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Mazzei F.,Istituto Superiore di Sanita | Viel A.,Centro Of Riferimento Oncologico | Bignami M.,Istituto Superiore di Sanita
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis | Year: 2013

MUTYH, a human ortholog of MutY, is a post-replicative DNA glycosylase, highly conserved throughout evolution, involved in the correction of mismatches resulting from a faulty replication of the oxidized base 8-hydroxyguanine (8-oxodG). In particular removal of adenine from A:8-oxodG mispairs by MUTYH activity is followed by error-free base excision repair (BER) events, leading to the formation of C:8-oxodG base pairs. These are the substrate of another BER enzyme, the OGG1 DNA glycosylase, which then removes 8-oxodG from DNA. Thus the combined action of OGG1 and MUTYH prevents oxidative damage-induced mutations, i.e. GC-. >. TA transversions. Germline mutations in MUTYH are associated with a recessively heritable colorectal polyposis, now referred to as MUTYH-associated polyposis (MAP). Here we will review the phenotype(s) associated with MUTYH inactivation from bacteria to mammals, the structure of the MUTYH protein, the molecular mechanisms of its enzymatic activity and the functional characterization of MUTYH variants. The relevance of these results will be discussed to define the role of specific human mutations in colorectal cancer risk together with the possible role of MUTYH inactivation in sporadic cancer. © 2013 Elsevier B.V.

Carbone A.,Centro Of Riferimento Oncologico
Blood | Year: 2013

In this issue of Blood, Cader et al show that tumor microenvironment promotes Epstein-Barr virus (EBV)-driven lymphomagenesis in Hodgkin lymphoma by a novel pathway involving latent membrane protein 1 (LMP1) and discoidin domain receptor 1 (DDR1), which is activated by collagen(s) and contributes to the survival of Reed-Sternberg (RS) cells. Copyright © 2011 by The American Society of Hematology; all rights reserved.

Aldinucci D.,Italian National Cancer Institute | Gloghini A.,Italian National Cancer Institute | Pinto A.,Italian National Cancer Institute | De Filippi R.,Italian National Cancer Institute | And 3 more authors.
Journal of Pathology | Year: 2010

It has become clear that cancer is not merely a growth of autonomously proliferating cells, but that other non-malignant cell types are a functional part of the disease. Immune cells, fibroblasts, specialized mesenchymal cells and microvasculature together make up the tumour microenvironment and have functional interactions with tumour cells. Classical Hodgkin's lymphoma (cHL) is characterized by only a few malignant cells and an abundance of inflammatory cells. Hodgkin and Reed-Sternberg (HRS) cells are surrounded by T and B cells admixed with plasma cells, macrophages, eosinophils and mast cells. A constitutive activity of NF-κB and an altered JAK-STAT signalling pathway are part of the biological background associated with the increased expression of cytokines and cytokine receptors seen in HRS cells. Over-expression of the members of the TNF receptor family, especially CD30 and CD40, is a hallmark of HRS cells. cHL is a tumour where aberrant cytokine production contributes not only to the proliferation of HRS cells but also to the maintenance of an appropriate environment for the tumour cells. In addition, several chemokines contribute to the composition of the inflammatory background in cHL. This review summarizes updated information on the complex interactions between the HRS cells and their tissue microenvironment and highlights the development of newer therapeutic strategies aimed at targeting the non-malignant inflammatory/immune cellular components of HL that are involved in cancer cell growth and/or immune escape. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

University of Udine and Centro Of Riferimento Oncologico | Date: 2014-04-03

Apparatus for analyzing the process of formation of aggregates in a biological fluid, such as blood or hematic fluids, comprising a perfusion chamber provided with at least one micro-channel through which the biological fluid flows, and in which at least one reactive substrate is present, such as a cyto-adhesive substrate, to stimulate the aggregation process in the biological fluid, and impedenziometric detection means associated with the micro-channel, in correspondence to at least one investigation area and disposed, during use, in contact with the flow of biological fluid in transit, in order to detect impedance data of the biological fluid. The impedenziometric detection means comprise at least two first electrodes with an oblong development disposed in the micro-channel, and a plurality of second electrodes with an oblong development disposed in the space comprised between the first electrodes and according to a pattern defining substantially the perimeter of a geometric figure.

Muzzatti B.,Centro Of Riferimento Oncologico | Annunziata M.A.,Centro Of Riferimento Oncologico
Supportive Care in Cancer | Year: 2012

Objectives Taking care of oncological patients holistically from a biological, social, and psychological point of view also involves evaluating the social aspects of the disease. In the present study, we provide further insights on how investigations regarding the social impact of an oncological disease are conducted with specifically designed tools on patientswho have personally been affected. The objective is then to understand how the social dimension is theorized and, therefore, which practical aspects of subjective experience are employed to assess the social impact. Method We performed a systematic review of the literature identified by MedLine and PsycINFO databases. Results Of the 469 articles obtained from the search, 27 deal with 14 different measurement instruments of the social impact of the oncological experience. Of the identified tools, 71% were specifically designed for the oncological setting and were heterogeneous both in the investigated domains as well as social referrals; 64% of these had a multidimensional structure. Internal consistency was reported for all instruments, while temporal stability only for 36% of the tools. Construct validity and concurrent validity were reported for 79% of the instruments, criterion and predictive validity for one instrument only, external validity for 18% of the tools, and cross-cultural validity for one instrument only. The content was directly available for most instruments. Conclusions The great interest in this subject as borne out by the amount of studies published in international psychooncological literature confirms the importance of having a valid and reliable instrument specifically dedicated to measuring the social impact of the oncological experience. At the same time, further investigation is required to investigate the psychometric properties of the existing tools. © 2012 Springer-Verlag.

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