China
Africa
Explore chapters and articles related to this topic
Nuclear Receptor Coactivators: Mechanism and Therapeutic Targeting in Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Andrew Cannon, Christopher Thompson, Rakesh Bhatia, Sushil Kumar
Given their ability to potentiate the function of various nuclear receptors, several nuclear receptor coactivators have been shown to play critical roles in the development and progression of cancer. While most of the work regarding the function of nuclear receptor coactivators in cancer has been conducted in the setting of hormone sensitive cancers, a significant body of literature exists for cancers that are not classically associated with hormone sensitivity. In the following section, we address the role of several nuclear receptor co-activator in hormone sensitive and hormone insensitive cancers (Table 1).
Histogenesis of Irreversible Changes in the Female Genital Tract After Perinatal Exposure to Hormones and Related Substances
Published in Takao Mori, Hiroshi Nagasawa, Toxicity of Hormones in Perinatal Life, 2020
The estrogen response in the neonatal period has previously been primarily studied in rats. A full estrogen response can be obtained when estradiol is given in adequate repeated doses.158,159 Thus, autoradiographic and biochemical studies of the receptor in neonatal uterine or vaginal tissue from acutely low-dose estrogen-treated females may not reflect an in vivo situation under continuous treatment with higher doses. Nuclear receptors could be induced in uterine and vaginal epithelia under prolonged treatment with proper doses, and the role of the receptor mechanism in the induction of permanent estrogen-induced changes should not be excluded.
Nutrigenomics and Nutrigenetics in Cancer Prevention
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Komal Parmar, Jayvadan K. Patel
Epigenetic changes that mediate changes in genetic expression without changing the DNA sequence include DNA methylation and histone modification. Such changes accumulate with increase in age, which increases the sensitivity toward cancer development in body. Use of bioactive compounds may prove as potential tool for treatment/prevention of cancer. Nuclear receptors are group of transcription factors that function as sensors to dietary constituents and thereby mediate the response to dietary factors (Romagnolo et al. 2014). Nutrient–gene interactions influencing cancer process are modulated by genetic mutations, epigenetic modifications, interactions with dietary constituents, and heterogeneity of cells in tumor. Therefore, in order to find out how nutrigenomics and nutrigenetics will help in preventing cancer disease, knowledge of gene polymorphisms, gene targets that regulate cell and tissue pathways, and strategies to control clinical heterogeneity are important.
Global transcriptional response of oral squamous cell carcinoma cell lines to health-associated oral bacteria - an in vitro study
Published in Journal of Oral Microbiology, 2022
Divyashri Baraniya, Kumaraswamy Naidu Chitrala, Nezar Noor Al-Hebshi
Nuclear receptors also play key roles in inflammation and cancer [47,48]. In this study, H. parainfluenzae and N. flavescens downregulated LXR/RXR, PPARα/RXRα and PPAR signaling, which are known to have tumor suppressive effect [47]. On the other hand, H. parainfluenza also upregauted VDR/RXR signaling in SCC4, which has potential to control cancer cell growth by driving anti-proliferative pathways and by enhancing adhesion [49]. Furthermore, despite their potential anti-cancer roles, many of the NRs are also overexpressed in specific cancers [47,50]. S. mitis activated NRF2, which mediates antioxidant responses and thus plays a role in cancer prevention; however, there are also studies that implicate it in cancer progression [51]. Therefore, there is significant ambiguity about the nature of many of the observed transcriptional changes, i.e. it is not straightforward to predict whether they represent anti- or pro-cancer effects. There were other examples of such ambiguous changes. H. parainfluenzae, N. flavescens and P. gingivalis, upregulated nitric oxide and reactive oxygen species, which have a dual role in cancer depending on their concentration in the TME [52]. Similarily, Acetone degradation I (to Methyglyoxal) pathway, which was activated by H. parainfluenzae and N. flavescens, has recently been suggested to play a dual role in cancer depending on the rate of production [53].
Liver X receptor: a potential target in the treatment of atherosclerosis
Published in Expert Opinion on Therapeutic Targets, 2022
Shreya R. Savla, Kedar S Prabhavalkar, Lokesh K Bhatt
LXRs are ligand-activated transcription factors of the nuclear hormone receptor superfamily. Nuclear receptors are transcription factors involved in various physiological processes [8]. Nuclear receptors, like LXRs, the peroxisome proliferator-activator receptors (PPARs), and the farnesoid X receptors (FXRs), respond to cellular changes associated with levels of endogenous lipid ligands by regulation of gene expressions encoding the proteins that play a role in lipid metabolism. The family of LXRs comprise two isotypes, LXR alpha (LXRα) and beta (LXRβ), which are encoded by genes Nr1h3 and Nr1h2, respectively. LXRα and LXRβ show a high level of sequence homology but differ in tissue distribution. Metabolically active cells and tissues, like intestine, liver, macrophages, and adipose tissue, exhibit a high level of LXRα expression. LXRα is restricted to the myeloid lineage in hematopoietic cells. On the other hand, LXRβ exhibits a ubiquitous expression profile. The two isotypes of LXR, namely LXR α and β, show an overlapping expression pattern that is non-identical to each other [4].
The therapeutic potential of PROTACs
Published in Expert Opinion on Therapeutic Patents, 2021
Andrew B. Benowitz, Katherine L. Jones, John D. Harling
Nuclear receptors function as important signal transduction mechanisms within cells, playing a key role in sensing stimulating ligands and then regulating gene transcription in response to those ligands. It has been well characterized that the presence of excess signaling ligands or mutations in nuclear receptors resulting in inappropriate transcriptional program activation or propagation can exacerbate human disease, and approved medicines that antagonize these receptors have proven to be valuable treatment options for patients. However, patient benefit can be limited upon prolonged treatment with these medicines, and it has been hypothesized that degrading nuclear receptors through a PROTAC strategy may provide superior patient benefit versus antagonism [17]. To this end, multiple reports describing the PROTAC-mediated degradation of the androgen receptor (AR) for the treatment of prostate cancer [18–20], as well as the estrogen receptor (ER) for the treatment of breast cancer [21–23] have been disclosed.