Augustinas Želvys

Bio: Augustinas Želvys is an academic researcher. The author has contributed to research in topics: Medicine & Electrochemotherapy. The author has an hindex of 1, co-authored 1 publications receiving 4 citations.

Electrochemotherapy Using Doxorubicin and Nanosecond Electric Field Pulses: A Pilot in Vivo Study.

Abstract: Pulsed electric field (PEF) is frequently used for intertumoral drug delivery resulting in a well-known anticancer treatment-electrochemotherapy. However, electrochemotherapy is associated with microsecond range of electrical pulses, while nanosecond range electrochemotherapy is almost non-existent. In this work, we analyzed the feasibility of nanosecond range pulse bursts for successful doxorubicin-based electrochemotherapy in vivo. The conventional microsecond (1.4 kV/cm × 100 µs × 8) procedure was compared to the nanosecond (3.5 kV/cm × 800 ns × 250) non-thermal PEF-based treatment. As a model, Sp2/0 tumors were developed. Additionally, basic current and voltage measurements were performed to detect the characteristic conductivity-dependent patterns and to serve as an indicator of successful tumor permeabilization both in the nano and microsecond pulse range. It was shown that nano-electrochemotherapy can be the logical evolution of the currently established European Standard Operating Procedures for Electrochemotherapy (ESOPE) protocols, offering better energy control and equivalent treatment efficacy.

The Influence of Feeding with Colostrum and Colostrum Replacer on Major Blood Biomarkers and Growth Performance in Dairy Calves

Abstract: Simple Summary Bovine colostrum (BC) is known to exert immunomodulatory activity by stimulating mucosal immune responses as well as providing the passive transfer of immunoglobulins. Despite the evident role of BC-derived immunoglobulins for protection of the calves, the multifaceted BC activity on neonate calves could not be fully explained by passively acquired immunoglobulins. Therefore, it is critical to better understand the role of other, non-immunoglobulin-derived bioactive constituents on the growth and development of neonate calves. Our data demonstrated that colostrum administration is important for the growth performance of dairy calves as well as changes in major blood biomarkers. The timing of colostrum administration results in a decremental effect on the body mass growth in calves. Abstract Bovine colostrum (BC) is the first milk produced by lactating cows after parturition. BC is rich in various amino acids, proteins, and fats essential for the nutrition of the neonate calves. Despite the evident beneficial effect of BC on calves, the effect of BC on blood biomarkers is poorly understood. Calves that received BC showed significantly higher body mass at days 7 and 30 (38.54 kg and 43.42 kg, respectively) compared to the colostrum replacer group (p = 0.0064). BC induced greater quantities of blood neutrophils (0.27 × 109/L) and monocytes (4.76 × 109/L) in comparison to the colostrum replacer (0.08 and 0.06 × 109/L, respectively) (p = 0.0001). Animals that received BC showed higher levels of total serum protein (59.16 g/L) and albumin (29.96 g/L) in comparison to the colostrum replacer group (44.34 g/L and 31.58 g/L, respectively). In addition, BC induced greater intestinal mucus production in the Wistar rat model. Collectively, these results demonstrate that BC is important for the growth of calves and that it provides a significant beneficial effect on morphological and biochemical blood parameters.

Improving NonViral Gene Delivery Using MHz Bursts of Nanosecond Pulses and Gold Nanoparticles for Electric Field Amplification

Abstract: Gene delivery by the pulsed electric field is a promising alternative technology for nonviral transfection; however, the application of short pulses (i.e., nanosecond) is extremely limited. In this work, we aimed to show the capability to improve gene delivery using MHz frequency bursts of nanosecond pulses and characterize the potential use of gold nanoparticles (AuNPs: 9, 13, 14, and 22 nm) in this context. We have used bursts of MHz pulses 3/5/7 kV/cm × 300 ns × 100 and compared the efficacy of the parametric protocols to conventional microsecond protocols (100 µs × 8, 1 Hz) separately and in combination with nanoparticles. Furthermore, the effects of pulses and AuNPs on the generation of reactive oxygen species (ROS) were analyzed. It was shown that gene delivery using microsecond protocols could be significantly improved with AuNPs; however, the efficacy is strongly dependent on the surface charge of AuNPs and their size. The capability of local field amplification using AuNPs was also confirmed by finite element method simulation. Finally, it was shown that AuNPs are not effective with nanosecond protocols. However, MHz protocols are still competitive in the context of gene delivery, resulting in low ROS generation, preserved viability, and easier procedure to trigger comparable efficacy.

High-Frequency Nanosecond Bleomycin Electrochemotherapy and its Effects on Changes in the Immune System and Survival

Abstract: Simple Summary Standard microsecond electrochemotherapy (μsECT) is used in clinical trials for the elimination of tumours, while the first studies on nanosecond electrochemotherapy (nsECT) only started to appear recently. Nanosecond pulses enable more homogeneous treatment and better control of pulse burst energy, and thus the whole field of electroporation is moving towards the shorter pulse range. In order to ensure a full anticancer response and potentially prevent any metastases, the immunomodulatory effects should also be induced. Therefore, in this work, we used nsECT protocols based on kHz and MHz pulse bursts and characterized the response of the immune system to the novel modality of nano-electrochemotherapy. The results of this study are useful for the development of effective anticancer treatment strategies based on high frequency nanosecond electric fields. Abstract In this work, a time-dependent and time-independent study on bleomycin-based high-frequency nsECT (3.5 kV/cm × 200 pulses) for the elimination of LLC1 tumours in C57BL/6J mice is performed. We show the efficiency of nsECT (200 ns and 700 ns delivered at 1 kHz and 1 MHz) for the elimination of tumours in mice and increase of their survival. The dynamics of the immunomodulatory effects were observed after electrochemotherapy by investigating immune cell populations and antitumour antibodies at different timepoints after the treatment. ECT treatment resulted in an increased percentage of CD4+ T, splenic memory B and tumour-associated dendritic cell subsets. Moreover, increased levels of antitumour IgG antibodies after ECT treatment were detected. Based on the time-dependent study results, nsECT treatment upregulated PD 1 expression on splenic CD4+ Tr1 cells, increased the expansion of splenic CD8+ T, CD4+CD8+ T, plasma cells and the proportion of tumour-associated pro inflammatory macrophages. The Lin− population of immune cells that was increased in the spleens and tumour after nsECT was identified. It was shown that nsECT prolonged survival of the treated mice and induced significant changes in the immune system, which shows a promising alliance of nanosecond electrochemotherapy and immunotherapy.

Effects of Nanosecond Pulsed Electric Fields in Cell Vitality, Apoptosis, and Proliferation of TPC-1 Cells.

Abstract: Objective. To evaluate the effects of nanosecond pulsed electric fields (nsPEFs) with different pulse durations in cell vitality, apoptosis, and proliferation of TPC-1 cells, optimize pulse parameters and expand the application range of nsPEFs. Methods. The pulse duration of 0, 300 ns, 500 ns, and 900 ns is generated with nsPEF generator. CCK-8 was used to investigate the effect of nsPEFs on the viability of TPC-1 cells. Flow cytometry was used to evaluate the apoptosis of TPC-1 after pulse treatment. The effect of nsPEFs on the proliferation ability of TPC-1 cells was detected by 5-ethy-nyl-2 - deoxyuridine. The morphological changes of TPC-1 cells after pulse treatment were observed by transmission electron microscopy. Results. NsPEFs with 900 ns pulse duration can significantly affect the viability of TPC-1 cells and inhibit the proliferation ability of TPC-1 cells. In addition, nsPEFs can also induce apoptosis of TPC-1 cells. Conclusion. NsPEFs with longer pulse duration can significantly affect the biological behavior of TPC-1 cells, such as cell viability and proliferation ability, and can also induce cell apoptosis, thereby inhibiting cell growth.

Effects of Time Delay Between Unipolar Pulses in High Frequency Nano-Electrochemotherapy

Abstract: this work focuses on bleomycin electrochemotherapy using new modality of high repetition frequency unipolar nanosecond pulses.As a tumor model, Lewis lung carcinoma (LLC1) cell line in C57BL mice (n = 42) was used. Electrochemotherapy was performed with intertumoral injection of bleomycin (50 μL of 1500 IU solution) followed by nanosecond and microsecond range electrical pulse delivery via parallel plate electrodes. The 3.5 kV/cm pulses of 200 and 700 ns were delivered in a burst of 200 at frequencies of 1 kHz and 1 MHz. For comparison of treatment efficiency, a standard 1.3 kV/cm x 100 μs x 8 protocol was used.It was shown that it is possible to manipulate the efficacy of unipolar sub-microsecond electrochemotherapy solely by the time delay between the pulses.the results suggest that the sub-microsecond range pulses can be as effective as the protocols in European Standard Operating Procedures on Electrochemotherapy (ESOPE) using 100 μs pulses.

Key Points in Remote-Controlled Drug Delivery: From the Carrier Design to Clinical Trials.

Abstract: The increased research activity aiming at improved delivery of pharmaceutical molecules indicates the expansion of the field. An efficient therapeutic delivery approach is based on the optimal choice of drug-carrying vehicle, successful targeting, and payload release enabling the site-specific accumulation of the therapeutic molecules. However, designing the formulation endowed with the targeting properties in vitro does not guarantee its selective delivery in vivo. The various biological barriers that the carrier encounters upon intravascular administration should be adequately addressed in its overall design to reduce the off-target effects and unwanted toxicity in vivo and thereby enhance the therapeutic efficacy of the payload. Here, we discuss the main parameters of remote-controlled drug delivery systems: (i) key principles of the carrier selection; (ii) the most significant physiological barriers and limitations associated with the drug delivery; (iii) major concepts for its targeting and cargo release stimulation by external stimuli in vivo. The clinical translation for drug delivery systems is also described along with the main challenges, key parameters, and examples of successfully translated drug delivery platforms. The essential steps on the way from drug delivery system design to clinical trials are summarized, arranged, and discussed.