The tumor vessel network has been investigated as a precursor of an inhospitable tumor microenvironment, including its repercussions in tumor perfusion, oxygenation, interstitial fluid pressure, pH, and immune response. Dysfunctional tumor vasculature leads to the extravasation of blood to the interstitial space, hindering proper perfusion and causing interstitial hypertension. Consequently, the inadequate delivery of oxygen and clearance of by-products of metabolism promote the development of intratumoral hypoxia and acidification, hampering the action of immune cells and resulting in more aggressive tumors. Thus, pharmacological strategies targeting tumor vasculature were developed, but the overall outcome was not satisfactory due to its transient nature and the higher risk of hypoxia and metastasis. Therefore, physical exercise emerged as a potential favorable modulator of tumor vasculature, improving intratumoral vascularization and perfusion. Indeed, it seems that regular exercise practice is associated with lasting tumor vascular maturity, reduced vascular resistance, and increased vascular conductance. Higher vascular conductance reduces intratumoral hypoxia and increases the accessibility of circulating immune cells to the tumor milieu, inhibiting tumor development and improving cancer treatment. The present paper describes the implications of abnormal vasculature on the tumor microenvironment and the underlying mechanisms promoted by regular physical exercise for the re-establishment of more physiological tumor vasculature.
A 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.
Avaliar o estado de saúde oral de uma população institucionalizada com deficiência profunda e averiguar a sua relação com potenciais fatores determinantes. Métodos: A população-alvo consistiu nos residentes do Centro de Apoio a Deficientes Profundos Luís da Silva (Borba). A recolha de dados foi realizada através de exame intraoral e aplicação de um questionário aos cuidadores responsáveis pela higiene oral dos residentes. Foram avaliados o índice CPOD, o índice gengival e o índice de higiene oral simplificado e obtidos dados sobre comportamentos relativos à higiene oral, acesso a cuidados de saúde oral, tipo de alimentação e nível de dependência. A análise estatística foi realizada no SPSS, com testes de Qui-quadrado, Mann-Whitney e Kruskal-Wallis (α=0,05). Resultados: A amostra foi constituída por 55 indivíduos, maioritariamente do sexo masculino (63,6%), com paralisia cerebral enquanto patologia mais prevalente que motivou a institucionalização (29,1%). Obteve-se um CPOD médio de 11,15 (dp=10,06), prevalência de cárie de 80%, índice gengival de 1,71 (dp=0,73) e índice de higiene oral simplificado de 1,61 (dp=0,70). A escovagem era maioritariamente realizada bidiariamente (90%) com auxílio dos funcionários (80,4%) e 40% dos participantes nunca realizaram consultas de saúde oral. A maioria dos participantes apresentou alimentação de textura normal (50,9%). As variáveis que contribuíram significativamente (p<0,05) para o estado de saúde oral foram o sexo, a idade, o tipo de alimentação e a capacidade funcional para a higiene oral. Conclusões: As pessoas institucionalizadas com deficiência profunda apresentam um estado de saúde oral precário, necessidade de auxílio para a higiene oral e um escasso acesso a cuidados de saúde oral.
Introduction: Benefits of regular physical exercise were demonstrated as preventive and coadjuvant nonpharmacological anticancer therapy. However, the role of exercise in modulating prostate cancer behavior has yet to be established. Methods: Prostate tumors were induced in C57BL/6 male mice (n = 28) by subcutaneous inoculation of a suspension of murine androgen-independent RM1 cells (1.5 × 105 cells/500 μL phosphate-buffered saline) in the dorsal region. Mice were randomly allocated into 2 study groups: sedentary tumor-induced (n = 14) and exercised tumor-induced (n = 14). Exercise consisted of voluntary running in wheeled cages. Mice (n = 7 per group) were sacrificed either 14 or 28 days after cell inoculation to evaluate tumor weight and percentage of area occupied by immunohistochemistry stained cells for Ki-67 and TdT-mediated dUTP-biotin nick end labeling, used as surrogate markers of cell proliferation and apoptosis, respectively. Results: Compared with sedentary tumor-induced mice, the tumors developed by exercised tumor-induced mice were significantly smaller at 14 days (0.17 [0.12] g vs 0.48 [0.24] g, P < .05) and at 28 days (0.92 [0.73] g vs 2.09 [1.31] g, P < .05), with smaller Ki-67 and greater TdT-mediated dUTP-biotin nick end-labeling stained areas (P < .05). Conclusion: These results suggest that regular voluntary running inhibits prostate cancer cell growth by reducing cell proliferation and enhancing apoptosis.
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