الفهرس 
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Abstract
Breast cancer is the most common female malignancy accounting for 22.9% and
37.7% of all female cancers worldwide and in Egypt, respectively. Breast cancer in
Egypt carries an unfavorable prognosis with 29% mortality and 1: 3.7 incidences to
mortality ratio.(1)) Breast cancer accounts for 16% of all cancer deaths among women
globally, according to the report by the World Health Organization. It is the most
common solid tumor diagnosed in women. Although the incidence of breast cancer
increases with age, certain lifestyle and environmental factors play an important role
on breast cancer risk. In Egypt, breast cancer is the most common cancer among
women, representing 18.9% of total cancer cases (35.5% in women and 2.2% in men)
among the Egypt National Cancer Institute (NCI) series of 10,556 patients during the
year 2002-2003.(2)
Breast cancer and cancer related diseases have been treated using surgery,
chemotherapy, and radiation therapy, or a combination of these. But despite these
therapeutic options, cancer remains associated with high mortality. This is basically
due to difficulties in early diagnosis, exorbitant cost of treatment, with the often late
presentation of breast cancer that generally characterizes cancer diagnosis among
Egypt and other African women(4,5,10,28) Owing to these several shortcomings, there is
a need for better therapeutic options which will increase the chances of survival of
breast cancer patients with minimal or no side effects of treatment.
Phytochemical prevention for severe health problems has recently gained
scientific recognition worldwide. Studies on the pharmacological mechanisms and
search for chemical structures of herbal extracts responsible for anticancer activity
caught great interest(30-32)
The aim of this work is to evaluate the caveolin 1 expression under the effect of
Thuja occidentalis an ethanolic extract of Thuja occidentalis Linn. leaves and
doxorubicin drugs in mice breast tissues induced by 7,12-dimethylbenzeneanthracene
(DMBA) as well as biophysical and biochemical parameters..to fulfill this aim, 60
albino mice weighting 20-25 gm of 8-10 weeks of age were divided into two groups.
The experimental groups received different concentrations of thuja with respect to the
LD50 result as documented by Arthur et al.(31) Mice were treated with increasing
doses of thuja. Uses of experimental animals in the study protocol were carried out in
accordance with the ethical guidelines of the Medical Research Institute, Alexandria
University (Appendix 2, Guiding Principles for Biomedical Research Involving
Animals, 2011). group A: 10 Mice treated with distilled water only as a control
group. group B: 50 Mice treated with 20 mg/ml/week of DMBA. This group was
subdivided into five sub-groups; sub group B-1: 10 Mice treated with 20 mg/ml/week
of DMBA only and were not receive any treatment, sub group B-2: 10 Mice treated
with 10 mg/ml/day of thuja after DMBA administration, sub group B-3: 10 Mice
treated with 7.5 mg/ml/day of thuja after DMBA administration, Sub group B-4: 10
Mice treated with 5 mg/ml/day of thuja after DMBA administration and sub group B-
5: 10 Mice treated with 5 mg/ml/day of doxorubicin after DMBA administration.
For evaluation of the treatment effects to all studied groups the following
investigations were done:
1- The length, the width and the height of the tumor were measured with a
digital slide caliper every day before and after administration of different
treatment modality and tumor volume was calculated.
2- Tumor mass inhibition ratio and tumor volume growth ratio were
calculated.
3- Measurements of the dielectric properties of the tumor tissue and its
surrounding at the end of treatment period to monitor the efficiency of the
different treatment modality.
4- Analysis of toxic and trace metals: Analysis of the studied heavy metals and
trace elements [lead (Pb), cadmium (Cd), chromium (Cr), nickel (Ni), iron
(Fe), selenium (Se), copper (Cu) and zinc (Zn)] by Atomic Absorption.
5- Measurement of glutathione-S-transferase activity (GST), super oxide
dismutase activity (SOD), glutathione reductase activity (GR), catalase
activity (Cat), total antioxidant activity (TAC) and malondialdehyde
(MDA).
6- Measurement the serum levels of ALT, AST, urea and creatinine were
measured to detect the effect of thuja on liver and kidney functions.
7- Molecular detection of caveolin 1-mRNA gene expression by RT-PCR.
8- Evaluation of the structural changes induced by different treatment modality
in tumor tissue using H&E stain by microscope.
The experimental results showed that:
1) The antitumor effect of thuja increases with increasing of dose. Decreasing
in the tumor volume, tumor growth rate and inhibition ratio were observed
upon using increasing dose of thuja. However, the decline in the tumor
volume has minimum value at 5 mg/kg/body weight thuja.
2) Relative permittivity of the tumor tissue decreased exponentially with
increasing the administered dose of thuja. Relative permittivity of treated
tumor tissue with different treatment modalities decreased than that of
untreated tumor. The real conductivity increased exponentially with
increasing applied dose of thuja for all the modes of treatments, while
decreased in untreated tumor models. The variation of the imaginary
permittivity with frequency showed sharp increase at low dose of thuja
followed by exponential decreased with all methods of treatments used.
3) A significant decrease in both total body water and extracellular water
percentage while a significant increase in intracellular water percentage of
treated with 5mg thuja, 7.5mg thuja, doxorubicin and 10mg thuja
respectively compared to untreated group.
4) A statistically significant elevation of heavy metals and trace elements
(lead, cadmium, chromium, nickel and iron) concentrations was detected in
breast tissue of mice having malignant breast tumors in comparison to
control group. On the other hand, there is a significant decrease in the heavy
metals and trace elements in the animals administered both thuja and
carcinogen when compared with animals administered carcinogen alone.
5) All groups treated with DMBA, have a significant increase in the levels of
MDA as compared with normal group animals. Animals in groups received
thuja either simultaneously or post-treated exhibited significantly low levels
of MDA, when compared with animals treated with DMBA only.
6) A decreased activities of enzymatic antioxidants (SOD, CAT, GR, GST and
TAC) in comparison with normal animals. On the other hand, there is a
significant increase in the enzymatic and non-enzymatic antioxidant guard
in the animals administered both thuja and carcinogen when compared with
animals administered carcinogen alone.
7) It was observed that treatment with thuja ameliorated the levels of serum
creatinine and urea which is an indication of renal protection. This also
confirms the protective role of thuja against DMBA-induced renal toxicity.
Also treatment with thuja protected against increase in serum levels of
ALT, AST, and GGT, which is an indication of hepatoprotection by thuja.
This also confirms the protective role of thuja against DMBA-induced
hepatotoxicity.
8) Caveolin 1 gene expression significantly higher in mice groups treated thuja
extract (7.5 and 10 mg/kg body weight) than those treated with (5 mg/kg
body weight) while the lowest expression was among untreated cancerous
group.
9) The histological evaluation revealed that all tumors from the cancerous
control group were highly malignant cells and none of the tumors showed
necrosis. Tumors excised from animals receiving thuja extract (7.5 and 10
mg/kg body weight), significant areas of necrosis were present compared to
(5 mg/kg body weight) treated group while in case of doxorubicin treated
tumors, large foci of necrosis areas were present which were distinctly
appeared.