Search results for "MEK"
showing 10 items of 844 documents
Antiviral Agents From Fungi : Diversity, Mechanisms and Potential Applications
2018
Viral infections are amongst the most common diseases affecting people worldwide. New viruses emerge all the time and presently we have limited number of vaccines and only few antivirals to combat viral diseases. Fungi represent a vast source of bioactive molecules, which could potentially be used as antivirals in the future. Here, we have summarized the current knowledge of fungi as producers of antiviral compounds and discuss their potential applications. In particular, we have investigated how the antiviral action has been assessed and what is known about the molecular mechanisms and actual targets. Furthermore, we highlight the importance of accurate fungal species identification on ant…
Targeted Therapy in Advanced Melanoma With Rare BRAF Mutations
2019
PURPOSE BRAF/MEK inhibition is a standard of care for patients with BRAF V600E/K–mutated metastatic melanoma. For patients with less frequent BRAF mutations, however, efficacy data are limited. METHODS In the current study, 103 patients with metastatic melanoma with rare, activating non-V600E/K BRAF mutations that were treated with either a BRAF inhibitor (BRAFi), MEK inhibitor (MEKi), or the combination were included. BRAF mutation, patient and disease characteristics, response, and survival data were analyzed. RESULTS Fifty-eight patient tumors (56%) harbored a non-E/K V600 mutation, 38 (37%) a non-V600 mutation, and seven had both V600E and a rare BRAF mutation (7%). The most frequent mu…
A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments.
2017
We investigated PD-L1 changes in response to MEK and AKT inhibitors in KRAS mutant lung adenocarcinoma (adeno-NSCLC). PD-L1 expression was quantified using immunofluorescence and co-culture with a jurkat cell-line transfected with NFAT-luciferase was used to study if changes in PD-L1 expression in cancer cell lines were functionally relevant. Five KRAS mutant cell lines with high PD-L1 expression (H441, H2291, H23, H2030 and A549) were exposed to GI50 inhibitor concentrations of a MEK inhibitor (trametinib) and an AKT inhibitor (AZD5363) for 3 weeks. Only 3/5 (H23, H2030 and A549) and 2/5 cell lines (H441 and H23) showed functionally significant increases in PD-L1 expression when exposed to…
Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafen…
2020
Abstract Background BRAF/MEK inhibitor combinations are established treatments for BRAF V600–mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Here, we report an updated analysis of the COLUMBUS (COmbined LGX818 [encorafenib] Used with MEK162 [binimetinib] in BRAF mutant Unresectable Skin cancer) trial with long-term follow-up. Methods In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600–mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib …
The protective value of a defensive display varies with the experience of wild predators
2019
AbstractPredation has driven the evolution of diverse adaptations for defence among prey, and one striking example is the deimatic display. While such displays can resemble, or indeed co-occur with, aposematic ‘warning’ signals, theory suggests deimatic displays may function independently of predator learning. The survival value of deimatic displays against wild predators has not been tested before. Here we used the mountain katydid Acripeza reticulata to test the efficacy of a putative deimatic display in the wild. Mountain katydids have a complex defence strategy; they are camouflaged at rest, but reveal a striking red-, blue-, and black-banded abdomen when attacked. We presented live kat…
Mucin induces CRISPR-Cas defense in an opportunistic pathogen
2022
It is unknown what circumstances promote particular bacterial defenses against bacterial viruses (phages). Almeida & Hoikkala et al. show that mucin, derived from mucus, greatly accelerates CRISPR-Cas defenses against phage in an opportunistic pathogen. Parasitism by bacteriophages has led to the evolution of a variety of defense mechanisms in their host bacteria. However, it is unclear what factors lead to specific defenses being deployed upon phage infection. To explore this question, we co-evolved the bacterial fish pathogen Flavobacterium columnare and its virulent phage V156 in presence and absence of a eukaryotic host signal (mucin) for sixteen weeks. The presence of mucin leads to a …
Measurement of spin-orbital angular momentum interactions in relativistic heavy-ion collisions
2020
The first evidence of spin alignment of vector mesons ($K^{*0}$ and $\phi$) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The spin density matrix element $\rho_{00}$ is measured at midrapidity ($|y| <$ 0.5) in Pb-Pb collisions at a center-of-mass energy ($\sqrt{s_{\rm NN}}$) of 2.76 TeV with the ALICE detector. $\rho_{00}$ values are found to be less than 1/3 (1/3 implies no spin alignment) at low transverse momentum ($p_{\rm T} <$ 2 GeV/$c$) for $K^{*0}$ and $\phi$ at a level of 3$\sigma$ and 2$\sigma$, respectively. No significant spin alignment is observed for the $K^0_S$ meson (spin = 0) in Pb-Pb collisions and for the vector mesons in $pp$ collisions. The meas…
Probing the Effects of Strong Electromagnetic Fields with Charge-Dependent Directed Flow in Pb-Pb Collisions at the LHC
2020
The first measurement at the LHC of charge-dependent directed flow ($v_{1}$) relative to the spectator plane is presented for Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 5.02 TeV. Results are reported for charged hadrons and $\rm D^{0}$ mesons for the transverse momentum intervals $p_{\rm T}>0.2$ GeV/$c$ and $3<p_{\rm T}<$ 6 GeV/$c$ in the 5-40% and 10-40% centrality classes, respectively. The difference between the positively and negatively charged hadron $v_{1}$ has a positive slope as a function of pseudorapidity $\eta$, ${\rm d}\Delta{v_1}/{\rm d}\eta=$[1.68 $\pm$ 0.49 (stat.) $\pm$ 0.41 (syst.)] $\times 10^{-4}$. The same measurement for $\rm D^{0}$ and $\rm\bar{D}{}^0$ mesons yields a p…
Modeling of the Achilles Subtendons and Their Interactions in a Framework of the Absolute Nodal Coordinate Formulation
2022
Experimental results have revealed the sophisticated Achilles tendon (AT) structure, including its material properties and complex geometry. The latter incorporates a twisted design and composite construction consisting of three subtendons. Each of them has a nonstandard cross-section. All these factors make the AT deformation analysis computationally demanding. Generally, 3D finite solid elements are used to develop models for AT because they can discretize almost any shape, providing reliable results. However, they also require dense discretization in all three dimensions, leading to a high computational cost. One way to reduce degrees of freedom is the utilization of finite beam elements…