Detection of Herplex Simplex Virus-1 and -2 in Cardiac Myxomas

The etiology of sporadic cardiac myxomas remains elusive. The tendency for these lesions to recur following resection, their immunopathological characteristics, along with their histological and molecular profile, may implicate the presence of an infective agent in this type of tumor. In this study, we investigated the presence of herpes simplex virus (HSV) DNA in a cohort of cardiac myxomas in a tertiary referral centre. Twenty-nine formalin-fixed paraffin-embedded (FFPE) sporadic cardiac myxomas were obtained, 17 of which were shown to be informative. These were compared to 19 macroscopically and microscopically normal heart tissue specimens. The detection of HSV-1 and -2 genomic sequences was achieved with the use of a combined nested PCR-Restriction Fragment Length Polymorphism methodology. The presence of HSV-1 and/or -2 DNA was demonstrated in 6 of 17 (35%) informative sporadic cardiac myxomas, whereas no HSV DNA was detected in normal heart tissues (P < 0.01). The existence of HSV-1/2 DNA in sporadic cardiac myxomas, along with its absence from normal heart tissues, reinforces the possibility that HSV infection might be involved in the development of these lesions. Our findings raise the point of anti-HSV medication postsurgically with a potential benefit in reducing the rate of recurrences

Detection of Herplex Simplex Virus-1 and -2 in Cardiac Myxomas

The etiology of sporadic cardiac myxomas remains elusive. The tendency for these lesions to recur following resection, their immunopathological characteristics, along with their histological and molecular profile, may implicate the presence of an infective agent in this type of tumor. In this study, we investigated the presence of herpes simplex virus (HSV) DNA in a cohort of cardiac myxomas in a tertiary referral centre. Twenty-nine formalin-fixed paraffin-embedded (FFPE) sporadic cardiac myxomas were obtained, 17 of which were shown to be informative. These were compared to 19 macroscopically and microscopically normal heart tissue specimens. The detection of HSV-1 and -2 genomic sequences was achieved with the use of a combined nested PCRRestriction Fragment Length Polymorphism methodology. The presence of HSV-1 and/or -2 DNA was demonstrated in 6 of 17 (35%) informative sporadic cardiac myxomas, whereas no HSV DNA was detected in normal heart tissues (P &lt; 0.01). The existence of HSV-1/2 DNA in sporadic cardiac myxomas, along with its absence from normal heart tissues, reinforces the possibility that HSV infection might be involved in the development of these lesions. Our findings raise the point of anti-HSV medication postsurgically with a potential benefit in reducing the rate of recurrences

Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins

The Cdc6 replication licensing factor acts as a molecular switch at the E-cadherin locus, leading to E-cadherin transcriptional repression and local activation of replication

Single and double multiphoton ionization of alkaline earth atoms via autoionizing states

In the present study single and double one-colour multiphoton ionization of Alkaline-Earth atoms (Mg, Ca and Sr) is investigated experimentally (collection ions and fluorescence) in the vicinity of the four-photon doubly excited mp² ¹S₀ autoionizing states (m = 3,4,5 for Mg, Ca and Sr correspondingly). Especially for the Mg atom the experimental findings are reproduced by a theoretical model based on a combination of density matrix calculations and rate equations taking into account the near-resonant strong one-photon coupling between the 3p² ¹S₀ and 3p3d ¹P₁ autoionizing states. The experimental setup consists of an atomic beam apparatus (equipped with a TOF mass spectrometer) where the single and double photoionization experiments have been performed and a vapour-cell devoted to the studies of fluorescence detection. In both cases the laser radiation is provided by a Nd:YAG pumped dye laser system delivering linearly polarized pulses of ~5ns duration while the employed intensities under our focusing conditions are moderate (10¹¹ W/cm² ≤ I <10¹² W/cm²). The choice of the four-photon excitation of the mp² ¹S₀ states is dictated by the desire for the photon energy to be low enough so that it favours their (single or multiple) photon radiative couplings to higher (autoionizing) as well to lower (bound) atomic states. It may be anticipated that such ladder excitation schemes favours the absorption of a significant number of ATI-photons within the continuum, allowing the production of ions in excited states resulting in a subsequent very efficient doubly charged ion production. The experimental observations reveal that within the ns laser pulse regime the role of autoionizing states in the dynamics of the atom-laser field interaction emerges more clearly. In all cases the main mechanism of the doubly charged ion production is the sequential process via excited ionic states, while a confrontation of the present results to those of the existing relevant literature suggests that absorption of high numbers of above threshold photons in Alkaline Earth atoms, and with pulses of ns duration, occurs predominantly with low photon energy radiation (as compared to the single and double ionization potentials).Στην παρούσα εργασία μελετήθηκε πειραματικά (συλλέγοντας ιόντα και φθορισμό) ο απλός και διπλός μονοχρωματικός πολυφωτονικός ιονισμός ατόμων των Αλκαλικών Γαιών (Mg, Ca και Sr) στην περιοχή των τετραφωτονικά διεγερμένων αυτοϊονιζόμενων καταστάσεων mp² ¹S₀ (με m = 3, 4 και 5 για τα Mg, Ca και Sr αντίστοιχα). Ειδικά για το άτομο του Mg τα πειραματικά ευρήματα αναπαράγονται από ένα θεωρητικό μοντέλο που συνδυάζει υπολογισμούς πίνακα πυκνότητας και εξισώσεις ρυθμών, λαμβάνοντας υπόψη την ισχυρή μονοφωτονική σύζευξη μεταξύ των αυτοϊονιζόμενων καταστάσεων 3p² ¹S₀ και 3p3d ¹P₁. Η πειραματική διάταξη αποτελείται από ένα πείραμα ατομικής δέσμης (εφοδιασμένο με φασματογράφο μάζας ελεύθερου χρόνου πτήσης) όπου διεξάγονται τα πειράματα απλού και διπλού φωτοϊονισμού, καθώς και από ένα κελί παραγωγής ατμών αφιερωμένο στην μελέτη ανίχνευσης φθορισμού. Η ακτινοβολία και για τις δύο πειραματικές διατάξεις προσφέρεται από ένα αντλούμενο από Nd:YAG σύστημα laser χρωστικής το οποίο παράγει παλμούς διάρκειας ~5ns ενώ οι εμπλεκόμενες εντάσεις υπό τις πειραματικές συνθήκες εστίασής μας χαρακτηρίζονται ως μέτριες (10¹¹ W/cm² ≤ I <10¹² W/cm²). Η επιλογή της τετραφωτονικής διέγερσης των αυτοϊονιζόμενων καταστάσεων mp² ¹S₀ υπαγορεύεται από την επιθυμία να είναι σχετικά μικρή η ενέργεια του φωτονίου ώστε να ευνοηθεί η (μονοφωτονική ή πολυφωτονική) ακτινοβολητική τους σύζευξη με υψηλότερα διεγερμένες (αυτοϊονιζόμενες) όπως επίσης και με χαμηλότερα (δέσμιες) καταστάσεις. Αναμένεται ότι τέτοια σχήματα κλιμακωτής διέγερσης θα ευνοήσουν την απορρόφηση σημαντικού αριθμού φωτονίων πάνω από το πρώτο κατώφλι ιονισμού μέσα στο ενεργειακό συνεχές, επιτρέποντας τη δημιουργία ιόντων σε διεγερμένες καταστάσεις οδηγώντας επακόλουθα σε πολύ αποδοτική παραγωγή διπλά φορτισμένων ιόντων. Οι πειραματικές παρατηρήσεις αποκαλύπτουν πως στην περιοχή των ns παλμών ο ρόλος των αυτοϊονιζόμενων καταστάσεων στη δυναμική της αλληελεπίδρασης ατόμου-laser αποτυπώνεται πιο καθαρά. Σε όλες τις περιπτώσεις ο κύριος μηχανισμός σχηματισμού διπλά φορτισμένων ιόντων είναι ο διαδοχικός ιονισμός μέσω διεγερμένων ιοντικών καταστάσεων, ενώ αντιπαράθεση των αποτελεσμάτων της παρούσας εργασίας με αυτά της υπάρχουσας βιβλιογραφίας προτείνει ότι η απορρόφηση υψηλού αριθμού φωτονίων πάνω από το κατώφλι ιονισμού, και για παλμούς διάρκειας ns, γίνεται κυρίως για φωτόνια σχετικά μικρής ενέργειας (σε σύγκριση με τα απλά και διπλά δυναμικά ιονισμού)

DNA damage, tumor mutational load and their impact on immune responses against cancer

Advances in immunotherapy have changed the therapeutic landscape in many malignancies. Immune checkpoint inhibitors have already received regulatory approval in melanomas, lung, renal and bladder carcinomas. A common feature of these neoplasms is the increased mutational load, related to a possible increase number of tumor neoantigens that are recognized by the immune system. The mechanisms that DNA damage could confer to the mutational load and the formation of neoantigens and how this could be exploited to advance our immunotherapeutic strategies is discussed in this review. © Annals of Translational Medicine

Systemic therapy in cervical cancer: 30 years in review

Advanced-inoperable cervical cancer is a challenging entity due to increased percentage of locoregional and distant recurrences. Furthermore, recurrent cervical cancer not amenable to radical treatment as well as de novo metastatic disease are considered incurable with dismal prognosis. Well-designed clinical trials conducted during the last 30 years have revealed the active chemotherapeutic agents as well as their optimal combinations. The rational approach that has led to the current treatment algorithms as well as the introduction of targeted therapies based on the knowledge of the molecular pathogenesis of the disease are discussed in this review. © 2019 Elsevier B.V