الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 118 |  |  |
| | | from | 118 | | |
Abstract
Breast cancer is a deadly disease due to immense difficulties in prevention and treatment. Multidrug resistance of tumor cells is the main reason for the failure of anticancer drugs. Finding novel therapeutic strategies is therefore of great significance in the treatment of highly malignant breast cancer. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Tumor treating fields (TTFields) have emerged as a promising noninvasive treatment modality, utilizing continuous low-intensity (1–3 V/cm) and intermediate-frequency (100–300 kHz) alternating electric fields applied through skin electrodes positioned over localized tumor regions. TTFields target cancer cells through multiple mechanisms, resulting in the disruption of crucial processes and ultimately leading to cell death. The effectiveness of TTFields therapy relies on several factors, including the frequency, intensity, and duration of treatment.
The aim of this study was finding the optimum conditions for non-insulated electrode/s that produce the same TTFs or better effect with minimum metal ions release and much shorter time and to investigate the mechanism of action.
Eight rectangle gold, silver/ silver chloride, and stainless-steel plate electrodes were manufactured. Four of each electrode material had surface areas of 0.5 cm2 while the other four electrodes had surface areas of 1 cm2. Electric pulses was applied to the cells through digital function generator. Application of 2 V/cm, 1500 Hz (TTFs) electric field will take place. The most appropriate time for electric field exposure was determined at first. The exposure will be performed by placing the cells between the following electrodes’ conditions:
G0: Control group; Cells will not be exposed to the electric field.
G1: The electric pulses will be generated to the cells through two gold electrodes of 0.5 cm2 surface area.
Summary, Conclusion and Recommendations
78
G2: The electric pulses will be generated to the cells through four gold electrodes of 0.5 cm2 surface area.
G3: The electric pulses will be generated to the cells through two gold electrodes of 1 cm2 surface area.
G4: The electric pulses will be generated to the cells through four gold electrodes of 1 cm2 surface area.
G5: The electric pulses will be generated to the cells through two silver/ silver chloride electrodes of 0.5 cm2 surface area.
G6: The electric pulses will be generated to the cells through four silver/ silver chloride electrodes of 0.5 cm2 surface area.
G7: The electric pulses will be generated to the cells through two silver/ silver chloride electrodes of 1 cm2 surface area.
G8: The electric pulses will be generated to the cells through four silver/ silver chloride electrodes of 1 cm2 surface area.
G9: The electric pulses will be generated to the cells through two stainless steel electrodes of 0.5 cm2 surface area.
G10: The electric pulses will be generated to the cells through four stainless steel electrodes of 0.5 cm2 surface area.
G11: The electric pulses will be generated to the cells through two stainless steel electrodes of 1 cm2 surface area.
G12: The electric pulses will be generated to the cells through four stainless steel electrodes of 1 cm2 surface area.
The results of the present study revealed that the cell viability reduction was time dependent, and the best exposure time selected for this study was 15 minutes.
The results indicated a significant reduction in normal cells and a significant increase in necrotic, early apoptotic, and dead cells in all the electric-exposed groups for all electrode types compared to the control group.
Summary, Conclusion and Recommendations
79
The obtained results clarified that cells exposed to the electric field conducted through gold electrodes, silver electrodes or stainless steel electrodes, the effect of increasing surface area produces a more significant effect than increasing the number of electrodes.
At the constant electrode numbers, as the electrode surface area increases, the electric effect increases as at 2 electrodes; upon using 0.5 cm2 surface area, the normal cells percentages significantly decreased from 86.21 %,84.5 % and 91.89 % to 81.52 % , 76.1 % and 83.45 % when 1 cm2 surface area electrodes were used for gold, silver and Stainless steel electrodes respectively, while using 4 electrodes; the normal cells percentages significantly decreased from 84.7 %, 81.32 % and 84.94 % upon using 0.5 cm2 surface area to 80.1 %, 73.62 % and 79.99 % when 1 cm2 surface area electrodes were used for gold, silver and Stainless steel electrodes respectively.
At the constant surface area, as the number of electrodes increases, the electric effect increases as at 0.5 cm2; the normal cells percentages significantly decreased from 86.21 %, 84.5 % and 91.89 % upon using 2 electrodes to 84.7%, 81.32 % and 84.94 when 4 electrodes were used. Also at 1 cm2; the normal cells percentages significantly decreased from 81.52 %, 76.1 % and 83.45 % upon using 2 electrodes to 80.1 %, 73.62 % and 79.99 % when 4 electrodes were used for gold, silver and Stainless steel electrodes respectively.
The obtained results revealed that all the exposed groups have a great significant reduction in the normal cells with a clear significant increase in necrosis and apoptosis.
The results indicated that comparing the gold, silver, and stainless-steel electrodes at the same number of electrodes and the same surface area, the reduction of the normal cell percentages was the greatest upon using silver electrodes at a significance level of p<0.001.
The obtained results clarified that the greatest effect was obtained by using 4 silver electrodes with an electrode surface area of 1 cm2 which caused a reduction in the normal cells by 20.64% compared with 14.16% for gold electrodes, and 14.27% for stainless-steel electrodes. The comparison of the electrode type clearly indicates the order of preference of the electrode material in TTFs to be silver then gold and finally stainless-steel.
The results illustrated that a non-significant change of the determined cyclins A, B, or E for all the examined electrode types and conditions. These results indicate that cyclins A, B, and E have no role in the death effect caused by TTFs.
Summary, Conclusion and Recommendations
80
The current results showed that a decrease in BCL-2 levels was accompanied by an increase in BAX levels in the TTFs exposed cells compared to control cells. Thus, BAX/BCL-2 ratio was significantly higher in the TTFs exposed cells compared to control cells.
For gold electrodes, silver electrodes and stainless-steel electrodes a significant increase in BAX level was accompanied by a significant decrease in BCL-2 level resulting in a significant increase in BAX/BCL-2 level as the electrode surface area increased from 0.5 cm2 to 1 cm2, while there was a non-significant change with increasing the number of electrodes of the same surface area.
Results showed that highly significant changes in the total antioxidant capacity were observed after TTFs exposure to stainless steel electrodes as compared to control cells. The results indicated that TAC significantly decreased upon conducting the TTFs through gold and stainless-steel electrodes for all the used conditions. While upon using silver electrodes, there was a non-significant change with the control for 0.5 cm2 either the 2 or 4 electrodes, and this decrease in TAC started with 1 cm2 compared to the control.
ICP-MS elemental analysis of silver in cells revealed an increase in silver accumulation during TTFs conduction through silver electrodes, and ICP-MS elemental analysis of ferrous ions in cells revealed an increase in ferrous accumulation during TTFs conduction through stainless-steel electrodes.
Summary, Conclusion and Recommendations
81
6.2. Conclusion
from this study we concluded that:
Tumour Treating field has good therapeutic effects in breast cancer.
Treatment with silver electrodes was more effective than gold or stainless-steel electrodes.
Changing electrode condition had effective role in the effect of TTField during treatment.
TTF is a promising therapeutic agent for breast cancer treatment.
6.3. Recommendations
1. Further studies are required to investigate the effects of TTF on normal cells and its Mechanism.
2. Further studies are required to investigate the effects of TTF on different types of cancer.
3. Further studies are required to investigate the effects of TTF in combination with other therapy.
4. Further studies are required to investigate the effects of TTF with a wider frequency.