However, it seems that a well-designed combination of VDAs with other anti-cancer drugs may bring a significant therapeutic effect. In this article, we describe three groups of vascular disruptive agents with their advantages and disadvantages. We mention VDAs clinical trials. Finally, we present the current possibilities of VDAs combination with other anti-cancer drugs.Esophageal cancer is a prominent worldwide illness that is divided into two main subtypes esophageal squamous cell carcinoma and esophageal adenocarcinoma. Mortality rates are alarming, and the understanding of the mechanisms involved in esophageal cancer development, becomes essential. Purinergic signaling is related to many diseases and among these various types of tumors. Here we studied the effects of the P2Y2 receptor activation in different types of esophageal cancer. Esophageal tissue samples of healthy controls were used for P2Y2R expression quantification. Two human esophageal cancer cell lines Kyse-450 (squamous cell carcinoma) and OE-33 (adenocarcinoma) were used to perform in vitro analysis of cell proliferation, migration, adhesion, and the signaling pathways involved in P2Y2R activation. Data showed that P2Y2R was expressed in biopsies of patients with ESCC and adenocarcinoma, as well as in the two human esophageal cancer cell lines studied. Menadione mouse The RT-qPCR analysis demonstrated that OE-33 cells have higher P2RY2 expression than Kyse-450 squamous cell line. Results showed that P2Y2R activation, induced by ATP or UTP, promoted esophageal cancer cells proliferation and colony formation. P2Y2R blockage with the selective antagonist, AR-C 118925XX, led to decreased proliferation, colony formation and adhesion. Treatments with ATP or UTP activated ERK 1/2 pathway in ESCC and ECA cells. The P2Y2R antagonism did not alter the migration of esophageal cancer cells. Interestingly, the esophageal cancer cell lines presented a distinct profile of nucleotide hydrolysis activity. The modulation of P2Y2 receptors may be a promising target for esophageal cancer treatment.In the context of the current SARS-CoV-2 pandemic, associations of drugs which interfere with specific steps of the viral infectious cycle are currently being exploited as therapeutic strategies since a specific treatment by vaccination is still unavailable. A widespread association of repurposed agents is the combination of the antimalarial drug Hydroxychloroquine and the macrolide antibiotic Azithromycin in the setting of clinical trials. But a closer analysis of their mechanism of action suggests that their concomitant administration may be impractical, and this is supported by experimental data with other agents of the same classes. However a sequential administration of the lysosomotropic antimalarial with the addition of the macrolide proton pump inhibitor after the first has reached a certain threshold could better exploit their antiviral potential.Lower midlife physical activity is associated with higher risk of neurodegenerative disease in late life. However, it remains unknown whether physical exercise and fitness are associated with brain structural integrity during midlife. The purpose of this study was to compare brain structures between middle-aged aerobically trained adults (MA), middle-aged sedentary (MS), and young sedentary (YS) adults. Thirty MA (54±4 years), 30 MS (54±4 years), and 30 YS (32±6 years) participants (50% women) underwent measurements of brain volume, cortical thickness, and white matter (WM) fiber integrity using MRI. MA participants had aerobic training for 24.8±9.6 years and the highest cardiorespiratory fitness level (i.e., peak oxygen uptake VO2peak) among all groups. Global WM integrity, as assessed with fractional anisotropy (FA) from diffusion tensor imaging, was lower in the MS compared with the YS group. However, global FA in the MA group was significantly higher than that in the MS group (P less then 0.05) and at a similar level to the YS group. Furthermore, tract-based spatial statistical analysis demonstrated that FA in the anterior, superior, and limbic WM tracts (e.g., the genu of the corpus callosum, superior longitudinal fasciculus, uncinate fasciculus) was higher in the MA compared with MS groups, and positively associated with VO2peak, independently from age and sex. From cortical thickness analysis, MS and MA participants showed thinner prefrontal and parieto-temporal areas than the YS group. On the other hand, the MA group exhibited thicker precentral, postcentral, pericalcarine, and lateral occipital cortices than the MS and YS groups. But, the insula and right superior frontal gyrus showed thinner cortical thickness in the MA compared with the MS groups. Collectively, these findings suggest that midlife aerobic exercise is associated with higher WM integrity and greater primary motor and somatosensory cortical thickness.Despite dissimilarities among scripts, a universal hallmark of literacy in skilled readers is the convergent brain activity for print and speech. Little is known, however, whether this differs as a function of grapheme to phoneme transparency in beginning readers. Here we compare speech and orthographic processing circuits in two contrasting languages, Polish and English, in 100 7-year-old children performing fMRI language localizer tasks. Results show limited language variation, with speech-print convergence evident mostly in left frontotemporal perisylvian regions. Correlational and intersect analyses revealed subtle differences in the strength of this coupling in several regions of interest. Specifically, speech-print convergence was higher for transparent Polish than opaque English in the right temporal area, associated with phonological processing. Conversely, speech-print convergence was higher for English than Polish in left fusiform, associated with visual word recognition. We conclude that speech-print convergence is a universal marker of reading even at the beginning of reading acquisition with minor variations that can be explained by the differences in grapheme to phoneme transparency. This finding at the earliest stages of reading acquisition conforms well with claims that reading exhibits a good deal of universality despite writing systems differences.