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Acta Dermato-venereologica Jan 2020
Topics: Administration, Oral; Alitretinoin; Chronic Disease; Cyclosporine; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Patient Safety; Retrospective Studies; Skin; Time Factors; Treatment Outcome
PubMed: 31821516
DOI: 10.2340/00015555-3392 -
Annals of Dermatology Jun 2019
PubMed: 33911606
DOI: 10.5021/ad.2019.31.3.347 -
Annals of Dermatology Nov 2023
PubMed: 38061756
DOI: 10.5021/ad.21.109 -
International Journal of Nanomedicine 2007Kaposi's sarcoma is a vascular tumor of skin and viscera first described in 1872. Prior to the 1980s, this disease was rarely seen in the Western world, but was quite... (Review)
Review
Kaposi's sarcoma is a vascular tumor of skin and viscera first described in 1872. Prior to the 1980s, this disease was rarely seen in the Western world, but was quite prevalent in Sub-Saharan African countries. Since the onset of the HIV pandemic in the 1980s, the incidence of Kaposi's sarcoma has increased markedly in Africa and continues to be a significant problem in association with AIDS in Western countries. Many therapies have been demonstrated to be effective in the treatment of HIV-related Kaposi's sarcoma, including alitretinoin gel, interferon alpha, and various forms of cytotoxic chemotherapy. Antiretroviral therapy combined with cytotoxic agents has yielded significantly greater efficacy than chemotherapy alone. However, as reviewed in this report, pegylated liposomal doxorubicin has been established as the treatment of choice for patients with AIDS-associated Kaposi's sarcoma in Western countries. Compelling preclinical and clinical evidence, reviewed herein, has demonstrated that the nanoparticle (pegylated liposome) delivery system of this formulation leads to greater tumor localization of doxorubicin and consequent improved efficacy, as well as reduced toxicity.
Topics: Acquired Immunodeficiency Syndrome; Chemistry, Pharmaceutical; Drug Carriers; Herpesvirus 8, Human; Humans; Liposomes; Nanomedicine; Nanostructures; Particle Size; Polyethylene Glycols; Sarcoma, Kaposi
PubMed: 18019833
DOI: No ID Found -
Frontiers in Pharmacology 2023In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their...
Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.
In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.
PubMed: 37663263
DOI: 10.3389/fphar.2023.1207976 -
Nucleic Acids Research Jul 2018Allostery tweaks innumerable biological processes and plays a fundamental role in human disease and drug discovery. Exploration of allostery has thus been regarded as a...
Allostery tweaks innumerable biological processes and plays a fundamental role in human disease and drug discovery. Exploration of allostery has thus been regarded as a crucial requirement for research on biological mechanisms and the development of novel therapeutics. Here, based on our previously developed allosteric data and methods, we present an interactive platform called AlloFinder that identifies potential endogenous or exogenous allosteric modulators and their involvement in human allosterome. AlloFinder automatically amalgamates allosteric site identification, allosteric screening and allosteric scoring evaluation of modulator-protein complexes to identify allosteric modulators, followed by allosterome mapping analyses of predicted allosteric sites and modulators in human proteome. This web server exhibits prominent performance in the reemergence of allosteric metabolites and exogenous allosteric modulators in known allosteric proteins. Specifically, AlloFinder enables identification of allosteric metabolites for metabolic enzymes and screening of potential allosteric compounds for disease-related targets. Significantly, the feasibility of AlloFinder to discover allosteric modulators was tested in a real case of signal transduction and activation of transcription 3 (STAT3) and validated by mutagenesis and functional experiments. Collectively, AlloFinder is expected to contribute to exploration of the mechanisms of allosteric regulation between metabolites and metabolic enzymes, and to accelerate allosteric drug discovery. The AlloFinder web server is freely available to all users at http://mdl.shsmu.edu.cn/ALF/.
Topics: Alitretinoin; Allosteric Regulation; Allosteric Site; Datasets as Topic; Drug Discovery; Gene Expression Regulation; Humans; Internet; Ligands; Molecular Docking Simulation; Mutagenesis, Site-Directed; Receptors, Retinoic Acid; Receptors, Thyroid Hormone; STAT3 Transcription Factor; Small Molecule Libraries; Software; Transcription, Genetic; Triiodothyronine
PubMed: 29757429
DOI: 10.1093/nar/gky374 -
Biochimica Et Biophysica Acta May 2011Cellular retinol binding-protein I (CRBPI) and cellular retinol binding-protein II (CRBPII) serve as intracellular retinoid chaperones that bind retinol and retinal with...
BACKGROUND
Cellular retinol binding-protein I (CRBPI) and cellular retinol binding-protein II (CRBPII) serve as intracellular retinoid chaperones that bind retinol and retinal with high affinity and facilitate substrate delivery to select enzymes that catalyze retinoic acid (RA) and retinyl ester biosynthesis. Recently, 9-cis-RA has been identified in vivo in the pancreas, where it contributes to regulating glucose-stimulated insulin secretion. In vitro, 9-cis-RA activates RXR (retinoid × receptors), which serve as therapeutic targets for treating cancer and metabolic diseases. Binding affinities and structure-function relationships have been well characterized for CRBPI and CRBPII with all-trans-retinoids, but not for 9-cis-retinoids. This study extended current knowledge by establishing binding affinities for CRBPI and CRBPII with 9-cis-retinoids.
METHODS
We have determined apparent dissociation constants, K'(d), through monitoring binding of 9-cis-retinol, 9-cis-retinal, and 9-cis-RA with CRBPI and CRBPII by fluorescence spectroscopy, and analyzing the data with non-linear regression. We compared these data to the data we obtained for all-trans- and 13-cis-retinoids under identical conditions.
RESULTS
CRBPI and CRBPII, respectively, bind 9-cis-retinol (K'(d), 11nM and 68nM) and 9-cis-retinal (K'(d), 8nM and 5nM) with high affinity. No significant 9-cis-RA binding was observed with CRBPI or CRBPII.
CONCLUSIONS
CRBPI and CRBPII bind 9-cis-retinol and 9-cis-retinal with high affinities, albeit with affinities somewhat lower than for all-trans-retinol and all-trans-retinal.
GENERAL SIGNIFICANCE
These data provide further insight into structure-binding relationships of cellular retinol binding-proteins and are consistent with a model of 9-cis-RA biosynthesis that involves chaperoned delivery of 9-cis-retinoids to enzymes that recognize retinoid binding-proteins.
Topics: Algorithms; Alitretinoin; Animals; Binding, Competitive; Diterpenes; Fluorometry; Humans; Kinetics; Protein Binding; Retinaldehyde; Retinoid X Receptors; Retinol-Binding Proteins, Cellular; Tretinoin; Vitamin A
PubMed: 21382444
DOI: 10.1016/j.bbagen.2011.02.009 -
Scientific Reports Jul 2021Retinoids play a pivotal role in adrenal development and differentiation. Recent clinical trials revealed therapeutic potential of both all-trans and 9-cis retinoic acid...
Retinoids play a pivotal role in adrenal development and differentiation. Recent clinical trials revealed therapeutic potential of both all-trans and 9-cis retinoic acid in patients with cortisol excess due to a pituitary ACTH-secreting adenoma and indicated that retinoids might act also on the adrenal. Aim of the present study was to evaluate the effect of 9-cis retinoic acid on adrenals from patients with ACTH-dependent Cushing's syndrome. Adrenal specimens from six patients with Cushing's disease were incubated with 10 nM-1 µM 9-cis retinoic acid with and without 10 nM ACTH. Cortisol secretion was measured by immunoassay and expression of genes involved in steroidogenesis as well as retinoic acid action were evaluated by real-time RT-PCR. Incubation with 10-100 nM 9-cis retinoic acid increased spontaneous cortisol secretion and expression of STAR and CYP17A. On the other hand, in wells treated with ACTH, 9-cis retinoic acid markedly diminished ACTH receptor upregulation and no stimulatory effect on cortisol secretion or steroidogenic enzyme synthesis was observed. ACTH itself increased ligand-induced retinoic acid receptor expression, possibly enhancing sensitivity to retinoic acid. Our findings indicate that the effect of 9-cis retinoic acid in presence of ACTH is distinct from unchallenged wells and support the hypothesis of a direct adrenal action in patients with Cushing's disease.
Topics: Adrenal Glands; Adrenocorticotropic Hormone; Alitretinoin; Cushing Syndrome; Humans; Hydrocortisone; Pituitary ACTH Hypersecretion; Receptors, Retinoic Acid; Translational Research, Biomedical; Tretinoin
PubMed: 34253781
DOI: 10.1038/s41598-021-93672-0 -
Cancer Letters Mar 2020Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote...
Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote therapy resistance. Through bioinformatic analyses of TCGA and CPC-GENE patient cohorts, we identified higher miR-191 expression in tumor versus normal tissue, and increased expression in higher Gleason scores. In vitro and in vivo experiments demonstrated that miR-191 overexpression promotes radiation survival, and contributes to a more aggressive phenotype. Retinoid X receptor alpha, RXRA, was discovered to be a novel target of miR-191, and knockdown recapitulated radioresistance. Furthermore, treatment of prostate cancer cells with the RXRA agonist 9-cis-retinoic acid restored radiosensitivity. Supporting this relationship, patients with high miR-191 and low RXRA abundance experienced quicker biochemical recurrence. Reduced RXRA translated to a higher risk of distant failure after radiotherapy. Notably, this miR-191/RXRA interaction was conserved in a novel primary cell line derived from radiorecurrent prostate cancer. Together, our findings demonstrate that miR-191 promotes prostate cancer survival after radiotherapy, and highlights retinoids as a potential option to improve radiotherapy response.
Topics: Alitretinoin; Animals; Antineoplastic Agents; Biomarkers, Tumor; Cell Line, Tumor; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Kallikreins; Kaplan-Meier Estimate; Male; Mice; MicroRNAs; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Primary Cell Culture; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiation Tolerance; Retinoid X Receptor alpha; Survival Rate; Time Factors; Xenograft Model Antitumor Assays
PubMed: 31874245
DOI: 10.1016/j.canlet.2019.12.025 -
Cureus Feb 2021Kaposi sarcoma (KS) is a vascular neoplasm caused by human gammaherpesvirus 8 (HHV-8). Four subtypes of KS are described: classic (Mediterranean), epidemic (acquired...
Kaposi sarcoma (KS) is a vascular neoplasm caused by human gammaherpesvirus 8 (HHV-8). Four subtypes of KS are described: classic (Mediterranean), epidemic (acquired immunodeficiency syndrome (AIDS)-associated), endemic (sub-Saharan Africa), and iatrogenic. Iatrogenic KS due to tumor necrosis factor-alpha (TNF-α) inhibitor therapy is particularly rare. A 66-year-old female with a history of seropositive rheumatoid arthritis (RA) presented with a skin lesion on her right second toe. Diagnosed with RA four years prior, she failed to respond to methotrexate, hydroxychloroquine, and etanercept. As a result, she was started on adalimumab. Approximately two months into therapy, she presented to the emergency room with a dark brown skin lesion on her right second toe. She underwent excisional biopsy of the mass, which demonstrated a tumor composed of spindle cells forming slit-like spaces with extravasated red blood cells. The tumor was positive for cluster of differentiation 31 (CD31), CD34, and HHV-8 immunostains and negative for smooth muscle antibody (SMA) and desmin immunostains, consistent with Kaposi sarcoma. Human immunodeficiency virus (HIV) serology was negative. The patient was diagnosed with iatrogenic KS. Adalimumab was discontinued. The patient was started on alitretinoin and underwent adjuvant radiation therapy to minimize recurrence. TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases and in cell apoptosis. While anti-TNF-α agents have improved outcomes in many immune-mediated diseases, higher rates of infections and malignancy have also been reported. The incidence of KS with anti-TNF-α therapy remains a rare entity. Therefore, it is extremely important for patients receiving biologic agents, including TNF-α inhibitors, to have a close follow-up and receive routine skin evaluation for malignancy. Clinicians should have a high index of suspicion for KS in such non-HIV patients started on immunosuppressive agents.
PubMed: 33754107
DOI: 10.7759/cureus.13384