Matriptase-2, a serine protease expressed in hepatocytes, is a negative regulator of hepcidin expression. The purpose of the study was to investigate the interaction of matriptase-2 with hemojuvelin protein in vivo. Mice lacking the matriptase-2 proteolytic activity (mask mice) display decreased content of hemojuvelin protein. Vice versa, the absence of hemojuvelin results in decreased liver content of matriptase-2, indicating that the two proteins interact. To further characterize the role of matriptase-2, we investigated iron metabolism in mask mice fed experimental diets. Administration of iron-enriched diet increased liver iron stores as well as hepcidin expression. Treatment of iron-overloaded mask mice with erythropoietin increased hemoglobin and hematocrit, indicating that the response to erythropoietin is intact in mask mice. Feeding of an iron-deficient diet to mask mice significantly increased spleen weight as well as the splenic content of erythroferrone and transferrin receptor proteins, indicating stress erythropoiesis. Liver hepcidin expression was decreased; expression of Id1 was not changed. Overall, the results suggest a complex interaction between matriptase-2 and hemojuvelin, and demonstrate that hepcidin can to some extent be regulated even in the absence of matriptase-2 proteolytic activity.

• Klíčová slova
• Hjv, Tfr2, Tfrc, Tmprss6, hepcidin, neogenin, transferrin receptor,
• MeSH
• deficit železa MeSH
• dietní železo farmakologie   MeSH
• erythropoetin farmakologie   MeSH
• GPI-vázané proteiny biosyntéza   nedostatek   genetika   fyziologie   MeSH
• hepcidiny biosyntéza   genetika   MeSH
• inhibitor diferenciace 1 biosyntéza   genetika   MeSH
• játra metabolismus   MeSH
• kostní morfogenetický protein 6 biosyntéza   genetika   MeSH
• membránové proteiny nedostatek   genetika   fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• orgánová specificita MeSH
• přetížení železem metabolismus   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• protein hemochromatózy biosyntéza   nedostatek   genetika   fyziologie   MeSH
• proteinové domény MeSH
• regulace genové exprese účinky léků   MeSH
• rekombinantní proteiny metabolismus   MeSH
• serinové endopeptidasy nedostatek   genetika   fyziologie   MeSH
• slezina metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Bmp6 protein, mouse MeSH Prohlížeč
• dietní železo MeSH
• erythropoetin MeSH
• GPI-vázané proteiny MeSH
• Hamp protein, mouse MeSH Prohlížeč
• hepcidiny MeSH
• HJV protein, mouse MeSH Prohlížeč
• Idb1 protein, mouse MeSH Prohlížeč
• inhibitor diferenciace 1 MeSH
• kostní morfogenetický protein 6 MeSH
• matriptase 2 MeSH Prohlížeč
• membránové proteiny MeSH
• protein hemochromatózy MeSH
• rekombinantní proteiny MeSH
• serinové endopeptidasy MeSH

BACKGROUND: With the aim to show the feasibility of early tumor shrinkage (ETS) concept implementation into daily clinical practice in the Czech Republic, a non-interventional, multicentric, single arm, prospective study in real world set-up was performed. MATERIAL AND METHODS: The study objectives were to explore the time interval from the treatment starting date to the date of the first radiographic control (TFRC) and evaluate the proportion of patients who achieved ≥ 20% tumor regression within the first 8 weeks of first-line therapy, in the real-world settings. RESULTS: The medians of TFRC in all individual participating centers were > 12 weeks (range 14.0-36.4 weeks). TFRC ≤ 8 weeks was reported for only 3% of patients in the cohort with first-line therapy, and there were only 3 patients (1%) who achieved tumor regression of ≥ 20% by day 60 (8.6 weeks). CONCLUSION: These findings indicate that the basic time parameter of ETS could not realistically be employed in routine oncology care of patients with metastatic colorectal cancer (mCRC) in the Czech Republic, unless there would be a strict request to perform TRFC by week 8 since the initiation of the therapy. In addition, the frequency of objective tumor response to first-line therapy with cetuximab + chemotherapy was evaluated. Based on the relative regression in the sum of diameters of measurable metastatic lesions, unconfirmed partial responses were achieved in 42.4 % and unconfirmed complete response in 8.6% of patients, altogether corresponding to the overall response rate of 51% with first-line therapy. The frequency of responses was higher among patients with left than right sided primary tumors. It seems that the regimen of cetuximab/FOLFOX might be more active in frontline therapy of right sided RAS wild type mCRC than cetuximab/FOLFIRI.

• Klíčová slova
• Chemotherapy, chemother­apy, colorectal cancer,
• MeSH
• cetuximab * terapeutické užití   MeSH
• kolorektální nádory * farmakoterapie   patologie   genetika   MeSH
• leukovorin terapeutické užití   MeSH
• lidé MeSH
• prospektivní studie MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• studie proveditelnosti * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cetuximab * MeSH
• leukovorin MeSH
• protinádorové látky imunologicky aktivní MeSH

Chromosomal locations of 19 horse immunity-related loci (CASP1, CD14, EIF5A, FCER1A, IFNG, IL12A, IL12B, IL12RB2, IL1A, IL23A, IL4, IL6, MMP7, MS4A2, MYD88, NOS2A, PTGS2, TFRC and TLR2) were determined by fluorescence in situ hybridization. For IFNG and PTGS2, this study is a confirmation of their previously reported position. In addition, microsatellite (HMBr1) was localized in the same region as IFNG. All genes were assigned to regions of conserved synteny and the data obtained in this study enhance the comparative human-horse map. Cytogenetic localization of IL6 to ECA4q14-q21.1 suggested a new breakage point that changes the order of loci compared with HSA7. The map assignments of these loci serve as anchors for other loci and will aid in the search for candidate genes associated with traits in the horse.

• MeSH
• DNA primery MeSH
• druhová specificita MeSH
• geny genetika   imunologie   MeSH
• hybridizace in situ fluorescenční MeSH
• koně genetika   imunologie   MeSH
• lidé MeSH
• mapování chromozomů * MeSH
• mikrosatelitní repetice genetika   MeSH
• syntenie genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA primery MeSH

New findings in schizophrenia genetics are based on genome-wide association studies (GWAS), research into DNA copy number variations (CNVs), and endophenotypes. More than 70 genes have recently been suspected to be involved in the genetic background of schizophrenia based on the GWAS´s results. They are typically related to neurodevelopment/neuroplasticity, immunology and neuroendocrinology. Nevertheless, for many detected genes their possible relationship to schizophrenia etiopathogenesis is still unknown. The CNVs at genome loci 1q21.1 (candidate gene e.g., PRKAB2), 2p16.3 (candidate gene e.g., NRXN1), 3q29 (candidate genes e.g., BDH1, DLG1, PAK2 or TFRC), 15q11.2 (candidate gene e.g., CYFIP1), 15q13.3 (candidate gene e.g., CHRNA7), 16p13.1 (candidate genes e.g.,NTAN1 or NDE1) and 22q11.2 (candidate genes e.g., COMT, GSTT2 or PRODH) were associated with schizophrenia most frequently. Genetic research of schizophrenia endophenotypes, usually neurophysiological, neuromotoric, neurocognitive, neuroanatomical, neurological or personality-related, will help us to discover the role of relevant genes in the pathogenesis of schizophrenia. It is also necessary to integrate knowledge from other research platforms in schizophrenia, like epigenetics, studies of gene-environment interactions, transcriptomics, proteomics, metabolomics, neuroimaging and psychopathology. A better knowledge of the genetic background of schizophrenia can lead to changes in the treatment, prevention and genetic counselling. It may also reduce stigma in this severe mental disorder.

• Klíčová slova
• Copy number variations, Endophenotypes, Genetics, Genome-wide association study, Schizophrenia,
• Publikační typ
• časopisecké články MeSH

The importance of iron in the growth and progression of tumors has been widely documented. In this report, we show that tumor-initiating cells (TICs), represented by spheres derived from the MCF7 cell line, exhibit higher intracellular labile iron pool, mitochondrial iron accumulation and are more susceptible to iron chelation. TICs also show activation of the IRP/IRE system, leading to higher iron uptake and decrease in iron storage, suggesting that level of properly assembled cytosolic iron-sulfur clusters (FeS) is reduced. This finding is confirmed by lower enzymatic activity of aconitase and FeS cluster biogenesis enzymes, as well as lower levels of reduced glutathione, implying reduced FeS clusters synthesis/utilization in TICs. Importantly, we have identified specific gene signature related to iron metabolism consisting of genes regulating iron uptake, mitochondrial FeS cluster biogenesis and hypoxic response (ABCB10, ACO1, CYBRD1, EPAS1, GLRX5, HEPH, HFE, IREB2, QSOX1 and TFRC). Principal component analysis based on this signature is able to distinguish TICs from cancer cells in vitro and also Leukemia-initiating cells (LICs) from non-LICs in the mouse model of acute promyelocytic leukemia (APL). Majority of the described changes were also recapitulated in an alternative model represented by MCF7 cells resistant to tamoxifen (TAMR) that exhibit features of TICs. Our findings point to the critical importance of redox balance and iron metabolism-related genes and proteins in the context of cancer and TICs that could be potentially used for cancer diagnostics or therapy.

• Klíčová slova
• FeS cluster, breast cancer, iron metabolism, stem cells, tumor-initiating cells,
• MeSH
• akutní promyelocytární leukemie enzymologie   genetika   MeSH
• analýza hlavních komponent MeSH
• antitumorózní látky farmakologie   MeSH
• biologický transport MeSH
• buněčné sféroidy MeSH
• chelátory železa farmakologie   MeSH
• chemorezistence MeSH
• fenotyp MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• mitochondrie enzymologie   MeSH
• myši transgenní MeSH
• nádorové kmenové buňky účinky léků   enzymologie   patologie   MeSH
• nádory prostaty farmakoterapie   enzymologie   genetika   patologie   MeSH
• nádory prsu farmakoterapie   enzymologie   genetika   patologie   MeSH
• regulace genové exprese enzymů MeSH
• regulace genové exprese u nádorů MeSH
• stanovení celkové genové exprese MeSH
• tamoxifen farmakologie   MeSH
• transkriptom * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• chelátory železa MeSH
• tamoxifen MeSH
• železo MeSH