Oxaliplatin induces muscle loss and muscle‐specific molecular changes in Mice

Feather, Claire E.; Lees, Justin G.; Makker, Preet G S; Goldstein, David; Moalem‐Taylor, Gila; Polly, Patsie

doi:10.1002/mus.25966

Cited by 23 publications

(33 citation statements)

References 51 publications

(130 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the lack of SOS in our oxaliplatin model is not unexpected, and the splenomegaly we observed has an aetiology independent of SOS. In conjunction with the fact that mice appeared to develop severe signs of anaemia in the extremities, and our previous findings indicating oxaliplatin-treated mice exhibit signs of fatigue such as reduced exploratory behaviour [40], the evidence indicates that the primary pathology causing splenomegaly in this model is oxaliplatininduced haematological toxicity. These findings warrant future clinical investigation to ascertain if the incidence of splenomegaly occurring in a substantial number of CRC patients is related to the oxaliplatin-induced haematological toxicity, as observed in the mouse model reported here.…”

Section: Plos Onesupporting

confidence: 74%

Oxaliplatin-induced haematological toxicity and splenomegaly in mice

et al. 2020

Self Cite

View full text Add to dashboard Cite

Haematological toxicities occur in patients receiving oxaliplatin. Mild anaemia (grade 1-2) is a common side effect and approximately 90% of recipients develop measurable spleen enlargement. Although generally asymptomatic, oxaliplatin-induced splenomegaly is independently associated with complications following liver resection for colorectal liver metastasis and separately with poorer patient outcomes. Here, we investigated oxaliplatin-induced haematological toxicities and splenomegaly in mice treated with escalating dosages comparable to those prescribed to colorectal cancer patients. Methods Blood was analysed, and smears assessed using Wright-Giemsa staining. Paw coloration was quantified as a marker of anaemia. Spleen weight and morphology were assessed for abnormalities relating to splenomegaly and a flow cytometry and multiplex cytokine array assessment was performed on splenocytes. The liver was assessed for sinusoidal obstructive syndrome.

show abstract

Section: Plos Onesupporting

confidence: 74%

Oxaliplatin-induced haematological toxicity and splenomegaly in mice

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…These data support the hypothesis proposed by van der Werf et al [ 37 ] in their published protocol about muscle mass loss and treatment failure in patients with metastatic CRC. Because chemotherapy has an unfavorable effect on muscle mass and sufficient protein intake and physical activity have a combined positive effect on the induction of muscle protein anabolism in patients with metastatic CRC, they argued that during treatment with first-line chemotherapy, preserving muscle mass may improve clinical and patient-reported HRQOL [ 37 ].…”

Section: Discussionsupporting

confidence: 91%

Body Composition and Biochemical Parameters of Nutritional Status: Correlation with Health-Related Quality of Life in Patients with Colorectal Cancer

et al. 2020

View full text Add to dashboard Cite

Up to 60% of colorectal cancer (CRC) patients develop malnutrition, affecting treatment effectiveness, increasing toxicity, postoperative complications, hospital stay, and worsening health-related quality of life (HRQOL). This cross-sectional study analyzed data from 48 women and 65 men with CRC. We correlated scores of the scales from the questionnaires EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30 (QLQ)-C30 and Colorectal Cancer module Colorectal 29 (QLQ-CR29) with patients’ body composition and clinical and biochemical indicators of nutritional status. Results: Scores on quality of life were negatively associated with the lymphocyte count (rP = −0.386) and the fat trunk percentage (rP = −0.349) in the women’s group. Scores on the physical and role functioning were inversely associated with the adiposity percentage (rP = −0.486 and rP = −0.411, respectively). In men, total skeletal muscle mass (SMM) was positively associated with emotional functioning (rP = 0.450); the trunk SMM was negatively related to fatigue (rP = −0.586), nausea and vomiting (rP = −0.469), pain (rP = −0.506), and financial difficulties (rP = −0.475); additionally, serum albumin was positively related to physical, emotional, and social functioning scales (rPs = 0.395, 0.453, and 0.363, respectively) and negatively to fatigue (rP = −0.362), nausea and vomiting (rP = −0.387), and appetite loss (rP = −0.347). Among the men, the reduced SMM and biochemical, nutritional parameters were related to low scores on the EORTC QLQ-C30 and QLQ-CR29 functioning scales. In conclusion, in patients with CRC, malnourishment could have a profound effect on the patients’ functionality and QoL (quality of life).

show abstract

“…Recently, it has been pointed out that excessive mitophagy in skeletal muscle cells would promote cachexia development. Alterations in BNIP3 or PINK1 [325] transcript levels are found in cachectic muscle of cancer patients [323,325,328] as well as in mouse models [329,330], but whether and how they regulate mitophagy-induced cachexia remains to be further studied.…”

Section: Mitophagy and Anti-cancer Therapiesmentioning

confidence: 99%

Mitophagy in Cancer: A Tale of Adaptation

Vara-Pérez

Felipe‐Abrio

Agostinis

2019

Cells

193

134

View full text Add to dashboard Cite

In the past years, we have learnt that tumors co-evolve with their microenvironment, and that the active interaction between cancer cells and stromal cells plays a pivotal role in cancer initiation, progression and treatment response. Among the players involved, the pathways regulating mitochondrial functions have been shown to be crucial for both cancer and stromal cells. This is perhaps not surprising, considering that mitochondria in both cancerous and non-cancerous cells are decisive for vital metabolic and bioenergetic functions and to elicit cell death. The central part played by mitochondria also implies the existence of stringent mitochondrial quality control mechanisms, where a specialized autophagy pathway (mitophagy) ensures the selective removal of damaged or dysfunctional mitochondria. Although the molecular underpinnings of mitophagy regulation in mammalian cells remain incomplete, it is becoming clear that mitophagy pathways are intricately linked to the metabolic rewiring of cancer cells to support the high bioenergetic demand of the tumor. In this review, after a brief introduction of the main mitophagy regulators operating in mammalian cells, we discuss emerging cell autonomous roles of mitochondria quality control in cancer onset and progression. We also discuss the relevance of mitophagy in the cellular crosstalk with the tumor microenvironment and in anti-cancer therapy responses.

show abstract

Oxaliplatin induces muscle loss and muscle‐specific molecular changes in Mice

Abstract: The findings suggest that oxaliplatin treatment can directly disrupt skeletal muscle homeostasis and promote muscle loss, which may be clinically relevant in the context of targeting fatigue and weakness in cancer patients. Muscle Nerve 57: 650-658, 2018.

Cited by 23 publications

References 51 publications

Oxaliplatin-induced haematological toxicity and splenomegaly in mice

Oxaliplatin-induced haematological toxicity and splenomegaly in mice

Body Composition and Biochemical Parameters of Nutritional Status: Correlation with Health-Related Quality of Life in Patients with Colorectal Cancer

Mitophagy in Cancer: A Tale of Adaptation

Contact Info

Product

Resources

About