The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-analysis

Author(s):  
Mário Esteves ◽  
Mariana P. Monteiro ◽  
Jose Alberto Duarte

AbstractA wealth of evidence supports an association between physical exercise, decreased tumor growth rate, and reduced risk of cancer mortality. In this context, the tumor vascular microenvironment may play a key role in modulating tumor biologic behavior. The present systematic review and meta-analysis aimed to summarize the evidence regarding the effects of physical exercise on tumor vasculature in pre-clinical studies. We performed a computerized research on the PubMed, Scopus, and EBSCO databases to identify pre-clinical studies that evaluated the effect of physical exercise on tumor vascular outcomes. Mean differences were calculated through a random effects model. The present systematic review included 13 studies involving 373 animals. From these, 11 studies evaluated chronic intratumoral vascular adaptations and 2 studies assessed the acute intratumoral vascular adaptations to physical exercise. The chronic intratumoral vascular adaptations resulted in higher tumor microvessel density in 4 studies, increased tumor perfusion in 2 studies, and reduced intratumoral hypoxia in 3 studies. Quantitatively, regular physical exercise induced an increased tumor vascularization of 2.13 [1.07, 3.20] (p<0.0001). The acute intratumoral vascular adaptations included increased vascular conductance and reduced vascular resistance, which improved tumor perfusion and attenuated intratumoral hypoxia. In pre-clinical studies, physical exercise seems to improve tumor vascularization.

Author(s):  
Willeke R. Naaktgeboren ◽  
David Binyam ◽  
Martijn M. Stuiver ◽  
Neil K. Aaronson ◽  
Arco J. Teske ◽  
...  

Background Physical exercise is an intervention that might protect against doxorubicin‐induced cardiotoxicity. In this meta‐analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin‐induced cardiotoxicity and to evaluate mechanisms underlying exercise‐mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk‐of‐bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise‐mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin‐induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin‐induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise‐induced cardioprotection, of which the latter could act as an overarching mechanism. Conclusions Animal studies indicate that various exercise interventions can protect against doxorubicin‐induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer. Registration URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42019118218.


2021 ◽  
Vol 117 ◽  
pp. 105088
Author(s):  
Zhao Hu ◽  
Atipatsa Chiwanda Kaminga ◽  
Jun Yang ◽  
Jiefeng Liu ◽  
Huilan Xu

2021 ◽  
pp. 174248
Author(s):  
Kiarash Saleki ◽  
Shakila Yaribash ◽  
Mohammad Banazadeh ◽  
Ehsan Hajihosseinlou ◽  
Mahdi Gouravani ◽  
...  

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nazanin Razazian ◽  
Mohsen Kazeminia ◽  
Hossein Moayedi ◽  
Alireza Daneshkhah ◽  
Shamarina Shohaimi ◽  
...  

Author(s):  
Júlio Araújo Rendeiro ◽  
Cesar Augusto Medeiros Paiva Rodrigues ◽  
Letícia de Barros Rocha ◽  
Rodrigo Santiago Barbosa Rocha ◽  
Marianne Lucena da Silva ◽  
...  

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 351
Author(s):  
Massimiliano Creta ◽  
Giuseppe Celentano ◽  
Luigi Napolitano ◽  
Roberto La Rocca ◽  
Marco Capece ◽  
...  

Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30–0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22–0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.


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