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EN
A 43-year-old man was admitted to the hematology department due to second recurrence of anaplastic lymphoma T-cell ALK+. Lymphoma was diagnosed 28 years earlier. The patient received COP regimen (17 cycles) and CHOP (5 cycles), radiotherapy and underwent splenectomy. He achieved complete remission at that time. Relapse of the disease was diagnosed 8 years later, which was treated with 6 cycles of chemotherapy (cytarabine, mitoxantrone, vepeside and glucocorticoids) and high-dose chemotherapy followed by hematopoietic stem cell transplantation. Second disease recurrence was found in 2013, it was anaplastic lymphoma T-cell ALK+ stage IIA by Ann Arbor. Echocardiography and myocardial perfusion scintigraphy revealed chronic heart failure NYHA class I. Angiotensin receptor antagonist (ramipril) and β-blocker (carvedilol) were recommended. The patient underwent 6 cycles of ESHAP, complete remission was reported after the second cycle. High-dose therapy with autologous stem cell rescue was considered at that time. However, having T-cell ALK+ lymphoma with a relatively good prognosis, previous prolonged complete remissions (respectively – 12 and 8 years), an insufficient yield from the harvest (3,33 × 106/kg CD34+ cells), heart failure and chronic active viral hepatitis B, the high risk intensive chemotherapy followed by hematopoietic stem cells transplantation was discontinued. The chemotherapy was complicated by brachial vein and superficial vein thrombosis of left upper limb and hypogammaglobulinemia. Follow-up echocardiography performed after completion of chemotherapy showed improvement in EF (64%).
EN
A theoretical model for predicting the free energy of binding between anthracycline antibiotics and DNA was developed using the electron density functional (DFT) and molecular mechanics (MM) methods. Partial DFT-ESP charges were used in calculating the MM binding energies for complexes formed between anthracycline antibiotics and oligodeoxynucleotides. These energies were then compared with experimental binding free energies. The good correlation between the experimental and theoretical energies allowed us to propose a model for predicting the binding free energy for derivatives of anthracycline antibiotics and for quickly screening new anthracycline derivatives.
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Introduction: The most common form of cardiotoxicity in cancer treatment is anthracycline-related cardiomyopathy. Objective: To study the factors affecting response to heart failure (HF) therapy in patients with anthracycline- related cardiomyopathy (ARC). Methods: Patients with ARC were included in the study. ARC was defined as left ventricular ejection fraction (LVEF) < 50% in patients who had received anthracycline based chemotherapy. 2Decho was done at baseline and every 3 months after starting anti-heart failure treatment. The primary endpoint of the study was response to anti-heart failure treatment. The patients were considered as responders when LVEF increased at least 10 absolute points. The secondary endpoint was overall survival. Results: 177 patients with ARC were included in the study. The median cumulative dose of doxorubicin was 275 mg/m2. Median clinical follow up duration was 19 months (range 3–73 months). 55% were responders. 25 cumulative doxorubicin dose of more than 200 mg/m2 increased the likelihood of non-response (p = 0.008), by a factor of 3.07 (95% CI: 1.34–7.05). 25 patients expired. There was a significant difference in overall survival among responders as compared to non-responders (p value: 0.002, log rank test). Conclusions: In patients with ARC cumulative doxorubicin dose of more than 200 mg/m2 increased the likelihood of non-response to anti-heart failure treatment. Responders have a better overall survival compared to non-responders in patients with ARC.
EN
Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.
EN
This article concerns synthesis and biological activity of anthracenedione analogues which are considered as prodrugs.
PL
W pracy przedstawiono możliwość otrzymania bioresorbowalnego nośnika leku o optymalnym działaniu terapeutycznym w leczeniu glejaka mózgu, który w określonym czasie uwalnia lek cytostatyczny o odpowiednim sterowanym stężeniu bezpośrednio do zmienionej tkanki nowotworowej lub loży pooperacyjnej, przy czym sam nośnik ulega degradacji i wchłonięciu w zamierzonym czasie. Jako materiał polimerowy zastosowano poliestry glikolidu, laktydu, e-kaprolaktonu i trimetylenowęglanu o ściśle zaprojektowanej mikrostrukturze łańcuchów polimerowych.
EN
In this work, formation of bioresorbable drug release system with optimal therapeutic action in brain glioma diseases was described. This system delivers cytotoxic drug with suitable concentration directly to brain tumor or postoperative brain site with degradation and absorption of the carrier in intended time. As carrier materials copolymers obtained from glycolide, lactide, e-caprolactone and trimethylenecarbonate with strictly defined chain microstructure were applied.
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