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Sini V.,Internal Medicine | Buonomo O.,Surgery | Orlandi A.,University of Rome Tor Vergata | Masuelli L.,University of Rome La Sapienza | And 4 more authors.
Cancer Science | Year: 2011

A common carboxyl-terminal epitope (C-22 P0) of the ribosomal P proteins (P0, P1 and P2) was shown to elicit autoantibodies in systemic lupus erythematosus (SLE) and in head and neck cancer patients. In this report we provide evidence for the in vivo immunogenicity of the P0 protein in breast cancer patients. Using recombinant P proteins, we demonstrated that sera from breast carcinoma patients (8/75) displayed significant reactivity to P0 protein when compared with healthy donor sera (0/45). Four out of the eight sera showed simultaneous reactivity to all P proteins. Breast benign tumor (3/17) and mammary hyperplasia (3/17) patient sera also showed significant reactivity to P proteins, thus suggesting that the occurrence of P protein autoantibodies might reveal mammary cell cycle dysregulation. Patient sera reacting with all P proteins recognized C-22 P0. Anti-P0 autoantibodies did not correlate with prognostic parameters of breast carcinomas. High level expression of C-22 P0 was found in mammary carcinomas compared with normal adjacent epithelium and benign lesions. To determine the antitumor activity of P0 as an immunogen, BALB-neuT transgenic mice displaying age-related breast cancer progression were vaccinated using xenogeneic P0 at the stage of mammary atypical hyperplasia. P0 vaccination significantly delayed the onset of mouse mammary tumors that overexpressed C-22 P0. Sera from P0 vaccinated mice recognized C-22 P0. Evidence for immunity to the P0 protein, its overexpression in carcinomas and its peculiar surface localization on cancer cells, along with its antitumor activity as an immunogen might be relevant for the use of P0 protein in monitoring cancer progression and in planning immunotherapeutic strategies. © 2010 Japanese Cancer Association.

Ingrosso G.,University of Rome Tor Vergata | Fantini M.,University of Rome Tor Vergata | Nardi A.,University of Rome Tor Vergata | Benvenuto M.,University of Rome Tor Vergata | And 9 more authors.
Oncology Reports | Year: 2013

Prostate cancer is a common cancer among men in developed countries. Although hormonotherapy and radiotherapy (RT) represent valid therapies for prostate cancer treatment, novel immunological approaches have been explored. The development of clinical trials employing cancer vaccines has indicated that immune response to tumor antigens can be boosted and that vaccine administration can improve patient survival. Immune response to tumor antigens could also be enhanced after standard therapies. In the present study, we determined the occurrence of antibodies to extracellular matrix (ECM) molecules, heat shock protein (HSP), ribosomal P0 protein, EGFR, ErbB2 and prostate-specific antigen (PSA) in 35 prostate cancer patients prior to and following local RT and hormonotherapy. We demonstrated that immunity to P0, ECM molecules [collagens (C) CI, CIII, C V, fibronectin (FN) and laminin (LM)] and to HSP90 was associated with malignancy in untreated patients. None of the patient sera showed antibodies to EGFR, while 2 and 1 patients showed reactivity to ErbB2 and PSA, respectively. We also demonstrated that 8 months after therapy the IgG serum levels to CI, CIII, FN and HSP90 significantly decreased. Conversely, the level of P0 autoantibodies increased after therapy in 10 patients. Five of the 10 patients with increased levels of P0 autoantibodies were treated with RT plus hormonotherapy. Treatment of patients did not change the levels of antibodies against EGFR, ErbB2 and PSA. Our results indicated that the modification of antibody level to self molecules after standard treatment of prostate cancer patients is influenced by the type of antigen. Ribosomal P0 protein appears to be a high immunogenic antigen and its immunogenicity increases following RT. In addition, 10 patients with increased levels of autoantibodies to P0 showed PSA mean levels lower than the remaining 25 patients at 18 months. This study may contribute to a better understanding of the immunobiological behavior of prostate cancer patients following standard treatment.

Bacillus anthracis and Yersinia pestis are etiological agents of anthrax and plague respectively, and are also considered among the most feared potential bioterrorism agents. These microorganisms show intraspecies genome homogeneity, making strains differentiation difficult, while strains identification and comparison with known genotypes may be crucial for naturally occurring outbreaks vs. bioterrorist events discrimination. Here an MLVA application for B. anthracis and Y. pestis strains differentiation is described on Microchip Capillary electrophoresis apparatus. The platform is a candidate for on-site MLVA genotyping of biothreat agents as well as other bacterial pathogens. This microfluidics-based electrophoresis analysis system represents an alternative to the more expensive and demanding capillary electrophoresis methods, and to the less expensive but more time-consuming standard agarose gel approach. © 2012 Springer Science+Business Media, LLC.

Gentile B.,Army Medical Research Center | Lista F.,Army Medical Research Center | D'Amelio R.,University of Rome La Sapienza
Environment International | Year: 2015

Purpose: Anthrax is caused by Bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. However, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, B. anthracis has been considered the most serious bioterrorism agent for a long time. During the last century anthrax evolved from limited natural disease to potentially global threat if used as bioweapon. Several factors may mitigate the consequences of an anthrax attack, including 1. the capability to promptly recognize and manage the illness and its public health consequences; 2. the limitation of secondary contamination risk through an appropriate decontamination; and 3. the evolution of genotyping methods (for microbes characterization at high resolution level) that can influence the course and/or focus of investigations, impacting the response of the government to an attack. Methods: A PubMed search has been done using the key words "bioterrorism anthrax". Results: Over one thousand papers have been screened and the most significant examined to present a comprehensive literature reviewin order to discuss the current knowledge and strategies in preparedness for a possible deliberate release of B. anthracis spores and to indicate the most current and complete documents in which to deepen. Conclusions: The comprehensive analysis of the two most relevant unnatural anthrax release events, Sverdlovsk in the former Soviet Union (1979) and the contaminated letters in the USA (2001), shows that inhalational anthraxmay easily and cheaply be spread resulting in serious consequences. The damage caused by an anthrax attack can be limited if public health organization, first responders, researchers and investigators will be able to promptly manage anthrax cases and use new technologies for decontamination methods and in forensic microbiology. © 2015 Elsevier Ltd.

Fasanella A.,Anthrax Reference Institute of Italy | Garofolo G.,Anthrax Reference Institute of Italy | Galante D.,Anthrax Reference Institute of Italy | Quaranta V.,Anthrax Reference Institute of Italy | And 4 more authors.
New Microbiologica | Year: 2010

Anthrax is a disease of humans and animals caused by the encapsulated, spore-forming Bacillus anthracis. In Italy, anthrax is normally a sporadic disease. During the summer 2004, anthrax broke out in the Basilicata, in southern Italy, a region with a low prevalence of anthrax in which vaccination had been suspended since 1998. The disease involved several animals in few weeks and in a large area. Over 41 days, 81 cattle died, as well as 15 sheep, 9 goats, 11 horses and 8 deer. The Multiple-locus Variable-Number Tandem Repeats Analysis (MLVA) showed that all the 53 isolates belonged to the Cluster Ala, genotype 1. The results of the Single Nucleotide Repeats (SNRs) Analysis showed that 48/53 B.anthacis strains belonged to a single clonal lineage, the sub-genotype sgt - eB. Two sporadic mutants, sgt - eB,ml and sgt- eB, m2, were isolated, only one managing to infect other herds. Factors that could have contributed to the spread of infection, such as the transmission of spores by insect vectors and the favourable weather conditions were evaluated.

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