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https://www.readbyqxmd.com/read/29131833/mek-inhibitors-enhance-therapeutic-response-towards-atra-in-nf1-associated-malignant-peripheral-nerve-sheath-tumors-mpnst-in-vitro
#1
Susan Fischer-Huchzermeyer, Anna Dombrowski, Gordon Wilke, Verena Stahn, Anna Streubel, Victor Felix Mautner, Anja Harder
OBJECTIVE: Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome characterized by an increased risk of malignant peripheral nerve sheath tumors (MPNST). Chemotherapy of MPNST is still insufficient. In this study, we investigated whether human tumor Schwann cells derived from NF1 associated MPNST respond to all-trans retinoic acid (ATRA). We analyzed effects of ATRA and MEK inhibitor (MEKi) combination therapy. METHODS: MPNST cell lines S462, T265, NSF1 were treated with ATRA and MEKi U0126 and PD0325901...
2017: PloS One
https://www.readbyqxmd.com/read/28960386/diethylstilbestrol-impaired-oogenesis-of-yellow-catfish-juveniles-through-disrupting-hypothalamic-pituitary-gonadal-axis-and-germ-cell-development
#2
Yaqin Wang, Yingwen Li, Qiliang Chen, Zhihao Liu
Diethylstilbestrol (DES), a non-steroidal estrogen, has been found to cause altered germ cell development and disordered ovarian development in fish females. However, the mechanisms that might be involved are poorly understood. In this study, female juveniles of yellow catfish (Pelteobagrus fulvidraco) (120 days post-hatching) were exposed to two doses (10 and 100 ng l(-1) ) of DES for 28 days. After the endpoint of exposure, decreased ovary weight and gonadosomatic index, as well as various ovarian impairments were observed in response to DES...
September 28, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28865861/liver-transcriptome-analysis-reveals-important-factors-involved-in-the-metabolic-adaptation-of-the-transition-cow
#3
N-T Ha, C Drögemüller, C Reimer, F Schmitz-Hsu, R M Bruckmaier, H Simianer, J J Gross
During early lactation, dairy cows experience a severe metabolic load often resulting in the development of various diseases. The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. We conducted a whole-liver transcriptome analysis for the transition cow to identify novel factors crucial for metabolic adaptation. Liver samples were obtained from 6 Red Holstein dairy cows (parity 2 to 7, mean ± standard deviation: 3...
November 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28811909/a-fourth-subtype-of-retinoic-acid-receptor-related-orphan-receptors-is-activated-by-oxidized-all-trans-retinoic-acid-in-medaka-oryzias-latipes
#4
Kotowa Sakai, Haruka Fukushima, Yuya Yamamoto, Toshitaka Ikeuchi
BACKGROUND: The three known subtypes of the retinoic acid receptor-related orphan receptor (ROR) have been implicated in the control of immunity, brain function, and circadian rhythm in mammals. Here, we demonstrate by phylogenetic analysis that there were originally four subtypes of RORs in vertebrates. One of the novel ror paralogs, rord1 (rorca in the Ensembl database), is conserved among teleosts, but absent in mammals. Using medaka (Oryzias latipes) as a model teleost, we evaluated the expression pattern of this gene, its transactivational properties for endogenic chemicals, and its ability to activate the promoters of putative target genes...
2017: Zoological Letters
https://www.readbyqxmd.com/read/28735443/retinoic-acid-regulates-avian-lung-branching-through-a-molecular-network
#5
Hugo Fernandes-Silva, Patrícia Vaz-Cunha, Violina Baranauskaite Barbosa, Carla Silva-Gonçalves, Jorge Correia-Pinto, Rute Silva Moura
Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development...
December 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28715412/cell-fate-specification-in-the-lingual-epithelium-is-controlled-by-antagonistic-activities-of-sonic-hedgehog-and-retinoic-acid
#6
Maha El Shahawy, Claes-Göran Reibring, Cynthia L Neben, Kristina Hallberg, Pauline Marangoni, Brian D Harfe, Ophir D Klein, Anders Linde, Amel Gritli-Linde
The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28651018/meta-analysis-of-mirna-expression-profiles-for-prostate-cancer-recurrence-following-radical-prostatectomy
#7
Elnaz Pashaei, Elham Pashaei, Maryam Ahmady, Mustafa Ozen, Nizamettin Aydin
BACKGROUND: Prostate cancer (PCa) is a leading reason of death in men and the most diagnosed malignancies in the western countries at the present time. After radical prostatectomy (RP), nearly 30% of men develop clinical recurrence with high serum prostate-specific antigen levels. An important challenge in PCa research is to identify effective predictors of tumor recurrence. The molecular alterations in microRNAs are associated with PCa initiation and progression. Several miRNA microarray studies have been conducted in recurrence PCa, but the results vary among different studies...
2017: PloS One
https://www.readbyqxmd.com/read/28643469/atra-signaling-regulates-the-expression-of-col9a1-through-bmp2-wnt4-runx1-pathway-in-antler-chondrocytes
#8
Hong-Liang Zhang, Bin Guo, Zhan-Qing Yang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue
Although all-trans retinoic acid (ATRA) is involved in the regulation of cartilage growth and development, its regulatory mechanisms remain unknown. Here, we showed that ATRA could induce the expression of COL9A1 in antler chondrocytes. Silencing of cellular retinoic acid binding protein 2 (CRABP2) could impede the ATRA-induced upregulation of COL9A1, whereas overexpression of CRABP2 presented the opposite effect. RARα agonist Am80 induced the expression of COL9A1, whereas treatment with RARα antagonist Ro 41-5253 or RXRα small-interfering RNA (siRNA) caused an obvious blockage of ATRA on COL9A1...
September 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28612832/a-novel-de-novo-mutation-in-myt1-the-unique-oavs-gene-identified-so-far
#9
Marie Berenguer, Angele Tingaud-Sequeira, Mileny Colovati, Maria I Melaragno, Silvia Bragagnolo, Ana B A Perez, Benoit Arveiler, Didier Lacombe, Caroline Rooryck
Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by hemifacial microsomia associated with ear, eyes and vertebrae malformations showing highly variable expressivity. Recently, MYT1, encoding the myelin transcription factor 1, was reported as the first gene involved in OAVS, within the retinoic acid (RA) pathway. Fifty-seven OAVS patients originating from Brazil were screened for MYT1 variants. A novel de novo missense variant affecting function, c.323C>T (p.(Ser108Leu)), was identified in MYT1, in a patient presenting with a severe form of OAVS...
September 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28570941/diet-dependent-retinoid-effects-on-liver-gene-expression-include-stellate-and-inflammation-markers-and-parallel-effects-of-the-nuclear-repressor-shp
#10
Meghan Maguire, Justin R Bushkofsky, Michele Campaigne Larsen, Yee Hoon Foong, Sherry A Tanumihardjo, Colin R Jefcoate
For mice, a maternal vitamin A (VA)-deficient diet initiated from midgestation (GVAD) produces serum retinol deficiency in mature offspring. We hypothesize that the effects of GVAD arise from preweaning developmental changes. We compare the effect of this GVAD protocol in combination with a postweaning high-fat diet (HFD) or high-carbohydrate diet (LF12). Each is compared to an equivalent VA-sufficient combination. GVAD extensively decreased serum retinol and liver retinol, retinyl esters, and retinoid homeostasis genes (Lrat, Cyp26b1 and Cyp26a1)...
September 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28558289/toxicity-of-triphenyltin-on-the-development-of-retinal-axons-in-zebrafish-at-low-dose
#11
Yue Xiao, Jieqiong Jiang, Wenxin Hu, Yanbin Zhao, Jianying Hu
The impacts of triphenyltin (TPT) on ecological health are of particular concern due to the unexpectedly high levels found in wild fish around the world. Here, zebrafish embryos were exposed to TPT via in ovo nano-injection to study its toxicity on the development of retinal axons in fish. Lipophilic dye labeling revealed obvious defects in retinal axon development in larvae with normally shaped eyes, with incidences of 0, 1.08%, 2.66%, 4.26%, and 6.85% observed in the control, 0.8, 4.0, 20.0, and 100ng TPT-Cl/g wet weight (ww) exposure groups, respectively, showing a dose-dependent increase...
August 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28446509/inhibition-of-the-all-trans-retinoic-acid-atra-hydroxylases-cyp26a1-and-cyp26b1-results-in-dynamic-tissue-specific-changes-in-endogenous-atra-signaling
#12
Faith Stevison, Cathryn Hogarth, Sasmita Tripathy, Travis Kent, Nina Isoherranen
All-trans retinoic acid (atRA), the active metabolite of vitamin A, is a ligand for several nuclear receptors and acts as a critical regulator of many physiologic processes. The cytochrome P450 family 26 (CYP26) enzymes are responsible for atRA clearance, and are potential drug targets to increase concentrations of endogenous atRA in a tissue-specific manner. Talarozole is a potent inhibitor of CYP26A1 and CYP26B1, and has shown some success in clinical trials. However, it is not known what magnitude of change is needed in tissue atRA concentrations to promote atRA signaling changes...
July 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28436029/wnt4-acts-downstream-of-bmp2-to-mediate-the-regulation-of-atra-signaling-on-runx1-expression-implications-for-terminal-differentiation-of-antler-chondrocytes
#13
Hong-Liang Zhang, Zhan-Qing Yang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue, Bin Guo
Although ATRA is involved in regulating the proliferation and differentiation of chondrocytes, its underlying mechanism remains unknown. Here we showed that ATRA could stimulate the proliferation of antler chondrocytes and expression of COL X and MMP13 which were two well-known markers for hypertrophic chondrocytes. Silencing of CRABP2 prevented the induction of ATRA on chondrocyte terminal differentiation, while overexpression of CRABP2 exhibited the opposite effects. CYP26A1 and CYP26B1 weakened the sensitivity of antler chondrocytes to ATRA...
April 24, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28422378/cellular-retinoic-acid-bioavailability-in-various-pathologies-and-its-therapeutic-implication
#14
REVIEW
Makoto Osanai
Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling molecule in various cell types. We found that RA depletion caused by expression of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that the biological effect of RA on target cells is primarily determined by "cellular RA bioavailability", which is defined as the RA level in an individual cell, rather than by the serum concentration of RA...
April 19, 2017: Pathology International
https://www.readbyqxmd.com/read/28361034/combinatorial-ranking-of-gene-sets-to-predict-disease-relapse-the-retinoic-acid-pathway-in-early-prostate-cancer
#15
Hieu T Nim, Milena B Furtado, Mirana Ramialison, Sarah E Boyd
BACKGROUND: Quantitative high-throughput data deposited in consortia such as International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) present opportunities and challenges for computational analyses. METHODS: We present a computational strategy to systematically rank and investigate a large number (2(10)-2(20)) of clinically testable gene sets, using combinatorial gene subset generation and disease-free survival (DFS) analyses. This approach integrates protein-protein interaction networks, gene expression, DNA methylation, and copy number data, in association with DFS profiles from patient clinical records...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28339981/transcriptome-analysis-of-comb-and-testis-from-rose-comb-silky-chicken-r1-r1-and-beijing-fatty-wild-type-chicken-r-r
#16
Y Wang, J Li, C Feng, Y Zhao, X Hu, N Li
Rose-comb was one of the chicken comb-variants first used by Bateson and Punnet in 1902 to demonstrate Mendelian inheritance in animals. Rose-comb is a monogenic trait that has been widely described in chickens. It is caused by a large structural rearrangement that leads to mis-expression of transcription factor MNR2 on chromosome 7. Rose-comb has pleiotropic effects in homozygous roosters, which is associated with poor sperm mobility. It was postulated that this is caused by the disruption of the CCDC108 gene located at the distal inversion breakpoint...
June 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28275201/physiologically-based-pharmacokinetic-model-of-all-trans-retinoic-acid-with-application-to-cancer-populations-and-drug-interactions
#17
Jing Jing, Cara Nelson, Jisun Paik, Yoshiyuki Shirasaka, John K Amory, Nina Isoherranen
All-trans retinoic acid (atRA) is a front-line treatment of acute promyelocytic leukemia (APL). Due to its activity in regulating the cell cycle, it has also been evaluated for the treatment of other cancers. However, the efficacy of atRA has been limited by atRA inducing its own metabolism during therapy, resulting in a decrease of atRA exposure during continuous dosing. Frequent relapse occurs in patients receiving atRA monotherapy. In an attempt to combat therapy resistance, inhibitors of atRA metabolism have been developed...
May 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28253328/reprogramming-of-the-retinoic-acid-pathway-in-decidualizing-human-endometrial-stromal-cells
#18
Rie Ozaki, Keiji Kuroda, Yuko Ikemoto, Asako Ochiai, Akemi Matsumoto, Jun Kumakiri, Mari Kitade, Atsuo Itakura, Joanne Muter, Jan J Brosens, Satoru Takeda
Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28238841/vitamin-a-status-affects-the-plasma-parameters-and-regulation-of-hepatic-genes-in-streptozotocin-induced-diabetic-rats
#19
Yang Li, Yang Liu, Guoxun Chen
Vitamin A (VA) status regulates metabolism in rats. Whether VA status and availability of retinoic acid (RA) contribute to the insulin-regulated hepatic gene expression remains to be determined. Zucker lean rats with VA sufficient (VAS) or VA deficient (VAD) status were treated with streptozotocin (STZ) to induce insulin-dependent diabetes. They were treated with saline (STZ-VAS-C or STZ-VAD-C), RA (STZ-VAS-RA or STZ-VAD-RA), insulin (STZ-VAS-INS or STZ-VAD-INS), or insulin + RA (STZ-VAS-INS + RA or STZ-VAD-INS + RA) for 3 h...
June 2017: Biochimie
https://www.readbyqxmd.com/read/28213303/diethylstilbestrol-flutamide-and-their-combination-impaired-the-spermatogenesis-of-male-adult-zebrafish-through-disrupting-hpg-axis-meiosis-and-apoptosis
#20
Pan Yin, Ying-Wen Li, Qi-Liang Chen, Zhi-Hao Liu
Both diethylstilbestrol (DES, an environmental estrogen) and flutamide (FLU, an anti-androgen) are found to impair spermatogenesis by disrupting hypothalamic-pituitary-gonadal (HPG) axis and altering androgen levels through different mechanisms/modes of action in fish with poorly understood underlying mechanisms. Furthermore, it is not known whether and how a combined exposure of DES and FLU has a stronger effect than the compounds alone. In this study, male zebrafish adults were exposed to DES, FLU and their combination (DES+FLU) for 30days, and their effects on histological structure and sperm count in testis, androgen level in plasma, as well as the mRNA levels of genes involved in HPG axis, meiotic regulation and apoptosis were analyzed...
April 2017: Aquatic Toxicology
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