Exercise-Induced Myokines as Emerging Therapeutic Agents In Colorectal Cancer Prevention and Treatment

Roy, Priya; Chowdhury, Shantanu; Roy, Hemant K.

doi:10.2217/fon-2017-0555

Cited by 17 publications

(12 citation statements)

References 20 publications

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“…One of the key factors is myokine, which is a cytokine produced and released by skeletal muscles [35]. It was recently discovered that myokines mediate anti-inflammatory response and have potential anti-cancer functions [36]. Myokines, such as interleukin (IL)-6, can have anti-tumorigenic effects by interacting with NK cells and inducing the production of IL-1 receptor antagonist and IL-10 by blood mononuclear cells, which are molecules with anti-inflammatory effects [37,38].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Yoon

Ahn

et al. 2020

Cancers

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Backgrounds: The relationship between sarcopenia, characterized by loss of muscle mass and strength, and survival outcomes of esophageal cancer is controversial. This study aimed to assess the effect of sarcopenia and skeletal muscle loss on overall survival (OS) and recurrence-free survival (RFS) of esophageal cancer patients. Methods: We retrospectively collected the medical records of 248 male patients diagnosed with squamous cell esophageal cancer and who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgery. We measured the cross-sectional area of the skeletal muscle at the L3 vertebra level using computed tomography images and calculated the skeletal muscle index (SMI). Sarcopenia was defined as SMI <52.4 cm2/m2, and excessive muscle loss was defined as SMI change <−10.0%/50 days during NACRT. Moreover, laboratory test results, such as albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) before and after NACRT, were collected. Results: In the univariable Cox analysis, pre- (p = 0.689) and post-radiotherapy (RT) sarcopenia (p = 0.669) were not associated with OS. However, excessive muscle loss had a significant association with OS in both the univariable and multivariable analyses (all p = 0.001). Excessive muscle loss was also related to RFS in both the univariable (p = 0.011) and multivariable (p = 0.022) Cox analysis. Patients with excessive muscle loss had significantly lower levels of post-RT albumin (p < 0.001) and PNI (p < 0.001), higher levels of post-RT NLR (p = 0.031) and PLR (p = 0.071), larger decrease in albumin (p < 0.001) and PNI (p < 0.001) after NACRT, and larger increase in NLR (p = 0.051) and PLR (p = 0.088) after NACRT than in those with non-excessive muscle loss. Conclusion: Excessive muscle loss rather than pre- and post-RT sarcopenia was a significant prognostic factor for OS and RFS, and it was also related to nutritional and inflammatory markers.

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Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Yoon

Ahn

et al. 2020

Cancers

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“…Myokines, which are proteins secreted from skeletal muscles, have recently gained attention in anticancer research since they mediate exercise-induced metabolic improvement and antiinflammatory effects (47). In particular, specific myokines have been associated with anticancer immune function (47,48). Thus, reduction of skeletal muscle may cause weakened immune function against cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Sarcopenia and Systemic Inflammatory Response in Patients With Esophageal Cancer

et al. 2018

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Background/Aim: The association between the presence of sarcopenia and systemic inflammatory response is unclear in patients with esophageal cancer. This study was performed to investigate the relationship between sarcopenia and systemic inflammatory response and clarify the effect of these factors on the prognosis in patients with esophageal cancer. Patients and Methods: This study included 163 patients with esophageal cancer. The patients' body composition was assessed before esophagectomy using multifrequency bioelectrical impedance. The relationship between sarcopenia and inflammatory factors were investigated before surgery. Results: Sarcopenia was significantly associated with a high C-reactive protein-to-albumin (CRP/Alb) ratio (p=0.046). Patients with sarcopenia significantly associated with worse overall survival (OS) (p=0.025) and tended to show a worse recurrence-free survival (RFS) (p=0.065). A high CRP/Alb ratio was significantly associated with worse OS and RFS. Multivariate analysis revealed that among all inflammatory factors, only a high CRP/Alb ratio was an independent prognostic factor for RFS (p=0.022). Conclusion: Sarcopenia is associated with systemic inflammatory response such as high CRP/Alb ratio, while the latter is an independent prognostic marker in patients with esophageal cancer. Esophageal cancer is a highly aggressive malignant disease and has a high metastatic potential (1). Despite the development of multimodal therapies such as surgery, chemotherapy, and chemoradiation therapy, postoperative recurrence is observed in more than half of patients who have undergone transthoracic esophagectomy, and the prognosis of patients with esophageal cancer remains poor (2-4). In addition to various clinicopathological factors and the tumor stage, some other prognostic indicators have been discovered in previous studies of esophageal cancer because of the poor prognosis (5-7). Inflammatory factors are reportedly prognostic factors of cancer, and the close correlation between cancer and inflammation was first discovered by Virchow in 1863 (8). Many inflammatory markers that can be used to predict prognosis have been reported, such as the C-reactive protein (CRP)-to-albumin ratio (CRP/Alb ratio), modified Glasgow prognostic score (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). These markers reportedly associated with the prognosis of various types of cancer, including esophageal cancer (9-14). Sarcopenia, which is characterized by loss of skeletal muscle mass (SMM), has been mainly studied in older people and is known to impair physical performance and survival in this population (15-17). Sarcopenia has recently received great attention in the oncology field and is recognized as an important factor in predicting long-term prognosis in patients undergoing surgery for various types of cancer (18-21). The reason for the relationship between sarcopenia and poor cancer prognosis remains unclear, but inflammation may play a role (22). Previous evidence has support...

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“…Several of the currently described myokines have been shown to transduce anti-neoplastic effect, e.g. SPARC (secreted protein acidic and rich in cysteine) in colon cancer, FNDC5 (fibronectin type III domain-containing protein 5) in breast cancer, etc., although some have also been shown to exert pro-neoplastic actions (Roy et al 2018). Through their EPS protocol and corresponding gene expression experiments, Schwappacher and colleagues (2020) demonstrated the upregulation of several myokines including brain-derived neutrophic factor, IGF binding protein 3, C-C motif chemokine ligand 2, interleukins 5, 6, 7 and 8, and vascular endothelial growth factor.…”

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confidence: 99%

“…However, their study did not characterize the exact roles of the myokines potentially involved in the observed anti-cancer effects. Unravelling the specific effects of the anti-neoplastic myokines not only represents a critical step in our understanding of the molecular and genetic mechanisms mediating the putative therapeutic benefits of exercise in cancer, but opens up a novel modelling landscape for myokine-based anti-neoplastic drug design (catalysts, inhibitors or mimetics, including the futuristic potential of 'exercise encapsulated in a pill') (Roy et al 2018).…”

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confidence: 99%

“…On the other hand, it is not fully clear how cachexia alters the response of muscles to exercise and myokine secretion; or if muscle-fibre metabolic types (oxidative vs. glycolytic) or exercise modes (aerobic vs. anaerobic) display differential specificity to the type of secreted myokine. Moreover, it is likely that the therapeutically relevant myokines exhibit specificity for different cancer phenotypes or subtypes or show similarity in heterogeneous cancers with common molecular signalling mediators (Thomas et al 2017;Roy et al 2018).…”

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confidence: 99%

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Physical activity and cancer biology: navigating a pathophysiological maze and broadening therapeutic imagination

Ugwoke

Umek

2020

The Journal of Physiology

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Exercise-Induced Myokines as Emerging Therapeutic Agents In Colorectal Cancer Prevention and Treatment

Cited by 17 publications

References 20 publications

Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Prognostic Significance of Sarcopenia and Systemic Inflammatory Response in Patients With Esophageal Cancer

Physical activity and cancer biology: navigating a pathophysiological maze and broadening therapeutic imagination

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