Anke Brüning-Richardson

Human babesiosis is a disease transmitted by the bite of an infected tick or via blood transfusions involving contaminated blood products; in humans, it can lead to severe complications and even death, depending on the clinical history, age and health status of the affected patient. Babesiosis is caused by members of the Babesia spp., protozoan parasites whose life cycle includes sexual reproduction in the arthropod vector and asexual reproduction in the mainly mammalian host. Cases of human babesiosis have been rare, but there are increasing reports of human babesiosis associated with climatic changes affecting the geographical distribution of the parasite and tick vector, enhanced vector–human interactions and improved awareness of the disease in humans. Diagnostics and treatment options for humans are based around discoveries in veterinary research, such as point-of-care testing in cases of bovine babesiosis, and include direct diagnosis by blood smears, polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) technologies, and indirect diagnosis by ELISA, immunofluorescence tests (IFAT) and fluorescent in situ hybridisation. Treatment involves a combination of drugs such as azithromycin and atovaquone, or clindamycin and quinine, but more effective options are being investigated, including, but not limited to, trans-chalcones and tafenoquine. Improved surveillance, awareness and diagnosis, as well as advanced technologies to interrupt vector–host interactions, are crucial in managing the increased threat posed by this once-neglected disease in humans.

This review explores the pivotal role of preanalytical variables in bringing liquid biopsy approaches into the clinic for brain tumors. Preanalytical variables encompass a range of critical issues, from blood sample collection and handling to the impact of tumor heterogeneity and patient-specific factors. These variables introduce challenges such as false positives, false negatives, and variability in the analysis of tumor signals, which can hinder the diagnostic and prognostic utility of liquid biopsies. Understanding the nuances of preanalytical variables is essential for the successful implementation of liquid biopsy in clinical settings. This paper delves into strategies aimed at mitigating the influence of preanalytical variables by emphasizing the importance of standardized sample collection protocols, optimized sample processing and storage, quality control measures, and the integration of multiple liquid biopsy modalities.

Background: Glioblastoma multiforme (GBM) is the most prevalent primary brain tumour, with an incidence of 2 per 100,000. The standard clinical treatments do not sufficiently target cell migration and invasion, leading to recurrence after surgical resection and resistance after chemotherapy and radiotherapy. Pre-clinical studies are being conducted to construct artificial substrates that can mimic the tumour microenvironment (TME) to prevent GBM cells from migrating along their primary route through blood vessels and white matter tracts. Alongside, targeted therapies using anti-migratory or ‘migrastatic’ drugs are also being developed. This study aimed to review the therapeutic translational strategies emerging from the study of the GBM microenvironment and anti-migratory drugs. Methods: A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria. Results: From the systems interrogated, the ‘Nanofibre’ assay is suitable to simulate white matter tracts, while hydrogel-based invasion assays and GBM cerebral organoid (GLICO) mimic the brain extracellular matrix. Inhibitors with anti-migratory activity found in this study are active involving distinct molecular mechanisms and have been tested on cell migration assays. Conclusion: Overall, we have analysed therapeutic strategies emerging from an artificial GBM TME approach and from the identification of anti-migratory inhibitors. Both carry potential to improve treatment options to prevent tumour dissemination and spread for GBM.

Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumour recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumour dissemination and regrowth. One current aim of GBM research focuses on assessing the anti-migratory properties of novel or repurposed inhibitors, including plant-based drugs which display anti-cancer properties. We investigated the potential anti-migratory activity of plant-based products with known cytotoxic effects in cancers, using a range of two-dimensional (2D) and three-dimensional (3D) migration and invasion assays as well as immunofluorescence microscopy to determine the specific anti-migratory and phenotypic effects of three plant-derived compounds, Turmeric, Indigo and Magnolia bark, on established glioma cell lines. Migrastatic activity was observed in all three drugs, with Turmeric exerting the most inhibitory effect on GBM cell migration into scratches and from the spheroid edge at all the timepoints investigated (p < 0.001). We also observed novel cytoskeletal phenotypes affecting actin and the focal adhesion dynamics. As our in vitro results determined that Turmeric, Indigo and Magnolia are promising migrastatic drugs, we suggest additional experimentation at the whole organism level to further validate these novel findings.