71 research outputs found
Identification of a Novel Ligand Independent Function of the Cytoplasmic Vitamin D Receptor in Breast Cancer
No full textThis thesis aims to define the role of the vitamin D receptor (VDR) in breast cancer (BC), hypothesising that in contrast to the anti-proliferative effects of its ligand, 1.25-dihydroxy vitamin D3, VDR knockdown would enhance BC cell growth. Using stable shRNA expression, VDR expression was knocked down (VDR-KD) in two human BC cell lines, namely MDA-Tx-SA and MCF-7 cells. Parental (PA) and non-target (shNT) cells served as controls. In ligand-free culture, VDR-KD significantly reduced BC cell growth and induced cell apoptosis. In vivo, VDR-KD suppressed BC cell growth in both the mammary fat pad and the bone environment. However, VDR-KD cells exhibited increased invasive potential, likely via changes in beta-catenin and E-cadherin signaling. These findings suggest a ligand-independent effect of the VDR on BC cell behaviour. Transfection of VDR-KD BC cells with a mutant VDR construct unable to translocate to the nucleus restored normal growth of VDR-KD BC cells. I conclude that in contrast to the known anti-proliferative actions of the liganded VDR, the cytoplasmic VDR promotes BC cell growth. This discovery adds to our understanding of VDR signaling in BC and may help to resolve discrepancies regarding the association between vitamin D status and BC prognosis
Protein expression of CD44 in patients with meningioma tumors: association with clinicopathological parameters and survival
No full textAbstract Objective Meningiomas are a molecularly ill-defined heterogeneous group of indolent intracranial tumors. Though, WHO grade 1 tumors are histologically benign, sometimes they transform into malignant and may be recurrent which remains always challenging to clinicians. Therefore, the current study sought to discover the clinical relevance of CD44 in meningioma patients. Method Protein expression of CD44 was investigated using immunohistochemistry in a total of 70 meningioma patients. Immunoscore performed using modified H-score, CD44 expression correlated with clinicopathological parameters and progression-free survival (PFS) and overall survival (OS). Univariate and multivariate survival analysis was analyzed. The data was evaluated using SPSS statistical software and P-value ≤ 0.05 was considered as significant. Results The membranous and cytoplasmic protein expression of CD44 was noted in meningioma tumors. Based on H-score, the weak (0–190 score) and strong (191–300 score) immunoreactivity was observed in 62.9% and 37.1% of patients, respectively. A statistically significant positive correlation was found between strong CD44 expression and WHO grade 2/3 tumors (χ 2 = 33.551, r = + 0.692, P = 0.0001), and with the presence of brain invasion (χ 2 = 19.521, r = + 0.528, P = 0.001). In Kaplan–Meier univariate survival analysis for PFS and OS, apart from WHO grade of tumors (PFS; log-rank = 12.309, P = 0.0001, OS; log-rank = 17.830, P = 0.0001) and brain invasion status (PFS; log-rank = 11.941, P = 0.001, OS; log-rank = 13.554, P = 0.0001) CD44 expression (PFS; log-rank = 14.942, P = 0.0001, OS; log-rank = 20.986, P = 0.0001) remained significant prognostic factor for PFS and OS. In multivariate survival analysis, at step 1, only CD44 remained independent prognosticator for PFS (HR = 11.014, 95% CI = 2.256–23.602, P = 0.001) and OS (HR = 8.553, 95% CI = 2.831–25.847, P = 0.0001). In relation to treatment offered, patients with strong CD44 expression and if treated with surgery followed by adjuvant radiotherapy showed a high incidence of death (log-rank = 13.402, P = 0.0001) as compared to patients treated with surgery only. Receiver operating characteristic (ROC) curves also confirmed a good efficacy of CD44 as a prognosticator for disease outcome (PFS; P = 0.0001, OS; P = 0001). Conclusion Our overall findings addressed that a study of CD44 protein expression would be beneficiated to meningioma patients from unnecessary overtreatment and drug-induced toxicity. Also, CD44 could be one of the promising biomarkers that might differentiate high-risk meningioma patients for better treatment management
Hydrothermally synthesized reduced graphene oxide/nickel hydroxide (rGO/Ni(OH)2) nanocomposite: A promising material in dye removal
No full textFabrication, characterization and annealing of polymer-fullerene bulk heterojunction organic solar cells
No full textElectrocatalytic activity of silver nanoparticles decorated reduced graphene oxide (AgNP@rGO) nanocomposites
No full textA Paramount Factor in Sustainable Growth at the Workplace for the Worldwide Community
Get PDFThis paper represents the importance of workplace innovation to the sustainable development of the organization. Workplace revamps have been renowned for everything from technical innovation and its significance to intuitive service improvements. It has covered the relationship between workplace productivity, health, safety, and well-being and sustainable development.
Additionally, the author made an effort to compare the three sustainable development pillars to the six sustainable development pillars from the perspective of earlier research. The results of earlier research focused on the economic, social, and environmental aspects of sustainable development, but a recent study added three more dimensions—cultural, political, and technological—that stem from the already-existing aspects. Thus, the purpose of the study is to discuss workplace innovation, its significance, and its effects on global society's ability to develop sustainabl
An investigation on the operation of Solid Oxide Fuel Cells and micro-turbine for load-following performances
No full textFuel cells are prominently known and researched extensively by scientists and companies globally for its use as alternative form of energy without any further degradation of Mother Nature. In a few years, the quantity of coal and oil would be reaching an all-time low making it absolutely necessary to find for other viable
solution for the survival of mankind. Here, fuel cells offer a sanctuary for clean and green energy making it the most sought after technology in today’s time. However, more research and improvements has to be done so that more companies could
employ such technologies in their establishments.
In this project, the author has established the SIMULINK modelling technique for a 100kW SOFC plant. Activation, ohmic and concentration losses has also been taken into account for the plant to give a more accurate picture of the system. Upon a
sudden increase in the power demanded by the consumer, the SOFC plant reaches to it maximum possible fuel utilization permissible and within a few reaches to the
steady state value. This shows the operation of the SOFC in real time subjected to load disturbances. In addition, a split-shaft microturbine has been implemented to provide addition
power to a plant. Likewise, with a sudden disturbance, the electrical and mechanical power oscillates to a steady state value. Hence, it is able to withstand a sudden disturbance. With the two SIMULINK models established, the author has examined
the load following performance of the two systems. SOFC being more efficient is able to take on more power as compared to microturbine. In the future, distribution system can be established with such tie line flow to ensure that power can be attained in a cleaner way. Future works includes combining the microturbine and the SOFC to increase efficiency of the operation for combined heat and power generation.Bachelor of Engineerin
Translational Strategies to Target Metastatic Bone Disease
No full textMetastatic bone disease is a common and devastating complication to cancer, confounding treatments and recovery efforts and presenting a significant barrier to de-escalating the adverse outcomes associated with disease progression. Despite significant advances in the field, bone metastases remain presently incurable and contribute heavily to cancer-associated morbidity and mortality. Mechanisms associated with metastatic bone disease perpetuation and paralleled disruption of bone remodeling are highlighted to convey how they provide the foundation for therapeutic targets to stem disease escalation. The focus of this review aims to describe the preclinical modeling and diagnostic evaluation of metastatic bone disease as well as discuss the range of therapeutic modalities used clinically and how they may impact skeletal tissue
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