Liquid biopsy and glioblastoma.

Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), or extracellular vesicles (EVs) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations, and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.

Medulloblastoma: From TP53 Mutations to Molecular Classification and Liquid Biopsy.

A recent paradigm shift in the diagnostics of medulloblastoma allowed the distinction of four major groups defined by genetic data rather than histology. This new molecular classification correlates better with prognosis and will allow for the better clinical management of therapies targeting druggable mutations, but also offer a new combination of monitoring tumor development in real-time and treatment response by sequential liquid biopsy. This review highlights recent developments after a century of milestones in neurosurgery and radio- and chemotherapy, but also controversial theories on the cell of origin, animal models, and the use of liquid biopsy.

Liquid Biopsy and Primary Brain Tumors.

Two decades of "promising results" in liquid biopsy have led to both continuing disappointment and hope that the new era of minimally invasive, personalized analysis can be applied for better diagnosis, prognosis, monitoring, and therapy of cancer. Here, we briefly highlight the promises, developments, and challenges related to liquid biopsy of brain tumors, including circulating tumor cells, cell-free nucleic acids, extracellular vesicles, and miRNA; we further discuss the urgent need to establish suitable biomarkers and the right standards to improve modern clinical management of brain tumor patients with the use of liquid biopsy.

Community standards for open cell migration data.

Cell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited owing to the diversity of experimental protocols and non-standardized output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardized data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardization efforts by the Cell Migration Standardisation Organisation (CMSO), an open community-driven organization to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration.

Measurements of fast fluctuations of viscoelastic properties with the quartz crystal microbalance.

The quartz crystal microbalance (QCM) was used to study the variability of acoustic properties of living cells on the sub-second time scale. A confluent cell layer of rat cardiac myocytes was grown onto the electrode of quartz crystal resonator. The cell layer performed periodic, synchronous contractions at a rate of about 1.5 Hz. In order to monitor these rather fast changes in the state of the cells, the QCM was operated in a "fast mode", which allows sampling of the shift of the resonance frequency and energy dissipation with a rate of up to 100 Hz. The contractions were clearly reflected in periodic variations of the resonance frequency and the bandwidth. The rate of the contractions, in particular, could be easily detected in this way. Building on the rate of contraction, the setup can be used to monitor the response of the cell layer to heart stimulating drugs like isoproterenol. Depending on the concentration of isoproterenol, the beat rate was found to increase by up to a factor of two.

Atomic force microscopy measurements of protein-ligand interactions on living cells.

Cell adhesion receptors are expressed on the surface of cells and can mediate binding to other cells and to the extracellular matrix. Here, we describe in detail the use of atomic force microscopy (AFM)-based force spectroscopy for studying cell detachment forces on living leukocytes. With this technique it is now possible to measure force with resolution down to the level of individual molecules. AFM force spectroscopy is particularly well suited for research in cell adhesion, which has relevance in both the medical and life sciences including immunology, cancer and stem cell research, and human pharmacology. Along with its limitations, we herein, describe how the rupture force of a single complex formed between the integrin receptor leukocyte function-associated antigen (LFA)-1, expressed on the surface of a living leukocyte, and immobilized intercellular adhesion molecule-1 (ICAM-1) was measured. With only minor modifications this protocol can be used to study other adhesion receptors on almost any mammalian cell or bacterial system. This protocol is also suitable for studying single-molecule de-adhesion events in cell-free systems as well as between two living cells.