Suppressive effects of exercise-conditioned serum on cancer cells: A narrative review of the influence of exercise mode, volume, and intensity

Cancer is a major cause of morbidity and mortality worldwide, and the incidence is increasing, highlighting the need for effective strategies to treat this disease. Exercise has emerged as fundamental therapeutic medicine in the management of cancer, associated with a lower risk of recurrence and increased survival. Several avenues of research demonstrate reduction in growth, proliferation, and increased apoptosis of cancer cells, including breast, prostate, colorectal, and lung cancer, when cultured by serum collected after exercise in vitro (i.e., the cultivation of cancer cell lines in an experimental setting, which simplifies the biological system and provides mechanistic insight into cell responses). The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors, such as skeletal muscle-induced cytokines (i.e., myokines) and hormones. However, exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated, constraining more precise application of exercise medicine within clinical oncology. To date, it remains unclear what role different training modes (i.e., resistance and aerobic training) as well as volume and intensity have on exercise-conditioned serum and its effects on cancer cells. Nevertheless, the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects, while for chronic training interventions, exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode. Insights for future research investigating training modes, volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells. [Abstract copyright: Copyright © 2023. Production and hosting by Elsevier B.V.

The association between naevi and melanoma in populations with different levels of sun exposure: a joint case-control study of melanoma in the UK and Australia.

Two case-control studies were set up to investigate the relationship between melanocytic naevi and risk of melanoma and to compare the naevus phenotype in two countries exposed to greatly different levels of sun exposure and different melanoma rates. In England 117 melanoma cases and 163 controls were recruited from the North-East Thames Region and 183 melanoma cases and 162 controls from New South Wales, Australia. Each subject underwent a whole-body naevus count performed by the same examiner in each country. Relative risks associated with melanocytic naevi in each country were calculated with comparison of naevus data in controls between Australia and England. Atypical naevi were strong risk factors for melanoma in both countries: the odds ratio (OR) for three or more atypical naevi was 4.6 (95% CI 2.0-10.7) in Australia compared with 51.7 (95% CI 6.5-408.4) in England. Common naevi were also significant risk factors in Australia and England with similar odds ratios in the two countries. Prevalence of atypical naevi was greater in Australian controls than in English controls: OR 9.7 (95% CI 1.2-81.7) for three or more atypical naevi in Australia compared with England. For young age groups, the median number of common naevi was greater in Australia than in the UK, whereas for older individuals this difference in naevi number between the two countries disappeared. The prevalence of naevi on non-sun-exposed sites in controls was not significantly different between the two countries. The atypical mole syndrome (AMS) phenotype was more prevalent in Australian controls (6%) than in English controls (2%). The results of this study support the role of sun exposure in the induction of atypical naevi in adults. There was a trend towards stronger risk factors associated with atypical naevi in England compared with Australia. The atypical mole syndrome, usually associated with a genetic susceptibility to melanoma, was more common in Australia than in England, suggesting genetic environmental interactions with the possibility of phenocopies induced by sunlight

A population-based analysis of germline BAP1 mutations in melanoma

Germline mutation of the BRCA1 associated protein-1 (BAP1) gene has been linked to uveal melanoma, mesothelioma, meningioma, renal cell carcinoma and basal cell carcinoma. Germline variants have also been found in familial cutaneous melanoma pedigrees, but their contribution to sporadic melanoma has not been fully assessed. We sequenced BAP1 in 1,977 melanoma cases and 754 controls and used deubiquitinase assays, a pedigree analysis, and a histopathological review to assess the consequences of the mutations found. Sequencing revealed 30 BAP1 variants in total, of which 27 were rare (ExAc allele frequency <0.002). Of the 27 rare variants, 22 were present in cases (18 missense, one splice acceptor, one frameshift and two near splice regions) and 5 in controls (all missense). A missense change (S98R) in a case that completely abolished BAP1 deubiquitinase activity was identified. Analysis of cancers in the pedigree of the proband carrying the S98R variant and in two other pedigrees carrying clear loss-of-function alleles showed the presence of BAP1-associated cancers such as renal cell carcinoma, mesothelioma and meningioma, but not uveal melanoma. Two of these three probands carrying BAP1 loss-of-function variants also had melanomas with histopathological features suggestive of a germline BAP1 mutation. The remaining cases with germline mutations, which were predominantly missense mutations, were associated with less typical pedigrees and tumours lacking a characteristic BAP1-associated histopathological appearances, but may still represent less penetrant variants. Germline BAP1 alleles defined as loss-of-function or predicted to be deleterious/damaging are rare in melanoma

MX 2 is a novel regulator of cell cycle in melanoma cells

MX2 protein is a dynamin‐like GTPase2 that has recently been identified as an interferon‐induced restriction factor of HIV‐1 and other primate lentiviruses. A single nucleotide polymorphism (SNP), rs45430, in an intron of the MX2 gene, was previously reported as a novel melanoma susceptibility locus in genome‐wide association studies. Functionally, however, it is still unclear whether and how MX2 contributes to melanoma susceptibility and tumorigenesis. Here, we show that MX2 is differentially expressed in melanoma tumors and cell lines, with most metastatic cell lines showing lower MX2 expression than primary melanoma cell lines and melanocytes. Furthermore, high expression of MX2 RNA in primary melanoma tumors is associated with better patient survival. Overexpression of MX2 reduces in vivo proliferation partially through inhibition of AKT activation, suggesting that it can act as a tumor suppressor in melanoma. However, we have also identified a subset of melanoma cell lines with high endogenous MX2 expression where downregulation of MX2 leads to reduced proliferation. In these cells, MX2 downregulation interfered with DNA replication and cell cycle processes. Collectively, our data for the first time show that MX2 is functionally involved in the regulation of melanoma proliferation but that its function is context‐dependent

Exercise training mode effects on myokine expression in healthy adults: A systematic review with meta-analysis

Background: The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle–organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment. Methods: A systematic search was undertaken in PubMed, Medline, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on IL-15, irisin, SPARC, OSM, and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change. Results: Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn. Conclusion: Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response