Myoepithelial neoplasms of the skin and soft tissue still represent a confusing and somewhat controversial field in pathology as it appears that this category includes several different entities. However, recent studies have suggested that both apocrine mixed tumors (AMT) and cutaneous myoepitheliomas (CM) harbor identical chromosomal rearrangements involving the PLAG1 gene and hence may represent a morphological spectrum. The aim of the present study was to share our institutional experience with these tumors and specifically focus on studying their immunohistochemical and molecular features to further assess their relatedness. Eleven cases of AMT and 7 cases of CM were collected and analyzed using immunohistochemistry (IHC), PLAG1 FISH, and Archer FusionPlex assay. There were 14 male and 4 female patients with ages ranging from 26 to 85 years (median 55.8 years, mean 58.5 years). AMTs were mainly located in the head and neck (n = 10), while CMs were mainly located in the acral sites (n = 5). PLAG1 IHC was diffusely strongly positive in 14/17 (82%) cases, whereas a single case of AMT diffusely expressed HMGA2. Both tumor groups showed PLAG1 gene fusions which were detected in 6/13 analyzable samples (AMT, n = 4 and CM, n = 2), and included TRPS1::PLAG1 (n = 3), NDRG1::PLAG1 (n = 1), CTNNB1::PLAG1 (n = 1) and a novel PXDNL::PLAG1 fusion (n = 1). The remaining 5 cases were negative, 5 were not analyzable and the single case positive for HMGA2 by IHC revealed a potential HMGA2 gene rearrangement. The cases were further studied by FISH, with 12/17 cases showing PLAG1 gene rearrangement (AMT, n = 8 and CM, n = 4). Altogether, 14/18 cases showed PLAG1 gene rearrangement by at least one of the methods. PLAG1 immunohistochemistry had a 92% specificity and sensitivity. Our study provided additional data to suggest that AMT and CM share overlapping morphological and immunohistochemical features as well as molecular background characterized by PLAG1 gene fusions and thus represent a morphological spectrum. In addition, we identified a novel PXDNL::PLAG1 fusion and suggested that rare cases may harbor HMGA2 gene alterations which seem to be mutually exclusive with PLAG1 gene fusions. The relatedness of these tumors to salivary gland myoepithelial neoplasms and distinctness from eccrine mixed tumors and other skin and soft tissue myoepithelial neoplasms with EWSR1/FUS fusions is discussed.
- MeSH
- DNA-Binding Proteins * genetics MeSH
- Adult MeSH
- Gene Rearrangement * MeSH
- In Situ Hybridization, Fluorescence MeSH
- Immunohistochemistry * MeSH
- Middle Aged MeSH
- Humans MeSH
- Myoepithelioma * genetics pathology MeSH
- Biomarkers, Tumor * genetics analysis MeSH
- Neoplasms, Complex and Mixed genetics pathology chemistry MeSH
- Skin Neoplasms * genetics pathology MeSH
- Sweat Gland Neoplasms genetics pathology MeSH
- HMGA2 Protein * genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
The widely distributed ray-finned fish genus Carassius is very well known due to its unique biological characteristics such as polyploidy, clonality, and/or interspecies hybridization. These biological characteristics have enabled Carassius species to be successfully widespread over relatively short period of evolutionary time. Therefore, this fish model deserves to be the center of attention in the research field. Some studies have already described the Carassius karyotype, but results are inconsistent in the number of morphological categories for individual chromosomes. We investigated three focal species: Carassius auratus, C. carassius and C. gibelio with the aim to describe their standardized diploid karyotypes, and to study their evolutionary relationships using cytogenetic tools. We measured length (q+plength) of each chromosome and calculated centromeric index (i value). We found: (i) The relationship between q+plength and i value showed higher similarity of C. auratus and C. carassius. (ii) The variability of i value within each chromosome expressed by means of the first quartile (Q1) up to the third quartile (Q3) showed higher similarity of C. carassius and C. gibelio. (iii) The fluorescent in situ hybridization (FISH) analysis revealed higher similarity of C. auratus and C. gibelio. (iv) Standardized karyotype formula described using median value (Q2) showed differentiation among all investigated species: C. auratus had 24 metacentric (m), 40 submetacentric (sm), 2 subtelocentric (st), 2 acrocentric (a) and 32 telocentric (T) chromosomes (24m+40sm+2st+2a+32T); C. carassius: 16m+34sm+8st+42T; and C. gibelio: 16m+22sm+10st+2a+50T. (v) We developed R scripts applicable for the description of standardized karyotype for any other species. The diverse results indicated unprecedented complex genomic and chromosomal architecture in the genus Carassius probably influenced by its unique biological characteristics which make the study of evolutionary relationships more difficult than it has been originally postulated.
- MeSH
- Chromosomes genetics MeSH
- Diploidy MeSH
- Phylogeny MeSH
- Genetic Variation genetics MeSH
- Genome genetics MeSH
- In Situ Hybridization, Fluorescence methods MeSH
- Carps genetics MeSH
- Goldfish genetics MeSH
- Karyotype MeSH
- Karyotyping methods MeSH
- Chromosome Mapping methods MeSH
- Polyploidy MeSH
- Fishes genetics MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Hereditární nádorové syndromy s možnou manifestací v oblasti ženského vnitřního genitálu představují heterogenní skupinu onemocnění. Mezi dva nejčastější syndromy patří syndrom hereditárního karcinomu prsu a ovarií a Lynchův syndrom. Méně časté syndromy zahrnují syndrom predispozice k maligním rabdoidním nádorům, Cowdenův syndrom, komplex tuberózní sklerózy, DICER1 syndrom, syndrom névoidního bazocelulárního karcinomu, Peutz-Jeghersův syndrom, von Hippelova-Lindauova choroba a syndrom hereditární leiomyomatózy a renálního karcinomu. Cílem následujícího sdělení je podat přehled problematiky hereditárních nádorových syndromů s manifestací v oblasti ženského genitálu se zaměřením na jejich přehled, charakteristiky nádorů, které se v souvislosti s jednotlivými syndromy vyskytují, postup při vyšetřování profylakticky odstraněných tkání a orgánů a problematiku screeningu Lynchova syndromu.
Hereditary tumor syndromes with a possible manifestation in the female internal genital tract represent a heterogeneous group of diseases. The two most common entities are the hereditary breast and ovarian cancer syndrome, and the Lynch syndrome. The less common syndromes include the rhabdoid tumor predisposition syndrome, Cowden syndrome, tuberous sclerosis complex, DICER1 syndrome, nevoid basal cell carcinoma syndrome, Peutz-Jeghers syndrome, von Hippel-Lindau disease, and hereditary leiomyomatosis and renal cell cancer syndrome. The goal of this manuscript is to provide a comprehensive overview of those hereditary tumor syndromes which can manifest in the area of the female genital system, with an emphasis on their summary, the characteristics of the tumors which can develop in association with these syndromes, and the approach to the processing of prophylactically removed tissues and organs. The issue of Lynch syndrome screening is also discussed.
- MeSH
- Neoplastic Syndromes, Hereditary * diagnosis genetics MeSH
- Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis genetics MeSH
- Hereditary Breast and Ovarian Cancer Syndrome * diagnosis genetics MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Testing MeSH
- Immunohistochemistry MeSH
- Humans MeSH
- Mutation genetics MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The aim of this study was to compare the antibacterial mode of action of silver ions (Ag+) and selected silver nanoformulations against E. coli strains (E. coli J53, Escherichia coli BW25113 and its derivatives: Δ ompA, Δ ompC, Δ ompF, Δ ompR, ompRG596AcusSG1130A, cusSG1130A). In this research we used various experimental methods and techniques such as determination of the minimal inhibitory concentration, flow cytometry, scanning electron microscopy, circular dichroism as well as computational methods of theoretical chemistry. Thanks to the processing of bacteria and silver samples (ions and nanoformulations), we were able to determine the bacterial sensitivity to silver samples, detect reactive oxygen species (ROS) in the bacterial cells, visualize the interaction of silver samples with the bacterial cells, and identify their interactions with proteins. Differences between the mode of action of silver ions and nanoformulations and the action of nanoformulations themselves were revealed. Based on the results of computational methods, we proposed an explanation of the differences in silver-outer protein interaction between silver ions and metallic silver; in general, the Ag0 complexes exhibit weaker interaction than Ag+ ones. Moreover, we identified two gutter-like areas of the inner layer of the ion channel: one more effective, with oxygen-rich side chains; and another one less effective, with nitrogen-rich side chains.
- Publication type
- Journal Article MeSH
In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.
- MeSH
- Acromegaly complications genetics metabolism MeSH
- Biomarkers MeSH
- Adult MeSH
- Immunohistochemistry MeSH
- Cadherins genetics MeSH
- Clinical Decision-Making MeSH
- Combined Modality Therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Disease Management MeSH
- Young Adult MeSH
- Pituitary Neoplasms diagnosis etiology therapy MeSH
- Prognosis MeSH
- Protein Isoforms MeSH
- Receptors, Somatostatin genetics metabolism MeSH
- Gene Expression Regulation * MeSH
- ROC Curve MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Two silver(I) aminoacidate complexes {[Ag4(L-HAla)4(NO3)3]NO3}n (AgAla, complex 1, Ala = alanine) and {[Ag(L-Phe)]}n (AgPhe, complex 2, Phe = phenylalanine) were prepared and characterized by elemental, spectral analysis (FT-IR, NMR techniques) and single crystal X-ray analysis in solid state and their solution stability was measured in biological testing time-scale by 1H NMR. The bridging coordination modes of the zwitterionic Ala and deprotonated Phe ligands led to the formation of 1D polymeric chains of the complexes. The significant argentophilic interactions are presented in the structure of AgAla. Antimicrobial testing of prepared Ag(I) complexes was evaluated by IC50 and MIC values and were compared with AgGly, silver(I) sulfadiazine and AgNO3 samples. Moreover, MTS test was used to the testing of broad range antiproliferative activity of studied compounds against different cancer cell lines and also to the investigation of calf thymus DNA interactions by absorption spectroscopy, fluorescence spectroscopy, Ethidium bromide/Hoechst 33258 displacement experiments and circular dichroism spectroscopy. To evaluate the pUC19 DNA fragmentation by silver(I) complexes, the agarose gel electrophoresis was used. In addition to biological evaluation we used lipophilicity measurement results in the discussion about structure-activity relationship (SAR).
- MeSH
- Alanine chemistry metabolism pharmacology MeSH
- Anti-Bacterial Agents chemistry metabolism pharmacology MeSH
- Antifungal Agents chemistry metabolism pharmacology MeSH
- Candida parapsilosis drug effects MeSH
- DNA metabolism MeSH
- Escherichia coli drug effects MeSH
- Phenylalanine chemistry metabolism pharmacology MeSH
- Catalysis MeSH
- Coordination Complexes chemistry metabolism pharmacology MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemistry metabolism pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Cattle MeSH
- Staphylococcus aureus drug effects MeSH
- DNA Cleavage drug effects MeSH
- Silver chemistry MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In photosynthetic electron transport, large multiprotein complexes are connected by small diffusible electron carriers, the mobility of which is challenged by macromolecular crowding. For thylakoid membranes of higher plants, a long-standing question has been which of the two mobile electron carriers, plastoquinone or plastocyanin, mediates electron transport from stacked grana thylakoids where photosystem II (PSII) is localized to distant unstacked regions of the thylakoids that harbor PSI. Here, we confirm that plastocyanin is the long-range electron carrier by employing mutants with different grana diameters. Furthermore, our results explain why higher plants have a narrow range of grana diameters since a larger diffusion distance for plastocyanin would jeopardize the efficiency of electron transport. In the light of recent findings that the lumen of thylakoids, which forms the diffusion space of plastocyanin, undergoes dynamic swelling/shrinkage, this study demonstrates that plastocyanin diffusion is a crucial regulatory element of plant photosynthetic electron transport.
- MeSH
- Models, Biological MeSH
- Photosystem I Protein Complex metabolism MeSH
- Photosystem II Protein Complex metabolism MeSH
- Magnoliopsida physiology MeSH
- Plastocyanin metabolism MeSH
- Computer Simulation MeSH
- Gene Expression Regulation, Plant physiology MeSH
- Electron Transport MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The effects of combining naturally evolved photosynthetic pigment-protein complexes with inorganic functional materials, especially plasmonically active metallic nanostructures, have been a widely studied topic in the last few decades. Besides other applications, it seems to be reasonable using such hybrid systems for designing future biomimetic solar cells. In this paper, we describe selected results that point out to various aspects of the interactions between photosynthetic complexes and plasmonic excitations in Silver Island Films (SIFs). In addition to simple light-harvesting complexes, like peridinin-chlorophyll-protein (PCP) or the Fenna-Matthews-Olson (FMO) complex, we also discuss the properties of large, photosynthetic reaction centers (RCs) and Photosystem I (PSI)-both prokaryotic PSI core complexes and eukaryotic PSI supercomplexes with attached antenna clusters (PSI-LHCI)-deposited on SIF substrates.
- MeSH
- Chlorophyll A metabolism MeSH
- Spectrometry, Fluorescence methods MeSH
- Formaldehyde chemistry MeSH
- Photosynthesis * MeSH
- Photosystem I Protein Complex metabolism MeSH
- Glucose chemistry MeSH
- Carotenoids metabolism MeSH
- Nanostructures chemistry ultrastructure MeSH
- Silver chemistry MeSH
- Light-Harvesting Protein Complexes metabolism MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The globally increasing incidence of cancer, including melanoma, requires novel therapeutic strategies. Development of successful novel drugs is based on clear identification of the target mechanisms responsible for the disease progression. The specific cancer microenvironment represents a critically important aspect of cancer biology, which cannot be properly studied in simplistic cell culture conditions. Among other traditional options, the study of melanoma cell growth on the chicken chorioallantoic membrane offers several significant advantages. This model offers increased complexity compared to usual in silico culture models and still remains financially affordable. Using this model, we studied the growth of three established human melanoma cell lines: A2058, BLM, G361. The combination of histology, immunohistochemistry with the application of human-specific antibodies, intravascular injection of contrast material such as filtered Indian ink, Mercox solution and phosphotungstic acid, and X-ray micro-CT and live-cell monitoring was employed. Melanoma cells spread well on the chicken chorioallantoic membrane. However, invasion into the stroma of the chorioallantoic membrane and the limb primordium graft was rare. The melanoma cells also significantly influenced the architecture of the blood vessel network, resulting in the orientation of the vessels to the site of the tumour cell inoculation. The system of melanoma cell culture on the chorioallantoic membrane is suitable for the study of melanoma cell growth, particularly of rearrangement of the host vascular pattern after cancer cell implantation. The system also has promising potential for further development.
- MeSH
- Models, Biological * MeSH
- Chorioallantoic Membrane metabolism pathology MeSH
- Immunohistochemistry MeSH
- Chickens MeSH
- Chick Embryo MeSH
- Humans MeSH
- Melanoma, Experimental metabolism pathology MeSH
- Tumor Cells, Cultured MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
V rutinním diagnostickém provozu se problematika diagnostiky mezenchymálních nádorů gastrointestinálního traktu až na výjimky často zužuje na potvrzení diagnózy gastrointestinálního stromálního tumoru a jeho další diagnosticko-terapeutický management. S rozvojem endoskopických technik však narůstá i množství bioptovaných mezenchymálních lézí, které dříve často pro malé rozměry a asymptomatický průběh unikaly pozornosti. Část z nich je diagnostikovatelná již na základě charakteristického histologického obrazu, k diagnóze některých lze přispět užitím tkáňově specifických protilátek ve vztahu k předpokládané diferenciační linii nádorové buňky. Vzácné však nejsou ani případy s nejasnou linií diferenciace, jejichž precizní diagnóza je založena na detekci patognomické genetické alterace nádorových buněk prokazatelné metodami molekulární biologie a v některých případech i imunohistochemickou vizualizací alterovaného proteinového produktu. Vzhledem k tomu, že tyto genetické alterace většinou nejsou unikátní, ale mohou se vyskytovat v různých typech nádorů, je stále nutné dodržovat komplexní diagnostický přístup se zohledněním znaků histologických, imunohistochemických a molekulárně genetických.
Although, in routine practice, the differential diagnostics of mesenchymal tumors of the gastrointestinal tract is still focused mainly on the correct diagnosis of gastrointestinal stromal tumor and its further therapeutic management based on predictive diagnostics, recent progress in the development of endoscopic techniques has led to increased detection of other mesenchymal lesions, which were previously commonly neglected due to their small size or absence of symptoms requiring surgical exploration. Diagnosis of some of these lesions may be reached based on their histologic pattern alone, while others may be recognized with the use of tissue specific antibodies related to the probable lineage of differentiation of the neoplastic cells. Finally, a subset of tumors, commonly with uncertain lineage of differentiation, is defined by pathognomonic genetic alterations of neoplastic cells. Recognition of such alterations, based either on methods of molecular genetics or immunohistochemical detection of an altered protein product, enables a precise diagnosis in a growing number of these cases. However, regarding the fact that most of these alterations are not unique to a single tumor type, but are often shared by more neoplastic entities, the diagnosis must still be based on a complex diagnostic attitude, reflecting histological, immunohistochemical and molecular genetic features of the investigated tumor.
- Keywords
- mezenchymální nádory,
- MeSH
- Diagnosis, Differential MeSH
- Gastrointestinal Stromal Tumors * diagnosis genetics MeSH
- Immunohistochemistry methods MeSH
- Humans MeSH
- Molecular Biology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH