The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most ...patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes.
Patients with distal or middle third, T3–T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A—preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B—four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS).
A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively.
Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.
Glycobiology is the comprehensive biological investigation of carbohydrates. The study of the role and function of complex carbohydrates often requires the attachment of carbohydrates to surfaces, ...their tagging with fluorophores, or their conversion into natural or non‐natural glycoconjugates, such as glycopeptides or glycolipids. Glycobiology and its “omics”, glycomics, require easy and robust chemical methods for the construction of these glycoconjugates. This review gives an overview of the rapidly expanding field of chemical reactions that selectively convert unprotected carbohydrates into glycoconjugates through the anomeric position. The discussion is divided in terms of the anomeric bond type of the newly formed glycoconjugates, including O‐, N‐, S‐, and C‐glycosides.
Let's make it easier: Glycoconjugates are fundamental in chemical biology and medicinal chemistry for investigation of glycan–protein interactions, as drugs, for glyco‐engineering of biopharmaceutical proteins, and for development of new diagnostic tools, among other roles. This review provides an overview of available methods for direct and protecting‐group‐free preparation of glycoconjugates from native carbohydrate ligands.
► ELEC-NRTL is a powerful thermodynamic model for concentrated electrolyte solutions. ► Simulation proposed scheme is flexible enough to reproduce a wide range of conditions. ► pH and CO2 pressure ...are main variables involved in CaCO3 solubility equilibria. ► Apparently different experimental data can be compared through calculated values.
Crude oil is usually co-produced with reservoir water, with increasing content in the production fluid along field life. Changes in temperature, pressure, and/or chemical composition may cause significant precipitation of inorganic salts (“scales”) during production. Therefore, the knowledge of the influence that different variables may have on salt solubility is critical to anticipate or identify potential flow assurance problems related to scales. The present work is specifically focused in the study of calcium carbonate precipitate formation as a main component of “scales”. Due to the number of variables involved in calcium carbonate precipitation (temperature, pressure, CO2 partial pressure, other salt content) and the heterogeneity of reservoir conditions, there are serious limitations to perform a full experimental study covering all the possible precipitation scenarios. Solubility data presented in this work, both previously reported and experimentally determined, cover a wide range of experimental conditions.
A simulation model that allows quantitative predictions in different scenarios is an interesting tool. A versatile simulation algorithm was developed using ASPEN PLUS® 7.1 from Aspen Technology, Inc., that allows different experimental conditions and the quantification of the influence of temperature, pressure and pH in CaCO3 solubility. This simulation scheme was applied to describe both literature and new experimental solubility data. Predicted results were in reasonable agreement with experimental information. The solubility of calcium carbonate decreases with temperature, increases with pressure and shows a maximum in presence of NaCl. The CO2 partial pressure has strong effect because it is direct relation with solution pH that modify the amount of ionic species present in the aqueous solution, and hence increasing the solubility of calcium carbonate. Special attention was devoted to such pH effect but, in order to have a fully predictive model, no parameters fit was carried out. The main conclusion of this work is the suitable simulation scheme to describe and predict the solubility of calcium carbonate at different conditions.
The potential of preoperative chemotherapy in rectal cancer is the subject of investigation in a number of global randomized trials. In this overview and expert discussion, Professor Cervantes ...summarizes the findings of numerous Phase II trials testing neoadjuvant chemotherapy. The crucial points in the next phase of trials include: patient selection, whether radiotherapy can be omitted altogether and whether chemotherapy can be used to augment the initial response to chemoradiotherapy. Finally, with the emergence of Magnetic Resonance Tumour Regression Grade a reliable method for assessing response after initial chemoradiotherapy, we ask if this can be used to drive the use of further selective chemotherapy to augment response.
The water gas shift reaction is an essential process to adjust the CO/H2 ratio in the industrial production of hydrogen. FeCr catalysts have been widely used in this reaction at high temperature but ...have environmental and safety concerns related to chromium content. In this work, the replacement of chromium by molybdenum in magnetite-based catalysts is studied. The materials were prepared by oxidation–precipitation and wet impregnation and they were characterized using X-ray powder diffraction, X-ray fluorescence, transmission electron microscopy, and temperature programmed reduction. Specific surface areas of samples were also measured. The results obtained indicate that molybdenum increases thermal stability of the magnetite active phase and prevents metallic iron formation during the reaction. The oxidation–precipitation method allows obtaining the material directly in the active phase and molybdenum is incorporated into magnetite lattice.
Developing methodology for computing accurate forecasts of electricity prices in liberalised markets is necessary to improve the bids submitted to the market operator by both consumers and producers ...to maximise their benefits and utilities, respectively. Here, the authors propose the extraction of common factors from the 24-dimensional vector of prices, and using them for one-day-ahead forecasting. This methodology is based on the Pena-Box and Lee-Carter models and is able to take into account the multivariate structure of the data. The data selected to illustrate the proposed methodology are those from the Iberian Market in the period January 2007 to January 2009, and numerical results in terms of prediction accuracy have also been compared with those by Garcia-Martos et al, obtaining a statistically significant improvement. A very important feature of the proposed methodology, the Dynamic Factor Model (DFM) is that is a powerful tool for mid- and long-term forecasting. This is an important difference between DFM and other methodologies for which the accuracy dramatically degrades when increasing the forecasting horizon.
Methods for site-selective chemistry on proteins are in high demand for the synthesis of chemically modified biopharmaceuticals, as well as for applications in chemical biology, biosensors and more. ...Inadvertent N-terminal gluconoylation has been reported during expression of proteins with an N-terminal His tag. Here we report the development of this side-reaction into a general method for highly selective N-terminal acylation of proteins to introduce functional groups. We identify an optimized N-terminal sequence, GHHH
- for the reaction with gluconolactone and 4-methoxyphenyl esters as acylating agents, facilitating the introduction of functionalities in a highly selective and efficient manner. Azides, biotin or a fluorophore are introduced at the N-termini of four unrelated proteins by effective and selective acylation with the 4-methoxyphenyl esters. This Gly-His
tag adds the unique capability for highly selective N-terminal chemical acylation of expressed proteins. We anticipate that it can find wide application in chemical biology and for biopharmaceuticals.
Primary chemotherapy has been tested as a possible approach for patients with high risk features but predicted clear mesorectal margins on preoperative MRI assessment. This study investigates the ...prognostic relevance of baseline and post-treatment MRI and pathology staging in rectal cancer patients undergoing primary chemotherapy.
Forty-six patients with T3 tumour>=2mm from the mesorectal fascia were prospectively treated with Neoadjuvant Capecitabine, Oxaliplatin and Bevacizumab prior to surgery between 2009 and 2011. The baseline and post-treatment MRI: T, Nodal and Extra-mural venous invasion (EMVI) status were recorded as well as post-treatment MRI Tumour regression grade (TRG) and modified-RECIST assessment of tumour length. The post-treatment pathology (yp) assessments of T3 substage, N, EMVI and TRG status were also recorded. Three-year disease-free survival (DFS) and cumulative incidence of recurrence were estimated by using the Kaplan–Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging and response on MRI and pathology with survival outcomes.
About 46 patients underwent neoadjuvant chemotherapy alone for high risk margin safe primary rectal cancer. The median follow-up was 41 months, 5 patients died and 11 patients experienced relapse (2 local, 8 distant and 1 both). In total 23/46 patients were identified with MRI features of EMVI at baseline. mrEMVI positive status carried independent prognostic significance for DFS (P=0.0097) with a hazard ratio of 31.33 (95% CI: 2.3–425.4). The histopathologic factor that was of independent prognostic importance was a final ypT downstage of ypT3a or less, hazard ratio: 14.0 (95% CI: 1.5–132.5).
mrEMVI is an independent prognostic factor at baseline for poor outcomes in rectal cancer treated with neoadjuvant chemotherapy while≤ypT3a is associated with an improvement in DFS. Future preoperative therapy evaluation in rectal cancer patients will need to stratify treatment according to baseline EMVI status as a crucial risk factor for recurrence in patients with predicted CRM clear rectal cancer.
We have evaluated a matrix‐assisted laser desorption ionization–time of flight mass spectrometry (MALDI‐TOF MS) method for the identification of carbapenemases and for distinguishing ...metallo‐β‐lactamases (MBLs). A total of 49 noncarbapenemase‐producing and 14 carbapenemase‐producing Enterobacteriaceae and Pseudomonas aeruginosa clinical strains, previously characterized by PCR, were included in the study. With MALDI‐TOF MS, the presence of carbapenemases was confirmed by the detection of ertapenem hydrolysis (lost of molecular peaks: 476·5 Da, 498·5 Da, 520·5 Da and presence of degradation products) in the mixture of the bacteria with the antibiotic, and classification was achieved by selective inhibition of carbapenemase activity (the ertapenem molecular peak was maintained) with ethylenediaminetetraacetic acid (EDTA). We obtained a good concordance among the results of PCR and MALDI‐TOF MS. This method appears to be simple, fast and reliable for distinguishing in few hours different classes of carbapenemases, which can be very useful for epidemiological studies or to establish a specific antimicrobial therapy. SIGNIFICANCE AND IMPACT OF THE STUDY: MALDI‐TOF mass spectrometry is increasingly present in microbiology laboratories due to its increasing use for bacterial identification. This study describes a method for detection of carbapenemase activity using MALDI‐TOF, which is similar to the reference method: the detection of imipenem hydrolysis using UV spectrometry.
Divinyl sulfone (DVS) has been used to activate agarose beads. The DVS activated agarose resulted quite stable in the pH range 5-10 at 25 °C under wet conditions, and can react rapidly with α-amides ...of Cys and His, at pH 5-10, with Lys mainly at pH 10 and with Tyr in a much slower fashion. After blocking with different nucleophiles, the support lost all reactivity, confirming that this protocol could be useful as an enzyme-support reaction end point. Then, chymotrypsin was immobilized on this support at pH 5, 7 and 10. Even though the enzyme was immobilized at all pH values, the immobilization rate decreased with the pH value. The effect of the immobilization on the activity depended on the immobilization pH, at pH 7 the activity decreased (to 50%) more than at pH 10 (by a 25%), while at pH 5 the immobilization has no effect. Then, the effect of blocking with different reagents was analyzed. It was found that blocking with ethylenediamine improved the enzyme activity by 70% and gave the best stability. The stability of all enzyme preparations improved when 24 h incubation was performed at pH 10, but the qualitative stabilization depended on the inactivation conditions. The analysis of the amino acids of the preparation immobilized at pH 10 showed that Lys, Tyr and Cys residues were involved in the immobilization, involving a minimum of 10 residues (glyoxyl agarose gave 4 Lys involved in the immobilization). The new preparation was 4-5 fold more stable than glyoxyl agarose preparation, considered a very stable one, and in some instances was more active than the free enzyme (170% for the enzyme immobilized at pH 10). Thus, DVS activated supports are very promising to permit the multipoint covalent attachment of enzymes, and that way to improve their stability.
DVS supports are very suitable to stabilize enzymes
via
multipoint covalent attachment.
PDF
