الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Breast cancer is a leading cause of death in over 100 countries worldwide,
accounting for 24.2 % incidence and 15% mortality in 2018 between all types of cancers
according to GLOBOCAN 2018. It accounts for 37.3% incidence in EGYPT in 2014. This
may 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 breast cancer include surgical removal of the tumor, radiation
therapy and adjuvant systemic therapy, the later includes chemotherapy, neo-adjuvant
chemotherapy, adjuvant chemotherapy, hormonal therapy and palliative chemotherapy.
Phytochemicals is a major class of natural products that used as a chemo preventive
agents for all types of cancers in general and breast cancer specifically because of their
high content of antioxidants. Epidemiological studies have indicated that high intake of
fruits and vegetables is associated with a significant decrease in the risk of cancer
incidence and development. Many studies evaluated the potential effect of pomegranate on
breast cancer in-vitro and in-vivo.
Our study aimed to assess the effect of pomegranate extract (PE) on apoptosis,
angiogenesis and antioxidant power during adjuvant chemotherapy on females with breast
cancer.
It was carried out on 51 female breast cancer patients receiving AC as chemotherapy.
They were divided into two groups (group I, 20 females receiving 6 cycles of AC only)
and (group II, 31 females receiving 6 cycles of AC and 500 mg daily PE for 105 days).
Blood samples were collected from hospital of medical research institute. 3 ml blood
was drawn and separated into serum in gel tubes and tested for measuring caspase-3,
VEGF, FRAP, kidney, liver functions and complete blood count before and after treatment.
The results of the present study revealed that:
Hemoglobin levels showed significant decrease in the two studied groups after
treatment (p= 0.001,0.002) respectively.
RBCS count showed significant decrease after treatment in the two studied groups
(p<0.005) for both.
WBCs count showed significant decrease after treatment in the two studied groups
(p<0.001) for both.
Treatment with chemotherapy and pomegranate significantly increased ALP, AST
and ALT levels (but were in normal range) in the two studied groups.
FRAP level was significantly increased after treatment (p=0.016) with 19.17%
increase in group I and (p= 0.041) with 16% increase in group II.
Summary and Conclusion
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VEGF level, both treatment protocols caused significant decrease (p =0.002) in the
two groups and 34%, 36.5% decrease respectively.
Caspase-3 level in (group I) did not show any significant increase (p=0.180), but
group II patients showed a significant increase in their caspase-3 level (p
=0.014) with a 74.4% increase.
A higher percentage of increase in FRAP was observed in patients with positive ER
compared to those with negative ER who received PE (17.4% increase in ER+ve
compared to 9.5% increase in ER –ve), and (20.18 % increase compared to 16.5 %
increase) who received AC only respectively.
A higher percentage of decrease in VEGF was observed in patients with negative ER
in the first group, compared to those with negative ER in the second group. However
patients treated with chemotherapy and PE showed a higher ratio of decrease in ER
positive than those treated with chemotherapy alone, (38.5% decrease compared to
30% decrease) respectively.
A markedly higher percentage of increase for caspase-3 level in both ER and PR
status was observed in group II patients compared to group I.
The initial VEGF (before treatment) in grade III patients had a statistically significant
higher levels compared to grade II patients (p= 0.041). On the other hand, no
significant statistical difference was observed in VEGF levels between different
stages (p= 0.079).
Caspase-3 had a statistically significant increase with stage (p= 0.018*) but no
significant difference was observed with different grades before treatment (p=0.114).
VEGF has a positive correlation with grade of breast cancer before treatment.
Caspase-3 has a positive correlation with FRAP level in group II patients who
received pomegranate supplementation with chemotherapy.
from the present study we can conclude:
Our findings regarding FRAP level in response to PE supplementation was not as
high as expected, possibly due to the presence of superabundant free radicals resulting
from effect of chemotherapy in addition to the reduced dose and duration we used
compared to the previous clinical trials on other types of cancer.
Pomegranate supplementation affected angiogenesis by decreasing level of VEGF,
despite of the observable action of pomegranate on VEGF and thereafter, angiogenesis, it
didn’t appear statistically. This may be attributed to the low dose and duration of
pomegranate in our study compared to the higher doses and durations in the previous
studies affirming that pomegranate is a dose dependent natural therapy.
Most interestingly, the most apparent effect of pomegranate was on apoptosis by the
major increase in caspase-3 levels recorded in patients receiving pomegranate together
with chemotherapy as compared to patients receiving chemotherapy alone by activating
signal transduction that lead to apoptosis.
It is also important to note that our study asserted that pomegranate showed no
toxicity or side effects on liver or kidney functions as well as on blood chemistry, besides
no adverse events was observed in patients during the whole duration of the study.
As stated, inactive ellagitinin derived metabolites are produced by colonic microflora
which may account for individual differences in the response to pomegranate
conconsumption (206).
In the present study, high percentage of our patients were at late stage which may
have altered biotransformation for PE.