BackgroundIron binding, naturally occurring protein bovine lactoferrin (bLf) has attracted attention as a safe anti-cancer agent capable of inducing apoptosis. Naturally, bLf exists partially saturated (15-20%) with Fe3+ however, it has been demonstrated that manipulating the saturation state can enhance bLf’s anti-cancer activities.MethodsApo-bLf (Fe3+ free) and Fe-bLf (>90% Fe3+ Saturated) were therefore, tested in MDA-MB-231 and MCF-7 human breast cancer cells in terms of cytotoxicity, proliferation, migration and invasion. Annexin-V Fluos staining was also employed in addition to apoptotic protein arrays and Western blotting to determine the specific mechanism of bLf-induced apoptosis with a key focus on p53 and inhibitor of apoptosis proteins (IAP), specifically survivin.ResultsApo-bLf induced significantly greater cytotoxicity and reduction in cell proliferation in both cancer cells showing a time and dose dependent effect. Importantly, no cytotoxicity was detected in normal MCF-10-2A cells. Both forms of bLf significantly reduced cell invasion in cancer cells. Key apoptotic molecules including p53, Bcl-2 family proteins, IAP members and their inhibitors were significantly modulated by both forms of bLf, though differentially in each cell line. Most interestingly, both Apo-bLf and Fe-bLf completely inhibited the expression of survivin protein (key IAP), after 48 h at 30 and 40 nM in cancer cells.ConclusionsThe capacity of these forms of bLf to target survivin expression and modulation of apoptosis demonstrates an exciting potential for bLf as an anti-cancer therapeutic in the existing void of survivin inhibitors, with a lack of successful inhibitors in the clinical management of cancer.
There are extensive studies reporting different treatment regimens for cancer, however, they still result in systemic toxicity, reduced bioavailability and ineffective delivery. Novel approaches involve the use of biocompatible nanomaterials together with gene or drug molecules to target proteins such as survivin, which is overexpressed in cancerous cells. These nanoformulations allow the benefits of protecting easily degradable molecules, allow controlled release, and enhance targeted delivery and effectiveness. Hence, nanotherapy utilizing survivin targeting can be considered to play a key role in the development of personalized nanomedicine for cancer.
Cell-penetrating peptides (CPPs) are short chains of amino acids with the distinct ability to cross cell plasma membranes. They are usually between seven and 30 residues in length. The mechanism of action is still a highly debated subject among researchers; it seems that a commonality between all CPPs is the presence of positively charged residues within the amino acid chain. Polyarginine and the transactivator of transcription peptide are two widely used CPPs. One distinct application of these CPPs is the ability to further enhance the therapeutic properties of a range of different agents. One group of agents of particular importance are nanoparticles (NPs). Most NPs have no mechanism for cellular uptake. Hence, by conjugating CPPs to NPs, the amount of NPs taken up by cells can be increased, and therefore, the therapeutic benefits can be maximized. Some examples of this will be explored further in this review. In addition to CPPs, the concept of conjugation with the anticancer drug arsenic trioxide is reviewed and the prospect of transactivator of transcription-conjugated arsenic trioxide albumin microspheres is also discussed. Recent locked nucleic acid technology to stabilize nucleotides (RNA or DNA) aptamer complexes able to target cancer cells more specifically and selectively to kill tumour cells and spare normal body cells. NPs tagged with modified locked nucleic acid-aptamers have the potential to kill cancer cells more specifically and effectively while sparing normal cells.
Previously we identified that biomedical science students commonly misunderstand “creativity,” mistaking it for “freedom.” In the present study, we describe and evaluate a workshop designed to increase students' awareness of creativity as a highly sought‐after employability skill and cognitive process applicable to scientific endeavors. To achieve this, we developed and introduced students to a process called the “Diamond Model,” utilizing a case study to contextualize and signpost the creative processes of divergent and convergent thinking. This model was introduced to students in the first workshop of a 12‐week undergraduate biochemistry unit (subject) within the Bachelor of Biomedical Science at Monash University, Australia. Students completed pre‐ and post‐workshop surveys to gauge the impact of the workshop on their conceptions of creativity and Bloom's taxonomy of learning. In addition, reflective journals were completed by a small subset of students (n = 9) following the workshop. Following the workshop, over 65% of students indicated that their conception of creativity had changed. Thematic analysis of students' survey responses and reflections indicated that this change in the conception of creativity included broadening their definition of creativity, increased awareness of creativity as a skill and science as a creative process, and that creativity can be applied to different areas of life. Students attributed the signposting of creative elements as a contributing factor to their increased awareness. These results indicate the positive impact the workshop and our novel Diamond model had on student conception of creativity, highlighting the importance of explicit communication and signposting in skill development.
Laboratory classes are a central element of all biochemistry and molecular biology programs. These play a role in developing students' hands-on and technical skills and also offer much more. The design of laboratory classes depends on many factors including the programs the students are enrolled in, the level they are at, employment destinations, and learning outcomes. This conference session considered the design and outcomes of laboratory experiences for undergraduate students.
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