Combined Analysis of HPV DNA and p16INK4a Expression to Predict Prognosis in ASCUS and LSIL Pap Smears

Human papillomavirus (HPV) is known to play an important etiological role in the genesis of cervical cancer, but only a very small proportion of infected women develop invasive cervical cancer. The purpose of cervical cancer prevention is early diagnosis of its precursors. The molecular detection of HPV DNA as a diagnostic test to cervical carcinogenesis gave a low positive predictive value as compared to the use of biomarkers. p16INK4a has been proposed as putative surrogate biomarkers that would allow identification of dysplastic cervical epithelia. Serial consecutive cervical smears were test for high-risk HPV, stained with immunocytochemistry for p16INK4a and followed-up for 36 months. The aim of the study was to evaluate the immunohistochemical expression of p16INK4a as a marker of progression risk in low-grade dysplastic lesions of the cervix uteri. In the present series, significant p16 overexpression was observed in the group that progressed from low to high-grade squamous intraepithelial lesion when compared with the group that did not progress. In conclusion, overexpression of p16INK4a acts as potential biomarkers for cervical cancer progression from premalignant lesions

Multimodal lung cancer screening using the ITALUNG Biomarker Panel and Low Dose Computed Tomography. Results of the ITALUNG biomarker study

Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1356), in which samples of blood and sputum were analysed for plasma DNA quantification (cut off 5ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71%% and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%

Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection

Abstract Changes in cervico-vaginal microbiota with Lactobacillus depletion and increased microbial diversity facilitate human papillomavirus (HPV) infection and might be involved in viral persistence and cancer development. To define the microbial Community State Types (CSTs) associated with high-risk HPV−persistence, we analysed 55 cervico-vaginal samples from HPV positive (HPV+) women out of 1029 screened women and performed pyrosequencing of 16S rDNA. A total of 17 samples from age-matched HPV negative (HPV−) women were used as control. Clearance or Persistence groups were defined by recalling women after one year for HPV screening and genotyping. A CST IV subgroup, with bacterial genera such as Gardnerella, Prevotella, Megasphoera, Atopobium, frequently associated with anaerobic consortium in bacterial vaginosis (BV), was present at baseline sampling in 43% of women in Persistence group, and only in 7.4% of women in Clearance group. Atopobium genus was significantly enriched in Persistence group compared to the other groups. Sialidase-encoding gene from Gardnerella vaginalis, involved in biofilm formation, was significantly more represented in Persistence group compared to the other groups. Based on these data, we consider the CST IV-BV as a risk factor for HPV persistence and we propose Atopobium spp and sialidase gene from G. vaginalis as microbial markers of HPV−persistence

A feasibility study of the use of the AutoPap screening system as a primary screening and location-guided rescreening device

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Givinostat-Liposomes: Anti-Tumor Effect on 2D and 3D Glioblastoma Models and Pharmacokinetics

Glioblastoma is the most common and aggressive brain tumor, associated with poor prognosis and survival, representing a challenging medical issue for neurooncologists. Dysregulation of histone-modifying enzymes (HDACs) is commonly identified in many tumors and has been linked to cancer proliferation, changes in metabolism, and drug resistance. These findings led to the development of HDAC inhibitors, which are limited by their narrow therapeutic index. In this work, we provide the proof of concept for a delivery system that can improve the in vivo half-life and increase the brain delivery of Givinostat, a pan-HDAC inhibitor. Here, 150-nm-sized liposomes composed of cholesterol and sphingomyelin with or without surface decoration with mApoE peptide, inhibited human glioblastoma cell growth in 2D and 3D models by inducing a time-and dose-dependent reduction in cell viability, reduction in the receptors involved in cholesterol metabolism (from −25% to −75% of protein levels), and reduction in HDAC activity (−25% within 30 min). In addition, liposome-Givinostat formulations showed a 2.5-fold increase in the drug half-life in the bloodstream and a 6-fold increase in the amount of drug entering the brain in healthy mice, without any signs of overt toxicity. These features make liposomes loaded with Givinostat valuable as potential candidates for glioblastoma therapy

Distribution of high and low risk HPV types by cytological status: a population based study from Italy

<p>Abstract</p> <p>Background</p> <p>HPV type distribution by cytological status represents useful information to predict the impact of mass vaccination on screening programs.</p> <p>Methods</p> <p>women aged from 25 to 64 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11.</p> <p>Results</p> <p>3410 women had a valid HCII and Pap-test. The prevalence of HR and LR infections was 7.0% and 3.6%, 29.1% and 13.7%, 68.1% and 31.9%, 60.0% and 0.0%, 65.0% and 12.0%, for negative, ASC-US, L-SIL, ASC-H and H-SIL cytology, respectively. The fraction of ASC-US+ cytology due to HPV 16 and 18 ranged from 11.2 (HPV 16/18 alone) to 15.4% (including HPV 16/18 in co-infection with other virus strains), and that due to HPV 6 and 11 ranged from 0.2% (HPV 6/11 alone) to 0.7% (including HPV 6/11 in co-infection with other LR virus strains).</p> <p>Conclusions</p> <p>mass vaccination with bivalent or quadrivalent HPV vaccine would modestly impact on prevalence of abnormal Pap-test in screening.</p

Fecal Collection and Stabilization Methods for Improved Fecal DNA Test for Colorectal Cancer in a Screening Setting

Early detection of CRC and adenomas reduces CRC-related mortality. The optimal screening test for CRC is still a subject of debate, and molecular stool sample analysis could provide a valid alternative to conventional methods in terms of compliance and practicability. Seven fecal DNA storage systems were evaluated in two successive phases. In the first phase of the study was selected the preservative buffer able to ensure the best human DNA recovery. In the second phase was evaluated human DNA stability, amplificability and integrity in DNA extracted from selected buffer. Results showed that the best performance was obtained in samples stored in 100 mM EDTA buffer and Genefec buffer. Likewise buffer addition yielded a significant increase in DNA stability and integrity without PCR inhibition, compared to the matched aliquots with no buffer added. Our study shows that samples collected in stabilization solution stabilize DNA so that intact nucleic acids, are more effectively detectable in the molecular assay. DNA buffer preservation and storage conditions could be useful to guarantee the most consistent yield in human DNA. Stabilization buffer addition to stool samples prior to transport presents an easily implemented solution that appears to be highly effective. Overall DNA extracted from faeces preserved in preservative buffer can feasibility been used for molecular analysis leading to an increase of assay sensitivity

Glass fabric reinforced cementitious matrix: Tensile properties and bond performance on masonry substrate

Fibre-reinforced composite materials have gained an increasing success, mostly for strengthening, retrofitting, and repairing existing structures. However some problems may arise with the use of traditional FRP (Fiber Reinforced Polymer), particularly when the compatibility with the substrate and the reversibility of the intervention are required, as in case of cultural heritage buildings, or specific exposition conditions may compromise the long term effectiveness of the reinforcement, as in presence of high temperature and humidity. Starting from these considerations new composite materials are emerging as a more effective solution in certain fields of application and under specific service conditions; in this context, mortar-based composite systems, consisting of one or more layers of uni- or bi-directional fibre nets embedded in cement/lime-based matrix layers, can be used as reinforcement of both concrete and masonry structures. However, the research work dealing with these emerging materials and their performances when used as a strengthening system for existing structures is still limited. Both experimental and theoretical investigations are needed in order to deliver reliable design methodologies. In this work, a Round Robin Test aimed to the characterization of both bond with the existing substrate and tensile performance of glass fabric (in the form of grids) coupled with inorganic mortar matrices is presented. The investigation was conducted at fifteen laboratories involved in the RILEM Technical Committee 250-CSM (Composites for the Sustainable Strengthening of Masonry). With the aim of studying the bond behaviour between Fabric Reinforced Cementitious Matrix (FRCM) composites and masonry substrate, single and double lap shear tests were carried out on brick-masonry prisms. Results provide useful informations about the mechanical properties, the bond capacity and the failure mechanisms of different commercially available glass FRCM systems. Finally, critical aspects are underlined to address the progress of research work.info:eu-repo/semantics/publishedVersio