Non-calorimetric determination of absorbed power during magnetic nanoparticle based hyperthermia

Nanomagnetic hyperthermia (NMH) is intensively studied with the prospect of cancer therapy. A major challenge is to determine the dissipated power during in vivo conditions and conventional methods are either invasive or inaccurate. We present a non-calorimetric method which yields the heat absorbed during hyperthermia: it is based on accurately measuring the quality factor change of a resonant radio frequency circuit which is employed for the irradiation. The approach provides the absorbed power in real-time, without the need to monitor the sample temperature as a function of time. As such, it is free from the problems caused by the non-adiabatic heating conditions of the usual calorimetry. We validate the method by comparing the dissipated power with a conventional calorimetric measurement. We present the validation for two types of resonators with very different filling factors: a solenoid and a so-called birdcage coil. The latter is a volume coil, which is generally used in magnetic resonance imaging (MRI) under in vivo condition. The presented method therefore allows to effectively combine MRI and thermotherapy and is thus readily adaptable to existing imaging hardware.Comment: 7 pages, 3 figures+Supplementary Material (2 pages, 3 figures

Ultrafast sensing of photoconductivity decay using microwave resonators

Microwave reflectance probed photoconductivity (or $\mu$-PCD) measurement represents a contactless and non-invasive method to characterize impurity content in semiconductors. Major drawbacks of the method include a difficult separation of reflectance due to dielectric and conduction effects and that the $\mu$-PCD signal is prohibitively weak for highly conducting samples. Both of these limitations could be tackled with the use of microwave resonators due to the well-known sensitivity of resonator parameters to minute changes in the material properties combined with a null measurement. A general misconception is that time resolution of resonator measurements is limited beyond their bandwidth by the readout electronics response time. While it is true for conventional resonator measurements, such as those employing a frequency sweep, we present a time-resolved resonator parameter readout method which overcomes these limitations and allows measurement of complex material parameters and to enhance $\mu$-PCD signals with the ultimate time resolution limit being the resonator time constant. This is achieved by detecting the transient response of microwave resonators on the timescale of a few 100 ns \emph{during} the $\mu$-PCD decay signal. The method employs a high-stability oscillator working with a fixed frequency which results in a stable and highly accurate measurement.Comment: 7 pages, 6 figures+Supplementary Material

Extracelluláris vezikulák és hematológiai malignitásokban játszott szerepük

Absztrakt Extracelluláris vesiculák minden szervezetben képződnek. Három legintenzívebben vizsgált csoportjuk az apoptotikus testek, a microvesiculák és az exosomák. A sejtek közötti kommunikációban, immunreakciókban, angiogenezisben betöltött szerepük csak néhány az eddig megismertek közül. A fiziológiás folyamatok mellett sokféle betegségben leírták változásaikat; a patomechanizmusban betöltött szerepük mellett felvetődik potenciális használatuk biomarkerekként. A szerzők betekintést kívánnak nyújtani az extracelluláris vesiculák kutatásába, kiemelve azt a néhány tanulmányt, amely a hematológiai malignitásokra fókuszált. A microvesiculák és exosomák vérplazmában mért mennyisége, a terápia során megfigyelt minőségi változása miatt felmerült, hogy a diagnosztikában, prognosztikában, illetve a minimális residualis betegség monitorozásában is használhatók lehetnek. Akut myeloid leukaemiában a természetes ölősejtek aktivitásának szupresszálásában bizonyított a blasteredetű exosomák szerepe. Krónikus lymphoid leukaemiában a microvesiculák közreműködése valószínű a gyógyszer-rezisztencia kialakulásában is. Orv. Hetil., 2016, 157(35), 1379–1384. | Abstract Extracellular vesicles are produced in all organisms. The most intensively investigated categories of extracellular vesicles include apoptotic bodies, microvesicles and exosomes. Among a very wide range of areas, their role has been confirmed in intercellular communication, immune response and angiogenesis (in both physiological and pathological conditions). Their alterations suggest the potential use of them as biomarkers. In this paper the authors give an insight into the research of extracellular vesicles in general, and then focus on published findings in hematological malignancies. Quantitative and qualitative changes of microvesicles and exosomes may have value in diagnostics, prognostics and minimal residual disease monitoring of hematological malignancies. The function of extracellular vesicles in downregulation of natural killer cells’ activity has been demonstrated in acute myeloid leukemia. In chronic lymphocytic leukemia, microvesicles seem to play a role in drug resistance. Orv. Hetil., 2016, 157(35), 1379–1384

Új és hagyományos irányok a gyermekkori akut lymphoblastos leukaemia biológiájában és ellátásában

Owing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy. The number of genes with identified alterations in leukemic lymphoblasts is over thirty and their pathobiologic role is only partly clear. There are known patient groups where the use of specific drugs is based on gene expression profiling (e.g., tyrosine kinase inhibitors in Philadelphia-like B-cell ALL). The continuous assessment of minimal residual disease became a routine due to the determination of a leukemia-associated immunophenotype by flow cytometry or a sensitive molecular marker by molecular genetics at diagnosis. Epitopes of cluster differentiation antigens on blast surface (primarily CD19, CD20 and CD22 on malignant B cells) can be attacked by monoclonal antibodies. Moreover, antitumor immunity can be strengthened utilizing either cell surface markers (bispecific T cell engagers, chimeric antigen receptor T cell therapy) or tumor-specific immune cells (immune checkpoint inhibitors). This review gives an insight into current knowledge in these innovative therapeutic directions. Orv Hetil. 2018; 159(20): 786-797

Circulating microRNAs as minimal residual disease biomarkers in childhood acute lymphoblastic leukemia

Treatment stratification based on bone marrow minimal residual disease (MRD) at set time points has resulted in considerably improved survival in pediatric acute lymphoblastic leukemia (ALL). Treatment response is assessed using bone marrow samples. MicroRNAs (miRs) easily traffic among fluid spaces and are more stable than most other RNA classes. We examined the role of circulating miRs as putative less invasive MRD biomarkers.In an exploratory experiment, expression of 46 preselected miRs was studied in platelet-free blood plasma samples of 15 de novo, 5 relapsed ALL patients and 10 controls by Custom TaqMan Array Advanced MicroRNA Card. Based on their high expression in ALL compared to controls, and on the reduction observed along the induction therapy, four miRs were selected for further analyses: miR-128-3p, -181a-5p, -181b-5p and 222-3p. Their expression was measured by qPCR at 4 time points in 27 de novo ALL patients treated in the ALL IC-BFM 2009 study.The expression of all 4 miRs significantly decreased over the first week of therapy (miR-128-3p: log2 fold change - 2.86; adjusted p 3.6 × 10-7; miR-181b-5p: log2 fold change - 1.75; adjusted p 1.48 × 10-2; miR-181a-5p: log2 fold change -1.33; adjusted p 3.12 × 10-2; miR-222-3p: log2 fold change - 1.25; adjusted p 1.66 × 10-2). However, no significant further reduction in miR expression was found after the 8th day of therapy. Measured drop in expression of 2 miRs at day 8 strongly correlated with day 15 bone marrow flow cytometry MRD results (miR-128-3p: Pearson's r = 0.88, adjusted p = 2.71 × 10-4; miR-222-3p: r = 0.81, adjusted p = 2.99 × 10-3).In conclusion, these circulating miRs might act as biomarkers of residual leukemia. MiR-128-3p and miR-222-3p in blood predict day 15 flow cytometry MRD results 7 days earlier. Although, their sensitivity falls behind that of bone marrow flow cytometry MRD at day 15