51 research outputs found
Η κλινική σημασία των ανοσοϋποδοχέων PD σε ασθενείς με διάχυτα λεμφώματα από μεγάλα Β κύτταρα: συσχέτιση με κλινικά και παθολογοανατομικά ευρήματα των ασθενών.
No full textΤο διάχυτο λέμφωμα από μεγάλα Β κύτταρα (Diffuse Large B-Cell Lymphoma, DLBCL) αποτελεί το συνηθέστερο non-Hodgkin λέμφωμα και ανήκει στα υψηλής κακοήθειας λεμφώματα. Σε κυτταρικό και μοριακό επίπεδο, η κλινική πορεία και πρόγνωση των ασθενών με αυτή την κακοήθεια φαίνεται πως εξαρτώνται σε σημαντικό βαθμό από την διαφυγή των λεμφωματικών κυττάρων από τους αμυντικούς μηχανισμούς του ανοσοποιητικού συστήματος και συγκεκριμένα από τα Τ λεμφοκύτταρα. Ανασταλτικό ρόλο στον πολλαπλασιασμό και στην ενεργοποίηση των T λεμφοκυττάρων και επομένως στην ανοσοεπιτήρηση και καταστροφή των νεοπλασματικών κυττάρων διαδραματίζει ο ανοσοκατασταλτικός υποδοχέας των λεμφοκυττάρων programmed cell death-1 (PD-1) μέσω της σύνδεσής του με 2 μόρια-συνδέτες, τα PD-L1 (CD274 ή B7-H1) και PD-L2 (CD273 ή B7-DC). Η σηματοδότηση μέσω του PD-1 φυσιολογικά αμβλύνει την διέγερση των Τ λεμφοκυττάρων και προστατεύει τους γειτονικούς ιστούς από την επέκταση της φλεγμονής, παρέχοντας μία ισορροπία μεταξύ αποτελεσματικής ανοσιακής απάντησης και ανοσοεπαγόμενης ιστικής καταστροφής, αλλά στην περίπτωση κακοηθειών διαδραματίζει αρνητικό ρόλο αφού συμβάλλει στην ανοσοδιαφυγή των νεοπλασματικών κυττάρων. Ο PD-L1 έχει ανιχνευθεί σε βιοψίες κυρίως από ασθενείς με πρωτοπαθές λέμφωμα μεσοθωρακίου (Primary Mediastinal Large B-cell Lymphoma, PMLBCL) αλλά και σε ασθενείς με DLBCL του ιστολογικού υπότυπου του μη προερχόμενου από το βλαστικό κέντρο (non-Germinal Center B-cell like, non-GCB). Επίσης, σε ασθενείς με DLBCL, ο PD-1 υποδοχέας έχει ανιχνευθεί τόσο στα λεμφωματικά κύτταρα όσο και στα λεμφοκύτταρα που ανευρίσκονται μεταξύ των νεοπλασματικών κυττάρων (Tumor Infiltrating Lymphocytes, TILs). Η παρούσα εργασία στόχευε στην διερεύνηση πιθανών παθογενετικών οδών και μοριακών μηχανισμών χημειοανθεκτικότητας στα DLBCL και συγκεκριμένα στα DLBCL, not otherwise specified (NOS), τα οποία και συνιστούν τουλάχιστον το 25-30% των DLBCL. Στην μελέτη που πραγματοποιήσαμε φάνηκε ότι η έκφραση του PD-L1 δεν αποτελεί ανεξάρτητο προγνωστικό παράγοντα για την συνολική επιβίωση των ασθενών με DLBCL, NOS, φαίνεται ωστόσο ότι η ανοσοϊστοχημική ανίχνευση των ανοσοϋποδοχέων και των συνδετών τους στα DLBCL, NOS απέχει ακόμα από το να θεωρηθεί αντικειμενική ή αξιόπιστη. Ένα άλλο εύρημα της μελέτης μας είναι ότι τα PD-L1 θετικά DLBCL, NOS συσχετίζονται κατά κύριο λόγο με τον non-GCB ιστολογικό υπότυπο, όπως περιγράφεται και σε άλλες μελέτες. Συνοψίζοντας, από την μελέτη μας φαίνεται ότι η έκφραση του PD-L1 στον νεοπλασματικό ιστό ασθενών με DLBCL, NOS θα μπορούσε να οδηγήσει σε επιθετικότερες βιολογικές συμπεριφορές και η αναστολή της PD-1/PD-L1 οδού με μονοκλωνικά αντισώματα μπορεί να έχει θέση σε αυτούς τους ασθενείς. Ωστόσο, θα πρέπει να προσδιοριστούν με σαφήνεια οι ασθενείς εκείνοι που θα ωφεληθούν περισσότερο από τις στοχευμένες ανοσοτροποποιητικές θεραπείες (όπως και εκείνοι που είναι πιο πιθανό να εμφανίσουν σοβαρού βαθμού παρενέργειες), ο πλέον κατάλληλος χρόνος και τρόπος χορήγησής τους και η διάρκειά τους, αλλά και δείκτες ανταπόκρισης στη θεραπεία. Ιδιαίτερο ενδιαφέρον παρουσιάζει και ο πιθανός συνδυασμός κυτταροτοξικών θεραπειών με αναστολείς των ανοσοϋποδοχέων. Η μεγαλύτερη ωστόσο πρόκληση στο εγγύς μέλλον θα είναι η εύρεση του βέλτιστου δυνατού συνδυασμού θεραπειών που στοχεύουν στους διάφορους μηχανισμούς ανοσοδιαφυγής των λεμφωματικών κυττάρων. Αυτή η ανακάλυψη θα ανοίξει τον δρόμο για εντελώς εξατομικευμένες θεραπείες για τον ασθενή που έχει υποτροπιάζον / ανθεκτικό στην θεραπεία λέμφωμα ή ακόμα και σε θεραπείες 1ης γραμμής.Diffuse Large B-Cell Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and belongs to the aggressive subtypes. At cellular and molecular level its clinical course and the prognosis of patients with this malignancy appear to depend to a large extent on the escape of lymphoma cells from the immune system and specifically from T lymphocytes. The immunosuppressive receptor of lymphocytes, programmed cell death-1 (PD-1), plays an inhibitory role in the proliferation and activation of T lymphocytes and, therefore, in the immune surveillance and destruction of neoplastic cells through its binding to 2 ligands, PD-L1 (CD274 or B7-H1) and PD-L2 (CD273 or B7-DC). PD-1 signaling physiologically attenuates T cell activation and protects adjacent tissues from the spread of inflammation, providing a balance between an effective immune response and immune-induced tissue damage, but in the case of malignant cells PD-1 plays a negative role as it contributes to the immune escape of neoplastic cells. PD-L1 has been detected in biopsies mainly of patients with Primary Mediastinal Large B-cell Lymphoma (PMLBCL) but also in patients with DLBCL of the non-germinal center histological subtype (non-GCB). Moreover, in patients with DLBCL, the PD-1 receptor has been detected in both lymphoma cells and tumor infiltrating lymphocytes (TILs). The present study aimed to investigate possible pathogenetic pathways and molecular mechanisms of refractoriness to chemotherapy of DLBCL cells, specifically among DLBCL, not otherwise specified (NOS) patients, who constitute at least 25-30% of all DLBCL cases. Our study showed that PD-L1 expression is not an independent prognostic factor for the overall survival in patients with DLBCL, NOS, it appears however that immunohistochemical detection of immunoreceptors and their ligands in DLBCL, NOS is still far from being objective or trustworthy. Another finding of our study is that PD-L1 positive DLBCL, NOS is primarily associated with the non-GCB histological subtype, as described in other studies as well. In summary, our study suggests that PD-L1 expression in patients with DLBCL, NOS could lead to more aggressive biological behaviors and inhibition of the PD-1 / PD-L1 pathway with monoclonal antibodies may be of value in these patients. However, the patients who will benefit the most from targeted immunomodulatory therapies (as well as those who are most likely to experience severe side effects), the most appropriate time and route of administration, and their duration are still unknown and should be clearly identified, as well as predictors of response to treatment. Of great interest is the possible combination of cytotoxic therapies with immunoreceptor inhibitors. However, the biggest challenge in the near future will be to find the optimal possible combination of therapies that target the various mechanisms by which lymphoma cells evade immune system mechanisms. This discovery will pave the way for completely personalized treatments for patients with recurrent or refractory lymphoma, or even under 1st line treatment
Clinical significance of PD immunoreceptors among diffuse large B-cell lymphoma patients: correlation with clinical and pathological findings
No full textDiffuse Large B-Cell Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and belongs to the aggressive subtypes. At cellular and molecular level its clinical course and the prognosis of patients with this malignancy appear to depend to a large extent on the escape of lymphoma cells from the immune system and specifically from T lymphocytes. The immunosuppressive receptor of lymphocytes, programmed cell death-1 (PD-1), plays an inhibitory role in the proliferation and activation of T lymphocytes and, therefore, in the immune surveillance and destruction of neoplastic cells through its binding to 2 ligands, PD-L1 (CD274 or B7-H1) and PD-L2 (CD273 or B7-DC). PD-1 signaling physiologically attenuates T cell activation and protects adjacent tissues from the spread of inflammation, providing a balance between an effective immune response and immune-induced tissue damage, but in the case of malignant cells PD-1 plays a negative role as it contributes to the immune escape of neoplastic cells.PD-L1 has been detected in biopsies mainly of patients with Primary Mediastinal Large B-cell Lymphoma (PMLBCL) but also in patients with DLBCL of the non-germinal center histological subtype (non-GCB). Moreover, in patients with DLBCL, the PD-1 receptor has been detected in both lymphoma cells and tumor infiltrating lymphocytes (TILs).The present study aimed to investigate possible pathogenetic pathways and molecular mechanisms of refractoriness to chemotherapy of DLBCL cells, specifically among DLBCL, not otherwise specified (NOS) patients, who constitute at least 25-30% of all DLBCL cases. Our study showed that PD-L1 expression is not an independent prognostic factor for the overall survival in patients with DLBCL, NOS, it appearshowever that immunohistochemical detection of immunoreceptors and their ligands in DLBCL, NOS is still far from being objective or trustworthy. Another finding of our study is that PD-L1 positive DLBCL, NOS is primarily associated with the non-GCB histological subtype, as described in other studies as well. In summary, our study suggests that PD-L1 expression in patients with DLBCL, NOS could lead to more aggressive biological behaviors and inhibition of the PD-1 / PD-L1 pathway with monoclonal antibodies may be of value in these patients. However, the patients who will benefit the most from targeted immunomodulatory therapies (as well as those who are most likely to experience severe side effects), the most appropriate time and route of administration, and their duration are still unknown and should be clearly identified, as well as predictors of response to treatment.Of great interest is the possible combination of cytotoxic therapies with immunoreceptor inhibitors. However, the biggest challenge in the near future will be to find the optimal possible combination of therapies that target the various mechanisms by which lymphoma cells evade immune system mechanisms. This discovery will pave the way for completely personalized treatments for patients with recurrent or refractory lymphoma, or even under 1st line treatment.Το διάχυτο λέμφωμα από μεγάλα Β κύτταρα (Diffuse Large B-Cell Lymphoma, DLBCL) αποτελεί το συνηθέστερο non-Hodgkin λέμφωμα και ανήκει στα υψηλής κακοήθειας λεμφώματα. Σε κυτταρικό και μοριακό επίπεδο, η κλινική πορεία και πρόγνωση των ασθενών με αυτή την κακοήθεια φαίνεται πως εξαρτώνται σε σημαντικό βαθμό από την διαφυγή των λεμφωματικών κυττάρων από τους αμυντικούς μηχανισμούς του ανοσοποιητικού συστήματος και συγκεκριμένα από τα Τ λεμφοκύτταρα. Ανασταλτικό ρόλο στον πολλαπλασιασμό και στην ενεργοποίηση των T λεμφοκυττάρων και επομένως στην ανοσοεπιτήρηση και καταστροφή των νεοπλασματικών κυττάρων διαδραματίζει ο ανοσοκατασταλτικός υποδοχέας των λεμφοκυττάρων programmed cell death-1 (PD-1) μέσω της σύνδεσής του με 2 μόρια-συνδέτες, τα PD-L1 (CD274 ή B7-H1) και PD-L2 (CD273 ή B7-DC). Η σηματοδότηση μέσω του PD-1 φυσιολογικά αμβλύνει την διέγερση των Τ λεμφοκυττάρων και προστατεύει τους γειτονικούς ιστούς από την επέκταση της φλεγμονής, παρέχοντας μία ισορροπία μεταξύ αποτελεσματικής ανοσιακής απάντησης και ανοσοεπαγόμενης ιστικής καταστροφής, αλλά στην περίπτωση κακοηθειών διαδραματίζει αρνητικό ρόλο αφού συμβάλλει στην ανοσοδιαφυγή των νεοπλασματικών κυττάρων.Ο PD-L1 έχει ανιχνευθεί σε βιοψίες κυρίως από ασθενείς με πρωτοπαθές λέμφωμα μεσοθωρακίου (Primary Mediastinal Large B-cell Lymphoma, PMLBCL) αλλά και σε ασθενείς με DLBCL του ιστολογικού υπότυπου του μη προερχόμενου από το βλαστικό κέντρο (non-Germinal Center B-cell like, non-GCB). Επίσης, σε ασθενείς με DLBCL, ο PD-1 υποδοχέας έχει ανιχνευθεί τόσο στα λεμφωματικά κύτταρα όσο και στα λεμφοκύτταρα που ανευρίσκονται μεταξύ των νεοπλασματικών κυττάρων (Tumor Infiltrating Lymphocytes, TILs).Η παρούσα εργασία στόχευε στην διερεύνηση πιθανών παθογενετικών οδών και μοριακών μηχανισμών χημειοανθεκτικότητας στα DLBCL και συγκεκριμένα στα DLBCL, not otherwise specified (NOS), τα οποία και συνιστούν τουλάχιστον το 25-30% των DLBCL. Στην μελέτη που πραγματοποιήσαμε φάνηκε ότι η έκφραση του PD-L1 δεν αποτελεί ανεξάρτητο προγνωστικό παράγοντα για την συνολική επιβίωση των ασθενών με DLBCL, NOS, φαίνεται ωστόσο ότι η ανοσοϊστοχημική ανίχνευση των ανοσοϋποδοχέων και των συνδετών τους στα DLBCL, NOS απέχει ακόμα από το να θεωρηθεί αντικειμενική ή αξιόπιστη. Ένα άλλο εύρημα της μελέτης μας είναι ότι τα PD-L1 θετικά DLBCL, NOS συσχετίζονται κατά κύριο λόγο με τον non-GCB ιστολογικό υπότυπο, όπως περιγράφεται και σε άλλες μελέτες. Συνοψίζοντας, από την μελέτη μας φαίνεται ότι η έκφραση του PD-L1 στον νεοπλασματικό ιστό ασθενών με DLBCL, NOS θα μπορούσε να οδηγήσει σε επιθετικότερες βιολογικές συμπεριφορές και η αναστολή της PD-1/PD-L1 οδού με μονοκλωνικά αντισώματα μπορεί να έχει θέση σε αυτούς τους ασθενείς. Ωστόσο, θα πρέπει να προσδιοριστούν με σαφήνεια οι ασθενείς εκείνοι που θα ωφεληθούν περισσότερο από τις στοχευμένες ανοσοτροποποιητικές θεραπείες (όπως και εκείνοι που είναι πιο πιθανό να εμφανίσουν σοβαρού βαθμού παρενέργειες), ο πλέον κατάλληλος χρόνος και τρόπος χορήγησής τους και η διάρκειά τους, αλλά και δείκτες ανταπόκρισης στη θεραπεία.Ιδιαίτερο ενδιαφέρον παρουσιάζει και ο πιθανός συνδυασμός κυτταροτοξικών θεραπειών με αναστολείς των ανοσοϋποδοχέων. Η μεγαλύτερη ωστόσο πρόκληση στο εγγύς μέλλον θα είναι η εύρεση του βέλτιστου δυνατού συνδυασμού θεραπειών που στοχεύουν στους διάφορους μηχανισμούς ανοσοδιαφυγής των λεμφωματικών κυττάρων. Αυτή η ανακάλυψη θα ανοίξει τον δρόμο για εντελώς εξατομικευμένες θεραπείες για τον ασθενή που έχει υποτροπιάζον / ανθεκτικό στην θεραπεία λέμφωμα ή ακόμα και σε θεραπείες 1ης γραμμής
Stamatis remarks on Freeman Article
No full textThis collection includes:
• Shaikh, A. (1984, April 7). Discussion of Willi Semmler and Peter Flashel on prices, profit, and sales [Handwritten notes]. Manuscript in possession of the author.
• Shaikh, A. (1983, March 7). Note on joint production: Differentiated capital [Handwritten notes]. Manuscript in possession of the author.
• Shaikh, A. (1984, April 6). Duncan Foley’s “Prices of production in a general model of production” [Handwritten notes]. Manuscript in possession of the author.
• Shaikh, A. (n.d.). Seminar/discussion notes with comments on the work of Duncan Foley, Peter Flashel, Gérard Duménil, and Bertram Schefold [Handwritten notes]. Manuscript in possession of the author.
• Shaikh, A. (1984, April 5–6). Marxian competition, neoclassical competition, and some implications: Response to Steedman/Morishima critique [Handwritten notes]. Manuscript in possession of the author.
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• Shaikh, A. (n.d.). Prices of production as centers of gravity, profitability, and traditional approaches to depreciation [Handwritten notes, citing Charles Landen, Dale Gerboth, & Thomas McRae, Accounting for depreciable assets (1975)]. Manuscript in possession of the author.
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Chest pain with increased troponin level; not always a cardiology issue
No full textThrombotic Thrombocytopenic Purpura (TTP) is a thrombotic microangiopathy syndrome resulting from decrease or absence of “a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13” (ADAMTS13). TTP has been characterized by the classical pentad of thrombocytopenia, hemolysis, fever, renal injury and neurological deficits, yet the patient may present with any atypical symptom related to microthrombi formation in the microcirculation. Here we present a rare case of a young patient with retrosternal chest pain and myocardial injury as the first manifestation of TTP
Traffic Safety of Disabled Pedestrians at Signalized Crosswalks
No full textMobility of disabled people has as a basic guarantee the traffic safety. Walking for disabled may have improved considerably compared to the past, but there are stillissues such as the safe crossing at signalized crosswalks. Also, the availability of studies on safe crossing for disabled pedestrians is limited. While it has been understood how pedestrians perceive safety at crosswalks, no similar study has been done for disabled pedestrians. The main purpose of this study is to fill the gap and make it more understandable how disabled pedestrians perceive traffic safety at signalized crosswalks. The literature showed significant factors that influence the pedestrian crossing behavior, such as the gender, the kind of disability, the presence of traffic lights at crosswalks, and weather conditions. Most ofthese factors are significantly related to the perception of safety.The main methodology included the interviews, and the survey, using the statistical analysis with the hypothesis tests and the Generalized Linear Model for the process of the data. The results proved that factors such as gender, age, kind of disability, the walking frequency had a significant impact on the perceived safety of disabled pedestrians. Yet, the study brought up important solutions that can improve safety perception, such as technological solutions like artificial intelligence traffic lights and infrastructure solutions such as the construction of underground crosswalks and refuges islands at long distance crosswalks. A recommendation is that the authorities and transport planners should emphasize to the solutions proposed to improve safety. A further scientific recommendation would the study of the objective safety in the future, comparing it with the perceived safety. This study has contributed significantly to the understanding of the issues faced by disabled pedestrians at crosswalks and it can be a starting point for further improvements in the mobility of disabled pedestrians and their lives in the future.Transport, Infrastructure and Logistic
Mechanical and corrosion behaviour of 3D printed aluminium bronzes produced by wire+arc additive manufacturing: In collaboration with RAMLAB
No full textThe emerging field of 3D printing has expanded to the fabrication of metallic components during the last decade. Among the most prominent applications is the production of aluminium bronze marine propellers by the Wire+Arc Additive Manufacturing (WAAM) method. This method incorporates a welding system attached to a robotic arm. The final product results after sequential bead depositions. The main assets of the method are the efficient material usage and the minimization of lead time, which both have a positive environmental and economic impact. The aim of this project is to evaluate the feasibility to produce 3D printed aluminium bronze (CMA and NAB alloys) blocks with the WAAM method and compare the mechanical and corrosion properties of the blocks with the market requirements. In order to achieve that, rectangular blocks were manufactured at the facilities of Delft University of Technology and at Rotterdam Additive Manufacturing Fieldlab (RAMLAB). Cross sectional areas were extracted and used for microstructural investigation and for hardness measurement. Subsequently, the blocks were machined to produce tensile and Charpy specimens along the built height. Finally, corrosion tests were performed, including open circuit potential measurements, polarization experiments and Scanning Kelvin Probe (SKP) tests.The microstructural investigation revealed that the 3D printed CMA block consisted of a banded structure. The deposited layers consisted of two dominant phases, α and β, and a variety of precipitates. The Widmanstätten α phase nucleates at the grain boundaries mainly. The tempering promotes the growth of the α phase, making the grain boundaries more indistinguishable, while the β phase decomposes.The mechanical testing results depicted that the hardness, the tensile strength and the absorption energy of the 3D printed blocks exceeded the specifications of the cast products, according to the ASTM standards. The built height direction is weaker than the welding direction; however, the deposition height plays no significant role in the mechanical properties. Samples were also tested after a heat treatment of 675 °C for 6 hours, as recommended in the literature. The result was a 25% reduction of the tensile yield strength and a 10% reduction of the ultimate tensile strength. However, the scatter in the measured values was reduced too. Regarding the corrosion results, the built height has little effect on the corrosion susceptibility, according to the polarization curves. The material exhibits a remarkable low corrosion rate, which justifies its use in marine applications. The Scanning Kelvin Probe (SKP) tests illustrated the beneficial aspect of the tempering heat treatment, which alleviates the large potential differences of adjacent deposited areas.It can be concluded that the CMA alloys are tolerable to the oscillations of the production parameters, making them appealing to the additive manufacturing industry. The mechanical properties achieved, outmatch not only the specifications for the cast CMA products, but also the performance of similar 3D printed aluminium bronze structures, found in the literature.Materials Science and Engineerin
The use of novel oral anticoagulants in cancer patients with venous thromboembolism
No full textVenous thromboembolism (VTE) is not uncommon among patients with cancer and is one of the major causes of mortality and morbidity. Treatment with low-molecular-weight heparin (LMWH) is effective, yet accompanied by the need for daily administration of injections for a prolonged time and (even rarely) thrombocytopenia. The discovery of novel oral anticoagulants (NOACs) was based on an effort to improve the pharmacodynamic and pharmacokinetic properties of previous generation anticoagulants while maintaining efficacy without the need for daily subcutaneous administration and frequent laboratory monitoring. The MEDLINE database was searched using PubMed in order to find relevant studies on the use of NOACs in patients with active malignancy and VTE. Furthermore, critical reading of references in recently published studies and reviews was performed. NOACs appear to be at least equivalent to coumarin anticoagulants in terms of efficacy and safety and their administration is easier, but data specifically concerning patients with active malignancy or comparing them to LMWH in this specific clinical setting are not yet available. Furthermore, patients with active cancer present several unique characteristics and drawing conclusions from studies involving other patient groups may not be appropriate. Specific studies in cancer patients are still pending that will help decide if NOACs will be the drugs of choice in this group of patients in need of efficient and simple to administer treatments. (C) 2016 Elsevier Inc. All rights reserved
Programmed death 1 and B and T lymphocyte attenuator immunoreceptors and their association with malignant T‐lymphoproliferative disorders: brief review
No full textPesticide inputs from the sewage treatment plant of Agrinio to River Acheloos, western Greece: occurrence and removal
No full textPublisher‘s note. We regret that the published version of this article erroneously denoted the first author as corresponding author; in fact the formal corresponding author of this paper is Professor Ioannis Konstantinou, whose address is repeated below.</jats:p
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