China
Africa
Explore chapters and articles related to this topic
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The retinoids are natural and synthetic derivatives of vitamin A that regulate a variety of important cellular functions. Retinol (Figure 6.106), also known as vitamin A1, is a vitamin found in many food types and used as a dietary supplement to treat and prevent vitamin A deficiency. In the body retinol is converted to retinal and then retinoic acid which acts on cell-surface receptors to control processes including cell growth and metabolism (Figure 6.105). In particular, it is a regulator of epithelial and bone tissue cell growth and differentiation, and so analogues have been developed for use in skin-related proliferative diseases such as psoriasis and bone tissue disorders. Through the activation of tumor-suppressor genes, it is also known to play a role in maintaining vision and immune function. Retinol was discovered in 1909, isolated in 1931 and first synthesized in 1947, and dietary sources rich in the molecule include dairy products, meat, and fish. All-trans-retinoic acid (RA) works by activating the Nuclear Retinoic Acid receptors (RARs), while 9-cis-retinoic acid activates the non-classical nuclear Retinoid X Receptors (RXRs) along with the RARs. Altogether, there are six genes encoding the retinoid receptors: RARa, RARb, and RARg, and RXRa, RXRb, and RXRg (Figure 6.105).
Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
The effects of RA on cells are mediated by RA responsive receptors (RAR): retinoic acid receptor alpha (RARA or RAR-α), beta (RARB or RAR-β), and gamma (RARG or RAR-γ) and the peroxisome proliferator-activated receptor beta and delta (PPARB or PPAR-β and PPARD or PPAR-δ) which belong to the nuclear receptor superfamily (6). They function as RA ligand-dependent transcription factors which form heterodimers with the retinoid X receptors (RXRs), and mediate transcription by binding to DNA. Heterodimers RAR/RXR bind to cis acting RA response elements (RAREs), while PPAR/RXR heterodimers bind to peroxisome proliferator response element (PPRE) (Figure 8.1) (7–9). The precise control of RARs is necessary for the correct balance between self-renewal and differentiation of tissue stem cells. The loss, accumulation, mutations, or aberrant modifications of RARs results in oncogenic transformation with disturbance in differentiation and uncontrolled proliferation of cells (10). The targets of RA and RARs/PPAR-β/δ include many structural genes, oncogenes, transcription factors, and cytokines.
Future directions in cardio-oncology research
Published in Susan F. Dent, Practical Cardio-Oncology, 2019
Li-Ling Tan, Sean Zheng, Alexander R. Lyon
Relying on cardiac biomarkers alone to predict the risk of cardiotoxicity is insufficient in light of the various caveats discussed earlier. There is growing research in the field of genomics with the aim of identifying genetic markers that can improve cardiotoxicity risk stratification and guide cancer and cardioprotective treatment strategies. Aminkeng et al. have singled out a coding variant in RARG (retinoic acid receptor γ) that increases the risk of anthracycline-induced cardiotoxicity in patients treated for childhood cancer (15). A recent study by Hildebrandt et al. identified two hypertension susceptibility gene variants that may protect one from anthracycline cardiotoxicity (16). In addition to circulating biomarkers and imaging parameters, the ongoing SAPhIRE study aims to identify genetic mutations that predispose Asian patients to anthracycline cardiotoxicity (17).
Acute myeloid leukemia with NUP98::RARG resembling acute promyelocytic leukemia accompanying ARID1B gene mutation
Published in Hematology, 2023
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by fatal coagulation abnormalities. More than 98% of patients with APL have a promyelocytic leukemia–retinoic acid receptor alpha (PML::RARA) fusion gene caused by the chromosomal translocation t (15; 17) (q22; q21), which is sensitive to therapy with ATRA and arsenic trioxide (ATO) therapy[1,2]. However, certain AML subtypes exhibit the APL phenotype and APL-like syndromes, with X::RARs fusion genes rather than the PML–RARA fusion gene [2]. In the past few years, X::RARA has been well described, including PLZF::RARA, NPM1::RARA, and STAT5B::RARA. Furthermore, retinoic acid receptor beta(RARB) and retinoic acid receptor gamma(RARG) rearrangements have been discovered to contribute to APL-like syndromes [3]. Notably, RARB and RARG share high sequence homology with RARA[4], and unlike PML::RARA fusions, most novel X::RAR fusions are ATRA or ATO resistant. In this study, we report the case of a patient with AML with a NUP98::RARG rearrangement and review our current understanding of patients with AML harboring X::RAR fusion gene.
A short report of novel RARG-HNRNPM fusion gene in resembling acute promyelocytic leukemia
Published in Hematology, 2022
Yang Song, Jiangxue Hou, Li Wan, Kaiqi Liu, Chunlin Zhou, Shuning Wei, Guangji Zhang, Dong Lin, Yan Li, Qiuyun Fang, Yuntao Liu, Benfa Gong, Xiaoyuan Gong, Ying Wang, Hui Wei, Jianxiang Wang, Yingchang Mi
Acute promyelocytic leukemia (APL) with typically PML-RARA fusion gene caused by t (15;17) (q22; q21) was distinguished from other types of acute myeloid leukemia (AML) according to the World Health Organization (WHO) 2016 criteria [1,2]. The clinical features of APL include severe hemorrhagic and coagulation disorder and sensitivity to arsenic trioxide (ATO), all-trans retinoic acid (ATRA), and anthracyclines. Nowadays, APL is considered ‘curable leukemia’ [1]. Resembling APL is referring to those rare cases that sharing clinical, morphological, and immunophenotypic features with APL, but lacking evidence of PML-RARA fusion gene and usually resistance to ATRA [3,4]. Herein, we reported a 25-year-old female case with a novel fusion gene involving the retinoic acid receptor gamma (RARG) gene and heterogeneous nuclear ribonucleoprotein M (HNRNPM) gene in a leukemic phenotype resembling APL.
Identification of key transcription factors in preeclampsia
Published in Hypertension in Pregnancy, 2019
Junhu Wang, Huijie Liu, Yunxia Guo, Chunxiao Zhou, Tingting Qi
Retinoic acid (RA) signaling through its receptors (RARA, RARB, RARG, and the retinoic X receptor RXRA) is essential for healthy placental and fetal development. It was proposed that increased RA may contribute to preeclampsia pathogenesis by reducing sFLT1 accumulation at the maternal–fetal interface (24). Thus, it is coincidence with our finding that RA was a key factor in preeclampsia. TP53 plays a crucial role in regulating cell apoptosis by activating the expression of proapoptotic protein Bax and inhibiting antiapoptotic protein Bcl-2 and BIRC5 expressions at the transcriptional level (25,26). It is proposed that upregulation of P53 was involved in triggering cell apoptosis in cultured human umbilical vein endothelial cell (HUVECs) from preeclampsia pregnancies by regulating Bax gene, Bcl-2, and BIRC5 genes (27). Besides, an upregulation of the TP53 pathway was reported to induce the deportation of microparticles, including high levels of antiangiogenic factors, and that this might facilitate maternal systemic symptoms in preeclampsia (28).