Glioblastomas are considered the most common and aggressive primary brain tumor in adults, with an average of 15 months’ survival rate. The treatment is surgery resection, followed by chemotherapy with temozolomide, and/or radiotherapy. Glioblastoma must have wild-type IDH gene and some characteristics, such as TERT promoter mutation, EGFR gene amplification, microvascular proliferation, among others. Glioblastomas have great heterogeneity at cellular and molecular levels, presenting distinct phenotypes and diversified molecular signatures in each tumor mass, making it difficult to define a specific therapeutic target. It is believed that the main responsibility for the emerge of these distinct patterns lies in subcellular populations of tumor stem cells, capable of tumor initiation and asymmetric division. Studies are now focused on understanding molecular mechanisms of chemoresistance, the tumor microenvironment, due to hypoxic and necrotic areas, cytoskeleton and extracellular matrix remodeling, and in controlling blood brain barrier permeabilization to improve drug delivery. Another promising therapeutic approach is the use of oncolytic viruses that are able to destroy specifically glioblastoma cells, preserving the neural tissue around the tumor. In this review, we summarize the main biological characteristics of glioblastoma and the cutting-edge therapeutic targets that are currently under study for promising new clinical trials.

The viscoelastic properties of cells have been investigated by a variety of techniques. However, the experimental data reported in literature for viscoelastic moduli differ by up to three orders of magnitude. This has been attributed to differences in techniques and models for cell response as well as to the natural variability of cells. In this work we develop and apply a new methodology based on optical tweezers to investigate the rheological behavior of fibroblasts, neurons and astrocytes in the frequency range from 1Hz to 35Hz, determining the storage and loss moduli of their membrane-cortex complex. To avoid distortions associated with cell probing techniques, we use a previously developed method that takes into account the influence of under bead cell thickness and bead immersion. These two parameters were carefully measured for the three cell types used. Employing the soft glass rheology model, we obtain the scaling exponent and the Young’s modulus for each cell type. The obtained viscoelastic moduli are in the order of Pa. Among the three cell types, astrocytes have the lowest elastic modulus, while neurons and fibroblasts exhibit a more solid-like behavior. Although some discrepancies with previous results remain and may be inevitable in view of natural variability, the methodology developed in this work allows us to explore the viscoelastic behavior of the membrane-cortex complex of different cell types as well as to compare their viscous and elastic moduli, obtained under identical and well-defined experimental conditions, relating them to the cell functions.

In the last years, the extracellular matrix (ECM) has been reported as playing a relevant role in esophageal cancer (EC) development, with this compartment being related to several aspects of EC genesis and progression. This sounds very interesting due to the complexity of this highly incident and lethal tumor, which takes the sixth position in mortality among all tumor types worldwide. The well-established increase in ECM stiffness, which is able to trigger mechanotransduction signaling, is capable of regulating several malignant behaviors by converting alteration in ECM mechanics into cytoplasmatic biochemical signals. In this sense, it has been shown that some molecules play a key role in these events, particularly the different collagen isoforms, as well as enzymes related to its turnover, such as lysyl oxidase (LOX) and matrix metalloproteinases (MMPs). In fact, MMPs are not only involved in ECM stiffness, but also in other events related to ECM homeostasis, which includes ECM remodeling. Therefore, the crucial role of distinct MMPs isoform has already been reported, especially MMP-2, -3, -7, and -9, along EC development, thus strongly associating these proteins with the control of important cellular events during tumor progression, particularly in the process of invasion during metastasis establishment. In addition, by distinct mechanisms, a vast diversity of glycoproteins and proteoglycans, such as laminin, fibronectin, tenascin C, galectin, dermatan sulfate, and hyaluronic acid exert remarkable effects in esophageal malignant cells due to the activation of oncogenic signaling pathways mainly involved in cytoskeleton alterations during adhesion and migration processes. Finally, the wide spectrum of interactions potentially mediated by ECM may represent a singular intervention scenario in esophageal carcinogenesis natural history and, due to the scarce knowledge on the cellular and molecular mechanisms involved in EC development, the growing body of evidence on ECM’s role along esophageal carcinogenesis might provide a solid base to improve its management in the future.

We measure the colloidal interaction between two silica microspheres in an aqueous solution in the distance range from 0.2 to $0.5\mu \mathrm{m}$ with the help of optical tweezers. When employing a sample with a low salt concentration, the resulting interaction is dominated by the repulsive double-layer interaction which is fully characterized. The double-layer interaction is suppressed when adding $0.22\mathrm{M}$ of salt to our sample, thus leading to a purely attractive Casimir signal. When analyzing the experimental data for the potential energy and force, we find good agreement with theoretical results based on the scattering approach. At the distance range probed experimentally, the interaction arises mainly from the unscreened transverse magnetic contribution in the zero-frequency limit, with nonzero Matsubara frequencies providing a negligible contribution. In contrast, such unscreened contribution is not included by the standard theoretical model of the Casimir interaction in electrolyte solutions, in which the zero-frequency term is treated separately as an electrostatic fluctuational effect. As a consequence, the resulting attraction is too weak in this standard model, by approximately one order of magnitude, to explain the experimental data. Overall, our experimental results shed light on the nature of the thermal zero-frequency contribution and indicate that the Casimir attraction across polar liquids has a longer range than previously predicted.

Glioblastoma is a highly aggressive brain tumor with a poor prognosis. Recent studies have suggested that mechanobiology, the study of how physical forces influence cellular behavior, plays an important role in glioblastoma progression. Several signaling pathways, molecules, and effectors, such as focal adhesions, stretch-activated ion channels, or membrane tension variations, have been studied in this regard. Also investigated are YAP/TAZ, downstream effectors of the Hippo pathway, which is a key regulator of cell proliferation and differentiation. In glioblastoma, YAP/TAZ have been shown to promote tumor growth and invasion by regulating genes involved in cell adhesion, migration, and extracellular matrix remodeling. YAP/TAZ can be activated by mechanical cues such as cell stiffness, matrix rigidity, and cell shape changes, which are all altered in the tumor microenvironment. Furthermore, YAP/TAZ have been shown to crosstalk with other signaling pathways, such as AKT, mTOR, and WNT, which are dysregulated in glioblastoma. Thus, understanding the role of mechanobiology and YAP/TAZ in glioblastoma progression could provide new insights into the development of novel therapeutic strategies. Targeting YAP/TAZ and mechanotransduction pathways in glioblastoma may offer a promising approach to treating this deadly disease.