The invasive capabilities of glioblastoma (GBM) define the cancer’s aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences the molecular behavior of cells, both epigenetically and genetically. Current forces being studied include properties of the extracellular matrix (ECM), such as stiffness and “sensing” capabilities. There is currently limited data on the physical forces in GBM—both relating to how they influence their environment and how their environment influences them. This review outlines the advances that have been made in the field. It is our hope that further investigation of the physical forces involved in GBM will highlight new therapeutic options and increase patient survival. A search of the PubMed database was conducted through to 23 March 2022 with the following search terms: (glioblastoma) AND (physical forces OR pressure OR shear forces OR compression OR tension OR torsion) AND (migration OR invasion). Our review yielded 11 external/applied/mechanical forces and 2 tumor microenvironment (TME) forces that affect the ability of GBM to locally migrate and invade. Both external forces and forces within the tumor microenvironment have been implicated in GBM migration, invasion, and treatment resistance. We endorse further research in this area to target the physical forces affecting the migration and invasion of GBM.

The cortical motor system can be reorganized following a stroke, with increased recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to movement impairments. This proof-of-concept study assessed somatosensory evoked potentials (SEPs), P50 and N100, in hemiparetic stroke participants and age-matched controls using high-density electroencephalograph (EEG) recordings during tactile finger stimulation. The laterality index was calculated to determine the hemispheric dominance of the SEP and re-confirmed with source localization. The study found that latencies of P50 and N100 were significantly delayed in stroke brains when stimulating the paretic hand. The amplitude of P50 in the contralateral (to stimulated hand) hemisphere was negatively correlated with the Fügl–Meyer upper extremity motor score in stroke. Bilateral cortical responses were detected in stroke, while only contralateral cortical responses were shown in controls, resulting in a significant difference in the laterality index. These results suggested that somatosensory reorganization after stroke involves increased recruitment of ipsilateral cortical regions, especially for the N100 SEP component. This reorganization delays the latency of somatosensory processing after a stroke. This research provided new insights related to the somatosensory reorganization after stroke, which could enrich future hypothesis-driven therapeutic rehabilitation strategies from a sensory or sensory-motor perspective.

Background. Aging is a major risk factor for a range of chronic diseases. Oxidative stress theory of aging has been previously proposed as one of the mechanisms responsible for the age‐related decline in organ/tissue function and the development of age‐related diseases. Urine contains rich biological information on the health status of every major organ system and can be an important noninvasive source for biomarkers of systemic oxidative stress in aging. Aims. The objective of this cross‐sectional study was to validate a novel panel of urinary oxidative stress biomarkers. Methods. Nucleic acid oxidation adducts and oxidative damage markers of lipids and proteins were assessed in urine samples from nondiabetic and currently nonsmoking subjects (n = 198) across different ages (20 to 89 years old). Urinary parameters and chronological age were correlated then the biological age of enrolled individuals was determined from the urinary oxidative stress markers using the algorithm of Klemera and Doubal. Results. Our findings showed that 8‐oxo‐7,8‐deoxyguanosine (8‐oxoG), 8‐oxo‐7,8‐dihydroguanosine (8‐OHdG), and dityrosine (DTyr) positively correlated with chronological age, while the level of an F₂‐isoprostane (iPF₂α‐VI) correlated negatively with age. We found that 8‐oxoG, DTyr, and iPF₂α‐VI were significantly higher among accelerated agers compared to nonaccelerated agers and that a decision tree model could successfully identify accelerated agers with an accuracy of >92%. Discussion. Our results indicate that 8‐oxoG and iPF₂α‐VI levels in the urine reveal biological aging. Conclusion. Assessing urinary biomarkers of oxidative stress may be an important approach for the evaluation of biological age by identifying individuals at accelerated risk for the development of age‐related diseases.

Radiation therapy for cervical cancer involves a team of specialists, including diagnostic radiologists (DRs), radiation oncologists (ROs), and medical physicists (MPs), to optimize imaging‐based radiation therapy planning. The purpose of the study was to investigate the interobserver variations in tumor delineation on MR images of cervical cancer within the same and among different specialties. Twenty MRI cervical cancer studies were independently reviewed by two DRs, two ROs, and two MPs. For every study, each specialist contoured the tumor regions of interest (ROIs) on T2‐weighted Turbo Spin Echo sagittal images on all slices containing tumor, and the total tumor volume was computed for statistical analysis. Analysis of variance (ANOVA) was used to compare the differences in tumor volume delineation among the observers. A graph of all tumor‐delineated volumes was generated, and differences between the maximum and minimum volumes over all the readers for each patient dataset were computed. Challenges during the evaluation process for tumor delineation were recorded for each specialist. Interobserver variations of delineated tumor volumes were significant among all observers based on a repeated measures ANOVA, which produced an . The median difference between the maximum delineated volume and minimum delineated volume was 33.5 cm³ (which can be approximated by a sphere of 4.0 cm diameter) across all 20 patients. Challenges noted for tumor delineation included the following: (1) partial voluming by parametrial fat at the periphery of the uterus; (2) extension of the tumor into parametrial space; (3) similar signal intensity of structures proximal to the tumor such as ovaries, muscles, bladder wall, bowel loops, and pubic symphysis; (4) postradiation changes such as heterogeneity and necrosis; (5) susceptibility artifacts from bowels and vaginal tampons; (6) presence of other pathologies such as atypical myoma; (7) factors that affect pelvic anatomy, including the degree of bladder distension, bowel interposition, uterine malposition, retroversion, and descensus. Our limited study indicates significant interobserver variation in tumor delineation. Despite rapid progress in technology, which has improved the resolution and precision of image acquisition and the delivery of radiotherapy to the millimeter level, such “human” variations (at the centimeter level) may overshadow the gain from technical advancement and impact treatment planning. Strategies of standardization and training in tumor delineation need to be developed.PACS number(s):

We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from Solanum nigrum Linn, against HCC. Recently, the U.S. FDA approved Utt-B as an ‘orphan drug’ against HCC. The current study validates the superior anti-HCC efficacy of Utt-B over sorafenib, the first-line treatment option against HCC. The therapeutic efficacies of Utt-B vs. sorafenib against HCC were compared in vitro, using various liver cancer cell lines and in vivo, utilizing NOD.CB17-Prkdcscid/J mice bearing human HCC xenografts. Our data indicate that Utt-B holds an augmented anti-HCC efficacy over sorafenib. Our previous report demonstrated the pharmacological safety of Utt-B in Chang Liver, the normal immortalized hepatocytes, and in the acute and chronic toxicity murine models even at elevated Utt-B concentrations. Here, we show that higher concentrations of sorafenib induce severe toxicity, in Chang Liver, as well as in acute and chronic in vivo models, indicating that, apart from the superior therapeutic benefit over sorafenib, Utt-B is a pharmacologically safer molecule, and the drug-induced undesirable effects can, thus, be substantially alleviated in the context of HCC chemotherapy. Clinical studies in HCC patients utilizing Utt-B, is a contiguous key step to promote this drug to the clinic.