Centro Of Riferimento Oncologico
Centro Of Riferimento Oncologico
Vinča Institute of Nuclear Sciences and Centro Of Riferimento Oncologico | Date: 2015-04-29
The present invention refers to peptides functionally related to Toll-like receptor 5 (TLR-5) ligand, having a sequence of amino acids ordered by means of the protein informational analysis techniques using the informational spectrum method with reference to the informational properties of flagellin. The sequence has in the informational spectrum the frequency of virtually the same value as the frequency characteristic determining the flagellin/TLR-5 interaction.
De Paoli P.,Centro Of Riferimento Oncologico
Expert Opinion on Therapeutic Patents | Year: 2010
Importance of the field: Therapeutic strategies against EpsteinBarr virus (EBV) infection and associated cancers are still limited. Due to the primary role of this virus in the pathogenesis of these diseases, molecules interfering with EBV protein functions may represent effective therapeutic tools to treat EBV-associated diseases. Areas covered in this review: Active immunotherapeutic protocols targeting EBV and EBV-associated cancers are reviewed first; then, we reviewed adoptive cellular therapies, innovative pharmacological approaches and other non-conventional therapeutic molecules. What the reader will gain: The published literature, in particular patent publications on EBV therapeutic options, has been searched for relevant information. This information has been organized and discussed. Take home message: Many promising therapeutic opportunities are identified. Among these, vaccination protocols and adoptive cellular therapies are the most advanced and reached Phase I/II clinical trials. Pharmacological approaches are at the moment limited to the laboratory phase. © 2010 Informa UK Ltd.
Loupakis F.,University of Pisa |
Cremolini C.,University of Pisa |
Masi G.,University of Pisa |
Lonardi S.,University of Pisa |
And 16 more authors.
New England Journal of Medicine | Year: 2014
BACKGROUND A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects.METHODS We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival.RESULTS The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62 to 0.90; P = 0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P = 0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P = 0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group.CONCLUSIONS FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; ClinicalTrials.gov number, NCT00719797.). Copyright © 2014 Massachusetts Medical Society. 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.
Mazzei F.,Instituto Superiore Of Sanita |
Viel A.,Centro Of Riferimento Oncologico |
Bignami M.,Instituto Superiore Of 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.
De Paoli P.,Centro Of Riferimento Oncologico |
Carbone A.,Centro Of Riferimento Oncologico
Seminars in Cancer Biology | Year: 2015
When stringent criteria have been used, the Epstein Barr virus (EBV), the Kaposi's sarcoma herpesvirus (KSHV), human immunodeficiency virus type 1 (HIV-1) and human hepatitis C virus (HCV) have been identified with sufficient evidence to be causative agents of non-Hodgkin's Lymphomas. Initially, single viral infection was considered fully responsible for the oncogenic properties of each virus, while it is now established that in many cases, multiple viral agents collaborate as cofactors in inducing lymphomas, especially in the presence of HIV-dependent immunodeficiency. Viruses cooperate by using their specific pathogenetic mechanisms in different combinations. The aim of this review is to describe the cooperation between different viruses in the development of lymphomas including the evidences supporting their pathogenetic role. Viral cooperation, a mechanism by which different viruses coinfecting human tissues have synergistic or regulatory effects on carcinogenesis, targets neoplastic B cells as well as cells of the microenvironment, such as reactive T-cells, B cells and macrophages, as well as non-immune cells such as endothelial cells, that contribute to tumor microenvironment. The most important viral genes involved in cooperation include HIV-1 tat and vpu, EBV LMP-1 and EBNA-2 and KSHV KIE2, Rta and LANA. Lymphomagenesis related to viral cooperation represents an interesting topic where microenvironmental abnormalities may be particularly relevant, particularly because antiviral targeted therapies and therapies producing the reconstitution of the immune system may constitute areas of interest aiming at improving the outcome of virus associated lymphomas. While the immune component of the lymphoma microenvironment can be easily studied by immunological and molecular techniques, the definition of the non-immune component of the lymphoma microenvironment is largely incomplete and may be the issue of future investigations. Understanding the pathogenetic role of viral infection in specific malignancies and defining microenvironmental abnormalities and mechanisms of viral carcinogenesis are important steps toward precise diagnosis and accurate treatment strategies for HIV-associated cancers. © 2015 The Authors.
De Paoli P.,Instituto Nazionale Tumori Aviano |
Carbone A.,Centro Of Riferimento Oncologico
International Journal of Cancer | Year: 2013
Viral infections are important risk factors for tumor development in humans. Selected types of cancers, either lymphomas or carcinomas, for which there is sufficient evidence in humans of a causal association with specific viruses, have been identified. Experimental and clinical data on the possible association of other tumor types and carcinogenic viruses are presently controversial. In this article, we review the current evidence on the relationship between breast, colorectal and lung cancers and carcinogenic viruses. The majority of the publications reviewed do not provide definitive evidence that the viruses studied are associated with breast, colon and lung cancers. However, since this association may be clinically relevant for some tumor subtypes (i.e., lung cancer and papillomaviruses), there is an urgent need for further investigation on this topic. Using innovative laboratory techniques for viral detection on well-defined tumor types, National and International networks against cancer should encourage and organize concerted research programs on viruses and solid cancer association. Copyright © 2013 UICC.
Carbone A.,Centro Of Riferimento Oncologico |
Gloghini A.,Instituto Nazionale Dei Tumori
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.
Cappelletti P.,Centro Of Riferimento Oncologico
Rivista Italiana della Medicina di Laboratorio | Year: 2010
P4 Medicine is a term coined for "predictive, preventive, personalized, and participatory medicine", an idea rapidly becoming practical as a result of advances in biomedical research and know-how. The diagnostic capability determined by "omics" and novel biomarkers allow an efficient and individual prediction of person's health status and future and consequently an individual concrete prevention. Personalized Medicine can be viewed as a comprehensive, prospective approach to preventing, diagnosing, treating, and monitoring disease in ways that achieve optimal individual health care decisions. As a result of personalization, medicine should become participatory: healthcare consumers should be encouraged to actively participate in their own healthcare, by correct lifestyle and awareness of disease/treatment history. In this new "prospective health care", Laboratory Medicine has a central and exciting role. The Metabolic Syndrome offers an interesting example of the present and future Laboratory role in the prospective medicine: criteria for Syndrome are based on Laboratory measurements; Laboratory Medicine is necessary for prediction, prevention and monitoring of the Syndrome; Laboratory data could aid patients to take responsibility of their own health and healing. Moreover, the debate about the real existence of Metabolic Syndrome focuses the necessity of a systems biology approach instead of a reductionist approach to explain the "emergent properties" of the metabolic system, resulted by interactions between the parts of the system and not attributed to any single part.
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.