Corrado Rubini

Università Politecnica delle Marche, Ancona, The Marches, Italy

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Publications (152)367.94 Total impact

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    ABSTRACT: TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC/OPSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = .002). There was no statistical correlation between TLR4 intensity and PCR HPV results (p more than 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). These data have shown that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.
    No preview · Article · Dec 2015 · Frontiers in bioscience (Elite edition)
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    ABSTRACT: Fourier transform infrared imaging (FTIRI) is a powerful tool for analyzing biochemical changes in tumoral tissues. The head and neck region is characterized by a great variety of lesions, with different degrees of malignancy, which are often difficult to diagnose. Schneiderian papillomas are sinonasal benign neoplasms arising from the Schneiderian mucosa; they can evolve into malignant tumoral lesions (squamous cell carcinoma). In addition, they can sometimes be confused with the more common inflammatory polyps. Therefore, an early and definitive diagnosis of this pathology is mandatory. Progressing in our research on the study of oral cavity lesions, 15 sections consisting of inflammatory sinonasal polyps, benign Schneiderian papillomas, and sinonasal undifferentiated carcinomas were analyzed using FTIRI. To allow a rigorous description of these pathologies and to gain objective diagnosis, the epithelial layer and the adjacent connective tissue of each section were separately investigated by following a multivariate analysis approach. According to the nature of the lesion, interesting modifications were detected in the average spectra of the different tissue components, above all in the lipid and protein patterns. Specific band-area ratios acting as spectral markers of the different pathologies were also highlighted. © 2015 Society of Photo-Optical Instrumentation Engineers (SPIE).
    No preview · Article · Dec 2015 · Journal of Biomedical Optics
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    ABSTRACT: In this study, we investigate the relation between vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) in periodontal disease of diabetic and non-diabetic individuals. We evaluated immunohistochemical VEGF and iNOS expressions in gingival biopsies from healthy individuals (no chronic periodontitis (CP)), patients with periodontitis alone (CP), patients with diabetes alone (DM) and diabetic patients with chronic periodontitis (DM + CP). We found a significant positive correlation between VEGF and iNOS expression in non-diabetic groups, but not in diabetic ones. Periodontal clinical parameters were not found to be significantly correlated with the inflammatory markers in no-CP, CP, and DM groups, whereas in DM + CP, positive and significant correlations were found between all the considered periodontal parameters and epithelial VEGF and endothelial iNOS. The uncoupling of VEGF and iNOS expression in diabetic individuals could allow a greater involvement of the markers in the inflammatory process of periodontitis.
    Full-text · Article · Dec 2015 · Inflammation
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    ABSTRACT: Cytomegalovirus (CMV) is one of eight herpes virus that can cause disease in humans affecting the 30-100% of the population. In the oral cavity, CMV infection appears as a common ulcerated lesion, without clinical pathognomonic signs. The locations of oral lesions are hard palate, soft palate, tongue and floor of the mouth. This case report describes the case of a 59-year-old woman with a painful roundish ulcerated lesion covered with fibrinous exudate located on the cheek. The patient underwent kidney transplantation for a reduced kidney function secondary to the Good pasturesyndrome and was receiving immunosuppressive chemotherapy. The ulcer improved rapidly following the initiation of ganciclovir treatment.
    Full-text · Article · Sep 2015
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    ABSTRACT: Infection with high-risk human papillomavirus (HPV) is linked to a sub-group of squamous cell oropharyngeal tumors (OPSCC). Our aim was to compare an HPV Polymerase Chain Reaction (PCR) assay and p16(INK4A) expression status by immunohistochemistry (IHC) as a surrogate marker. This was a retrospective study considering patients affected by squamous cell oropharyngeal tumors. All included samples were processed for IHC for p16(INK4A) and tested by PCR for detection of HPV DNA and HPV genotyping. A total of 84 patients affected by squamous cell oropharyngeal tumors were included and tested. A significant positive correlation was found between HPV PCR and p16(INK4A) IHC but the agreement was poor (k coefficient of 0.25). In fact, the sensitivity of p16(INK4A) IHC positivity in detecting HPV PCR positivity was low (28.21%, 95% confidence interval=16.54% - 43.78%). Positivity of p16(INK4A) by IHC had a low sensitivity in detecting HPV DNA and our results suggest the need at least to test p16(INK4A) IHC- negative samples using HPV PCR to increase detection accuracy and provide valuable information for the clinical management of these patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Full-text · Article · Sep 2015 · Anticancer research
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    ABSTRACT: Objectives: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage. Materials and methods: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated. Results and conclusion: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.
    Full-text · Article · Sep 2015 · Lung cancer (Amsterdam, Netherlands)
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    ABSTRACT: Oral lichen planus (OLP) is a chronic disease, with a central role to cell-mediated autoimmunity. Osteopontin promotes migration and recruitment of immune cells, CD44 is its receptor, and Survivin seems to be important in skin/mucosa homeostasis. The aim of this study was to investigate their expression in biopsy specimens of patients with different OLP clinical types and healthy controls.Biopsy specimens from 30 patients with OLP (15 atrophic and 15 hyperplastic) and 15 healthy controls were subjected to immune-histochemical analysis, to detect the expression of osteopontin, CD44, and Survivin in oral epithelia. The distributions of positively stained cells were evaluated with a quantitative method, while the inflammation degree was evaluated with a semi-quantitative one.Expression of osteopontin and CD44 was higher in OLP than controls, while Survivin expression was lower in OLP patients. There was a greater reduction of Survivin expression in atrophic OLP than hyperplastic OLP. A correlation between osteopontin expression and a high degree of inflammation was found. Furthermore, Survivin expression was higher in cases with low intensity of inflammation.Osteopontin, CD44, and Survivin seem to be involved in OLP pathogenesis, and further investigations are needed for clarifying their role in this oral disease. © The Author(s) 2015.
    No preview · Article · Aug 2015 · International journal of immunopathology and pharmacology

  • No preview · Article · Aug 2015 · Endoscopy
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    ABSTRACT: An age-dependent model of the periodontium was reproduced to evaluate the effect of life-long feeding on a low coenzyme Q10 dosage in n-6, n-3 polyunsaturated fatty acid or monounsaturated fatty acid-based diets on periodontal tissues of young and old rats. Results shown that exacerbated age-related alveolar bone loss previously associated to n-6 polyunsaturated fatty acid diet was attenuated by coenzyme Q10. Gene expression analysis suggests that involved mechanisms might be related to a restored capacity of mitochondria to adapt to aging in gingival cells from rats fed on n-6 polyunsaturated fatty acid. In particular, this could be due to an age-related increase of the rate of mitochondrial biogenesis and a better oxidative and respiratory balance in these animals. From the nutritional and clinical point of view, it is noteworthy that supplementation with coenzyme Q10 could counteract the negative effects of n-6 polyunsaturated fatty acid on alveolar bone loss (a major feature of periodontitis) associated to age. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail:
    Full-text · Article · Jul 2015 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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    ABSTRACT: Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival. Retrospective cohort study. Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences. NA Laryngoscope, 2015. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
    No preview · Article · Jul 2015 · The Laryngoscope
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy. © 2015 S. Karger AG, Basel.
    No preview · Article · May 2015 · Cellular Physiology and Biochemistry
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    ABSTRACT: To investigate survivin, AKT and VEGF expression in primary mucosal oral melanoma and explore their correlation with clinicopathological features and prognosis. Twenty malignant primary oral melanomas were immunostained with antibodies against survivin, AKT, VEGF, CD34. Histological parameters and disease-specific survival were related to marker expressions. Survivin localization was both nuclear and cytoplasmic with a higher expression of nuclear survivin. High melanocyte survivin expression significantly correlated with higher thickness of primary melanoma. A significant positive correlation was found between melanocyte survivin and phospho Akt and VEGF expression. Survivin was significantly associated with the presence of metastasis. High melanocyte survivin and high endothelial VEGF expression were inversely correlated to both overall and disease-specific 5-year survival. Survivin, via AKT and VEGF, seems to play an important role in oral melanoma and could represent an important prognostic marker of melanoma progression. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Full-text · Article · Apr 2015 · Anticancer research
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    ABSTRACT: The incidence of cutaneous malignant melanoma is increasing worldwide, resulting in the demand for clinically useful prognostic biomarkers, especially for invasive and metastatic disease. We studied the immunohistochemical expression of interleukin-17 (IL-17), IL-23, and p73 in 35 malignant melanomas and compared them with benign melanocytic nevi and Spitz nevi, correlating them with clinical-pathological variables. A higher and statistically significant difference (P<0.05) in the intensity and percentage of stained cells of IL-17 and IL-23 was found in the melanoma group than in ordinary benign nevi that did not correlate with Breslow thickness nor Clark level. Moreover, p73 staining and percentage of stained cells was significantly higher (P<0.05) in all the melanomas studied, with a peculiar cytoplasmatic distribution. Our findings could suggest a possible IL-17, IL-23, and p73 involvement in cutaneous melanomas with a hypothetical impact on melanoma invasiveness.
    No preview · Article · Mar 2015 · Melanoma research
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    ABSTRACT: A high risk of neoplastic transformation of nasal and paranasal sinuses mucosa is related to the occupational exposure to wood dust. However, the role of occupational exposures in the aetiology of the airway cancers remains largely unknown. Here, an in vitro model was performed to investigate the carcinogenic effect of wood dusts. Human bronchial epithelial cells were incubated with hard and soft wood dusts and the DNA damage and response to DNA damage evaluated. Wood dust exposure induced accumulation of oxidised DNA bases, which was associated with a delay in DNA repair activity. By exposing cells to wood dust at a prolonged time, wood dust-initiated cells were obtained. Initiated-cells were able to form colonies in soft agar, and to induce blood vessel formation. These cells showed extensive autophagy, reduced DNA repair, which was associated with reduced OGG1 expression and oxidised DNA base accumulation. These events were found related to the activation of EGFR/AKT/mTOR pathway, through phosphorylation and subsequent inactivation of tuberin. The persistence in the tissue of wood dusts, their repetitious binding with EGFR may continually trigger the activation switch, leading to chronic down-regulation of genes involved in DNA repair, leading to cell transformation and proliferation. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail:
    Full-text · Article · Feb 2015 · Mutagenesis
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    ABSTRACT: The aim of this systematic review was to determine the prognostic value of Bcl-2 immunostaining in patients affected by laryngeal squamous cell carcinoma. An appropriate search was conducted on PubMed to retrieve articles dealing with this topic. A double cross-check was performed on citations and full-text articles by 2 investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 115 abstracts identified, 15 articles were included. These studies reported on 1,150 patients with histologically confirmed diagnosis of laryngeal squamous cell carcinoma. Only a few studies showed a statistical correlation between Bcl-2 immunohistochemical expression and at least 1 of the clinical and histopathological parameters considered by the authors. Moreover, these findings were also discordant between them. Overall the studies analyzed suggested that Bcl-2 expression was statistically connected with N stage (2/14), grading (2/14), disease-free survival (3/14) and overall survival (5/14). Interestingly, all of the 3 studies investigating the relation between Bcl-2 and radioresistance showed significant results in terms of recurrence-free survival and overall survival. Our review strongly suggests that the immunohistochemical staining of Bcl-2 does not correlate with tumoral aggressiveness and prognosis of patients affected by laryngeal squamous cell carcinoma and treated with primary surgery. However, an interesting connection of this protein could be demonstrated with tumoral radioresistance. Further, high-quality prospective studies should be carried out to confirm this hypothesis.
    No preview · Article · Dec 2014 · The International journal of biological markers
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    ABSTRACT: Objectives Oral squamous cell carcinoma (OSCC) represents about ninety percent of all oral neoplasms with a poor clinical prognosis. In order to improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity.Materials And Methods We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through Real-Time PCR, western blot and immunohistochemical analyses in tumor and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed.ResultsPokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor versus normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC versus normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion.Conclusion This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Oral Diseases
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    ABSTRACT: Raw cement asbestos (RCA) undergoes a complete solid state transformation when heated at high temperatures. The secondary raw material produced, high temperatures-cement asbestos (HT-CA) is composed of newly-formed crystals in place of the asbestos fibers present in RCA. Our previous study showed that HT-CA exerts lower cytotoxic cell damage compared to RCA. Nevertheless further investigations are needed to deepen our understanding of pathogenic pathways involving oxidative and nitrative damage. Our aim is to deepen the understanding of the biological effects on A549 cells of these materials regarding DNA damage related proteins (p53, its isoform p73 and TRAIL) and nitric oxide (NO) production during inducible nitric oxide synthase (iNOS)-mediated inflammation. Increments of p53/p73 expression, iNOS positive cells and NO concentrations were found with RCA, compared to HT-CA and controls mainly at 48 h. Interestingly, ferrous iron causing reactive oxygen species (ROS)-mediated DNA damage was found in RCA as a contaminant.HT-CA thermal treatment induces a global recrystallization with iron in a crystal form poorly released in media. HT-CA slightly interferes with genome expression and exerts lower inflammatory potential compared to RCA on biological systems. It could represent a safe approach for storing or recycling asbestos and an environmentally friendly alternative to asbestos waste.
    Full-text · Article · Nov 2014 · Acta Histochemica
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    ABSTRACT: Fractal dimension (FD) in tissue specimens from patients with oral squamous cell carcinoma (OSCC) was evaluated. FD values in different stages of OSCC, and the correlations with clinicopathological variables and patient survival were investigated. Histological sections from OSCC and control non-neoplastic mucosa specimens were stained with hematoxylin–eosin for pathological analysis and with Feulgen for nuclear evaluation. FD in OSCC groups vs. controls revealed statistically significant differences (P < 0.001). In addition, a progressive increase of FD from stage I and II lesions and stage III and IV lesions was observed, with statistically significant differences (P = 0.003). Moreover, different degrees of tumor differentiation showed a significant difference in the average nuclear FD values (P = 0.001). A relationship between FD and patients' survival was also detected with lower FD values associated to longer survival time and higher FD values with shorter survival time (P = 0.034). These data showed that FD significantly increased during OSCC progression. Thus, FD could represent a novel prognostic tool for OSCC, as FD values significantly correlated with patient survival. Fractal geometry could give insights into tumor morphology and could become an useful tool for analyzing irregular tumor growth patterns.
    No preview · Article · Nov 2014 · Journal of Oral Pathology and Medicine
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    ABSTRACT: Abstract Lung cancer is the second most commonly diagnosed neoplasm, and represents the leading cause of tumor death worldwide. Since patients are often diagnosed at a late stage, current therapeutic strategies have limited effectiveness and the prognosis remains poor. Successful treatment depends on early diagnosis and knowledge concerning molecular mechanisms underlying lung carcinogenesis. In the present study, we focused on nicotinamide N-methyltransferase (NNMT), which is overexpressed in several malignancies. First, we analysed NNMT expression in a cohort of 36 patients with non-small cell lung cancer (NSCLC) by immunohistochemistry. Subsequently, we examined NNMT expression levels in the human lung cancer cell line A549 by Real-Time PCR, Western blot and catalytic activity assay, and evaluated the effect of NNMT knockdown on cell proliferation and anchorage independent cell growth by MTT and soft-agar colony formation assays, respectively. NSCLC displayed higher NNMT expression levels compared to both tumor-adjacent and surrounding tissue. Moreover, shRNA-mediated gene silencing of NNMT led to a significant inhibition of cell proliferation and colony formation ability on soft agar. Our results show that the downregulation of NNMT significantly reduced in vitro tumorigenicity of A549 cells and suggest that NNMT could represent an interesting molecular target for lung cancer therapy.
    Full-text · Article · Sep 2014 · Biological Chemistry
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    ABSTRACT: Proteolytic tissue degradation is a typical phenomenon in inflammatory periodontal diseases. HtrA1 (High temperature requirement A 1) has a serine protease activity and is able to degrade fibronectin whose fragments induce the expression and secretion of several matrix metalloproteinases (MMPs). The aim of this study was to investigate for the first time if HtrA1 has a role in gingivitis and in generalized forms of chronic and aggressive periodontitis. Expression of HtrA1 was investigated in 16 clinically healthy gingiva, 16 gingivitis, 14 generalized chronic periodontitis and 10 generalized aggressive periodontitis by immunohistochemistry and real-time PCR. Statistical comparisons were performed by the Kruskall-Wallis test. Significantly higher levels of HtrA1 mRNA and protein expression were observed in pathological respect to healthy tissues. In particular, we detected an increase of plasma cell HtrA1 immunostaining from gingivitis to chronic and aggressive periodontitis, with the higher intensity in aggressive disease. In addition, we observed the presence of HtrA1 in normal and pathological epithelium, with an increased expression, particularly in its superficial layer, associated with increasingly severe forms of periodontal disease. We can affirm that HtrA1 expression in plasma cells could be correlated with the destruction of pathological periodontal tissue, probably due to its ability to trigger the overproduction of MMPs and to increase the inflammatory mediators TNF-α and IL-1β by inhibition of TGF-β. Moreover, epithelial HtrA1 immunostaining suggests a participation of the molecule in the host inflammatory immune responses necessary for the control of periodontal infection.
    Full-text · Article · Jun 2014 · PLoS ONE

Publication Stats

2k Citations
367.94 Total Impact Points


  • 2001-2015
    • Università Politecnica delle Marche
      • • Department of Biomedical Sciences and Public Health
      • • Chair of Human Anatomy
      • • Institute of Pathological Anatomy
      Ancona, The Marches, Italy
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • Division of Restorative Dentistry
      Chieta, Abruzzo, Italy
  • 2010
    • Università degli studi di Foggia
      • Department of Surgical Science
      Foggia, Apulia, Italy
  • 2008
    • University of Bologna
      • Institute of Haematology
      Bologna, Emilia-Romagna, Italy
  • 2004
    • University of Ferrara
      • Department of Morphology, Surgery and Experimental Medicine
      Ferrare, Emilia-Romagna, Italy
  • 2000-2001
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom