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.
When talking about children’s abilities, they indeed cannot be separated from their educational or training background. Moreover, he has entered the working age that must have productivity in his work, especially at this time, where the era has entered the industrial revolution 4.0. The industrial revolution 4.0 is marked by the development of digitalization in various lines of life. On the one hand, the industrial revolution 4.0 had many positive impacts. However, on the other hand, as the McKinsey Global Institute states that as a result of the 4.0 industrial revolution in the next five years, there will be 52.6 million jobs that will decline and even disappear. This certainly will be a challenge for the centennial generation (children born from 1996-2011) at this time, which they have to survive with the existing conditions and situations. This paper will discuss several factors that describe and address issues such as what is meant by the centennial generation, literacy, and the urgency of literacy education for the centennial generation in the digital age. According to authors, thi is essential to discuss, given the increasingly rapid development and technological progress resulting in the loss of much work.
Virtual education is a distance mode of education which imparts education through synchronous and asynchronous types of educational technologies. It aims to provide equal educational opportunities to large number of learners beyond the gender biasness, geographical boundaries and cultural issues. It is cost effective, learner centered, activity based and flexible education system. It also provides educational opportunities to in service people, physically defected and persons bound to live in boundaries. Virtual education facilitates people to continue their education with ease and comfort without disturbing their normal routine responsibilities. Virtual learners can attend their teaching learning activities according to their own pace, time and schedule. With the advancement, application and vide acceptance of modern educational technologies virtual education is getting popularity day by day. In Pakistan first virtual education university was established in 2002 with clear mission “not for profit”. It is a federal charted university which has established 27 its own campuses and has affiliated 137 private virtual campuses in short spell of time. More than 100000 virtual learners have been enrolled in this university up to 2015. The present study was conducted with the main objectives (i) to study the framework of virtual education model, (ii) to highlight the instructional paradigms of virtual education, (iii) to identify the significance of virtual education in Pakistan, (iv) to evaluate the components of virtual education model in Pakistan, (v) to explore the challenges faced by virtual students in Pakistan, and (vi) to recommend measures for improving virtual education model in Pakistan. The population of the study consisted of faculty members and the virtual learners of the MBA program of the virtual university of Pakistan. The convenient sampling technique was adopted for study. The total sample of the study was (451) consisted of one hundred (100) faculty members, three hundred and fifty one (351) virtual learners. The study was descriptive in nature therefore survey approach was considered appropriate and adopted for its completion. Two (02) questionnaires on five points rating (likert) scale were prepared. Research tools were finalized after their pilot testing with the calculated reliability of the research instruments. The samples could only be found virtually therefore research tools were converted into google.doc to collect data. Collected data was coded in SPSS version 20 and was statistically analyzed by using percentage, mean score and standard deviation. Form the data analysis it was found that virtual education was an effective mode of education in Pakistan. The study also concluded that virtual education model of Pakistan was providing quality education based upon the parameters of learner centeredness, cost effectiveness, activity based, need based and meeting international standards of education. Therefore, the study also recommended some suggestions to improve the virtual education model. Some other public and private sector universities should also start virtual education in Pakistan to endorse quality education. Teacher student interaction should be made more cohesive. Private virtual campuses should ensure accountability and accreditation. Co-curricular activities should also be given proper weightage in virtual education.