Tijana Djukic

Electromagnetic field investigation on different cancer cell lines

BackgroundThere is a strong interest in the investigation of extremely low frequency Electromagnetic Fields (EMF) in the clinic. While evidence about anticancer effects exists, the mechanism explaining this effect is still unknown.MethodsWe investigated in vitro, and with computer simulation, the influence of a 50 Hz EMF on three cancer cell lines: breast cancer MDA-MB-231, and colon cancer SW-480 and HCT-116. After 24 h preincubation, cells were exposed to 50 Hz extremely low frequency (ELF) radiofrequency EMF using in vitro exposure systems for 24 and 72 h. A computer reaction-diffusion model with the net rate of cell proliferation and effect of EMF in time was developed. The fitting procedure for estimation of the computer model parameters was implemented.ResultsExperimental results clearly showed disintegration of cells treated with a 50 Hz EMF, compared to untreated control cells. A large percentage of treated cells resulted in increased early apoptosis after 24 h and 72 h, compared to the controls. Computer model have shown good comparison with experimental data.ConclusionUsing EMF at specific frequencies may represent a new approach in controlling the growth of cancer cells, while computer modelling could be used to predict such effects and make optimisation for complex experimental design. Further studies are required before testing this approach in humans.

Computational Medicine in Data Mining and Modeling

This book presents an overview of a variety of contemporary statistical, mathematical and computer science techniques which are used to further the knowledge in the medical domain. The authors focus on applying data mining to the medical domain, including mining the sets of clinical data typically found in patients medical records, image mining, medical mining, data mining and machine learning applied to generic genomic data and more. This work also introduces modeling behavior of cancer cells, multi-scale computational models and simulations of blood flow through vessels by using patient-specific models. The authors cover different imaging techniques used to generate patient-specific models. This is used in computational fluid dynamics software to analyze fluid flow. Case studies are provided at the end of each chapter. Professionals and researchers with quantitative backgrounds will find Computational Medicine in Data Mining and Modeling useful as a reference. Advanced-level students studying computer science, mathematics, statistics and biomedicine will also find this book valuable as a reference or secondary text book.

Virtual reality aided visualization of fluid flow simulations with application in medical education and diagnostics

Medical education, training and preoperative diagnostics can be drastically improved with advanced technologies, such as virtual reality. The method proposed in this paper enables medical doctors and students to visualize and manipulate three-dimensional models created from CT or MRI scans, and also to analyze the results of fluid flow simulations. Simulation of fluid flow using the finite element method is performed, in order to compute the shear stress on the artery walls. The simulation of motion through the artery is also enabled. The virtual reality system proposed here could shorten the length of training programs and make the education process more effective.

Computer simulation of thromboexclusion of the complete aorta in the treatment of chronic type B aneurysm.

The purpose of this computational study was to examine the hemodynamic parameters of the velocity fields, shear stress, pressure and drag force field in the complex aorta system, based on a case of type B aortic dissection. The extra-anatomic reconstruction of the complete aorta and bipolar exclusion of the aneurysm was investigated by computational fluid dynamics. Three different cases of the same patient were analyzed: the existing preoperative condition and two alternative surgical treatment options, cases A and B, involving different distal aorto-aortic anastomosis sites. The three-dimensional Navier-Stokes equations and the continuity equation were solved with an unsteady stabilized finite element method. The aorta and large tube graft geometries were reconstructed based on CT angiography images to generate a patient-specific 3D finite element mesh. The computed results showed velocity profiles with smaller intensity in the aorta than in the graft tube in the postoperative case. The shear stress distribution showed low zones around 0.5 Pa in the aneurysm part of the aorta for all three cases. Pressure distribution and, particularly, drag force had much higher values in the preoperative aneurysm zones (7.37 N) than postoperatively (2.45 N), which provides strong evidence of the hemodynamic and biomechanical benefits of this type of intervention in this specific patient. After assessing the outcome obtained with each of the two alternatives A and B, for which we found no significant difference, it was decided to use option A to treat the patient. In summary, computational studies could complement surgical preoperative risk assessment and provide significant insight into the benefits of different treatment alternatives.

Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo.

Introduction Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo. Materials and Methods Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations. Results Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 μmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001). Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01) and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03). Discussion In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.

A novel approach to process improvement in small and medium manufacturing enterprises

Continuous business process improvement is a well-known strategy referred to as the “Japanese approach” to industrial production. Nowadays, it presents one of the basic requirements set by the ISO 9004:2000 standard. A new fuzzy model based on the Ishikawa diagram is proposed, whereby the rank of business losses of the main process at the manufacturing company level is determined, respecting the values of identified causes that lead to the formation of business losses, as well as their relative importance. In this article, it is assumed that the relative importance and values of causes are determined by descriptive linguistic expressions. The linguistic expressions are obtained by the fuzzy rating of a management team. The proposed algorithm determines the business losses with the highest possibility of occurrence and calculates the degrees of beliefs that some business losses are more likely to happen than the others. Real-life industrial data on small and medium companies operating in central Serbia and numerical examples are given to illustrate the method.

Modeling of liver metastatic disease with applied drug therapy.

Colorectal carcinoma is acknowledged as the second leading cause of total cancer-related death in the European Region. The majority of deaths related to colorectal carcinoma are connected with liver metastatic disease. Approximately, in 25% of all patients, liver metastatic disease is diagnosed at the same time as the primary diagnosis, while up to a quarter of others would develop liver metastases in the course of the illness. In this study, we developed reaction-diffusion model and analyzed the effect of drug therapy on liver metastatic disease for a specific patient. Tumor volumes in specific time points were obtained using CT scan images. The nonlinear function for cell proliferation rate as well as data about clinically applied drug therapy was included in the model. Fitting procedure was used for parameter estimation. Good agreement of numerical and experimental results shows the feasibility and efficacy of the proposed system.

Real-time monitoring of cytotoxic effects of electroporation on breast and colon cancer cell lines.

PURPOSE To study the effects of electroporation on different cell lines. MATERIAL The effects of electroporation on human breast cancer (MDA-MB-231), human colon cancer (SW-480 and HCT-116), human fibroblast cell line (MRC-5), primary human aortic smooth muscle cells (hAoSMC) and human umbilical vein endothelial cells (HUVEC) were studied. Real-time technology was used for cell viability monitoring. Acridine orange/ethidium bromide assay was applied for cell death type determination. A numerical model of electroporation has been proposed. RESULTS Electroporation induced inhibition of cell viability on dose (voltage) dependent way. The electroporation treatment 375-437.5Vcm-1 caused irreversible electroporation of cancer cells and reversible electroporation of healthy cells. The application of lower voltage rating (250Vcm-1) led to apoptosis as the predominant type of cell death, whereas the use of higher voltage (500Vcm-1) mainly caused necrosis. CONCLUSION Electroporation represents a promising method in cancer treatment. Different cancer cell lines had different response to the identical electroporation treatment. Electroporation 375-437.5Vcm-1 selectively caused permanent damage of cancer cells (SW-480), while healthy cells (MRC-5, hAoSM and HUVEC) recovered after 72h. The type of cell death is dependent of electroporation conditions. The proposed numerical model is useful for the analysis of phenomena related to electroporation treatment.

Experimental and numerical investigation of electromagnetic field at different cancer cell lines

There is a strong interest of investigation of Extremely Low Frequency (ELF) ElectroMagnetic (EM) fields in the clinic. In this study we investigated experimentally in-vitro and in-sillico with computer simulation influence of 50 Hz EM field at three different cancer cell lines: breast cancer MDA-MB-231 and colon cancer SW-480 and HCT-116. Computer reaction-diffusion model with the net rate of cell proliferation and effect of electromagnetic field in time was developed. The fitting procedure for estimation of the computer model parameters was implemented. Experimental and computer model data have shown good comparison. These findings can open a new avenue for better controlling the growth of cancer cells at specific frequencies without affecting normal tissues, which may have a great influence in clinical oncology.

Numerical modeling of the cupular displacement and motion of otoconia particles in a semicircular canal

Balance is achieved and maintained by a balance system called a labyrinth that is composed of three semicircular canals and the otolith organs that sense linear gravity and acceleration. Within each semicircular canal, there is a gelatinous structure called the cupula, which is deformed under the influence of the surrounding endolymph. One of the balance disorders is benign paroxysmal positional vertigo, and one of the pathological conditions that have been identified as possible causes of this syndrome is canalithiasis—disturbance of the endolymph flow and cupular displacement caused by the free-moving otoconia particles within the lumen of the canal. Analysis of phenomena occurring within the semicircular canal can help to explain some balance-related disorders and the response of the vestibular system to external perturbations under various pathological conditions. Numerical simulations allow a study of the influence of a wide range of factors, without the need to perform experiments and clinical examinations. In case of canalithiasis, an accurate explanation and tracking of the motion of otoconia particles in vivo is obviously nearly impossible. In this study, a numerical model was developed to predict the motion of otoconia particles within the semicircular canal and the effect of the endolymph flow and particles on the deformation of the cupula.