Corrado Rubini

Università degli studi di Foggia, Foggia, Apulia, Italy

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Publications (228)464.52 Total impact

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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.
    Biological chemistry. 09/2014;
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    ABSTRACT: The aim of this study was to determine the prognostic value of Ki-67 immunostaining in patients affected by laryngeal squamous cell carcinoma. A systematic review was carried out in a tertiary university referral center. An appropriate string was run on PubMed to retrieve articles dealing with Ki-67 immunohistochemical staining and laryngeal squamous cell carcinoma. A double cross-check was performed on citations and full-text articles by two investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 85 abstracts identified, 18 articles were included. These studies reported on 1,342 patients with histological confirmed diagnosis of laryngeal squamous cell carcinoma. Most studies showed a statistical association between Ki-67 immunohistochemical expression and at least one of the clinical and histopathological parameters considered by the authors. Overall the studies analyzed suggested that the tumoral proliferative index was statistically connected respectively with T stage (2/18), N stage (4/18), grading (6/18), disease-free survival (10/18) and overall survival (4/18). Our review strongly suggests that immunohistochemical staining of Ki-67 correlates with tumoral aggressiveness and worse prognosis in patients affected by laryngeal squamous cell carcinoma. Further high-quality prospective studies should be carried out to confirm our finding and determine the eventual differences between cancers of specific laryngeal subsites.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 06/2014; · 1.46 Impact Factor
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    ABSTRACT: Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity. Human cancers are characterized by an imbalance of regulatory mechanisms controlling different cellular pathways, including apoptosis. Apoptosis occurs in a wide variety of physiological processes, such as embryonic development, tissue homeostasis or immune defense, and its role is to remove harmful, damaged, or unwanted cells. Defective apoptosis represents an important causative factor in the development/progression of cancer, and the ability of tumor cells to evade apoptosis can play a significant role in their resistance to conventional anticancer treatment. We investigated the expression profile of genes involved in the apoptotic mechanism in 21 paired tissue samples (OSCC and adjacent normal oral mucosa) by cDNA macroarray, in order to identify differentially expressed genes in oral cancer compared to normal tissue. To validate the results obtained by cDNA macroarray, quantitative real-time PCR, Western blot, and immunohistochemical analyses were performed. Results obtained by cDNA macroarray analysis showed different expression levels of CRADD, FADD, ATM, APAF1, and TP63 genes in OSCC compared to normal mucosa. Differential gene expression measurements (tumor vs. normal tissue) performed by real-time PCR showed an overexpression of FADD and a downregulation of ATM. Moreover, Western blot analysis confirmed that both CRADD and APAF-1 were decreased in OSCC compared to normal oral mucosa. As showed by immunohistochemistry, OSCC exhibited increased expression of p63 compared to normal tissue. Interestingly, a statistically significant positive correlation was found between p63 expression and the histological grade. © 2012 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 04/2014; 53(4). · 4.27 Impact Factor
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    ABSTRACT: Gene expression and cell behavior are regulated by several factors, including small non-coding RNAs. MicroRNAs affecting cell growth, differentiation, and apoptosis are thought to play an important role in tumorigenesis. The levels of miR-146 appear to be associated with cancer development and progression, including that of oral squamous cell carcinoma. The aim of this investigation was to ascertain whether the single nucleotide polymorphism, rs2910164, mapping in the MIR146A gene, has a role in oral squamous cell carcinoma progression. A genetic association study was performed with a sample set of 346 oral squamous cell carcinomas collected in Italy. Our data indicate that the rs2910164 polymorphism is not associated with tumor development. However, a slight increase in the frequency of the variant allele was observed in Stage II tumors. Further investigations are needed to verify a possible role of the variant allele or rs2910164 in oral squamous cell carcinoma progression.
    European Journal Of Oral Sciences 03/2014; · 1.42 Impact Factor
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    ABSTRACT: To examine the prognostic significance of the immunohistochemical expression of p63 and Ki-67 oncoproteins in patients with laryngeal squamous cell carcinoma, a retrospective evaluation was carried out on a cohort of 108 patients with primary laryngeal squamous cell carcinoma (LSCC) treated by primary surgery. For the immunohistochemical evaluation, tissue section obtained by formalin-fixed and paraffin-embedded tissue blocks from resection of each patient was used. Clinicopathologic data were associated with the immunostaining results. The association among the considered variables was assessed by Fisher's exact test, Mann-Whitney test, non-parametric χ (2) test, and Spearman's rho rank test was used to assess the relations among them. Differences in p63 and Ki-67 immunoreactivity among the different groups were compared via Kruskal-Wallis test and post hoc tests were performed using Mann-Whitney test with Bonferroni correction. The overall survival rate was estimated via Kaplan-Meier method, and the cumulative incidence functions for different groups were compared using log-rank statistics. Cox proportional hazard model was employed in a multivariate analysis to assess the effect of prognostic factors in the overall survival rate. Furthermore, taking into account death due to other causes, we estimated LSCC-related survival and disease-free survival rates using competing risk analysis. The results of immunohistochemical examination showed a statistically significant relationship between the up-regulation of P63 and Ki-67, an increase in histological grading, and primary tumours associated with lymph node metastases. p63 and Ki-67 up-regulation was related to a shorter disease-free survival and a significant association was found between p63 and Ki-67 percentage of positive cells and patient survival. Finally, we noticed a significant relation between p63 and Ki-67 (ρ = 0.87). On the other hand, no statistically significant associations were found between p63 and Ki-67 down-regulation and clinicopathologic data. Our findings suggest that abnormal p63 and Ki-67 immunoreactivity may be involved in the early phases of laryngeal tumorigenesis and may become a significant prognostic predictor for both overall and disease-free survivals. These biomarkers could thus help in the selection of high-risk patients with LSCC who may benefit from more aggressive therapy or chemoprevention.
    Archives of Oto-Rhino-Laryngology 01/2014; · 1.29 Impact Factor
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    ABSTRACT: Introduction. Although altered regulation of the Wnt pathway via beta-catenin is a frequent event in several human cancers, its potential implications in oral/oropharyngeal squamous cell carcinomas (OSCC/OPSCC) are largely unexplored. Work purpose was to define association between beta-catenin expression and clinical-pathological parameters in 374 OSCCs/OP-SCCs by immunohistochemistry (IHC). Materials and Methods. Association between IHC detected patterns of protein expression and clinical-pathological parameters was assessed by statistical analysis and survival rates by Kaplan-Meier curves. Beta-catenin expression was also investigated in OSCC cell lines by Real-Time PCR. An additional analysis of the DNA content was performed on 22 representative OSCCs/OPSCCs by DNA-image-cytometric analysis. Results and Discussion. All carcinomas exhibited significant alterations of beta-catenin expression (P < 0.05). Beta-catenin protein was mainly detected in the cytoplasm of cancerous cells and only focal nuclear positivity was observed. Higher cytoplasmic expression correlated significantly with poor histological differentiation, advanced stage, and worst patient outcome (P < 0.05). By Real-Time PCR significant increase of beta-catenin mRNA was detected in OSCC cell lines and in 45% of surgical specimens. DNA ploidy study demonstrated high levels of aneuploidy in beta-catenin overexpressing carcinomas. Conclusions. This is the largest study reporting significant association between beta-catenin expression and clinical-pathological factors in patients with OSCCs/OPSCCs.
    BioMed research international. 01/2014; 2014:948264.
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    ABSTRACT: The glandular odontogenic cyst (GOC) was a rare jawbone cyst described in 1988 as a distinct entity. This lesion can involve either jaw, and the anterior region of the mandible was the most commonly affected area. Clinical and radiographic findings were not specific, and the diagnosis of GOC can be extremely difficult due to the rarity of this lesion. The cyst presented a wall constituted by fibrous connective tissue and was lined by a non-keratinized stratified squamous epithelium of variable thickness. Large areas of the lining epithelium presented cylinder cells, sometimes ciliated. A variable amount of mucina was occasionally noted. Due to the strong similarities, this cyst can be easily misdiag-nosed as a central mucoepidermoid carcinoma (CMEC). Immunohistochemistry may be an aid in diagnosis; in fact has been demonstrated that there were differences in the expression of cytokeratins (CK) in GOC and CMEC. In this study, we reported a new case of GOC in a 38 year female patient. In addition, we carried out a review of 110 previous cases reported in literature.
    The Open Dentistry Journal 01/2014; 8:1-12.
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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.
    PLoS ONE 01/2014; 9(6):e96978. · 3.53 Impact Factor
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    ABSTRACT: Background: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with E-cadherin protein expression, clinicopathological characteristics and patient outcome. Methods: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Co-localization of E-cadherin with EGF receptor was evidenced by confocal microscopy and by immunoprecipitation analyses. Results: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA down-regulation and CDH1 promoter hypermethylation. In a model in vitro of OSCC the treatment with epidermal growth factor (EGF) caused internalization and co-localization of E-cadherin with EGF receptor (EGFR) and the addition of demethylating agents increased E-cadherin expression. Conclusion: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.
    Current cancer drug targets 11/2013; · 5.13 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the influence of the place of living on periodontal status of 62 Down's syndrome (DS) subjects resident at home (DSH) or in specialized institutes (DSI) in central-eastern Italy. The demographic characteristics of the subjects and the periodontal variables were evaluated according to their living conditions. Descriptive analyses were conducted by stratifying subjects into three age groups (0-13; 14-22; >23 years), using medians and 25th-75th percentiles to summarized data. Comparisons between DSH and DSI subjects were performed using Wilcoxon rank sum test. The effect of demographic and clinical variables on periodontal status was evaluated by means of quantile regression analysis. No significant differences resulted between DSH and DSI patients, when compared for gender, age and mental retardation. No significant differences were found in the periodontal variables for the subjects with 0-13 years, while DSI subjects between 14 and 22 years of age presented higher levels of plaque index, probing depth, clinical attachment loss and a lower number of surviving teeth compared to DSH subjects. When DSI and DSH groups ≥23 years of age were compared, no differences were observed in the periodontal conditions except for PI and the number of surviving teeth. Age, body mass index and severe mental retardation were found to be significant predictors of periodontal conditions. Institutionalization has a negative effect on surviving teeth number of Down's syndrome subjects. Furthermore, the home care seems to produce benefits on the periodontal conditions of DSH 14-22 years of age.
    International Journal of Dental Hygiene 11/2013; · 0.80 Impact Factor
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    ABSTRACT: Fourier-Transform Infrared microspectroscopy, a largely used spectroscopic technique in basic and industrial researches, offers the possibility to analyze the vibrational features of molecular groups within a variety of environments. In the bioclinical field, and, in particular, in the study of cells, tissues and biofluids, it could be considered a supporting objective technique able to characterize the biochemical processes involved in relevant pathologies, such as tumoral diseases, highlighting specific spectral markers associable with the principal biocomponents (proteins, lipids and carbohydrates). In this article, we review the applications of infrared spectroscopy to the study of tumoral diseases of oral cavity compartments with the aim to improve understanding of biological processes involved during the onset of these lesions and to afford to an early diagnosis. Spectral studies on mouth, salivary glands and oral cystic lesions, objectively discriminate normal from dysplastic and cancer states characterizing also the grading.
    Journal of Molecular Structure 11/2013; · 1.40 Impact Factor
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    ABSTRACT: Objective: Oral squamous cell carcinoma (OSCC) is the most common phenotype of oral cancer. Despite the progress in the treatment of OSCC, the overall survival has not improved substantially for the last three decades due to the resistance to conventional chemo or radiotherapy. Therefore, the identification of reliable biomarkers becomes essential to develop effective anti-cancer therapy. In this study we focused on the enzyme Nicotinamide N-methyltransferase (NNMT), which catalyses the transmethylation from S-adenosyl-L-methionine to nicotinamide and to some other azaheterocycles, playing a fundamental role in the biotransformation of many xenobiotics. Several tumors have been associated with abnormal NNMT expression, however its role in cancer cell metabolism remains largely unknown. Method: 7 human oral cancer cell lines were examined for NNMT expression by Real-Time PCR, Western blot and HPLC-based catalytic assay. Subsequently, we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation in vitro and in vivo. NNMT mRNA was detected in all cancer cell lines tested, showing a very high expression level in the PE/CA PJ-15 cells, in keeping with the results of Western blot and catalytic activity assay. PE/CA PJ-15 cell line was stably transfected with shRNA plasmids against NNMT and analyzed by MTT and Soft agar Assay. Transfected and control cells were injected into athymic mice in order to evaluated the effect of NNMT silencing on tumor growth. ShRNA vectors targeted against NNMT efficiently suppressed gene expression, at both the mRNA and protein levels. Result: Downregulation of NNMT expression by shRNA resulted in a decrease in cell proliferation and colony formation ability on soft agar. In athymic mice, NNMT silencing induced a marked reduction in tumour volume. Conclusion: Our results seem to suggest that NNMT is involved in cell proliferation and its inhibition could represent a potential molecular approach to the treatment of oral carcinoma.
    Annual Meeting of the IADR Continental European Division 2013; 09/2013
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    ABSTRACT: The authors report a case of oral tuberculosis in a 38-year-old heavy cigarette smoker man. He showed a painful, non-healing ulc er with indurated borders of the lateral surface of the tongue. No tonsil or lymph node enlargement was also noted. The medical history was not significant for systemic disease. Histopathological examination showed granulomas exhibiting a central caseinating necrotic focus, surrounded by mononucl ear cell s, epithelioid histiocytes and multi nucl eated Langhans giant cell s. A mantle of lympocytes and fibrous tissue surrounded the granulomas. Since the morphologic picture oriented for tubercoloid granulomata, a Ziehl- Neelsen staining of the tissue was performed. Chest radiography did not detect any pulmonary or nodal disease. On the bases of these results a diagnosis of oral tuberculosis was establ ished.
    Minerva stomatologica 06/2013;
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    ABSTRACT: OBJECTIVES: p120ctn is a component of the catenin family. To date, there have only been two studies examining expression levels of p120ctn in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Paraffined specimens of 113 OSCCs and 12 of normal mucosa were examined by immunohistochemistry. Frozen samples of 20 OSCCs and 5 of normal mucosa were examined by Western blot (WB). Results were correlated with clinicopathological parameters. Five cell lines were examined by immunofluorescence, immunocytochemistry, and WB to show immunoreactivity and cellular localization of p120ctn. RESULTS: Altered p120ctn expression was observed in 109/113 cases of OSCC. Heterogenous cytoplasmic/nuclear expression was associated with loss of membranous distribution (88/113 cases). Complete loss of expression was noted in 21/113 cases. Increased cytoplasmic expression was evident in all positive cases, without significant correlation among p120ctn staining/pattern and grading/stage. Reduction/absence of p120ctn expression was related to poor prognosis (P < .05). CONCLUSION: p120ctn delocalization/loss of expression could be an independent prognostic marker in OSCC.
    Oral surgery, oral medicine, oral pathology and oral radiology. 06/2013; 115(6):789-798.
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    ABSTRACT: Lung cancer, predominantly non-small cell lung cancer (NSCLC), is currently the most common cause of malignancy-related death in the world. Despite advances in both detection and treatment, its incidence rate is still increasing. Therefore, effective strategies for early detection as well as molecular therapeutic targets are urgently needed. We focused on the enzyme nicotinamide N-methyltransferase (NNMT). NNMT expression levels were investigated in tumor, tumor-adjacent, and surrounding tissue samples of 25 patients with NSCLC by Real-Time PCR, Western blot analysis, and catalytic activity assay. NNMT enzyme activity in NSCLC was then correlated with clinicopathological characteristics. Results obtained showed NNMT upregulation (mRNA and protein) in tumor compared with both tumor-adjacent and surrounding tissue. Moreover, NSCLC displayed significantly higher activity levels than those determined in both tumor-adjacent and surrounding tissue. Interestingly, both tumor-adjacent and surrounding tissue samples of unfavorable cases (N+) seem to display higher activity levels than those of favorable NSCLCs (N0). The present work shows a marked increase of NNMT enzyme activity in NSCLC and suggests that normal-looking tissue of unfavorable cases seems to change toward cancer. Further studies may establish whether NNMT could represent a target for an effective anti-cancer therapy.
    Cell biochemistry and biophysics 03/2013; · 3.34 Impact Factor
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    ABSTRACT: Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats. Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations. The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.
    PLoS ONE 01/2013; 8(9):e74234. · 3.53 Impact Factor
  • Annali di stomatologia. 01/2013; 4(Suppl 2):33.
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    ABSTRACT: To analyse the relationship of the immunohistochemical p63 expression with tumoral extent, histologic grade, lymph node involvement and clinical stage in laryngeal squamous cell carcinoma (LSCC), a series of 81 patients with primary LSCC treated by primary surgery was retrospectively evaluated. Immunohistochemistry was performed on formalin-fixed and paraffin-embedded tissue blocks from surgical samples. Clinicopathologic data were correlated with the p63 staining results. Differences in p63 immunoreactivity between the different groups were compared using both parametric analysis of variance (ANOVA) and non-parametric Kruskal-Wallis test. Statistical significance was set at p less than 0.05. All statistical analyses were performed using the R statistical package. We found a statistically significant association between p63 protein expression and increase of tumor extension (T1 vs T3), of histological grading, of level of lymph node involvement (N0 vs N1 and N2), and clinical stage (I vs IV). Our findings suggest that abnormal expression of p63 may be involved in the early phases of laryngeal tumorigenesis and this oncoprotein might become a useful predictor of clinical outcome.
    Journal of biological regulators and homeostatic agents 01/2013; 27(1):121-129. · 5.18 Impact Factor
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    ABSTRACT: Introduction. Despite their histological resemblance to colorectal adenocarcinoma, there is some information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). To evaluate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) gene defects in ITAC, by investigating the immunohistochemical expression of TRAIL gene product in a group of ethmoidal ITACs associated with occupational exposure. Material and Methods. Retrospective study on 23 patients with pathological diagnosis of primary ethmoidal ITAC. Representative formalin-fixed, paraffin-embedded block from each case was selected for immunohistochemical studies using the antibody against TRAIL. Clinicopathological data were also correlated with the staining results. Results. The immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of TRAIL expressing cells compared to well-differentiated cases. No correlation was found with other clinicopathological parameters, including T, stage and relapses. Conclusion. The relationship between upregulation of TRAIL and poorly differentiated ethmoidal adenocarcinomas suggests that the mutation of this gene, in combination with additional genetic events, could play a role in the pathogenesis of ITAC.
    International journal of surgical oncology. 01/2013; 2013:203873.
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    ABSTRACT: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. Despite progress in the treatment of OSCC, overall survival has not improved substantially in the last three decades. Therefore, identification of reliable biomarkers becomes essential to develop effective anti-cancer therapy. In this study, we focused on the enzyme Nicotinamide N-methyltransferase (NNMT), which plays a fundamental role in the biotransformation of many xenobiotics. Although several tumors have been associated with abnormal NNMT expression, its role in cancer cell metabolism remains largely unknown. In this report, 7 human oral cancer cell lines were examined for NNMT expression by Real-Time PCR, Western blot and HPLC-based catalytic assay. Subsequently, we evaluated the in vitro effect of shRNA-mediated silencing of NNMT on cell proliferation. In vivo tumorigenicity of oral cancer cells with stable knockdown of NNMT was assayed by using xenograft models. High expression levels of NNMT were found in PE/CA PJ-15 cells, in keeping with the results of Western blot and catalytic activity assay. PE/CA PJ-15 cell line was stably transfected with shRNA plasmids against NNMT and analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and soft agar Assays. Transfected and control cells were injected into athymic mice in order to evaluate the effect of NNMT silencing on tumor growth. NNMT downregulation resulted in decreased cell proliferation and colony formation ability on soft agar. In athymic mice, NNMT silencing induced a marked reduction in tumour volume. Our results show that the downregulation of NNMT expression in human oral carcinoma cells significantly inhibits cell growth in vitro and tumorigenicity in vivo. All these experimental data seem to suggest that NNMT plays a critical role in the proliferation and tumorigenic capacity of oral cancer cells, and its inhibition could represent a potential molecular approach to the treatment of oral carcinoma.
    PLoS ONE 01/2013; 8(8):e71272. · 3.53 Impact Factor

Publication Stats

2k Citations
464.52 Total Impact Points

Institutions

  • 2005–2014
    • Università degli studi di Foggia
      • Department of Surgical Science
      Foggia, Apulia, Italy
  • 2003–2014
    • Università Politecnica delle Marche
      • • Department of Molecular Pathology and Innovative Therapies
      • • Department of Biochemistry, Biology and Genetics
      • • Institute of Pathological Anatomy
      • • Department of Materials, Environmental Sciences and Urban Planning SIMAU
      Ancona, The Marches, Italy
  • 2007–2010
    • University of Bologna
      • • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      • • Institute of Haematology
      Bologna, Emilia-Romagna, Italy
  • 1998–2010
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • Division of Restorative Dentistry
      Chieta, Abruzzo, Italy
  • 2009
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
  • 2008
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
  • 2004–2008
    • Universita degli studi di Ferrara
      • Department of Morphology, Surgery and Experimental Medicine
      Ferrara, Emilia-Romagna, Italy
  • 1999–2007
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 2001
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2000
    • University of Naples Federico II
      • Section of Psychology
      Napoli, Campania, Italy
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy