الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Cancer is one of the leading causes of death worldwide and the incidence is on the rise in both developing and developed countries. Prevention of cancer may be more effective and less costly since the condition is closely associated with lifestyle factors.
Natural products have been long used for the treatment of various diseases and are becoming an important research area for novel drug and therapy discovery. These products, in particular phytochemicals,were extensively studied and have been shown topossess anti-carcinogenic activity by interfering with the initiation, development and progression of cancer through the modification of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis.
Many successful anti-cancer drugs now available are phytochemicals or their analogues, and some are in the human clinical trials phase.Sono-photodynamic therapy (SPDT) is a breakthrough modern technology to eliminate tumor and affected tissues without affecting any healthy tissue adjacent to or away from the tumor. This requires the use of a so-called sonophotosenstiser, which is highly concentrated in the tumor area, and responds ideally to photonic energy and ultrasonic waves. This works to halt tumor growth and speed up its elimination, which is a promising technique to eliminate superficial and deep cancer tumors.
The present work aims to cure Ehrlich ascites carcinoma tumor implanted to groups of mice, as experimental animals, using theSPDT modality in combination with protoporphyrin as a sono-photosensitizer drug. Two sources of energy were used; namely infrared laser and ultrasound (pulsed and continuous wave mode) for 3 minutes.
A total of 130 male Swiss albino mice with age 60– 65 day, weighing 20 25 g, were purchased from National Cancer Institute, Cairo University. The animals were housed in plastic cages and were kept under natural light with diet and water at available. When the tumor had grown to about 10 mm in diameter at day 10 after inoculation, the treatment study was started. Use of experimental animals in the study protocol was carried out in accordance with the ethical guidelines of the Medical Research Institute, Alexandria University (Guiding Principles for Biomedical Research Involving Animals, 2011).
group I: (30 mice)
a) 10 mice:Normal mice without treatment.
b) 10 mice:Tumor bearing mice without treatment.
c) 10 mice:Tumor bearing mice treated with (protoporphyrin) only.
group II: (20 mice, laser irradiated group)
a) 10 mice: were exposed to 4000 Hz Infra-Red Laser, for 3 minutes.
b) 10 mice: were exposed to 7000 Hz Infra-Red Laser, for 3 minutes.
group III: (20 mice, ultrasound group)
a) 10 mice: were exposed to pulsed ultrasound for 3 minutes.
b) 10 mice: were exposed to continuous ultrasound for 3 minutes.
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group IV: (20 mice, (protoporphyrin), laser group)
The mice of this group were injected intraperitoneally (IP) with (protoporphyrin), then were divided into 2 sub-groups. The tumor site was irradiated to laser at same conditions of group II.
group V: (20 mice, (protoporphyrin), ultrasound group)
The mice of this group were injected (IP) with (protoporphyrin), then were divided into 2 sub-groups. The tumor site was irradiated to ultrasound at same conditions of group III.
group VI: (20 mice, combined treatment groups)
a) 10 mice: The tumor site was irradiated to laser light for 3 minutes, followed by ultrasound for 3 minutes.
b) 10 mice:Injected (IP) with (protoporphyrin). The tumor site was irradiated to laser light for3 minutes, followed by ultrasound for 3 minutes.
Evaluation of treatment effects:
The dimensions of the tumor, e.g., the length, the width and the height of were measured using a slide digital caliper every day before any treatment modality. The tumor volume was calculated.
Tumor mass inhibition ratio and tumor volume growth ratio were also calculated.
Biochemical examinations were applied to detect serum levels of ALT, AST, urea and creatinine to detect the effect of protoporphyrin injection on liver and kidney functions.
Activities of some antioxidants were measured, namely; glutathione-S-transferase activity (GST), super oxide dismutase activity (SOD), glutathione reductase activity (GR), catalase activity (Cat), total antioxidant activity (TAC) and malondialdehyde (MDA).
Evaluating the histopathological changes in the tumor tissues following the different treatment methods using Hematoxylin and Eosin (H&E) stain using light microscope and ultrastructures using transmission electron microscope (TEM).
Results of the study:
The injection of the sono-photosensitizer (protoporphyrin only without activation) has little effect on the tumor volume.
The effect of exposing the tumor to IR laser as a photodynamic therapy increased with increasing the laser energy resulted in decreasing the tumor volume, tumor growth rate and increasing tumor volume inhibition ratio. These effects were observed either on using infrared laser alone (with its two frequencies) or in the presence of the protoporphyrin.
According to IR results the inhibition in the tumor volume has maximum value on using 7000 Hz IR laser in the presence of the protoporphyrin.
The effect of exposure to pulsed ultrasound wave was more than that in case of using continuous ultrasound wave. Similar variations occurred in case of using
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ultrasound exposure only or in the presence of the protoporphyrin, with maximum effect occurred on using ultrasound in the presence of the protoporphyrin.
Combined treatment of IR laser at 7000 Hz and pulsed ultrasound wave in the presence of protoporphyrin was more effective than either IR laser or ultrasound alone.
In the group of mice carrying the tumor only, a significant increase in the levels of MDA as compared to the control group of animals. The combination of photodynamic and sonodynamic therapy in the presences of protoporphyrin decreased significantly the levels of MDA.
In all Ehrlich bearing mice groups decreased activities of enzymatic antioxidants (SOD, CAT, GR, GST and TAC) in comparison with normal group were observed.
A significant increase in the enzymatic and non-enzymatic antioxidant guard was observed in the groups subjected to combination of photodynamic and sonodynamic therapy in the presences of protoporphyrin.
It was observed that treatment with protoporphyrin ameliorated the levels of serum creatinine and urea which is an indication of renal protection. This also confirms the protective role of protoporphyrin against renal toxicity. Also treatment with protoporphyrin protected against increase in serum levels of ALT, AST, and GGT, which is an indication of hepatoprotection by protoporphyrin. This also confirms the protective role of protoporphyrin against hepatotoxicity. The histological evaluation revealed that all tumors from the group of mice bearing the tumor included highly malignant cells. Tumors excised from animals receiving treatment protoporphyrin showed significant areas of necrosis compared to groups without sensitizer. In the group of animals subjected to combination of photodynamic and sonodynamic therapy in the presences of protoporphyrin, large foci distinct necrosis areas were appeared.