The Epstein-Barr virus (EBV) infection status varies among BL subtypes. There are unresolved questions regarding the contribution of EBV, which is strongly associated with Burkitt lymphoma, to BL path Show more
The Epstein-Barr virus (EBV) infection status varies among BL subtypes. There are unresolved questions regarding the contribution of EBV, which is strongly associated with Burkitt lymphoma, to BL pathogenesis. Differences between EBV-positive and EBV-negative BL have been previously reported. A long-debated and studied topic is the differing origins of EBV-positive and EBV-negative BL cells. Studies have suggested that miRNAs, which are post-transcriptional elements involved in many pathways, play a role in this process. In our study, in silico analyses and a literature review were used to identify miRNAs potentially involved in lymphoma and B lymphocyte development pathways. Three miRNAs (miR-182, miR-320a, miR-144) targeting the Show less
FGF, VEGFR-2 and CSF1R signalling pathways play a key role in the pathogenesis of multiple sclerosis (MS). Selective inhibition of FGFR by infigratinib in MOG Female C57BL/6J mice were treated with fe Show more
FGF, VEGFR-2 and CSF1R signalling pathways play a key role in the pathogenesis of multiple sclerosis (MS). Selective inhibition of FGFR by infigratinib in MOG Female C57BL/6J mice were treated with fexagratinib (6.25 or 12.5 mg·kg In the prevention experiment, treatment with 6.25 or 12.5 mg·kg Multi-kinase inhibition by fexagratinib in a well-tolerated dose of 1 mg·kg Show less
Blood vessels in tumors are often dysfunctional. This impairs the delivery of therapeutic agents to and distribution among the cancer cells. Subsequently, treatment efficacy is reduced, and dose escal Show more
Blood vessels in tumors are often dysfunctional. This impairs the delivery of therapeutic agents to and distribution among the cancer cells. Subsequently, treatment efficacy is reduced, and dose escalation can increase adverse effects on non-malignant tissues. The dysfunctional vessel phenotypes are attributed to aberrant pro-angiogenic signaling, and anti-angiogenic agents can ameliorate traits of vessel dysfunctionality. However, they simultaneously reduce vessel density and thereby impede drug delivery and distribution. Exploring possibilities to improve vessel functionality without compromising vessel density in the tumor microenvironment, we evaluated transcription factors (TFs) involved in epithelial-mesenchymal transition (EMT) as potential targets. Based on similarities between EMT and angiogenic activation of endothelial cells, we hypothesized that these TFs, Snai1 in particular, might serve as key regulators of vessel dysfunctionality. In vitro, experiments demonstrated that Snai1 (similarly Slug and Twist1) regulates endothelial permeability, permissiveness for tumor cell transmigration, and tip/stalk cell formation. Endothelial-specific, heterozygous knock-down of Snai1 in mice improved vascular quality in implanted tumors. This resulted in better oxygenation and reduced metastasis. Notably, the tumors in Snai1KD mice responded significantly better to chemotherapeutics as drugs were transported into the tumors at strongly increased rates and more homogeneously distributed. Thus, we demonstrate that restoring vessel homeostasis without affecting vessel density is feasible in malignant tumors. Combining such vessel re-engineering with anti-cancer drugs allows for strategic treatment approaches that reduce treatment toxicity on non-malignant tissues. Show less