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Cancer immunotherapy is a clinically validated therapeutic modality for cancer and has been rapidly advancing in recent years. Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a viable method of controlling the immune system against cancer. Recent evidence indicates that even immune-cell-released vesicles such as NK-cell-derived exosomes also exert anticancer effect. Nevertheless, the underlying mechanisms remain elusive. In the present study, the anticancer potential of isolated extracellular vesicles (EVs) from expanded and activated NK-cell-enriched lymphocytes (NKLs) prepared by house-developed protocol was evaluated both in vitro and in vivo. Moreover, isolated EVs were characterized by using two-dimensional electrophoresis (2-DE)-based proteome and network analysis, and functional study using identified factors was performed. Our data indicated that the EVs from expanded and active NKLs had anticancer properties, and a number of molecules, such as Fas ligand, TRAIL, NKG2D, β-actin, and fibrinogen, were identified as effector candidates based on the proteome analysis and functional study. The results of the present study suggest the possibility of NK-cell-derived EVs as a viable immunotherapeutic strategy for cancer.Filoviruses are among the deadliest infectious agents known to man, causing severe hemorrhagic fever, with up to 90% fatality rates. The 2014 Ebola outbreak in West Africa resulted in over 28,000 infections, demonstrating the large-scale human health and economic impact generated by filoviruses. Zaire ebolavirus is responsible for the greatest number of deaths to date and consequently there is now an approved vaccine, Ervebo, while other filovirus species have similar epidemic potential and remain without effective vaccines. Recent clinical success of REGN-EB3 and mAb-114 monoclonal antibody (mAb)-based therapies supports further investigation of this treatment approach for other filoviruses. While efficacious, protection from passive mAb therapies is short-lived, requiring repeat dosing to maintain therapeutic concentrations. An alternative strategy is vectored immunoprophylaxis (VIP), which utilizes an adeno-associated virus (AAV) vector to generate sustained expression of selected mAbs directly in vivo. This approach takes advantage of validated mAb development and enables vectorization of the top candidates to provide long-term immunity. In this review, we summarize the history of filovirus outbreaks, mAb-based therapeutics, and highlight promising AAV vectorized approaches to providing immunity against filoviruses where vaccines are not yet available.Recently discovered hybrid perovskites based on hypophosphite ligands are a promising class of compounds exhibiting unusual structural properties and providing opportunities for construction of novel functional materials. find more Here, we report for the first time the detailed studies of phonon properties of manganese hypophosphite templated with methylhydrazinium cations ([CH3NH2NH2][Mn(H2PO2)3]). Its room temperature vibrational spectra were recorded for both polycrystalline sample and a single crystal. The proposed assignment based on Density Functional Theory (DFT) calculations of the observed vibrational modes is also presented. It is worth noting this is first report on polarized Raman measurements in this class of hybrid perovskites.
to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with
FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation.
a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0-G2 acute HT to further proceed with the trial. We employed
FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0.
from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0-G2 events, way above the threshold set by the trial design.
FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.
18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.Fungi and the mycobiome are a fundamental part of the human microbiome that contributes to human health and development. Despite this, relatively little is known about the mycobiome of the preterm infant gut. Here, we have characterised faecal fungal communities present in 11 premature infants born with differing degrees of prematurity and mapped how the mycobiome develops during early infancy. Using an ITS1 sequencing-based approach, the preterm infant gut mycobiome was found to be often dominated by a single species, typically a yeast. Candida was the most abundant genus, with the pathobionts C.albicans and C.parapsilosis highly prevalent and persistent in these infants. Gestational maturity at birth affected the distribution and abundance of these Candida, with hospital-associated C.parapsilosis more prevalent and abundant in infants born at less than 31 weeks. Fungal diversity was lowest at 6 months, but increased with age and change of diet, with food-associated Saccharomycescerevisiae most abundant in infants post weaning. This study provides a first insight into the fungal communities present within the preterm infant gut, identifying distinctive features including the prominence of pathobiont species, and the influence age and environmental factors play in shaping the development of the mycobiome.
My Website: https://www.selleckchem.com/MEK.html
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