BACKGROUND: Infantile myofibromatosis belongs to a family of soft tissue tumors. The majority of these tumors have benign behavior but resistant and malignant courses are known, namely in tumors with visceral involvement. The standard of care is surgical resection. Observations suggest that low dose chemotherapy is beneficial. The treatment of resistant or relapsed patients with multifocal disease remains challenging. Patients that harbor an actionable mutation in the kinase domain are potential subjects for targeted tyrosine kinase inhibitor therapy. CASE PRESENTATION: An infant boy with inborn generalized infantile myofibromatosis that included bone, intracranial, soft tissue and visceral involvement was treated according to recent recommendations with low dose chemotherapy. The presence of a partial but temporary response led to a second line of treatment with six cycles of chemotherapy, which achieved a partial response again but was followed by severe toxicity. The generalized progression of the disease was observed later. Genetic analyses were performed and revealed a PDGFRB gene c.1681C>A missense heterozygous germline mutation, high PDGFRβ phosphokinase activity within the tumor and the heterozygous germline Slavic Nijmegen breakage syndrome 657del5 mutation in the NBN gene. Targeted treatment with sunitinib, the PDGFRβ inhibitor, plus low dose vinblastine led to an unexpected and durable response without toxicities or limitations to daily life activities. The presence of the Slavic NBN gene mutation limited standard chemotherapy dosing due to severe toxicities. Sister of the patient suffred from skull base tumor with same genotype and histology. The same targeted therapy led to similar quick and durable response. CONCLUSION: Progressive and resistant incurable infantile myofibromatosis can be successfully treated with the new approach described herein. Detailed insights into the biology of the patient's tumor and genome are necessary to understand the mechanisms of activity of less toxic and effective drugs except for up to date population-based chemotherapy regimens.

• MeSH
• chemorezistence účinky léků   genetika   MeSH
• cílená molekulární terapie metody   MeSH
• heterozygot MeSH
• indoly aplikace a dávkování   MeSH
• lidé MeSH
• myofibromatóza vrozené   farmakoterapie   genetika   metabolismus   MeSH
• novorozenec MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• pyrroly aplikace a dávkování   MeSH
• růstový faktor odvozený z trombocytů - receptor beta antagonisté a inhibitory   genetika   metabolismus   MeSH
• vinblastin aplikace a dávkování   MeSH
• výsledek terapie MeSH
• zárodečné mutace * MeSH
• zdraví rodiny MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• analýza přežití MeSH
• aniliny terapeutické užití   MeSH
• bcr-abl fúzní proteiny genetika   MeSH
• časové faktory MeSH
• chemorezistence účinky léků   MeSH
• chinoliny terapeutické užití   MeSH
• chronická fáze myeloidní leukemie farmakoterapie   genetika   MeSH
• chronická myeloidní leukemie farmakoterapie   genetika   MeSH
• genetická transkripce účinky léků   MeSH
• indukce remise MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• nitrily terapeutické užití   MeSH
• piperaziny terapeutické užití   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• pyrimidiny terapeutické užití   MeSH
• thiazoly terapeutické užití   MeSH
• tyrosinkinasy antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• souhrny MeSH

Apple scab, caused by Venturia inaequalis, is a major fungal disease worldwide. Cultivation of scab-resistant cultivars would reduce the chemical footprint of apple production. However, new apple cultivars carrying durable resistances should be developed to prevent or at least slow the breakdown of resistance against races of V. inaequalis. One way to achieve durable resistance is to pyramid multiple scab resistance genes in a cultivar. The choice of the resistance genes to be combined in the pyramids should take into account the frequency of resistance breakdown and the geographical distribution of apple scab isolates able to cause such breakdowns. In order to acquire this information and to make it available to apple breeders, the VINQUEST project (www.vinquest.ch) was initiated in 2009. Ten years after launching this project, 24 partners from 14 countries regularly contribute data. From 2009 to 2018, nearly 9,000 data points have been collected. This information has been used to identify the most promising apple scab resistance genes for developing cultivars with durable resistance, which to date are: Rvi5, Rvi11, Rvi12, Rvi14, and Rvi15. As expected, Rvi1, together with Rvi3 and Rvi8, were often overcome, and have little value for scab resistance breeding. Rvi10 may also belong to this group. On the other hand, Rvi2, Rvi4, Rvi6, Rvi7, Rvi9, and Rvi13 are still useful for breeding, but their use is recommended only in extended pyramids of ≥3 resistance genes.

• MeSH
• Ascomycota * MeSH
• chov MeSH
• Malus genetika   MeSH
• nemoci rostlin MeSH
• rostlinné geny MeSH
• Publikační typ
• časopisecké články MeSH

This study investigates the durability of functional diamond-like carbon (DLC) coated titanium alloy (Ti-6Al-4V) under edge loading conditions for application in artificial hip joints. The multilayered (ML) functional DLC coatings consist of three key layers, each of these layers were designed for specific functions such as increasing fracture strength, adapting stress generation and enhancing wear resistance. A 'ball-on-disk' multi-directional wear tester was used in the durability test. Prior to the wear testing, surface hardness, modulus elasticity and Raman intensity were measured. The results revealed a significant wear reduction to the DLC coated Ti-6Al-4V disks compared to that of non-coated Ti-6Al-4V disks. Remarkably, the counterpart Silicon Nitride (Si3N4) balls also yielded lowered specific wear rate while rubbed against the coated disks. Hence, the pairing of a functional multilayered DLC and Si3N4 could be a potential candidate to orthopedics implants, which would perform a longer life-cycle against wear caused by edge loading.

• MeSH
• diamant chemie   MeSH
• kyčelní protézy * MeSH
• lidé MeSH
• povrchové vlastnosti MeSH
• protézy - design MeSH
• slitiny MeSH
• testování materiálů * MeSH
• titan chemie   MeSH
• uhlík MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Early identification of resistant cancer cells is currently a major challenge, as their expansion leads to refractoriness. To capture the dynamics of these cells, we made a comprehensive analysis of disease progression and treatment response in a chronic lymphocytic leukemia (CLL) patient using a combination of single-cell and bulk genomic methods. At diagnosis, the patient presented with unfavorable genetic markers, including notch receptor 1 (NOTCH1) mutation and loss(11q). The initial and subsequent treatment lines did not lead to a durable response and the patient developed refractory disease. Refractory CLL cells featured substantial dysregulation in B-cell phenotypic markers such as human leukocyte antigen (HLA) genes, immunoglobulin (IG) genes, CD19 molecule (CD19), membrane spanning 4-domains A1 (MS4A1; previously known as CD20), CD79a molecule (CD79A) and paired box 5 (PAX5), indicating B-cell de-differentiation and disease transformation. We described the clonal evolution and characterized in detail two cell populations that emerged during the refractory disease phase, differing in the presence of high genomic complexity. In addition, we successfully tracked the cells with high genomic complexity back to the time before treatment, where they formed a rare subpopulation. We have confirmed that single-cell RNA sequencing enables the characterization of refractory cells and the monitoring of their development over time.

• MeSH
• analýza jednotlivých buněk * metody   MeSH
• chemorezistence genetika   MeSH
• chronická lymfatická leukemie * genetika   patologie   MeSH
• lidé MeSH
• sekvenční analýza RNA MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 μg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.

• MeSH
• bakteriální toxiny terapeutické užití   MeSH
• chemorezistence účinky léků   MeSH
• dospělí MeSH
• exotoxiny terapeutické užití   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   patologie   MeSH
• míra přežití MeSH
• následné studie MeSH
• prognóza MeSH
• protinádorové látky terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vlasatobuněčná leukemie farmakoterapie   patologie   MeSH
• záchranná terapie * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH

This study was aimed on the detection of methicillin resistant Staphylococcus aureus (MRSA) in different categories of retailed ready-to-eat (RTE) meat products from the Czech producers and determination of their genetic properties, antimicrobial resistance and virulence. In RTE meat products, 2% (4/181) of examined samples were MRSA positive. MRSA strains were detected only in durable fermented meat products made exclusively from pork meat. Detection of livestock-associated MRSA (LA-MRSA) clonal lineages (ST398 and ST4999), SCCmec cassette type V and tetracycline resistance indicate a source of contamination from raw pork. The study confirms the ability of these strains to survive the technological process rather than contamination of meat products from the food processing environment. MRSA strains did not carry any of the tested genes encoding staphylococcal enterotoxins or virulence genes (for Panton-Valentine leukocidin, exfoliative toxins A, B and toxic shock syndrome). Our results point out the spread of LA-MRSA through the meat processing chain.

• MeSH
• antibakteriální látky farmakologie   MeSH
• dobytek MeSH
• masné výrobky * MeSH
• maso MeSH
• methicilin rezistentní Staphylococcus aureus * genetika   MeSH
• mikrobiální testy citlivosti MeSH
• stafylokokové infekce * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

There are limited data on retreatment with monoclonal antibodies (mAb) in patients with chronic lymphocytic leukaemia (CLL). In a pivotal study, ofatumumab (human anti-CD20 mAb) monotherapy demonstrated a 47% objective response rate (ORR) in fludarabine refractory CLL patients. From this study, a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions (induction treatment period), followed by monthly infusions for up to 2 years (maintenance treatment period). The ORR after 8 weeks of induction retreatment was 45% and 24% had continued disease control after maintenance at 52 weeks. Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study. Response duration was 24.1 months vs. 6.8 months; time to next therapy was 14.8 months vs. 12.3 months; and progression-free survival was 7.4 months vs. 7.9 months (medians). Upon retreatment, 72% had infusion reactions, mostly Grade 1-2. Three patients had fatal infections. In summary, ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile.

• MeSH
• chemorezistence MeSH
• chronická lymfatická leukemie farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• opakovaná terapie MeSH
• progrese nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• senioři MeSH
• udržovací chemoterapie MeSH
• vidarabin analogy a deriváty   farmakologie   MeSH
• Check Tag
• 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

The development of orthodontics has improved thanks to the introduction of adhesives which are physically and chemically akin to tooth enamel and brackets. These materials often fall short of the required durability standards. The objective was to evaluate the real strength of the adhesives and to introduce a proprietary device, generating multiple vectors of strength between dental brackets and the surface of enamel. 11 types of adhesive materials have been studied. 990 applications have been made using removed teeth, followed by a randomised creation of 11 groups containing 90 samples each. The threshold values of the strength needed to break the brackets off were determined in torsional, shear and tension strength tests. A comparison between tensometric and planimetric methods was made by means based on ARI index. Resistance was highest for torsional stress, weaker for shear stress and the weakest for tension stress. A correlation was found between tensometric results. The study attempted to systematise the methodology of direct tests.

• MeSH
• biomechanika účinky léků   MeSH
• lidé MeSH
• mechanický stres MeSH
• ortodontické zámky * MeSH
• testování materiálů metody   MeSH
• vazba zubní * MeSH
• zubní cementy farmakologie   MeSH
• zubní sklovina chemie   MeSH
• žvýkání účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The adhesive systems have the function to establish the connection between the restorative material and dental tissue, therefore it is of fundamental importance, because failures in the adhesive interface can reduce the life of a dental restoration. This study investigated the possibility of using the adhesive layer as a chlorhexidine modified release system evaluating their impact on the properties of these systems as well as evaluating the impact of these systems on immediate and post-aging dentin adhesion. Were used a matrix with BisGMA, UDMA, HEMA and TEGDMA copolymer and clay particles (Dellite 67G); associated with a chlorhexidine and a camphorquinone photoinitiator system. The properties of these systems were evaluated by the XRD, FTIR spectrophotometer, flexural strength, elasticity modulus, drug release, enzymatic inhibition and dentin adhesion resistance. The presence of the clay can raise the mechanical properties of the adhesive systems engendering a more resistant hybrid layer and led to a more sustained release of chlorhexidine in the systems, allowing a longer effective period of MMP-2 inhibition. The hypothesis that the addition of clays as release modulators could increase the effectiveness of these drugs in inhibiting the dentin's MPPs and consequently enhancing the adhesive durability was confirmed. These results indicate that the controlled release of chlorhexidine is able to reduce the process of loss of adhesion presenting itself as a promising system to increase the longevity of dental restorations.

• MeSH
• biokompatibilní materiály MeSH
• časové faktory MeSH
• chlorhexidin chemie   MeSH
• dentin chemie   MeSH
• dentinová adheziva MeSH
• jíl chemie   MeSH
• léky s prodlouženým účinkem MeSH
• pevnost v tahu MeSH
• testování materiálů MeSH
• uvolňování léčiv * MeSH
• zubní materiály * MeSH
• Publikační typ
• časopisecké články MeSH