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Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model.

Publication ,  Journal Article
Paris, ND; Kallenbach, JG; Bachman, JF; Blanc, RS; Johnston, CJ; Hernady, E; Williams, JP; Chakkalakal, JV
Published in: Sci Rep
November 11, 2020

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.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 11, 2020

Volume

10

Issue

1

Start / End Page

19501

Location

England

Related Subject Headings

  • Vincristine
  • Transplantation, Isogeneic
  • Rotarod Performance Test
  • Rhabdomyosarcoma
  • Muscle Fibers, Skeletal
  • Mice, Inbred C57BL
  • Male
  • Hypertrophy
  • Hindlimb
  • Dose Fractionation, Radiation
 

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Paris, N. D., Kallenbach, J. G., Bachman, J. F., Blanc, R. S., Johnston, C. J., Hernady, E., … Chakkalakal, J. V. (2020). Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model. Sci Rep, 10(1), 19501. https://doi.org/10.1038/s41598-020-75913-w
Paris, Nicole D., Jacob G. Kallenbach, John F. Bachman, Roméo S. Blanc, Carl J. Johnston, Eric Hernady, Jacqueline P. Williams, and Joe V. Chakkalakal. “Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model.Sci Rep 10, no. 1 (November 11, 2020): 19501. https://doi.org/10.1038/s41598-020-75913-w.
Paris ND, Kallenbach JG, Bachman JF, Blanc RS, Johnston CJ, Hernady E, et al. Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model. Sci Rep. 2020 Nov 11;10(1):19501.
Paris, Nicole D., et al. “Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model.Sci Rep, vol. 10, no. 1, Nov. 2020, p. 19501. Pubmed, doi:10.1038/s41598-020-75913-w.
Paris ND, Kallenbach JG, Bachman JF, Blanc RS, Johnston CJ, Hernady E, Williams JP, Chakkalakal JV. Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model. Sci Rep. 2020 Nov 11;10(1):19501.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 11, 2020

Volume

10

Issue

1

Start / End Page

19501

Location

England

Related Subject Headings

  • Vincristine
  • Transplantation, Isogeneic
  • Rotarod Performance Test
  • Rhabdomyosarcoma
  • Muscle Fibers, Skeletal
  • Mice, Inbred C57BL
  • Male
  • Hypertrophy
  • Hindlimb
  • Dose Fractionation, Radiation