p63 expression correlates with pathological features and biological behaviour of odontogenic tumours.
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DNA-Binding Proteins↗
Biomedical subjects
F Carinci
Publications and source records attributed to F Carinci.
Study of the PVRL1 gene in Italian nonsyndromic cleft lip patients with or without cleft palate.
Nonsyndromic cleft lip with or without cleft palate (CL/P) is a complex genetic trait and little is known about its aetiology. Recent investigations on rare clefting syndromes provided interesting clues about genes involved in face development. The PVRL1 gene encodes nectin1, a cell-to-cell adhesion molecule. Mutations in its sequence have been shown to cause the rare autosomal recessive syndrome CL/P-ectodermal dysplasia syndrome (CLPED1), while heterozygosity for the mutation W185X seemed to increase the risk of non syndromic CL/P in a population from northern Venezuela. In the present study, we screened 143 Italian CL/P patients for mutations in PVRL1. Three rare sequence variants in exon 3 that create amino-acid changes were detected in a total of 7 patients. Two of these mutations were not found in a panel of 292 unaffected controls, while the third was found in two controls. This study describes new mutations that may represent genetic risk factors for CL/P. Even though a study to look at the effects of the mutations on nectin1 function was not feasible, supporting evidence was reported, thus confirming the involvement of PVRL1 in the aetiology of non-syndromic CL/P malformation.
Cell Adhesion Molecules↗
Effects of Emdogain on osteoblast gene expression.
OBJECTIVE: Emdogain (EMD) is a protein extract purified from porcine enamel and has been introduced in clinical practice to obtain periodontal regeneration. EMD is composed mainly of amelogenins (90%), while the remaining 10% is composed of non-amelogenin enamel matrix proteins such as enamelins, tuftelin, amelin and ameloblastin. Enamel matrix proteins seem to be involved in root formation. EMD has been reported to promote proliferation, migration, adhesion and differentiation of cells associated with healing periodontal tissues in vivo. DESIGN: How this protein acts on osteoblasts is poorly understood. We therefore attempted to address this question by using a microarray technique to identify genes that are differently regulated in osteoblasts exposed to enamel matrix proteins. RESULTS: By using DNA microarrays containing 20,000 genes, we identified several upregulated and downregulated genes in the osteoblast-like cell line (MG-63) cultured with enamel matrix proteins (Emd). The differentially expressed genes cover a broad range of functional activities: (i) signaling transduction, (ii) transcription, (iii) translation, (iv) cell cycle regulation, proliferation and apoptosis, (v) immune system, (vi) vesicular transport and lysosome activity, and (vii) cytoskeleton, cell adhesion and extracellular matrix production. CONCLUSIONS: The data reported are the first genome-wide scan of the effect of enamel matrix proteins on osteoblast-like cells. These results can contribute to our understanding of the molecular mechanisms of bone regeneration and as a model for comparing other materials with similar clinical effects.
Animals↗
p63 expression in odontogenic cysts.
A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. In RCs p63 positivity was not only in basal and parabasal layers but also in the intermediate layer and about 1/3 of cases displayed a percentage of stained cells comprised between 0 and <5%, and about 2/3 between >5% and <50%. In FCs positivity was confined to basal and parabasal layers of the epithelium and in the majority of FCs the stained cells were comprised between 0 and <5%. OKCs displayed the most intense and diffuse p63 labeling. In conclusion, these data suggest that p63 expression may be useful to identify cysts type with more aggressive and invasive phenotype supporting the hypothesis of a suprabasal proliferative compartment in OKCs.
DNA-Binding Proteins↗
In vitro human osteoblast and extracellular matrix changes after transforming growth factor beta 1 treatment.
AIMS: Normal bone tissue is characterised by a balancing of osteoblast and osteoclast activity. The activity and differentiation of these cells are regulated by vitamins, hormones and cytokines. The action of these factors on bone tissue cells depends on the composition and mineralisation of extracellular bone matrix. In particular, transforming growth factor beta 1 (TGFbeta1) acts on collagen fibres, glycosaminoglycan secretion and on the enzymes correlated to the turnover of glycosaminoglycans. The normal functions of bone tissue also depend on its mineralisation, which is highly altered in the process of uraemia. METHODS: In this study, we analysed in vitro the effect of transforming growth factor beta on osteoblast proliferation, collagen synthesis and glycosaminoglycan secretion with 3H-thymidine, 3H-proline or 3H-glucosamine incorporation, and on enzymes, such as beta-N-acetyl-D-glucosaminidase and beta-glucuronidase, involved in extracellular matrix turnover. Moreover, phosphatase alkaline activity and osteocalcin related to mineralisation of extracellular matrix were determined. RESULTS: Our data show that TGFbeta1 significantly decreases 3H-thymidine and 3H-proline incorporation and increases (p < or = 0.01) extracellular sulphated glycosaminoglycan synthesis. It also increases osteocalcin levels, phosphatase alkaline, beta-N-acetyl-D-glucosaminidase and beta-glucoronidase activities. CONCLUSION: TGFbeta1 changes the synthesis of extracellular matrix components by osteoblasts. These variations favour the action of cytokine and osteoclasts. Since the TGFbeta1 accumulates in bone tissue and increases during uraemia, with due limitations this action leads to an imbalance between synthesis and degradation and could explain bone alterations in uraemic patients.
Acetylglucosaminidase↗
Genetic expression profiling of parotid neoplasms by cDNA microarrays.
Differentially expressed genes in various benign and malignant salivary gland tumours were identified by use of cDNA microarrays containing 19,000 human expressed sequence tags. Samples were derived from 5 patients with pleomorphic adenoma, 4 with Warthin's tumour, one with clear cell carcinoma, and 2 with mucoepidermoid carcinoma. Tumours were classified by using a subset of 486 genes. Benign Warthin's tumour and pleomorphic adenoma showed very distinctive gene expression patterns. A total of 133 genes differentiated the single malignant clear cell carcinoma from non-tumour salivary glands (p < 0.01), whereas only 16 genes separated it from the highly related benign pleomorphic adenoma (p < 0.01). A total of 57 cDNAs were associated with mucoepidermoid carcinoma (p < 0.01). The results show gene expression alterations common to all tumours and unique to each benign and malignant tumour. The numerous Expressed Sequence Tags of unknown function we identified could also become useful as tumour markers and represent a set of novel tumour-associated genes.
Gene Expression Profiling↗
Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate.
The pathogenesis of cleft lip with or without cleft palate (CL/P) is complex; its onset could be due to the interaction of various genetic and environmental factors. Recently MTHFR functional polymorphisms were found to increase the risk of this common malformation; however, this finding is still debated. We investigated 110 sporadic CL/P patients, their parents and 289 unrelated controls for c.665C>T (commonly known as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala) polymorphism in the MTHFR gene. Transmission disequilibrium test (TDT) showed no distortion in allele transmission. Nevertheless, association studies revealed significant differences in allele frequencies between mothers of CL/P patients and controls. This work supports the hypothesis that a lower MTHFR enzyme activity in pregnant women, mostly related to the c.665C>T variant form, is responsible for a higher risk of having CL/P affected offspring.
Adult Children↗
Titanium-cell interaction: analysis of gene expression profiling.
Titanium and its alloys are used worldwide in surgery. Dental implants, screws and plates, prostheses, and surgical instruments are made with titanium-based metals. The favorable characteristics that make this material desirable for implantation are (a) mechanical proprieties and (b) biocompatibility. The latter has been demonstrated by in vivo studies with animal models and clinical trials over a 40-year period. However, the exact effect of titanium on cells is still not well characterized. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of gene expression in a cell system. Several genes whose expression was significantly up- or downregulated in an osteoblast-like cell line (MG-63) on titanium were identified with the use of DNA microarrays containing 19,200 genes. The differentially expressed genes are associated with a broad range of functional activities, including apoptosis, vesicular transport, and structural function. It was also possible to detect some genes whose function is unknown. The data reported are, to the author's knowledge, the first genetic portrait of titanium-cell interaction. They may help to provide a better understanding of the molecular mechanisms of titanium biocompatibility and serve as a model for studying the biocompatibility of other materials.
Animals↗
Genetic portrait of malignant granular cell odontogenic tumour.
Odontogenic tumours are rare neoplasms whose classification is sometime controversial. Among these entities, granular cell odontogenic tumour (GCOT) is extremely rare and usually has a benign clinical behaviour. While the histogenesis of GCOT remains to be clarified, we documented the existence of a malignant counterpart of this neoplasm and proposed the name of malignant GCOT. Expression profiling by cDNA microarrays is a molecular technology that enables a global gene expression analysis. By using cDNA microarrays, we identified in malignant GCOT several genes with significantly differentially regulated genes when compared to non neoplastic tissues. These cancer specific genes include a range of functional activities: (1) transcription, (2) signaling transduction, (3) cell-cycle regulation, (4) apoptosis, (5) differentiation and (6) angiogenesis. In conclusion, we show that cDNA microarrays is a useful approach to investigate the biology of tumours. Moreover, this technology might lead to identification of gene targets for cancer therapy and to molecular classification of odontogenic tumours.
Adult↗
Eccrine spiradenoma of the ear: case report.
A case of eccrine spiradenoma of the left pinna is described. To the best of our knowledge, this is the first report regarding this site. The treatment was a surgical excision in safe margins. This rare benign tumour should be considered for the differential diagnosis of solitary or multiple soft tissue lesions of the head and neck.
Adenoma, Sweat Gland↗
Genetic expression profiling of six odontogenic tumors.
Odontogenic tumors are rare neoplasms arising from the odontogenic apparatus. We aimed to identify molecular characteristics associated with odontogenic tumorigenesis and malignancy. To this end, we investigated the expression level of human genes by using, for the first time in odontogenic tumors, the technique of expression profiling. Gene expression alterations common to all six odontogenic tumors were identified by the use of cDNA microarrays containing 19,000 human cDNAs. Statistical analysis on a subset of 4974 cDNAs present in the biopsies identified 506 distinct genes associated with the tumors (p-value < 0.01). Gene ontology analysis of the cellular processes which were differentially regulated in odontogenic tumors was accomplished by the use of a subset of 1409 annotated genes. Finally, 43 cDNAs differentiated the three malignant odontogenic tumors (ameloblastic carcinoma, clear cell odontogenic tumor, granular cell odontogenic tumor) from the three benign ameloblastoma biopsies (p < 0.01). The identified genes might help us better classify borderline odontogenic tumors.
Ameloblastoma↗
Orofacial cleft in Southern Italy.
AIM: Cleft lip and palate or orofacial cleft (OFC) is one of the most common congenital malformations. The average incidence is around 1 every 1 000 live births. Different types of cleft lip and palate exist: cleft lip (CL), cleft lip and alveolus (CLA), cleft lip, alveolus and palate (CLP), and cleft palate only (CPO). Genetic studies on human samples have demonstrated that OFC has a heterogeneous genetic background and environmental factors also contribute to disclose this malformation. Because of the complex aetiology of OFC, studies on different and homogeneous populations can be useful in detecting environmental and genetic factors involved in the onset of this disease. The aim of the present study is to evaluate the relation between gender, type of cleft and affected side in a group of patients in Southern Italy. METHODS: Six hundred and fifty patients were enrolled in this retrospective study. They were operated at the Dental Clinic of the Second University of Naples in the period 1980-2002. Gender, type of cleft and affected side were analysed by means of the "Test for comparing two proportions". RESULTS: Among the analysed variables it was statistically demonstrated that overall CLP is more frequent in males as well as bilateral CLP whereas overall CPO is more frequent in females as well as right microform of CL. CONCLUSION: The identification of gender related subtypes of cleft is in accordance with data reported in similar studies on different populations and confirms that OFC is an heterogeneous disease even in a homogeneous ethnic group.
Cleft Lip↗
Classification of oral clefts by affection site and laterality: a genotype-phenotype correlation study.
OBJECTIVES: The aim of this study was to classify the phenotypes found in a series of patients with non-syndromic cleft lip (CL) with or without cleft palate (CP) and isolated cleft palate. Additionally, the frequency distribution of cases belonging to families linked to markers on chromosomes 6 and 2 within these phenotypic patterns were estimated. DESIGN: A retrospective examination of all the available affected cases collected in Italy. SETTING AND SAMPLE POPULATION: Ninety-seven affected subjects aged 5-18 years belonging to 38 families were considered. Patterns were identified by variance of the cleft (lip, primary palate, secondary palate) and stratified according to the side of occurrence (right, left, or bilateral). Latent class analysis was used as main statistical tool for carrying out the results. RESULTS: Three homogenous classes were identified (P < 0.0001) by means of latent class analysis. Individuals were assigned to the most suited class. All three variables (lip, primary and secondary cleft palate) generated a specific class. Optimal findings were reported in cases having 'any isolated cleft lip' (class 1); 'secondary CP with or without bilateral/right primary cleft palate + bilateral/right cleft lip' (class 2); and 'left primary cleft palate + left/bilateral cleft lip with or without secondary CP' (class 3). Correspondence to the evidence of linkage to chromosome 6 showed that 9 of 10 cases presenting with 'right primary CP + right CL with secondary cleft palate' (class 2) belonged to a linked family. The same combination, but occurring on the left side (class 3), revealed that only three of nine cases belong to families linked to chromosome 6 (P-value = 0.02). The two patterns (right and left) never occurred in the same family. Three reliable groups were identified based on laterality and the presence of a cleft. A single right sided pattern displayed a statistically different distribution of linkage to chromosome 6 when compared with the homologous left side. CONCLUSION: Non-syndromic CL with/without CP can be classified according to laterality that can be under genetic control.
Adolescent↗
Mucoceles of the frontal sinus. Clinical and therapeutical considerations.
BACKGROUND: Mucocele is an epithelial lined mucus-containing sac completely filling a paranasal sinus and capable of expansion by virtue of a dynamic process of bone resorption and new bone formation. It is the most common lesion causing expansion of the paranasal sinuses. Even though mucoceles of paranasal sinuses are increasingly treated by endoscopic surgery, the external approach with or without the obliteration of the sinus still remains a useful and sometimes the only tool in the treatment of this disease. METHODS: The results obtained in seven patients observed at the ENT Department of the University of Ferrara (Italy) in the period ranging from 1989 to 1999 are presented; they were affected by massive fronto-ethmoidal mucoceles and treated with the external approach alone or combined with an endonasal approach and osteoplastic flap. They were five males and two females, with a mean age of 56.5 years. Locations were bilateral in one mucocele, while in six patients only one side was involved, with a prevalence of the left frontal sinus (4:2). RESULTS: No patient showed any local or general complication in the postoperative period. The follow-up showed no recurrence of the disease. CONCLUSIONS: Since the osteoplastic flap was introduced one hundred years ago, it still remains the optimal surgical treatment for fronto-ethmoidal mucoceles. Even though, today, endoscopic surgery represents the new horizon in the management of the sinonasal disease, mucoceles need a surgical treatment which allows the total vision of the cavity to obtain radical treatment and any recurrence of disease.
Aged↗
C677T variant form at the MTHFR gene and CL/P: a risk factor for mothers?
Maternal folic acid supplementation in early pregnancy has been suggested to play a role in the prevention of nonsyndromic orofacial cleft, i.e., cleft lip with or without cleft palate (CL/P). Moreover, some authors demonstrated association of the C-->T mutation (C677T), converting an alanine to a valine residue in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with other congenital anomalies such as neural tube defects (NTDs). Because of MTHFR's involvement in the metabolism of folate, we investigated 64 CL/P patients and their parents for C677T MTHFR mutation. No linkage disequilibrium was found using the transmission disequilibrium test (TDT). However, a significantly higher mutation frequency was detected in mothers of CL/P patients compared to controls. The odds ratios calculated for mothers having CT or TT genotype, compared to the normal CC genotype, were 2.75 (95% confidence interval 1.30-5.57) and 2.51 (1.00-6.14), respectively. These results support the involvement of the folate pathway in the etiology of CL/P, and indicate an effect of the maternal genotype, rather than influence of the embryo's genotype.
Alleles↗
Parotid gland carcinoma: 1987 and 1997 UICC T classifications compared for prognostic accuracy at 5 years.
In order to compare the correlation of 1987 and 1997 UICC T categories with the survival rate in parotid gland carcinoma, 134 patients attending the ENT clinics at the University of Ferrara (from 1970 and 1993) and Firenze (from 1970 to 1990) were analyzed by means of survival analyses (Kaplan-Meier and Cox algorithms). This study demonstrated that both systems showed a significant correlation with the survival rate, but T 1997 resulted in a more reliable prognostic value by means of a higher odds ratio. We conclude that the newer (1997) UICC T category better defines the prognosis for cancer of the parotid gland and should have a higher impact on the clinical evaluation of patients.
Adolescent↗
Linkage analysis of three candidate regions of chromosome 1 in nonsyndromic familial orofacial cleft.
Linkage analysis and mouse model knockout studies indicate that loci/genes mapping in different chromosome 1 regions are good candidates for nonsyndromic orofacial cleft (OFC) malformation. On this basis, three different regions of the chromosome 1 have been analysed, by linkage analysis, in 38 families with nonsyndromic OFC. Positive scores were obtained by pairwise analysis and a non-parametric linkage approach for the 1p36 region, with markers close to the MTHFR locus. Additional results allowed us to exclude the presence of an OFC susceptibility gene in the 1q21 and 1q32-42.3 regions.
Chromosomes, Human, Pair 1↗
Comparison between TANIS and UICC 1997 stage grouping in parotid gland carcinoma.
To compare the correlation of T and N Integer Score (TANIS) and International Union Against Cancer (UICC) '97 stage grouping with survival rate in parotid gland carcinoma, a series of 134 patients affected by primary carcinoma of the parotid gland was considered in this retrospective study. Data set was classified according to 1997 UICC T-category and then grouped as recommended by the two systems. Data were analyzed by means of survival analyses (Kaplan-Meier and Cox algorithms). Results showed a crude survival rate of 64.9%. Univariate analysis by means of log-rank test yielded significant P values both for TANIS and UICC '97 systems (both P < 0.0001). Multivariate analysis (Cox regression adjusted for age and gender) showed a significant correlation between the two staging systems with the mortality rate. Odds ratios were 2.64 (95% CI 1.84-3.80) and 1.79 (95% CI 1.46-2.20) for UICC '97 and TANIS, respectively. In testing the superiority, UICC '97 resulted in a higher prognostic value and TANIS did not add any statistical contribution in determining survival. In conclusion, the new UICC stage grouping better defines the prognosis for cancer of the parotid gland.
Adolescent↗