Gabriella Calviello

The Catholic University of America, Washington, Washington, D.C., United States

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Publications (92)354.66 Total impact

  • S Serini · G Calviello ·
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    ABSTRACT: Plenty of evidence has shown that an enhanced oxidative or nitrosative stress may play a central role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). The suppressive effect of n-3 polyunsaturated fatty acids (n-3 PUFA) against oxidative/nitrosative stress-induced injury in nervous tissues has recently received increasing interest. A number of human experimental studies have concurred to demonstrate that they may exert a substantial preventive role, especially in the very early phase of mild cognitive impairment (MCI) preceding AD. It has been suggested that they may exert an indirect antioxidant/anti-nitrosative role by modulating the expression/activity of several proteins involved in the modulation of oxidative stress in nervous tissues. In particular, recent data have supported the hypothesis that in the early phase of MCI the light to moderate oxidative stress triggered by not cytotoxic doses of n-3 PUFA can positively regulate the transcriptional activity of nuclear factor erythroid 2-related factor 2 (Nrf2). This may result in the induced expression of heme oxygenase-1 (HO-1) and other antioxidant proteins transcriptionally regulated by Nrf2. Alternatively, the anti-inflammatory and antioxidant/anti-nitrosative effects of n-3 PUFA have been lately related to their ability to blunt microglia persistent activation occurring during chronic inflammation involved in the pathogenesis of neurodegenerative diseases. Evidences have been presented that n-3 PUFA may convert microglia from the macrophage M1 to an M2 phenotype showing lower production of neurotoxic- oxidative factors and enhanced phagocytic activity toward Aβ peptide, or even to a further phenotype with neurotrophic/protective properties.
    Current Alzheimer research 09/2015; 12(999). DOI:10.2174/1567205012666150921101147 · 3.89 Impact Factor
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    ABSTRACT: Almost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake. However, particularly in recent years, contradictory results have been obtained in human studies focusing on cardiovascular disease and the clinical evidence in other diseases, particularly chronic inflammatory and neoplastic diseases, was never established to a degree that led to clear approval of treatment with omega-3 PUFA. Recent data not in line with the previous findings have sparked a debate on the health efficacy of omega-3 PUFA and the usefulness of increasing their intake for the prevention of a number of pathologies. In this review, we aim to examine the controversies on the possible use of these fatty acids as preventive/curative tools against the development of cardiovascular, metabolic, and inflammatory diseases, as well as several kinds of cancer.
    08/2015; 2015(6):1-24. DOI:10.1155/2015/143109
  • Elena Fasano · Simona Serini · Achille Cittadini · Gabriella Calviello ·
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    ABSTRACT: The potential antineoplastic effect of the long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) remains a highly controversial issue. Numerous animal studies have supported the anticancer role of these dietary fatty acids, whereas conflicting results have been obtained in population studies, and only a few intervention human trials have been so far performed. In view of the possibility that the anticancer effects may be maximally observed within a defined range of EPA and DHA doses, herein we critically review the results and doses used in both animal studies and human clinical trials focusing on the possible n-3 PUFA protective effects against breast and prostate cancer. Our main aim is to identify the EPA and/or DHA ranges of doses needed to obtain clear anticancer effects. This may be of great help in designing future animal studies, and also in understanding the most appropriate dose for further human intervention studies. Moreover, since the healthy effects of these fatty acids have been strictly related to their increased incorporation in plasma and tissue lipids, we also examine and discuss the incorporation changes following the administration of the effective anticancer EPA and/or DHA doses in animals and humans.
    Critical reviews in food science and nutrition 04/2015; DOI:10.1080/10408398.2013.850060 · 5.18 Impact Factor
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    ABSTRACT: Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, α-tocopherol, and selenium) contained in a dietary supplement used for the prevention of skin disorders were investigated in vitro. Each component was administered, alone or in combination, to human keratinocytes, and the inhibition of Reactive Oxygen Species production and lipid peroxidation as well as the ability to reduce inflammatory cytokine secretion and to modulate Nuclear Factor-κB pathway was evaluated. The combination exhibited high antioxidant activity and in specific conditions the combination's efficiency was higher than that of the most powerful components administered individually. Moreover, the combination showed remarkable anti-inflammatory properties. It reduced more efficiently than each component the secretion of Monocyte Chemoattractant Protein-1, a crucial cytokine for the development of chronic inflammation in skin, and inhibited Nuclear Factor-κB molecular pathway. Overall, our findings suggest that the combined formulation may have the potential to powerfully inhibit oxidative stress and inflammation at skin level.
    BioMed Research International 08/2014; 2014:327452. DOI:10.1155/2014/327452 · 1.58 Impact Factor
  • Janel Suburu · Kyu Lim · Gabriella Calviello · Yong Q Chen ·

    Journal of the National Cancer Institute 03/2014; 106(4). DOI:10.1093/jnci/dju023 · 12.58 Impact Factor
  • Simona Serini · Elena Fasano · Leonardo Celleno · Achille Cittadini · Gabriella Calviello ·
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    ABSTRACT: The possible antineoplastic activity of dietary long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) has been supported by ample preclinical studies that have identified a number of molecular factors and pathways affected by these fatty acids and involved in cell growth, apoptosis, invasion, and angiogenesis. The aim of this critical review is to assess the current state of knowledge on the potential anticancer effects of LC n-3 PUFAs against malignant melanoma, one of the most common cancers among Western populations. The results of preclinical as well as human observational and interventional studies investigating the effects of LC n-3 PUFAs in melanoma were examined. Overall, the analysis of the literature reveals that, even though a large body of information is available, further effort is needed to identify the main molecular targets of LC n-3 PUFAs in melanoma. Moreover, additional well-designed human observational studies are essential to shed further light on the issue. The results of these studies could provide support and specific information for the development of clinical studies, especially those performed in combination with conventional or innovative antineoplastic therapies.
    Nutrition Reviews 03/2014; 72(4). DOI:10.1111/nure.12093 · 6.08 Impact Factor
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    Achille Cittadini · Gabriella Calviello · Hui-Min Su · Karsten H. Weylandt ·

    09/2013; 2013:905986. DOI:10.1155/2013/905986
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    P Palozza · S Serini · S Trombino · L Lauriola · F O Ranelletti · G Calviello ·

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    ABSTRACT: A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action of ω-3 polyunsaturated fatty acids (PUFAs), as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others' laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects of ω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects of ω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases.
    04/2013; 2013:743171. DOI:10.1155/2013/743171
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    ABSTRACT: In 54 stage I and II human lung adenocarcinomas, HuR and PTHrP levels were positively correlated and the PTHr-HuR status of the tumor was an independent prognostic marker of the clinical outcomes of patients. The possibility that HuR could upregulate PTHrP expression in lung adenocarcinoma was investigated by immunohistochemical, Western blot and RT-PCR analyses in HCC44 and DV90 human lung adenocarcinoma cell lines. In both cell lines, knockdown of HuR by specific siRNAs reduced PTHrP mRNAs and both cellular and secreted protein. Moreover, it inhibited cell growth and induced cell apoptosis, as revealed by the increase of caspase-3 activity. These effects were partially rescued by the addition of exogenous PTHrP (1-34). Analysis by actinomycin D assay revealed that in both cell lines HuR silencing produced a decrease of PTHrP mRNA half-life by about 70%. These findings add PTHrP to the list of lung cancer-associated genes, whose mRNA is stabilized by HuR.
    Histology and histopathology 04/2013; 28(9). · 2.10 Impact Factor
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    ABSTRACT: n-3 polyunsaturated fatty acids exert growth-inhibitory and pro-apoptotic effects in colon cancer cells. We hypothesized that the anti-apoptotic glucose related protein of 78kDa (GRP78), originally described as a component of the unfolded protein response in endoplasmic reticulum (ER), could be a molecular target for docosahexaenoic acid (DHA) in these cells. GRP78 total and surface overexpression was previously associated with a poor prognosis in several cancers, whereas its down-regulation with decreased cancer growth in animal models. DHA treatment induced apoptosis in three colon cancer cell lines (HT-29, HCT116 and SW480), and inhibited their total and surface GRP78 expression. The cell ability to undergo DHA-induced apoptosis was inversely related to their level of GRP78 expression. The transfection of the low GRP78-expressing SW480 cells with GRP78-GFP cDNA significantly induced cell growth and inhibited the DHA-driven apoptosis, thus supporting the essential role of GRP78 in DHA pro-apoptotic effect. We suggest that pERK1/2 could be the first upstream target for DHA, and demonstrate that, downstream of GRP78, DHA may exert its proapoptotic role by augmenting the expression of the ER resident factors ERdj5 and inhibiting the phosphorylation of PKR-like ER kinase (PERK), known to be both physically associated with GRP78, and by activating caspase-4. Overall, the regulation of cellular GRP78 expression and location is suggested as a possible route through which DHA can exert pro-apoptotic and antitumoral effects in colon cancer cells.
    Biochimica et Biophysica Acta 08/2012; 1822(11):1762-72. DOI:10.1016/j.bbadis.2012.08.003 · 4.66 Impact Factor
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    ABSTRACT: It has been hypothesized that pro-inflammatory cytokines may play a pathogenic role in Alzheimer's disease (AD), and that n-3 polyunsaturated fatty acids may be protective against the development and progression of this disease. A reduced release of inflammatory cytokines by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from AD patients dietary supplemented with a mixture of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) was recently reported. On this basis, we investigated the possible differential effects of the two purified fatty acids on inflammatory cytokine release, a subject still not explored, even though of great pharmacological interest. We treated in vitro phytohaemagglutinin (PHA)- or LPS-stimulated PBMCs from AD patients and age-matched healthy controls (HCs) with purified EPA or DHA. Higher pro- to anti-inflammatory cytokine ratios, indicative of a pro-inflammatory profile, were observed in PHA-stimulated PBMCs from AD patients in basal conditions. The addition of both EPA and DHA markedly reduced the cytokine release, with DHA showing always a more prominent effect than EPA. However, whereas DHA reduced only the high IL-1β/IL-10 ratio, EPA was able to reduce also the IL-6/IL-10 ratio. In stimulated PMBCs from HCs the reducing effect on cytokine release was not always observed, or observed at a lower degree. In conclusion, whereas DHA appeared more powerful in inhibiting each single inflammatory cytokine, the proinflammatory profile of the AD patients' cells was better reverted by EPA to a profile more similar to that found in HCs. A combination of both the fatty acids, seems to be still the best solution.
    Current Alzheimer research 01/2012; 9(8):913-23. DOI:10.2174/156720512803251147 · 3.89 Impact Factor
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    ABSTRACT: The pro-inflammatory phenotype accompanying melanoma progression includes an enhanced expression of cyclooxygenase-2 (COX-2), which plays an important role in the acquisition of apoptosis resistance, and is a suitable target for melanoma prevention and therapy. We observed that the WM266-4 metastatic melanoma cell line showed a constitutive COX-2 expression higher than that of the primary WM115 cells, an increased cytosolic level of the COX-2 messenger RNA (mRNA)-stabilizer human antigen R (HuR) and a lower susceptibility to basal apoptosis. The transfection of HuR siRNA induced apoptosis and reduced COX-2 protein abundance in both the cells. The same effects were observed treating the cells with the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), which reduced the cytoplasmic location and expression of HuR and, correspondently, decreased COX-2 protein expression and induced apoptosis. DHA also decreased the expression and stability of COX-2 mRNA, increased the β-catenin expression in the nuclei and reduced it in the cytosol, where it forms a complex with HuR and COX-2 mRNA. DHA had also a pro-differentiating effect, which is compatible with the nuclear translocation of β-catenin. These findings allow us to associate for the first time the constitutive expression of COX-2 in melanoma cells to the HuR-mediated stabilization of its mRNA and suggest that also β-catenin may play a role in HuR-mediated COX-2 stabilization in these cells. The data demonstrate that the HuR-mediated stabilization of COX-2 may represent a target of DHA action in melanoma cells and suggest the application of DHA in the prevention and therapy of melanoma.
    Carcinogenesis 10/2011; 33(1):164-73. DOI:10.1093/carcin/bgr240 · 5.33 Impact Factor
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    ABSTRACT: There is some evidence to support the toxicity of polyunsaturated fatty acids (PUFAs) and their oxidative products, suggesting their involvement in the pathogenesis of different chronic diseases, including cancer. It has been shown that products of PUFA oxidation may exert a carcinogenic action by forming mutagenic adducts with DNA. However, a large amount of evidence accumulated over several decades has indicated the beneficial effects of administration of n-3 PUFAs in the prevention and therapy of a series of diseases. In particular, there is much evidence that n-3 PUFAs exert anti-inflammatory and antineoplastic effects, whereas n-6 PUFAs promote inflammation and carcinogenesis. In our tissues, both of the two classes of PUFAs can be converted into bioactive products, incorporated into membrane phospholipids or bound to membrane receptors, where they may alter, often in opposite ways, transduction pathways and affect important biological processes, such as cell death and survival, inflammation, and neo-angiogenesis. In the present review, we intend to shed light on the paradox of the coexisting healthy and toxic effects of n-3 PUFAs, focusing on their possible pro-oxidant cytotoxic and carcinogenic effect, in order to understand if their increased intake, recommended by a number of health agencies worldwide and promoted by nutraceutical producers, may or may not represent a hazard to human health.
    Chemical Research in Toxicology 09/2011; 24(12):2093-105. DOI:10.1021/tx200314p · 3.53 Impact Factor
  • S Serini · E Fasano · E Piccioni · A.R.M. Cittadini · G Calviello ·
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    ABSTRACT: As the concepts of pharmaconutrition are receiving increasing attention, it seems essential to clearly assess the effects of specific dietary compounds in specific groups of patients or clinical conditions. We are herein interested in better defining the differential anti-neoplastic effects of the two major n-3 long chain polyunsaturated fatty acids present in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The efficiency of these fatty acids represents a subject of intense interest and debate, and whereas plenty of preclinical studies have strongly demonstrated their preventive and therapeutic effect in different kinds of cancers, the results of the epidemiologic studies are still controversial, and only a few trials have been performed. It has been reported that EPA and DHA may act either through the same or different mechanisms, thus suggesting that a differential efficacy could exist. At present, however, this point has not been clarified, although its better comprehension would allow a more proper and effective use of these fatty acids in the human interventional studies. In an attempt to elucidate this aspect we have herein analyzed the data obtained in the studies which have directly compared the antitumor effects of separate treatments with EPA or DHA. Most of the in vitro data indicate DHA as the more powerful antineoplastic agent. However, an equivalent efficiency of EPA and DHA is suggested by the few in vivo studies. Possible reasons for this discrepancy are discussed and pathways of cell growth that could be differentially influenced by EPA and DHA are described.
    Current Medicinal Chemistry 08/2011; 18(26):4065-75. DOI:10.2174/092986711796957310 · 3.85 Impact Factor
  • Stefano Manfredini · Silvia Vertuani · Gabriella Calviello · Paola Palozza ·

    Expert Opinion on Therapeutic Targets 03/2011; 1(1). DOI:10.1517/14728222.1.1.241 · 5.14 Impact Factor
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    ABSTRACT: The dramatic increase in the incidence of nonmelanoma skin cancer over the last decades has been related to the augmented exposure to ultraviolet (UV) radiation (UVR). It is known that apoptosis is induced as a protective mechanism after the acute irradiation of keratinocytes, whereas apoptotic resistance and carcinogenesis may follow the chronic exposure to UVR. We found that not all the human keratinocytes lines studied underwent apoptosis following acute exposure to UVR (10-60 mJ/cm(2)). Whereas UVR induced apoptosis in the HaCaT cells, NCTC 2544 and nr-HaCaT cells showed apoptosis resistance. The cytokeratin pattern of the apoptosis-resistant cells indicated that they possessed a degree of differentiation lower than that of HaCaT cells. They also showed an enhanced expression of cyclooxygenase-2 (COX-2), an early marker of carcinogenesis in various tissues, including skin. n-3 polyunsaturated fatty acids have drawn increasing interest as nutritional factors with the potential to reduce UVR carcinogenesis, and since they are apoptosis inducers and COX-2 inhibitors in cancer cells, we investigated the ability of n-3 polyunsaturated fatty acids to influence the resistance to UVR-induced apoptosis in keratinocytes. We observed that docosahexaenoic acid (DHA) reverted the resistance of nr-HaCaT cells to UVR-induced apoptosis, increasing the Bax/Bcl-2 ratio and caspase-3 activity, and reduced COX-2 levels by inhibiting the expression of the human antigen R (HuR), a known COX-2 mRNA stabilizer in keratinocytes. The transfection of nr-HaCaT cells with HuR siRNA mimicked the proapoptotic effect of DHA. Overall, our findings further support the role of DHA as a suitable anticarcinogenic factor against nonmelanoma skin cancers.
    The Journal of nutritional biochemistry 12/2010; 22(9):874-85. DOI:10.1016/j.jnutbio.2010.08.004 · 3.79 Impact Factor
  • E Fasano · S Serini · E Piccioni · I Innocenti · G Calviello ·
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    ABSTRACT: Different intervention trials have been so far conducted and others are ongoing to evaluate the effect of increased intake of n-3 polyunsaturated fatty acids (PUFAs) in the prevention of several disorders affecting lungs and airways. They have been focused on chronic obstructive pulmonary disease, acute respiratory distress syndrome, acute lung injury, pulmonary fibrosis, alteration of lung function in cystic fibrosis, as well as asthma and cachexia in lung cancer patients. Their outcomes are not always consistent, but, if beneficial effects were observed, they have been related mainly to the anti-inflammatory action of n-3 PUFAs. On the contrary, trials investigating their effects on the development and progression of lung cancer are still not available. This in spite of the huge number of equivalent studies performed on other kind of cancers (breast, colon and prostate cancer), which share with lung cancer the highest incidence in Western countries and an elevated sensitivity to chemoprevention. Contrasting results were also obtained by the few epidemiological studies available on lung cancer. However, different experimental studies, performed in vivo and in vitro, provided strong indications of the anti-tumor action of n-3 PUFAs against lung cancer, and identified molecular mechanisms for their action. In this review our effort will concentrate in critically reviewing the current evidence for the beneficial effect of n-3 PUFAs in inflammatory and neoplastic disorders of lungs and airways, and in identifying possible molecular mechanisms underlying their effects.
    Current Medicinal Chemistry 10/2010; 17(29):3358-76. DOI:10.2174/092986710793176401 · 3.85 Impact Factor
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    ABSTRACT: The beneficial health effects of n-3 polyunsaturated fatty acids (PUFAs) from marine fish are widely recognized. However, concern exists about the safety of fish intake, since the water in which they live is often highly contaminated. In the present work we analyzed the n-3 PUFA and α- and γ-tocopherol composition of 12 fish species from an artificial lake located in an Italian region far from metropolitan and industrial sites, to evaluate whether the n-3 PUFA content could be comparable to that of marine fish, and whether the levels of the antioxidant tocopherols were enough to ensure a correct preservation of the fish after being caught. Moreover, we studied the chemical and physical features of the lake water and the levels of chemical pollutants present. The benthic macro-invertebrates representing the main food source for freshwater fish were also analyzed. The good chemical–physical quality of the water, as well as the n-3 PUFA and tocopherol levels in the fish, would constitute the basis for advising the dietary usage of these fish to increase intakes of these important nutrients. Pregnant or lactating women, and infants after weaning, in particular, could benefit from eating them, since safe and adequate n-3 PUFA dietary supplementation is required to guarantee the correct pre- and post-natal development of cerebral tissues in children.
    Journal of Food Composition and Analysis 03/2010; 23(2-23):133-141. DOI:10.1016/j.jfca.2009.08.010 · 1.99 Impact Factor
  • Simona Serini · Elisabetta Piccioni · Gabriella Calviello ·
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    ABSTRACT: Colon cancer represents one of the most frequent forms of cancer worldwide. There is plenty of evidence to support the notion that chemoprevention is a major component of colon cancer control, and that dietary fats influence the rate of incidence of this kind of cancer. In particular, a variety of experimental studies conducted on animals subject to chemical carcinogenesis of colon, transplanted with colon cancer cells, or representing a genetic model of colon cancer have demonstrated the ability of diets at high content of ω-3 polyunsaturated fatty acids (PUFAs) to reduce the risk, growth, and progression of colon cancer. Several of these studies have also emphasized the importance of a reduced dietary ω-6 PUFA/ω-3 PUFA ratio to diminish the risk. The beneficial anti-tumor effects of ω-3 PUFAs have been also largely demonstrated in colon cancer cells treated in vitro with these fatty acids. The synergic action of combinations of ω-3 PUFAs and other anti-neoplastic agents has also been demonstrated both in vivo and in vitro. On the contrary, just a few human interventional trials have been conducted so far, but there is complete agreement among them and with the experimental studies on the anti-tumor efficacy of increased dietary intakes of ω-3 PUFAs. Keywordsω-3 PUFAs-Growth-inhibiting effect-Colon cancer-Experimental studies-Interventional trials
    Dietary Omega-3 Polyunsaturated Fatty Acids and Cancer, 12/2009: pages 67-89;

Publication Stats

2k Citations
354.66 Total Impact Points


  • 1981-2014
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 1995-2012
    • Catholic University of the Sacred Heart
      • Institute of General Pathology
      Milano, Lombardy, Italy
  • 2011
    • Università Cattolica del Sacro Cuore
      Milano, Lombardy, Italy
  • 1994
    • University of Rome Tor Vergata
      Roma, Latium, Italy