Mechanisms of cisplatin-induced muscle atrophy

Sakai, Hiroyasu; Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara; Sato, Ken; Chiba, Yoshihiko; Yamazaki, Mitsuaki; Matoba, Motohiro; Narita, Minoru

doi:10.1016/j.taap.2014.05.001

Cited by 72 publications

(108 citation statements)

References 38 publications

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“…On day 5, 2 h after hexarelin or JMV2894 injection, rats were sacrificed. This regimen was selected based on previous studies showing: i) cisplatin-induced weight loss without overt-nephrotoxicity 16,18 ; ii) a partial prevention of cisplatin-induced weight loss mediated by hexarelin or JMV2894 beginning from day 5 during 12-day GHS treatments duration 17 . Body weight and food intake were assessed daily by weighing the food and the animals before the AM injection.…”

Section: Methodsmentioning

confidence: 99%

Growth hormone secretagogues hexarelin and JMV2894 protect skeletal muscle from mitochondrial damages in a rat model of cisplatin-induced cachexia

Sirago

Conte

Fracasso

et al. 2017

Sci Rep

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Chemotherapy can cause cachexia, which consists of weight loss associated with muscle atrophy. The exact mechanisms underlying this skeletal muscle toxicity are largely unknown and co-therapies to attenuate chemotherapy-induced side effects are lacking. By using a rat model of cisplatin-induced cachexia, we here characterized the mitochondrial homeostasis in tibialis anterior cachectic muscle and evaluated the potential beneficial effects of the growth hormone secretagogues (GHS) hexarelin and JMV2894 in this setting. We found that cisplatin treatment caused a decrease in mitochondrial biogenesis (PGC-1α, NRF-1, TFAM, mtDNA, ND1), mitochondrial mass (Porin and Citrate synthase activity) and fusion index (MFN2, Drp1), together with changes in the expression of autophagy-related genes (AKT/FoxO pathway, Atg1, Beclin1, LC3AII, p62) and enhanced ROS production (PRX III, MnSOD). Importantly, JMV2894 and hexarelin are capable to antagonize this chemotherapy-induced mitochondrial dysfunction. Thus, our findings reveal a key-role played by mitochondria in the mechanism responsible for GHS beneficial effects in skeletal muscle, strongly indicating that targeting mitochondrial dysfunction might be a promising area of research in developing therapeutic strategies to prevent or limit muscle wasting in cachexia.

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Section: Methodsmentioning

confidence: 99%

Growth hormone secretagogues hexarelin and JMV2894 protect skeletal muscle from mitochondrial damages in a rat model of cisplatin-induced cachexia

Sirago

Conte

Fracasso

et al. 2017

Sci Rep

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“…The loss of lean body mass (LBM) during treatment is likely to be multifactorial and HNSCC patients are particularly susceptible for several reasons: Cancer disease per se can cause muscle wasting [8, 9]; along with cisplatin chemotherapy [10, 11] and prednisolone [12, 13], which is often used as antiemetic treatment. Furthermore, many HNSCC patients fail to maintain sufficient energy and protein intake for a period of time [14, 15] due to treatment side effects, e.g.…”

Section: Introductionmentioning

confidence: 99%

Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy -- design of the DAHANCA 31 randomized trial

et al. 2017

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BackgroundHead and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects.MethodsAt the Departments of Oncology at Herlev and Aarhus University Hospitals, patients with stage III/IV squamous cell carcinoma of the head and neck, scheduled for CCRT are randomized 1:1 to either a 12-week PRT program or control group, both with 1 year follow-up. Planned enrollment is 72 patients, and stratification variables are study site, sex, p16-status, and body mass index. Primary endpoint is difference in change in lean body mass (LBM) after 12 weeks of PRT, assessed by dual-energy X-ray absorptiometry (DXA). The hypothesis is that 12 weeks of PRT can attenuate the loss of LBM by at least 25%. Secondary endpoints include training adherence, changes in body composition, muscle strength, functional performance, weight, adverse events, dietary intake, self-reported physical activity, quality of life, labor market affiliation, blood biochemistry, plasma cytokine concentrations, NK-cell frequency in blood, sarcomeric protein content in muscles, as well as muscle fiber type and fiber size in muscle biopsies. Muscle biopsies are optional.DiscussionThis randomized study investigates the impact of a 12-week progressive resistance training program on lean body mass and several other physiological endpoints, as well as impact on adverse events and quality of life. Furthermore, a translational approach is integrated with extensive biological sampling and exploration into cytokines and mechanisms involved. The current paper discusses decisions and methods behind exercise in head and neck cancer patients undergoing concomitant chemoradiotherapy.Trial registrationApproved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov (NCT02557529) September 11th 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3388-0) contains supplementary material, which is available to authorized users.

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“…I read with great interest the recent article by Ji-an Chen et al 1 Calorie intake is a major factor for the body composition including muscle mass 2. So, increase of food intake by the ghrelin administration in vivo could be one of the mechanisms for improvement of muscle wasting.…”

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confidence: 99%