Application of repetitively pulsed X-ray radiation in experimental oncology

Development of new technologies in the field of radiation required new approaches and strategies for their application. Power radiation when one continued pulsed divided to serial pulses with different specific repetition rate could provide more complicated and expressed reaction of the biological objects. We used different normal and tumor cell lines in vivo and in vitro to compare efficacy of different pulse repetition rate of X-ray radiation when the total absorbed dose didn’t exceed 1 Gy. We observed strong dependent of tumor cell reaction to repetition rate. Using this parameter we can stimulate or inhibit tumor growth up to 90% compare to control group. Irradiation of tumor-bearing mice inhibited growth of primary tumor up to 60% with the total absorbed dose 0.4 Gy. Moreover same experimental conditions allowed to reduce number of metastasis in mouse lung at 70%. That resulted in longer survival of experimental animals compare to control group. Thus we can conclude that pulsed radiation with nanosecond pulse duration has a potential for application in oncology

Different sensitivity of normal and tumor cells to pulsed radiofrequency exposure

The effect of nanosecond radiofrequency pulses (nsRF) on tumor and normal cells has been studied. To determine the viability of cells, an MTT test was used, as well as a real time system for analyzing cell cultures-iCELLigence. It has been shown that ns RF pulses under certain combinations of operating conditions reduce cell proliferation of both tumor and normal cells. Double exposure to 1000 pulses leads to the most effective inhibition of tumor cell proliferation and was 40% after 5 days. Inhibition of the proliferative activity of normal cells was 10% and was maximum after 3 days, then cell growth resumed. The results obtained allow to consider ns RF pulses with different parameters as a promising effective factor for controlling cellular processes for biomedical purposes

Macrophage and tumor cell responses to repetitive pulsed X-ray radiation

To study a response of tumor cells and macrophages to the repetitive pulsed low-dose X-ray radiation. Methods. Tumor growth and lung metastasis of mice with an injected Lewis lung carcinoma were analysed, using C57Bl6. Monocytes were isolated from a human blood, using CD14+ magnetic beads. IL6, IL1-betta, and TNF-alpha were determined by ELISA. For macrophage phenotyping, a confocal microscopy was applied. "Sinus-150" was used for the generation of pulsed X-ray radiation (the absorbed dose was below 0.1 Gy, the pulse repetition frequency was 10 pulse/sec). The irradiation of mice by 0.1 Gy pulsed X-rays significantly inhibited the growth of primary tumor and reduced the number of metastatic colonies in the lung. Furthermore, the changes in macrophage phenotype and cytokine secretion were observed after repetitive pulsed X-ray radiation. Conclusion. Macrophages and tumor cells had a different response to a low-dose pulsed X-ray radiation. An activation of the immune system through changes of a macrophage phenotype can result in a significant antitumor effect of the low-dose repetitive pulsed X-ray radiation

Effect of atmospheric-pressure plasma jet on normal and tumor cells in vitro

The purpose of this work is to investigate the effect of low-temperature plasma on tumor and normal cells. As a result of in vitro experiments, plasma-exposed tumor and normal cells demonstrate several effects such as cell detachment, apoptosis or necrosis according to cell type and exposure parameters (power, time of exposure, frequency). In experiments, the inhibition of tumor cell growth was observed up to 70% on the 5th day after exposure. The effect of gas discharge plasma on normal cells was the opposite, and by 5 days there was a stimulation of cell proliferation. The obtained data demonstrate the prospects of using this atmospheric-pressure plasma jet in biomedical research aimed at the treatment of cancer

Smoking-related DNA adducts as potential diagnostic markers of lung cancer: new perspectives

In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in high-risk groups (smokers, manufacturing workers, urban dwellers)

Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44+CD24- stemness

Intratumor morphological heterogeneity in breast cancer is represented by different morphological structures (tubular, alveolar, solid, trabecular, and discrete) and contributes to poor prognosis; however, the mechanisms involved remain unclear. In this study, we performed 3D imaging, laser microdissection-assisted array comparative genomic hybridization and gene expression microarray analysis of different morphological structures and examined their association with the standard immunohistochemistry scorings and CD44+CD24- cancer stem cells. We found that the intratumor morphological heterogeneity is not associated with chromosomal aberrations. By contrast, morphological structures were characterized by specific gene expression profiles and signaling pathways and significantly differed in progesterone receptor and Ki-67 expression. Most importantly, we observed significant differences between structures in the number of expressed genes of the epithelial and mesenchymal phenotypes and the association with cancer invasion pathways. Tubular (tube-shaped) and alveolar (spheroid-shaped) structures were transcriptionally similar and demonstrated co-expression of epithelial and mesenchymal markers. Solid (large shapeless) structures retained epithelial features but demonstrated an increase in mesenchymal traits and collective cell migration hallmarks. Mesenchymal genes and cancer invasion pathways, as well as Ki-67 expression, were enriched in trabecular (one/two rows of tumor cells) and discrete groups (single cells and/or arrangements of 2-5 cells). Surprisingly, the number of CD44+CD24- cells was found to be the lowest in discrete groups and the highest in alveolar and solid structures. Overall, our findings indicate the association of intratumor morphological heterogeneity in breast cancer with the epithelial-mesenchymal transition and CD44+CD24- stemness and the appeal of this heterogeneity as a model for the study of cancer invasion