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retinoid investigation

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https://www.readbyqxmd.com/read/28427429/vitamin-d-receptor-retinoid-x-receptor-and-peroxisome-proliferator-activated-receptor-%C3%AE-are-overexpressed-in-brca1-mutated-breast-cancer-and-predict-prognosis
#1
Sabine Heublein, Doris Mayr, Alfons Meindl, Alexandra Kircher, Udo Jeschke, Nina Ditsch
BACKGROUND: BRCA1 mutated breast cancers are commonly diagnosed as negative for classical hormone receptors i.e. estrogen receptor, progesterone receptor and/or Her2. Due to these common targets being absent the application of anti-endocrine therapies is rather limited and a certain focus has been set on discovering alternative target molecules. We recently highlighted thyroid hormone receptors (TRs) to predict prognosis in breast cancer patients that had been diagnosed a BRCA1 germline mutation...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28423369/mdi-301-a-synthetic-retinoid-depressed-levels-of-matrix-metalloproteinases-and-oxidative-stress-in-diabetic-dermal-fibroblasts
#2
Jianhua Zhai, Yuli Wang
Diabetic foot ulcerations could result in serious consequences such as amputations. The up-regulation of matrix metalloproteinases and down-regulation of TIMP1 were remarked as distinctive biological characteristics in the diabetic dermal fibroblast. The current study was performed in order to clarify the effect of high glucose on formation of diabetic dermal fibroblast cell. In addition, the effect of MDI 301 on ameliorating diabetic fibroblasts was investigated in this study. The mRNA and protein expression levels of MMPs, TIMP1 and catalase were evaluated against fibroblasts treated with high glucose (30 mM) using qRT-PCR, western blotting and zymography assays...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396297/the-co-regulators-src-1-and-smrt-are-involved-in-interleukin-6-induced-androgen-receptor-activation
#3
Qi Wang, Hui Wang, Qiang Ju, Zhen Ding, Xing Ge, Qiao-Mei Shi, Ji-Long Zhou, Xiao-Long Zhou, Jin-Peng Zhang, Mei-Rong Zhang, Hong-Min Yu, Li-Chun Xu
BACKGROUND: The androgen receptor (AR) can be stimulated by interleukin-6 (IL-6) in the absence of androgens to induce prostate cancer progression. The purpose of this study was to investigate whether the co-activator steroid receptor coactivator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) are involved in IL-6-induced AR activation. METHODS: The effects of IL-6 on LNCaP cell proliferation were monitored using real-time cell analysis (RTCA) iCELLigence system...
November 1, 2016: European Cytokine Network
https://www.readbyqxmd.com/read/28391333/clinical-trials-in-minimal-change-disease
#4
Pietro Ravani, Enrica Bertelli, Simardeep Gill, Gian Marco Ghiggeri
Minimal change disease (MCD) is a pathological condition characterized by subtle glomerular lesions causing massive and reversible proteinuria that is usually steroid sensitive. Recurrence of symptoms of active disease following successful treatment (including proteinuria, oedema and oliguria) and steroid toxicity requires the use of other drugs to attain or maintain remission. Unresolved MCD is considered the initial step in the pathological pathway leading to focal and segmental glomerulosclerosis (FSGS)...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28381532/single-high-dose-vitamin-a-supplementation-to-neonatal-piglets-results-in-a-transient-dose-response-in-extrahepatic-organs-and-sustained-increases-in-liver-stores
#5
Bryan M Gannon, Christopher R Davis, Nivedita Nair, Michael Grahn, Sherry A Tanumihardjo
Background: Neonatal vitamin A (VA) supplementation is being evaluated as a public health policy for preventing infant mortality, but inconsistencies in mortality trials demand mechanistic work to determine biological plausibility.Objectives: We investigated the absorption, distribution, and storage of single large oral VA doses administered shortly after birth.Methods: Fifty pregnant sows (Sus scrofas domesticas) were fed a VA-free diet. Male and female newborn piglets (n = 313) were orally administered 0, 25,000, 50,000, or 200,000 IU VA in oil within 12 h of birth when mean ± SD weight was 1...
April 5, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28359780/potential-role-of-retinoids-in-ovarian-physiology-and-pathogenesis-of-polycystic-ovary-syndrome
#6
REVIEW
Yanwen Jiang, Chunjin Li, Lu Chen, Fengge Wang, Xu Zhou
Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide...
March 27, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28350049/activation-of-the-crabpii-rar-pathway-by-curcumin-induces-retinoic-acid-mediated-apoptosis-in-retinoic-acid-resistant-breast-cancer-cells
#7
Padmamalini Thulasiraman, Galen Garriga, Veena Danthuluri, Daniel J McAndrews, Imran Q Mohiuddin
Due to the anti-proliferative and anti-apoptotic effects of retinoic acid (RA), this hormone has emerged as a target for several diseases, including cancer. However, development of retinoid resistance is a critical issue and efforts to understand the retinoid signaling pathway may identify useful biomarkers for future clinical trials. Apoptotic responses of RA are exhibited through the cellular RA-binding protein II (CRABPII)/retinoic acid receptor (RAR) signaling cascade. Delivery of RA to RAR by CRABPII enhances the transcriptional activity of genes involved in cell death and cell cycle arrest...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28335003/identification-of-genetic-variants-affecting-vitamin-d-receptor-binding-and-associations-with-autoimmune-disease
#8
Giuseppe Gallone, Wilfried Haerty, Giulio Disanto, Sreeram V Ramagopalan, Chris P Ponting, Antonio J Berlanga-Taylor
Large numbers of statistically significant associations between sentinel SNPs and case-control status have been replicated by genome-wide association studies. Nevertheless, few underlying molecular mechanisms of complex disease are currently known. We investigated whether variation in binding of a transcription factor, the vitamin D receptor (VDR) whose activating ligand vitamin D has been proposed as a modifiable factor in multiple disorders, could explain any of these associations. VDR modifies gene expression by binding DNA as a heterodimer with the Retinoid X receptor (RXR)...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28298266/metabolic-effects-of-inflammation-on-vitamin-a-and-carotenoids-in-humans-and-animal-models
#9
REVIEW
Lewis P Rubin, A Catharine Ross, Charles B Stephensen, Torsten Bohn, Sherry A Tanumihardjo
The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency...
March 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28267642/fundamental-studies-of-adrenal-retinoid-x-receptor-protein-isoform-tissue-expression-subcellular-distribution-and-ligand-availability
#10
Behling Cheng, Fatema H Al-Shammari, Isra'a A Ghader, Fatima Sequeira, Jitendra Thakkar, Thazhumpal C Mathew
Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRβ (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRβ and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions...
March 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28264498/retinoic-acid-negatively-impacts-proliferation-and-mctc-specific-attributes-of-human-skin-derived-mast-cells-but-reinforces-allergic-stimulability
#11
Magda Babina, Metin Artuc, Sven Guhl, Torsten Zuberbier
The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, FcεRI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays...
February 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28251414/molecular-dynamics-simulations-and-molecular-flooding-studies-of-the-retinoid-x-receptor-ligand-binding-domain
#12
Geoffrey M Gray, Ning Ma, Carl E Wagner, Arjan van der Vaart
Bexarotene is an FDA approved retinoid X-receptor (RXR) agonist for the treatment of cutaneous T-cell lymphoma, and its use in other cancers and Alzheimer's disease is being investigated. The drug causes serious side effects, which might be reduced by chemical modifications of the molecule. To rationalize known agonists and to help identify sites for potential substitutions we present molecular simulations in which the RXR ligand-binding domain was flooded with a large number of drug-like molecules, and molecular dynamics simulations of a series of bexarotene-like ligands bound to the RXR ligand-binding domain...
March 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28249598/the-prognostic-utility-of-the-transcription-factor-srf-in-docetaxel-resistant-prostate-cancer-in-vitro-discovery-and-in-vivo-validation
#13
D J Lundon, A Boland, M Prencipe, G Hurley, A O'Neill, E Kay, S T Aherne, P Doolan, S F Madden, M Clynes, C Morrissey, J M Fitzpatrick, R W Watson
BACKGROUND: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel...
March 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28230922/adipose-derived-aldehyde-dehydrogenase-expressing-cells-promote-dermal-regenerative-potential-with-collagen-glycosaminoglycan-scaffold
#14
Hajime Matsumine, Kazuyuki Numakura, Satoshi Tsunoda, Huan Wang, Rui Matsumine, Mihail Climov, Giorgio Giatsidis, Vikas P Sukhatme, Dennis P Orgill
Aldehyde dehydrogenase (ALDH) is an enzyme that plays an important role in retinoid metabolism and highly expressed in stem cells. This study isolated ALDH-expressing cells from subcutaneous adipose tissue and investigated their potential to enhance healing in a full-thickness skin wound in rats by co-implanting them with collagen-glycosaminoglycan (c-GAG) scaffolds. ALDH-positive cells were isolated by a fluorescence-activated cell sorting technique from Lewis rat's stromal-vascular-fraction (SVF) and transplanted with c-GAG scaffolds in a rat full-thickness skin wound model...
November 7, 2016: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#15
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28222789/is-ccnu-lomustine-valuable-for-treatment-of-cutaneous-epitheliotropic-lymphoma-in-dogs-a-critically-appraised-topic
#16
REVIEW
Aurore Laprais, Thierry Olivry
BACKGROUND: CCNU and other treatment protocols are commonly offered to owners for the treatment of dogs diagnosed with cutaneous (epitheliotropic) T-cell lymphoma (CTCL). Chemotherapy protocols provide variable benefits; they have different side-effects, and they typically require monitoring to detect drug toxicity at a non-negligible cost to the owner. At this time, even though CCNU is most often recommended to treat dogs with CTCL, there is no clear consensus on the benefit of this drug...
February 21, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28155143/autofluorescence-spectroscopy-for-monitoring-metabolism-in-animal-cells-and-tissues
#17
Anna C Croce, Giovanni Bottiroli
Excitation of biological substrates with light at a suitable wavelength can give rise to a light emission in the ultraviolet (UV)-visible, near-infrared (IR) spectral range, called autofluorescence (AF). This is a widespread phenomenon, ascribable to the general presence of biomolecules acting as endogenous fluorophores (EFs) in the organisms of the whole life kingdom. In cytochemistry and histochemistry, AF is often an unwanted signal enhancing the background and affecting in particular the detection of low signals or rare positive labeling spots of exogenous markers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28153738/myocilin-expression-is-regulated-by-retinoic-acid-in-the-trabecular-meshwork-derived-cellular-environment
#18
Cécile Prat, Corinne Belville, Aurélie Comptour, Geoffroy Marceau, Gael Clairefond, Frédéric Chiambaretta, Vincent Sapin, Loïc Blanchon
Glaucoma is the leading cause of irreversible blindness and is usually classified as angle closure and open angle glaucoma (OAG). Primary open angle glaucoma represents the most frequent clinical presentation leading to ganglion cell death and optic nerve degeneration as a main consequence of an intraocular pressure' (IOP) increase. The mechanisms of this IOP increase in such pathology remain unclear but one protein called Myocilin could be a part of the puzzle in the trabecular meshwork (TM). Previously described to be transcriptionally regulated by glucocorticoids, the comprehension of the trabecular regulation of Myocilin' expression has only weakly progressed since 15 years...
January 30, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28123100/hepatic-detoxification-of-bisphenol-a-is-retinoid-dependent
#19
Igor O Shmarakov, Vira L Borschovetska, William S Blaner
Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl) propane) is a widely used industrial chemical. The extensive distribution of BPA in the environment poses risks to humans however the molecular mechanisms underlying BPA toxicity as well as its effective detoxification and elimination are not well understood. We have investigated specifically for BPA the notion raised in the literature that the optimal sensing, detoxification and elimination of xenobiotics requires retinoid (natural derivatives and synthetic analogs of vitamin A) actions...
January 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28119491/reactive-oxygen-species-mediated-synergism-of-fenretinide-and-romidepsin-in-preclinical-models-of-t-cell-lymphoid-malignancies
#20
Monish R Makena, Balakrishna Koneru, Thinh H Nguyen, Min H Kang, C Patrick Reynolds
T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitor romidepsin and the synthetic cytotoxic retinoid fenretinide both have achieved durable clinical responses in T-cell lymphomas as single agents. We investigated the potential for using these two agents in combination in TCLMs. We demonstrated cytotoxic synergy between romidepsin and fenretinide in fifteen TCLM cell lines at clinically-achievable concentrations that lacked cytotoxicity for non-malignant cells (fibroblasts and blood mononuclear cells)...
January 23, 2017: Molecular Cancer Therapeutics
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