Ferroptosis is a type of programmed cell death induced by the accumulation of lipid peroxidation and lipid reactive oxygen species in cells. It has been recently demonstrated that cancer cells are ...vulnerable to ferroptosis inducers (FIN). However, the therapeutic potential of FINs in prostate cancer in preclinical settings has not been explored. In this study, we demonstrate that mediators of ferroptosis, solute carrier family 7 member 11, SLC3A2, and glutathione peroxidase, are expressed in treatment-resistant prostate cancer. We further demonstrate that treatment-resistant prostate cancer cells are sensitive to two FINs, erastin and RSL3. Treatment with erastin and RSL3 led to a significant decrease in prostate cancer cell growth and migration
and significantly delayed the tumor growth of treatment-resistant prostate cancer
, with no measurable side effects. Combination of erastin or RSL3 with standard-of-care second-generation antiandrogens for advanced prostate cancer halted prostate cancer cell growth and migration
and tumor growth
. These results demonstrate the potential of erastin or RSL3 independently and in combination with standard-of-care second-generation antiandrogens as novel therapeutic strategies for advanced prostate cancer. SIGNIFICANCE: These findings reveal that induction of ferroptosis is a new therapeutic strategy for advanced prostate cancer as a monotherapy and in combination with second-generation antiandrogens.
Here, the inclusive cross section of top quark-antiquark pairs produced in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV is measured in the lepton+jets and dilepton decay channels. The data sample ...corresponds to 9.7 fb-1 of integrated luminosity recorded with the D0 detector during Run II of the Fermilab Tevatron Collider. Employing multivariate analysis techniques we measure the cross section in the two decay channels and we perform a combined cross section measurement. For a top quark mass of 172.5 GeV, we measure a combined inclusive top quark-antiquark pair production cross section of σ$t\bar{t}$=7.26±0.13(stat)$+0.57\atop{-0.50}$(syst) pb which is consistent with standard model predictions. We also perform a likelihood fit to the measured and predicted top quark mass dependence of the inclusive cross section, which yields a measurement of the pole mass of the top quark. The extracted value is mt=172.8±1.1(theo)$+3.3\atop{-3.1}$(exp) GeV.
Summary Background Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for ...the treatment of moderate-to-severe Crohn's disease. Methods We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries. We enrolled eligible patients aged 18–75 years with a documented history of ileal, colonic, or ileocolonic Crohn's disease for 3 months or more before screening, as assessed by colonoscopy and supported by histology, and a Crohn's Disease Activity Index (CDAI) score during screening between 220 and 450 inclusive. Patients were randomly assigned (3:1) to receive filgotinib 200 mg once a day or placebo for 10 weeks. Patients were stratified according to previous anti-tumour necrosis factor alpha exposure, C-reactive protein concentration at screening (≤10 mg/L or >10 mg/L), and oral corticosteroid use at baseline, using an interactive web-based response system. The primary endpoint was clinical remission, defined as CDAI less than 150 at week 10. After week 10, patients were assigned based on responder status to filgotinib 100 mg once a day, filgotinib 200 mg once a day, or placebo for an observational period lasting a further 10 weeks. The filgotinib and placebo treatment groups were compared using ANCOVA models and logistic regression models containing baseline values and randomisation stratification factors as fixed effects. Analyses were done on the intention-to-treat non-responder imputation set. The trial was registered at ClinicalTrials.gov , number NCT02048618. Findings Between Feb 3, 2014, and July 10, 2015, we enrolled 174 patients with active Crohn's disease confirmed by centrally read endoscopy (130 in the filgotinib 200 mg group and 44 in the placebo group). In the intention-to-treat population, 60 (47%) of 128 patients treated with filgotinib 200 mg achieved clinical remission at week 10 versus ten (23%) of 44 patients treated with placebo (difference 24 percentage points 95% CI 9–39, p=0·0077). In a pooled analysis of all periods of filgotinib and placebo exposure over 20 weeks, serious treatment-emergent adverse effects were reported in 14 (9%) of 152 patients treated with filgotinib and three (4%) of 67 patients treated with placebo. Interpretation Filgotinib induced clinical remission in significantly more patients with active Crohn's disease compared with placebo, and had an acceptable safety profile. Funding Galapagos.
Measurement of the W boson mass with the D0 detector Acharya, B. S.; Augsten, K.; Bagby, L. ...
Physical review. D, Particles, fields, gravitation, and cosmology,
2014, Letnik:
89, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We give a detailed description of the measurement of the W boson mass, MW, performed on an integrated luminosity of 4.3 fb super(-1), which is based on similar techniques as used for our previous ...measurement done on an independent data set of 1 fb super(-1) of data. The data were collected using the DO detector at the Fermilab Tevatron Collider. This data set yields 1.68 x 10 super(6) W arrow right ev candidate events. We measure the mass using the transverse mass, electron transverse momentum, and missing transverse energy distributions. The MW measurements using the transverse mass and the electron transverse momentum distributions are the most precise of these three and are combined to give MW = 80.367 + or - 0.013(stat) + or - 0.022(syst) GeV = 80. 367 + or - 0.026 GeV. When combined with our earlier measurement on 1 fb super(-1) of data, we obtain MW = 80.375 + or - 0.023 GeV.
Laurel (Laurus nobilis L.) is a plant species from Lauraceae family, and is native to the Mediterranean region. The goal of this study was to compare chemical composition of laurel leaves and ...antibacterial activity of its essential oil (EO) from wild-grown trees in Greece and Georgia. The laurel leaves from the two native habitats had dissimilar concentrations of phenolic acids. Of the conjugated flavonols and flavons, kaempferol (1981.3 μg/g) and apigenin (1433.6 μg/g) were the major representatives in the leaves from Greece, while luteolin (839.1 μg/g) and kaempferol (688.1 μg/g) were the major ones in the leaves from Georgia, respectively. The EO content was 1.42% and 4.54% in the leaves from Greece and Georgia, respectively. The main EO constituents of the Greek laurel plants were 1,8-cineole (30.8%), α-terpinyl acetate (14.9%), α-terpineol (8.0%), sabinene (7.9%), and terpinen-4-ol (6.0%). The main EO constituents of the Georgian laurel plants were 1,8-cineole (29.2%), α-terpinyl acetate (22.6%), sabinene (12.2%), and methyleugenol (8.1%). The EO antimicrobial activities against 20 microorganisms were determined. Among the Gram-positive bacteria, the Enterococcus faecalis strain was the most sensitive, followed by Staphylococcus aureus ATCC 6538. Among the Candida species, C. albicans ATCC 10231 was the most sensitive to the laurel leaf EOs.
Laurel; Polyphenolsw; Essential oil; Chemistry; Natural product chemistry; Food Science; Agricultural Science; Biochemistry.
Laurel,
L. is an evergreen plant belonging to the Lauraceae family, native to Southern Europe and the Mediterranean area. This is the first report on the composition and bioactivity of laurel ...essential oil (EO) from Bulgaria. The oil yield was 0.78%, 0.80%, and 3.25% in the fruits, twigs, and leaves, respectively. The main constituents in the fruit EO were 1,8-cineole (33.3%),
-terpinyl acetate (10.3%),
-pinene (11.0%),
-elemene (7.5%), sabinene (6.3%),
-phellandrene (5.2%), bornyl acetate (4.4%), and camphene (4.3%); those in the twig EO were 1,8-cineole (48.5%),
-terpinyl acetate (13.1%), methyl eugenol (6.6%),
-linalool (3.8%),
-pinene (3.4%), sabinene (3.3%) and terpinene-4-ol (3.3%); and the ones in the leaf EO were 1,8-cineole (41.0%),
-terpinyl acetate (14.4%), sabinene (8.8%), methyl eugenole (6.0%),
-linalool (4.9%), and
-terpineol (3.1%). The antibacterial and antifungal properties of laurel EOs were examined according to the agar well diffusion method. The leaf EO showed antibacterial and antifungal activities against almost all strains of the microorganisms tested, whereas the twig EO was only able to inhibit
.
ATCC 9027 and
ATCC 8739 were the bacterial strains that showed the highest resistance to the laurel EO. The results can benefit the EO industry and biopesticide development.
We report the observation of the X(3872) in the J/psipi(+)pi(-) channel, with J/psi decaying to mu(+)mu(-), in p (p) over bar collisions at roots=1.96 TeV. Using approximately 230 pb(-1) of data ...collected with the Run II D0 detector, we observe 522+/-100 X(3872) candidates. The mass difference between the X(3872) state and the J/psi is measured to be 774.9+/-3.1(stat)+/-3.0(syst) MeV/c(2). We have investigated the production and decay characteristics of the X(3872) and find them to be similar to those of the psi(2S) state.
•Glass-ceramic has been developed using industrial wastes for its use on thin film solar cell.•Low porosity, low water absorption and high mechanical resistance were achieved.•The device allows both, ...functionality and energy saving.
Cu(In,Ga)Se2 (CIGS) is a p-type semiconductor material and an attractive absorber for thin films solar cells due to its unique optical and electrical properties. The low cost of this technology is based on its application on ecological substrates (glass, ceramic or glass-ceramic materials), effective uses of raw materials and lower thickness of the film (range from 1.5 to 3 µm). In this work, a new glass-ceramic substrate has been developed using industrial wastes materials (recycled glass, bottom ash and fly ash from a thermal power plant) used as support in thin film solar cell technology. The CIGS absorber has been synthesized by an easy and low-cost way of preparation using the co-precipitation method. The solar cell device has been completed and fully characterized. The obtained films were characterized by X-Ray diffraction (XRD), scanning electron microscope (SEM) and electrical characterization. The short circuit current (Jsc), open circuit voltage (Voc), fill factor (FF), and total area power conversion efficiency (η) of the device are 8,11 mA/cm2, 168,2 mV, 27,6% and 0,4% respectively.
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