Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials

Rothwell, Peter M.; Wilson, Michelle; Price, Jackie F.; Belch, J. J. F.; Meade, T W; Mehta, Ziyah

doi:10.1016/s0140-6736(12)60209-8

Cited by 866 publications

(756 citation statements)

References 37 publications

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“…Indeed, recent clinical data show that patients that have been on low dose aspirin for cardiovascular disease for several years have a dramatically decreased risk to develop metastatic cancer. 149,150 This connection has therapeutic relevance since aspirin efficiently prevents platelet activation.…”

Section: Platelet-derived Tgfb and Nf-kb Signaling Asmentioning

confidence: 99%

Reprogramming during epithelial to mesenchymal transition under the control of TGFβ

Tan¹,

Olsson

Moustakas

2014

Cell Adhesion & Migration

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Epithelial-mesenchymal transition (EMT) refers to plastic changes in epithelial tissue architecture. Breast cancer stromal cells provide secreted molecules, such as transforming growth factor b (TGFb), that promote EMT on tumor cells to facilitate breast cancer cell invasion, stemness and metastasis. TGFb signaling is considered to be abnormal in the context of cancer development; however, TGFb acting on breast cancer EMT resembles physiological signaling during embryonic development, when EMT generates or patterns new tissues. Interestingly, while EMT promotes metastatic fate, successful metastatic colonization seems to require the inverse process of mesenchymal-epithelial transition (MET). EMT and MET are interconnected in a timedependent and tissue context-dependent manner and are coordinated by TGFb, other extracellular proteins, intracellular signaling cascades, non-coding RNAs and chromatin-based molecular alterations. Research on breast cancer EMT/MET aims at delivering biomolecules that can be used diagnostically in cancer pathology and possibly provide ideas for how to improve breast cancer therapy.

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Section: Platelet-derived Tgfb and Nf-kb Signaling Asmentioning

confidence: 99%

Reprogramming during epithelial to mesenchymal transition under the control of TGFβ

Tan¹,

Olsson

Moustakas

2014

Cell Adhesion & Migration

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“…Suppressing platelet activity may improve outcomes in patients with cancer. Several recent studies have investigated treatments with antiplatelet agents, particularly aspirin [3,8], because aspirin caused a reduction of platelet activities [9]. A correlative study of randomized controlled trials evaluating the cardiovascular benefits of aspirin reported that aspirin also reduced the risk of distant metastasis after cancer incidence [8].…”

Section: Introductionmentioning

confidence: 99%

“…Several recent studies have investigated treatments with antiplatelet agents, particularly aspirin [3,8], because aspirin caused a reduction of platelet activities [9]. A correlative study of randomized controlled trials evaluating the cardiovascular benefits of aspirin reported that aspirin also reduced the risk of distant metastasis after cancer incidence [8]. This antitumor effect is considered to be driven by the inhibition of cyclooxygenase-2 (COX-2), which is overexpressed in cancer cells [10,11], or by platelet adhesion to tumor cells, the latter of which is essential for preventing immune surveillance by natural killer cells [12].…”

Section: Introductionmentioning

confidence: 99%

Antitumor effect of antiplatelet agents in gastric cancer cells: an in vivo and in vitro study

et al. 2015

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Background The antitumor effects of antiplatelet agents in gastric cancer cells are not well known. In this study, the possibility of gastric cancer treatment with an antiplatelet agent, mainly aspirin, was examined both in vivo and in vitro. Methods For in vivo experiments, tumor-bearing mice were treated by an antiplatelet antibody or aspirin, and the tumor growth was compared. For in vitro experiments, human gastric cancer cell lines were used to confirm the cancer cell growth and inhibition by reducing the platelet count or using aspirin. We also examined several cytokines by using an ELISA assay and conducted microRNA microarray analysis of MKN-45 tumor cells to determine the influence of platelets or aspirin. Results In vivo experiments showed that tumor growth was inhibited by halving the circulating platelet count by using an antiplatelet antibody or peroral daily aspirin. In vitro experiments showed that the proliferation rates of gastric cancer cell lines were increased after coincubation with platelets and that the effect was inhibited by aspirin. Although the expression of interleukin-6, platelet-derived growth factor, transforming growth factor-b, and prostaglandin E2 did not correlate with tumor growth inhibition by aspirin, seven microRNAs showed altered expression in cancer cells in response to coincubation with platelets or addition of aspirin. Cells transfected with mir-4670-5p showed a significant increase in proliferation compared to negative control cells. Conclusions Our study showed that platelets increased the proliferation of gastric cancer cells and that this increase was inhibited by antiplatelet antibody or aspirin. Mir-4670-5p may play an important role in these responses.

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“…In contrast to these findings, four other observational studies found little evidence of an association between aspirin use after diagnosis and breast cancer survival or recurrence [13][14][15][16][17]. A meta-analysis of 5 randomized controlled trials of low-dose aspirin to prevent vascular events showed that cancer patients (including patients with breast cancer) initiating aspirin treatment before cancer diagnosis had a reduced risk of metastasis and improved survival [18]. However, as these patients were taking aspirin before cancer diagnosis, it remains unclear whether low-dose aspirin use after cancer diagnosis, a time point more relevant for clinical intervention, confers any benefit.…”

Section: Introductionmentioning

confidence: 93%

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study

McMenamin

Cardwell

Hughes

et al. 2017

Cancer Epidemiology

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Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials

Cited by 866 publications

References 37 publications

Reprogramming during epithelial to mesenchymal transition under the control of TGFβ

Reprogramming during epithelial to mesenchymal transition under the control of TGFβ

Antitumor effect of antiplatelet agents in gastric cancer cells: an in vivo and in vitro study

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study

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