obTtm45z-izLapzMjHAsHtQheV1tTJXK39Xm9nHf_5gR952mYHjLXBlLGz-7SQ_vFjcWpZbhYkJfuwUKnyXDa85k1_fnUl2Spcfm09v5Nv6Fz_jwIs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1367483877</pqid></control><display><type>article</type><title>Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Panosyan, Eduard H. ; Laks, Dan R. ; Masterman-Smith, Michael ; Mottahedeh, Jack ; Yong, William H. ; Cloughesy, Timothy F. ; Lazareff, Jorge A. ; Mischel, Paul S. ; Moore, Theodore B. ; Kornblum, Harley I.</creator><creatorcontrib>Panosyan, Eduard H. ; Laks, Dan R. ; Masterman-Smith, Michael ; Mottahedeh, Jack ; Yong, William H. ; Cloughesy, Timothy F. ; Lazareff, Jorge A. ; Mischel, Paul S. ; Moore, Theodore B. ; Kornblum, Harley I.</creatorcontrib><description>Background
Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown.
Methods
Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients. Potential associations between neurosphere formation and clinical outcome were analyzed retrospectively.
Results
Thirty‐seven percent of all samples formed renewable neurospheres. Analysis of available clinical outcome data from 51 patients demonstrated significantly increased hazard ratios (HR) for both disease progression (HR = 9.9, P < 0.001) and death (HR = 16.6, P < 0.01) in the neurosphere forming group. Furthermore, neurosphere formation correlated with adverse progression free survival (PFS) in glial and embryonal tumors, but not in mixed glioneuronal tumors. Overall survival (OS) was significantly worse for neurosphere‐forming patients with embryonal tumors, as a group and amongst the subgroup with medulloblastoma, but not in the glial group. Multivariate analysis showed that neurosphere formation was associated with diminished PFS and OS independent of age, gender, or treatment. Neurosphere formation was an independent predictor of diminished PFS of glial tumors after adjusting for grade. Multivariate analysis, adjusting for both Ki67 staining and neurosphere formation, demonstrated that neurosphere formation remained predictive of progression whereas Ki67 did not.
Conclusions
Neurosphere formation is more predictive of pediatric brain tumor progression than semi‐quantitative Ki67 staining. Pediatric brain tumor derived neurospheres may provide a predictive model for preclinical explorations. Pediatr Blood Cancer. 2010;55:644–651. © 2010 Wiley‐Liss, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>ISSN: 1545-5017</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.22627</identifier><identifier>PMID: 20589659</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; brain ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; brain tumors ; cancer biology ; Cell Line, Tumor ; Child ; Child, Preschool ; CNS tumors ; Female ; Glioma - mortality ; Glioma - pathology ; Humans ; Infant ; Male ; Neoplasms, Germ Cell and Embryonal - mortality ; Neoplasms, Germ Cell and Embryonal - pathology ; neuro-oncology ; outcomes research ; Prognosis ; Proportional Hazards Models ; tumors</subject><ispartof>Pediatric blood & cancer, 2010-10, Vol.55 (4), p.644-651</ispartof><rights>Copyright © 2010 Wiley‐Liss, Inc.</rights><rights>Copyright 2010 Wiley-Liss, Inc.</rights><rights>2010 Wiley-Liss, Inc. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4857-239433635754e2c2d88dd192e28c580b492a980faf0cdc6ae1f49be6f47d49ad3</citedby><cites>FETCH-LOGICAL-c4857-239433635754e2c2d88dd192e28c580b492a980faf0cdc6ae1f49be6f47d49ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.22627$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.22627$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20589659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Panosyan, Eduard H.</creatorcontrib><creatorcontrib>Laks, Dan R.</creatorcontrib><creatorcontrib>Masterman-Smith, Michael</creatorcontrib><creatorcontrib>Mottahedeh, Jack</creatorcontrib><creatorcontrib>Yong, William H.</creatorcontrib><creatorcontrib>Cloughesy, Timothy F.</creatorcontrib><creatorcontrib>Lazareff, Jorge A.</creatorcontrib><creatorcontrib>Mischel, Paul S.</creatorcontrib><creatorcontrib>Moore, Theodore B.</creatorcontrib><creatorcontrib>Kornblum, Harley I.</creatorcontrib><title>Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation</title><title>Pediatric blood & cancer</title><addtitle>Pediatr. Blood Cancer</addtitle><description>Background
Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown.
Methods
Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients. Potential associations between neurosphere formation and clinical outcome were analyzed retrospectively.
Results
Thirty‐seven percent of all samples formed renewable neurospheres. Analysis of available clinical outcome data from 51 patients demonstrated significantly increased hazard ratios (HR) for both disease progression (HR = 9.9, P < 0.001) and death (HR = 16.6, P < 0.01) in the neurosphere forming group. Furthermore, neurosphere formation correlated with adverse progression free survival (PFS) in glial and embryonal tumors, but not in mixed glioneuronal tumors. Overall survival (OS) was significantly worse for neurosphere‐forming patients with embryonal tumors, as a group and amongst the subgroup with medulloblastoma, but not in the glial group. Multivariate analysis showed that neurosphere formation was associated with diminished PFS and OS independent of age, gender, or treatment. Neurosphere formation was an independent predictor of diminished PFS of glial tumors after adjusting for grade. Multivariate analysis, adjusting for both Ki67 staining and neurosphere formation, demonstrated that neurosphere formation remained predictive of progression whereas Ki67 did not.
Conclusions
Neurosphere formation is more predictive of pediatric brain tumor progression than semi‐quantitative Ki67 staining. Pediatric brain tumor derived neurospheres may provide a predictive model for preclinical explorations. Pediatr Blood Cancer. 2010;55:644–651. © 2010 Wiley‐Liss, Inc.</description><subject>Adolescent</subject><subject>Adult</subject><subject>brain</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - pathology</subject><subject>brain tumors</subject><subject>cancer biology</subject><subject>Cell Line, Tumor</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>CNS tumors</subject><subject>Female</subject><subject>Glioma - mortality</subject><subject>Glioma - pathology</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Neoplasms, Germ Cell and Embryonal - mortality</subject><subject>Neoplasms, Germ Cell and Embryonal - pathology</subject><subject>neuro-oncology</subject><subject>outcomes research</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>tumors</subject><issn>1545-5009</issn><issn>1545-5017</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhSNERUthwQsg74BFWsex43iDVKZQCiN-BIil5Tg3MwbHTm2nZVa8Oi7TjmABq2vrfufIPqcoHlX4qMKYHE-dPiKkIfxOcVAxykqGK353d8Ziv7gf47eMNpi194p9kodomDgofi6scUYri_yctB8BGYcm6I1KwWi0siavlOsRjF3YeJdvXVCZSfPoQ0TahwBWJYjoyqT1tfrSpODRONtkyknFqFagOgvIwRx8nNYQAA0-jCoZ7x4Ue4OyER7ezMPiy6uXnxevy-X7s_PFybLUtGW8JLWgdd3UjDMKRJO-bfu-EgRIq1mLOyqIEi0e1IB1rxsF1UBFB81AeU-F6uvD4vnWd5q7EXoNLgVl5RTMqMJGemXk3xtn1nLlLyXNUQpCssGTG4PgL2aISY4marBWOfBzlJwKXOVUcSaf_pes6obTtm45z-izLapzMjHAsHtQheV1tTJXK39Xm9nHf_5gR952mYHjLXBlLGz-7SQ_vFjcWpZbhYkJfuwUKnyXDa85k1_fnUl2Spcfm09v5Nv6Fz_jwIs</recordid><startdate>201010</startdate><enddate>201010</enddate><creator>Panosyan, Eduard H.</creator><creator>Laks, Dan R.</creator><creator>Masterman-Smith, Michael</creator><creator>Mottahedeh, Jack</creator><creator>Yong, William H.</creator><creator>Cloughesy, Timothy F.</creator><creator>Lazareff, Jorge A.</creator><creator>Mischel, Paul S.</creator><creator>Moore, Theodore B.</creator><creator>Kornblum, Harley I.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>201010</creationdate><title>Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation</title><author>Panosyan, Eduard H. ; Laks, Dan R. ; Masterman-Smith, Michael ; Mottahedeh, Jack ; Yong, William H. ; Cloughesy, Timothy F. ; Lazareff, Jorge A. ; Mischel, Paul S. ; Moore, Theodore B. ; Kornblum, Harley I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4857-239433635754e2c2d88dd192e28c580b492a980faf0cdc6ae1f49be6f47d49ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>brain</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - pathology</topic><topic>brain tumors</topic><topic>cancer biology</topic><topic>Cell Line, Tumor</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>CNS tumors</topic><topic>Female</topic><topic>Glioma - mortality</topic><topic>Glioma - pathology</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Neoplasms, Germ Cell and Embryonal - mortality</topic><topic>Neoplasms, Germ Cell and Embryonal - pathology</topic><topic>neuro-oncology</topic><topic>outcomes research</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Panosyan, Eduard H.</creatorcontrib><creatorcontrib>Laks, Dan R.</creatorcontrib><creatorcontrib>Masterman-Smith, Michael</creatorcontrib><creatorcontrib>Mottahedeh, Jack</creatorcontrib><creatorcontrib>Yong, William H.</creatorcontrib><creatorcontrib>Cloughesy, Timothy F.</creatorcontrib><creatorcontrib>Lazareff, Jorge A.</creatorcontrib><creatorcontrib>Mischel, Paul S.</creatorcontrib><creatorcontrib>Moore, Theodore B.</creatorcontrib><creatorcontrib>Kornblum, Harley I.</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Panosyan, Eduard H.</au><au>Laks, Dan R.</au><au>Masterman-Smith, Michael</au><au>Mottahedeh, Jack</au><au>Yong, William H.</au><au>Cloughesy, Timothy F.</au><au>Lazareff, Jorge A.</au><au>Mischel, Paul S.</au><au>Moore, Theodore B.</au><au>Kornblum, Harley I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr. Blood Cancer</addtitle><date>2010-10</date><risdate>2010</risdate><volume>55</volume><issue>4</issue><spage>644</spage><epage>651</epage><pages>644-651</pages><issn>1545-5009</issn><issn>1545-5017</issn><eissn>1545-5017</eissn><abstract>Background
Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown.
Methods
Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients. Potential associations between neurosphere formation and clinical outcome were analyzed retrospectively.
Results
Thirty‐seven percent of all samples formed renewable neurospheres. Analysis of available clinical outcome data from 51 patients demonstrated significantly increased hazard ratios (HR) for both disease progression (HR = 9.9, P < 0.001) and death (HR = 16.6, P < 0.01) in the neurosphere forming group. Furthermore, neurosphere formation correlated with adverse progression free survival (PFS) in glial and embryonal tumors, but not in mixed glioneuronal tumors. Overall survival (OS) was significantly worse for neurosphere‐forming patients with embryonal tumors, as a group and amongst the subgroup with medulloblastoma, but not in the glial group. Multivariate analysis showed that neurosphere formation was associated with diminished PFS and OS independent of age, gender, or treatment. Neurosphere formation was an independent predictor of diminished PFS of glial tumors after adjusting for grade. Multivariate analysis, adjusting for both Ki67 staining and neurosphere formation, demonstrated that neurosphere formation remained predictive of progression whereas Ki67 did not.
Conclusions
Neurosphere formation is more predictive of pediatric brain tumor progression than semi‐quantitative Ki67 staining. Pediatric brain tumor derived neurospheres may provide a predictive model for preclinical explorations. Pediatr Blood Cancer. 2010;55:644–651. © 2010 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20589659</pmid><doi>10.1002/pbc.22627</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Adult brain Brain Neoplasms - mortality Brain Neoplasms - pathology brain tumors cancer biology Cell Line, Tumor Child Child, Preschool CNS tumors Female Glioma - mortality Glioma - pathology Humans Infant Male Neoplasms, Germ Cell and Embryonal - mortality Neoplasms, Germ Cell and Embryonal - pathology neuro-oncology outcomes research Prognosis Proportional Hazards Models tumors |
| title | Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation |
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