Muscle‐specific functional deficits and lifelong fibrosis in response to paediatric radiotherapy and tumour elimination

Autor: Jacob G. Kallenbach, John F. Bachman, Nicole D. Paris, Roméo S. Blanc, Thomas O'Connor, Esraa Furati, Eric Hernady, Carl J. Johnston, Jacqueline P. Williams, Joe V. Chakkalakal
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 13, Iss 1, Pp 296-310 (2022)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12902
Popis: Abstract Background As paediatric cancer survivors are living into adulthood, they suffer from the age‐related, accelerated decline of functional skeletal muscle tissue, termed sarcopenia. With ionizing radiation (radiotherapy) at the core of paediatric cancer therapies, its direct and indirect effects can have lifelong negative impacts on paediatric growth and maintenance of skeletal muscle. Utilizing our recently developed preclinical rhabdomyosarcoma mouse model, we investigated the late effects of paediatric radiation treatment on skeletal muscles from late adolescent (8 weeks old) and middle‐aged (16 months old) mice. Methods Paediatric C57BL/6J male mice (3 weeks old) were injected with rhabdomyosarcoma cells into their right hindlimbs, and then fractionated irradiation (3 × 8.2 Gy) was administered to those limbs at 4 weeks old to eliminate the tumours. Radiation‐alone and tumour‐irradiated mice were assessed at either 8 weeks (3 weeks post‐irradiation) or 16 months (14 months post‐irradiation) of age for muscle physiology, myofibre characteristics, cell loss, histopathology, fibrosis, inflammatory gene expression, and fibrotic gene expression. Results Mice that received only paediatric radiation demonstrated reduced muscle mass (−17%, P
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