فیملی بزنس میں'' ابہام'' سے پیدا ہونے والے مسائل کا شرعی و تحقیقی جائزہ

ABSTRACTFamily Business is a very important form of business in this era and especially because of this it merely does not matter the business, but more sensitivity is of close relatives and relationships. That is why it has many administrative, Shariah and ethical complications. That is why, this theme has been created as a field of discussion and research. If the issues of Family Business are reviewed, their root is to leave the matters undefined, uncleared and undocumented. Then the solution to all these issues is to overcome their ‘Unclarity’ found in different aspects. To finish the matter, we should clear and correct for example ‘business status’ between father and sons, uncle and nephew or a few brothers. Similarly, in case of death of elders, the inheritance is to be determined. Then that all the matters should be written in a very brief manner and arranged. It is also possible to calculate the income and expenditure account. It is not appropriate that every partner should spend without any speculation. Then one time it becomes difficult to face each other. In this article, we have tried to review all the dimensions where there may be more problems due to ‘unclearity’ in mutual business dealings. In this context, the first business status of family members has been explained. Then mentioned the problems raised after the death of the family leader. Later on, more aspects of the problem are presented by presenting some other observation examples on this subject.

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.