Disease relevance of Tigason

• We describe a syndrome of tendon and ligament calcification, primarily in extraspinal locations, that we have observed after long-term therapy for psoriasis and disorders of keratinization with etretinate, another synthetic retinoid [1].
• Of 38 patients who had received etretinate (average dose, 0.8 mg per kilogram of body weight per day; average duration, 60 months), 32 (84 percent) had radiographic evidence of extraspinal tendon and ligament calcification [1].
• Isotretinoin, a synthetic retinoid that has been prescribed for over 500,000 patients with cystic acne, has been associated with both spinal hyperostosis and a disorder similar to diffuse idiopathic skeletal hyperostosis [1].
• Central hypothyroidism associated with retinoid X receptor-selective ligands [2].
• This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP [3].

Psychiatry related information on Tigason

• Evidence for defective retinoid transport and function in late onset Alzheimer's disease [4].
• Reduced retinoid content in hepatocellular carcinoma with special reference to alcohol consumption [5].
• In summary, alcohol abuse may help promote the hepatocarcinogenesis in man by depleting the liver of the antitumor promoter, retinoid [5].
• The early induced genes identified may play a regulatory role in RA-mediated growth suppression and terminal differentiation and may have physiologic or pharmacologic importance during normal human development and retinoid-based cancer therapy or prevention [6].
• Hypothesized mechanisms include effects of diet modification on gonadal hormones, retinoid-like activities of carotenoids, and other protective effects of biologically active dietary constituents [7].

High impact information on Tigason

• Nuclear receptors act as ligand-inducible transcription factors by directly interacting as monomers, homodimers, or heterodimers with the retinoid X receptor with DNA response elements of target genes, as well as by "cross-talking" to other signaling pathways [8].
• The similarity of the effects of retinoid ligand knockouts to effects of compound retinoid receptor knockouts on embryogenesis is presented [9].
• Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium [10].
• A key step in the visual cycle is isomerization of an all-trans retinoid to 11-cis-retinol in the RPE (refs. 9-11) [11].
• In addition, we evaluated the in vitro effect of triiodothyronine, 9-cis-retinoic acid, and the retinoid X receptor-selective ligand LGD346 on the activity of the thyrotropin beta-subunit gene promoter [2].

Chemical compound and disease context of Tigason

• Thus, retinoid receptors are involved in the regulation of brain functions, and retinoic acid signaling defects may contribute to pathologies such as Parkinson's disease and schizophrenia [12].
• A panel of retinoid compounds (tretinoin, isotretinoin, acitretin, and RO13-1470) were tested for inhibitory activity against Kaposi's sarcoma cell (KSC) cultures in vitro [13].
• Fenretinide [N-(4-hydroxyphenyl)retinamide; HPR] is a synthetic retinoid with minimal toxicity and favorable pharmacokinetics during long-term administration to patients in clinical trials [14].
• KLN 205 murine squamous carcinoma cells were grown in medium supplemented with the retinoid 13-cis-retinoic acid (RA) to study the relationship between RA-induced cell surface changes and alterations of the metastatic phenotype [15].
• Moreover, cellular retinoid-binding protein, F-type (an oncofetal protein), also newly appeared exclusively in the hepatoma tissues, suggesting that the preventive effect of E-5166 on hepatocarcinogenesis was mediated, at least in part, through its binding with the new retinoid receptor [16].

Biological context of Tigason

• Our results suggest that interference with retinoid signalling, and not disruption of PML organization, is essential to the APL phenotype and implicates for the first time an element of the mitotic apparatus in the molecular pathogenesis of human malignancy [17].
• To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne [18].
• Novel retinoid-related molecules as apoptosis inducers and effective inhibitors of human lung cancer cells in vivo [19].
• Retinoid activities are mediated by specific nuclear receptors, the RARs and RXRs, which can induce transcriptional activation through specific DNA sites or by inhibiting the transcription factor AP-1 (refs 12-15), which usually mediates cell proliferation signals [20].
• These results show that the floor plate is a local source of a ZPA-like polarizing signal, possibly a retinoid, which may regulate the pattern of cell differentiation in the developing CNS [21].

Anatomical context of Tigason

• A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord [22].
• Motor neuron-derived retinoid signaling specifies the subtype identity of spinal motor neurons [23].
• Extraspinal tendon and ligament calcification associated with long-term therapy with etretinate [1].
• These retinoids do not induce differentiation in F9 cells but inhibit effectively the proliferation of several tumour cell lines, and could thus serve as candidates for new retinoid therapeutic agents with reduced side effects [20].
• This indicates a migration of retinoid between the two tissues, the direction of which is dictated by the state of light or dark adaptation of the photoreceptors [24].

Associations of Tigason with other chemical compounds

• These observations suggest that retinoid X receptors meet the criteria for biochemically characterized cellular coregulators and serve to selectively target the high affinity binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate DNA response elements [25].
• These defects were previously observed in vitamin A-deficient animals and could be prevented by RA administration, demonstrating that RAR gamma mediates some of the retinoid signal in vivo [26].
• In the adult mouse, single and compound null mutations in the genes for retinoic acid receptor beta and retinoid X receptors beta and gamma resulted in locomotor defects related to dysfunction of the mesolimbic dopamine signaling pathway [12].
• Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein specific for the retina and pineal gland, induces inflammatory changes in these two organs in immunized animals [27].
• Although overexpression of a constitutively active Akt in premalignant and malignant HBE cells had no effect on growth inhibition mediated by N-(4-hydroxyphenyl)retinamide (4-HPR), a novel chemopreventive retinoid, it blocked deguelin-induced growth arrest and apoptosis [28].

Gene context of Tigason

• Replacement of USP with retinoid X receptor produces heterodimers with distinct pharmacological and functional properties [29].
• Consistent with these observations, inhibitors of histone deacetylase dramatically potentiate retinoid-induced differentiation of RA-sensitive, and restore retinoid responses of RA-resistant, APL cell lines [30].
• Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle [31].
• BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect [32].
• To investigate the role of E2F in retinoid signaling, transient transfection assays were performed using reporter plasmids containing E2F-binding sites [33].

Analytical, diagnostic and therapeutic context of Tigason

• Retinoid chemoprevention trial begins against bladder cancer [34].
• Specific retinoid receptor (retinoic acid receptor [RAR] and retinoid X receptor) messenger RNA (mRNA) levels were measured by northern blot hybridization [35].
• Expression of retinoid receptors (RARalpha and RXRalpha) and PPARgamma was determined by western blot analysis [36].
• METHODS: Expression of retinoid receptors in paired specimens of normal and cancerous tissues from the lungs of 76 patients with NSCLC was studied by use of antiretinoid receptor antibodies (except those against RXRgamma) and immunohistochemistry [37].
• Molecular epidemiology and retinoid chemoprevention of head and neck cancer [38].

References