Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model
Pediatric cancer treatment often involves chemotherapy and radiation, where off-target effects can include skeletal muscle decline. The effect of such treatments on juvenile skeletal muscle growth has yet to be investigated. We employed a small animal irradiator to administer fractionated hindlimb i...
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| Veröffentlicht in: | Scientific reports 2020-11, Vol.10 (1), p.19501, Article 19501 |
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| description | Pediatric cancer treatment often involves chemotherapy and radiation, where off-target effects can include skeletal muscle decline. The effect of such treatments on juvenile skeletal muscle growth has yet to be investigated. We employed a small animal irradiator to administer fractionated hindlimb irradiation to juvenile mice bearing implanted rhabdomyosarcoma (RMS) tumors. Hindlimb-targeted irradiation (3 × 8.2 Gy) of 4-week-old mice successfully eliminated RMS tumors implanted one week prior. After establishment of this preclinical model, a cohort of tumor-bearing mice were injected with the chemotherapeutic drug, vincristine, alone or in combination with fractionated irradiation (5 × 4.8 Gy). Single myofiber analysis of fast-contracting extensor digitorum longus (EDL) and slow-contracting soleus (SOL) muscles was conducted 3 weeks post-treatment. Although a reduction in myofiber size was apparent, EDL and SOL myonuclear number were differentially affected by juvenile irradiation and/or vincristine treatment. In contrast, a decrease in myonuclear domain (myofiber volume/myonucleus) was observed regardless of muscle or treatment. Thus, inhibition of myofiber hypertrophic growth is a consistent feature of pediatric cancer treatment. |
| doi_str_mv | 10.1038/s41598-020-75913-w |
| format | Article |
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The effect of such treatments on juvenile skeletal muscle growth has yet to be investigated. We employed a small animal irradiator to administer fractionated hindlimb irradiation to juvenile mice bearing implanted rhabdomyosarcoma (RMS) tumors. Hindlimb-targeted irradiation (3 × 8.2 Gy) of 4-week-old mice successfully eliminated RMS tumors implanted one week prior. After establishment of this preclinical model, a cohort of tumor-bearing mice were injected with the chemotherapeutic drug, vincristine, alone or in combination with fractionated irradiation (5 × 4.8 Gy). Single myofiber analysis of fast-contracting extensor digitorum longus (EDL) and slow-contracting soleus (SOL) muscles was conducted 3 weeks post-treatment. Although a reduction in myofiber size was apparent, EDL and SOL myonuclear number were differentially affected by juvenile irradiation and/or vincristine treatment. In contrast, a decrease in myonuclear domain (myofiber volume/myonucleus) was observed regardless of muscle or treatment. Thus, inhibition of myofiber hypertrophic growth is a consistent feature of pediatric cancer treatment.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-75913-w</identifier><identifier>PMID: 33177579</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136 ; 631/136/1425 ; 631/136/532 ; 631/136/7 ; 631/136/83 ; 631/532 ; 631/532/2118 ; 631/532/2439 ; 631/532/7 ; 631/67 ; 631/67/1059 ; 631/67/1798 ; 631/67/2332 ; 631/67/70 ; Aging ; Animals ; Antineoplastic Agents, Phytogenic - pharmacology ; Cancer therapies ; Cell Line, Tumor ; Chemoradiotherapy ; Chemoradiotherapy - adverse effects ; Chemotherapy ; Disease Models, Animal ; Dose Fractionation, Radiation ; Hindlimb - drug effects ; Hindlimb - pathology ; Hindlimb - radiation effects ; Humanities and Social Sciences ; Hypertrophy ; Male ; Mice, Inbred C57BL ; multidisciplinary ; Muscle Fibers, Skeletal - drug effects ; Muscle Fibers, Skeletal - pathology ; Muscle Fibers, Skeletal - radiation effects ; Musculoskeletal system ; Pediatrics ; Radiation ; Rhabdomyosarcoma ; Rhabdomyosarcoma - therapy ; Rotarod Performance Test ; Science ; Science (multidisciplinary) ; Skeletal muscle ; Transplantation, Isogeneic ; Tumors ; Vincristine ; Vincristine - pharmacology</subject><ispartof>Scientific reports, 2020-11, Vol.10 (1), p.19501, Article 19501</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-5b336efb9e684f3278c31c8193fb3352aa8fea1e66ec025b6b0716c6f48d9a83</citedby><cites>FETCH-LOGICAL-c474t-5b336efb9e684f3278c31c8193fb3352aa8fea1e66ec025b6b0716c6f48d9a83</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/PMC7659015/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659015/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33177579$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paris, Nicole D.</creatorcontrib><creatorcontrib>Kallenbach, Jacob G.</creatorcontrib><creatorcontrib>Bachman, John F.</creatorcontrib><creatorcontrib>Blanc, Roméo S.</creatorcontrib><creatorcontrib>Johnston, Carl J.</creatorcontrib><creatorcontrib>Hernady, Eric</creatorcontrib><creatorcontrib>Williams, Jacqueline P.</creatorcontrib><creatorcontrib>Chakkalakal, Joe V.</creatorcontrib><title>Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Pediatric cancer treatment often involves chemotherapy and radiation, where off-target effects can include skeletal muscle decline. The effect of such treatments on juvenile skeletal muscle growth has yet to be investigated. We employed a small animal irradiator to administer fractionated hindlimb irradiation to juvenile mice bearing implanted rhabdomyosarcoma (RMS) tumors. Hindlimb-targeted irradiation (3 × 8.2 Gy) of 4-week-old mice successfully eliminated RMS tumors implanted one week prior. After establishment of this preclinical model, a cohort of tumor-bearing mice were injected with the chemotherapeutic drug, vincristine, alone or in combination with fractionated irradiation (5 × 4.8 Gy). Single myofiber analysis of fast-contracting extensor digitorum longus (EDL) and slow-contracting soleus (SOL) muscles was conducted 3 weeks post-treatment. Although a reduction in myofiber size was apparent, EDL and SOL myonuclear number were differentially affected by juvenile irradiation and/or vincristine treatment. In contrast, a decrease in myonuclear domain (myofiber volume/myonucleus) was observed regardless of muscle or treatment. Thus, inhibition of myofiber hypertrophic growth is a consistent feature of pediatric cancer treatment.</description><subject>631/136</subject><subject>631/136/1425</subject><subject>631/136/532</subject><subject>631/136/7</subject><subject>631/136/83</subject><subject>631/532</subject><subject>631/532/2118</subject><subject>631/532/2439</subject><subject>631/532/7</subject><subject>631/67</subject><subject>631/67/1059</subject><subject>631/67/1798</subject><subject>631/67/2332</subject><subject>631/67/70</subject><subject>Aging</subject><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Chemoradiotherapy</subject><subject>Chemoradiotherapy - adverse effects</subject><subject>Chemotherapy</subject><subject>Disease Models, Animal</subject><subject>Dose Fractionation, Radiation</subject><subject>Hindlimb - drug effects</subject><subject>Hindlimb - pathology</subject><subject>Hindlimb - 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pharmacology</topic><topic>Cancer therapies</topic><topic>Cell Line, Tumor</topic><topic>Chemoradiotherapy</topic><topic>Chemoradiotherapy - adverse effects</topic><topic>Chemotherapy</topic><topic>Disease Models, Animal</topic><topic>Dose Fractionation, Radiation</topic><topic>Hindlimb - drug effects</topic><topic>Hindlimb - pathology</topic><topic>Hindlimb - radiation effects</topic><topic>Humanities and Social Sciences</topic><topic>Hypertrophy</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>multidisciplinary</topic><topic>Muscle Fibers, Skeletal - drug effects</topic><topic>Muscle Fibers, Skeletal - pathology</topic><topic>Muscle Fibers, Skeletal - radiation effects</topic><topic>Musculoskeletal system</topic><topic>Pediatrics</topic><topic>Radiation</topic><topic>Rhabdomyosarcoma</topic><topic>Rhabdomyosarcoma - therapy</topic><topic>Rotarod Performance Test</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Skeletal muscle</topic><topic>Transplantation, Isogeneic</topic><topic>Tumors</topic><topic>Vincristine</topic><topic>Vincristine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paris, Nicole D.</creatorcontrib><creatorcontrib>Kallenbach, Jacob G.</creatorcontrib><creatorcontrib>Bachman, John F.</creatorcontrib><creatorcontrib>Blanc, Roméo S.</creatorcontrib><creatorcontrib>Johnston, Carl J.</creatorcontrib><creatorcontrib>Hernady, Eric</creatorcontrib><creatorcontrib>Williams, Jacqueline P.</creatorcontrib><creatorcontrib>Chakkalakal, Joe V.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paris, Nicole D.</au><au>Kallenbach, Jacob G.</au><au>Bachman, John F.</au><au>Blanc, Roméo S.</au><au>Johnston, Carl J.</au><au>Hernady, Eric</au><au>Williams, Jacqueline P.</au><au>Chakkalakal, Joe V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-11-11</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>19501</spage><pages>19501-</pages><artnum>19501</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Pediatric cancer treatment often involves chemotherapy and radiation, where off-target effects can include skeletal muscle decline. The effect of such treatments on juvenile skeletal muscle growth has yet to be investigated. We employed a small animal irradiator to administer fractionated hindlimb irradiation to juvenile mice bearing implanted rhabdomyosarcoma (RMS) tumors. Hindlimb-targeted irradiation (3 × 8.2 Gy) of 4-week-old mice successfully eliminated RMS tumors implanted one week prior. After establishment of this preclinical model, a cohort of tumor-bearing mice were injected with the chemotherapeutic drug, vincristine, alone or in combination with fractionated irradiation (5 × 4.8 Gy). Single myofiber analysis of fast-contracting extensor digitorum longus (EDL) and slow-contracting soleus (SOL) muscles was conducted 3 weeks post-treatment. Although a reduction in myofiber size was apparent, EDL and SOL myonuclear number were differentially affected by juvenile irradiation and/or vincristine treatment. In contrast, a decrease in myonuclear domain (myofiber volume/myonucleus) was observed regardless of muscle or treatment. Thus, inhibition of myofiber hypertrophic growth is a consistent feature of pediatric cancer treatment.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33177579</pmid><doi>10.1038/s41598-020-75913-w</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/136 631/136/1425 631/136/532 631/136/7 631/136/83 631/532 631/532/2118 631/532/2439 631/532/7 631/67 631/67/1059 631/67/1798 631/67/2332 631/67/70 Aging Animals Antineoplastic Agents, Phytogenic - pharmacology Cancer therapies Cell Line, Tumor Chemoradiotherapy Chemoradiotherapy - adverse effects Chemotherapy Disease Models, Animal Dose Fractionation, Radiation Hindlimb - drug effects Hindlimb - pathology Hindlimb - radiation effects Humanities and Social Sciences Hypertrophy Male Mice, Inbred C57BL multidisciplinary Muscle Fibers, Skeletal - drug effects Muscle Fibers, Skeletal - pathology Muscle Fibers, Skeletal - radiation effects Musculoskeletal system Pediatrics Radiation Rhabdomyosarcoma Rhabdomyosarcoma - therapy Rotarod Performance Test Science Science (multidisciplinary) Skeletal muscle Transplantation, Isogeneic Tumors Vincristine Vincristine - pharmacology |
| title | Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model |
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