Mapping and counter-mapping COVID-19: From crisis to cartocracy

Editorial

Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Rock Fracture Sorptivity as Related to Aperture Width and Surface Roughness

Fractures in low-porosity rocks can provide conduits for fluid flow. Numerous researchers have investigated fluid flow through fractures under saturated conditions. However, relatively little information exists on spontaneous imbibition in fractures, whereby a wetting fluid displaces a non-wetting fluid by capillarity. We investigated spontaneous imbibition of water displacing air in a suite of fractured low-porosity sedimentary and igneous rock cores (5.08-cm length by 2.54-cm diameter). Mode I fractures were induced in the cores by compression between opposing parallel flat plates. The following physical properties were measured: bulk density, ρ; solid-phase density, ρ; porosity, ϕ; contact angle, θ; fracture aperture width, and fracture surface roughness, . The wetting front in each fracture was imaged using dynamic neutron radiography. Early-time uptake exhibited a square root of time dependency, and was quantified by linear regression, with the slope equal to the fracture sorptivity, . Estimates of ranged from 10.1 to 40.5 mm s, with a median value of 25.0 mm s. There was a statistically significant effect of rock type on , with igneous rocks generally having lower mean values than sedimentary rocks. Differences in ρ, ρ, ϕ, and θ between the rock types did not contribute significantly to the variation in . However, and were significantly correlated with . These correlations indicated that increases with increasing , as predicted by early-time capillary theory, and decreases with increasing , analogous to the decrease in fracture permeability with increasing surface roughness observed under saturated flow conditions

Kinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets

10.1186/s13045-017-0540-xJournal of Hematology and Oncology10117

Effect of dasatinib against thyroid cancer cell lines in vitro and a xenograft model in vivo

Tyrosine kinase inhibitors (TKIs) have emerged as a promising class of agents against thyroid cancer. The aim of the present study was to investigate the in vitro and in vivo activity of dasatinib against a panel of thyroid cancer cell lines and explore possible mechanisms of action, using various assays and western blotting. Our results showed that dasatinib exhibits prominent cytostatic activity both in vitro and in vivo against thyroid cancer cell lines with RET/PTC rearrangement (BHP2-7) and KRAS mutation (Cal62). Although dasatinib has primarily been described as an ABL/SRCfamily kinase inhibitor, the cytostatic activity observed in the present study is mediated by several off-target effects of dasatinib, some of which have not previously been reported. These effects include a reduction in phospho-FAK, FAK, RAS, Caveolin and SYK protein levels and an increase in β-catenin protein expression, which leads to the induction of senescence, an increase in the adhesiveness of the cells, a decrease in reactive oxygen species level, and changes in the expression profile of molecules involved in cellular adhesion such as integrins. Therefore, we propose that dasatinib is an effective therapeutic agent for certain patients with thyroid cancer, and these candidate patients may be identifiable on the basis of standard genotypic analyses

Proteolysis targeting chimeric molecules as therapy for multiple myeloma: Efficacy, biomarker and drug combinations

10.3324/haematol.2018.201483Haematologica10461209-122

Identification of a novel SYK/c-MYC/MALAT1 signaling pathway and its potential therapeutic value in Ewing sarcoma

10.1158/1078-0432.CCR-16-2185Clinical Cancer Research23154376-438

Ascochlorin, an isoprenoid antibiotic inhibits growth and invasion of hepatocellular carcinoma by targeting STAT3 signaling cascade through the induction of PIAS3

10.1016/j.molonc.2014.12.008Molecular Oncology94818-83

Mutations in G protein β subunits promote transformation and kinase inhibitor resistance.

Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds Gα subunits as well as downstream effectors and disrupt Gα interactions with the Gβγ dimer. Different mutations in Gβ proteins clustered partly on the basis of lineage; for example, all 11 GNB1 K57 mutations were in myeloid neoplasms, and seven of eight GNB1 I80 mutations were in B cell neoplasms. Expression of patient-derived GNB1 variants in Cdkn2a-deficient mouse bone marrow followed by transplantation resulted in either myeloid or B cell malignancies. In vivo treatment with the dual PI3K-mTOR inhibitor BEZ235 suppressed GNB1-induced signaling and markedly increased survival. In several human tumors, mutations in the gene encoding GNB1 co-occurred with oncogenic kinase alterations, including the BCR-ABL fusion protein, the V617F substitution in JAK2 and the V600K substitution in BRAF. Coexpression of patient-derived GNB1 variants with these mutant kinases resulted in inhibitor resistance in each context. Thus, GNB1 and GNB2 alterations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling