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In children, therapy-related hematologic neoplasms (t-HN) are uncommon. Many are driven by genetic events independent of clonal hematopoiesis. We sought to understand the clinical and genetic factors of pediatric t-HN in a large independent cohort. Fifty-six t-HN were retrospectively identified. Chromosome microarray, next-generation and/or RNA sequencing were performed. Patients had primary hematologic, solid, or central nervous system tumors. t-HN included myeloid (t-MN) and lymphoblastic (t-ALL) phenotypes. Approximately half of the cases harbored KMTA2A rearrangement (KMT2Ar). Among t-HN without KMT2Ar, genetic drivers were heterogeneous, including diverse fusions or aneuploidy. Approximately 18% harbored 17p deletions and/or TP53 mutations. EFS/OS was not associated with t-HN lineage or KMT2Ar, but HSCT was associated with improved EFS and OS. We detail one of the largest cohorts to date of pediatric t-HN, confirming frequent KMT2Ar and t-ALL.
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Acquired thrombotic thrombocytopenic (aTTP) purpura is a life-threatening condition that can lead to devastating thromboembolic events. Recently, caplacizumab has been shown to rapidly restore platelet numbers and reduce the risk of severe end-organ damage when added to plasma exchanges (PEXs) and immunosuppression (IST). Here, we report the outcomes in 3 children with aTTP who were treated with caplacizumab in combination with PEXs and IST. In all 3 patients, platelet count increased to >15,000/mm 3 in 24 h and normalized on day 4, whereas normalization of ADAMTS13 activity >50% and elimination of the inhibitor was achieved after 18 to 89 days. Epistaxis was observed in 2 patients and was the only side effect related to caplacizumab. Caplacizumab is a promising agent for first-line treatment of children with aTTP.
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Púrpura Trombocitopénica Trombótica , Anticuerpos de Dominio Único , Niño , Humanos , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Intercambio Plasmático , Factor de von Willebrand , Terapia de Inmunosupresión , Proteína ADAMTS13RESUMEN
The plant flavonoids taxifolin and rutin are among the best known and best studied antioxidants. In addition to their antioxidant properties, other pharmacobiological properties have been established for these substances. At the same time, taxifolin and rutin are chemically labile. They are prone to oxidative degradation and have poor water solubility. Under conditions of their real consumption, all this can lead to a significant reduction or complete loss of bioactivity of these flavonoids. Flavonoid modification and encapsulation techniques can be used to overcome these barrier factors. The use of micronization process for taxifolin and rutin allows changing the lipophilicity values of antioxidants. For micronized taxifolin, the log P value is 1.3 (1.12 for the control forms), and for rutin, it was 0.15 (-0.64 for the control forms). The antioxidant activity of micronized flavonoids has increased about 1.16 times compared to control forms. The present study evaluates the possibility of using encapsulation of premyconized flavonoids by complex coacervation, in order to preserve their antioxidant properties. The results of an in vitro digestion study show that the encapsulated forms of antioxidants retain their bioactivity and bioavailability better than their original forms. The bioavailability indices for the encapsulated forms of flavonoids are more than 1.6 times higher than for their original forms. The digested fractions of the encapsulated properties reveal better antioxidant properties than their original forms in in vitro tests evaluating the antioxidant properties on cultures of the protozoan Paramecium caudatum and human neuroblastoma SH-SY5Y cells. Encapsulated rutin indicates the highest activity, 0.64 relative to PMA. Thus, the studies represent the feasibility of using encapsulation to protect flavonoids during digestion and ensure the preservation of their antioxidant properties.
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Langerhans cell histiocytosis (LCH) is a disorder with a variety of clinical signs. The most severe forms affect risk organs (RO). The established role of the BRAF V600E mutation in LCH led to a targeted approach. However, targeted therapy cannot cure the disease, and cessation leads to quick relapses. Here, we combined cytosine-arabinoside (Ara-C) and 2'-chlorodeoxyadenosine (2-CdA) with targeted therapy to achieve stable remission. Nineteen children were enrolled in the study: 13 were RO-positive (RO+) and 6 RO-negative (RO-). Five patients received the therapy upfront, whereas the other 14 received it as a second or third line. The protocol starts with 28 days of vemurafenib (20 mg/kg), which is followed by 3 courses of Ara-C and 2-CdA (100 mg/m2 every 12 h, 6 mg/m2 per day, days 1-5) with concomitant vemurafenib therapy. After that, vemurafenib therapy was stopped, and 3 courses of mono 2-CdA followed. All patients rapidly responded to vemurafenib: the median disease activity score decreased from 13 to 2 points in the RO+ group and from 4.5 to 0 points in the RO- group on day 28. All patients except 1 received complete protocol treatment, and 15 of them did not have disease progression. The 2-year reactivation/progression-free survival (RFS) for RO+ was 76.9% with a median follow-up of 21 months and 83.3% with a median follow-up of 29 months for RO-. Overall survival is 100%. Importantly, 1 patient experienced secondary myelodysplastic syndrome after 14 months from vemurafenib cessation. Our study demonstrates that combined vemurafenib plus 2-CdA and Ara-C is effective in a cohort of children with LCH, and the toxicity is manageable. This trial is registered at www.clinicaltrials.gov as NCT03585686.
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Cladribina , Histiocitosis de Células de Langerhans , Niño , Humanos , Cladribina/uso terapéutico , Vemurafenib/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Citarabina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/genéticaRESUMEN
We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin (hATG) and cyclosporin A (CsA) with (n = 49) or without (n = 49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR + IST and IST groups was similar (65% vs 53%; P = .218); however, the complete response (CR) rate was significantly higher in the ELTR + IST group (31% vs 12%; P = .027). In severity subgroups, the ORR was 89% vs 57% (P = .028) in favor of IST + ELTR in SAA, but it did not differ in patients with vSAA (52% vs 50%; P = .902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared with 17% of initial ELTR(+) patients (P = .016). No significant difference in ELTR + IST and IST groups was observed in the 3-year overall survival (OS) (89% vs 91%; P = .673) or the 3-year event-free survival (EFS) (53% vs 41%; P = .326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. This trial was registered at Clinicaltrials.gov as #NCT03413306.
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Anemia Aplásica , Inmunosupresores , Humanos , Inmunosupresores/efectos adversos , Anemia Aplásica/diagnóstico , Anemia Aplásica/tratamiento farmacológico , Resultado del Tratamiento , Terapia de InmunosupresiónRESUMEN
Visualization of the microstructure of the food matrix of both raw materials and the final product is one of the keys to understanding the processes occurring during its formation. It is the fixation of the results at the microlevel that allows us to form a hypothesis and then confirm it with the obtained array of experimental data. The presented study is aimed at studying the effect of ultrasonic water treatment on the change in the microstructure of wheat grain during its humidification. The article also presents the results of studying the microstructure of dough and wheat flour bread obtained using water after ultrasonic water treatment and the intensity of the processes of staling of finished bread in storage. The object of the study was grain of soft spring white wheat (Triticum aestivum L.), varieties of Lubava, harvest 2014-2018, Russia (the protein content was 12.5 ± 0.3 g/100 g in terms of humidity); dough and bread made from wheat flour (ash content 0.55%, mass fraction of gluten 28.5%), produced using the technology of plain bread, a classic recipe without improvers. Ultrasound-treated water with an exposure frequency of 22 ± 1.65 kHz and with a power variation of 252-630 W/l was used in test technology. The experimental data obtained made it possible to establish the intensification of the processes of swelling of wheat grain during soaking. In the experimental samples, after 8 hours of soaking, the loosened structure of the endosperm and evenly swollen components of the grain were observed, and the loop of the groove was closed. Activation of the processes of dough science was established, and gluten flour in the dough formed a single monolithic frame, in which the swollen starch grains are tightly packed. The interstitial walls of the crumb of the prototypes consisted of a solid mass of protein coagulated during baking, inside of which swollen gelatinized starch grains are interspersed, they are closely adjacent to the mass of coagulated protein with their entire surface, and therefore, there is no sharp, clearly visible boundary between them. The most pronounced changes in the structure of the dough and bread crumb were noted when using water, after ultrasonic water treatment at a power of 504 and 630 W/l. This method of exposure can be recommended as the best for obtaining good quality bread with less pronounced staling during storage.
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Today, food products not only should serve the source of main nourishment but also must minimize the risk of negative impact on the human body. Products enriched with antioxidants can be referred to such category. For food producers, the development of products "for health" is usually connected with significant investment, whereas the final success of innovative products does not always meet the expectations. The greatest part of such products is withdrawn from the market during the first year. It is important for manufacturers to learn consumer behavior in order to ensure sale growth and a stable market position. The purpose of this study was to study consumer reception of products containing antioxidants. (It is important to conduct market research to identify the needs of buyers in order to maintain a stable position in the market. In order to study this issue, we analyzed the consumer perception of foods with antioxidant properties.) We studied the consumer perception of products with antioxidant properties with regard to choice predictors and barriers for purchasing, which finally determine the success of the product on the market. For this purpose, we conducted a survey of 721 consumers of the South Urals. The results of the statistical analysis done with the help of SPSS proved that South Ural consumers in general are ready to purchase products containing antioxidants. Besides, producers must bring information concerning the real value of the product and win the consumer trust and confidence as far as these are the main predictors determining the choice for purchasing the products containing antioxidants. Misunderstanding of the role antioxidants play in the human body may lead to perception of risk concerning consumption of such products and rejection of the purchase.
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Whole wheat flour from sprouted wheat grain is a full-fledged raw ingredient containing essential amino acids, easily digestible sugars, and dietary fiber, with increased digestibility and enzymatic activity. The use of this raw material in the production of food products will contribute to the creation of products for a healthy diet of the population. This study is aimed at studying the possibility of using whole grain flour from sprouted wheat in the production of bread and its effect on the rheological and microstructural properties of dough and finished products. It was found that whole wheat flour from sprouted wheat grain had an even particle size and was characterized by a uniform distribution of particles over the size range (from 53 to 209 microns-61 ± 3%); large particles from 297 to 497 microns were present in an amount of no more than 10 ± 3%. The replacement of 20% refined flour with whole wheat flour from sprouted wheat grain resulted in better values of the farinograph quality index (200 ± 3 mm). The bread obtained according to this recipe had a high specific volume (4.21 ± 0.62 mL.g-1) and optimal rheological characteristics: total deformation13.7 ± 0.3 mm, plastic4.3 ± 0.3 mm, and elastic9.4 ± 0.3 mm. The study of the microstructure of dough and bread also confirmed the established dependencies. This percentage of replacement of refined flour with whole wheat flour from sprouted wheat grain can be recommended as the best for obtaining bread of good quality with high rheological characteristics.
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BACKGROUND: Langerhans cell histiocytosis (LCH) is a disease that arises from myeloid cells that phenotypically resemble Langerhans cells (LC), which is typically driven by the BRAF V600E mutation. High-risk LCH has a poor prognosis. PROCEDURE: Fifteen children with BRAF V600E + LCH received vemurafenib between March 2016 and February 2020. The median age at LCH onset was 2 months and the median age at the start of vemurafenib treatment was 22 months. The median disease activity score (DAS) at the start of vemurafenib treatment was 12 points. RESULTS: The median duration of vemurafenib treatment was 29 months. All patients responded to treatment, with median DAS of 4 points at week 4 and 1 point at 6 months. Two patients died: 1 of hepatic failure after NSAID overdose and 1 of neutropenic sepsis. Cessation of vemurafenib resulted in relapse in 5 patients and was only possible for 1 patient. Serial measurements of BRAF V600E using cell-free circulating DNA revealed that 7 patients had persistently high mutant allele levels. CONCLUSION: Vemurafenib is effective in children with BRAF V600E + LCH. However, treatment with vemurafenib does not eradicate the disease and its long-term toxicity has not been established.
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Antineoplásicos/uso terapéutico , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Vemurafenib/uso terapéutico , Alelos , Sustitución de Aminoácidos , Preescolar , Femenino , Histiocitosis de Células de Langerhans/diagnóstico , Humanos , Lactante , Masculino , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Resultado del Tratamiento , Vemurafenib/farmacologíaRESUMEN
Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. The study included 151 children with ITP, of whom 56 had disease duration less than 12 months (grouped together as acute/persistent) and 95 were chronic. Samples of 57 healthy children were used as controls, while 5 patients with leukemia, 5 with aplastic anemia, 4 with MYH9-associated thrombocytopenia, and 7 with Wiskott-Aldrich syndrome were used as non-ITP thrombocytopenia controls. Whole blood flow cytometry revealed that platelets in both acute/persistent and chronic ITP were increased in size compared with healthy donors. They were also pre-activated as assessed by PAC1, CD62p, cytosolic calcium, and procoagulant platelet levels. This pattern was not observed in other childhood thrombocytopenias. Pre-activation by CD62p was higher in the bleeding group in the chronic ITP cohort only. Romiplostim treatment decreased size and pre-activation of the patient platelets, but not calcium. Our data suggest that increased size, pre-activation, and cytosolic calcium are common for all ITP platelets, but their association with bleeding could depend on the disease phase.
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Plaquetas/efectos de los fármacos , Señalización del Calcio , Hemorragia/etiología , Púrpura Trombocitopénica Idiopática/sangre , Receptores Fc/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Trombopoyetina/uso terapéutico , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pruebas de Función Plaquetaria , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Proteínas Recombinantes de Fusión/farmacología , Trombopoyetina/farmacologíaRESUMEN
INTRODUCTION: Accurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions. METHODS: The DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high-throughput sequencing (HTS). RESULTS: Acquired GATA1 mutations were identified in 43 cases (98%). Additional mutations in the genes of JAK/STAT signaling, cohesin complex, and RAS pathway activation were revealed by HTS in 48%, 36%, and 16% of the cases, respectively. CONCLUSIONS: The GATA1 mutations were reliably determined by fragment analysis and/or Sanger sequencing in a single PCR amplicon manner. For patients with extremely low blast counts and/or rare variants, the rapid screening with simple molecular approaches must be complemented with HTS. The JAK/STAT and RAS pathway-activating mutations may represent an extra option of targeted therapy with kinase inhibitors.
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Síndrome de Down/genética , Factor de Transcripción GATA1/genética , Leucemia Mieloide Aguda/genética , Niño , Síndrome de Down/complicaciones , Exones , Femenino , Humanos , Leucemia Mieloide Aguda/complicaciones , Masculino , MutaciónAsunto(s)
Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Glucocorticoides/uso terapéutico , Intercambio Plasmático , Púrpura Trombocitopénica Idiopática/terapia , Rituximab/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológicoRESUMEN
We retrospectively analyzed sequential therapy with romiplostim and eltrombopag in 23 children with immune thrombocytopenia: switching from romiplostim to eltrombopag (10 patients) or vice versa (13 patients). The median age of patients at enrollment in the study was 5.6 years (2-15 years). Switching from romiplostim to eltrombopag was effective in eight (80%) patients, whereas switching from eltrombopag to romiplostim was effective in eight (62%) patients. The response rate was similar in patients failing the first thrombopoietin receptor agonist and those who had previous response. To date, all responders continue to maintain platelets over 50 × 109 /L at 13-39 months after switching.
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Benzoatos/administración & dosificación , Hidrazinas/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/administración & dosificación , Receptores Fc/administración & dosificación , Receptores de Trombopoyetina/agonistas , Proteínas Recombinantes de Fusión/administración & dosificación , Centros de Atención Terciaria/normas , Trombopoyetina/administración & dosificación , Adolescente , Niño , Preescolar , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recuento de Plaquetas , Pronóstico , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/clasificación , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
We evaluated the outcome of αß T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory acute myelogenous leukemia (AML). Twenty-two patients with either primary refractory (nâ¯=â¯10) or relapsed refractory (nâ¯=â¯12) AML in active disease status received a transplant from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent myeloablative conditioning with treosulfan and thiotepa. Antithymocyte globulin was substituted with tocilizumab in all patients and also with abatacept in 10 patients. Grafts were peripheral blood stem cells engineered by αß T cell and CD19 depletion. Post-transplantation prophylactic therapy included infusion of donor lymphocytes, composed of a CD45RA-depleted fraction with or without a hypomethylating agent. Complete remission was achieved in 21 patients (95%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 18%, and the cumulative incidence of chronic GVHD was 23%. At 2 years, transplantation-related mortality was 9%, relapse rate was 42%, event-free survival was 49%, and overall survival was 53%. Our data suggest that αß T cell-depleted haploidentical HSCT provides a reasonable chance of long-term survival in a cohort of children with chemorefractory AML and creates a solid basis for further improvement.
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Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Depleción Linfocítica/métodos , Receptores de Antígenos de Linfocitos T alfa-beta , Terapia Recuperativa/métodos , Niño , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/mortalidad , Transfusión de Linfocitos , Análisis de Supervivencia , Trasplante Haploidéntico , Trasplante Homólogo , Resultado del TratamientoRESUMEN
T(16;21)(p11;q22)/FUS-ERG is a rare but recurrent translocation in acute leukemias and in some types of solid tumors. Due to multiple types of FUS-ERG transcripts, PCR-based minimal residual disease detection is impeded. In this study, we evaluated a cohort of pediatric patients with t(16;21)(p11;q22)/FUS-ERG and revealed fusion gene breakpoints. We implemented next-generation sequencing (NGS) on long PCR amplicons for the detection of fusion genes with unknown partners or DNA breakpoints. That allowed us to describe different fusion variants of FUS/ERG in different patients and to detect MRD on both RNA and DNA levels. We also found several accompanying mutations in epigenetic regulators (DNMT3A, ASXL1, BCOR) by targeted NGS approach in AML cases. These mutations preceded full transformation by t(16;21)(p11;q22)/FUS-ERG and allowed us to trace clonal evolution on all steps of therapy. As a casual observation, the ASXL1 mutation was found in the unrelated donor hematopoietic cells.
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Cromosomas Humanos Par 16 , Cromosomas Humanos Par 21 , Leucemia Mieloide Aguda/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína FUS de Unión a ARN/genética , Translocación Genética , Sustitución de Aminoácidos , Preescolar , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 22 , Estudios de Cohortes , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A , Análisis Mutacional de ADN , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/prevención & control , Leucemia Mieloide Aguda/terapia , Masculino , Mutación , Recurrencia Local de Neoplasia/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Carga TumoralRESUMEN
We describe an infant who developed juvenile myelomonocytic leukemia (JMML) at the age of 6 months. Myeloproliferation was effectively controlled by low-dose cytosine arabinoside and 13-cis retinoic acid therapy. Two years after therapy for JMML was stopped, at the age of 5 years, the patient developed autoimmune thrombotic thrombocytopenic purpura (TTP). TTP was transiently controlled by plasma exchange, prednisolone, rituximab, and cyclophosphamide, but relapsed within a short time. Long-term control of TTP was established by sirolimus. Somatic N-RAS G38AâGly13Asp substitution was restricted to hematopoietic cells. The somatic N-RAS mutation may link myeloproliferation and autoimmunity.
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Antibióticos Antineoplásicos/uso terapéutico , Genes ras , Leucemia Mielomonocítica Juvenil/genética , Mutación , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/genética , Sirolimus/uso terapéutico , Edad de Inicio , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Preescolar , Citarabina/administración & dosificación , Humanos , Lactante , Isotretinoína/administración & dosificación , Leucemia Mielomonocítica Juvenil/complicaciones , Leucemia Mielomonocítica Juvenil/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/complicacionesRESUMEN
The reaction of Na2WO4 and SeO2 under moderately acidic conditions yielded a novel 39-tungsto-6-selenite, [(Se2W12O46(WO(H2O))3](24-) (1), isolated as Na24[H6Se6W39O144]·74H2O. The macrocyclic polyanion consists of three {Se2W12} fragments connected via three trans-{WO(H2O)}(4+) groups. The same {Se2W12} building block is present in the structure of [(Se2W12O46)2{Mn2Cl(H2O)2}{Mn(H2O)2}2(SeO)2](13-) (2), which was obtained from the same reagents in the presence of MnCl2. The compounds were characterized by single-crystal X-ray diffraction, (77)Se NMR, Fourier transform infrared, and Raman spectroscopy.
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Complejos de Coordinación/síntesis química , Ácido Selenioso/química , Tungsteno/química , Complejos de Coordinación/química , Cristalografía por Rayos X , Ciclización , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
We used single-walled carbon nanotube (CNT) films to modulate the morpho-functional and proliferative characteristics of astrocytes. When plated on the CNT films of various thicknesses, astrocytes grow bigger and rounder in shape with a decrease in the immunoreactivity of glial fibrillary acidic protein along with an increase in their proliferation, changes associated with the dedifferentiation of astrocytes in culture. Thus, CNT films, as a coating material for electrodes used in brain machine interface, could reduce astrogliosis around the site of implantation.
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Astrocitos/citología , Nanotubos de Carbono/química , Astrocitos/química , Desdiferenciación Celular , Línea Celular , Proliferación Celular , ElectrodosRESUMEN
We evaluated frequencies of NPM1, FLT3, c-KIT mutations in childhood acute myeloid leukemia (AML) in Russia and assessed prognostic relevance of the mutations. RNA and DNA were extracted from bone marrow samples of 186 (106 male and 80 female) pediatric patients younger than 17 year with de novo AML. Mutations and chromosomal rearrangements were detected by sequencing of a corresponding gene. NPM1 mutations were found in 5.2%, FLT3 mutations in 12.1%, c-KIT mutations in 3.7% of the patients. NPM1 mutations were associated with the absence of chromosomal aberrations (P=0.007) and FLT3/ITD (P=0.018). New data on incidence of c-KIT mutations in various AML subtypes as well as new variations of c-KIT mutations in the exon 8 are presented. The results are compared to previously published studies on NPM1, FLT3, c-KIT mutations in various populations. No statistically significant differences in survival rates between groups with or without of FLT3, NPM1, c-KIT mutations were found (P>0.05). Meanwhile, 4-year overall survival rates were higher in patients having NPM1 mutations comparing with NPM1/WT patients (100% vs. 50%) and in patients having FLT3 mutations comparing with FLT3/WT patients (70% vs. 50%). The data presented contribute to knowledge on incidence and prognostic significance of the mutations in pediatric AML.