Extracellular vesicle-based nucleic acid delivery: Current advances and future perspectives in cancer therapeutic strategies

Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential therapeutic systems in many diseases, including cancer, due to their low immunogenicity, non-toxicity, and elevated bioavailability. They might serve as safe and effective vehicles for the transport of therapeutic molecules to specific tissues and cells. In this review, we focus on EVs as a vehicle for gene therapy in cancer. We describe recent developments in EV engineering to achieve efficient intracellular delivery of cancer therapeutics and avoid off-target effects, to provide an overview of the potential applications of EV-mediated gene therapy and the most promising biomedical advances

Single-Cell Photothermal Analysis Induced by MoS2 Nanoparticles by Raman Spectroscopy

Two-dimensional nanomaterials, such as MoS2 nanosheets, have been attracting increasing attention in cancer diagnosis and treatment, thanks to their peculiar physical and chemical properties. Although the mechanisms which regulate the interaction between these nanomaterials and cells are not yet completely understood, many studies have proved their efficient use in the photothermal treatment of cancer, and the response to MoS2 nanosheets at the single-cell level is less investigated. Clearly, this information can help in shedding light on the subtle cellular mechanisms ruling the interaction of this 2D material with cells and, eventually, to its cytotoxicity. In this study, we use confocal micro-Raman spectroscopy to reconstruct the thermal map of single cells targeted with MoS2 under continuous laser irradiation. The experiment is performed by analyzing the water O-H stretching band around 3,400 cm−1 whose tetrahedral structure is sensitive to the molecular environment and temperature. Compared to fluorescence-based approaches, this Raman-based strategy for temperature measurement does not suffer fluorophore instability, which can be significant under continuous laser irradiation. We demonstrate that irradiation of human breast cancer MCF7 cells targeted with MoS2 nanosheets causes a relevant photothermal effect, which is particularly high in the presence of MoS2 nanosheet aggregates. Laser-induced heating is strongly localized near such particles which, in turn, tend to accumulate near the cytoplasmic membrane. Globally, our experimental outcomes are expected to be important for tuning the nanosheet fabrication process

A six sigma DMAIC methodology as a support tool for health technology assessment of two antibiotics

Health Technology Assessment (HTA) and Six Sigma (SS) have largely proved their reliability in the healthcare context. The former focuses on the assessment of health technologies to be introduced in a healthcare system. The latter deals with the improvement of the quality of services, reducing errors and variability in the healthcare processes. Both the approaches demand a detailed analysis, evidence-based decisions, and efficient control plans. In this paper, the SS is applied as a support tool for HTA of two antibiotics with the final aim of assessing their clinical and organizational impact in terms of postoperative Length Of Stay (LOS) for patients undergoing tongue cancer surgery. More specifically, the SS has been implemented through its main tool, namely the DMAIC (Define, Measure, Analyse, Improve, Control) cycle. Moreover, within the DMAIC cycle, a modelling approach based on a multiple linear regression analysis technique is introduced, in the Control phase, to add complementary information and confirm the results obtained by the statistical analysis performed within the other phases of the SS DMAIC. The obtained results show that the proposed methodology is effective to determine the clinical and organizational impact of each of the examined antibiotics, when LOS is taken as a measure of performance, and guide the decision-making process. Furthermore, our study provides a systematic procedure which, properly combining different and well-assessed tools available in the literature, demonstrated to be a useful guidance for choosing the right treatment based on the available data in the specific circumstance

A health technology assessment between two pharmacological therapies through Six Sigma: the case study of bone cancer

Purpose: Head and neck cancers are multi-factorial diseases that can affect many sides of people's life and are due to a lot of risk factors. According to their characteristics, the treatment can be surgical, use of radiation or chemotherapy. The use of a surgical treatment can lead to surgical infections that are a main theme in medicine. At the University hospital of Naples “Federico II”, two antibiotics were employed to tackle the issue of the infections and they are compared in this paper to find which one implies the lowest length of hospital stay (LOS) and the reduction of infections. Design/methodology/approach: The Six Sigma methodology and its problem-solving strategy DMAIC (define, measure, analyse, improve, control), already employed in the healthcare sector, were used as a tool of a health technology assessment between two drugs. In this paper the DMAIC roadmap is used to compare the Ceftriaxone (administered to a group of 48 patients) and the association of Cefazolin plus Clindamycin (administered to a group of 45 patients). Findings: The results show that the LOS of patients treated with Ceftriaxone is lower than those who were treated with the association of Cefazolin plus Clindamycin, the difference is about 41%. Moreover, a lower number of complications and infections was found in patients who received Ceftriaxone. Finally, a greater number of antibiotic shifts was needed by patients treated with Cefazolin plus Clindamycin. Research limitations/implications: While the paper enhances clearly the advantages for patients' outcomes regarding the LOS and the number of complications, it did not analyse the costs of the two antibiotics. Practical implications: Employing the Ceftriaxone would allow the Department of Maxillofacial Surgery to obtain lower LOS and a limited number of complications/infections for recovered patients, consequently reducing the hospitalization costs. Originality/value: There is a double value in this paper: first of all, the comparison between the two antibiotics gives an answer to one of the main issues in medicine that is the reduction of hospital-acquired infections; secondly, the Six Sigma through its DMAIC cycle can be employed also to compare two biomedical technologies as a tool of health technology assessment studies

Three-dimensional superimposition for patients with facial palsy: an innovative method for assessing the success of facial reanimation procedures

Facial palsy is a severe condition that may be ameliorated by facial reanimation, but there is no consensus about how to judge its success. In this study we aimed to test a new method for assessing facial movements based on 3-dimensional analysis of the facial surfaces. Eleven patients aged between 42 and 77 years who had recently been affected by facial palsy (onset between 6 and 18 months) were treated by an operation based on triple innervation: the masseteric to temporofacial nerve branch, 30% of the hypoglossal fibres to the cervicofacial nerve branch, and the contralateral facial nerve through two cross-face sural nerve grafts. Each patient had five stereophotogrammetric scans: at rest, smiling on the healthy side (facial stimulus), biting (masseteric stimulus), moving the tongue (hypoglossal stimulus), and corner-of-the-mouth smile (Mona Lisa). Each scan was superimposed onto the facial model of the "rest" position, and the point-to-point root mean square (RMS) value was automatically calculated on both the paralysed and the healthy side, together with an index of asymmetry. One-way and two-way ANOVA tests, respectively, were applied to verify the significance of possible differences in the RMS and asymmetry index according to the type of stimulus (p = 0.0329) and side (p < 0.0001). RMS differed significantly according to side between the facial stimulus and the masseteric one on the paralysed side (p = 0.0316). Facial stimulus evoked the most asymmetrical movement, whereas the masseteric produced the most symmetrical expression. The method can be used for assessing facial movements after facial reanimation

Performance of a deep learning algorithm for the evaluation of CAD-RADS classification with CCTA

Background and aims: Artificial intelligence (AI) is increasing its role in diagnosis of patients with suspicious coronary artery disease. The aim of this manuscript is to develop a deep convolutional neural network (CNN) to classify coronary computed tomography angiography (CCTA) in the correct Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Methods: Two hundred eighty eight patients who underwent clinically indicated CCTA were included in this single-center retrospective study. The CCTAs were stratified by CAD-RADS scores by expert readers and considered as reference standard. A deep CNN was designed and tested on the CCTA dataset and compared to on-site reading. The deep CNN analyzed the diagnostic accuracy of the following three Models based on CAD-RADS classification: Model A (CAD-RADS 0 vs CAD-RADS 1–2 vs CAD-RADS 3,4,5), Model 1 (CAD-RADS 0 vs CAD-RADS&gt;0), Model 2 (CAD-RADS 0–2 vs CAD-RADS 3–5). Time of analysis for both physicians and CNN were recorded. Results: Model A showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 47%, 74%, 77%, 46% and 60%, respectively. Model 1 showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 66%, 91%, 92%, 63%, 86%, respectively. Conversely, Model 2 demonstrated the following sensitivity, specificity, negative predictive value, positive predictive value and accuracy: 82%, 58%, 74%, 69%, 71%, respectively. Time of analysis was significantly lower using CNN as compared to on-site reading (530.5 ± 179.1 vs 104.3 ± 1.4 sec, p=0.01) Conclusions: Deep CNN yielded accurate automated classification of patients with CAD-RADS

Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells

<p>Abstract</p> <p>Background:</p> <p>BPA (bisphenol A or 2,2-bis(4-hydroxy-phenol)propane) is present in the manufacture of polycarbonate plastic and epoxy resins, which can be used in impact-resistant safety equipment and baby bottles, as protective coatings inside metal food containers, and as composites and sealants in dentistry. Recently, attention has focused on the estrogen-like and carcinogenic adverse effects of BPA. Thus, it is necessary to investigate the cytotoxicity and apoptosis-inducing activity of this compound.</p> <p>Methods:</p> <p>Cell cycle, apoptosis and differentiation analyses; western blots.</p> <p>Results:</p> <p>BPA is able to induce cell cycle arrest and apoptosis in three different acute myeloid leukemias. Although some granulocytic differentiation concomitantly occurred in NB4 cells upon BPA treatment, the major action was the induction of apoptosis. BPA mediated apoptosis was caspase dependent and occurred by activation of extrinsic and intrinsic cell death pathways modulating both FAS and TRAIL and by inducing BAD phosphorylation in NB4 cells. Finally, also non genomic actions such as the early decrease of both ERK and AKT phosphorylation were induced by BPA thus indicating that a complex intersection of regulations occur for the apoptotic action of BPA.</p> <p>Conclusion:</p> <p>BPA is able to induce apoptosis in leukemia cells via caspase activation and involvement of both intrinsic and extrinsic pathways of apoptosis.</p