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The use of Spheroids in the Study of Invasion
Published in Rolf Bjerkvig, Spheroid Culture in Cancer Research, 2017
Marc Bracke, Hans Romijn, Vakaet Luc, Barbara Vyncke, Marc de Mets, Marc Mareel
In many cells retinoic acid binds to a cytoplasmic retinoic acid-binding protein (CRABP)85,86 before it is passed to the nuclear retinoic acid receptors (RAR).87,88 Retinoic acid is considered to be a regulator of cell differentiation and embryonic morphogenesis89 and is one of the most potent teratogens known.90 Addition of 10−6M all-trans-retinoic acid to the culture medium has an antithetic effect on the invasion of MCF-7 cell variants. The constitutively noninvasive variant (MCF-7/AZ) becomes invasive, while invasion of the MCF-7/6 variant is inhibited.
Inverse Psoriasis
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Mark G. Lebwohl, Mild to Moderate Psoriasis, 2014
Lara Wine-Lee, Robert A. Lee, Abby S. Van Voorhees
Topical or oral retinoids have multiple effects on keratinocyte differentiation and proliferation and inflammatory processes that contribute to psoriasis. There are two classes of nuclear retinoid receptors that have been identified: the retinoic acid receptor (RAR) and retinoid X receptor (RXR) [51]. The function of these RARs and RXRs is not well understood in skin. In animal models, retinoids block induction of ornithine decarboxylase activity that is associated with cell proliferation and expression. In vitro skin models and cell cultures also demonstrate that retinoids suppresses epidermal hyperproliferation.
Systemic Retinoids
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb, Moderate to Severe Psoriasis, 2014
Daniel C. Butler, Tina Bhutani, Ethan C. Levin, Eva Wang, John Y. M. Koo
Retinoids act on retinoic acid receptors (RAR α, β, γ) and retinoid X receptors (RXR α, β, γ) [4–6]. Acitretin is a second-generation systemic retinoid that binds poorly but activates all three RAR subtypes. Unlike other systemic antipsoriatic medications that function predominantly via immunosuppressive mechanisms, acitretin’s antipsoriatic effects are thought to be secondary to interaction with nuclear receptors, resulting in enhancement of skin cell differentiation and maturation and leading to antiproliferative effects.
All-Trans Retinoic Acid Promotes M2 Macrophage Polarization in Vitro by Activating the p38MAPK/STAT6 Signaling Pathway
Published in Immunological Investigations, 2023
Ya-nan Zhu, Xiao-li Gu, Lin-yuan Wang, Ning Guan, Chen-guang Li
Retinoic acid bioactivity is mediated through the nuclear receptor protein RAR. It is known that RAR interacts with a different nuclear receptor protein, the retinoic acid X receptor (RXR), to form RAR/RXR heterodimers, with three different isoforms of RAR and RXR, namely α, β and γ These dimers bind to the retinoic acid response element (RARE) thereby affecting gene expression and regulating the function of multiple immune cells (Veldhoen and Ferreira 2015). Brown et al. (2015) found that retinoic acid directly regulates the expression of key genes in the differentiation of CD4+ T cells to Th1 cells and inhibits their differentiation to Th17 cells through the association with retinoic acid nuclear receptor RARα. Peritoneal macrophages express abundant amounts of the retinoic acid nuclear receptor RARβ, and Yu et al. (2022) demonstrated that ATRA enhanced the secretion of anti-inflammatory repair-related inflammatory factors by M2 macrophages by acting on RARβ receptors. In recent years, more studies have shown that retinoic acid receptors interact with multiple other signaling pathways by regulating transcription, translation as well as phosphorylation, which then affects immune cell function. In this study, we demonstrated that all-trans retinoic acid promotes M2 macrophage polarization through activation of the p38MAPK/STAT6 signaling pathway, but the role of retinoic acid receptors in ATRA promotion of M2-type macrophage polarization remains unknown.
Emerging drugs for the treatment of acne: a review of phase 2 & 3 trials
Published in Expert Opinion on Emerging Drugs, 2022
Siddharth Bhatt, Rohit Kothari, Durga Madhab Tripathy, Sunmeet Sandhu, Mahsa Babaei, Mohamad Goldust
Retinoids are Vitamin A analogues. These molecules bind to the Retinoic acid receptor (RAR) and Retinoid X receptor (RXR), heterodimerize or homodimerize and then translocate to the nucleus where they bind to the Retinoic acid response element (RARE) bringing about their biological effects. In the skin, retinoids modulate the proliferation and differentiation of the keratinocytes and regulate the activity of the adhesion molecules also. It also down-regulates the expression of TLR 2 receptor which reduces Cutibacterium acnes mediated inflammation. Reduction in the size of sebaceous glands and sebum production is of particular importance in the treatment of acne. Currently, FDA approves the use of Isotretinoin for acne vulgaris. The most dreaded side effect which limits the use of retinoids is teratogenicity. Furthermore, as acne is commoner in adolescents and young adults, the risk of teratogenicity always needs to be weighed while prescribing it. Side effects include dose dependent muco-cutaneous problems like are dryness of mouth, lipid abnormalities which may rarely lead to pancreatitis, hepatitis. Pseudotumor cerebri neuropsychiatric manifestations like depression, sexual dysfunction have also remain a significant concern though these side effects are uncommon [2,5].
Retinoic acid receptor agonist as monotherapy for early-stage mycosis fungoides: does it work?
Published in Journal of Dermatological Treatment, 2019
Iris Amitay-Laish, Ofer Reiter, Hadas Prag-Naveh, Ruben Kershenovich, Emmilia Hodak
Retinoids are signaling molecules that are structurally related to vitamin A. Their biological effects are triggered through specific intracellular retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) (1–3). By forming various heterodimers, they act as ligand-inducible transcription-regulatory factors and exert antiproliferative, antiangiogenic, immunomodulating and differentiation effects (3–6). Retinoids have been successfully used in the treatment of a broad range of inflammatory and neoplastic skin diseases and have proven effective in reducing cutaneous dysplasia as well as the frequency of squamous cell cancer developing in immunocompromised patients (7,8). In the treatment of cancer, retinoids are considered “biologic response modifiers” because they induce an effect without immune suppression and even frequently augment the immune response (8–14).