الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 117 |  |  |
| | | from | 117 | | |
Abstract
Breast cancer is the most frequent diagnosed disease and the leading cause of cancer death in women all over the world. The incidence and mortality rates of breast cancer represented 24% and 15% respectively of all cancer types among females in 2018. BC may be attributed to many risk factors, that have a great influence on the development of the malignant tumor, including modifiable risk factors such as: obesity, smoking, alcohol consumption as a life style risk factors in addition to exposure to radiation, hormonal factors, and socioeconomic factors and many other non-modifiable risk factors such as: gender, age, race, family history, benign diseases and genetic factors.
Treatment strategies of BC include surgical removal of the tumor, radiation therapy and adjuvant systemic therapy, the later includes adjuvant chemotherapy, neo-adjuvant chemotherapy, hormonal and palliative therapy.
Phytochemicals are a major class of natural products that were previously used as chemo-preventive agents for all types of cancers in general including breast cancer because of their high content of antioxidants. Epidemiological studies have indicated that high intake of fruits and vegetables are associated with a significant decrease in the risk of cancer incidence and development. Many studies have evaluated the potential effect of pomegranate extract on breast cancer in-vitro and in-vivo, pomegranate fruit especially its peel contains many polyphenols and tannins that found to have antitumor effect.
The present study aimed to assess the effect of PE on the methylation status of Caspase-3 and VEGF promoter regions before and after PE intake in healthy control females and chemotherapy (AC) treated breast cancer patients.
The study was carried out on 50 female participants; group I: 10 control healthy females receiving 500 mg PE daily for 105 days; group II: 15 females receiving 6 cycles of AC only for 105 days; group III: 25 females receiving 6 cycles of AC + 500 mg PE daily for 105 days.
Blood samples were collected from all participants and tested for Caspase-3 and VEGF methylation status using methylation-sensitive PCR before and after treatment. Moreover, kidney & liver functions test analysis were performed to assess the safety of long-term PE intake.
The results of the present study revealed that:
• There was no significant difference (p=0.109) between the mean age of controls (46.8±7.9 years) and patients treated with chemotherapy or Chemotherapy + pomegranate extract (48.53±8.31 and 50.5±9.5 years), respectively. As in age, no significant difference in BMI was recorded between the studied groups (p=0.214). On the contrary, cancer family history showed a significant difference (p= 0.001) between controls which had 0% positive history and patients who received chemotherapy or Chemotherapy + pomegranate extract which had 40% and 48% positive history, respectively.
• There was no statistical significant difference between the two patient treated groups concerning tumor size (p= 0.442) vascular invasion (p= 0.586), tumor side (p= 0.216) and menstrual status (p=0.414).
• There was no statistical significant difference between the two patients studied treated groups concerning histological type (p = 0.34), pathological grade (p=0.41) and TNM Staging (p= 0.721). There was no statistical significant difference concerning ER (p= 0.5911), PR (p= 0.285) and Her-2 neu status (p= 1.00) between the two studied groups.
• There was no statistical difference between serum AST, ALT activities, and blood urea as well as serum creatinine levels before treatment between the two patient groups or control, before and after treatment within the same group.
• The percentage of healthy individuals with Caspase-3 methylated promoter decreased from 30% to 20 % after pomegranate extract intake, however the decrease was statistically insignificant (p=0.154). Chemotherapy treatment caused a statistically significant (p= 0.014) increase in Caspase-3 methylation (from 0% to 27%). Interestingly and on the contrary to patients treated with chemotherapy alone, patients receiving Chemotherapy + Pomegranate had a statistically significant (p= 0.048) decrease in Caspase-3 methylation (from 12% to 0%).
• VEGF promoter methylation did not show any difference in healthy individuals before and after pomegranate intake as none of individuals showed methylated VEGF promoter before and after intake. Importantly, treatment of patients with Chemotherapy alone or Chemotherapy + PE caused a statistically significant increase in methylation of VEGF promoter (p= 0.0036, 0.018 and from 0 to 40% and 40% to 68% respectively).
• The association of Caspase-3 and VEGF promoter methylation status with clinico-pathological parameters of patients before treatment was assessed and shown in table 4.7. The Caspase-3 promoter methylation status was shown to be significantly associated (p ≤0.05) with all clinico-pathological parameters. On the other hand, VEGF promoter methylation status was significantly associated (p ≤0.05) with the same clinico-pathological parameters except for pathological grade (p= 0.107) and Lymph node involvement (p= 0.107).