Akné je chronické zánětlivé onemocnění pilosebaceózní jednotky, které postihuje výlučně lidskou populaci. Výraznou účinnost při systémové léčbě těžkých forem akné prokázal izotretinoin ze skupiny retinoidů, který má i přímý protizánětlivý účinek. Cílem studie bylo vyhodnotit zánětlivé změny, změny exprese androgenového receptorů (AR) a retinoidního receptorů Xα (RXRα) v kožních bioptických vzorcích u pacientů před léčbou a po 6měsíční terapii izotretinoinem (Roaccutane®) a porovnat je se skupinou neléčených pacientů s akné a s kontrolní skupinou pacientů bez akné. Sledované faktory byly vyšetřeny u 40 probandů pomocí standardní nepřímé imunohistochemické metody. Prokázali jsme významné snížení exprese antigenů HLA-DR u pacientů léčených izotretinoinem. Nebylo prokázáno snížení exprese AR po 6měsíční terapii. I když léčená skupina vykazuje mírné snížení exprese AR, změny před léčbou a po léčbě nejsou statisticky signifikantní. Dále jsme neprokázali změny exprese RXRα, z čehož usuzujeme, že podobně jako při lokální terapii není exprese receptorů RXRα celkovou terapií izotretinoinem výrazně ovlivněna. Předpokládáme tedy, že protizánětlivý účinek izotretinoinu u akné může souviset s redukcí exprese antigenů HLA-DR.

Acne is a chronic inflammatory disease of pilosebaceous unit affecting only humans. Isotretinoin, a member of retinoid family, has shown marked efficacy in systemic treatment of serious forms of acne and possesses a direct anti-inflammatory effect. The aim of the present study was to assess inflammatory changes and expression of androgen receptor (AR) and retinoid X receptor α in skin biopsies of patients before and after six-month isotretinoin (Roaccutane®) therapy in comparison to untreated acne patients and healthy skin controls. Forty cases were studied using standard indirect immunohistochemical method. Significant decrease of HLA-DR antigens expression in patients treated with isotretinoin was found. Reduced AR expression was not found after 6–month therapy. Despite slightly decreased expression of androgen receptor in treated group the changes before and after treatment were not significant. No changes in retinoid X receptor α were found. Therefore it seems probable that similarly to local therapy systemic treatment does not influence RXRα expression. We assume that anti-inflammatory effect of retinoids in acne treatment depends on reduction of HLA-DR antigens expression.

• MeSH
• acne vulgaris farmakoterapie   MeSH
• androgenní receptory biosyntéza   MeSH
• isotretinoin analogy a deriváty   terapeutické užití   MeSH
• kůže anatomie a histologie   imunologie   MeSH
• lidé MeSH
• retinoidní X receptor alfa biosyntéza   MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

Adapalen je užitečným novým lékem v léčbě akné, a to vzhledem k snášenlivosti a stabilitěúčinku. Je vhodný v kombinaci s ostatními lokálními i celkovými léky, např. antimikrobiálnímipřípravky nebo benzoylperoxidem. Při kombinované léčbě i aplikaci samotného adapalenu se zlepšujespolupráce pacienta vzhledem k většímu komfortu použití a podstatně slabšímu iritačnímupotenciálu této nové látky. Soustavné a významné omezení kožní iritace potvrzuje řada autorů.V léčbě kožních onemocnění nacházejí uplatnění některé přirozené i syntetické retinoidy, např.kyselina retinová a jeden z jejích izomerů, kyselina 13-cis-retinová (13-cis RA), se používají jakolokální i celkové léky na akné. Značná iritace kůže, působená kyselinou retinovou, je důvodem prohledání retinoidů se zlepšeným poměrem mezi terapeutickým efektem a vedlejšími účinky.Moderníchemicko-farmakologický program vedl k objevu nového syntetického retinoidu adapalenu, účinnéhoa pacienty lépe snášeného než kyselina retinová.Farmakologické studie in vitro i in vivo prokázaly aktivitu adapalenu v oblasti proliferacea diferenciace buněk i tkání. Adapalen také působí protizánětlivě, což je dáno jeho anti-AP1 účinkem.Vstupuje do selektivních interakcí s jadernými receptory RABβ a RABγ a jeho účinek naproliferaci a diferenciaci je blokovatelný antagonistou RABβ-γ. Vzhledem k tomu že RABβ nejsou nalidských keratinocytech vyjádřeny, je jisté, že účinek adapalenu na tento hlavní buněčný typepidermis je zprostředkován interakcí s RARγ. Jedinečnými farmakologickými vlastnostmi adapalenulze - díky zlepšené toleranci - vysvětlit jeho lepší terapeutický poměr ve srovnání s tretinoinem.

Adapalene is a useful new drug in the treatment of acne due to its tolerance and stability of effect.It is suitable in combination with other local and systemic drugs, e.g. antimicrobial preparations orbenzoyl peroxide. After combined treatment and administration of adapalene alone the patientscollaboration improves due to more comfortable use and much weaker irritant potential of this newsubstance. A number of authors confirm the reduced skin irritation.In the treatment of skin diseases some natural and synthetic retinoids are used. E.g. retinoic acidand one of its isomers, 13-cis retinoic acid (13-cis RA), are used as local and systemic drugs in acne.Considerable skin irritation caused by retinoic acid is the reasonwhy retinoids with a better relationbetween the therapeutic effect and side effects are sought. A modern chemical and pharmacologicalprogramme led to the discovery of a new synthetic retinoid, adapalene, which is effective andtolerated better by patients than retinoic acid.Pharmacological studies in vitro and in vivo provided evidence of the activity of adapalene asregards proliferation and differentiation of cells and tissues. Adapelene has also an anti-inflammatoryeffect which is due to its anti-AP1 action. It enters selective interactions with nuclear receptorsRARβ and RARγ and its effect on proliferation and differentiation can be blocked by the antagonistofRARβ-γ.AsRARβ are not expressed inhumankeratinocytes, it is certain that the effect of adapaleneon this main cellular type of epidermis is mediated by interaction with RARγ. The unique pharmacologicalproperties of adapalene explain - due to the improved tolerance - its better therapeuticeffect as compared with tretinoin.

• MeSH
• acne vulgaris etiologie   farmakoterapie   MeSH
• adapalen MeSH
• buněčné dělení účinky léků   MeSH
• fixní kombinace léků MeSH
• lidé MeSH
• retinoidy farmakologie   fyziologie   chemie   MeSH
• steroidní receptory fyziologie   MeSH
• tretinoin farmakologie   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Important key players in the regulatory machinery within the cells are nuclear retinoid X receptors (RXRs), which compose heterodimers in company with several diverse nuclear receptors, playing a role as ligand inducible transcription factors. In general, nuclear receptors are ligand-activated, transcription-modulating proteins affecting transcriptional responses in target genes. RXR molecules forming permissive heterodimers with disparate nuclear receptors comprise peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstan receptor (CAR). Retinoid receptors (RARs) and thyroid hormone receptors (TRs) may form conditional heterodimers, and dihydroxyvitamin D3 receptor (VDR) is believed to form nonpermissive heterodimer. Thus, RXRs are the important molecules that are involved in control of many cellular functions in biological processes and diseases, including cancer or diabetes. This article summarizes both naturally occurring and synthetic ligands for nuclear retinoid X receptors and describes, predominantly in mammals, their role in molecular mechanisms within the cells. A focus is also on triorganotin compounds, which are high affinity RXR ligands, and finally, we present an outlook on human microbiota as a potential source of RXR activators. Nevertheless, new synthetic rexinoids with better retinoid X receptor activity and lesser side effects are highly required.

• MeSH
• lidé MeSH
• ligandy MeSH
• mikrobiota MeSH
• organocínové sloučeniny farmakologie   MeSH
• receptory cytoplazmatické a nukleární fyziologie   MeSH
• retinoidní X receptory agonisté   fyziologie   MeSH
• tretinoin analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIM: Polymorphisms in retinoid X receptors (RXRs) are very interesting from the point of view of a possible association of their variability with psoriasis. METHODS: A total of 293 patients with plaque psoriasis, 82 patients with psoriasis guttata and 202 control subjects were enrolled in this study focused on 3 polymorphisms in RXRA and RXRB gene associations. RESULTS: A marginally significant increase in AA allelic frequency of the RXRA A39526AA polymorphism in plaque psoriatic men compared to healthy men was proved. In women with psoriasis guttata, the higher risk for genotypes AA and TT in the RXRB 3'+140A/T polymorphism compared to healthy women was identified (p(corr) = 0.01). The genotypes A/A and AA/AA are more frequent in plaque psoriasis patients with a positive family history of psoriasis compared to the patients with a negative family history of psoriasis (p(corr) = 0.02). The A/A genotype is more frequent in patients with plaque psoriasis and repeated tonsillitis/tonsillectomy (p = 0.02). In the RXRB polymorphism, no genotype TT is observed in patients with psoriasis guttata with a positive personal history of repeated tonsillitis (p(corr) = 0.001). CONCLUSION: Individual gene characteristics of patients with psoriasis improve the possibilities of pharmacotherapy using pharmacogenomic approaches which could be further stratified in future according to the subtypes of psoriasis. Copyright 2007 S. Karger AG, Basel.

• MeSH
• angiotensinogen genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• mladiství MeSH
• polymorfismus genetický MeSH
• psoriáza genetika   klasifikace   patologie   MeSH
• retinoidní X receptor alfa genetika   MeSH
• retinoidní X receptor beta genetika   MeSH
• retinoidní X receptory genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tonzilitida genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

The main intention of this study was the investigation of impact of natural biologically active ligands of nuclear retinoid/retinoid X receptors (all-trans and 9-cis retinoic acid) on proteomic pattern in human estrogen receptor negative breast cancer cell line MDA-MB-231. For this purpose, proteomic strategies based on bottom-up method were applied. The total cell proteins were extracted utilizing a commercially Radio-Immunoprecipitation Assay (RIPA) buffer and separated on 2D sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE). The proteins were subsequently digested in-gel by trypsin and their characterization was achieved by MALDI-TOF/TOF. By employing PDQuest™ software, we identified more than 50 proteins affected by retinoic acid isomers. For more information, 9 proteins which are associated with tumor process were selected. We determined that derivatives of retinoic acid led to significantly reduced level of proteins belonging to metabolic pathway (e.g. glyceraldehyde-3-phosphate dehydrogenase or pyruvate kinase 2) or to other cellular processes as apoptosis, regulation of transcription process or epithelial-mesenchymal transition (e.g. annexins, nucleoside diphosphate kinase B, vimentin). On the other hand all-trans retinoic acid treatment indicates up-regulated effect for heterogeneous nuclear ribonucleoprotein A2/B1.

• MeSH
• apoptóza účinky léků   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• epitelo-mezenchymální tranzice účinky léků   MeSH
• heterogenní jaderné ribonukleoproteiny skupiny A-B genetika   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• nádory prsu genetika   MeSH
• proteomika * MeSH
• protinádorové látky farmakologie   MeSH
• regulace genové exprese u nádorů * MeSH
• retinoidní X receptory genetika   metabolismus   MeSH
• tretinoin farmakologie   MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Renal cell carcinoma (RCC) is a urologic malignancy with a steady rise in incidence and high mortality rate. Between 60 to 70% of patients with renal cell carcinoma can only be cured with surgery but despite advances in early diagnostis, in around 20-30% of cases there is metastasis. For these patients, chemotherapy and radiotherapy are ineffective and hence the prognosis is poor. Retinoids are biologically active compounds of either natural or synthetic origin that are involved in complex physiological and developmental processes in many tissues including cell proliferation and activation of tumour suppression genes. This article reviews the role of retinoids and their cognate nuclear retinoid/rexinoid receptors in relation to renal cell carcinoma. METHODS: A literature search using ScienceDirect and Medline with a focus on the relationship between renal cell carcinoma and nuclear retinoid/rexinoid receptors. RESULTS: Use of retinoids/rexinoids in the treatment of locally advanced and metastatic RCC significantly prolongs median time of tumour progression and overall survival of patients. Combination therapy with other preparations has greater efficacy than treatment with retinoids alone. Patient survival can be predicted on the basis of the expression of different all-trans retinoic acid receptor (RAR) and 9-cis retinoic acid receptor (RXR) subtypes. CONCLUSIONS: Since nuclear retinoid receptors play a crucial role as ligand-activated, DNA binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes, retinoids might be an alternative approach for the treatment of renal cell carcinoma.

• MeSH
• karcinom z renálních buněk etiologie   MeSH
• lidé MeSH
• nádory ledvin etiologie   MeSH
• receptory cytoplazmatické a nukleární fyziologie   MeSH
• receptory kyseliny retinové fyziologie   MeSH
• retinoidní X receptory fyziologie   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

An attempt has been made to delineate the role of natural and synthetic retinoid receptor ligands on vimentin expression in the human triple-negative breast cancer cells. The effects of currently synthesized triorganotin derivatives of the general formula R3SnX (R is butyl or phenyl, X is isothiocyanate), which are considered RXR ligands, were investigated in the human MDA-MB-231 breast cancer cell line. Studies were evaluated in the presence and absence of all-trans retinoic acid (ATRA), a natural RAR ligand. Vimentin represents the major protein associated with epithelial-mesenchymal transition (EMT), an essential process when the primary tumour transforms into a malignant one. mRNA and proteomic data obtained in this study, based on the PDQuest software protein evaluation and further quantification of proteins by iTRAQ analysis, suggest that vimentin was significantly reduced in the combination of RAR ligand and RXR ligand treatment. Both tested triorganotin compounds showed similarly reduced expression of vimentin, but tributyltin isothiocyanate (TBT-ITC) proved to be more effective than triphenyltin isothiocyanate (TPT-ITC). Furthermore, the effect of natural (9cRA) and synthetic RXR ligands, both chloride and isothiocyanate derivatives, on vimentin expression was compared.

• MeSH
• 2D gelová elektroforéza MeSH
• down regulace MeSH
• epitelo-mezenchymální tranzice účinky léků   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• organocínové sloučeniny farmakologie   MeSH
• proteomika metody   MeSH
• protinádorové látky farmakologie   MeSH
• retinoidní X receptory agonisté   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• tandemová hmotnostní spektrometrie MeSH
• tretinoin farmakologie   MeSH
• trialkylcínové sloučeniny farmakologie   MeSH
• vimentin metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

• MeSH
• acne vulgaris farmakoterapie   MeSH
• aplikace kožní MeSH
• retinoidy farmakologie   analogy a deriváty   MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• farmacie a farmakologie
• dermatovenerologie
• dermatovenerologie

Several commercially available triorganotin compounds were previously found to function as agonist ligands for nuclear retinoid X receptor (RXR) molecules. Triphenyltin isoselenocyanate (TPT-NCSe), a novel selenium atom containing a derivative of triorganotin origin, was found to represent a new cognate bioactive ligand for RXRs. TPT-NCSe displayed a concentration- and time-dependent decrease in the cell viability in both human breast carcinoma MCF-7 (estrogen receptor positive) and MDA‐MB‐231 (triple negative) cell lines. Reactive oxygen species levels generated in response to TPT-NCSe were significantly higher in both carcinoma cell lines treated with TPT-NCSe when compared to mock-treated samples. Treatment with 500 nM TPT-NCSe caused a decrease in SOD1 and increased SOD2 mRNA in MCF-7 cells. The levels of SOD2 mRNA were more increased following the treatment with TPT-NCSe along with 1 μM all-trans retinoic acid (AtRA) in MCF-7 cells. An increased superoxide dismutase SOD1 and SOD2 mRNA levels were also detected in combination treatment of 500 nM TPT-NCSe and 1 μM AtRA in TPT-NCSe-treated MDA-MB-231 cells. The data have also shown that TPT-NCSe induces apoptosis via a caspase cascade triggered by the mitochondrial apoptotic pathway. TPT-NCSe modulates the expression levels of apoptosis‐related proteins, Annexin A5, Bcl‐2 and BAX family proteins, and finally, it enhances the expression levels of its cognate nuclear receptor subtypes RXRalpha and RXRbeta.

• MeSH
• apoptóza účinky léků   MeSH
• lidé MeSH
• ligandy MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory prsu * farmakoterapie   metabolismus   patologie   MeSH
• organocínové sloučeniny * farmakologie   MeSH
• organoselenové sloučeniny farmakologie   chemie   MeSH
• proliferace buněk účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• retinoidní X receptory metabolismus   MeSH
• superoxiddismutasa 1 metabolismus   genetika   MeSH
• superoxiddismutasa metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Retinoids, rexinoids and their biologically active derivatives are involved in a complex arrangement of physiological and developmental responses in many tissues of higher vertebrates. Both retinoids and rexinoids are either natural or synthetic compounds related to retinoic acids that act through interaction with two basic types of nuclear receptors belonging to the nuclear receptor superfamily: All-trans retinoic acid receptors (RARalpha, RARbeta, and RARgamma) and retinoid X receptors (RXRalpha, RXRbeta and RXRgamma) as retinoid-inducible transcription factors. AIM: Summarization of selected effects of biologically active natural or synthetic retinoids and rexinoids and their exploitation in chemoprevention of various types of cancer. RESULTS: Retinoid receptors play a role as ligand-activated, DNA-binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. They exert both beneficial and detrimental activity; they have tumour-suppressive activity but on the other hand they are teratogenic. A number of nuclear receptor selective retinoids and rexinoids, have been successfully tested using a variety of cell lines or animal models. Retinoids inhibit carcinogenesis, suppress premalignant epithelial lesions and tumour growth and invasion in a variety of tissues. CONCLUSIONS: Natural and synthetic retinoids exert important biological effects due to their antiproliferative and apoptosis-inducing effects. They are also known to cause redifferentiation or to prevent further dedifferentiation of various tumour tissues.

• MeSH
• lidé MeSH
• nádory patofyziologie   prevence a kontrola   MeSH
• receptory cytoplazmatické a nukleární fyziologie   MeSH
• receptory kyseliny retinové fyziologie   MeSH
• retinoidní X receptory fyziologie   MeSH
• retinoidy fyziologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH