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1.
Oncol Rep ; 25(2): 499-502, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21165567

ABSTRACT

WWOX is a tumour suppressor gene altered in various human neoplasms. Deletion of WWOX is associated with bone metabolic defects and development of osteosarcoma in mice. We hypothesized that alterations of this gene are associated with the development of benign and malignant mesenchymal bone related lesions of the jaws. We investigated WWOX mRNA by nested reverse transcription-PCR and direct sequencing and quantitative real-time PCR in two osteosarcoma, two fibrosarcoma, eight ossifying fibroma and two fibrous dysplasia fresh samples. Malignancy was associated with a decreased WWOX mRNA expression. Aberrant transcription pattern was found in five samples; however, the relative quantification (RQ) of the WWOX mRNA in such lesions was not different from those carrying only the wild-type. We provide new evidence of WWOX alterations in osteosarcomas and demonstrate for the first time alterations of this gene in fibrosarcomas as well as in ossifying fibromas of the jaws.


Subject(s)
Bone Neoplasms/genetics , Fibroma, Ossifying/genetics , Fibrosarcoma/genetics , Jaw Neoplasms/genetics , Oxidoreductases/genetics , Tumor Suppressor Proteins/genetics , Adolescent , Adult , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Child , Female , Fibroma, Ossifying/metabolism , Fibroma, Ossifying/pathology , Fibrosarcoma/metabolism , Fibrosarcoma/pathology , Gene Expression Regulation, Neoplastic/genetics , Genes, Tumor Suppressor , Humans , Jaw Neoplasms/metabolism , Jaw Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Oxidoreductases/metabolism , RNA, Messenger/analysis , RNA, Messenger/metabolism , Tumor Suppressor Proteins/metabolism , WW Domain-Containing Oxidoreductase , Young Adult
2.
Exp Ther Med ; 1(1): 217-221, 2010 Jan.
Article in English | MEDLINE | ID: mdl-23136618

ABSTRACT

MicroRNAs (miRNAs) mir15a and let7a are important regulators of bcl-2, ras and c-myc proteins. Considering that these miRNAs are commonly altered in many human cancers and that these proteins are reported to be altered in oral squamous cell carcinoma (OSCC), we investigated them in a set of OSCC cases. The miRNAs as well as the proteins were evaluated in the tumor and blood of 20 patients by real-time quantitative PCR and immunohistochemistry, respectively. The expression of mir15a and bcl-2 proteins in the tumors was not associated with each other or with tumor staging. On the other hand, we found reduced expression of this miRNA in the blood of patients with an advanced stage of OSCC and with lymph node metastasis. The expression of let7a in the tumor and blood was not associated with tumor size, lymph node metastasis, tumor staging and immunoexpression of ras and c-myc proteins. In conclusion, the present study shows that reduced expression of mir15a is associated with OSCC staging.

3.
Oral Oncol ; 44(2): 153-5, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17368082

ABSTRACT

Cherubism is an autosomal dominant inherited syndrome characterized by excessive bone degradation of upper and lower jaw and its replacement with large amounts of fibrous tissue, which causes a characteristic facial swelling. A correlation with a mutation in the gene SH3BP2 has been previously demonstrated, but a model for its pathogenesis is not yet available. Here we describe a novel mutation in an aggressive case of cherubism located in the pleckstrin homology domain (PH) of the SH3BP2.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Cherubism/genetics , Mutation , Base Sequence , Child , DNA Mutational Analysis , Humans , Male , Molecular Sequence Data , src Homology Domains
4.
Oral Oncol ; 44(8): 753-8, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18061530

ABSTRACT

Oral leukoplakia is the most prevalent and potentially malignant disorder of the oral mucosa. Previous studies have demonstrated that molecular changes of the WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor gene located at 16q23.3-24.1 that spans FRA16D, the second most common fragile site, are present in several malignant neoplasias, including oral squamous cell carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA transcription and/or reduced Wwox protein expression was observed in 35% of the lesions when compared with normal mucosa. The majority of lesions (4/6) with altered transcripts had a reduction in the expression of Wwox protein. Although normal WWOX expression was found in some lesions with dysplasia, all lesions with WWOX mRNA and/or protein expression showed histological evidence of dysplasia and none of the cases without dysplasia presented this alteration. These results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis.


Subject(s)
Genes, Tumor Suppressor , Leukoplakia, Oral/genetics , Oxidoreductases/genetics , Tumor Suppressor Proteins/genetics , Adult , Aged , Case-Control Studies , Chromosome Fragile Sites , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Leukoplakia, Oral/metabolism , Leukoplakia, Oral/pathology , Male , Middle Aged , Oxidoreductases/metabolism , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tobacco Use Disorder/genetics , Tobacco Use Disorder/pathology , Tumor Suppressor Proteins/metabolism , WW Domain-Containing Oxidoreductase
5.
Anticancer Res ; 27(4B): 2339-43, 2007.
Article in English | MEDLINE | ID: mdl-17695523

ABSTRACT

BACKGROUND: DARPP-32 is a neuronal protein that plays a central role in dopaminergic neurotransmission. Although DARPP-32 may contribute to the pathogenesis of several human malignancies, its expression has never been investigated in oral premalignant and malignant lesions. MATERIALS AND METHODS: DARPP-32 expression was examined using immunohistochemistry in 14 normal oral mucosa, 5 normal lower lip mucosa, 41 oral leukoplakia (OL), 30 oral squamous cell carcinoma (OSCC) and 20 lower lip squamous cell carcinoma (LLSCC) specimens. Differences of its expression between groups were analyzed. RESULTS: OSCC and OL with moderate or severe dysplasia showed lower DARPP-32 expression in relation to normal oral mucosa. LLSCC showed lower DARPP-32 expression than normal lower lip mucosa and OSSC. CONCLUSION: The decreased expression of DARPP-32 in oral premalignant and malignant lesions suggests a tumor suppressor role for this protein in the tumorigenesis of these lesions.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Dopamine and cAMP-Regulated Phosphoprotein 32/biosynthesis , Leukoplakia, Oral/metabolism , Mouth Neoplasms/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Mucosa/metabolism
6.
Eur Arch Otorhinolaryngol ; 264(7): 829-32, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17285332

ABSTRACT

Intraoral sebaceous carcinoma (SC) is a rare tumour in the oral cavity thought to arise from malignant transformation of oral sebaceous glands. To our knowledge, only six cases of intraoral SC have been reported in the English language literature. The purpose of the present article is to report an additional case and review the literature.


Subject(s)
Adenocarcinoma, Sebaceous/diagnosis , Mouth Neoplasms/diagnosis , Sebaceous Gland Neoplasms/diagnosis , Adenocarcinoma, Sebaceous/drug therapy , Biopsy , Combined Modality Therapy , Diagnosis, Differential , Follow-Up Studies , Humans , Male , Middle Aged , Mouth Neoplasms/therapy , Radiography, Panoramic , Sebaceous Gland Neoplasms/therapy , Tomography, X-Ray Computed
7.
Oral Oncol ; 42(7): 735-9, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16458039

ABSTRACT

Ossifying fibroma (OF) is a benign neoplasm related to bone characterized by a progressive enlargement of the affected jaw. Recently, the candidate tumor suppressor gene HRPT2 was identified and alterations in this gene were related with the Hyperparathyroidism-jaw tumor syndrome that is characterized by parathyroid adenoma or carcinoma, fibro-osseous lesions (mainly OF) of the jaws, and renal lesions. The purpose of the present study was to evaluate the HRPT2 gene in OF. Tumour and blood samples were obtained from 3 patients with OF and one with juvenile ossifying fibroma (JOF). The results demonstrated three novel mutations in two out of three genotyped OF's. Interestingly, one of these patients showed a germ-line mutation after blood analysis. RT-PCR amplification was performed to analyze HRPT2 mRNA expression and only wild-type HRPT2 transcript was found in all tumours. Investigation of the parafibromin protein by immunohistochemistry showed a similar pattern of immunolocalization with strong nuclear and cytoplasmic staining in all cases. In conclusion, the present study shows for the first time mutations of HRPT2 gene in OF and suggests that OF may arise due to haploinsufficiency of the HRPT2 gene.


Subject(s)
Fibroma, Ossifying/genetics , Genes, Tumor Suppressor , Mandibular Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Adolescent , Adult , Female , Fibroma, Ossifying/metabolism , Gene Expression , Humans , Male , Mandibular Neoplasms/metabolism , Middle Aged , Mutation , RNA, Messenger/genetics , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Tumor Suppressor Proteins/metabolism
8.
J Oral Pathol Med ; 34(10): 583-7, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16202077

ABSTRACT

BACKGROUND: The aim of this study was to determinate the relative frequency of odontogenic tumors (OTs) in a Brazilian population and to compare this data with previous reports. METHODS: We reviewed the achieves of 19 123 specimens from oral pathology laboratory of Universidade Federal de Minas Gerais, from 1954 to 2004. Using the criteria of histologic typification published by the World Health Organization in 1992, we classified the OTs. RESULTS: A total of 340 OTs were found. The frequency of OTs comprises 1.78% of all pathologic specimens in our laboratory. The most frequent tumor was ameloblastoma (45.2%), followed by odontomas (24.91%), and myxomas (9.1%). CONCLUSIONS: Odontogenic tumors are uncommon lesions in this Brazilian population and malignant OTs are very rare. The relative frequency of various types of OTs, age, and gender distribution are similar to those reported in African, Asian but not to Chilean and North American series.


Subject(s)
Odontogenic Tumors/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Ameloblastoma/epidemiology , Brazil/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Male , Mandibular Neoplasms/epidemiology , Maxillary Neoplasms/epidemiology , Middle Aged , Odontogenic Cyst, Calcifying/epidemiology , Odontoma/epidemiology , Retrospective Studies , Sex Factors
9.
J Oral Pathol Med ; 34(8): 494-7, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16091117

ABSTRACT

BACKGROUND: Considerable evidence indicates that serotonergic mechanisms, particularly the serotonin transporter (5-HTT) may be involved in psychological alterations. Recent findings have demonstrated that depression and stress are influenced by polymorphism of the promoter region of 5-HTT (5-HTTLPR) and that the short allele (S) is associated with reduced transcriptional efficiency resulting in reduced serotonin expression and uptake. As psychological and genetic factors have been implicated in the pathogenesis of recurrent aphthous stomatitis (RAS), the purpose of the present study was to investigate 5-HTTLPR polymorphism in patients with RAS compared with control subjects. METHODS: Sixty-nine consecutive subjects affected by minor and major forms of RAS and 70 healthy volunteers were genotyped at 5-HTTLPR. The chi-square test was used for statistical analysis. RESULTS: A significant increase in the genotype of SS (P = 0.05) and of the allele S (P = 0.04) in the group of RAS were observed. CONCLUSION: Our findings demonstrate that RAS patients have a tendency to show polymorphism associated with anxiety-related traits.


Subject(s)
Anxiety/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins/genetics , Nerve Tissue Proteins/genetics , Serotonin/genetics , Stomatitis, Aphthous/genetics , Adolescent , Adult , Aged , Alleles , Anxiety/complications , Case-Control Studies , Chi-Square Distribution , Child , Female , Gene Frequency , Humans , Male , Middle Aged , Polymorphism, Genetic , Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins , Stomatitis, Aphthous/complications , Stomatitis, Aphthous/psychology
11.
Int J Med Sci ; 1(3): 146-151, 2004.
Article in English | MEDLINE | ID: mdl-15912193

ABSTRACT

Lichen planus is a mucocutaneous disease of inflammatory nature and unknown etiology. It is characterized by a cell-mediated immunological response to induced antigenic change in skin and/or mucosa. The possible malignant transformation of lichen planus remains a subject of controversial discussions in the literature. hMSH2 is one of the human DNA mismatch repair (hMMR) genes and it plays an important role in reducing mutation and maintaining genomic stability. hMSH2 alterations have been reported in oral squamous cell carcinoma and there are evidences suggesting the association between oral lichen planus and squamous cell carcinoma. In this study, we aim to investigate the immunolocalization of hMSH2 protein in oral lichen planus compared to oral normal mucosa epithelium. We examined the expression of hMSH2 protein by immunohistochemistry in twenty-six cases of oral lichen planus. Clinically, 12 of them were categorized into reticular subtype and 14 were atrophic/erosive. Ten cases of normal mucosa were added to the control group. Results showed that the percentage of positive cells to hMSH2 was smaller in reticular (46.54%; p=0,006) and atrophic/erosive (48.79%; p=0,028) subtypes of oral lichen planus compared to normal mucosa (61.29%). The reduced expression of hMSH2 protein in oral lichen planus suggests that this lesion is more susceptible to mutation and therefore facilitate the development of oral squamous cell carcinoma.

12.
Article in English | MEDLINE | ID: mdl-12973294

ABSTRACT

OBJECTIVE: The purpose of this study was to determine the immunolocalization of the interleukin (IL) 4, IL-6, and lymphotoxin (LT) alpha in dental granulomas and correlate their expression with the intensity of the inflammatory infiltrate. Study design Fifteen paraffin specimens of dental granulomas were selected, and the streptavidin-biotin complex stain was used to detect IL-4, IL-6, and LT-alpha. RESULTS: Our results revealed a significant statistical correlation between the intensity of inflammatory infiltrate and the percentage of mononuclear cells positive for IL-4. Moreover, we observed a statistically significant correlation between the frequency of cells expressing IL-6 and LT-alpha. CONCLUSION: These data suggest that the predominance of a helper T cell subtype 2 response in dental granulomas is correlated with the exacerbation of the inflammatory reaction and its evolution. Moreover, a correlation between the frequency of IL-6-positive and LT-alpha-positive cells suggests that the synergistic activities of these 2 cytokines may be involved in the pathogenesis of this inflammatory condition.


Subject(s)
Interleukin-4/analysis , Interleukin-6/analysis , Lymphotoxin-alpha/analysis , Periapical Granuloma/pathology , Adult , Humans , Immunoenzyme Techniques , Leukocyte Count , Leukocytes, Mononuclear/pathology , Lymphocyte Count , Middle Aged , Statistics, Nonparametric , T-Lymphocytes, Helper-Inducer/pathology
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