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Biomedical subjects

Francesco Carinci

Publications and source records attributed to Francesco Carinci.

At least 37 records · Page 2Linked to original sources
PubMed2005

P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation.

Unregulated fibroblast growth factor 2 (FGF2) signaling caused by mutations in the fibroblast growth factor receptor (FGFR2) leads to human craniosynostosis such as the Apert syndrome. In an in vitro control model of calvarial osteoblasts from Apert patients carrying the FGFR2 P253R mutation, we studied the changes in cellular phenotype and evaluated the effects of FGF2. Compared with wild-type controls, osteocalcin mRNA was down-regulated in Apert osteoblasts, Runt-related transcription factor-2 (RUNX2) mRNA was differentially spliced, and FGF2 secretion was greater. Total protein synthesis, fibronectin and type I collagen secretion were up-regulated, while protease and glycosidase activities and matrix metalloproteinase-13 (MMP-13) transcription were decreased, suggesting an altered ECM turnover. Adding FGF2 increased protease and glycosidase activities and down-regulated fibronectin and type I collagen secretion in Apert osteoblasts. High affinity FGF2 receptors were up-regulated in Apert osteoblasts and analysis of signal transduction showed elevated levels of Grb2 tyrosine phosphorylation and the Grb2-p85 beta association, which FGF2 stimulation strongly reduced. All together these findings suggest increased constitutive receptor activity in Apert mutant osteoblasts and an autocrine loop involving the FGF2 pathway in modulation of Apert osteoblast behavior.

Acrocephalosyndactylia↗
PubMed2005

p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma.

p63 belongs to a protein family that includes 2 structurally related proteins, p53 and p73. The aim of this study was to investigate the biologic role of p63 in oral tumorigenesis and its possible role as prognostic marker in oral cancer. Ninety-four cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analyzed for p63 expression by immunohistochemistry. Normal oral mucosa showed a basal and parabasal expression of p63. Five (5.3%) cases of oral cancer showed less than 10% of positive tumor cells; in 33 (35.1%) cases the positive tumor cells comprised between 10% and less than 30%, in 36 (38.3%) cases the positive tumor cells comprised between 30% and less than 50%, and in 20 (21.3%) cases the positive tumor cells were more than 50%. There was also a statistically significant correlation between p63 expression and tumor differentiation: p63 expression was amplified in poorly differentiated tumors (P < .05). When analyzed for prognostic significance, patients with perineural infiltration had poorer survival rates than the group with no perineural infiltration (P < .05) and patients with increased p63 expression had poorer survival rates than the group with reduced p63 expression (P < .05). The statistical analysis showed no significant correlation between p63 expression, sex, age, tumor size, staging, recurrence, and metastasis. Cases with diffuse p63 expression were more aggressive and poorly differentiated and related to a poorer prognosis. These data suggest that p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.

Adolescent↗
PubMed2005

Non-syndromic orofacial clefts in Southern Italy: pattern analysis according to gender, history of maternal smoking, folic acid intake and familial diabetes.

BACKGROUND: Genetic studies have demonstrated that non-syndromic clefts of the lip, alveolus and palate have an heterogeneous genetic background, and that environmental factors contribute to the onset of this malformation. Therefore studies on different and homogeneous populations can be useful in detecting potentially related environmental and genetic factors. PURPOSE: The aim of the present study was to evaluate whether gender, folic acid intake, family history of diabetes and/or smoking during pregnancy were associated with a specific type of cleft in a group of patients affected by non-syndromic clefts, collected from Southern Italy. MATERIAL AND METHODS: Data from one hundred and twenty-six patients were evaluated retrospectively. Each cleft was described as composed by separate antomical entities such as lip, alveolus, primary and secondary palate. None had an isolated alveolar cleft and this was used as internal control. Pattern analysis was used to detect differences in the frequencies of any possible combination of 7 types of clefting stratified according to the studied variables. Data were analysed by comparing observed proportions. RESULTS: Isolated cleft palate as well as right-sided clefts of lip, alveolus and palate were more frequent in females (p = 0.0014 and 0.0281, respectively), while left sided clefts were more frequent in males (p = 0.0359). A lack of consumption of folic acid was associated with an higher incidence of clefts of the left lip (p = 0.018), while familial diabetes was associated more often with isolated cleft palate (p = 0.0014). CONCLUSIONS: Gender-related results were comparable with those found in Northern Italy and other countries. Environmentally related results disclosed specific subclasses of clefting associated with lack of folic acid consumption and familial diabetes.

Cleft Lip↗
PubMed2005

Genetic portrait of mild and severe lingual dysplasia.

Squamous cell carcinoma is the most frequent malignant tumor of the oral cavity and often arises from premalignant lesions. Traditional methods used by the pathologist are subjective and lack the sensitivity to predict accurately which precancers may progress with time. Therefore, it is important to search for markers that may identify progression of premalignant lesions. Microarray technology can be use with this aim. Here, we define the genetic expression profile of lingual dysplasia (DS) progression. By using cDNA microarray containing 19.2K clones and a baseline of 11 normal tissues, we compared 5 mild and 4 severe DS. We identified 270 genes differentially expressed in normal tissue vs. mild DS (i.e. 161 up- and 109 down-regulated) and 181 genes differentially expressed in mild vs. severe DS (i.e. 63 up- and 118 down-regulated). The described genes cover a broad range of functional activities: (a) anti-oxidative, (b) DNA-repair, (c) inflammatory response, (d) cell-adhesion/mobility, (e) extracellular matrix depolymerization, and (f) cell-cycle regulation. The data reported better define DS progression and can help in classifying premalignant lesions.

Adult↗
PubMed2005

An in vitro model for dissecting distraction osteogenesis.

Distraction osteogenesis (DO) is a mechanotransduction process capable of generating viable osseous tissue by the gradual separation of osteotomized bone edges. Several variables are implicated in DO: magnitude of mechanical strain, distraction rate, and type of distracted bone. The combination of these factors acts on different types of cells inducing apoptosis, cell proliferation, and differentiation. The elucidation of the molecular mechanisms has important clinical implications because it may facilitate the use of recombinant proteins or gene therapy to accelerate bone regeneration. Previous reports have analyzed several molecules such as extracellular matrix proteins, cytokines, bone morphogenetic proteins, hormones, and angiogenic factors. Moreover, a single protein can have multifunctional roles. With such a huge number of mechanical, histologic, cellular, and molecular variables, there is the need to have a cell culture model that enables the selection of the effect of a specific strength to a single cell type at different time points and with or without cytokines. The analysis of the genetic profiling of a cell line cultured on an equibiaxial stretch device has such characteristic. Because there is a recruitment and commitment of preosteoblastic cells during bone lengthening and no previous report has focus on them, the authors used a preosteoblast MC3T3-E1 cell line to detect the early molecular effects of distraction on mesenchymal cells. By using DNA microarrays containing 15,000 clones, the authors identified several genes the expression of which was significantly up- or down-regulated. The differentially expressed genes cover a broad range of biological processes: cell growth, metabolism, morphogenesis, cell communication, response to stress, and cell death. The data reported are the first genetic portrait of stretched preosteoblasts. They can be relevant in the better understanding of the molecular mechanism of DO and as a model for comparing the effect of distraction on different cell lines and primary cultures, rate and strength of distraction, and with or without cytokines.

3T3 Cells↗
PubMed2005

Apert and Crouzon syndromes: clinical findings, genes and extracellular matrix.

Apert and Crouzon syndromes are well known craniostenosis. In the last 10 years several studies were performed to provide a better understanding of the etiology and pathogenesis of these diseases. Both have an autosomal dominant mode of transmission, and a mutation in the gene encoding for the fibroblast growth factor receptor 2 (FGFR2) is the cause in most patients. However, the fact that the same mutation can produce a wide range of phenotypic expression makes the mechanism of anomalous development more complex. The extracellular matrix (ECM) is composed of proteins, glycosaminoglycans, and cytokines that are secreted in an autocrine and paracrine manner and are able to modify the ECM. Fibroblast growth factors are complexed with heparan sulfate, a component of the ECM, before binding the FGFR2. Data exist about different expressions of cytokines and ECM macromolecule in craniostenosis-derived fibroblasts and osteoblasts. Changes in ECM composition could explain the altered osteogenic process and account for pathologic variations in cranial development in addition to the FGFR2 mutations.

Acrocephalosyndactylia↗
PubMed2005

Clinical outcome of 285 Medpor grafts used for craniofacial reconstruction.

Porous polyethylene (Medpor) is an alloplastic material worldwide used for craniofacial reconstruction. To evaluate complications and risk factors associated with this synthetic graft, a retrospective study was performed. A series of 285 Medpor grafts were placed in 187 patients. Age, sex, diagnosis at admission, site, type of surgical insertion, type of fixation, and outcome (no complications, anesthesia, exposure, infection, and implant remodeling and removal) are considered. By means of univariate and multivariate analyses, we detect variables most associated with poor outcome. Univariate analysis showed that graft "survival" curves stratified according to (1) diagnosis at admission and (2) site are statistically significant. Subsequently, a Cox analysis was performed: both variables are also predictors of graft outcome. Porous polyethylene is a reliable alloplastic material that can be satisfactory used for craniofacial reconstruction. However, some sites (i.e., nose, maxilla, and ear) and diagnosis at admission (i.e., syndromic patients previously operated) are related to an higher risk of implant failure.

Adolescent↗
PubMed2005

Genetic profiling of central giant cell granuloma of the jaws.

Central giant cell granuloma (CGCG) of the jaws is a central osteolytic lesion characterized histologically by multinucleated giant cells in a background of ovoid to spindle-shaped mesenchymal cells. Whether CGCG is a reactive lesion or a truly benign neoplasm remains undetermined, and the mechanism determining the onset of the disease remains unknown. To have more information regarding the genetic events involved in CGCG, the authors decided to perform an expression profile. Samples were derived from two surgically resected CGCG of the mandible. RNA extracted from a pool of three normal bone tissues was used as control. By using DNA microarrays containing 19,200 genes, the authors identified several genes whose expression was significantly up- or down-regulated. The differentially expressed genes cover a broad range of functional activities: cell cycle regulation; signal transduction; and vesicular transport. It was also possible to detect some genes whose function is unknown. The authors believe the data reported to be the first genetic portrait of CGCG of the jaws. Several markers have been identified that can potentially help in identifying some biological behavior (ie, quiescent versus aggressive lesions), as well as genes whose products could be potentially disease-specific targets for therapy. However, the authors think that more cases are needed, especially those comparing quiescent and aggressive lesions, before the exact profile of CGCG is known.

Gene Expression↗
PubMed2005

Alveolar ridge augmentation: a comparative longitudinal study between calvaria and iliac crest bone grafrs.

Insertion of endosseous implants is often difficult because of lack of supporting bone. In the case of severe atrophy of the jaws, a large volume of autogenous bone can be harvested from the iliac crest and calvaria. Both grafts undergo partial resorption with time, but the rate of bone loss has not been fully elucidated. The aim of this study was to evaluate the alveolar bone height gain (ABHG) obtained with iliac crest and calvaria bone grafts. Twenty-five patients had mandibular bone grafts, 32 had maxillary bone grafts, and 11 had both mandibular and maxillary bone grafts. Measures were made on preoperative, postoperative, and follow-up radiographs. A general linear model was used to evaluate the rate of ABHG plotted against months elapsed from the time of the operation to the time of follow-up. General linear model output showed a statistically significant effect for only the type of donor bone graft (P =.004), with a better ABHG for calvaria. The iliac crest bone grafts lost most of the ABHG in the first 6 months, whereas calvaria bone grafts lost ABHG over a greater interval of time. The type of bone graft is the strongest predictor of ABHG, and calvaria bone graft had a higher stability than did iliac bone graft. However, the gap in ABHG between the 2 grafts tended to decrease over time.

Adult↗
PubMed2005

Immediate functional loading of edentulous maxilla: a 5-year retrospective study of 388 titanium implants.

BACKGROUND: Immediate functional loading is a new surgical-prosthetic technique that can be used extensively in implant placement. Because of a lack of experimental reports regarding edentulous maxilla, we decided to evaluate the survival rate of immediately loaded dental implants in this area. METHODS: Forty-three patients (44.4% male) with a median age of 55 years receiving 388 implants (mean 9.0 per case) were enrolled in this study. Cross-arch acrylic provisional restorations were performed in the same stage. Data were analyzed by Kaplan-Meier product limit estimation. Stratification of implants survival was performed for the available variables of interest, and comparisons were analyzed by a log rank test. Cox algorithm was used for multivariable analysis. RESULTS: At 5-year follow-up, the crude survival rate (overall survival not stratified according to any available variable) was 98%. All failures occurred within 6 months from loading. We found differences in survival relating to: 1) implant diameter (99.37% for diameter < or =5.25 mm and 93.75% for diameter >5.25 mm); 2) number of implants (99.29% for < or =10 implants and 96.30% for >10); and 3) gender (97.08% and 99.54% for males and females, respectively). Cox regression analysis showed that diameter of implants adjusted for patient age and gender was associated to an average risk of failure (hazard rate) of 3.13 (P value = 0.042, 95% confidence interval 1.04 to 9.43) per mm (from 3 to 6.5). CONCLUSIONS: Immediate functional loading is a reliable surgical-prosthetic procedure in edentulous maxillae. Implants with wider diameter are associated with a higher risk of failure.

Adult↗
PubMed2005

Bcl-2 as prognostic factor in head and neck squamous cell carcinoma.

A series of 66 cases of oral squamous cell carcinoma (OSCC) was retrospectively analyzed by immunohisto-chemistry for bcl-2 expression to verify its predictive value for clinical outcome in patients with OSCC. After grouping for bcl-2 expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, staging, recurrence, and overall survival rate. Univariate and multivariate (Cox regression) analyses were performed. Thirty-six OSCC (54.5%) showed expression for bcl-2, whereas 30 (44.5%) were negative. No statistical association was found between bcl-2 expression and any variables considered at baseline. Overall disease-specific survival rate at 72 months was 51%, independently from the extent of the tumor. In terms of prognostic significance, the bcl-2-positive group showed more than 60% survival at 72 months whereas the bcl-2-negative group showed none. An independent association of bcl-2 expression was found with an improved overall survival rate (p = 0.048), although grading and staging were established to be the best baseline markers of prognosis. On the basis of these results, it is possible to suggest bcl-2 as an early marker of prognosis: lack of bcl-2 expression could constitute a hallmark of aggressive biological behavior in OSCC.

Adolescent↗
PubMed2004

Survivin as prognostic factor in squamous cell carcinoma of the oral cavity.

A series of 78 cases of oral squamous cell carcinoma was analysed by immunohistochemistry for expression of survivin, a recent apoptosis inhibitor. All cases were positive for survivin expression and were divided into two groups using a system of scores. Disease-specific survival curves were calculated according to Kaplan-Meier algorithm, and log rank test was used to compare survival curves. Then, Cox regression analysis was applied to determine the single contribution of covariates on survival rate. So, Cox analysis allowed us to detect the variables most associated to survival. Among the studied variables, such as grade of differentiation, tumor size, stage, recurrence of disease, lymph node presence, only stage and recurrence of disease were predictors of outcome; however, when we analyzed the survival without considering recurrence (that was the stronger predictor of death), a stepwise Cox analysis showed that Survivin, stage and grade of differentiation are significantly associated to survival, with a higher value for Survivin. These data suggest that survivin expression may identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype and, therefore, could influence the decision for the therapy at the time of diagnosis.

Adolescent↗
PubMed2004

Strong evidence of linkage disequilibrium between polymorphisms at the IRF6 locus and nonsyndromic cleft lip with or without cleft palate, in an Italian population.

Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects, but its etiology is largely unknown. It is very likely that both genetic and environmental factors contribute to this malformation. Mutations in the gene for interferon regulatory factor 6 (IRF6) have been shown to be the cause of Van der Woude syndrome, a dominant disorder that has CL/P as a common feature. Recently, it has been reported that genetic polymorphisms at the IRF6 locus are associated with nonsyndromic CL/P, with stronger association in Asian and South American populations. We investigated four markers spanning the IRF6 locus, using the transmission/disequilibrium test. A sample of 219 Italian triads of patients and their parents were enrolled in the study. Strong evidence of linkage disequilibrium was found between markers and disease in both single-allele (P=.002 at marker rs2235375) and haplotype (P=.0005) analyses. These findings confirm the contribution of IRF6 in the etiology of nonsyndromic CL/P and strongly support its involvement in populations of European ancestry.

Cleft Lip↗
PubMed2004

Calcium sulfate: analysis of MG63 osteoblast-like cell response by means of a microarray technology.

Calcium sulfate (CaS) is an highly biocompatible material that has the characteristic of being one of the simplest as well as one of the synthetic bone-like graft with the longest clinical history, spanning more than 100 years. Solidified or crystallized CaS is very osteogenic in vivo. As the surface CaS dissolves in body fluid, the calcium ions form calcium phosphate that reprecipitates on the surface forming an osteoblast "friendly" environment. How this "friendly" environment alters osteoblast activity to promote bone formation is poorly understood. We therefore attempted to address this question by using microarray techniques to identified genes that are differently regulated in osteoblasts exposed to CaS. By using DNA microarrays containing 19,200 genes, we identified in osteoblast-like cells line (MG-63) cultured with CaS (Surgiplaster, Classimplant, Roma, Italy) several genes that expression was significantly upregulated. The differentially expressed genes cover a broad range of functional activities: (a) immunity, (b) lysosomal enzymes production, (c) cell cycle regulation, (d) and signaling transduction. It was also possible to detect some genes whose function is unknown. The data reported are, to our knowledge, the first genetic portrait of CaS effects. They can be relevant to better understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.

Calcium Sulfate↗
PubMed2004

Prognostic evaluation in supracricoid partial laryngectomy with cricohyoidopexy.

Identification of prognostic factors related to supracricoid partial laryngectomy may optimise indications for this surgical technique. We analysed several clinical and histopathological variables in a series of 81 patients treated with SPL at our department. Attention was focused on neoplastic spread of the anterior commissure, thyroid cartilage and prelaryngeal soft tissue of the neck. Statistical analysis (Kaplan-Meier method and Cox regression test) showed a significant decrease in survival for prelaryngeal soft tissue invasion. Due to the fact that the survival rate is not modified by the anterior commissure and thyroid cartilage infiltration, the prognostic value of prelaryngeal invasion is extremely relevant. Therefore, we suggest the oncological value of SPL even in cases of invasion of the anterior commissure or thyroid cartilage, but not beyond the outer perichondrium.

Adult↗
PubMed2004

Zirconium oxide: analysis of MG63 osteoblast-like cell response by means of a microarray technology.

Zirconium oxide ceramics have outstanding mechanical properties, a high biocompatibility and a high resistance to scratching. Expression profiling by DNA microarray is a molecular technology that allows the analysis of gene expression in a cell system. By using DNA microarrays containing 19,200 genes, we identified in osteoblast-like cells line (MG-63) cultured on zirconium oxide discs (Cercon, Degussa Dental, Hanau, Germany) several genes whose expression was significantly up or down-regulated. The differentially expressed genes cover a broad range of functional activities: (a) immunity, (b) vesicular transport and (c) cell cycle regulation. It was also possible to detect some genes whose function is unknown. The data reported are, to our knowledge, the first genetic portrait of a zirconium oxide surface. They can be relevant to better understand the molecular mechanism of biocompatibility and as a model for comparing other materials.

Animals↗
PubMed2004

Expression profiling of ameloblastic carcinoma.

Ameloblastic carcinoma (AC) is a malignant epithelial odontogenic tumor that histologically retains the features of ameloblastic differentiation and exhibits cytological features of malignancy in the primary or recurrent tumor. It may develop within a preexisting ameloblastoma or arise de novo or from an odontogenic cyst. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of cell and tissue gene expression. By using DNA microarrays containing 19,200 genes, several genes whose expression was significantly upregulated or downregulated were identified in a case of AC. The differentially expressed genes cover a broad range of functional activities: 1) transcription, 2) signaling transduction, 3) cell cycle regulation, 4) apoptosis control, and 5) differentiation. The data reported are, to our knowledge, the first genetic portrait of an AC. No final conclusion can be drawn; however, this portrait will be useful in investigating the biological behavior and in identifying possible gene targets for cancer therapy when more cases of this rare tumor are reported and compared.

Aged↗