An In Vitro 3D Model to Evaluate Behaviour of Breast Cancer Cells and Response to Treatment

The field of 3D culture models of disease has started to move towards systems that aim to recapitulate the complexity of human tissues. However, despite recent improvements, current 3D systems remain overly simplistic, lacking the biophysical characteristics and diverse structures found in most organs. In this project, the cellular behaviour of breast cancer and their responsiveness to chemotherapeutic agents were evaluated under different 3D cell culture conditions. MDA-MB231 and SKBR3 cells were prepared as spheroids using ultra-low attachment plates and as 'artificial cancer masses' (ACM) by embedding cells in a dense collagen type-I. The ACMs were maintained under flow (150 μL/min) and flow/pressure (550 μL/min, ~19 mmHg) conditions. A significant reduction in cell viability was observed when cancer cells were grown as ACM compared to 2D culture. Cell viability also declined significantly when ACMs were maintained in flow/pressure condition compared to static condition. Similarly, an increase in the expression levels of markers of EMT was observed when cells were cultured as ACM. However, compared to static 3D incorporation of flow and pressure was associated with decreased expression levels of vimentin, HIF1-α, whilst MMP14 expression increased and snail remained unchanged. HER2 levels were increased in SKBR3 when the cells were cultured under flow/pressure (1.5 fold) compared to static condition. Overall, cells cultured as ACMs exhibited reduced responsiveness to doxorubicin compared to those grown in the conventional 2D culture. A decrease sensitivity was also observed in 3D/flow/pressure and 3D/flow compared to 3D/static condition. The results obtained in this study show that cancer cell behaviour and their response to therapeutic agents are affected by different microenvironments. Therefore, a new generation of 3D in vitro models need to be developed as pre-clinical drug testing platforms

Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin.

3D laboratory models of cancer are designed to recapitulate the biochemical and biophysical characteristics of the tumour microenvironment and aim to enable studies of cancer, and new therapeutic modalities, in a physiologically-relevant manner. We have developed an in vitro 3D model comprising a central high-density mass of breast cancer cells surrounded by collagen type-1 and we incorporated fluid flow and pressure. We noted significant changes in cancer cell behaviour using this system. MDA-MB231 and SKBR3 breast cancer cells grown in 3D downregulated the proliferative marker Ki67 (P<0.05) and exhibited decreased response to the chemotherapeutic agent doxorubicin (DOX) (P<0.01). Mesenchymal markers snail and MMP14 were upregulated in cancer cells maintained in 3D (P<0.001), cadherin-11 was downregulated (P<0.001) and HER2 increased (P<0.05). Cells maintained in 3D under fluid flow exhibited a further reduction in response to DOX (P<0.05); HER2 and Ki67 levels were also attenuated. Fluid flow and pressure was associated with reduced cell viability and decreased expression levels of vimentin. In summary, aggressive cancer cell behaviour and reduced drug responsiveness was observed when breast cancer cells were maintained in 3D under fluid flow and pressure. These observations are relevant for future developments of 3D in vitro cancer models and organ-on-a-chip initiatives

PhytoCloud: A gamified Mobile Web Application to modulate diet and physical activity of women with breast cancer

Breast cancer incidence and mortality rates vary geographically reflecting factors including regional and cultural differences in diet and lifestyle. There are numerous successful commercial mobile apps to help people control their diet and manage weight. However, such products are not suitable for people with special medical conditions that may require targeted dietary as well as motivational support. The paper presents a user centered approach of developing a Mobile Web App that focuses on breast cancer patients looking at their specific dietary, physical and mental requirements depending on the stage of their medical treatment. The paper explores the effect of incorporating gamification and social media as motivational drive to engage and motivate people to achieve their goals of adopting healthier eating habits while increasing physical activity in order ensure lasting lifestyle behavioural change. The design of “PhytoCloud” is being described, a gamified Mobile Web App that enables users to record their dietary habits and physical activity and motivate their consumption of food with oestrogen-like properties (phytoestrogens) which are linked to the prevention of reappearance of breast cancer. The paper concludes with a discussion of future directions and adaptations to the current design to suite a Mobile Native Application design

Enhancing properties of iron and manganese ores as oxygen carriers for chemical looping processes by dry impregnation

The use of naturally occurring ores as oxygen carriers in CLC processes is attractive because of their relative abundance and low cost. Unfortunately, they typically exhibit lower reactivity and lack the mechanical robustness required, when compared to synthetically produced carriers. Impregnation is a suitable method for enhancing both the reactivity and durability of natural ores when used as oxygen carriers for CLC systems. This investigation uses impregnation to improve the chemical and mechanical properties of a Brazilian manganese ore and a Canadian iron ore. The manganese ore was impregnated with Fe2O3 and the iron ore was impregnated with Mn2O3 with the goal of forming a combined Fe/Mn oxygen carrier. The impregnated ore’s physical characteristics were assessed by SEM, BET and XRD analysis. Measurements of the attrition resistance and crushing strength were used to investigate the mechanical robustness of the oxygen carriers. The impregnated ore’s mechanical and physical properties were clearly enhanced by the impregnation method, with boosts in crushing strength of 11–26% and attrition resistance of 37–31% for the impregnated iron and manganese ores, respectively. Both the unmodified and impregnated ore’s reactivity, for the conversion of gaseous fuel (CH4 and syngas) and gaseous oxygen release (CLOU potential) were investigated using a bench-scale quartz fluidised-bed reactor. The impregnated iron ore exhibited a greater degree of syngas conversion compared to the other samples examined. Iron ore based oxygen carrier’s syngas conversion increases with the number of oxidation and reduction cycles performed. The impregnated iron ore exhibited gaseous oxygen release over extended periods in an inert atmosphere and remained at a constant 0.2% O2 concentration by volume at the end of this inert period. This oxygen release would help ensure the efficient use of solid fuels. The impregnated iron ore’s reactivity for CH4 conversion was similar to the reactivity of its unmodified counterpart. The unmodified manganese ore converted CH4 to the greatest extent of all the samples tested here, while the impregnated manganese ore exhibited a decrease in reactivity with respect to syngas and CH4 conversion.EPSR

The mediating role of spirituality between self-value and counselling attitudes among Nigerian students in Malaysian universities

This study examined the mediating role of spirituality between self-value and counselling attitudes towards seeking professional psychological help among Nigerian students in Malaysian universities. The sample consisted of 394 Nigerian students who are currently enrolled in 10 randomly selected universities across Malaysia. They completed self-report questionnaires administered one-on-one in each of the selected institutions. It was hypothesized that there is no mediating relationship between self-value and counselling attitudes through spirituality. Two levels of quantitative research are presented: descriptive and correlational. SPSS version 22 and SEM analyses (descriptive statistics/AMOS) gave a contrary result, therefore the null hypothesis was rejected and it was concluded that spirituality mediated the relationship between self-value and counselling attitudes. Limitations in the current study, such as sample size, and directions for future studies to address the limitations are discussed