Targeting nicotinamide N-methyltransferase decreased aggressiveness of osteosarcoma cells.

BACKGROUND: Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide N-methyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics. NNMT overexpression was reported in a wide variety of cancers, and several studies demonstrated that is able to promote cell proliferation, migration and resistance to chemotherapy. The aim of this study was to explore the potential involvement of NNMT in OS. METHODS: Immunohistochemical analyses have been performed to evaluate NNMT expression in selected OS and healthy bone tissue samples. Subsequently, OS cell lines have been transfected with vectors targeting NNMT mRNA (shRNAs) and the impact of this downregulation on migration, cell proliferation, and response to chemotherapeutic treatment was also analysed by wound healing, MTT, SRB and Trypan blue assays, respectively. RESULTS: Results showed that OS samples display a significantly higher NNMT expression compared with healthy tissue. Preliminary results suggest that NNMT silencing in OS cell lines is associated to a decrease of cell proliferation and migration, as well as to enhanced sensitivity to chemotherapy. Data obtained showed that NNMT may represent an interesting marker for OS detection and a promising target for effective anti-cancer therapy.

Non-neoplastic jaw cysts: a 30-year epidemiological study of 2150 cases in the Italian population.

Non-neoplastic jaw cyst (NJC) is one of the most common lesions in oral cavity, but there are only few detailed and extended epidemiological data based on the 2017 WHO classification. The aim of this study was to perform an epidemiological analysis of all NJCs treated from 1990 to 2019 at the Marche Polytechnic University, and to compare these data with those published in the literature. This retrospective study considered 2060 patients treated from 1990 to 2019. The NJCs were classified according to the 2017 WHO classification, and the main clinicopathological variables were analysed (sex, age, diagnosis, site of onset, size, and recurrences). Of 2150 total lesions, there were 2095 primary cysts and 55 recurrences; men are more frequently affected than women (M/F ratio of 1.73:1). The mean age of occurrence was 46.6 years, with a peak of frequency in the fifth decade. The mandible was more frequently involved than the maxilla, with a mean size of 1.9cm. Radicular cyst was the most frequently diagnosed cyst (56.6%), followed by dentigerous cyst (23.4%) and odontogenic keratocyst (12.9%). This is the first epidemiological study on NJCs in the Italian population according to 2017 WHO classification.

Prognostic impact of Ki-67 proliferative index in resectable pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by complex biological features and poor prognosis. A prognostic stratification of PDAC would help to improve patient management. The aim of this study was to analyse the expression of Ki-67 in relation to prognosis in a cohort of patients with PDAC who had surgical treatment. Methods: Patients who had pancreatic resection between August 2010 and October 2014 for PDAC at two Italian centres were reviewed retrospectively. Patients with metastatic or locally advanced disease, those who received neoadjuvant chemotherapy, patients with PDAC arising from intraductal papillary mucinous neoplasm and those with missing data were excluded. Clinical and pathological data were retrieved and analysed. Ki-67 expression was evaluated using immunohistochemistry and patients were stratified into three subgroups. Survival analyses were performed for disease-free (DFS) and disease-specific (DSS) survival outcomes according to Ki-67 expression and tumour grading. Results: A total of 170 patients met the selection criteria. Ki-67 expression of 10 per cent or less, 11-50 per cent and more than 50 per cent significantly correlated with DFS and DSS outcomes (P = 0·016 and P = 0·002 respectively). Ki-67 index was an independent predictor of poor DFS (hazard ratio (HR) 0·52, 95 per cent c.i. 0·29 to 0·91; P = 0·022) and DSS (HR 0·53, 0·31 to 0·91; P = 0·022). Moreover, Ki-67 index correlated strongly with tumour grade (P < 0·001). Patients with PDAC classified as a G3 tumour with a Ki-67 index above 50 per cent had poor survival outcomes compared with other patients (P < 0·001 for both DFS and DSS). Conclusion: Ki-67 index could be of use in predicting the survival of patients with PDAC. Further investigation in larger cohorts is needed to validate these results.

Antecedentes: El adenocarcinoma ductal de páncreas (pancreatic ductal adenocarcinoma, PDAC) es una enfermedad agresiva con características biológicas complejas y pronóstico pobre. La estratificación pronóstica del PDAC ayudaría a mejorar el tratamiento del paciente. El objetivo de este estudio era analizar la expresión de Ki­67 como marcador pronóstico en una cohorte de pacientes con PDAC tratados quirúrgicamente. Métodos: Se efectuó un análisis retrospectivo de pacientes sometidos a resección pancreática por PDAC en dos centros italianos entre agosto de 2010 y octubre de 2014. Se excluyeron los pacientes con enfermedad metastásica o localmente avanzada, los tratados con quimioterapia neoadyuvante, los pacientes con PDAC originado en una neoplasia papilar mucinosa intraductal y aquellos pacientes con datos incompletos. Se analizaron los datos clínicos y anatomopatológicos. La expresión de Ki­67 se evaluó por inmunohistoquímica y los pacientes se estratificaron en tres grupos. Se calculó la supervivencia libre de enfermedad (disease­free survival, DFS) y la supervivencia específica de la enfermedad (disease­specific survival, DSS) según la expresión de Ki­67 y el grado tumoral. Resultados: Un total de 170 pacientes cumplió los criterios de selección. La expresión de Ki­67 del ≤ 10%, 11­50% y > 50% mostró una correlación significativa con los resultados de DFS y DSS (P = 0,016 y P = 0,002, respectivamente). El índice Ki­67 fue un predictor independiente de pobre DFS (cociente de riesgos instantáneos, hazard ratio, HR 0,52, i.c. del 95% 0,29­0,91; P = 0,022) y DSS (HR 0,53, i.c. del 95% 0,31­0,91; P = 0,022). Asimismo, el índice Ki­67 se correlacionaba fuertemente con el grado tumoral (P < 0,001). Los pacientes con un PDAC clasificado como tumor grado G3 y con un índice Ki­67 > 50% tenían peores resultados de supervivencia en comparación con otros pacientes (P < 0,001 para ambos DFS y DSS). Conclusión: El índice Ki­67 se puede utilizar como predictor de supervivencia en pacientes con PDAC. Hace falta seguir investigando para validar estos resultados en cohortes más grandes.

Large cell neuroendocrine carcinoma of the submandibular gland: a case report and literature review.

Neuroendocrine tumors (NET) are a heterogeneous group of malignancies with a broad spectrum of histomorphologies, tissue origins, and clinical outcomes, which arise from neural crest cells with neuroendocrine differentiation. Salivary gland tumors account for 3-6% of all head and neck neoplasms, while large cell neuroendocrine carcinomas (LCNEC) of the salivary gland are extremely rare, with few cases reported in literature, and only 5 cases involving submandibular gland. The rarity of these tumors in salivary glands is probably related to the scarcity of neuroendocrine cells in this tissue, whose presence is still a matter of debate. Regardless of their low frequency, it is imperative to differentiate these tumors from the much more common squamous cell carcinomas and metastatic NETs, due to different therapeutic approach and prognosis. In this paper, we report the case of a 21-year-old man, with a LCNEC involving a submandibular gland followed by several recurrences over the years. In addition, we include a comprehensive review of the available literature on this topic.

Immunohistochemical study of osteopontin in oral squamous cell carcinoma allied to fractal dimension.

The aim of the study was to consider a possible correlation between the intensity of expression of osteopontin and grading established by the pathologist. Furthermore, a correlation was investigated between the increase of fractal dimension and osteopontin in order to use this marker as an early and reliable diagnostic tool for the degree of cell transformation in oral squamous carcinoma. Ten histologically healthy oral samples and sixty-four primary oral squamous cell carcinomas specimens were analysed by a single pathologist. Immunohistochemical analysis and Fulgen stain were performed in order to evaluate intensity of expression of osteopontin and fractal dimension. Data obtained were presented as mean and standard deviation and processed for the statistical analysis. Ostepontin expression revealed a statistical significance between groups (P less than 0.001). Fractal dimension in oral squamous cell carcinoma groups vs controls revealed statistically significant differences (P less than 0.001). The fractal dimension value and the osteopontin expression were compared, using two-dimensional scatter. The correlation was relevant in the G3 group. The results demonstrated a correlation between the growths of osteopontin expression and nuclear abnormality measured by fractal dimension. These results support the hypothesis that the level of osteopontin expression might be used as a marker for the evaluation of oral squamous cell carcinoma differentiation. Osteopontin and fractal dimension could support the histological grading to increase the predictability of the diagnosis, choices of treatment procedure and long-term prognosis.

Odontogenic tumors: a retrospective clinicopathological study from two Italian centers.

OBJECTIVE: The aim of this retrospective study was to perform an epidemiological analysis of all odontogenic tumors treated in the University Hospitals "Ospedali Riuniti" in Ancona and "Policlinico" in Bari, from 1990 to 2015. MATERIALS AND METHODS: A retrospective survey of 277 patients treated for odontogenic tumors from 1990 to 2015 was performed. Data were retrieved from the archives of the above quoted Sections of Pathology. The lesions were classified according to 2005 WHO histological classification, and the following variables were analyzed: age, sex, histopathological diagnosis, site distribution, tumor size, and relapses. Peripheral odontogenic tumors were analyzed considering these lesions separately from their central counterparts. RESULTS: In a total of 344 surgical specimens, there were 277 primary tumors and 67 recurrences. As regards primary lesions, there were 185 odontogenic keratocysts (keratocystic odontogenic tumors) (66.8%), 49 ameloblastomas (17.7%), and 40 other benign odontogenic tumors (14.4%). As to malignant tumors, only 3 ameloblastic carcinomas were found (1.1%). The mean age was 46.7 years, with a M:F ratio of 1.8:1. The mandible was the most common site of localization, with 211 cases (76.2%). Also, 21 cases of peripheral odontogenic tumors were found, ameloblastomas being the most common (8 cases, 38.1%). CONCLUSIONS: There is a wide variety of cysts, some of which are subject to variations according to sex, localization, and age. Odontogenic tumors are rare neoplasms and appear to show variations according to sex, localization, and age, and may be useful to the clinicians who need to make clinical judgments before biopsy about the most probable diagnosis.

Malignant transformation of sinonasal inverted papilloma and related genetic alterations: a systematic review.

Schneiderian papillomas are uncommon tumors which may develop within the nasal cavity and comprise three well-defined histological types: sinonasal inverted papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known the rate of Schneiderian papilloma may also present a malignant degeneration and SNIP represents the most important subgroup in consideration of its frequency and malignant propensity. Although HPV infection is always considered the first event favoring the development of SNIP, however, it is not established as an eventual connection between viral actions and malignant transformation. In fact, different molecular mechanisms are suspected to play a crucial role in this process and, currently, many authors agree that only by improving our knowledge about these mechanisms it will be possible to achieve new and effective targeted therapies. So the aim of this study was firstly to systematically review the literature focusing on different biomarkers that could be implicated in the stages of SNIP malignant degeneration. Secondly, a systematic review with meta-analysis was performed to better define the incidence of sinonasal malignancies originating from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma). Twenty-nine studies comprising a total of 3177 patients were statistically analyzed. Results showed a 9% (95% CI = 7-11) overall rate of malignant transformation from Schneiderian papilloma. In conclusion, this analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated. On the other hand, our review showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.

Fourier Transform Infrared Imaging analysis of dental pulp inflammatory diseases.

OBJECTIVES: Fourier Transform Infrared microspectroscopy let characterize the macromolecular composition and distribution of tissues and cells, by studying the interaction between infrared radiation and matter. Therefore, we hypothesize to exploit this analytical tool in the analysis of inflamed pulps, to detect the different biochemical features related to various degrees of inflammation. MATERIALS AND METHODS: IR maps of 13 irreversible and 12 hyperplastic pulpitis, together with 10 normal pulps, were acquired, compared with histological findings and submitted to multivariate (HCA, PCA, SIMCA) and statistical (one-way ANOVA) analysis. The fit of convoluted bands let calculate meaningful band area ratios (means ± s.d., P < 0.05). RESULTS: The infrared imaging analysis pin-pointed higher amounts of water and lower quantities of type I collagen in all inflamed pulps. Specific vibrational markers were defined for irreversible pulpitis (Lipids/Total Biomass, PhII/Total Biomass, CH2 /CH3 , and Ty/AII) and hyperplastic ones (OH/Total Biomass, Collagen/Total Biomass, and CH3 Collagen/Total Biomass). CONCLUSION: The study confirmed that FTIR microspectroscopy let discriminate tissues' biological features. The infrared imaging analysis evidenced, in inflamed pulps, alterations in tissues' structure and composition. Changes in lipid metabolism, increasing amounts of tyrosine, and the occurrence of phosphorylative processes were highlighted in irreversible pulpitis, while high amounts of water and low quantities of type I collagen were detected in hyperplastic samples.

Does cyclic guanosine monophosphate induce autophagy in thyroid malignant carcinoma through down-regulation of cyclic guanosine monophosphate phosphodiesterase?

The aim of this study was to evaluate whether or not the expression of cGMP- phosphodiesterases (cGMP-PDE) varies in different thyroid pathologies and to elucidate the relationship between the expression of cGMP-PDE, cGMP, and autophagy. Fifty-four thyroid biopsy samples, excised to perform the biopsy, were split into two parts and randomly assigned: one part was microscopically examined and histological classified, and the other was frozen and analysed in order to evaluate the cGMP-PDE activity. Intracellular cGMP was also measured. A strong expression of intracellular cGMP and cGMP-PDE activity was observed in carcinoma in respect to controls and benign pathologies. The level of cGMP-PDE in papillary carcinoma without lymph node involvement (N-) was approximately four-fold higher compared to those with lymph node invasion (N±). On the contrary, the cGMP was one and a half times higher in N± than N-. Our results are promising, although further epigenetical studies are needed to confirm this association. A correlation between the cGMP-degrading activity and the severity of thyroid pathology has been shown. The decrease of cGMP-PDE and the increase of cGMP in N± papillar carcinoma could be an autophagic stimulus, a defence mechanism of the body, against the cancer that is expanding and invading other tissues and organs.

Study of oral cavity lesions by infrared spectroscopy.

Fourier transform infrared (FTIR) microspectroscopy is considered a useful tool in the biomedical field, for analysing in situ and at cellular level, very small areas of tissues and cells, with minimal sample preparation and without the use of stains or probes. This spectroscopic technique has been successfully applied to analyse biological samples from patients affected by tumoral pathologies, with particular attention to oral cavity lesions. In this study, we describe the application of FTIR microspectroscopy to characterize and discriminate the most recurrent benign and malignant diseases of oral cavity compartment. Infrared maps were acquired on tissues affected by the following pathologies: squamous cell carcinoma, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, squamous dysplasia, keratocystic odontogenic tumor, radicular cyst, residual cyst, unicystic ameloblastoma, and ameloblastic fibroma, together with healthy tissue samples (used as control group). The epithelial and connective components of all samples were distinguished and submitted to multivariate analysis. The results were in agreement with histological suggestions.

CD133 EXPRESSION COULD BE A PREDICTIVE MARKER OF PERIODONTAL REGENERATION.

Periodontal regeneration needs formation of new connective tissue at the root surface, involving periodontal fibre development and angiogenesis. CD133 or prominin-1, is an important regulator of apoptosis, proliferation and angiogenesis. CD133 positive cells seem to be influenced in number and distribution by periodontal inflammatory changes. Studies showed different clinical and radiographic outcomes achieved with the used of Demineralized Freeze-Dried Bone Allografts (DFDBA) for periodontal intrabony defects treatment. Our aim was to investigate the relationship between CD133 expression in gingival biopsies before periodontal treatment and periodontal tissue response in the same site at 12 months post-surgery. We selected fifty-six patients with at least one intrabony defect with clinical attachment level (CAL)≥6 mm and needing periodontal regeneration. A gingival biopsy for each patient was obtained for CD133 immunostaining. Clinical and radiographical parameters were taken at baseline and 12 months post-surgery. We found a positive correlation between gingival CD133 expression and CAL gain achieved by use of DFDBA and measured 12 months post-surgery. Our results suggest that gingival CD133 expression could be a predictive marker of favourable periodontal healing. The CAL gain after periodontal regeneration seems to be related with a native gingival regenerative capacity.

Impact of smoking on guided tissue regeneration using a biocomposite poly (lactic-co-glycolic) acid/sub-micron size hydroxyapatite with a rubber dam as an alternative barrier.

The purpose of our study was to critically evaluate the results obtained from a guided tissue regeneration technique after 12 months using a bocomposite poly (lactic-co-glycolic) acid/sub-micron size hydroxyapatite (PLGA/HA) with a rubber dam as a barrier in smoking and non-smoking patients. We selected 36 patients (18 current smokers and 18 non-smokers) diagnosed with chronic advanced periodontitis with a periodontal site (probing depth [PD] >5) amenable to regenerative surgery. Twelve months after surgery, the periodontal parameters were found to have statistically improved, when non-smokers were compared with smokers, in: PD reduction (6.3 ± 2.1 mm vs. 3.6 ± 1.9 mm); CAL gain (4.4 ± 1.1 vs. 2.8 ± 2.2 mm); recession (1.8 ± 1.4 mm vs. 0.8 ± 0.9 mm); and hard tissue fill (4.7 ± 0.8 mm vs. 2.8 ± 2.1 mm). Furthermore, since we found PD baseline differences between groups, smoking seemed not to influence the outcomes achieved (CAL gain and ΔREC) 12 months post surgery with respect to PD baseline. The use of PLGA/HA with a rubber dam significantly improved the periodontal parameters in both smoking and non-smoking subjects. This improvement was nevertheless lower in smokers than the non-smokers, confirming the negative impact of smoking on periodontal regeneration.

Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. 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 immunohistochemistry 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. RESULTS: Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs 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 vs 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.

p63 and Ki-67 immunostainings in laryngeal squamous cell carcinoma are related to survival.

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.

Periodontal status in the Down's syndrome subjects living in central-eastern Italy: the effects of place of living.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The role of E-cadherin down-regulation in oral cancer: CDH1 gene expression and epigenetic blockage.

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 Ecadherin 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. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) 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 downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with 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.

Expression of poly(ADP-ribose) polymerase in bone regeneration.

Poly(ADP-ribose) polymerase (PARP) is a 116kDa enzyme catalysing the synthesis of ADP-ribose polymers from NAD+. PARP is activated in response to DNA strand breaks and plays a critical role in the maintenance of genomic integrity. However, considering its role also in transcription, proliferation as well as apoptosis in biological process, in the present study the role of PARP in bone regeneration was evaluated, in particular in bone cell proliferation and differentiation processes. Thus, formalin fixed paraffin embedded specimens of 10 human bone samples after sinus lift were collected and investigated by immunohistochemistry using a mouse monoclonal anti-human PARP antibody. PARP was expressed in cells with morphological features of osteoblasts in the areas of new bone formation at the junction between mineralized and unmineralized tissue, between osteoid tissue and bone. Few osteoclasts were observed and showed only focal nuclear expression of PARP, while osteocytes showed no positivity for PARP. Our data showed an overall involvement of PARP enzyme in human bone tissues, in particular during bone regeneration process.