Intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer

This article reviews intravesical application of electromotive drug administration (EMDA) for the treatment of bladder cancer and the evidence in support of intravesical passive diffusion chemotherapy in the management of non-muscle invasive bladder cancer. Two recently published randomised trials adopting protocols that use EMDA to enhance urothelial transport of intravesical mitomycin-C showed it provided a therapeutical advantage and suggested that intravesical passive diffusion administration of chemothera-peutic drugs may be suboptimal. Further studies are required to demonstrate feasibility and advantage of intravesical EMDA of mitomycin-C in the wider uro-oncological community

Risk factors for peri-operative high-grade complications in patients with prostate cancer treated with robotic radical prostatectomy

Aim of our study was to evaluate the risk factors for high-grade complications (Clavien Classification System ≥3a) in patients treated with with robotic assisted radical prostatectomy (RARP). Between 2012 and 2017, a consecutive series of patients with prostate cancer were treated with robotic radical prostatectomy (RRP). Demographic, clinical and histological characteristics of the patients were recorded. Histological specimens were graded according to the new PGG classification. Complications were classified according to the modified Clavien classification system (CCS). Logistic regression analysis was performed to evaluate the risk of high grade complications (CCS>3a)

Mortars and screeds containing polymeric aggregates recycled from industrial waste and tyres

Given the growing market demand for products containing recycled components dictated by European and national policies, the presented research aimed to replace part of the natural aggregates in construction mortars and screeds with recycled polymeric aggregates (RA): industrial technopolymers and ground tyre rubber (GTR). The strategy involved the substitution of aggregates, both in market products and in the design of standard mortars, first verifying the CE certification and then the achievable mechanical performance. The whole process has been discussed in the context of a circular approach, extended to the analysis of the aggregate production phase, highlighting factors that influence environmental and economic impacts

Notulae to the Italian alien vascular flora: 7

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, and status changes for Italy or for Italian administrative regions of taxa in the genera Abies, Actinidia, Alooe, Amaryllis, Anredera, Arctotheca, Bidens, Cardiospermum, Celosia, Commelina, Cotoneaster, Cyclamen, Eclipta, Euphorbia, Grevillea, Hedera, Hibiscus, Impatiens, Juglans, Kalanchoe, Koelreuteria, Lindernia, Melinis, Myriophyllum, Nandina, Nicotiana, Oenothera, Oxalis, Parthenocissus, Phoenix, Phyllanthus, Physalis, Plumbago, Pteris, Quercus, Setaria, Symphytum, Tagetes, and Washingtonia. Nomenclatural and distribution updates, published elsewhere are provided as Suppl. material 1

Molecular and Functional Characterization of the Odorant Receptor2 (OR2) in the Tiger Mosquito Aedes albopictus

In mosquitoes, the olfactory system plays a crucial role in many types of behavior, including nectar feeding, host preference selection and oviposition. Aedes albopictus, known also as the tiger mosquito, is an anthropophilic species, which in the last few years, due to its strong ecological plasticity, has spread throughout the world. Although long considered only a secondary vector of viruses, the potential of its vector capacity may constitute a threat to public health. Based on the idea that an improved understanding of the olfactory system of mosquitoes may assist in the development of control methods that interfere with their behavior, we have undertaken a study aimed at characterizing the A. albopictus Odorant Receptors. Here we report the identification, cloning and functional characterization of the AalOR2 ortholog, that represents the first candidate member of the odorant receptor (OR) family of proteins from A. albopictus. AalOR2 is expressed in the larval heads and antennae of adults. Our data indicate that A. albopictus OR2 (AalOR2) shares a high degree of identity with other mosquito OR2 orthologs characterized to date, confirming that OR2 is one of the most conserved mosquito ORs. Our data indicate that AalOR2 is narrowly tuned to indole, and inhibited by (-)-menthone. In agreement with this results, these two compounds elicit two opposite effects on the olfactory-based behavior of A. albopictus larvae, as determined through a larval behavioral assay. In summary, this work has led to the cloning and de-orphaning of the first Odorant Receptor in the tiger mosquito A. albopictus. In future control strategies this receptor may be used as a potential molecular target

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

Background: More effective chemotherapies are urgently needed for bladder cancer, a major cause of morbidity and mortality worldwide. We therefore explored the efficacy of the combination of gemcitabine and AZD7762, a checkpoint kinase 1/2 (CHK1/2) inhibitor, for bladder cancer. Methods: Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in urothelial cancer cell lines and various non-malignant urothelial cells treated with gemcitabine and AZD7762. DNA damage was assessed by ?H2A.X and 53-BP1 staining and checkpoint activation was followed by Western blotting. Pharmacological inhibition of CHK1 and CHK2 was compared to downregulation of either CHK1 or CHK2 using siRNAs. Results: Combined use of gemcitabine and AZD7762 synergistically reduced urothelial carcinoma cell viability and colony formation relative to either single treatment. Non-malignant urothelial cells were substantially less sensitive to this drug combination. Gemcitabine plus AZD7762 inhibited cell cycle progression causing cell accumulation in S-phase. Moreover, the combination induced pronounced levels of apoptosis as indicated by an increase in the fraction of sub-G1 cells, in the levels of cleaved PARP, and in caspase 3/7 activity. Mechanistic investigations showed that AZD7762 treatment inhibited the repair of gemcitabine-induced double strand breaks by interference with CHK1, since siRNA-mediated depletion of CHK1 but not of CHK2 mimicked the effects of AZD7762. Conclusions: AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy

Cornelia-de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect

Cornelia de Lange syndrome is a multisystem developmental disorder typically caused by mutations in the gene encoding the cohesin loader NIPBL. The associated phenotype is generally assumed to be the consequence of aberrant transcriptional regulation. Recently, we identified a missense mutation in BRD4 associated with a Cornelia de Lange-like syndrome that reduces BRD4 binding to acetylated histones. Here we show that, although this mutation reduces BRD4-occupancy at enhancers it does not affect transcription of the pluripotency network in mouse embryonic stem cells. Rather, it delays the cell cycle, increases DNA damage signalling, and perturbs regulation of DNA repair in mutant cells. This uncovers a role for BRD4 in DNA repair pathway choice. Furthermore, we find evidence of a similar increase in DNA damage signalling in cells derived from NIPBL-deficient individuals, suggesting that defective DNA damage signalling and repair is also a feature of typical Cornelia de Lange syndrome