الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Breast cancer is the most common malignant tumor in women and the second leading cause of cancer death in women worldwide. Although the aetiology of breast cancer is unknown, numerous predisposing risk factors for the disease have been determined. These factors include; genetic, epigenetic, hormonal, environmental, sociobiological and oxidative stress factors. Lines of treatment in breast cancer vary according to the stage of disease. These lines include surgery, radiotherapy, chemotherapy, targeted therapy and hormonal therapy.
Tamoxifen (TAM), the prototype selective estrogen receptor modulator (SERM) has been widely used as the hormonal therapy of first choice in the treatment of all stages of hormone-dependant breast cancer in both pre and post menopausal women, for more than three decades. Yet, the use of TAM is associated with increased risk of endometrial cancer, thromboembolic diseases and about two thirds of patients do not benefit from TAM therapy due to development of TAM resistance. The goal of subsequent generations of SERMs has been to develop a potent, pure antiestrogen in mammary tissue devoid of estrogenic uterine stimulation. The second generation SERM, raloxifene (RLX), is used clinically in postmenopausal osteoporosis and holds such a promise.
Furthermore, although hormones are a major contributing factor in breast cancer, other various mechanisms are involved in its pathogenesis. In view of such considerations, the design of the present work was set to detect the effect of RLX (another hormonal therapy), procainamide (PA) (epigenetic drug), selenium (Se) (antioxidant trace element) and lovastatin (hypocholesterolemic drug) on the growth and proliferation of mammary carcinoma induced in female rats.
Moreover, the current work was also meant to compare the efficacy of these probed drugs with the standard hormonal therapy TAM, and to investigate the possible mechanisms of action of all used drugs in order to achieve the best possible therapeutic management for breast cancer.
Eighty female albino rats weighing between 110-130g were used in the current study. Ten rats were allowed to feed normal diet and received only 1ml of sesame oil orally to serve as plain normal control. The other 70 rats were subjected to induction of mammary carcinoma by administering a single dose of 20mg of dimethyl benz (a) anthracene (DMBA) suspended in 1ml sesame oil /rat via an oral gavage syringe. Starting from the 6th week after DMBA administration, rats were palpated at weekly intervals to monitor the appearance of mammary tumors which took 24-36 weeks to appear and to reach a considerable size. Then rats were randomly assigned to six experimental groups as follows:
Group I:Tumor-bearing untreated control group (20 rats) which was subdivided into:
Ia: included 10 rats, that received 1ml of 2% gum acacia/day orally to serve as control for the orally-treated rats.
Ib: included 10 rats, that received 1ml of 1% dimethyl sulfoxide (DMSO)/day intraperitoneally (i.p.) to serve as control for the i.p.- treated rats.
Group II: TAM-treated group (10 rats); rats received tamoxifen 0.6mg/kg/day orally.
Group III: RLX-treated group (10 rats); rats received raloxifene 30mg/kg/day i.p.