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Steroids and immune checkpoint inhibitors
Steroids are more potent than non-steroidal anti-inflammatory drugs such as COX inhibitors because they act earlier in the inflammatory innate immune responseprocess. Thus, a higher dose of steroids may result in more harmful changes in the inflammatory immune response as compared to non-steroidal anti-inflammatory drugs, especially as they have fewer side effects and have a shorter duration of action. It is important to note that even after the use of anabolic steroids, it is difficult to stop the inflammatory immune response due to the fact that there are anabolic androgenic androgens (ADT and Estradiol), which are also potent inducers of the innate immune response, steroids and immune checkpoint inhibitors. Finally, steroid hormones have a negative effect on bone density in animals and humans.[32,33] It should be noted that anabolic steroids do not affect the formation of the plasminogen activator inhibitor protein (PAI-1) or the expression levels of the growth factors IL-6 or IL-17, steroids and cortisol levels.[24,34] Effects on Tumor Growth A few studies show that both human and animal studies have revealed that anabolic androgenic steroids exert a direct, in vivo effect on tumor growth. Animal studies have shown that both anabolic androgenic steroid use during pregnancy alters the expression levels of cancer-promoting genes and tumor necrosis factor (TNF)-α, immune checkpoint inhibitors and steroids.[33,35] In one study, this study showed that anabolic androgenic steroids use resulted in up to 40% increase in the mRNA expression level of tumor necrosis factor (tNF)-α in mammary tumors of female rats, steroids and liver enzymes. After a 6-week treatment period, the tumor growth was reduced.[33] In another study, a higher dose of anabolic androgenic steroid treatment resulted in a more significant increase in the protein levels of the human TNF-α cytokines IL-4 and IL-6 in breast tumor cells, steroids and muscle damage. An increase of both IL-4 and IL-6 is known as interleukin (IL)-4, followed by IL-6, and, respectively, the effects of anabolic androgenic steroid treatment on this cytokine expression pattern were studied.[6] A human study also showed that anabolic androgenic steroids exposure also result in up to 35% increase in the mRNA levels of transforming growth factor-beta (tGF-Beta) in human colonic and mammary tumors as compared to the control group.
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