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1.
Sensors (Basel) ; 23(4)2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36850450

RESUMEN

Soil bulk density is one of the most important soil properties. When bulk density cannot be measured by direct laboratory methods, prediction methods are used, e.g., pedotransfer functions (PTFs). However, existing PTFs have not yet incorporated information on soil structure although it determines soil bulk density. We aimed therefore at development of new PTFs for predicting soil bulk density using data on soil macrostructure obtained from image analysis. In the laboratory soil bulk density (BD), texture and total organic carbon were measured. On the basis of image analysis, soil macroporosity was evaluated to calculate bulk density by image analysis (BDim) and number of macropore cross-sections of diameter ≥5 mm was determined and classified (MP5). Then, we created PTFs that involve soil structure parameters, in the form BD~BDim + MP5 or BD~BDim. We also compared the proposed PTFs with selected existing ones. The proposed PTFs had mean prediction error from 0 to -0.02 Mg m-3, modelling efficiency of 0.17-0.39 and prediction coefficient of determination of 0.35-0.41. The proposed PTFs including MP5 better predicted boundary BDs, although the intermediate BD values were more scattered than for the existing PTFs. The observed relationships indicated the usefulness of image analysis data for assessing soil bulk density which enabled to develop new PTFs. The proposed models allow to obtain the bulk density when only images of the soil structure are available, without any other data.

2.
J Environ Manage ; 306: 114517, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35051815

RESUMEN

Waste management to reduce the loss of natural resources has become a basis of sustainable development and a circular economy. When using waste, the heavy metal (HM) concentration must be taken into account since HMs can be potentially released to the environment, posing a toxicity threat. The aim of the study was thus to estimate the availability for plants of Cr, Ni, Cu, Zn, Cd, and Pb introduced into the soil with waste. We hypothesized that the prepared waste mixtures containing coal or biomass ash and municipal sewage sludge would reduce the environmental risk compared to the studied waste used separately. The research was conducted during a 6-year field experiment with grasses and legumes. HM concentration in soil, waste, and plant biomass; tolerance index; and uptake of HMs by plants were measured. The ash-sludge mixtures had a more favourable effect on the soil in terms of pHKCl, TOC, total nitrogen, and total exchangeable bases than the waste used separately. This provided beneficial conditions for plant growth and development. Consequently, the ash-sludge mixtures increased the plant yield as compared to ash alone, while the mixture containing the biomass ash also enhanced the yield in relation to the sewage sludge. The study showed that the mixtures allowed for a reduction of environmental risk arising from the HM input with waste to the soil. It was proven that HM availability for plants could be beneficially modified by mixing waste. Combining the coal ash with the sewage sludge is particularly recommended, owing to the unfavourable properties of coal ash for plants. The application of the higher dose of the coal ash-sludge mixture showed a better effect than the lower dose, while the influence of both doses of the biomass ash-sludge mixture was similar. Under the ash-sludge treatment, plants took up more HM than under the ash used separately, and the HM concentration in the obtained biomass did not generally exceed that observed under single wastes. This should reduce the accumulation of HMs in the soil during a long-term use of the waste and facilitates the utilisation of the produced biomass.


Asunto(s)
Ceniza del Carbón , Metales Pesados , Contaminación Ambiental , Metales Pesados/análisis , Aguas del Alcantarillado/análisis , Suelo
3.
Sci Total Environ ; 747: 141201, 2020 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-32777500

RESUMEN

Our work addresses a neglected aspect of heavy metal (HM) pollution of sediments in small floodplain reservoirs. Very little is known about this type of water bodies, in contrast to oxbow lakes or old river beds. The study examines the spatial horizontal distribution of HM and the effect of texture, organic carbon (OC) content, morphometric and location features on HM concentrations. Moreover, the data from the assessment of sediment toxicity were analysed with respect to recent years' droughts to estimate the potential toxicity of sediments as soils. The statistical analyses showed that the texture and the OC content had a significant impact on the HM concentrations. Fine-grained and OC-rich sediments exhibited higher HM pollution. Only one morphometric/location factor was shown to affect HM levels in sediments - the angle between the reservoir axis and the riverbed. The angle value affected the texture and, consequently, the HM content: with a rising angle the share of the coarse-grained fraction increased leading to a decrease in the HM concentration. The spatial horizontal HM distribution did not show statistically significant results, nonetheless, HM content was found to rise along with the distance from the initial part of reservoir. The toxicity levels were not exceeded in sediments, however, the evaluation of the material as soil showed that, according to European Union guidelines, the content of at least one HM was toxic in 80% of the samples. Contaminated floodplain reservoirs should be regarded as a double threat to riverine ecosystems. On the one hand, they are one of the main non-point sources of river valley pollution; on the other hand, given the drying up of reservoirs, sediments become soils and the soil-bound heavy metals become more toxic to the environment.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , China , Cambio Climático , Ecosistema , Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados/análisis , Metales Pesados/toxicidad , Ríos , Suelo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
4.
J Environ Manage ; 264: 110450, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32217325

RESUMEN

Owing to the growing volumes of ash and sewage sludge waste, there is a requirement for theoretical and practical research into the use of these wastes as a source of nutrients. However, there are relatively few studies on the transfer of macronutrients in soil-plant systems amended with ash-sewage sludge mixtures under field conditions. The aim of the study was to determine the effect of bituminous coal ash (AC), biomass ash (AB), and municipal sewage sludge (MSS) on the quantity and quality of a grass-legume mixture. During a 6 year field experiment on a sandy loam soil treated with the wastes, applied as mixtures or separately, the plant yield; N, P, K, Na, Mg, and Ca uptake by plants; macronutrient content and ratios in the plant biomass; and the recovery rate of macronutrients by plants were evaluated. The AB-MSS treatment increased the yield in comparison to that where the wastes were applied separately. The N, P, and Ca contents in the plant biomass and N and P uptake under ash-sludge treatments were in the range observed for the ash and sewage sludge. The AB-MSS co-application resulted in the highest K uptake. The AC-MSS treatment increased K and Mg uptake in relation to AC treatment. When AC or AB was added to the MSS, the Ca uptake increased relative to the MSS treatment. The plant biomass under the AB treatment was optimal for biofuel purposes in terms of the chemical composition. The co-application of AC or AB with MSS resulted in the optimum Ca:Mg ratio for fodder purposes. The recovery rate of the macroelements decreased in the following order: K, N, P, Mg, Na, and Ca. The results support the co-application of solid wastes such as ash and municipal sewage sludge to improve productivity, support the recycling of macronutrients, improve sustainability through the reduction of ash and sewage sludge disposal, and reduce reliance on mineral fertilizer.


Asunto(s)
Aguas del Alcantarillado , Suelo , Biomasa , Ceniza del Carbón , Fertilizantes , Nutrientes
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 189: 330-341, 2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-28830038

RESUMEN

The structural study of five Schiff bases derived from diaminomaleonitrile (DAMN) and 2-hydroxy carbonyl compounds was performed using 1H, 13C and 15N NMR methods in solution and in the solid state as well. ATR-FTIR and X-Ray spectroscopies were used for confirmation of the results obtained by NMR method. The imine obtained from DAMN and benzaldehyde was synthesized as a model compound which lacks intramolecular hydrogen bond. Deprotonation of all synthesized compounds was done by treating with tetramethylguanidine (TMG). NMR data revealed that salicylidene Schiff bases in DMSO solution exist as OH forms without intramolecular hydrogen bonds and independent on the substituents in aromatic ring. In the case of 2-hydroxy naphthyl derivative, the OH proton is engaged into weak intramolecular hydrogen bond. Two of imines (salDAMN and 5-BrsalDAMN) exist in DMSO solution as equilibrium mixtures of two isomers (A and B). The structures of equilibrium mixture in the solid state have been studied by NMR, ATR-FTIR and X-Ray methods. The deprotonation of three studied compounds (salDAMN, 5-BrsalDAMN, and 5-CH3salDAMN) proceeded in two different ways: deprotonation of oxygen atom (X form) or of nitrogen atom of free primary amine group of DAMN moiety (Y form). For 5-NO2salDAMN and naphDAMN only one form (X) was observed.

6.
Medicine (Baltimore) ; 94(52): e2369, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26717380

RESUMEN

Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. The chemotherapy for ALL is associated with a profound secondary immune deficiency.We evaluated the number and phenotype of natural killer (NK) cells at diagnosis, after the intensive chemotherapy and following the completion of the entire treatment for patients with ALL. The fraction, absolute number, and percentage of NK cells expressing interferon-γ were determined in full blood samples. The fraction of NK cells expressing CD158a, CD158b, perforin, A, B, and K granzymes was examined in isolated NK cells.We have shown that patients assessed at ALL diagnosis showed significantly lower values of the fraction of NK cells and percentage of NK cells with the granzyme A expression. Additionally, the absolute number of NK cells, the expression of CD158a, CD158b, perforin, and granzyme A were significantly lower in patients who completed intensive chemotherapy. Also, there was a significantly higher fraction of NK cells expressing granzyme K in patients who completed the therapy.Abnormalities of NK cells were found at all stages of the treatment; however, the most pronounced changes were found at the end of intensive chemotherapy.


Asunto(s)
Células Asesinas Naturales/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Adolescente , Antineoplásicos/uso terapéutico , Niño , Preescolar , Femenino , Citometría de Flujo , Granzimas/inmunología , Humanos , Lactante , Interferón gamma/inmunología , Células Asesinas Naturales/efectos de los fármacos , Recuento de Linfocitos , Masculino , Perforina/inmunología , Fenotipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Receptores KIR2DL1/inmunología , Receptores KIR2DL3/inmunología , Adulto Joven
7.
Artículo en Inglés | MEDLINE | ID: mdl-23501717

RESUMEN

Seven imine derivatives obtained by condensation of appropriate aldehydes and salicylaldehydes with 4-aminoantipyrine were investigated in terms of intramolecular hydrogen bond structure. On the base of (1)H, (13)C and (15)N NMR measurements in solution and in the solid state we found out that all compounds which can form such structure exist as OH forms with strong H-bonds to nitrogen atom. The structure conclusions taken from NMR study were confirmed by pKa measurements. Surpassingly, the positions of protons in H-bridges only very slightly depend on the substituents in aldehyde used for condensation and on the phase (solution vs. solid state). The influence of antipyrine moiety seems to be the major factor defining H-bond structure.


Asunto(s)
Aldehídos/química , Ampirona/análogos & derivados , Enlace de Hidrógeno , Isomerismo , Espectroscopía de Resonancia Magnética , Bases de Schiff/química , Espectrofotometría Ultravioleta
8.
Leuk Lymphoma ; 54(6): 1256-62, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23088710

RESUMEN

A total number of 817 children with acute lymphoblastic leukemia (ALL) and 181 with acute myeloblastic leukemia (AML) were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, an impact on long-term response was shown in ITRT for 13 drugs, while in initial AML only for cytarabine. For patients with ALL, a combined five-drug ITRT profile for prednisolone, l-asparaginase, vincristine, cytarabine and daunorubicin or doxorubicin had predictive value for probability of disease-free survival (pDFS) in univariate analysis, whereas in multivariate analysis, bone marrow response by day 33 was the only prognostic factor. For patients with AML, no factor had prognostic value for pDFS in univariate analysis, while ITRT to cytarabine almost reached significance. In conclusion, ITRT can possibly be regarded as a risk factor in childhood acute leukemias.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Niño , Preescolar , Estudios de Seguimiento , Humanos , Recién Nacido , Pronóstico , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
9.
Anticancer Res ; 32(12): 5495-9, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23225457

RESUMEN

AIM: The analysis of the prognostic impact of residual disease at day 15 of induction therapy, individual tumor response testing (ITRT) at diagnosis, initial factors and initial therapy response to the risk of relapse in children with precursor B-cell acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A total of 87 children were tested at diagnosis for ITRT and for persistence of blasts in bone marrow at day 15 (BML15>0.5%) and were followed-up in long-term analysis. RESULTS: The probability of disease-free survival (pDFS) was significantly better for patients with an ITRT profile showing sensitivity to prednisolone, vincristine, daunorubicin, and L-asparaginase. Patients with BML15>0.5% had higher ITRT for prednisolone, daunorubicin, L-asparaginase, and etoposide. Three factors had predictive impact for relapse: BML15>0.5%, ITRT for prednisolone and high combined ITRT profile for prednisolone, vincristine and L-asparaginase (PVA score). CONCLUSION: Persistence of blasts in bone marrow at day 15, ITRT showing resistance to prednisolone and high PVA score were the strongest and comparable prognostic factors predicting relapse in childhood ALL.


Asunto(s)
Antineoplásicos/farmacología , Médula Ósea/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adolescente , Asparaginasa/farmacología , Niño , Preescolar , Daunorrubicina/farmacología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Etopósido/farmacología , Femenino , Humanos , Lactante , Masculino , Análisis Multivariante , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Prednisolona/farmacología , Pronóstico , Vincristina/farmacología
10.
Contemp Oncol (Pozn) ; 16(3): 210-4, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23788881

RESUMEN

AIM OF THE STUDY: Resistance to imatinib is one of the most important issues in treatment of chronic myeloid leukemia (CML) patients. The objective of the study was to analyze the ex vivo drug resistance profile to bortezomib and 22 other antileukemic drugs, including three tyrosine kinase inhibitors (TKIs), in CML in comparison to acute myeloid leukemia (AML). MATERIAL AND METHODS: A total of 82 patients entered the study, including 36 CML and 46 AML adults. Among CML patients, 19 had advanced disease, 16 were resistant to imatinib, and 6 had ABL-kinase domain mutations. The ex vivo drug resistance profile was studied by the MTT assay. RESULTS: CML CELLS WERE MORE RESISTANT THAN AML BLASTS TO THE FOLLOWING DRUGS: prednisolone, vincristine, doxorubicin, etoposide, melphalan, cytarabine, fludarabine, thiotepa, 4-HOO-cyclophosphamide, thioguanine, bortezomib, topotecan, and clofarabine. CML cells were 2-fold more sensitive to busulfan than AML cells. CML patients with clinical imatinib resistance had higher ex vivo resistance to vincristine, daunorubicin, etoposide, and busulfan. No significant differences to all tested drugs, including TKIs, were observed between CML patients with non-advanced and advanced disease. CML patients with mutation had higher ex vivo resistance to vincristine, idarubicin, thiotepa, and busulfan. CONCLUSIONS: CML cells are ex vivo more resistant to most drugs than acute myeloid leukemia blasts. Busulfan is more active in CML than AML cells. In comparison to AML cells, bortezomib has little ex vivo activity in CML cells. No differences between CML subgroups in sensitivity to 3 tested TKIs were detected.

11.
Anticancer Res ; 31(4): 1453-7, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21508402

RESUMEN

AIM: The predictive value of residual disease measured by flow cytometry at day 15 of induction therapy was analyzed in 182 children treated for acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Peripheral blood (PB) and bone marrow were assessed for leukemia cells by morphology and flow cytometry at days 0, 8, and 15. RESULTS: Absolute blast count (ABC) >200/µl in PB by day 15 assessed by flow cytometry predicted a lower probability of disease free survival (pDFS) (p=0.056). Patients with bone marrow lymphoblast (BML)>0.5% had a lower pDFS (p=0.002). Cumulative relapse incidence for patients with BML<0.5% was 8.9% vs. 47.1% (OR=4.6, p=0.036). In common/pre-B-ALL patients aged >10 years with BML>0.5%, pDFS value was significantly lower. In the multivariate analysis, the only significant factor with adverse prognostic value for pDFS was BML>0.5% (HR=5.3 p=0.030). CONCLUSION: BML>0.5% analyzed by flow cytometry at day 15 is possibly the strongest prognostic factor in pediatric ALL.


Asunto(s)
Crisis Blástica/patología , Médula Ósea/patología , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adolescente , Adulto , Niño , Preescolar , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Lactante , Masculino , Neoplasia Residual/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Adulto Joven
12.
Med Wieku Rozwoj ; 13(1): 66-70, 2009.
Artículo en Polaco | MEDLINE | ID: mdl-19648663

RESUMEN

BACKGROUND: KIR-NKAT2 receptor, present on NK (natural killer) cells, is responsible for recognition of human leukocyte antigen C (HLA-C) on cells infected with different types of viruses. Its presence might contribute to disabling in elimination of infected cells and causing chronic infection. Another unknown parameter related to functionality of the immune system might be monocyte ability to form dendritic cells. OBJECTIVES: To answer the question if impaired expression of KIR-NKAT2 or diminished ability to monocytoid dendritic cell formation is a cause of recurrent infections in children with no evident immunodeficiences or after splenectomy? PATIENTS AND METHODS: A study was performed in 38 children diagnosed for immune deficiencies due to recurrent infections, splenectomy, humoral or cellular deficiencies. Mononuclear cells were isolated from peripheral blood. Monocytes and NK cells were isolated by SuperMACS device. An expression of KIR-NKAT2 on NK cells was determined by flow cytometry. Isolated monocytes were cultured for 7-14 days on enriched Methocult medium in order to stimulate monocytoid dendritic cell transformation. CD83 and CD206 expression was assayed before culture and after 7-14 days by flow cytometry. RESULTS: The KIR-NKAT2 expression was present in 31/38 patients. Monocytes of 37/38 patients has begun transformation into dendritic cells after 7 days of culture, although a large variability of expression was observed. In splenectomized patients a trend towards higher KIR-NKAT2 expression and lower transformation of dendritic cells was revealed. No other subgroup of patients with significantly altered expression of analyzed receptors was detected. CONCLUSIONS: Immunological defects, related to incorrect function of NK cells caused by disturbed expression of KIR-NKAT2 receptors, or impairment monocyte ability for transformation to dendritic cells, seems to be irresponsible for susceptibility for infections. Splenectomy might be an important risk factor disturbing mechanisms of immunologic function, also with respect to analyzed parameters, however this aspect requires further studies.


Asunto(s)
Células Dendríticas/metabolismo , Síndromes de Inmunodeficiencia/inmunología , Receptores KIR2DL3/metabolismo , Receptores KIR/metabolismo , Adolescente , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Lactante , Infecciones/complicaciones , Masculino , Proyectos Piloto , Recurrencia , Esplenectomía
13.
Ann Hematol ; 88(12): 1193-8, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19352661

RESUMEN

Multidrug resistance 1 (MDR1) gene expression determined by real-time polymerase chain reaction and results of rhodamine assay were analyzed at diagnosis and after 3 days of ex vivo therapy with prednisolone in 36 pediatric patients with acute lymphoblastic leukemia (ALL). Only 62% patients with de novo ALL had significant decrease of MDR1 expression. These patients had over twofold lower rhodamine retention in the presence of cyclosporine A on day 3 than others and had better probability of disease-free survival. In this study, we have shown that changes in the expression of MDR1 gene after short-term incubation of lymphoblasts with prednisolone may have prognostic value in pediatric de novo ALL patients.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Antineoplásicos Hormonales/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prednisolona/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Pronóstico
14.
Anticancer Res ; 28(3B): 1927-31, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18630483

RESUMEN

BACKGROUND: The role of cellular drug resistance in childhood acute myeloid leukemia (AML) has not yet been established. The aim of the study was the analysis of the clinical value of ex vivo drug resistance in pediatric AML. PATIENTS AND METHODS: A cohort of 90 children with de novo AML were assayed for drug resistance profile by the 3-4,5-dimethylthiazol-2-yl-2,5-difenyl tetrazolium bromide (MTT) assay and prognostic model of in vitro drug sensitivity was analyzed. RESULTS: Children who relapsed during follow-up showed higher in vitro resistance of leukemic blasts to most of the drugs tested, except for cytarabine, cladribine, vincristine, mercaptopurine and thioguanine. A combined in vitro drug resistance profile to fludarabine, treosulfan and mitoxantrone (FTM score) was defined and it had an independent prognostic significance for disease free survival in pediatric AML. CONCLUSION: The combined fludarabine, treosulfan and mitoxantrone resistance profile to possibly may be used for better stratification of children with AML or indicate the necessity for additional therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Busulfano/administración & dosificación , Busulfano/análogos & derivados , Niño , Preescolar , Estudios de Cohortes , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/patología , Masculino , Mitoxantrona/administración & dosificación , Pronóstico , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados
16.
J Cancer Res Clin Oncol ; 133(11): 875-93, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17671794

RESUMEN

PURPOSE: Cellular resistance in childhood acute leukemias might be related to profile and function of multidrug resistance proteins and apoptosis regulating proteins. The aims of the study were: (1) analysis of expression of MRP1, PGP1, LRP, BCL-2 and p53 proteins; (2) correlation with ex vivo drug resistance, and (3) analysis of their prognostic impact on clinical outcome in childhood acute lymphoblastic (ALL) and acute myeloid (AML) leukemia. METHODS: Total number of 787 children diagnosed for initial ALL (n = 527), relapsed ALL (n = 104), initial AML (n = 133) and relapsed AML (n = 23) were included into the study. Mean follow-up period was 3.5 years. Drug resistance for up to 30 anticancer agents was performed by the MTT assay. Expression of all proteins was tested by flow cytometry. RESULTS: Both initial AML and relapsed ALL samples showed higher drug resistance than initial ALL samples. No significant differences were found in drug resistance between initial and relapsed AML samples. The presence of multidrug resistance and apoptosis proteins had no impact on pDFS in iALL and iAML, however strong trend towards adverse prognostic impact of MRP1, PGP and LRP on pDFS in rALL was observed. The same trend was observed for each of analyzed co-expressions of tested multidrug resistance proteins. CONCLUSIONS: The phenomenon of cellular drug resistance in childhood acute leukemias is multifactorial and plays an important role in response to therapy. Expression of MRP1, PGP and LRP proteins, as well as their co-expression play possible role in childhood relapsed ALL.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Partículas Ribonucleoproteicas en Bóveda/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Adolescente , Adulto , Antineoplásicos/farmacología , Niño , Preescolar , Femenino , Citometría de Flujo , Regulación Leucémica de la Expresión Génica , Humanos , Inmunofenotipificación , Lactante , Recién Nacido , Masculino , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Recurrencia Local de Neoplasia/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Partículas Ribonucleoproteicas en Bóveda/genética
17.
Anticancer Res ; 27(6B): 4021-5, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18225565

RESUMEN

BACKGROUND: Bortezomib is an inhibitor of proteasome and NF-kappaB, with activity in various solid tumors and hematological malignancies. AIM: The aim of the study was the analysis of in vitro drug resistance to bortezomib and other anticancer drugs in de novo and relapsed adult acute myeloid leukemia (AML). PATIENTS AND METHODS: The leukemic cells of 46 adult patients with AML were tested for the in vitro drug resistance profile. The group included 20 de novo and 26 relapsed AML patients, among whom, 12 relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) and 4 after autologous HSCT. The MTT assay was performed for 21 drugs. Expression of P-glycoprotein (PGP), multidrug resistance-associated protein-1 (MRP1) and lung resistance protein (LRP) proteins was measured by flow cytometry. RESULTS: No significant differences in drug resistance were found for all tested drugs between de novo and relapsed AML samples, while expression of PGP, MRP1 and LRP was higher in relapsed patients. Patients with refractory or relapsed disease, had higher resistance of myeloblasts to cyclophosphamide (RR = 2.4, p = 0.050), and better sensitivity to busulfan (RR = 0.4, p = 0.054) and topotecan (RR = 0.4, p = 0.031). Those who have died due to refractory/relapsed disease (n = 16) had better sensitivity to bortezomib (RR = 0.6, p = 0.046) and treosulfan (RR = 0.1, p = 0.018). CONCLUSION: In vitro drug resistance in relapsed adult AML is comparable to that in de novo disease. Activity in vitro of bortezomib might be a rationale for its use in refractory/relapsed AML adult patients.


Asunto(s)
Antineoplásicos/farmacología , Ácidos Borónicos/farmacología , Leucemia Mieloide/tratamiento farmacológico , Pirazinas/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Anciano , Bortezomib , Resistencia a Antineoplásicos , Femenino , Citometría de Flujo , Células HL-60 , Humanos , Leucemia Mieloide/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Partículas Ribonucleoproteicas en Bóveda/biosíntesis , Partículas Ribonucleoproteicas en Bóveda/metabolismo
18.
Anticancer Res ; 26(6B): 4499-503, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17201170

RESUMEN

BACKGROUND: Chemotherapy is the commonly accepted standard therapy for most types of brain tumor, especially in medulloblastoma, primitive neuroectodermal tumor and astrocytoma. However, no efficient therapy has been established to date for glioblastoma multiforme. The aim of the present study was to analyze the activity of bortezomib in glioblastoma cell lines in comparison with that in a pediatric acute lymphoblastic leukemia cell line. MATERIALS AND METHODS: Glioblastoma multiforme T98G, glioblastoma-astrocytoma U373M and T-lineage acute lymphoblastic leukemia CCRF-CEM cell lines were used. Proteasome inhibitor, bortezomib and 14 other anticancer drugs were tested using the MTT assay. RESULTS: Compared to the acute lymphoblastic cell line, both glioblastoma cell lines showed relatively good sensitivity to bortezomib, as well as to cisplatin, carboplatin, etoposide and actinomycin-D. The lines showed intermediate sensitivity to thiotepa and daunorubicin, but were highly resistant to first-line drugs used in the therapy of acute lymphoblastic leukemia, such as prednisolone, L-asparaginase, vincristine, doxorubicin and cytarabine. Bortezomib, which is not a substrate for PGP and MRP1, did not show cross resistance to drugs transported by these proteins. CONCLUSION: Our results support the necessity for further research on the role of bortezomib in the therapy of glioblastoma.


Asunto(s)
Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Pirazinas/uso terapéutico , Bortezomib , Línea Celular Tumoral , Humanos
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