Basal cell carcinoma: 10-year experience with electrochemotherapy

BACKGROUND: Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. METHODS: In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. RESULTS: Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Primary presentation (p = 0.004), tumor size <3 cm (p < 0.001), well-defined borders (p = 0.021), absence of tumor ulceration (p = 0.001), non-aggressive BCC histology (p = 0.046) and age 6469 years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (p 64 0.001). CONCLUSIONS: One or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation. Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered)

Fe/GeTe(111) heterostructures as an avenue towards 'ferroelectric Rashba semiconductors'-based spintronics

By performing density functional theory (DFT) and Green's functions calculations, complemented by X-ray Photoemission Spectroscopy, we investigate the electronic structure of Fe/GeTe(111), a prototypical ferromagnetic/Rashba-ferroelectric interface. We reveal that such system exhibits several intriguing properties resulting from the complex interplay of exchange interaction, electric polarization and spin-orbit coupling. Despite a rather strong interfacial hybridization between Fe and GeTe bands, resulting in a complete suppression of the surface states of the latter, the bulk Rashba bands are hardly altered by the ferromagnetic overlayer. This could have a deep impact on spin dependent phenomena observed at this interface, such as spin-to-charge interconversion, which are likely to involve bulk rather than surface Rashba states.Comment: 8 pages, 4 figure

The defining ideals of conjugacy classes of nilpotent matrices and a conjecture of Weyman

Tanisaki introduced generating sets for the defining ideals of the schematic intersections of the closure of conjugacy classes of nilpotent matrices with the set of diagonal matrices. These ideals are naturally labeled by integer partitions. Given such a partition λ, we define several methods to produce a reduced generating set for the associated ideal Iλ. For particular shapes we find nice generating sets. By comparing our sets with some generating sets of Iλ arising from a work of Weyman, we find a counterexample to a related conjecture of Weyman.Natural Sciences and Engineering Research Council of CanadaMinisterio de Educación y Cienci

Resolutions of De Concini-Procesi ideals of hooks

We find a minimal generating set for the defining ideal of the schematic intersection of the set of diagonal matrices with the closure of the conjugacy class of a nilpotent matrix indexed by a hook partition. The structure of this ideal allows us to compute its minimal free resolution and give an explicit description of the graded Betti numbers, and study its Hilbert series and regularity

Importin-beta and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function

Protein conjugation with small ubiquitin-related modifier (SUMO) is a post-translational modification that modulates protein interactions and localisation. RANBP2 is a large nucleoporin endowed with SUMO E3 ligase and SUMO-stabilising activity, and is implicated in some cancer types. RANBP2 is part of a larger complex, consisting of SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for the GTPase RAN. During mitosis, the RANBP2–SUMO-RANGAP1 complex localises to the mitotic spindle and to kinetochores after microtubule attachment. Here, we address the mechanisms that regulate this localisation and how they affect kinetochore functions. Using proximity ligation assays, we find that nuclear transport receptors importin-β and CRM1 play essential roles in localising the RANBP2–SUMO-RANGAP1 complex away from, or at kinetochores, respectively. Using newly generated inducible cell lines, we show that overexpression of nuclear transport receptors affects the timing of RANBP2 localisation in opposite ways. Concomitantly, kinetochore functions are also affected, including the accumulation of SUMO- conjugated topoisomerase-IIα and stability of kinetochore fibres. These results delineate a novel mechanism through which nuclear transport receptors govern the functional state of kinetochores by regulating the timely deposition of RANBP2

Preliminary data about Paraoxonase-1 (PON-1) as a maker for Feline Infectious Peritonitis (FIP)

Feline infectious peritonitis (FIP) is a fatal disease in which the definitive diagnosis is achieved by immunohistochemistry (IHC) on post-mortem biopsies. The clinical suspicion is aroused by signalment, clinical signs and several laboratory tests, including alpha-1-acid glycoprotein measurement for which the only validated kit is no longer available. Paraoxonase-1 (PON-1) is a serum enzyme with antioxidant activity, considered as a negative acute phase protein in several species. Since inflammation plays a major role in FIP, and due to the high susceptibility of cats to oxidation, it could be of great interest the evaluation of this enzyme as a diagnostic marker for FIP. The aim of this study was to measure paraoxonase-1 in healthy cats and cats with clinical signs consistent with FIP (both wet or dry form), in order to evaluate the utility of this parameter in the diagnosis of FIP. Sixty-two cats were enrolled and divided into three groups: healthy (n=16), confirmed FIP (n=22) and NON FIP with similar clinical signs (n=24). PON-1 was measured on serum, using a paraoxon-based enzymatic method, already validated in cats. Results showed significantly lower PON-1 activity in FIP cats (mean ± SD: 29.1 ± 16.3 U/mL; median: 24.4; IQR: 16.6-38.3), compared with healthy cats (90.1 ± 24.1 U/mL; median: 86.0; IQR: 76.7-105.7; P&lt;0.001) and with “non-FIP” cats (55.9 ± 28.3 U/mL; median: 51.9; IQR: 35.7-68.8, P&lt;0.001). A significant difference was also found between healthy and “non-FIP” cats (P&lt;0.001). The receiver operating characteristic (ROC) curve demonstrated that PON-1 may discriminate cats with and without FIP (Fig.1). At the cut-off that maximizes the diagnostic power of the test, sensitivity and specificity for FIP were 77% each, suggesting that PON-1 may be a reliable marker in association with other confirmatory tests and with signs consistent with the disease

The LRE Map disclosed

This paper describes a serialization of the LRE Map database according to the RDF model. Due to the peculiar nature of the LRE Map, many ontologies are necessary to model the map in RDF, including newly created and reused ontologies. The importance of having the LRE Map in RDF and its connections to other open resources is also addressed

Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites. We found that the most stable G-quadruplexes were in the promoter region of genes belonging to definite functional categories. Actual G-quadruplex folding of four selected sequences was assessed by biophysical and biomolecular techniques: all molecules formed stable G-quadruplexes, which were further stabilized by two G-quadruplex ligands. These compounds inhibited Mycobacterium tuberculosis growth with minimal inhibitory concentrations in the low micromolar range. These data support formation of Mycobacterium tuberculosis G-quadruplexes in vivo and their potential regulation of gene transcription, and prompt the use of G4 ligands to develop original antitubercular agents