MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

<p>Abstract</p> <p>Background</p> <p>MFSD2A (major facilitator superfamily domain containing 2) gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer.</p> <p>Results</p> <p>Here we show that MFSD2A expression is strongly downregulated in non-small cell lung cancer cell lines of different histotypes and in primary lung adenocarcinomas. Experimental modulation of MFSD2A in lung cancer cells is associated with alteration of mRNA levels of genes involved in cell cycle control and interaction with the extracellular matrix. Exogenous expression of MFSD2A in lung cancer cells induced a G1 block, impaired adhesion and migration <it>in vitro</it>, and significantly reduced tumor colony number <it>in vitro </it>(4- to 27-fold, P < 0.0001) and tumor volume <it>in vivo </it>(~3-fold, P < 0.0001). siRNA knockdown studies in normal human bronchial epithelial cells confirmed the role of MFSD2A in G1 regulation.</p> <p>Conclusion</p> <p>Together these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.</p

Informing women about hormone replacement therapy: the consensus conference statement

Background: The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/ benefits. Methods: We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: A literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. Results: Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone therapy" should be the preferred definition. Conclusion: This CC led to the identification of specific information drawbacks. Women are exposed to messages that are often partial, non evidence-based nor transparently developed. The structured and participative methodology of this CC allowed a multidisciplinary perspective and a substantial lay people input

NKp46-expressing human gut-resident intraepithelial V\u3b41 T cell subpopulation exhibits high anti-tumor activity against colorectal cancer

\u3b3\u3b4 T cells account for a large fraction of human intestinal intraepithelial lymphocytes (IELs) endowed with potent anti-tumor activities. However, little is known about their origin, phenotype and clinical relevance in colorectal cancer (CRC). To determine \u3b3\u3b4 IEL gut-specificity, homing and functions, \u3b3\u3b4 T cells were purified from human healthy blood, lymph nodes, liver, skin, intestine either disease-free or affected by CRC or generated from thymic precursors. The constitutive expression of NKp46 specifically identifies a new subset of cytotoxic V\u3b41 T cells representing the largest fraction of gut-resident IELs. The ontogeny and gut-tropism of NKp46pos/V\u3b41 IELs depends both on distinctive features of V\u3b41 thymic precursors and gut-environmental factors. Either the constitutive presence of NKp46 on tissue-resident V\u3b41 intestinal IELs or its induced-expression on IL-2/IL-15 activated V\u3b41 thymocytes are associated with anti-tumor functions. Higher frequencies of NKp46pos/V\u3b41 IELs in tumor-free specimens from CRC patients correlate with a lower risk of developing metastatic III/IV disease stages. Additionally, our in vitro settings reproducing CRC tumor-microenvironment inhibited the expansion of NKp46pos/V\u3b41 cells from activated thymic precursors. These results parallel the very low frequencies of NKp46pos/V\u3b41 IELs able to infiltrate CRC, thus providing new insights to either follow-up cancer progression or develop novel adoptive cellular therapies

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB

Transform Autism Education - Final Report

The Transform Autism Education (TAE) project focused on the domain of ‘good autism practice’ in the education of pupils with autism in the UK, Greece and Italy with the overall objectives to:• Research good autism practice in education.• Create professional development programmes in Greece and Italy.• Enhance the knowledge and practice of school staff.• Facilitate the inclusion of autistic children in primary schools in those countries.Funded by the European Commission through Erasmus Plus Key Action 2, Strategic Partnerships scheme, and led by Principal Investigator Dr. Karen Guldberg, the project involved a range of Greek, Italian and UK partners. It employed the Autism Education Trust (AET) collaborative training schemes in the UK as a founding model. While the requirements of each country were distinct, and so necessitated careful adaptations of the materials to their specific needs, what united all aspects of the project was a desire to improve the educational inclusion of autistic children, as well as their general experiences in school and their outcomes

The Italian Network for Tumor Biotherapy (NIBIT): Getting together to push the field forward

As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20–22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bio-immunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a) molecular and cellular mechanisms of tumor escape; b) therapeutic antibodies and recombinant constructs; c) clinical trials up-date and new programs; d) National Cooperative Networks and their potential interactions; e) old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting

A European multi-language initiative to make the general population aware of independent clinical research: the European Communication on Research Awareness Need project

BACKGROUND: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. METHODS: Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in science communication. We searched for, and evaluated, relevant existing materials and developed additional materials and tools, making them freely available under a Creative Commons licence. RESULTS: The principal communication materials developed were: 1. A website ( http://ecranproject.eu ) in six languages, including a Media centre section to help journalists to disseminate information about the ECRAN project 2. An animated film about clinical trials, dubbed in the 23 official languages of the European Community, and an interactive tutorial 3. An inventory of resources, available in 23 languages, searchable by topic, author, and media type 4. Two educational games for young people, developed in six languages 5. Testing Treatments interactive in a dozen languages, including five official European Community languages 6. An interactive tutorial slide presentation testing viewers' knowledge about clinical trials CONCLUSIONS: Over a 2-year project, our multidisciplinary and multinational consortium was able to produce, and make freely available in many languages, new materials to promote public knowledge about the importance of independent and international clinical trials. Sustained funding for the ECRAN information platform could help to promote successful recruitment to independent clinical trials supported through the European Clinical Research Infrastructure Network

A Preliminary Mixed-Method Investigation of Trust and Hidden Signals in Medical Consultations.

Background Several factors influence patients' trust, and trust influences the doctor-patient relationship. Recent literature has investigated the quality of the personal relationship and its dynamics by considering the role of communication and the elements that influence trust giving in the frame of general practitioner (GP) consultations. Objective We analysed certain aspects of the interaction between patients and GPs to understand trust formation and maintenance by focusing on communication channels. The impact of socio-demographic variables in trust relationships was also evaluated. Method A cross-sectional design using concurrent mixed qualitative and quantitative research methods was employed. One hundred adults were involved in a semi-structured interview composed of both qualitative and quantitative items for descriptive and exploratory purposes. The study was conducted in six community-based departments adjacent to primary care clinics in Trento, Italy. Results The findings revealed that patients trusted their GP to a high extent by relying on simple signals that were based on the quality of the one-to-one communication and on behavioural and relational patterns. Patients inferred the ability of their GP by adopting simple heuristics based mainly on the so-called social \u201chonest signals\u201d rather than on content-dependent features. Furthermore, socio-demographic variables affected trust: less literate and elderly people tended to trust more. Conclusions This study is unique in attempting to explore the role of simple signals in trust relationships within medical consultation: people shape trust and give meaning to their relationships through a powerful channel of communication that orbits not around words but around social relations. The findings have implications for both clinicians and researchers. For doctors, these results suggest a way of thinking about encounters with patients. For researchers, the findings underline the importance of analysing some new key factors around trust for future investigations in medical practice and education