- MeSH
- Fusion Proteins, bcr-abl genetics MeSH
- Blast Crisis * genetics drug therapy pathology MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive * drug therapy genetics pathology MeSH
- Imidazoles * therapeutic use administration & dosage MeSH
- Protein Kinase Inhibitors therapeutic use pharmacology MeSH
- Humans MeSH
- Mutation * MeSH
- Mice MeSH
- Niacinamide analogs & derivatives MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Pyrazoles MeSH
- Pyridazines * therapeutic use administration & dosage MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Letter MeSH
- Keywords
- nilotinib, bosutinib, ponatinib,
- MeSH
- Aniline Compounds administration & dosage therapeutic use MeSH
- Quinolines administration & dosage therapeutic use MeSH
- Leukemia, Myeloid, Chronic-Phase therapy MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive * therapy MeSH
- Dasatinib administration & dosage therapeutic use MeSH
- Imatinib Mesylate administration & dosage therapeutic use MeSH
- Imidazoles administration & dosage therapeutic use MeSH
- Protein Kinase Inhibitors administration & dosage therapeutic use MeSH
- Tyrosine Kinase Inhibitors administration & dosage therapeutic use MeSH
- Humans MeSH
- Graft vs Host Disease MeSH
- Nitriles administration & dosage therapeutic use MeSH
- Pyridazines administration & dosage therapeutic use MeSH
- Pyrimidines administration & dosage therapeutic use MeSH
- Retrospective Studies MeSH
- Hematopoietic Stem Cell Transplantation methods MeSH
- Check Tag
- Humans MeSH
Infantile myofibromatosis represents one of the most common proliferative fibrous tumors of infancy and childhood. More effective treatment is needed for drug-resistant patients, and targeted therapy using specific protein kinase inhibitors could be a promising strategy. To date, several studies have confirmed a connection between the p.R561C mutation in gene encoding platelet-derived growth factor receptor beta (PDGFR-beta) and the development of infantile myofibromatosis. This study aimed to analyze the phosphorylation of important kinases in the NSTS-47 cell line derived from a tumor of a boy with infantile myofibromatosis who harbored the p.R561C mutation in PDGFR-beta. The second aim of this study was to investigate the effects of selected protein kinase inhibitors on cell signaling and the proliferative activity of NSTS-47 cells. We confirmed that this tumor cell line showed very high phosphorylation levels of PDGFR-beta, extracellular signal-regulated kinases (ERK) 1/2 and several other protein kinases. We also observed that PDGFR-beta phosphorylation in tumor cells is reduced by the receptor tyrosine kinase inhibitor sunitinib. In contrast, MAPK/ERK kinases (MEK) 1/2 and ERK1/2 kinases remained constitutively phosphorylated after treatment with sunitinib and other relevant protein kinase inhibitors. Our study showed that sunitinib is a very promising agent that affects the proliferation of tumor cells with a p.R561C mutation in PDGFR-beta.
- MeSH
- Butadienes administration & dosage therapeutic use MeSH
- Child MeSH
- Erlotinib Hydrochloride administration & dosage therapeutic use MeSH
- Phosphorylation drug effects MeSH
- Protein Kinase Inhibitors administration & dosage therapeutic use MeSH
- Infant MeSH
- Humans MeSH
- Mutation * MeSH
- Myofibromatosis congenital drug therapy genetics MeSH
- Cell Line, Tumor MeSH
- Nitriles administration & dosage therapeutic use MeSH
- Cell Proliferation drug effects MeSH
- Pyrazoles administration & dosage therapeutic use MeSH
- Pyridazines administration & dosage therapeutic use MeSH
- Receptor, Platelet-Derived Growth Factor beta * genetics metabolism MeSH
- Sunitinib administration & dosage therapeutic use MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Keywords
- Iclusig (ponatinib),
- MeSH
- Fusion Proteins, bcr-abl drug effects MeSH
- Drug Resistance, Neoplasm MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive * drug therapy genetics MeSH
- Imidazoles administration & dosage pharmacology adverse effects MeSH
- Protein Kinase Inhibitors administration & dosage pharmacology adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Pyridazines administration & dosage adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Keywords
- bosutinib, ponatinib, omacetaxin mepesukcinát,
- MeSH
- Aniline Compounds administration & dosage pharmacology adverse effects therapeutic use MeSH
- Quinolines administration & dosage pharmacology adverse effects therapeutic use MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive * etiology drug therapy classification MeSH
- Antineoplastic Agents, Phytogenic therapeutic use MeSH
- Harringtonines therapeutic use MeSH
- Transplantation, Homologous MeSH
- Imatinib Mesylate administration & dosage pharmacology therapeutic use MeSH
- Imidazoles administration & dosage pharmacology adverse effects therapeutic use MeSH
- Protein Kinase Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Myocardial Ischemia complications MeSH
- Combined Modality Therapy MeSH
- Humans MeSH
- Nitriles administration & dosage pharmacology adverse effects therapeutic use MeSH
- Antineoplastic Protocols * MeSH
- Pyridazines administration & dosage pharmacology adverse effects therapeutic use MeSH
- Aged MeSH
- Stem Cell Transplantation MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
x
x
- Keywords
- ponatinib,
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy MeSH
- Fusion Proteins, bcr-abl MeSH
- Drug Resistance, Neoplasm MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive * drug therapy MeSH
- Adult MeSH
- Molecular Mechanisms of Pharmacological Action MeSH
- Philadelphia Chromosome MeSH
- Imatinib Mesylate analogs & derivatives MeSH
- Imidazoles administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Protein Kinase Inhibitors * administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Clinical Trials, Phase I as Topic MeSH
- Clinical Trials, Phase II as Topic MeSH
- Clinical Trials, Phase III as Topic MeSH
- Humans MeSH
- Young Adult MeSH
- Mutation MeSH
- Vascular Diseases chemically induced MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Antineoplastic Agents therapeutic use MeSH
- Pyridazines administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Aged MeSH
- Translocation, Genetic MeSH
- Protein-Tyrosine Kinases antagonists & inhibitors administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Aged MeSH
- Publication type
- Evaluation Study MeSH
- MeSH
- Anti-Arrhythmia Agents administration & dosage MeSH
- Digoxin administration & dosage MeSH
- Cardiomyopathy, Dilated * etiology drug therapy classification MeSH
- Atrial Fibrillation * diagnosis etiology drug therapy MeSH
- Dog Diseases MeSH
- Heart Valve Diseases drug therapy radiography ultrasonography MeSH
- Dogs MeSH
- Pyridazines administration & dosage MeSH
- Spironolactone administration & dosage MeSH
- Animals MeSH
- Check Tag
- Dogs MeSH
- Animals MeSH
- Keywords
- pozitivně inotropní látky, levosimendan,
- MeSH
- Acute Disease MeSH
- Analgesics therapeutic use MeSH
- Anticoagulants therapeutic use MeSH
- Diuretics administration & dosage adverse effects therapeutic use MeSH
- Drug Therapy * methods MeSH
- Hydrazones administration & dosage contraindications therapeutic use MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Cardiotonic Agents administration & dosage adverse effects therapeutic use MeSH
- Humans MeSH
- Prognosis MeSH
- Pyridazines administration & dosage contraindications therapeutic use MeSH
- Heart Failure * epidemiology etiology drug therapy mortality MeSH
- Vasodilator Agents administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
BACKGROUND: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. METHODS AND RESULTS: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. CONCLUSIONS: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.
- MeSH
- Chronic Disease MeSH
- Hydrazones administration & dosage MeSH
- Humans MeSH
- Pyridazines administration & dosage MeSH
- Practice Guidelines as Topic MeSH
- Heart Failure drug therapy MeSH
- Severity of Illness Index MeSH
- Vasodilator Agents administration & dosage MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Consensus Development Conference MeSH
Cíl: Cílem práce bylo zjistit vývoj renálních parametrů u neselektované populace nemocných s akutní dekompenzací pokročilého chronického srdečního selhání, kteří byli během hospitalizace léčeni levosimendanem. Soubor nemocných a metodika: Vývoj parametrů renálních funkcí byl hodnocen u souboru 91 pacientů, průměrná EF LK byla 23 %, průměrná koncentrace urey 12,12 mmol/l, koncentrace kreatininu byla 147,1 mmol/l a odhadovaná glomerulární filtrace (eGFR) 42,6 ml/min/1,73m2. Krevní odběry se stanovením koncentrace urey, kreatininu a odhad glomerulární filtrace podle MDRD byly provedeny před podáním infuze a před propuštěním/úmrtím pacienta. Výsledky: Interval mezi prvním a druhým hodnocením renálních parametrů byl průměrně 11 dnů (? 7,8). Mezi prvním a druhým hodnocením došlo k poklesu koncentrace urey z 12,12 na 11,37 mmol/l (p = 0,27), kreatininu z 147,1 na 142,5 (p = 0,33) a vzestupu eGFR z 42,6 na 45,8 ml/min/1,73m2 (p = 0,067). Zastoupení počtu případů, kdy došlo ke snížení koncentrace urey a kreatininu, nebylo významné, statisticky významný byl rozdíl v počtu případů zvýšení než snížení eGFR (68 % vs 32 %; p < 0,001). Závěr: Přes nevýznamný pokles koncentrace urey a kreatininu došlo u neselektované populace pacientů s pokročilým srdečním selháním léčených levosimendanem u většího počtu nemocných ke zvýšení než ke snížení eGFR.
The aim of the study was to evaluate the change of renal function parameters during hospital stay in unselected acute decompensated severe HF population treated with levosimendan. Patient population and methods: The change of renal parameters was assessed in 91 consecutive patients, the mean LV EF was 23%, mean urea level was 12.12 mmol/l, mean creatinine level was 147.1 mmol/l and estimated glomerular filtration rate (eGFR) was 42.6 ml/min/1.73m2. Results: Mean interval between the first (V1) and the second (V2) biochemical evaluation was 11 days (? 7.8). Mean urea level decreased (from 12.12 to 11.37 mmol/l, p = 0.27), as well as mean creatinine level decreased (from 147.1 to 142.5, p = 0.33), and mean eGFR increased (from 42.6 to 45.8 ml/min/1.73m2, p = 0.067) in the interval between V1 and V2. Urea and creatinine levels decreased in majority of the cases (not significant) and eGFR level significantly increased in majority of the cases (68% vs 32%, p < 0.001). Conclusion: Despite an insignificant change of urea and creatinine levels, the increase of eGFR was reported in majority of the cases.
- Keywords
- pokročilé srdeční selhání, dekompenzace, levosimendan,
- MeSH
- Renal Insufficiency, Chronic complications blood MeSH
- Glomerular Filtration Rate * drug effects MeSH
- Hydrazones administration & dosage therapeutic use MeSH
- Infusions, Intravenous MeSH
- Cardiotonic Agents * administration & dosage therapeutic use MeSH
- Creatinine blood MeSH
- Kidney drug effects MeSH
- Humans MeSH
- Urea blood MeSH
- Disease Progression MeSH
- Pyridazines administration & dosage therapeutic use MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Heart Failure * drug therapy MeSH
- Statistics as Topic MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
