Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Paris, ND; Kallenbach, JG; Bachman, JF; Blanc, RS; Johnston, CJ; Hernady, E; Williams, JP; Chakkalakal, JV

Published Date

  • November 11, 2020

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 19501 -

PubMed ID

  • 33177579

Pubmed Central ID

  • PMC7659015

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-020-75913-w

Language

  • eng

Conference Location

  • England