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Qingyi Tong, Huijuan You, Xintao Chen, Kongchao Wang, Weiguang Sun, Yufeng Pei, Xiaodan Zhao, Ming Yuan, Hucheng Zhu, Zengwei Luo, Yonghui Zhang
Despite All-trans retinoic acid (ATRA) has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, there remains a clinical challenge that many high-risk APL patients who fail to achieve a complete molecular remission or relapse and become resistant to ATRA. Herein, we report that 5-(4-methoxyphenethyl)-[1, 3] dioxolo [4, 5-j] phenanthridin-6(5H)-one (ZYH005) exhibits specific anticancer effects on APL and ATRA-resistant APL in vitro and vivo, while shows negligible cytotoxic effect on non-cancerous cell lines and peripheral blood mononuclear cells from healthy donors...
March 15, 2018: Nucleic Acids Research
Huanan Li, Deping Zeng, Zhenyu Wang, Liaoqiong Fang, Faqi Li, Zhibiao Wang
AIM: To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. MATERIALS & METHODS: A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs...
March 14, 2018: Nanomedicine
Rémi Patouret, Christelle Doebelin, Ruben D Garcia-Ordonez, Mi Ra Chang, Claudia Ruiz, Michael D Cameron, Patrick R Griffin, Theodore M Kamenecka
Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ, however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fig. 1). To our knowledge, this is one of only two small molecule RORβ inverse agonists identified in the primary literature from a tractable chemical series and represents an ideal starting point from which to design RORβ-selective modulators...
March 3, 2018: Bioorganic & Medicinal Chemistry Letters
Bong-Geum Jang, Boyoung Choi, Suyeon Kim, Jae-Yong Lee, Min-Ju Kim
Neuroblastoma cell differentiation is a valuable model for studying therapeutic methods in neuroblastoma and the mechanisms of neuronal differentiation. Here, we used trichostatin A (TSA) and sirtinol, which are inhibitors of cHDACs and sirtuins, respectively, to show that classical histone deacetylases (cHDACs) and sirtuins (silent mating type information regulation 2 homolog; SIRTs) affect all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. After first determining neurite elongation and expression levels of tyrosine hydroxylase and high size neurofilament as useful differentiation markers, we observed that TSA increased neuroblastoma cell differentiation, while sirtinol had the antagonistic effect of decreasing it...
March 7, 2018: Journal of Molecular Neuroscience: MN
Xiangchou Yang, Rongxin Yao, Hong Wang
Studies employing mouse transplantation have illustrated the role of aldehyde dehydrogenase (ALDH) defining hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs). Besides being a molecular marker, ALDH mediates drug resistance in AML, which induces poor prognosis of the patients. In AML patients, either CD34+ ALDHbr population or CD34+ CD38- ALDHint population was found to denote LSCs and minimal residual disease (MRD). A bunch of reagents targeting ALDH directly or indirectly have been evaluated. ATRA, disulfiram, and dimethyl ampal thiolester (DIMATE) are all shown to be potential candidates to open new perspective for AML treatment...
2018: BioMed Research International
Harrison T Supnick, Rodica P Bunaciu, Andrew Yen
Differentiation therapy is used in cancer treatment. Epidemiologic studies showed that higher vitamin D levels are associated with reduced cancer risks. However, the therapeutic doses needed for differentiation are accompanied by hypercalcemia and intolerable pathological sequelae. In the present work we evaluated if RRD-251, a small-molecule, can enhance vitamin D3-induced differentiation of leukemic cells, in the hope of decreasing the needed vitamin D3-dose. We demonstrate that RRD-251 enhances vitamin D3-induced differentiation of leukemic cells, the enrichment of the c-Raf kinase in the nucleus, the binding of nuclear c-Raf to GSK-3, increased phosphorylation of GSK-3 ser 21/9 inhibitory sites, and the binding of GSK-3 to VDR, where GSK-3 inhibition is known to enhance transcriptional activation by VDR...
February 9, 2018: Oncotarget
M D Ruiz, A Iriel, M S Yusseppone, N Ortiz, P Di Salvatore, A Fernández Cirelli, M C Ríos de Molina, J A Calcagno, S E Sabatini
This study investigated metal accumulation and oxidative effects in mantle, gill and digestive gland of the ribbed mussel Aulacomya atra from the Argentinean North Patagonian coastline. Mussels were transplanted over an 18-month period from a site with low anthropogenic impact to a harbor site with higher seawater concentration of aluminum, chromium, copper, manganese, nickel and zinc. Total trace metal concentration in seawater did not change throughout the 18-month transplant in either site. A. atra bioaccumulated metals in digestive gland, gills and mantle at different levels...
March 3, 2018: Ecotoxicology and Environmental Safety
H de la Salle, C Angénieux, F Lanza, C Gachet
In a recent report published in J Thromb Haemost, Schwertz et al. [1] investigated whether all-trans retinoic acid (atRA) controls mRNA translation in human platelets. This report concluded that atRA negatively controls the interaction between retinoic acid receptor alpha protein (RARα) and specific mRNAs, thereby positively regulating their translation in platelets. These interesting observations could open a new field in the understanding of platelet biology and we would like to discuss four important aspects of this work that deserve to be considered in this perspective...
March 5, 2018: Journal of Thrombosis and Haemostasis: JTH
Takahiro Hatayama, Ryosuke Segawa, Natsumi Mizuno, Sumiko Eguchi, Hiroshi Akamatsu, Misaki Fukuda, Fumihisa Nakata, Warren J Leonard, Masahiro Hiratsuka, Noriyasu Hirasawa
Many classical vaccines contain whole pathogens and, thus, may occasionally induce adverse effects, such as inflammation. Vaccines containing purified rAgs resolved this problem, but, owing to their low antigenicity, they require adjuvants. Recently, the use of several cytokines, including thymic stromal lymphopoietin (TSLP), has been proposed for this purpose. However, it is difficult to use cytokines as vaccine adjuvants in clinical practice. In this study, we examined the effects of all- trans retinoic acid (atRA) on TSLP production and Ag-induced Ab production...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Shu-Zhi Wang, Zheng-Hong Qin
Naja naja atra venom (NNAV) is composed of various proteins, peptides, and enzymes with different biological and pharmacological functions. A number of previous studies have reported that NNAV exerts potent analgesic effects on various animal models of pain. The clinical studies using whole venom or active components have confirmed that NNAV is an effective and safe medicine for treatment of chronic pain. Furthermore, recent studies have demonstrated that NNAV has anti-inflammatory and immune regulatory actions in vitro and in vivo...
February 28, 2018: Toxins
Yan Wu, Xiaobian Wang, Qing Zhou, Yi Wang, Jiali Zhou, Qiaoling Jiang, Yuan Wang, Huaqing Zhu
The aim of the present study was to explore the protective effects and possible mechanisms of all‑trans‑retinoic acid (ATRA) against atherosclerosis (AS). Rabbits were randomly allocated for standard or high‑fat diet with or without ATRA. After 12 weeks, the aortic rings of the rabbits were removed. Endothelium‑dependent relaxation (EDR) induced by acetylcholine and non‑endothelium‑dependent relaxation induced by sodium nitroprusside in the thoracic aorta were evaluated. NO level and eNOS activity were measured according to the protocol of NO and eNOS ELISA kits...
February 27, 2018: Molecular Medicine Reports
Hayeon Baik, Mathias Boulanger, Moshen Hosseini, Julie Kowalczyk, Sonia Zaghdoudi, Tamara Salem, Jean Emmanuel Sarry, Yosr Hicheri, Guillaume Cartron, Marc Piechaczyk, Guillaume Bossis
Differentiation therapies using all-trans retinoic acid (ATRA) are highly efficient at treating acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML). However, their efficacy, if any, is limited in the case of non-APL AML. We report here that inhibition of SUMOylation, a post-translational modification related to ubiquitination, restores the pro-differentiation and anti-proliferative activities of retinoids in non-APL AML. Controlled inhibition of SUMOylation with pharmacological inhibitors 2-D08 or anacardic acid, or via overexpression of SENP deSUMOylases, enhanced the ATRA-induced expression of key genes involved in differentiation, proliferation, and apoptosis in non-APL AML cells...
February 27, 2018: Cancer Research
Jasmin Segelken, Melanie Wallisch, Konrad Schultz, Jens Christoffers, Ulrike Janssen-Bienhold
The vitamin A derivative all-trans-retinoic acid (ATRA) is an important biologically active metabolite that regulates a variety of essential biological processes in particular via gene-regulatory mechanisms. In the retina, ATRA is a light-dependent byproduct of the phototransduction cascade. Here, ATRA is not only needed for proper retinal development, but it also acts as a neuromodulator on horizontal cells, second-order inhibitory neurons in the outer retina, which reveal morphological and physiological changes when the retina is treated with ATRA...
February 26, 2018: ACS Chemical Neuroscience
Guo Zhong, David Ortiz, Alex Zelter, Abhinav Nath, Nina Isoherranen
The clearance of retinoic acid (RA) and its metabolites is believed to be regulated by the CYP26 enzymes, but the specific roles of CYP26A1, CYP26B1 and CYP26C1 in clearing active vitamin A metabolites have not been defined. The goal of this study was to establish the substrate specificity of CYP26C1, and determine whether CYP26C1 interacts with cellular RA binding proteins (CRABPs). CYP26C1 was found to effectively metabolize all-trans- retinoic acid (atRA), 9-cis-retinoic acid (9-cis-RA), 13-cis-retinoic acid and 4-oxo-atRA with the highest intrinsic clearance towards 9-cis-RA...
February 23, 2018: Molecular Pharmacology
Kyle Burrows, Frann Antignano, Alistair Chenery, Michael Bramhall, Vladimir Korinek, T Michael Underhill, Colby Zaph
The intestinal immune system must be able to respond to a wide variety of infectious organisms while maintaining tolerance to non-pathogenic microbes and food antigens. The Vitamin A metabolite all-trans-retinoic acid (atRA) has been implicated in the regulation of this balance, partially by regulating innate lymphoid cell (ILC) responses in the intestine. However, the molecular mechanisms of atRA-dependent intestinal immunity and homeostasis remain elusive. Here we define a role for the transcriptional repressor Hypermethylated in cancer 1 (HIC1, ZBTB29) in the regulation of ILC responses in the intestine...
February 2018: PLoS Pathogens
Elodie Collinge, Isabelle Tigaud, Brigitte Balme, Luc-Marie Gerland, Pierre Sujobert, Violette Carlioz, Gilles Salles, Xavier Thomas, Etienne Paubelle
RATIONALE: Acute promyelocytic leukemia (APL) is a curable subtype of acute myeloid leukemia. APL is currently treated with combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) resulting in the induction of apoptosis and differentiation of the leukemic cells. Differentiation syndrome (so-called ATRA syndrome) is the main life-threatening complication of induction therapy with these differentiating agents. PATIENT CONCERNS: Herein, we report the case of a 49-year-old woman diagnosed with APL with, concomitantly, a bulky cutaneous lesion of 10 cm diameter with a red-to-purple background and a necrotic center, localized on her abdomen...
February 2018: Medicine (Baltimore)
Yi-Jun Shi, Liang-Jun Wang, Yuan-Chin Lee, Chia-Hui Huang, Wan-Ping Hu, Long-Sen Chang
This study presents two sensitive fluorescent assays for sensing heparin on the basis of the electrostatic interaction between heparin and Naja naja atra cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine-based molecular beacon (MB) or a DNA aptamer against CTX3, a reduction in the fluorescent signal of the aptamer or MB 5'-end labeled with carboxyfluorescein (FAM) and 3'-end labeled with 4-([4-(dimethylamino)phenyl]azo)-benzoic acid (DABCYL) was observed upon the addition of CTX3...
February 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Eduarda Schultze, Tiago Collares, Caroline Lucas, Fabiana K Seixas
All-trans retinoic acid (ATRA), a derivative of vitamin A, has been shown to potentiate cancer chemotherapy due to its ability to induce signals for cell differentiation or death, and inhibit cell proliferation. The combination of ATRA with taxoids, kinase inhibitors, natural compounds, retinoids, ER or HER2 inhibitors, chemotherapeutic drugs, proteasome inhibitors and nanoformulations of tretinoin have demonstrated additive or synergistic effects in anti-cancer activities. The mechanisms by which the compounds exert their synergistic effects depend on the tumor and the cell type...
February 16, 2018: Chemico-biological Interactions
Leyre Marzo, Santhosh K Pagire, Oliver Reiser, Burkhard König
Visible light photocatalysis has evolved over the last decade into a widely used method in organic synthesis. For many important transformations, such as cross-coupling reactions, alpha-amino functionalizations, cycloadditions, ATRA reactions, or fluorinations, photocatalytic variants have been reported. In this review, we try to compare classical and photocatalytic procedures for selected classes of reactions and highlight their advantages and limitations. In many cases, the photocatalytic reactions proceed at milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, like air oxygen or amines...
February 19, 2018: Angewandte Chemie
J Stephen Dumler, Sara H Sinclair, Amol C Shetty
Eukaryotic proteome diversity exceeds that encoded within individual genes, and results in part from alternative splicing events of pre-messenger RNA. The diversity of these splicing events can shape the outcome in development and differentiation of normal tissues, and is important in pathogenic circumstances such as cancer and some heritable conditions. A role for alternative splicing of eukaryotic genes in response to viral and intracellular bacterial infections has only recently been recognized, and plays an important role in providing fitness for microbial survival, while potentially enhancing pathogenicity...
2018: Frontiers in Cellular and Infection Microbiology
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