Promotional Effect on Selective Catalytic Reduction of NO x

W and Ce are known to be a good promoters to improve selective catalytic reduction (SCR) activity for V2O5/TiO2 catalysts. This work aimed at finding the optimum ratio and loading of promoters (W and Ce) on V2O5/TiO2 catalyst in order to improve SCR reactivity in low temperature region and to minimize N2O formation in high temperature region. In addition, we changed the order of impregnation between W and Ce precursors on V2O5/TiO2 catalyst during the preparation and observed its effect on SCR activity and N2 selectivity. We utilized various analytical techniques, such as N2 adsorption-desorption, X-ray diffraction (XRD), and temperature-programmed reduction with hydrogen (H2 TPR) to investigate the physicochemical properties of catalysts. It was found that W- and Ce-overloaded V2O5/TiO2 catalyst such as W/Ce/V/TiO2 (15 : 15 : 1 wt%) showed the most remarkable DeNOx properties over the wide temperature region. Additionally, this catalyst significantly suppressed N2O formation during SCR reaction, especially in high temperature region (350–400°C). Based on the characterization results, it was found that such superior activity originated from the improved reducibility and morphology of W and Ce species on V2O5/TiO2 catalyst when they are incorporated together at high loading

Promotional Effect on Selective Catalytic Reduction of NO x with NH 3 over Overloaded W and Ce on V 2 O 5 /TiO 2 Catalysts

W and Ce are known to be a good promoters to improve selective catalytic reduction (SCR) activity for V 2 O 5 /TiO 2 catalysts. This work aimed at finding the optimum ratio and loading of promoters (W and Ce) on V 2 O 5 /TiO 2 catalyst in order to improve SCR reactivity in low temperature region and to minimize N 2 O formation in high temperature region. In addition, we changed the order of impregnation between W and Ce precursors on V 2 O 5 /TiO 2 catalyst during the preparation and observed its effect on SCR activity and N 2 selectivity. We utilized various analytical techniques, such as N 2 adsorption-desorption, X-ray diffraction (XRD), and temperature-programmed reduction with hydrogen (H 2 TPR) to investigate the physicochemical properties of catalysts. It was found that W-and Ce-overloaded V 2 O 5 /TiO 2 catalyst such as W/Ce/V/TiO 2 (15 : 15 : 1 wt%) showed the most remarkable DeNO x properties over the wide temperature region. Additionally, this catalyst significantly suppressed N 2 O formation during SCR reaction, especially in high temperature region (350-400 ∘ C). Based on the characterization results, it was found that such superior activity originated from the improved reducibility and morphology of W and Ce species on V 2 O 5 /TiO 2 catalyst when they are incorporated together at high loading

Ammonium Inhibits Chromomethylase 3-Mediated Methylation of the Arabidopsis Nitrate Reductase Gene NIA2

Gene methylation is an important mechanism regulating gene expression and genome stability. Our previous work showed that methylation of the nitrate reductase (NR) gene NIA2 was dependent on chromomethylase 3 (CMT3). Here, we show that CMT3-mediated NIA2 methylation is regulated by ammonium in Arabidopsis thaliana. CHG sequences (where H can be A, T, or C) were methylated in NIA2 but not in NIA1, and ammonium [(NH4)2SO4] treatment completely blocked CHG methylation in NIA2. By contrast, ammonium had no effect on CMT3 methylation, indicating that ammonium negatively regulates CMT3-mediated NIA2 methylation without affecting CMT3 methylation. Ammonium upregulated NIA2 mRNA expression, which was consistent with the repression of NIA2 methylation by ammonium. Ammonium treatment also reduced the overall genome methylation level of wild-type Arabidopsis. Moreover, CMT3 bound to specific promoter and intragenic regions of NIA2. These combined results indicate that ammonium inhibits CMT3-mediated methylation of NIA2 and that of other target genes, and CMT3 selectively binds to target DNA sequences for methylation

Induction of IL-10-producing CD4(+)CD25(+ )T cells in animal model of collagen-induced arthritis by oral administration of type II collagen

Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4(+)CD25(+ )T-cell subsets in an animal model of collagen-induced arthritis (CIA). We found that joint inflammation in CIA mice peaked at 5 weeks after primary immunization with CII, which was significantly less in mice tolerized by repeated oral feeding of CII before CIA induction. Mice that had been fed with CII also exhibited increased serum IgG(1 )and decreased serum IgG(2a )as compared with nontolerized CIA animals. The T-cell proliferative response to CII was suppressed in lymph nodes of tolerized mice also. Production of IL-10 and of transforming growth factor-β from mononuclear lymphocytes was increased in the tolerized animals, and CD4(+ )T cells isolated from tolerized mice did not respond with induction of IFN-γ when stimulated in vitro with CII. We also observed greater induction of IL-10-producing CD4(+)CD25(+ )subsets among CII-stimulated splenic T cells from tolerized mice. These data suggest that when these IL-10-producing CD4(+)CD25(+ )T cells encounter CII antigen in affected joints they become activated to exert an anti-inflammatory effect

Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors: A Phase 1a/1b Nonrandomized Controlled Trial

Antibody; Atezolizumab; Advanced solid tumorsAnticuerpo; Atezolizumab; Tumores sólidos avanzadosAnticòs; Atezolizumab; Tumors sòlids avançatsImportance Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in programmed death ligand 1–selected tumors. Objective To evaluate the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its combination with atezolizumab in patients with advanced solid tumors. Design, Setting, and Participants The GO30103 open-label, first-in-human phase 1a/1b dose-escalation and dose-expansion nonrandomized controlled trial was conducted at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 1b. Patients were aged 18 years or older with measurable disease at baseline. The clinical cutoff date was October 1, 2021. Data analysis was performed on January 24, 2022. Interventions Patients received fixed-dose intravenous tiragolumab on day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients were treated until disease progression, loss of clinical benefit, or development of unacceptable toxicity. Main Outcomes and Measures The primary end points included the safety, tolerability, and recommended phase 2 dose (RP2D) of tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point included the investigator-assessed objective response rate (ORR). Counts and percentages are used for categorical variables, and medians and ranges are used for continuous variables. Results Among the phase 1a (n = 24) and 1b (n = 49) dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 25-81) years, respectively. More than half of patients were women (14 of 24 [58%] and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 or more prior cancer therapies. No dose-limiting toxicities occurred, and the maximum tolerated dose of tiragolumab was not reached (NR). The most frequent treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor activity in 6% of patients (n = 3) during phase 1b. The safety profile of combination tiragolumab plus atezolizumab in phase 1b was similar in the dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) in the non–small cell lung cancer (NSCLC) cohort (median duration of response [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 15.2 [95% CI, 7.0 to NR] months). Conclusions and Relevance In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed. Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy–naive metastatic NSCLC or EC. Trial Registration ClinicalTrials.gov Identifier: NCT02794571This study was sponsored by F. Hoffmann-La Roche Ltd. Medical writing support for the development of this article, under the direction of the authors, was provided by Demi Christofi, MSc, Ashfield MedComms (an Inizio company), and funded by F. Hoffmann-La Roche Ltd

A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma

BACKGROUND: The aim of this study was to examine the efficacy and safety of everolimus in patients with progressive unresectable adenoid cystic carcinoma (ACC). METHODS: Histologically confirmed ACC patients with documented disease progression within 12 months prior to the study entry were eligible. Everolimus was given at a dose of 10 mg daily until progression or occurrence of unacceptable toxicities. The primary endpoint was a 4-month progression-free survival (PFS). RESULTS: A total of 34 patients were enrolled. The 4-month PFS probability was 65.5% (95% one-sided confidence interval [CI], 47.7 to infinity). Median PFS duration was 11.2 months (95% CI, 3.6 to 15.8). Complete or partial response was not achieved. Twenty-seven (79.4%, 95% CI, 63.2 to 89.6) patients showed stable disease (SD). Tumor shrinkage within SD criteria was observed in 15 patients (44.1%) and SD lasting 6 months was observed in 13 patients (38.2%). Four patients had disease progression. Among the 18 patients with both pre- and post-treatment (at 8 weeks) FDG-PET scans available, 8 patients (44.4%) showed a partial metabolic response, defined as a ≥25% reduction in maximum standardized uptake values (SUVmax). The most common adverse events were stomatitis, anemia, asthenia, and leukopenia. No unexpected everolimus related toxicities were reported. CONCLUSIONS: Everolimus showed promising efficacy and good tolerability in progressive unresectable ACC. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT0115284

Adjuvant Chemotherapy in Microsatellite Instability-High Gastric Cancer

Purpose Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated. Materials and Methods This study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers. Results Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040). Conclusion MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.