Biophysical Parameters Can Induce Epithelial-to-Mesenchymal Phenotypic and Genotypic Changes in HT-29 Cells: A Preliminary Study.

Epithelial to mesenchymal transition (EMT) in cancer is the process described where cancer epithelial cells acquire mesenchymal properties which can lead to enhanced invasiveness. Three-dimensional cancer models often lack the relevant and biomimetic microenvironment parameters appropriate to the native tumour microenvironment thought to drive EMT. In this study, HT-29 epithelial colorectal cells were cultivated in different oxygen and collagen concentrations to investigate how these biophysical parameters influenced invasion patterns and EMT. Colorectal HT-29 cells were grown in physiological hypoxia (5% O2) and normoxia (21% O2) in 2D, 3D soft (60 Pa), and 3D stiff (4 kPa) collagen matrices. Physiological hypoxia was sufficient to trigger expression of markers of EMT in the HT-29 cells in 2D by day 7. This is in contrast to a control breast cancer cell line, MDA-MB-231, which expresses a mesenchymal phenotype regardless of the oxygen concentration. In 3D, HT-29 cells invaded more extensively in a stiff matrix environment with corresponding increases in the invasive genes MMP2 and RAE1. This demonstrates that the physiological environment can directly impact HT-29 cells in terms of EMT marker expression and invasion, compared to an established cell line, MDA-MB-231, which has already undergone EMT. This study highlights the importance of the biophysical microenvironment to cancer epithelial cells and how these factors can direct cell behaviour. In particular, that stiffness of the 3D matrix drives greater invasion in HT-29 cells regardless of hypoxia. It is also pertinent that some cell lines (already having undergone EMT) are not as sensitive to the biophysical features of their microenvironment.

The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review.

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.

Assessment of first-year medical students' perceptions of teaching and learning through team-based learning sessions.

Team-based learning (TBL) is an emerging teaching and learning strategy being employed in medical schools. The College of Medicine at Alfaisal University has adopted a TBL approach as an instructional method for first-year medical students. The aim of the present study was to describe the TBL method employed at Alfaisal University College of Medicine and to assess first-year medical students' perceptions of this learning modality for the anatomy- and physiology-based blocks/courses in organ systems form of curriculum. A five-point Likert scale questionnaire was structured based on Kirkpatrick's theory and assessed three major domains: reaction, learning, and behavior. Confirmatory factor analysis (CFA) and Cronbach's α-coefficient tests were used to assess the validity and reliability of the construct, respectively. CFA showed an adequate validity of the survey and Cronbach's α revealed an acceptable internal uniformity (0.69). A total of 185 respondents rated reaction, learning, and behavior toward introduction of TBL as 3.53 ± 1.01, 3.59 ± 1.12, and 3.57 ± 1.12, respectively. Excellent students rated TBL highly in all major domains compared with borderline students (reaction, behavior, and learning domains with P values of <0.049, <0.035, and <0.031, respectively). Students who had prior teamwork experience rated TBL higher in terms of their learning experience compared with those who were rarely involved in team work. This study demonstrated that Alfaisal University first-year medical students perceived TBL positively as a teaching and learning strategy for functional anatomy, and prior involvement in teamwork and academic performance correlates with higher ratings of TBL.