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TY - JOUR. T1 - Analysis of gene profiles involved in the enhancement of all-trans retinoic acid-induced HL-60 cell differentiation by sesquiterpene lactones identifies asparagine synthetase as a novel target for differentiation-inducing therapy. AU - Song, Ju Han. AU - Kim, Seung Hyun. AU - Cho, Kyung Min. AU - Hwang, Seung Yong. AU - Kim, Hyeoung Joon. AU - Kim, Tae Sung. PY - 2014/3/1. Y1 - 2014/3/1. N2 - All-trans retinoic acid (ATRA) is one of the most useful drugs in the treatment for acute promyelocytic leukemia (APL), but its adverse effects, which include drug resistance and hypercalcemia are obstacles to achieving complete remission. Our previous study showed that some sesquiterpene lactones (STLs), i.e., helenalin (HE) and parthenolide (PA) but not sclareolide (SC), enhance ATRA-induced differentiation of HL-60 APL cells with no unexpected effects, but the precise mechanism on underlying this synergism is not yet fully understood. In this study, we investigated the distinctive ...

The topical application of all- trans retinoic acid (ATRA) is an effective treatment for several skin disorders, including photo-aging. Unfortunately, ATRA is susceptible to light, heat, and oxidizing

Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression Johannes Haybaeck,1 Magdalena Postruznik,1 Christine L Miller,2 Jeannette R Dulay,3 Ida C Llenos,3,4 Serge Weis3,4 1Department of Neuropathology, Institute of Pathology, Medical University Graz, Graz, Austria; 2Department of Pediatrics, Johns Hopkins University, Baltimore, 3Laboratory of Brain Research and Neuropathology, Departments of Psychiatry and Pathology, Uniformed Services University of the Health Sciences, and Stanley Medical Research Institute, Bethesda, MD, USA; 4Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria Background: Retinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes,

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TY - JOUR. T1 - Retinoic acid-induced gene expression in normal and leukemic myeloid cells. AU - Murtaugh, Michael P.. AU - Dennison, Olivia. AU - Stein, Joseph P.. AU - Davies, Peter J.A.. PY - 1986/5/1. Y1 - 1986/5/1. UR - http://www.scopus.com/inward/record.url?scp=0022449402&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0022449402&partnerID=8YFLogxK. U2 - 10.1084/jem.163.5.1325. DO - 10.1084/jem.163.5.1325. M3 - Article. C2 - 2871126. AN - SCOPUS:0022449402. VL - 163. SP - 1325. EP - 1330. JO - Journal of Experimental Medicine. JF - Journal of Experimental Medicine. SN - 0022-1007. IS - 5. ER - ...

PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.

All-trans retinoic acid (ATRA) induces complete remission in a high proportion of acute promyelocytic leukemia (APL). Nevertheless it is be associated with adverse drug reactions that might be life-

TY - JOUR. T1 - Competition for a unique response element mediates retinoic acid inhibition of vitamin D3-stimulated transcription. AU - Cao, Xu. AU - Teitelbaum, Steven L.. AU - Zhu, Hui Jun. AU - Zhang, Liming. AU - Feng, Xu. AU - Patrick Ross, F.. PY - 1996/9/5. Y1 - 1996/9/5. N2 - We have identified a novel steroid hormone response element in the avian β3 integrin promoter. This sequence, comprising three hexameric direct repeat half-sites separated by nine and three nucleotides binds vitamin D receptor (VDR)-retinoid X receptor (RXR) and retinoic acid receptor (RAR)- RXR heterodimers. VDR-RXR binds direct repeats separated by three base pairs, and HAR-RXR recognizes half-sites separated by nine bases, whereas the central half-site interacts with both heterodimers. Retinoic acid and 1,25- dihydroxyvitamin D3 activate both a genomic fragment including the transcriptional start site and an oligonucleotide containing the three repeats, linked to a heterologous promoter. Co-addition of the ...

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All-trans retinoic acid (ATRA), a biologically active metabolite of vitamin A, is a powerful inducer of terminal differentiation and growth arrest of several myeloid cell lines in vitro. Although the efficacy of ATRA as an anti-cancer drug has been demonstrated by the successful treatment of acute promyelocytic leukemia (APL), knowledge concerning the molecular mechanisms directing ATRA-induced differentiation and cell cycle arrest of myeloid cells is lacking. Our results show, for the first time, that the complex regulation of cell cycle proteins and myeloid-specific transcription factors induced by ATRA relies on functional Stat1. We found that Stat1 is activated by both tyrosine-701 and serine-727 phosphorylation upon ATRA-induced differentiation of the human monoblastic cell line U-937. Expression of phosphorylation deficient mutants of Stat1 (Stat1Y701F or Stat1S727A) inhibited both ATRA-induced differentiation and cell cycle arrest of U-937 cells, pointing to a requirement of active Stat1 ...

TY - JOUR. T1 - Long-term follow-up of hemostatic molecular markers during remission induction therapy with all-trans retinoic acid for acute promyelocytic leukemia. AU - Watanabe, Reiko. AU - Murata, Mitsuru. AU - Takayama, Nobuyuki. AU - Tokuhira, Michihide. AU - Kizaki, Masahiro. AU - Okamoto, Shinichiro. AU - Kawai, Yohko. AU - Watanabe, Kiyoaki. AU - Murakami, Hiroshi. AU - Kikuchi, Masao. AU - Nakamura, Shin. AU - Ikeda, Yasuo. PY - 1997/4. Y1 - 1997/4. N2 - Hemostatic molecular markers were serially monitored in a prospective fashion during remission induction therapy with all-trans retinoic acid (ATRA) in sixteen patients with acute promyelocytic leukemia (APL). One patient with leukocytosis before treatment and three patients who later developed hyperleukocytosis also received chemotherapy with behenoyl Ara-C and daunorubicin. Plasma levels of E-fragment of fibrin and fibrinogen degradation product (FDP-E), FDP-D dimer (D-D), thrombin-antithrombin complex (TAT), and plasmin-α2 plasmin ...

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Cancer is a genetic and epigenetic disease that involves inactivation of tumor suppressor genes and activation of proto-oncogenes. All-trans retinoic acid (ATRA) is an isomer of retinoic acid involved in the onset of differentiation and apoptosis of a number of normal and cancer cells, functioning as an anti-cancer agent in several neoplasms. Ectopic changes in the expression of certain microRNAs (miRNAs) occur in response to ATRA, leading to phenotypic alterations in neoplastic cell lines. Moreover, the modulation of miRNA patterns upon ATRA-treatment may represent an effective chemopreventive and anti-cancer therapy strategy. The present systematic review was performed to provide an overview of the modulation of ATRA-induced miRNA expression in different types of neoplastic cells and identify the efficacy of intervention factors (i.e., concentration and duration of treatment) and how they influence expression profiles of oncogenesis-targeting miRNAs. A systematic search was conducted according to the

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Adaptive immunity licenses higher organisms to generate potent immune responses against foreign antigens. Two hallmarks of adaptive immunity are A) the ability of T and B cells to distinguish self from non-self and B) the ability to mount a qualitatively and quantitatively superior immune response upon secondary exposure to antigens. Due to the essential role of adaptive immunity in human disease, the soluble factors mediating the basic biology of cells within the adaptive immune system are of great importance. The gut is an anatomical situation where immune responses are chronically suppressed and the mechanism of how this occurs remains unknown. The studies presented demonstrate that all- trans retinoic acid, a factor found in great abundance in the gut, greatly enhances the induction of a suppressive population of cells called adaptive T regulatory cells. All- trans retinoic acid is thus a newly identified differentiation factor for T regulatory cells. These data implicates all- trans ...

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TY - JOUR. T1 - Phase 1/2 clinical trial of interferon α2b and weekly liposome-encapsulated all-trans retinoic acid in patients with advanced renal cell carcinoma. AU - Boorjian, Stephen A.. AU - Milowsky, Matthew I.. AU - Kaplan, Jodi. AU - Albert, Martin. AU - Cobham, Marta Vallee. AU - Coll, Deirdre M.. AU - Mongan, Nigel P.. AU - Shelton, Gary. AU - Petrylak, Daniel. AU - Gudas, Lorraine J.. AU - Nanus, David M.. PY - 2007/9. Y1 - 2007/9. N2 - To evaluate the feasibility, efficacy, and biologic effects of weekly liposome-encapsulated all-trans retinoic acid (ATRA-IV) plus interferon α2b (IFN) in patients with advanced renal cell carcinoma (RCC). Twenty-six patients with metastatic RCC were treated on a phase 1/2 trial with weekly ATRA-IV and IFN SQ daily 5 d/wk. Twelve patients received ATRA-IV at three dose levels (60, 75, and 90 mg/m) according to phase 1 methodology, and 14 additional patients received 90 mg/m. Response was assessed according to an intention-to-treat analysis. Serum ...

Apoptotic and anti-proliferative effects of all-trans retinoic acid. Adenine nucleotide translocase sensitizes HeLa cells to all-trans retinoic acid.

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TY - JOUR. T1 - Cloning of rat cytochrome P450RAI (CYP26) cDNA and regulation of its gene expression by all-trans-retinoic acid in vivo. AU - Wang, Y.. AU - Zolfaghari, R.. AU - Catharine, Ross A.. PY - 2002/5/15. Y1 - 2002/5/15. N2 - A novel retinoic acid (RA)-inducible cytochrome P450 (P450 RAI or CYP26), previously cloned from human, zebra fish, and mouse, functions in the metabolism of all-trans-RA to polar metabolites including 4-hydroxy-RA and 4-oxo-RA. To further study CYP26 in the rat model, we first cloned rat CYP26 cDNA. The nucleotide sequence predicts a 497-amino-acid protein whose sequence is 95% identical to mouse and 91% homologous to human CYP26. Animal studies showed that CYP26 mRNA expression is very low (0.01 ± 0.008; P , 0.05) in vitamin-A-deficient rats compared to pair-fed vitamin-A-sufficient rats (defined as 1.0). In a kinetic study, vitamin-A-deficient rats were treated with ∼ 100 μg of all-trans-RA and liver was collected after 3-72 h for analysis of CYP26 mRNA by ...

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Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid. Modulation of oestrogen receptor signalling by association with the activated dioxin receptor

BACKGROUND: The lung and thyroid are derived from the anterior endoderm. Retinoic acid and Fgf signalling are known to be essential for development of the lung in mouse but little is known on how the lung and thyroid are specified in Xenopus. RESULTS: If either retinoic acid or Fgf signalling is inhibited, there is no differentiation of the lung as assayed by expression of sftpb. There is no change in expression of thyroid gland markers when retinoic acid signalling is blocked after gastrulation and when Fgf signalling is inhibited there is a short window of time where pax2 expression is inhibited but expression of other markers is unaffected. If exogenous retinoic acid is given to the embryo between embryonic stages 20 and 26, the presumptive thyroid expresses sftpb and sftpc, specific markers of lung differentiation and expression of key thyroid transcription factors is lost. When the presumptive thyroid is transplanted into the posterior embryo, it also expresses sftpb, although pax2 expression is

G0/G1 switch gene 2 (G0S2) is a direct retinoic acid target gene that is widely expressed in diverse organs and has been reported to have a role in adipose lipolysis by negatively regulating adipose triglyceride lipase (ATGL). G0S2 is also commonly silenced by DNA methylation in a variety of solid tumors including glioma, head and neck and lung cancers, and G0S2 induction is associated with retinoic acid-mediated clinical remissions in acute promyelocytic leukemia. This evidence suggests that G0S2 may possess tumor suppressor activity although definitive proof and mechanistic details are lacking. We now clearly demonstrate using G0S2 null immortalized mouse embryonic fibroblasts (MEFs) that G0S2 can function to oppose oncogene-induced transformation. G0S2 null MEFs were readily transformed with H-RAS or EGFR while wild-type MEFs were not. Importantly, re-introduction of G0S2 reversed H-RAS transformation of G0S2 null MEFs. Although G0S2 is a known regulator of fat metabolism through attenuating ...

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Retinoids are known to have potent effects on hematopoietic cells, and all trans retinoic acid (ATRA) is widely used to treat patients with acute promyelocytic leukemia. Retinoids may normally maintain stem cell integrity, and our main objective was to learn if B lineage lymphoid progenitors express functional receptors. Total CD19+ cells increased substantially in the bone marrow, while early lymphoid progenitors (ELP) and pro-lymphocytes (Pro-L) were reduced in mice treated with time-release ATRA pellets. Culture experiments with highly enriched progenitors demonstrated they were direct drug targets. Overall cell yields at short culture intervals were reduced, but CFSE labeling indicated this did not result from reduced proliferation. ELP are very primitive progenitors and 10 days is normally required for them to generate CD19+ cells in culture. Remarkably, lymphoid cells and IL-7 responding progenitors emerged in just 7 days when ATRA was present. Treatment with a panel of agonists suggested ...

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Autori: Ioan Ovidiu Sirbu, Lionel Gresh, Jacqueline Barra and Gregg Duester. Editorial: Development, 132(11), p.2611-22, 2005.. Rezumat:. Retinoic acid (RA) generated by Raldh2 in paraxial mesoderm is required for specification of the posterior hindbrain, including restriction of Hoxb1 expression to presumptive rhombomere 4 (r4). Hoxb1 expression requires 3′ and 5′ RA response elements for widespread induction up to r4 and for r3/r5 repression, but RA has previously been detected only from r5-r8, and vHnf1 is required for repression of Hoxb1 posterior to r4 in zebrafish. We demonstrate in mouse embryos that an RA signal initially travels from the paraxial mesoderm to r3, forming a boundary next to the r2 expression domain of Cyp26a1 (which encodes an RA-degrading enzyme). After Hoxb1 induction, the RA boundary quickly shifts to r4/r5, coincident with induction of Cyp26c1 in r4. A functional role for Cyp26c1 in RA degradation was established through examination of RA-treated embryos. Analysis ...

Male germ cell tumors (GCTs) are a model for a curable solid tumor. GCTs can differentiate into mature teratomas. Embryonal carcinomas (ECs) represent the stem cell compartment of GCTs and are the malignant counterpart to embryonic stem (ES) cells. GCTs and EC cells are useful to investigate differentiation therapy and chemotherapy response. This study explored mechanistic interactions between all-trans-retinoic acid (RA), which induces differentiation of EC and ES cells, and the Hedgehog (Hh) pathway, a regulator of self-renewal and proliferation. RA was found to induce mRNA and protein expression of Patched 1 (Ptch1), the Hh ligand receptor and negative regulator of this pathway. PTCH1 is also a target gene of Hh signaling through Smoothened (Smo) activation. Yet, this observed RA-mediated Ptch1 induction was independent of Smo. It occurred despite co-treatment with RA and Smo inhibitors. Retinoid induction of Ptch1 also occurred in other RA-responsive cancer cell lines and in normal ES cells. Notably

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It has been reported that retinoic acid (RA) enhances regulatory T (T reg) cell conversion by inhibiting the secretion of cytokines that interfere with conversion. This report shows that these conclusions provide a partial explanation at best. First, RA not only interfered with cytokine secretion but also with the ability of these cytokines to inhibit T reg cell conversion of naive T cells. Furthermore, RA enhanced conversion even in the absence of inhibitory cytokines. The latter effect depended on the RA receptor α (RARα) but did not require Smad3, despite the fact that RA enhanced Smad3 expression. The RARα1 isoform was not essential for RA-dependent enhancement of transforming growth factor β-driven conversion, suggesting that conversion can also be mediated by RARα2. Interleukin (IL)-6 strongly reduced RARα expression levels such that a deficiency of the predominant RARα1 isoform leaves too little RARα2 for RA to inhibit the generation of Th17 cells in the presence of IL-6 ...

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This gene encodes a specific binding protein for a vitamin A family member and is thought to play an important role in retinoic acid-mediated differentiation and proliferation processes. It is structurally similar to the cellular retinol-binding proteins, but binds only retinoic acid at specific sites within the nucleus, which may contribute to vitamin A-directed differentiation in epithelial tissue.

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The lamin complement of nuclear matrix isolated from F9 embryonal carcinoma cells was studied during retinoic acid-induced differentiation in culture. Differentiation of the original cells into parietal endoderm-like cells was accompanied by the gradual appearance of lamins A and C while lamin B was present throughout all stages. Lamins were identified by their molecular masses, isoelectric points, recognition by a monoclonal antibody and a polyclonal antiserum, and by peptide mapping. The increase in the amounts of lamins A and C found in the matrix was due to de novo synthesis as no extranuclear pools of these lamins were detected in the undifferentiated cells. These results provide biochemical evidence that, as in amphibian embryogenesis, there are variations in nuclear lamina composition during mammalian development. ...

Ch 55 is a highly potent synthetic retinoid that has high affinity for RAR-α and RAR-β receptors and low affinity for cellular retinoic acid binding protein (CRABP) and Inhibits rabbit tracheal epithelial cell differentiation by inhibiting transglutaminase and increasing cholesterol sulfate (EC50 values are 0.02 and 0.03 nM respectively). Learn More ...

Retinoic acid syndrome (RAS) is a potentially life-threatening complication observed in patients with acute promyelocytic leukemia (APML) and first thought to be specifically associated with all-trans retinoic acid (ATRA) (also known as tretinoin) treatment. Subsequently, so-called RAS was recognized in APML patients who had been treated with another highly efficacious drug, arsenic trioxide, and yet did not appear in patients treated with tretinoin for other disorders. These facts and others support the notion that RAS depends on the presence of the malignant promyelocytes. This has led to the growing deprecation of the term retinoic acid syndrome and to an increasing use of the term differentiation syndrome to signify this APML treatment complication. The syndrome is characterized by dyspnea, fever, weight gain, hypotension, and pulmonary infiltrates. This is effectively treated by giving dexamethasone and withholding ATRA (or arsenic trioxide) in severe cases. An elevated white count is ...

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1CBQ: Crystal structures of cellular retinoic acid binding proteins I and II in complex with all-trans-retinoic acid and a synthetic retinoid.

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Introduction: Studies have shown that vitamin A (VA) status affected hepatic glycogen content and body lipid levels in rats. The active metabolite of VA, retinoic acid (RA), regulates gene expression via activation of both retinoic acid receptor (RAR) and retinoid X receptor (RXR) bound to retinoic acid responsive element (RARE). We have reported that retinoids synergized with insulin to induce glucokinase gene (Gck) in primary rat hepatocyes. Hypothesis: We hypothesize that the rat promoter of Gck contains RARE(s).. Methods: To identify the RARE(s) in the Gck promoter, we have made (1) a series of luciferase reporter gene constructs containing shortened DNA fragments of Gck promoter; (2) expression vectors containing cDNAs of rat RARα, RXRα and RXRγ; (3) linker-scan mutant reporter constructs covering 0.2 kb of the proximal Gck promoter region and a 20 bp region which disrupt the RA response. The responses of these reporter constructs to RA and the effects of the co-transfection of RAR and ...

1CBI: Crystal structure of cellular retinoic acid binding protein I shows increased access to the binding cavity due to formation of an intermolecular beta-sheet.

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TY - JOUR. T1 - Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin ± all-trans retinoic acid ± granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. AU - Estey, Elihu H.. AU - Thall, Peter F.. AU - Pierce, Sherry. AU - Cortes, Jorge. AU - Beran, Miloslav. AU - Kantarjian, Hagop. AU - Keating, Michael J.. AU - Andreeff, Michael. AU - Freireich, Emil. PY - 1999/4/15. Y1 - 1999/4/15. N2 - Preclinical data suggest that retinoids, eg, all-trans retinoic acid (ATRA), lower concentrations of antiapoptotic proteins such as bcl-2, possibly thereby improving the outcome of anti-acute myeloid leukemia (AML) chemotherapy. Granulocyte colony-stimulating factor (G-CSF) has been considered to be potentially synergistic with ATRA in this regard. Accordingly, we randomized 215 patients with newly diagnosed AML (153 patients) or high-risk myelodysplastic syndrome (MDS) (refractory anemia with excess blasts [RAEB] or ...

The retinoids exert potent growth and differentiation effects on normal, embryonic and neoplastic cells. Although retinoids are known to regulate gene transcription through activation of retinoid receptors, the direct target genes of retinoid receptors remain largely unknown. A human embryonal carcinoma (EC) model was employed to determine the importance of p53 in retinoid-mediated differentiation and signaling. The hypothesis was that one mechanism by which retinoids regulate gene expression and mediate beneficial anti-tumor effects is by activation of p53 transactivation activity. RA was found to enhance the transactivation function of p53 in the human EC line NT2/D1. A derived RA-resistant line, NT2/D1-R1, was deficient in this activity, and also exhibited cross-resistance to cisplatin. This suggested a model in which RA and cisplatin signaling pathways impinge upon p53 in human EC cells. Further evidence generated to support this model is the following: (1) RA-induced p53 activity could be ...

TY - JOUR. T1 - Inhibition of activation-induced apoptosis of thymocytes by all-trans- and 9-cis-retinoic acid is mediated via retinoic acid receptor α. AU - Szondy, Zsuzsa. AU - Reichert, Uwe. AU - Bernardon, Jean Michel. AU - Michel, Serge. AU - Tóth, Réka. AU - Karászi, Éva. AU - Fésüs, László. PY - 1998/5/1. Y1 - 1998/5/1. N2 - Thymocytes can be induced to undergo apoptotic cell death by activation through the T-cell receptor (TCR). This process requires macromolecular synthesis and has been shown to be inhibited by retinoic acids (RAs). Two groups of nuclear receptors for RAs have been identified: retinoic acid receptors (RARs) and retinoid X receptors (RXRs). All-trans-RA is the high-affinity ligand for RARs, and 9-cis-RA additionally binds to RXRs with high affinity. Because 9-cis-RA is much more potent in inhibiting TCR-mediated death than all-trans-RA, it was suggested that RXRs participate in the process. In the present study various synthetic retinoid analogues were used to ...

TY - JOUR. T1 - Disabled-2 Mediates c-Fos Suppression and the Cell Growth Regulatory Activity of Retinoic Acid in Embryonic Carcinoma Cells. AU - Smith, Elizabeth R.. AU - Capo-Chichi, Callinice D.. AU - He, Junqi. AU - Smedberg, Jennifer L.. AU - Yang, Dong Hua. AU - Prowse, Amanda H.. AU - Godwin, Andrew K.. AU - Hamilton, Thomas C.. AU - Xu, Xiang Xi. PY - 2001/12/14. Y1 - 2001/12/14. N2 - F9 embryonic stem cell-like teratocarcinoma cells are widely used to study early embryonic development and cell differentiation. The cells can be induced by retinoic acid to undergo endodermal differentiation. The retinoic acid-induced differentiation accompanies cell growth suppression, and thus, F9 cells are also often used as a model for analysis of retinoic acid biological activity. We have recently shown that MAPK activation and c-Fos expression are uncoupled in F9 cells upon retinoic acid-induced endodermal differentiation. The expression of the candidate tumor suppressor Disabled-2 is induced and ...

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Holoprosencephaly (HPE) is the most common human congenital forebrain defect, affecting specification of forebrain tissue and subsequent division of the cerebral hemispheres. The causes of HPE are multivariate and heterogeneous, and include exposure to teratogens, such as retinoic acid (RA), and mutations in forebrain patterning genes. Many of the defects in holoprosencephaly patients resemble animal models with aberrant retinoic acid levels, which also show severe forebrain abnormalities. RA plays an important role in early neural patterning of the vertebrate embryo: expression of RA-synthesizing enzymes initiates high RA levels in the trunk, which are required for proper anterior-posterior patterning of the hindbrain and spinal cord. In the forebrain and midbrain, RA-degrading enzymes are expressed, protecting these regions from the effects of RA. However, the mechanisms that regulate RA-synthesizing and RA-degrading enzymes are poorly understood. Mutations in the gene TGIF are associated with ...

Smith-Magenis syndrome; DKFZp4 §§). A polymorphic CAG repeat* on the C terminus contains a polyserine stretch underlying a serine-to-asparagine change at amino acid 1808 (S1808N), of the analogous a pathway when dominant negative CREB proteins with mutations underwent cell death in the CaG* b channel. And 3 RAI1 domains are a dosage-sensitive gene and an active metabolite of vitamin A involved in RA-induced neuritogenesis, that is a natural morphogen involved in body weight control and complex behavioral responses with a zinc finger-like plant homeodomain (PHD) at the C terminus that is conserved in the trithorax group of chromatin-based transcription regulators between human and mouse Dp(11)17 orthologs. Alcohol teratogenesis may be due in part to retinoic acid-induced expression of GDE2 [GDPD5] glycerols that plays essential roles in neuronal differentiation and neurite outgrowth that proceeds in multiple processes. In the hydrolysis of deacylated glycerophospholipids to glycerol ...

TY - JOUR. T1 - Evidence of epigenetic changes affecting the chromatin state of the retinoic acid receptor β2 promoter in breast cancer cells. AU - Sirchia, Silvia M.. AU - Ferguson, Anne T.. AU - Sironi, Elena. AU - Subramanyan, Smitha. AU - Orlandi, Rosaria. AU - Sukumar, Saraswati. AU - Sacchi, Nicoletta. PY - 2000/3/16. Y1 - 2000/3/16. N2 - Retinoic acid (RA)-resistance in breast cancer cells has been associated with irreversible loss of retinoic acid receptor β, RARβ, gene expression. Search of the causes affecting RARβ gene activity has been oriented at identifying possible differences either at the level of one of the RARβ promoters, RARβ2, or at regulatory factors. We hypothesized that loss of RARβ2 activity occurs as a result of multiple factors, including epigenetic modifications, which can pattern RARβ2 chromatin state. Using methylation-specific PCR, we found hypermethylation at RARβ2 in a significant proportion of both breast cancer cell lines and primary breast tumors. ...

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We investigated the benefit of adding all-trans retinoic acid (ATRA) to chemotherapy for younger patients with nonacute promyelocytic acute myeloid leukemia and high-risk myelodysplastic syndrome, and considered interactions between treatment and molecular markers. Overall, 1075 patients less than 60 years of age were randomized to receive or not receive ATRA in addition to daunorubicin/Ara-C/thioguanine chemotherapy with Ara-C at standard or double standard dose. There were data on FLT3 internal tandem duplications and NPM1 mutations (n = 592), CEBPA mutations (n = 423), and MN1 expression (n = 195). The complete remission rate was 68% with complete remission with incomplete count recovery in an additional 16%; 8-year overall survival was 32%. There was no significant treatment effect for any outcome, with no significant interactions between treatment and demographics, or cytarabine randomization. Importantly, there were no interactions by FLT3/ internal tandem duplications, NPM1, or CEBPA ...

TY - JOUR. T1 - All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3/ITD+ leukemia stem cells in vitro and in vivo. AU - Ma, Hayley S.. AU - Greenblatt, Sarah M.. AU - Shirley, Courtney M.. AU - Duffield, Amy S.. AU - Bruner, J. Kyle. AU - Li, Li. AU - Nguyen, Bao. AU - Jung, Eric. AU - Aplan, Peter D.. AU - Ghiaur, Gabriel. AU - Jones, Richard J.. AU - Small, Donald. N1 - Funding Information: This work was supported by grants from the National Institutes of Health National Cancer Institute (CA90668, CA006973), the Rally Foundation (The Truth 365 grant), and the Giant Food Pediatric Cancer Research Fund. D.S. is also supported by the Kyle Haydock Professorship. Publisher Copyright: © 2016, American Society of Hematology. All rights reserved.. PY - 2016/6/9. Y1 - 2016/6/9. N2 - FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles ...

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Several lines of evidence indicate that retinoids, derivates of vitamin A, affect reproductive function in birds, however, the mechanism of their action in the ovary is still unknown. Therefore, the present study was designed (i) to show whether in the domestic hen 9-cis retinoic acid (9-cis RA), one of the retinoids, influences steroid secretion in vitro by white and yellow chicken ovarian follicles, and (ii) to detect expression of retinoic acid RXR receptor mRNA in these follicles. The white follicles (small: 1-4 mm, medium: 4-6 mm and large 6-8 mm in diameter) and the three largest yellow preovulatory follicles (F3-F1; 25-37 mm) were isolated from the ovary 3 h before ovulation. The granulosa layer was separated from the theca layer in the preovulatory follicles, which were subsequently divided into 4 equal pieces. The isolated whole white follicles or parts of the granulosa or theca layers were incubated for 24 h at 38oC in Eagle's medium in the following 4 groups: control, ovine LH ...

Kawakami, S.; Suzuki, S.; Yamashita, F.; Hashida, M., 2005: Induction of apoptosis in A549 human lung cancer cells by all-trans retinoic acid incorporated in DOTAP/cholesterol liposomes

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9-cis retinoic acid (9-cis RA) is a retinoid receptor pan-agonist that binds with high affinity to both retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Using a variety of in vivo and in vitro cancer models, we present experimental data that 9-cis RA has activity as a potential chemot …

The nuclear orphan receptor constitutive active receptor (CAR) can be activated to induce CYP2B genes by the potent phenobarbital-type inducer 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in which the receptor forms a heterodimer with the retinoid X receptor (RXR) and binds to a conserved enhancer element NR1. Effects of retinoic acids on the activation of CAR were examined. Treatment with 9-cis- or all-trans-retinoic acid markedly repressed TCPOBOP induction of CYP2B10 mRNA in mouse primary hepatocytes. Both retinoic acids also repressed TCPOBOP-induced NR1 enhancer activity in both transfected hepatocytes and HepG2 cells. Moreover, coexpression of the retinoic acid receptor (RAR) increased the repression in the cotransfected HepG2 cells, whereas that of RXR decreased the repression. Thus, the increased heterodimerization of RXR with RAR by retinoic acid treatment seemed to reduce the RXR available for CAR heterodimerization, resulting in the repression of CAR activity. This type of ...

Rabbit polyclonal Retinoic Acid Receptor gamma antibody validated for WB, ICC/IF and tested in Human and Mouse. With 1 independent review. Immunogen…

Montesinos P and Sanz MA. The Differentiation Syndrome in Patients with Acute Promyelocytic Leukemia: Experience of the Pethema Group and Review of the Literature. Mediterr J Hematol Infect Dis. 2011; 3(1): e2011059. ...

Montesinos P and Sanz MA. The Differentiation Syndrome in Patients with Acute Promyelocytic Leukemia: Experience of the Pethema Group and Review of the Literature. Mediterr J Hematol Infect Dis. 2011; 3(1): e2011059. ...

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Otx2, a mouse homolog of the Drosophila orthodenticle gene, is first widely expressed in the epiblast but becomes progressively restricted to the anterior third of the embryo by the headfold stage. This progressive restriction correlates with the anterior migration of mesoderm in the embryo, suggesting that interactions with mesoderm may be involved in setting up the anterior domain of Otx2 expression in vivo. Using explant-recombination assays, we have obtained evidence that a positive signal from anterior mesendoderm is required to stabilize expression of Otx2 in vivo, whereas a negative signal from the later-forming posterior mesendoderm represses Otx2 expression in the posterior part of the embryo. We have also found that exogenous retinoic acid can mimic the effect of this negative signal and reduces the anterior domain of Otx2 expression.. ...

We report the isolation of two retinoic acid receptor isoforms (RAR gamma), which differ only in the 5untranslated and putative N-terminus A regions. The two isoforms appear to serve as early markers for the presumptive neural axis; however, their expression patterns differ. RAR-gamma 2.1 is first expressed at gastrulation at the dorsal lip and subsequently along the presumptive neural axis. RAR- gamma 2.2 represents the full-length sequence of a receptor cDNA already partially characterized and present as a maternal transcript [Ellinger-Ziegelbauer and Dreyer (1991); Genes Dev 5:94-104, (1993): Mech Dev 41:31-46; Pfeffer and DeRobertis, (1994) Mech Dev: 45:147-153]. Unlike RAR-gamma 2.2, the 2.1 variant is not expressed either in pre-somitic mesoderm or notochord. RAR-gamma 2.1 is strongly expressed in branchial arches and to a lesser extent in the neural floor plate. The two isoforms also exhibit differential sensitivity to retinoic acid. Constitutive expression of RAR gamma 2.2 following neurulation

Several variant RARA translocations have been reported in acute promyelocytic leukemia (APL) of which the t(11;17)(q23;q21), which results in a ZBTB16-RARA fusion, is the most widely identified and is largely resistant to therapy with all-trans retinoic acid (ATRA). The clinical course together with the cytogenetic and molecular characterization of a case of ATRA-unresponsive ZBTB16-RARA APL is described. Additional mutations potentially cooperating with the translocation fusion product in leukemogenesis have been hitherto unreported in ZBTB16-RARA APL and were sought by application of a next-generation sequencing approach to detect those recurrently found inmyeloid malignancies. This technique identified a solitary, low level mutation in the CEBPA gene. Molecular profiling of additional mutations may provide a platform to individualise therapeutic management in patients with this rare form of APL ...

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