Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, ...randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.
Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.
First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
Starch from cereal grains, pulse grains, and tubers is a major energy substrate in swine rations constituting up to 55% of the diet. In pigs, starch digestion is initiated by salivary and then ...pancreatic α-amylase, and has as final step the digestion of disaccharides by the brush-border enzymes in the small intestine that produce monosaccharides (glucose) for absorption. Resistant starch (RS) is the proportion of starch that escapes the enzymatic digestion and absorption in the small intestine. The undigested starch reaches the distal small intestine and hindgut for microbial fermentation, which produces short-chain fatty acids (SCFA) for absorption. SCFA in turn, influence microbial ecology and gut health of pigs. These fermentative metabolites exert their benefits on gut health through promoting growth and proliferation of enterocytes, maintenance of intestinal integrity and thus immunity, and modulation of the microbial community in part by suppressing the growth of pathogenic bacteria while selectively enhancing beneficial microbes. Thus, RS has the potential to confer prebiotic effects and may contribute to the improvement of intestinal health in pigs during the post-weaning period. Despite these benefits to the well-being of pigs, RS has a contradictory effect due to lower energetic efficiency of fermented vs. digested starch absorption products. The varying amount and type of RS interact differently with the digestion process along the gastrointestinal tract affecting its energy efficiency and host physiological responses including feed intake, energy metabolism, and feed efficiency. Results of research indicate that the use of RS as prebiotic may improve gut health and thereby, reduce the incidence of post-weaning diarrhea (PWD) and associated mortality. This review summarizes our current knowledge on the effects of RS on microbial ecology, gut health and growth performance in pigs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
Genera of phytopathogenic fungi: GOPHY 1 Marin-Felix, Y.; Groenewald, J.Z.; Cai, L. ...
Studies in mycology,
March 2017, 20170301, 2017-Mar, 2017-03-01, Letnik:
86, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Genera of Phytopathogenic Fungi (GOPHY) is introduced as a new series of publications in order to provide a stable platform for the taxonomy of phytopathogenic fungi. This first paper focuses on 21 ...genera of phytopathogenic fungi: Bipolaris, Boeremia, Calonectria, Ceratocystis, Cladosporium, Colletotrichum, Coniella, Curvularia, Monilinia, Neofabraea, Neofusicoccum, Pilidium, Pleiochaeta, Plenodomus, Protostegia, Pseudopyricularia, Puccinia, Saccharata, Thyrostroma, Venturia and Wilsonomyces. For each genus, a morphological description and information about its pathology, distribution, hosts and disease symptoms are provided. In addition, this information is linked to primary and secondary DNA barcodes of the presently accepted species, and relevant literature. Moreover, several novelties are introduced, i.e. new genera, species and combinations, and neo-, lecto- and epitypes designated to provide a stable taxonomy. This first paper includes one new genus, 26 new species, ten new combinations, and four typifications of older names.
Recent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is responsible for tumor growth in colorectal cancer. However, the role of CSCs in colorectal cancer ...metastasis is unclear. Here, we identified a subpopulation of CD26
+ cells uniformly present in both the primary and metastatic tumors in colorectal cancer patients with liver metastasis. Furthermore, in patients without distant metastasis at the time of presentation, the presence of CD26
+ cells in their primary tumors predicted distant metastasis on follow-up. Isolated CD26
+ cells, but not CD26
− cells, led to development of distant metastasis when injected into the mouse cecal wall. CD26
+ cells were also associated with enhanced invasiveness and chemoresistance. Our findings have uncovered a critical role of CSCs in metastatic progression of cancer. Furthermore, the ability to predict metastasis based on analysis of CSC subsets in the primary tumor may have important clinical implication as a selection criterion for adjuvant therapy.
► Metastatic colorectal cancers contain a subset of CD26
+ cancer stem cells ► Nonmetastatic tumors with CD26
+ CSCs frequently proceed to metastasis ► Isolated CD26
+ CSCs can initiate distant metastasis in a mouse model ► CD26
+ CSCs show enhanced invasiveness and migratory potential
A novel nano-adsorbent, carboxymethyl-β-cyclodextrin modified Fe
3O
4 nanoparticles (CMCD-MNPs) is fabricated for removal of copper ions from aqueous solution by grafting CM-β-CD onto the magnetite ...surface via carbodiimide method. The characteristics results of FTIR, TEM, TGA and XPS show that CM-β-CD is grafted onto Fe
3O
4 nanoparticles. The grafted CM-β-CD on the Fe
3O
4 nanoparticles contributes to an enhancement of the adsorption capacity because of the strong abilities of the multiple hydroxyl and carboxyl groups in CM-β-CD to adsorb metal ions. The adsorption of Cu
2+ onto CMCD-MNPs is found to be dependent on pH and temperature. Adsorption equilibrium is achieved in 30
min and the adsorption kinetics of Cu
2+ is found to follow a pseudo-second-order kinetic model. Equilibrium data for Cu
2+ adsorption are fitted well by Langmuir isotherm model. The maximum adsorption capacity for Cu
2+ ions is estimated to be 47.2
mg
/g at 25
°C. Furthermore, thermodynamic parameters reveal the feasibility, spontaneity and exothermic nature of the adsorption process. FTIR and XPS reveal that Cu
2+ adsorption onto CMCD-MNPs mainly involves the oxygen atoms in CM-β-CD to form surface-complexes. In addition, the copper ions can be desorbed from CMCD-MNPs by citric acid solution with 96.2% desorption efficiency and the CMCD-MNPs exhibit good recyclability.
There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness ...of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.
We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus ...OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032 + 4127 and the other mainly with a pulsar wind nebula PWN G75.2 + 0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.
ABSTRACT
The High Energy (HE) X-ray telescope on board the Hard X-ray Modulation Telescope (Insight-HXMT) can serve as a wide field of view (FOV) gamma-ray monitor with high time resolution (μs) and ...large effective area (up to thousands cm2). We developed a pipeline to search for gamma-ray bursts (GRBs), using the traditional signal-to-noise ratio (SNR) method for blind search and the coherent search method for targeted search. By taking into account the location and spectrum of the burst and the detector response, the targeted coherent search is more powerful to unveil weak and sub-threshold bursts, especially those in temporal coincidence with gravitational wave (GW) events. Based on the original method in literature, we further improved the coherent search to filter out false triggers caused by spikes in light curves, which are commonly seen in gamma-ray instruments (e.g. Fermi/GBM, POLAR). We show that our improved targeted coherent search method could eliminate almost all false triggers caused by spikes. Based on the first two years of Insight-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either Swift/BAT or Fermi/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of Insight-HXMT/HE is increased to about 1.5E-08 erg cm−2 (200 keV–3 MeV). We also used this targeted coherent method to search Insight-HXMT/HE data for electromagnetic counterparts of LIGO-Virgo GW events (including O2 and O3a runs). However, we did not find any significant burst associated with GW events.
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