Enterprise Ionic Liquids Database (ILUAM) for Use in Aspen ONE Programs Suite with COSMO-Based Property Methods

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in Industrial & Engineering Chemistry Research copyright © American Chemical Society after peer review and technical editing by the publisher . To access the final and published work see Enterprise Ionic Liquids Database (ILUAM) for Use in Aspen ONE Programs Suite with COSMO-Based Property Methods V. R. Ferro, C. Moya, D. Moreno, R. Santiago, J. de Riva, G. Pedrosa, M. Larriba, I. Diaz, and J. Palomar Industrial & Engineering Chemistry Research 2018 57 (3), 980-989 DOI: 10.1021/acs.iecr.7b04031An enterprise database of pure ionic liquids (ILs) for its use in the Aspen ONE programs is presented. The database is identified as ILUAM, and the first version (ILUAM01) contains 100 ILs composed of 30 cations and 23 anions. The IL components were introduced in Aspen Properties as pseudocomponents using information from the computational COSMO-RS method and from experimental viscosity data. ILUAM database was created to be used along with the COSMOSAC property model implemented in Aspen Plus, allowing evaluating IL process performance without needing further experimental data. Some validation tests were carried out to demonstrate the successful incorporation of ILs in the Aspen Plus property system. Then, the performance of ILUAM01 database in thermodynamic property predictions of mixtures involving ILs and conventional chemical compounds was revised in terms of activity coefficients at infinite dilution and phase equilibrium data. The property description of pure ILs and IL mixtures with conventional chemical compounds using COSMO-based/Aspen Plus approach was found with the accuracy level required in the conceptual design of new processes. ILUAM database offers the opportunity of performing systematic evaluation of potential industrial applications of ILs and their competitiveness as alternative to conventional solvents.The authors are grateful to the Comunidad de Madrid (project S2013- MAE-2800) and to the Ministerio de Economía y Competitividad of Spain (Project CTQ2014-52288-R) for financial support. M. Larriba also thanks Ministerio de Economía y Competitividad of Spain for awarding him a Juan de la Cierva-Formación Contract (Reference FJCI-2015-25343

1386pdimpower150 clinical safety tolerability and immune related adverse events in a phase iii study of atezolizumab atezo chemotherapy chemo bevacizumab bev vs chemo bev in 1l nonsquamous nsclc

n/

NADPH oxidase 1 as a new regulator of the WNT pathway and the protective effect of vitamin D in colorectal cancer

Trabajo presentado en el 43rd Annual Meeting of the SEBBM, celebrado en Barcelona (España) del 19 al 22 de julio de 2021.Worldwide, colorectal cancer (CRC) is the third most common malignant neoplasm and the second leading cause of cancer-associated mortality, with an estimated increase in global prevalence of 60% by 2030 (1,2). Mutational inactivation of adenomatous polyposis coli (APC) is the hallmark of CRC and leads to an overactivation of WNT signaling that favors the development and progression of CRC (3). Large epidemiological studies suggest that the diabetic population is at increased risk for site-specific cancers, including CRC (4). Our laboratory has shown that hyperglycemia induces the accumulation of ROS in CRC but not healthy cells, driving the activation of a newly described ROS/AMPK/EP300 axis that enhances Wnt/b-catenin signaling. Increased EP300 leads to increased acetylation of β-catenin at K354, a requirement for nuclear accumulation and transcriptional activation of WNT target genes (5,6). The critical role driven by ROS suggest a possible involvement of the NADPH oxidases (NOX family, as a source of ROS. Specifically, NOX 1 and NOX 4 are expressed in colon epithelial cells, and their overexpression in CRC cells promotes cell proliferation and invasiveness (7,8,9,10). Our results indicate that hyperglycemia significantly increases NOX1 levels, in correlation with increased ROS production in CRC cells, suggesting a possible regulation of the ROS/ AMPK/EP300 axis by NOX1. Antioxidant mechanisms dealing with NOX1-induced ROS should be effective against CRC. Vitamin D (1α, 25-dihydroxyvitamin D3) is a powerful antioxidant that inhibits proliferation and promotes differentiation of CRC cells at least partially through inhibition of Wnt/β-catenin signalling. Consequently, vitamin D deficiency is associated with poor survival to CRC (11,12). Our results indicate that vitamin D causes a reduction in the levels and / or activity of some members of the NOX family by turning off the ROS/AMPK/EP300/β-catenin axis and its proliferative and tumorigenic effects. The data suggest a new antitumor mechanism of vitamin D linked to its anti-oxidant action. Our results integrate independent epidemiological links between vitamin D deficiency, diabetes and cancer in one overarching and unifying mechanism

LungBEAM: A prospective multicenter study to monitor stage IV NSCLC patients with EGFR mutations using BEAMing technology

Objectives: The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non-small cell lung cancer (NSCLC) patients treated with first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods: Stage IV NSCLC patients with locally confirmed EGFR-TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first- or second-generation EGFR-TKI as first-line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression-free survival (PFS) event or until study completion (72-week follow-up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing. Results: A total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty-six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow-up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p < 0.001). The HR for progression in patients showing increasing plasma sensitizing mutation levels (positive MAF slope) versus patients showing either decreasing or unchanged plasma mutation levels (negative or null MAF slopes) was 3.85 (95% CI, 2.01–7.36; p < 0.001). Conclusion: Detection and quantification of EGFR mutations in circulating tumor DNA using the highly sensitive BEAMing method should greatly assist in optimizing treatment decisions for advanced NSCLC patients. © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy. © Copyright © 2021 Jantus-Lewintre, Massutí Sureda, González Larriba, Rodríguez-Abreu, Juan, Blasco, Dómine, Provencio Pulla, Garde, Álvarez, Maestu, Pérez de Carrión, Artal, Rolfo, de Castro, Guillot, Oramas, de las Peñas, Ferrera, Martínez, Serra, Rosell and Camps

Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-α as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population

Background: The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-α) treatment in patients with metastatic renal cell carcinoma (mRCC)

The Candida albicans Ku70 Modulates Telomere Length and Structure by Regulating Both Telomerase and Recombination

The heterodimeric Ku complex has been shown to participate in DNA repair and telomere regulation in a variety of organisms. Here we report a detailed characterization of the function of Ku70 in the diploid fungal pathogen Candida albicans. Both ku70 heterozygous and homozygous deletion mutants have a wild-type colony and cellular morphology, and are not sensitive to MMS or UV light. Interestingly, we observed complex effects of KU70 gene dosage on telomere lengths, with the KU70/ku70 heterozygotes exhibiting slightly shorter telomeres, and the ku70 null strain exhibiting long and heterogeneous telomeres. Analysis of combination mutants suggests that the telomere elongation in the ku70 null mutant is due mostly to unregulated telomerase action. In addition, elevated levels of extrachromosomal telomeric circles were detected in the null mutant, consistent with activation of aberrant telomeric recombination. Altogether, our observations point to multiple mechanisms of the Ku complex in telomerase regulation and telomere protection in C. albicans, and reveal interesting similarities and differences in the mechanisms of the Ku complex in disparate systems

SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications

Vitamin D analogues with reduced hypercalcemic activity are under clinical investigation for use against colon cancer and other neoplasias. However, only a subset of patients responds to this therapy, most probably due to loss of vitamin D receptor (VDR) expression during tumour progression. Recent data show that SNAIL transcription factor represses VDR expression, and thus abolishes the antiproliferative and prodifferentiation effects of VDR ligands in cultured cancer cells and their antitumour action in xenografted mice. Accordingly, upregulation of SNAIL in human colon tumours associates with downregulation of VDR. These findings suggest that SNAIL may be associated with loss of responsiveness to vitamin D analogues and may thus be used as an indicator of patients who are unlikely to respond to this therapy

Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study

BACKGROUND: Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD). METHODS: We genotyped 9131 individuals from the adult Danish population for cystic fibrosis 5T, 7T, 9T, and F508del alleles, and examined associations between 11 different genotype combinations, and annual FEV(1 )decline and risk of asthma or COPD. RESULTS: 5T heterozygotes vs. 7T homozygous controls had no increase in annual FEV(1 )decline, self-reported asthma, spirometry-defined COPD, or incidence of hospitalization from asthma or COPD. In 5T/7T heterozygotes vs. 7T homozygous controls we had 90% power to detect an increase in FEV(1 )decline of 8 ml, an odds ratio for self-reported asthma and spirometry-defined COPD of 1.9 and 1.7, and a hazard ratio for asthma and COPD hospitalization of 1.8 and 1.6, respectively. Both 5T homozygotes identified in the study showed evidence of asthma, while none of four 5T/F508del compound heterozygotes had severe pulmonary disease. 7T/9T individuals had annual decline in FEV(1 )of 19 ml compared with 21 ml in 7T homozygous controls (t-test:P = 0.03). 6.7% of 7T homozygotes without an F508del allele in the cystic fibrosis transmembrane conductance regulator gene reported asthma vs. 11% of 7T/9T individuals with an F508del allele (χ(2):P = 0.01) and 40% of 7T homozygotes with an F508del allele (P = 0.04). 7T homozygotes with vs. without an F508del allele also had higher incidence of asthma hospitalization (log-rank:P = 0.003); unadjusted and adjusted equivalent hazard ratios for asthma hospitalization were 11 (95%CI:1.5–78) and 6.3 (0.84–47) in 7T homozygotes with vs. without an F508del allele. CONCLUSION: Polythymidine 5T heterozygosity is not associated with pulmonary dysfunction or disease in the adult Caucasian population. Furthermore, our results support that F508del heterozygosity is associated with increased asthma risk independently of the 5T allele

Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-{alpha} as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population

BACKGROUND: The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-alpha) treatment in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN-alpha (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included. RESULTS: Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values. CONCLUSIONS: Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-alpha