This is the first histological and molecular analysis of two chondrosarcomas with target-like chondrocytes that were compared with a group of conventional chondrosarcomas and enchondromas. The unique histological feature of target-like chondrocytes is the presence of unusual hypertrophic eosinophilic APAS-positive perichondrocytic rings (baskets). In the sections stained with Safranin O/Fast green, the outer part of the ring was blue and the material in the lacunar space stained orange, similarly to intercellular regions. Immunohistochemical examination showed strong positivity for vimentin, factor XIIIa, cyclin D1, osteonectin, B-cell lymphoma 2 apoptosis regulator (Bcl-2), p53 and p16. The S-100 protein was positive in 25 % of neoplastic cells. Antibodies against GFAP, D2-40 (podoplanin), CD99, CKAE1.3 and CD10 exhibited weak focal positivity. Pericellular rings/baskets contained type VI collagen in their peripheral part, in contrast to the type II collagen in intercellular interterritorial spaces. Ultrastructural examination revealed that pericellular rings contained an intralacunar component composed of microfibrils with abundant admixture of aggregates of dense amorphous non-fibrillar material. The outer extralacunar zone was made up of a layer of condensed thin collagen fibrils with admixture of non-fibrillar dense material. NGS sequencing identified a fusion transcript involving fibronectin 1 (FN1) and fibroblast growth factor receptor 2 (FGFR2) at the RNA level. At the DNA level, no significant variant was revealed except for the presumably germline variant in the SPTA1 gene.

• MeSH
• chondrocyty chemie   patologie   ultrastruktura   MeSH
• chondrosarkom * chemie   diagnóza   patologie   MeSH
• extracelulární matrix chemie   metabolismus   ultrastruktura   MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádory kostí * diagnóza   metabolismus   MeSH
• proteiny S100 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

S100A11 (calgizzarin), a member of S100 family, is associated with several autoimmune diseases, including rheumatoid arthritis (RA). Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of RA and in the externalization of some S100 family members. Therefore, we aimed to determine the association between S100A11 and NETs in RA. For this purpose, the levels of S100A11 and NETosis markers were detected in the RA synovial fluid by immunoassays. The expression of S100A11 by neutrophils in the RA synovial tissue was assessed. Neutrophils isolated from peripheral blood were exposed to S100A11 or stimulated to release NETs. The levels of NETosis- and inflammation-associated proteins were analysed by immunoassays. NETs were visualized by immunofluorescence. We showed that S100A11 was expressed by the neutrophils in the RA synovial tissue. Moreover, S100A11 in the RA synovial fluid correlated with several NETosis markers. In vitro, S100A11 was abundantly released by neutrophils undergoing NETosis compared to untreated cells (p < 0.001). Extracellular S100A11 increased the secretion of IL-6 (p < 0.05) and TNF (p < 0.05) by neutrophils but did not induce NETosis. This study demonstrates, for the first time, that the release of S100A11 is dependent on NETosis and that extracellular S100A11 augments the inflammatory response by inducing pro-inflammatory cytokines in neutrophils.

• MeSH
• dospělí MeSH
• extracelulární pasti metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutrofily metabolismus   patologie   MeSH
• proteiny S100 metabolismus   MeSH
• revmatoidní artritida metabolismus   patologie   MeSH
• senioři MeSH
• synoviální tekutina metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

S100 proteins are involved in the pathogenesis of sporadic colorectal carcinoma through different mechanisms. The aim of our study was to assess tissue mRNA encoding S100 proteins in patients with non-advanced and advanced colorectal adenoma. Mucosal biopsies were taken from the caecum, transverse colon and rectum during diagnostic and/or therapeutic colonoscopy. Another biopsy was obtained from adenomatous tissue in the advanced adenoma group. The tissue mRNA for each S100 protein (S100A4, S100A6, S100A8, S100A9, S100A11 and S100P) was investigated. Eighteen biopsies were obtained from the healthy mucosa in controls and the non-advanced adenoma group (six individuals in each group) and thirty biopsies in the advanced adenoma group (ten patients). Nine biopsies were obtained from advanced adenoma tissue (9/10 patients). Significant differences in mRNA investigated in the healthy mucosa were identified between (1) controls and the advanced adenoma group for S100A6 (p = 0.012), (2) controls and the non-advanced adenoma group for S100A8 (p = 0.033) and (3) controls and the advanced adenoma group for S100A11 (p = 0.005). In the advanced adenoma group, differences between the healthy mucosa and adenomatous tissue were found in S100A6 (p = 0.002), S100A8 (p = 0.002), S100A9 (p = 0.021) and S100A11 (p = 0.029). Abnormal mRNA expression for different S100 proteins was identified in the pathological adenomatous tissue as well as in the morphologically normal large intestinal mucosa.

• MeSH
• adenom genetika   metabolismus   patologie   MeSH
• kalgranulin A genetika   metabolismus   MeSH
• kalgranulin B genetika   metabolismus   MeSH
• kolorektální nádory genetika   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové proteiny genetika   metabolismus   MeSH
• následné studie MeSH
• pilotní projekty MeSH
• prognóza MeSH
• protein S100A6 genetika   metabolismus   MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• proteiny S100 genetika   metabolismus   MeSH
• proteiny vázající vápník genetika   metabolismus   MeSH
• S100 kalcium vázající protein A4 genetika   metabolismus   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Interleukin-1α (IL-1α) and Annexin A2 (AnxA2) are pleiotropic molecules with both intracellular and extracellular roles. They share several characteristics including unconventional secretion aided by S100 proteins, anchoring of the externalized proteins at the outer surface of the plasma membrane and response to oxidative stress. Although IL-1α and AnxA2 have been implicated in a variety of biological processes, including cancer, little is known about the mechanisms of their cellular release. In the present study, employing the non-cancerous breast epithelial MCF10A cells, we demonstrate that IL-1α and AnxA2 establish a close association in response to oxidative stress. Stress conditions lead to translocation of both proteins towards lamellipodia rich in vimentin and association of full-length IL-1α and Tyr23 phosphorylated AnxA2 with the plasma membrane at peripheral sites depleted of F-actin. Notably, membrane-associated IL-1α and AnxA2 preferentially localize to the outer edges of the MCF10A cell islands, suggesting that the two proteins participate in the communication of these epithelial cells with their neighboring cells. Similarly, in U2OS osteosarcoma cell line both endogenous IL-1α and transiently produced IL-1α/EGFP associate with the plasma membrane. While benign MFC10A cells present membrane-associated IL-1α and AnxA2 at the edges of their cell islands, the aggressive cancerous U2OS cells communicate in such manner also with distant cells.

• MeSH
• aktiny metabolismus   MeSH
• annexin A2 metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• epitelové buňky metabolismus   MeSH
• fosforylace fyziologie   MeSH
• interleukin-1alfa metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• oxidační stres fyziologie   MeSH
• proteiny S100 metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Molecular determinants of the binding of various endogenous modulators to transient receptor potential (TRP) channels are crucial for the understanding of necessary cellular pathways, as well as new paths for rational drug designs. The aim of this study was to characterise interactions between the TRP cation channel subfamily melastatin member 4 (TRPM4) and endogenous intracellular modulators-calcium-binding proteins (calmodulin (CaM) and S100A1) and phosphatidylinositol 4, 5-bisphosphate (PIP2). We have found binding epitopes at the N- and C-termini of TRPM4 shared by CaM, S100A1 and PIP2. The binding affinities of short peptides representing the binding epitopes of N- and C-termini were measured by means of fluorescence anisotropy (FA). The importance of representative basic amino acids and their combinations from both peptides for the binding of endogenous TRPM4 modulators was proved using point alanine-scanning mutagenesis. In silico protein-protein docking of both peptides to CaM and S100A1 and extensive molecular dynamics (MD) simulations enabled the description of key stabilising interactions at the atomic level. Recently solved cryo-Electron Microscopy (EM) structures made it possible to put our findings into the context of the entire TRPM4 channel and to deduce how the binding of these endogenous modulators could allosterically affect the gating of TRPM4. Moreover, both identified binding epitopes seem to be ideally positioned to mediate the involvement of TRPM4 in higher-order hetero-multimeric complexes with important physiological functions.

• MeSH
• akvaporiny chemie   metabolismus   MeSH
• interakční proteinové domény a motivy * MeSH
• kalmodulin chemie   metabolismus   MeSH
• kationtové kanály TRPM chemie   metabolismus   MeSH
• kinetika MeSH
• konformace proteinů MeSH
• lidé MeSH
• molekulární modely MeSH
• multiproteinové komplexy chemie   metabolismus   MeSH
• peptidové fragmenty MeSH
• proteiny S100 chemie   metabolismus   MeSH
• sekvence aminokyselin MeSH
• vazba proteinů MeSH
• vazebná místa * MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: S100A11 (calgizzarin), a member of the S100 family, is associated with oncogenesis, inflammation and myocardial damage. Our aim was to analyse S100A11 in idiopathic inflammatory myopathies (IIMs) and its association with disease activity features and cancer development. METHODS: S100A11 in muscle was determined by immunohistochemistry in polymyositis (PM), dermatomyositis (DM), myasthenia gravis (MG) and in subjects without autoimmune inflammatory disease (HC). S100A11 in plasma was measured in 110 patients with IIMs (PM, DM, and cancer associated myositis (CAM) patients) and in 42 HC. Disease activity was assessed by myositis disease activity assessment (MYOACT), muscle enzymes and C-reactive protein (CRP) were measured by routine laboratory techniques; autoantibodies by immunoprecipitation or by immunoblot. RESULTS: We observed an accumulation of S100A11 in the cytoplasm of regenerating and necrotizing muscle fibres of PM and DM patients. S100A11 was increased in plasma of all myositis patients compared to HC (3.8 (1.5-16.8) vs 2.8 (1.7-11.2)ng/ml, p=0.011) and in DM and CAM patients compared to HC (4.0 (2.2-14.9) and 4.5 (1.5-9.1) vs 2.8 (1.7-11.2)ng/ml, p<0.001 and p=0.022, respectively). In all myositis patients, S100A11 correlated with the levels of lactate dehydrogenase (r=0.256, p=0.011), aspartate aminotransferase (AST) (r=0.312, p=0.002), CRP (r=0.254, p=0.022) and MYOACT (r=0.245, p=0.022). S100A11 was associated with MYOACT (r=0.377, p=0.030) and pulmonary and cutaneous disease activity in DM patients (r=0.408, p=0.017 and r=0.417, p=0.01, respectively). S100A11 was related to the levels of AST (r=0.412, p=0.027) in PM and to the levels of creatine phosphokinase (r=0.432, p=0.028) in CAM patients. CONCLUSIONS: We show for a first time a potential implication of S100A11 in the local inflammatory and tissue remodelling processes in myositis and an association of circulating S100A11 with disease activity and extra muscular manifestations in DM. Copyright © 2019 Elsevier Ltd. All rights reserved.

• MeSH
• autoimunitní nemoci imunologie   patologie   MeSH
• autoprotilátky imunologie   MeSH
• C-reaktivní protein analýza   MeSH
• dospělí MeSH
• kosterní svalová vlákna * patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymyozitida * imunologie   patologie   MeSH
• proteiny S100 * metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

Histological, immunohistochemical and molecular examination of bioptic samples of 30 normal adult auricular cartilages and small samples from 6 ear cartilages from aborted foetuses was performed. The adult cartilage was the tissue with minimal proliferative activity, which we were able to confirm with antibodies against Ki67 in contrast to a high proliferative activity in the auricular cartilage of foetal tissues. It may therefore be presumed that the process of foetal tissue maturation is undoubtedly associated with a significant reduction in proliferative activity. The mature lamella of the adult auricular cartilage has a histological tri-lamellar structure. There are a great number of elastic fibres in the intercellular matrix of the central zone, which are conversely present in only small amounts in both peripheral layers. While the external layer of the concave surface of the cartilage contains a fewer number of oval elements, the external layer of the convex side is composed of numerous fusiform chondrocytes. Antibodies against various subtypes of S-100 protein showed that auricular chondrocyte activity is modified depending on the configuration of individual distinct zones (isoforms A1, A6, B2 and P were positive in all layers, isoforms A2 and A2 in peripheral zones). The most active cells metabolically are most likely chondrocytes in both external layers adjacent to the perichondrium. We have also demonstrated α-smooth muscle actin (SMA)-positive chondrocytes in both peripheral layers of the auricular cartilage adjacent to the perichondrium. In addition, we found definite differences in the distribution of actin-positive cells depending on the external shape of the pinna. The majority of these fusiform cells were localised primarily in the areas of great curvature of the pinna, especially the convex side, as mentioned above. On the basis of these unique structural features we assume that the ear cartilage may embody an example of the socalled intelligent biological material, which has its internal structure made in such a way as to more easily develop and yet still maintain all the shape characteristics of the human auricle. The knowledge of these specific structural characteristics is important especially for use of auricular cartilage in auricular reconstruction.

• MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé MeSH
• plod cytologie   MeSH
• posmrtné změny MeSH
• proteiny S100 metabolismus   MeSH
• ušní chrupavka cytologie   embryologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Secretory carcinoma (SC) of salivary glands is a newly described low-grade malignancy characterized by the presence of ETV6 rearrangement. Only a few cases and very small series with cytomorphology were reported so far. Six cases of fine-needle aspirations (FNAs) from afterward histologically, immunohistochemically and genetically confirmed SCs were retrieved from the archives of the authors. Ancillary immunocytochemistry (ICC) and translocation detection were performed on cell blocks (CBs). All aspirates were sufficiently cellular and cells were arranged in more or less cohesive groups with only mild nuclear polymorphism. The cytoplasm was eosinophilic, granulated and vacuolated, especially in CBs. Secretory material within the microcystic spaces was periodic acid-Schiff (PAS) positive. Triple positivity of immunomarkers S-100 protein, mammaglobin and vimentin was present. The proliferation index was low. Ancillary techniques suggested the possibility of SC in a few cytology cases; nevertheless, the final diagnosis was based on histomorphology, immunohistochemistry and genetics. The SC of salivary glands is detectable pre-operatively using ICC and genetics. The presence of the diagnostic ETV6 rearrangement increases the accuracy of FNA to the maximum. According to the Milan system, cases genetically not confirmed should be categorized as Suspicious for Malignancy or Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP), both requiring surgery.

• MeSH
• cytodiagnostika metody   MeSH
• dospělí MeSH
• imunohistochemie metody   MeSH
• karcinom diagnóza   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory slinných žláz diagnóza   metabolismus   patologie   MeSH
• proteiny S100 metabolismus   MeSH
• protoonkogenní proteiny c-ets metabolismus   MeSH
• represorové proteiny metabolismus   MeSH
• senioři MeSH
• slinné žlázy metabolismus   patologie   MeSH
• tenkojehlová biopsie metody   MeSH
• vimentin metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We report a case of a 35-year old male patient with a tumor located in the deep dermis on his forearm. The lesion was completely excised but recurred 4 years later. The patient showed no signs of neurofibromatosis type 1. The morphology and immunophenotype of the tumor corresponded to the recently characterized group of soft tissue spindle cell lesions defined by a relatively uniform cytomorphology, patternless architecture, conspicuous stromal and perivascular hyalinization, S100 and CD34 coexpression and recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Using a 592-gene panel and massively parallel next-generation sequencing platform, we initially detected only NF1 gene mutation in our case. However, further molecular testing with Archer fusion assay revealed a novel NCOA4-RET gene fusion, adding it to the list of multiple kinase fusions originally reported in these tumors. Although break-apart FISH showed false negative result due to the presence of intrachromosomal rearrangement, RT-PCR confirmed the fusion transcript. Knowing the exact fusion is of great clinical importance especially for patients within the aggressive subset of these neoplasms that could be treated with selective kinase inhibitors. The presented case underscores the benefits of massively parallel sequencing as the types and number of gene fusions these tumors can potentially harbor render single-gene assays such as FISH impractical, and in this particular case, also insensitive.

• MeSH
• antigeny CD34 genetika   metabolismus   MeSH
• dospělí MeSH
• hyalin metabolismus   MeSH
• koaktivátory jaderných receptorů genetika   metabolismus   MeSH
• lidé MeSH
• mutace MeSH
• nádory měkkých tkání genetika   patologie   MeSH
• neurofibromin 1 genetika   MeSH
• onkogenní fúze * MeSH
• proteiny S100 genetika   metabolismus   MeSH
• protoonkogenní proteiny c-ret genetika   metabolismus   MeSH
• škára metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• lidé MeSH
• proteiny S100 * metabolismus   MeSH
• systémový lupus erythematodes * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH