• Klíčová slova
• resmetirom,
• MeSH
• jaterní cirhóza farmakoterapie   MeSH
• lidé MeSH
• nealkoholová steatóza jater * farmakoterapie   patologie   MeSH
• pyridaziny MeSH
• tyreoidální hormony, receptory beta agonisté   MeSH
• uracil analogy a deriváty   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• souhrny MeSH

A focal adenomatoid-microcystic pattern is not uncommon in peritoneal mesothelioma, but tumors composed almost exclusively of this pattern are distinctly rare and have not been well characterized. A small subset of mesotheliomas (mostly in children and young adults) are characterized by gene fusions including EWSR1/FUS::ATF1, EWSR1::YY1, and NTRK and ALK rearrangements, and often have epithelioid morphology. Herein, we describe five peritoneal mesothelial neoplasms (identified via molecular screening of seven histologically similar tumors) that are pure adenomatoid/microcystic in morphology and unified by the presence of an NR4A3 fusion. Patients were three males and two females aged 31-70 years (median, 40 years). Three presented with multifocal/diffuse and two with a localized disease. The size of the individual lesions ranged from 1.5 to 8 cm (median, 4.7). The unifocal lesions originated in the small bowel mesentery and the mesosigmoid. Treatment included surgery, either alone (three) or combined with hyperthermic intraperitoneal chemotherapy (two), and neoadjuvant or adjuvant chemotherapy (one case each). At the last follow-up (6-13 months), all five patients were alive and disease-free. All tumors were morphologically similar, characterized by extensive sieve-like microcystic growth with bland-looking flattened cells lining variably sized microcystic spaces and lacked a conventional epithelioid or sarcomatoid component. Immunohistochemistry confirmed mesothelial differentiation, but most cases showed limited expression of D2-40 and calretinin. Targeted RNA sequencing revealed an NR4A3 fusion (fusion partners were EWSR1 in three cases and CITED2 and NIPBL in one case each). The nosology and behavior of this morphomolecularly defined novel peritoneal mesothelial neoplasm of uncertain biological potential and its distinction from adenomatoid variants of conventional mesothelioma merit further delineation as more cases become recognized.

• MeSH
• adenom * MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• fúze genů MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezenterium patologie   MeSH
• mezoteliom * genetika   MeSH
• nádorové biomarkery genetika   MeSH
• peritoneální nádory * genetika   patologie   MeSH
• proteiny buněčného cyklu genetika   MeSH
• receptory thyreoidních hormonů genetika   MeSH
• represorové proteiny genetika   MeSH
• senioři MeSH
• steroidní receptory * genetika   MeSH
• trans-aktivátory genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain lineage. Insulinoma-associated protein 1 (INSM1) has recently been described as a highly specific and sensitive immunohistochemical marker for EMC. The goal of this study was to evaluate the diagnostic significance of INSM1 immunohistochemistry in EMC. Furthermore, correlations between molecular and morphological findings were performed. Sixteen of 17 EMC cases were stained with the INSM1 antibody. Tumors with at least 5% INSM1-positive cells and any staining intensity were considered positive. Molecular testing was successfully performed in 12/17 cases. The immunohistochemical analysis detected 13 INSM1-positive (81%) and 3 INSM1-negative tumors (19%). The extent of the staining was classified as 1+ in 7 cases (44%), 2+ in 2 cases (13%), 3+ in 2 cases (13%) and 4+ in 2 cases (13%). Intensity of immunostaining was weak in 5 cases (31%), moderate in 2 cases (13%) and strong in 6 cases (38%). Molecular assays revealed 8 EWSR1::NR4A3 positive tumors (67%), 2 TAF15::NR4A3 positive tumors (17%), 1 TCF12::NR4A3 positive tumor (8%) and 1 NR4A3 positive tumor (8%) in which no other gene alteration was identified. Two of them, namely TCF12 positive and one TAF15 positive tumors, were highly cellular and partially associated with pseudopapillary architecture. Our study found that moderate/strong expression of INSM1 in more than 25% of tumor cells was present in only 31% of cases. Thus, the diagnostic utility of INSM1 is rather low. Two morphologically unique cases of non-EWSR1 rearranged EMC with an extremely rare pseudopapillary growth pattern are also reported.

• MeSH
• chondrosarkom * diagnóza   genetika   MeSH
• DNA vazebné proteiny genetika   MeSH
• fúzní onkogenní proteiny genetika   metabolismus   MeSH
• lidé MeSH
• nádory z pojivové a měkké tkáně * genetika   MeSH
• receptory thyreoidních hormonů genetika   MeSH
• represorové proteiny genetika   MeSH
• sarkom * genetika   MeSH
• steroidní receptory * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Acinic cell carcinoma (AciCC) is a common salivary gland malignancy, typically composed of neoplastic acinic cells with zymogen granules. The vast majority of cases are driven by a t(4;9)(q13;q31) leading to enhancer hijacking and upregulation of the NR4A3 gene. However, a minority of cases do not display NR4A3 overexpression on immunohistochemical examination and are negative for the rearrangement involving the NR4A3 gene when tested by FISH. Such cases overexpress NR4A2, and the protein product is detectable by immunohistochemistry. In this study, we aimed to assess the utility of NR4A2 and NR4A3 immunohistochemistry in the differential diagnosis of salivary gland tumors. Eighty-five cases of classic low-grade ACiCC, as well as 36 cases with high-grade transformation (HGT) and 7 high-grade AciCC cases were included in the analysis. NR4A3 was at least focally positive in 105/128 (82%) cases. Out of the 23 cases that were immunohistochemically negative for NR4A3, 6 displayed nuclear immunopositivity with the NR4A2 antibody. The NR4A3 rearrangement was confirmed by FISH in 38/52 (73%) cases. In addition, this is the first report of an NR4A2 rearrangement being detected by FISH in 2 AciCC cases that were negative for the NR4A3 rearrangement. Our analysis confirms that the majority of AciCC, including high-grade cases and cases with HGT, are immunopositive for NR4A3, and suggests that NR4A3 immunohistochemistry is a powerful tool in the differential diagnosis of salivary gland tumors. However, its utility is limited in sub-optimally fixed samples which often display weaker and focal positivity. Our study also indicates that in a minority of cases, AciCC might be negative for NR4A3 immunostaining, because the pathogenic genetic event in these cases is instead a rearrangement involving the NR4A2 gene.

• MeSH
• acinární karcinom * diagnóza   genetika   metabolismus   MeSH
• buněčné jádro patologie   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• imunohistochemie MeSH
• jaderné receptory - podrodina 4, skupina A, člen 2 metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinných žláz * diagnóza   genetika   patologie   MeSH
• receptory thyreoidních hormonů metabolismus   MeSH
• slinné žlázy patologie   MeSH
• steroidní receptory * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

• MeSH
• androgenní receptory genetika   metabolismus   MeSH
• buňky PC-3 MeSH
• cholin aplikace a dávkování   analogy a deriváty   MeSH
• čipová analýza tkání MeSH
• down regulace * MeSH
• kohortové studie MeSH
• krystaliny genetika   metabolismus   MeSH
• lidé MeSH
• metabolomika MeSH
• nádorové buněčné linie MeSH
• nádory prostaty diagnostické zobrazování   genetika   metabolismus   patologie   MeSH
• PET/CT MeSH
• prognóza MeSH
• receptory thyreoidních hormonů genetika   MeSH
• regulace genové exprese u nádorů MeSH
• sekvenční analýza RNA MeSH
• signální transdukce * MeSH
• staging nádorů MeSH
• stanovení celkové genové exprese MeSH
• trijodthyronin antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Neural stem cells are fundamental to development of the central nervous system (CNS)-as well as its plasticity and regeneration-and represent a potential tool for neuro transplantation therapy and research. This study is focused on examination of the proliferation dynamic and fate of embryonic neural stem cells (eNSCs) under differentiating conditions. In this work, we analyzed eNSCs differentiating alone and in the presence of sonic hedgehog (SHH) or triiodothyronine (T3) which play an important role in the development of the CNS. We found that inhibition of the SHH pathway and activation of the T3 pathway increased cellular health and survival of differentiating eNSCs. In addition, T3 was able to increase the expression of the gene for the receptor smoothened (Smo), which is part of the SHH signaling cascade, while SHH increased the expression of the T3 receptor beta gene (Thrb). This might be the reason why the combination of SHH and T3 increased the expression of the thyroxine 5-deiodinase type III gene (Dio3), which inhibits T3 activity, which in turn affects cellular health and proliferation activity of eNSCs.

• MeSH
• jodidperoxidasa genetika   metabolismus   MeSH
• kultivované buňky MeSH
• myší embryonální kmenové buňky cytologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nervové kmenové buňky cytologie   metabolismus   MeSH
• neurogeneze * MeSH
• proteiny hedgehog genetika   metabolismus   MeSH
• receptor Smoothened genetika   metabolismus   MeSH
• trijodthyronin metabolismus   MeSH
• tyreoidální hormony, receptory beta genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Recently, we discovered the recurrent genomic rearrangement [t(4;9)(q13;q31)] enabling upregulation of the transcription factor Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) through enhancer hijacking as the oncogenic driver event in acinic cell carcinoma (AciCC) of the salivary glands. In the current study, we evaluated the usefulness of NR4A3 immunostaining and NR4A3 fluorescence in situ hybridization (FISH) in the differential diagnosis of AciCC, comparing a total of 64 AciCCs including 17% cases with high-grade transformation, 29 secretory (mammary analog) carcinomas (MASC), and 70 other salivary gland carcinomas. Nuclear NR4A3 immunostaining was a highly specific (100%) and sensitive (98%) marker for AciCC with only 1 negative case, whereas NR4A3 FISH was less sensitive (84%). None of the MASCs or other salivary gland carcinomas displayed any nuclear NR4A3 immunostaining. The recently described HTN3-MSANTD3 gene fusion was observed in 4 of 49 (8%) evaluable AciCCs, all with nuclear NR4A3 immunostaining. In summary, NR4A3 immunostaining is a highly specific and sensitive marker for AciCC, which may be especially valuable in cases with high-grade transformation and in "zymogen granule"-poor examples within the differential diagnostic spectrum of AciCC and MASC.

• MeSH
• acinární karcinom diagnóza   MeSH
• diferenciální diagnóza MeSH
• DNA vazebné proteiny analýza   biosyntéza   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové biomarkery analýza   MeSH
• nádory slinných žláz diagnóza   MeSH
• receptory thyreoidních hormonů analýza   biosyntéza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• steroidní receptory analýza   biosyntéza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We developed and characterized a novel human luciferase reporter cell line for the assessment of peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity, PAZ-PPARg. The luciferase activity induced by PPARγ endogenous agonist 15d-PGJ2 and prostaglandin PGD2 reached mean values of (87.9 ± 14.0)-fold and (89.6 ± 19.7)-fold after 24 h of exposure to 40 μM 15d-PGJ2 and 70 μM PGD2, respectively. A concentration-dependent inhibition of 15d-PGJ2- and PGD2-induced luciferase activity was observed after the application of T0070907, a selective antagonist of PPARγ, which confirms the specificity of response to both agonists. The PAZ-PPARg cell line, along with the reporter cell lines for the assessment of transcriptional activities of thyroid receptor (TR), vitamin D3 receptor (VDR), androgen receptor (AR), and glucocorticoid receptor (GR), were used for the screening of 27 commonly marketed flavored nonalcoholic beverages for their possible disrupting effects. Our findings indicate that some of the examined beverages have the potential to modulate the transcriptional activities of PPARγ, VDR, and AR.

• MeSH
• aktivace transkripce účinky léků   MeSH
• androgenní receptory genetika   metabolismus   MeSH
• buněčné linie MeSH
• chuťové esence škodlivé účinky   farmakologie   MeSH
• lidé MeSH
• nápoje škodlivé účinky   analýza   MeSH
• PPAR gama genetika   metabolismus   MeSH
• prostaglandin D2 farmakologie   MeSH
• receptory glukokortikoidů genetika   metabolismus   MeSH
• receptory kalcitriolu genetika   metabolismus   MeSH
• receptory thyreoidních hormonů genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Hypotyreóza je u pacientů se srdečním onemocněním častým nálezem. Je rizikovým faktorem aterosklerózy a ischemické choroby srdeční a má přímý negativní vliv na funkci levé i pravé srdeční komory (hypotyreózní kardio­myopatie). Potvrzená manifestní hypotyreóza je vždy důvodem k substituční léčbě levotyroxinem; u pacientů se srdečním onemocněním vždy začínáme léčbu malou dávku a zvyšujeme postupně. Léčba subklinické hypotyreózy je u pacientů se srdečním onemocněním kontroverzní a její benefity pravděpodobně závisí na věku. Ve vyšším věku často rizika léčby převáží, a proto se raději spokojíme s cílovými hodnotami tyreoidálního stimulačního hormonu v horním pásmu normálního rozmezí, nebo i lehce nad ním, než abychom pacienta předávkovali. Velmi zjednodušeně lze říci, že léčba subklinické hypotyreózy u pacientů se srdečním onemocněním je nejefektivnější u mladších osob, zejména < 65 let, zatímco ve vyšším věku > 80 let již riziko obvykle převyšuje benefit.

Hypothyroidism is frequently found in patients with heart disease. It is a risk factor for atherosclerosis and ischemic heart disease and has a direct negative effect on both the left and right ventricular functions (hypothyroidism-induced cardiomyopathy). The confirmed manifest hypothyroidism is always a reason for replacement therapy with levothyroxine; regarding patients with heart disease, we always begin treatment with a small dose and increase it gradually. The treatment of subclinical hypothyroidism in patients with heart disease is disputable and its benefits probably depend on age. At a higher age, the therapy-related risks often outweigh its benefits, so we make do with the target levels of the thyroid stimulating hormone being within the upper band of the normal range, or even slightly above it, rather than overdosing the patient. To summarize in a simplified way, the treatment of subclinical hypothyroidism in patients with heart disease is the most effective in younger individuals, mainly those aged below 65, while at a higher age > 80 years the risk usually outweighs the benefit.

• MeSH
• dysfunkce levé srdeční komory MeSH
• dysfunkce pravé srdeční komory MeSH
• hypotyreóza * diagnóza   etiologie   farmakoterapie   MeSH
• ischemická choroba srdeční MeSH
• jodidperoxidasa MeSH
• kardiomyopatie MeSH
• kardiovaskulární nemoci * MeSH
• komorbidita MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• receptory thyreoidních hormonů MeSH
• rizikové faktory MeSH
• thyreotropin analýza   MeSH
• thyroxin aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Nodulární fasciitis je způsobena nenádorovu proliferací fibroblastů a myofibroblastů v podkožním vazivu a hluboké fascii. Svým klinickým i histopatologickým vzhledem může imitovat maligní proces. Autoři popisují případ nodulární fasciitidy na stehně u 26leté pacientky v 6. týdnu gravidity. Diagnóza byla stanovena na základě histologického vyšetření. Po provedení probatorní excize došlo k postupné regresi ložiska bez jakékoliv další léčby. Článek poskytuje stručný přehled současných poznatků o tomto vzácném onemocnění.

Nodular fasciitis is caused by non-tumorous proliferation of fibroblasts and myofibroblasts in subcutaneous tissue and deep fascia. It can mimic a malignant process through its clinical and histopathological appearance. The authors describe a case of nodular fasciitis on the thigh of a 26-year old patient in the 6th week of pregnancy. The diagnosis was based on histopathological examination. The tumor gradually disappeared after diagnostic excision without need of other treatment. The article briefly summarizes a recent knowledge on this rare disease.

• Klíčová slova
• nodulární fasciitis,
• MeSH
• biochemická analýza krve MeSH
• dospělí MeSH
• fasciitida diagnóza   terapie   MeSH
• fibrom diagnóza   terapie   MeSH
• hypotyreóza MeSH
• komplikace těhotenství MeSH
• lidé MeSH
• receptory thyreoidních hormonů MeSH
• stehno abnormality   anatomie a histologie   patologie   MeSH
• thyroxin terapeutické užití   MeSH
• výsledek terapie MeSH
• vzácné nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH