DEVELOPMENT OF MOUSE MODELS OF ORAL SQUAMOUS CELL CARCINOMA (OSCC) METASTASIS FOR THE EVALUATION OF EMERGING ANTI-METASTATIC NANOMEDICINE DRUGS

Oral Squamous Cell Carcinoma (OSCC) is included in the Head and Neck Squamous Cell Carcinoma (HNSCC) group, which is the sixth most common cancer diagnosed worldwide. While the locoregional control has been increased thanks to the combination therapy, the incidence of distant metastasis is increasing. Nanomedicine therapies have been clinically approved for the treatment of several types of cancers and were used in few clinical trials on HNSCC patients. However, the efficacy of nanomedicine therapies was limited, especially for the treatment of metastatic OSCC. In the preclinical setting, more advanced nanomedicine platforms have been developed against metastatic cancers. One of this platform, iNPG-pDox, obtained promising results against lung metastasis in a preclinical model of breast cancer. The lungs are the most common site of distant metastasis reported in OSCC and there is an unmet need for novel therapies targeting distant metastasis. The aim of the present work was to establish two preclinical models of OSCC lung metastasis by orthotopic and tail vein injection of OSCC cells and to perform preliminary in vitro evaluations of pDox nanoparticles in two cell lines of metastatic OSCC (HSC-3 and HSC-3 M1, isolated from HSC- 3 lung metastases). In vitro, pDox nanoparticles were able to effectively kill both HSC-3 and HSC-3 M1 cells, without any significant difference between the two cell lines. In vivo, lung metastases of OSCC were observed in both preclinical models. In particular, the orthotopic model also developed regional lymph node metastases, characteristic of metastatic growth observed in OSCC patients. The other model obtained by tail vein injection presented only lung metastases. Therefore, orthotopic models should be preferred to non-orthotopic models for the preclinical evaluation of anti-metastatic nanomedicine therapies such as iNPG-pDox in OSCC. Moreover, such preclinical model of OSCC lung metastasis may be used to investigate the molecular mechanisms of OSCC regional and distant metastasis, which are still poorly understood

PIXE and ToF-SIMS analysis of streaker samplers filters

This paper presents methodological innovations introduced in the characterisation of urban aerosol collected in Italy in a recent campaign. Two complementary ion beam analysis (IBA) techniques were used to analyse Nuclepore filters used in continuous streaker samplers to collect airborne particles in four Italian towns. Na to Pb elemental concentrations were obtained by particle induced X-ray emission (PIXE), while time of flight secondary ion mass spectrometry (ToF-SIMS) produced, on the same samples, time trends for several elements and molecular fragments. In addition, light attenuation measurements were used as a tracer for black carbon. The data produced by these three techniques was merged into a unique data set to address the characterisation of particulate matter sources. Correlations between elemental concentration trends (PIXE) and relative trends for molecular fragments (ToF-SIMS) and black carbon (light attenuation) have been studied by cluster and principal component analysis

Nanomedicine, an emerging therapeutic strategy for oral cancer therapy

Oral cavity and oropharyngeal carcinomas (oral cancer) represents a significant cause of morbidity and mortality. Despite efforts in improving early diagnosis and treatment, the 5-year survival rate of advanced stage of the disease is less than 63%. The field of nanomedicine has offered promising diagnostic and therapeutic advances in cancer. Indeed, several platforms have been clinically approved for cancer therapy, while other promising systems are undergoing exploration in clinical trials. With its ability to deliver drugs, nucleic acids, and MRI contrast agents with high efficiency, nanomedicine platforms offer the potential to improve drug efficacy and tolerability. The aim of the present mini-review is to summarize the current preclinical status of nanotechnology systems for oral cancer therapy. The nanoplatforms for delivery of chemopreventive agents presented herein resulted in significantly higher anti-tumor activity than free forms of the drug, even against a chemo-resistant cell line. Impressive results have also been obtained using nanoparticles to deliver chemotherapeutics, resulting in reduced toxicity both in vitro and in vivo. Nanoparticles have also led to improvements in efficacy of photodynamic therapies through the development of targeted magnetic nanoparticles. Finally, gene therapy using nanoparticles demonstrated promising results specifically with regards to inhibition of gene expression. Of the few in vivo studies that have been reported, many of these used animal models with several limitations, which will be discussed herein. Lastly, we will discuss several future perspectives in oral cancer nanoparticle-based therapy and the development of appropriate animal models, distinguishing between oral cavity and oropharyngeal carcinoma

A summertime investigation on urban PM fine and coarse fractions using hourly elemental concentration data series

The summertime composition of particulate matter in the atmosphere of some Italian towns (Florence, Genoa and Milan) has been studied by means of Ion Beam Analysis (IBA) techniques. The aerosol has been collected simultaneously by two-stage continuous streaker samplers, which separate and collect the PM10 particulate matter in two fractions. The hourly concentrations in air of about 20 elements have been extracted in the fine and coarse fractions of PM10 by Particle Induced X-ray (and Gamma-ray) Emission, PIXE (and PIGE) analysis. Absolute Principal Component Factor Analysis (APCFA) has been used to obtain the apportionment of the sources of particulate matter

Platelet-rich plasma to treat experimentally-induced skin wounds in animals : a systematic review and meta-analysis

The objective of the study was to review current literature to determine whether the topical application of platelet-rich plasma (PRP) promotes healing in experimentally-induced full-thickness skin wounds in animals. The hypothesis was that the adjunct of PRP has a positive effect on wound healing. An electronic search was carried out on the following databases: Web of Science, Cochrane Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information Network. No publication date nor language restrictions were applied. Randomised and not randomised controlled clinical trials comparing PRP with placebo or with other treatments were included. The reduction of open wound area in PRP-treated (test) wounds compared to control wounds was the primary outcome. Secondary outcomes were healing time and number of healed cases in test group compared to control. The following effect sizes were calculated: the Hedges\u2019 g for continuous variables; the odds ratio for binary data. Eighteen controlled clinical trials were included in the qualitative and quantitative synthesis, with a total of 661 wounds. All studies were published in the period 2007\u20132016. Eight studies were carried out on rodent/lagomorph mammals and 10 on non-rodent/lagomorph mammals. In all included studies, control wounds underwent placebo or were left untreated. The PRP group showed a better healing performance than the control group in each outcome. The effect size was statistically significant considering the primary outcome and the overall aggregation of the three outcomes. The effect size, although in favour of the treatment with PRP, was not significant considering the healing time and the number of healings. The overall heterogeneity was mild or moderate. Five studies reported a high risk of selection bias. The publication bias was always mild or absent. The results support the hypothesis of the positive effects of the PRP when compared to control groups in the treatment of experimentally-induced full-thickness skin wounds in animals. PRP can therefore be considered an effective adjunctive therapy in stimulating second intention healing of acute wounds in healthy animals

Characterization of atmospheric aerosols at Monte Cimone, Italy, during summer 2004: Source apportionment and transport mechanisms

Atmospheric aerosols in the PM10 and PM1 fractions have been sampled at the Global Atmospheric Watch station Mount Cimone, Italy (2165 m above mean sea level) for 3 months during summer 2004, and simultaneous size distributions have been derived by means of an optical particle counter. Samples have been analyzed by X-ray fluorescence, ion chromatography, and thermal-optical methodology in order to quantify their elemental, ionic, and carbonaceous constituents. The concentration of PM10 was 16.1 \ub1 9.8 mg m3 (average and standard deviation). Source apportionment allowed us to identify, quantify and characterize the following aerosol classes: anthropogenic pollution (10 mg m3), mineral dust (4 mg m3), and sea salt (0.2 mg m3). Pollution has been further split into ammonium sulfate (44%), organic matter (42%), and other compounds (14%). The nitrate/sulfate ratio in the polluted aerosol was 0.1. Fine particles have been completely related to the polluted aerosol component, and they represented 70% in weight of pollution. Coarse particles characterized the dust and salt components, and crustal oxides have been found to be the largest responsible for the aerosol concentration variations that occurred during the campaign. Nitrate has also been found in the coarse particles, representing 10% of mineral dust. The analysis of the transport mechanisms responsible for aerosol fluctuations permitted us to identify the origin of the major aerosol components: Pollution has been ascribed to regional transport driven by boundary layer meteorology, whereas mineral dust has been related to long-range transport events originating in the Sahara and Sahel. A particularly significant Saharan episode has been identified on 10 August 2004 (PM10 daily concentration, 69.9 mg m3). Average elemental ratios for the African dust events were as follows: Si/Al = 2.31, Fe/Ca = 0.94, Ca/Al = 0.90, K/Ca = 0.44, Ti/Ca = 0.11, and Ti/Fe = 0.12