The serological responses to acute exercise in humans reduce cancer cell growth in vitro: A systematic review and meta-analysis.

We systematically reviewed and meta-analyzed the effects of acute exercise-conditioned serum on cancer cell growth in vitro. Five literature databases were systematically searched for studies that measured cancer cell growth after exposure to human sera obtained before and immediately after an acute bout of exercise. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a three-level random-effects model. Meta-regressions were also performed with participant age and disease status, exercise type, cell line TP53 status, and serum incubation time entered as covariates. Seven studies met the inclusion criteria encompassing a total of 21 effect estimates and 98 participants. Exercise-conditioned serum significantly reduced cancer cell growth compared with preexercise serum (SMD = -1.23, 95% CI: -1.96 to -0.50; p = .002; I2  = 75.1%). The weighted mean reduction as a percentage of preexercise values was 8.6%. The overall treatment effect and magnitude of heterogeneity were not statistically influenced by any covariate. There were concerns regarding the risk of bias within individual studies and Egger's test of the intercept showed evidence of small study effects (ß = -3.6, p = .004). These findings provide in vitro evidence that the transient serological responses to acute exercises reduce cancer cell growth, although many questions remain regarding the underlying mechanistic pathways and potential effect modifiers. To strengthen this evidence-base, future studies should seek to reduce the risk of bias by using more rigorous experimental designs, and consider using 3D cell culture models to better replicate in vivo tumor conditions. PROSPERO registration: CRD42020161333.

Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas.

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients' risk stratification.