نظام الحكم الديمقراطي في فلسفة سبينوزا السياسية

تُعنى هذه الدراسة ببيان نظام الحكم الديمقراطي عند سبينوزا ، والذي له أهمية كبيرة في الفلسفة الحديثة بصورة عامة، والفلسفة السياسية بصورة خاصة ، والذي يصفه سبينوزا بأنه الأفضل من بين أنظمة حكم الدولة الموجودة، وكل ذلك من خلال بيان الفلسفة السياسية عنده ، لتكون الصورة واضحة ومتكاملة، وقد استخدمنا المنهج الوصفي في بيان أفكاره السياسية ، وتتبع هذه الأفكار بصورة تفصيلية، من خلال مقدمة ومجموعة من المحاور وخاتمة ونتائج لهذه الدراسة، والتي توصلنا من خلالها إلى إن ما يدعو إليه سبينوزا من خلال فلسفة السياسية في إدارة الدولة هو النظام الديمقراطي، لأنه أفضل الأنظمة السياسية التي تحقق العدالة والمساواة والحرية للمجتمع ، والطمأنينة والسلام والسعادة للفرد.

Predictive Role of Cyclooxygenase-2 Expression in Her 2 Neu -Erbb2 Amplified Breast Cancer Patients

Worldwide, a major cause of cancer related deaths in females is breast cancer. Aspirin, a member of the NSAID family of drugs has been indicated by several epidemiological studies to lower the risk for breast cancer especially in hormone receptor positive patients. NSAIDs are known to target the cyclooxygenase enzymes. Two isoforms of COX have been described. COX-1 is inherently expressed in most tissues like gastrointestinal tract, kidney, stomach, platelets and is involved in tissue homeostasis. In contrast, COX-2 is stimuli specific and its expression depends on certain extracellular and intracellular stimuli including mitogens, cytokines, tumour proteins, growth factors. COX-2 has been associated with inflammation and carcinogenesis. It has been observed to be overexpressed in many malignant tumours. COX-2 increases the production of prostaglandin, which inhibits apoptosis, promotes angiogenesis, and induces tumour invasion and metastasis. High COX-2 expression is related to the formation of mammary tumours and is associated with parameters of aggressive breast cancer, like advanced tumour size, grade, lymph node metastasis and HER-2 positive status. The purpose of this study was to investigate the prognostic and predictive role of COX-2 in breast cancer. One hundred and fifty breast cancer paraffin embedded tissue specimens were screened. The age of patients ranged between 30 and 73 years their mean was 42.71 ± 9.4. This study results showed that frequencies of ER+/PR+/HER-2+ were (50.71%) followed by ER-/PR-/HER-2+ (12.7%) ER+/PR-/HER-2- (9.3%) and ER+/PR-/HER-2+ (8.0%). Increased frequency of high grade tumour was noted in luminal B and HER-2+ breast cancer patients. In addition, comparison between HER-2/neu gene amplified and non-amplified groups showed that high grade tumours and ER negative status were more common in HER-2 amplified group. Furthermore, same 150 tissue specimens from the breast cancer patients’ and 101 healthy controls (total 251 female participants) were screened for the functionally important COX-2 SNPs rs 689465, rs 689466 and rs 20417 in its promoter region. Analysis of rs689465, rs689466 and rs20417 was performed by PCR-based restriction fragment length polymorphism. In our study none of these polymorphisms were significantly associated with breast cancer in the single locus analysis. These observations are comparable with other studies that have reported no association of these COX-2 SNPs and breast cancer. However, haplotype G 1195 - A1290 - C 765 (GAC) was found to be associated with breast cancer risk (OR2.90, CI 95% 1.37-6.32 p=0.007). It means that polymorphism in regulatory region of COX-2 may interact in combinational manner. Moreover, GAC was significantly associated with tumour size (OR 5.13, 95% CI 1.140-23.13, p=0.033) and HER-2 status (OR 2.018, 95% CI: 1.061-3.831, p=0.032). In this study, we also observed significant correlation among rs20417CC+GC variants, tumour type (IDC) (P=0.03), ER negativity (P=0.016) and HER-2 positivity (P=0.02), however no association between rs689456, rs689466 and histopathological parameters was observed. On the other hand, in the same breast cancer patients group, in 35 (23%) subjects COX-2 expression was observed by immunohistochemistry (IHC), which showed significant association with HER-2 gene amplification (p = 0.028). In addition, we observed strong association of NF-kB, Akt in 35 HER-2 positive and COX-2 positive breast cancer patients. In summary, we investigated predictive and prognostic role of COX-2, and observed that Akt/NF-kB/COX-2 pathway is an important step in the control of cell survival in HER-2 positive tumour. We suggest that cell signaling mechanisms involving AKT/NF-κB/COX-2 that participates in HER-2 driven suppression of apoptosis requires it to be considered when designing drugs for targeting HER-2 positive tumours.