Silencing of R-Spondin1 increases radiosensitivity of glioma cells
Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma. We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and w...
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| Veröffentlicht in: | Oncotarget 2015, Vol.6 (12), p.9756-9765 |
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| creator | Gu, Xuefeng Wang, Xuefeng Xiao, Hong Ma, Guoda Cui, Lili Li, You Zhou, Haihong Liang, Wandong Zhao, Bin Li, Keshen |
| description | Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma. We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival. Rspo1 expression was also associated with reduced survival rates in glioma patients after treatment with radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically upregulated after radiation treatment in patients with glioma. Rspo1 silencing by shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential therapeutic approach. |
| doi_str_mv | 10.18632/oncotarget.3395 |
| format | Article |
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We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival. Rspo1 expression was also associated with reduced survival rates in glioma patients after treatment with radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically upregulated after radiation treatment in patients with glioma. Rspo1 silencing by shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential therapeutic approach.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.3395</identifier><identifier>PMID: 25865226</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Animals ; Antineoplastic Agents - therapeutic use ; Antineoplastic Agents, Alkylating - therapeutic use ; Astrocytes - metabolism ; Brain Neoplasms - genetics ; Brain Neoplasms - mortality ; Brain Neoplasms - therapy ; Cell Line, Tumor ; Combined Modality Therapy ; Dacarbazine - analogs & derivatives ; Dacarbazine - therapeutic use ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Glioma - genetics ; Glioma - mortality ; Glioma - therapy ; Humans ; Male ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Transplantation ; Proportional Hazards Models ; Radiation Tolerance - drug effects ; Radiotherapy - methods ; Rats ; Research Paper ; RNA, Small Interfering - metabolism ; Thrombospondins - genetics ; Treatment Outcome ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2015, Vol.6 (12), p.9756-9765</ispartof><rights>Copyright: © 2015 Gu et al. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-4eefd4ee44e05b6c043ec1489bca6ba4bc025f75103fa84596b5397bea4cb1e03</citedby><cites>FETCH-LOGICAL-c396t-4eefd4ee44e05b6c043ec1489bca6ba4bc025f75103fa84596b5397bea4cb1e03</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/PMC4496395/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496395/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25865226$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gu, Xuefeng</creatorcontrib><creatorcontrib>Wang, Xuefeng</creatorcontrib><creatorcontrib>Xiao, Hong</creatorcontrib><creatorcontrib>Ma, Guoda</creatorcontrib><creatorcontrib>Cui, Lili</creatorcontrib><creatorcontrib>Li, You</creatorcontrib><creatorcontrib>Zhou, Haihong</creatorcontrib><creatorcontrib>Liang, Wandong</creatorcontrib><creatorcontrib>Zhao, Bin</creatorcontrib><creatorcontrib>Li, Keshen</creatorcontrib><title>Silencing of R-Spondin1 increases radiosensitivity of glioma cells</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma. We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival. Rspo1 expression was also associated with reduced survival rates in glioma patients after treatment with radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically upregulated after radiation treatment in patients with glioma. Rspo1 silencing by shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential therapeutic approach.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Astrocytes - metabolism</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - therapy</subject><subject>Cell Line, Tumor</subject><subject>Combined Modality Therapy</subject><subject>Dacarbazine - analogs & derivatives</subject><subject>Dacarbazine - therapeutic use</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Silencing</subject><subject>Glioma - genetics</subject><subject>Glioma - mortality</subject><subject>Glioma - therapy</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Neoplasm Transplantation</subject><subject>Proportional Hazards Models</subject><subject>Radiation Tolerance - drug effects</subject><subject>Radiotherapy - methods</subject><subject>Rats</subject><subject>Research Paper</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Thrombospondins - genetics</subject><subject>Treatment Outcome</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUE1LAzEQDaLYUnv3JHv0sjXfu7kIWvwCQbB6Dtl0do1sk5psC_33trbWOoeZgXnz3sxD6JzgESklo1fB29CZ2EA3YkyJI9QniqucCsGOD_oeGqb0idcheFFSdYp6VJRSUCr76HbiWvDW-SYLdfaaT-bBT50nmfM2gkmQsmimLiTwyXVu6brVBti0LsxMZqFt0xk6qU2bYLirA_R-f_c2fsyfXx6exjfPuWVKdjkHqKfrxDlgUUmLOQNLeKkqa2RleGUxFXUhCGa1KblQshJMFRUYbisCmA3Q9ZZ3vqhmMLXgu2haPY9uZuJKB-P0_4l3H7oJS825kmt_1gSXO4IYvhaQOj1zafOC8RAWSRNZUk4LXG608BZqY0gpQr2XIVj_uK__3Ndsy35xeN5-4ddr9g1hdYUS</recordid><startdate>2015</startdate><enddate>2015</enddate><creator>Gu, Xuefeng</creator><creator>Wang, Xuefeng</creator><creator>Xiao, Hong</creator><creator>Ma, Guoda</creator><creator>Cui, Lili</creator><creator>Li, You</creator><creator>Zhou, Haihong</creator><creator>Liang, Wandong</creator><creator>Zhao, Bin</creator><creator>Li, Keshen</creator><general>Impact Journals LLC</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>5PM</scope></search><sort><creationdate>2015</creationdate><title>Silencing of R-Spondin1 increases radiosensitivity of glioma cells</title><author>Gu, Xuefeng ; Wang, Xuefeng ; Xiao, Hong ; Ma, Guoda ; Cui, Lili ; Li, You ; Zhou, Haihong ; Liang, Wandong ; Zhao, Bin ; Li, Keshen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-4eefd4ee44e05b6c043ec1489bca6ba4bc025f75103fa84596b5397bea4cb1e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antineoplastic Agents, Alkylating - therapeutic use</topic><topic>Astrocytes - metabolism</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - therapy</topic><topic>Cell Line, Tumor</topic><topic>Combined Modality Therapy</topic><topic>Dacarbazine - analogs & derivatives</topic><topic>Dacarbazine - therapeutic use</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Silencing</topic><topic>Glioma - genetics</topic><topic>Glioma - mortality</topic><topic>Glioma - therapy</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Neoplasm Transplantation</topic><topic>Proportional Hazards Models</topic><topic>Radiation Tolerance - drug effects</topic><topic>Radiotherapy - methods</topic><topic>Rats</topic><topic>Research Paper</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Thrombospondins - genetics</topic><topic>Treatment Outcome</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Gu, Xuefeng</creatorcontrib><creatorcontrib>Wang, Xuefeng</creatorcontrib><creatorcontrib>Xiao, Hong</creatorcontrib><creatorcontrib>Ma, Guoda</creatorcontrib><creatorcontrib>Cui, Lili</creatorcontrib><creatorcontrib>Li, You</creatorcontrib><creatorcontrib>Zhou, Haihong</creatorcontrib><creatorcontrib>Liang, Wandong</creatorcontrib><creatorcontrib>Zhao, Bin</creatorcontrib><creatorcontrib>Li, Keshen</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>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gu, Xuefeng</au><au>Wang, Xuefeng</au><au>Xiao, Hong</au><au>Ma, Guoda</au><au>Cui, Lili</au><au>Li, You</au><au>Zhou, Haihong</au><au>Liang, Wandong</au><au>Zhao, Bin</au><au>Li, Keshen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silencing of R-Spondin1 increases radiosensitivity of glioma cells</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2015</date><risdate>2015</risdate><volume>6</volume><issue>12</issue><spage>9756</spage><epage>9765</epage><pages>9756-9765</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Although radiation therapy is the most effective postoperative adjuvant treatment, it does not substantially improve the long-term outcomes of glioma patients because of the characteristic radioresistance of glioma. We found that R-Spondin1 (Rspo1) expression was elevated in high-grade gliomas and was associated with worse overall survival and disease-free survival. Rspo1 expression was also associated with reduced survival rates in glioma patients after treatment with radiotherapy and temozolomide (RT-TMZ). Importantly, Rspo1 was dramatically upregulated after radiation treatment in patients with glioma. Rspo1 silencing by shRNA potentiated glioma cell death upon radiation treatment. In a xenograft nude mouse model, combining radiation and silencing of Rspo1 potentiated tumor growth inhibition. Thus, combining radiotherapy with silencing of Rspo1 is a potential therapeutic approach.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>25865226</pmid><doi>10.18632/oncotarget.3395</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Animals Antineoplastic Agents - therapeutic use Antineoplastic Agents, Alkylating - therapeutic use Astrocytes - metabolism Brain Neoplasms - genetics Brain Neoplasms - mortality Brain Neoplasms - therapy Cell Line, Tumor Combined Modality Therapy Dacarbazine - analogs & derivatives Dacarbazine - therapeutic use Female Gene Expression Regulation, Neoplastic Gene Silencing Glioma - genetics Glioma - mortality Glioma - therapy Humans Male Mice Mice, Nude Middle Aged Neoplasm Transplantation Proportional Hazards Models Radiation Tolerance - drug effects Radiotherapy - methods Rats Research Paper RNA, Small Interfering - metabolism Thrombospondins - genetics Treatment Outcome Xenograft Model Antitumor Assays |
| title | Silencing of R-Spondin1 increases radiosensitivity of glioma cells |
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