Tumefações do soalho bucal relacionadas às glândulas sublinguais em pacientes edêntulos ou parcialmente edêntulos: estudo microscópico

Mouth floor enlargements (MFE) are observed in edentulous and partially edentulous patients, impairing denture fitting, and have recently been described in the literature as hyperplasias of the sublingual glands. OBJECTIVE: This study aims at describing the microscopic aspects of MFE that contribute to their final diagnosis. METHODS: Twenty-four specimens were surgically removed from the enlarged mouth floor of 19 patients (15 females and 4 males). Patient age ranged from 48 to 74 years, with a mean of 57 years. The main surgical indication was to permit or improve the fitting of dentures. Six patients were completely edentulous and 13 were partially edentulous. The material was processed for microscopic examination and stained with hematoxylin-eosin, Mallory's trichrome and periodic-acid Schiff (PAS). RESULTS AND CONCLUSIONS: The epithelium of the mouth floor was normal in 17 cases, hyperplastic in 4 and atrophic in 3. Six of the 24 sublingual glands removed were microscopically normal, while the other specimens presented acinar atrophy with hyperplasia of duct-like structures. Interstitial fibrosis was observed in 18 cases and was accompanied by adipose tissue infiltration in 15. Decreased lymphoid tissue was observed in 16 samples and oncocytosis was present in 5 cases. We suggest that MFE in edentulous or partially edentulous patients should be considered as an entity for the text books.Tumefações do soalho bucal (TSB) são observadas em pacientes edêntulos ou parcialmente edêntulos, prejudicando a adaptação de próteses, e têm sido descritas recentemente na literatura como hiperplasias das glândulas sublinguais. OBJETIVO: O objetivo desse estudo é descrever os aspectos microscópicos das TSB a fim de contribuir para o seu diagnóstico final. MATERIAL E MÉTODOS: Foram removidos cirurgicamente 24 espécimes de 19 pacientes (15 mulheres e 4 homens) que possuíam TSB. A idade variou de 48 a 74 anos, com média de 57 anos. A principal indicação cirúrgica era permitir ou melhorar a adaptação das próteses. Seis pacientes eram edêntulos e 13, parcialmente edêntulos. O material foi processado para exame microscópico e corado com hematoxilina-eosina, tricrômico de Mallory e ácido periódico de Schiff (PAS). RESULTADOS E CONCLUSÕES: O epitélio do soalho bucal estava normal em 17 casos, hiperplásico em 4 e atrófico em 3. Seis das 24 glândulas sublinguais removidas eram normais microscopicamente, enquanto que as demais apresentaram atrofia acinar com hiperplasia de estruturas ductiformes. Fibrose intersticial foi observada em 18 casos sendo acompanhada por infiltração de tecido adiposo em 15 casos. Uma diminuição no tecido linfóide foi observada em 16 espécimes e oncocitose em 5. Sugerimos que as TSB em pacientes edêntulos e parcialmente edêntulos devem ser classificadas como "entidade" nos livros texto

Contribuição para o diagnóstico do pequeno cisto dentígero ou do cisto paradentário

The aim of this study was to verify the relationship between the radiographically measured width of the pericoronal space (PS) and the microscopic features of the follicle in order to contribute to the diagnosis of small dentigerous cysts and paradental cysts. One hundred and thirty unerupted teeth (UT) and thirty-five partially erupted teeth (PET) were radiographed and extracted. The radiographic analysis consisted of measuring the width of the PS. The results of the radiographic analysis were compared with those of the histopathologic examination of the dental follicle. The width of the PS ranged from 0.1 to 5.6 mm. The most frequently observed lining of the follicles was a reduced enamel epithelium (REE) (68.4%) in UT and a hyperplastic stratified squamous epithelium (HSSE) (68.5%) in PET. Inflammation was present in 36.1% of the UT and in 82.8% of the PET. There was a statistically significant association between the presence of stratified squamous epithelium (SSE) and PS enlargement for UT (p < 0.05). There was a tendency of association between inflammation and PS enlargements in PET and, possibly, in UT, despite the absence of statistical significance. Surgically, we did not detect bone cavitation or luminal cystic contents in pericoronal spaces smaller than 5.6 mm. We suggest that the first radiographic diagnosis for a PS enlargement, in most of the routine clinical cases, should be of "inflammation of the follicle". The hypothesis of "dentigerous cyst" or "paradental cyst" is suggested as a second diagnosis. The final differential diagnosis between a small dentigerous or a paradental cyst and a pericoronal follicle depends on clinical and/or surgical findings, such as the presence of bone cavitation and cystic content.Foi propósito deste estudo verificar a relação entre a largura do espaço pericoronário (EP) medida radiograficamente e os aspectos microscópicos do folículo. O objetivo foi contribuir com o diagnóstico de pequenos cistos dentígeros e cistos paradentários. Cento e trinta dentes não-irrompidos (DNI) e trinta e cinco dentes parcialmente irrompidos (DPI) foram radiografados e extraídos. O estudo radiográfico consistiu na medição da largura do EP seguida pelo exame microscópico do folículo. A largura do EP variou de 0,1 a 5,6 mm. O revestimento mais freqüentemente observado em DNI foi o epitélio reduzido do esmalte (ERE = 68,4%). Em DPI foi o epitélio pavimentoso estratificado hiperplásico (EPEH = 68,5%). Inflamação estava presente em 36,1% dos DNI e 82,8% dos DPI. Houve uma associação estatisticamente significante entre a presença de epitélio pavimentoso estratificado (EPE) com o alargamento do espaço pericoronário em DNI (p < 0,05). Houve uma tendência da inflamação estar associada com o alargamento do EP em DPI. Em espaços pericoronários menores que 5,6 mm não foram detectados cavidade óssea e conteúdo cístico cirurgicamente. Na maioria dos casos clínicos de rotina com alargamento do EP, sugerimos que o primeiro diagnóstico radiográfico deva ser "folículo inflamado". "Cisto dentígero" ou "cisto paradentário" deve ser sugerido como segundo diagnóstico. O diagnóstico diferencial final entre um pequeno cisto dentígero ou cisto paradentário e um folículo pericoronário dependerá de achados clínicos e/ou cirúrgicos de cavidade e conteúdo

NK2 homeobox gene cluster: Functions and roles in human diseases

NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classified into two distinct families, NK2.1 and NK2.2. The former is constituted by NKX2-1 and NKX2-4 genes, which are homologous to the Drosophila scro gene; the latter includes NKX2-2 and NKX2-8 genes, which are homologous to the Drosophila vnd gene. Conservation of these genes is not only related to molecular structure and expression, but also to biological functions. In Drosophila and vertebrates, NK2 genes share roles in the development of ventral regions of the central nervous system. In vertebrates, NKX2 genes have a relevant role in the development of several other organs such as the thyroid, lung, and pancreas. Loss-of-function mutations in NKX2-1 and NKX2-2 are the monogenic cause of the brain-lung-thyroid syndrome and neonatal diabetes, respectively. Alterations in NKX2-4 and NKX2-8 genes may play a role in multifactorial diseases, autism spectrum disorder, and neural tube defects, respectively. NKX2-1, NKX2-2, and NKX2-8 are expressed in various cancer types as either oncogenes or tumor suppressor genes. Several data indicate that evaluation of their expression in tumors has diagnostic and/or prognostic value

Reading cancer: Chromatin readers as druggable targets for cancer treatment

The epigenetic machinery deputed to control histone post-translational modifications is frequently dysregulated in cancer cells. With epigenetics being naturally reversible, it represents a good target for therapies directed to restore normal gene expression. Since the discovery of Bromodomain and Extra Terminal (BET) inhibitors, a great effort has been spent investigating the effects of chromatin readers&rsquo; inhibition, specifically the class of proteins assigned to bind acetylated and methylated residues. So far, focused studies have been produced on epigenetic regulation, dissecting a specific class of epigenetic-related proteins or investigating epigenetic therapy in a specific tumor type. In this review, recent steps toward drug discovery on the different classes of chromatin readers have been outlined, highlighting the pros and cons of current therapeutic approaches

Dihydrotanshinone I exhibits antitumor effects via β-catenin downregulation in papillary thyroid cancer cell lines

Thyroid cancer is the most common endocrine carcinoma and, among its different subtypes, the papillary subtype (PTC) is the most frequent. Generally, PTCs are well differentiated, but a minor percentage of PTCs are characterized by a worse prognosis and more aggressive behavior. Phytochemicals, naturally found in plant products, represent a heterogeneous group of bioactive compounds that can interfere with cell proliferation and the regulation of the cell cycle, taking part in multiple signaling pathways that are often disrupted in tumor initiation, proliferation, and progression. In this work, we focused on 15,16-dihydrotanshinone I (DHT), a tanshinone isolated from Salvia miltiorrhiza Bunge (Danshen). We first evaluated DHT biological effect on PTC cells regarding cell viability, colony formation ability, and migration capacity. All of these parameters were downregulated by DHT treatment. We then investigated gene expression changes after DHT treatment by performing RNA-seq. The analysis revealed that DHT significantly reduced the Wnt signaling pathway, which plays a role in various diseases, including cancer. Finally, we demonstrate that DHT treatment decreases protein levels of β-catenin, a final effector of canonical Wnt signaling pathway. Overall, our data suggest a possible use of this nutraceutical as an adjuvant in the treatment of aggressive papillary thyroid carcinoma

GSK2801 Reverses Paclitaxel Resistance in Anaplastic Thyroid Cancer Cell Lines through MYCN Downregulation

Anaplastic thyroid cancer (ATC) is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. Treatment with taxanes (such as paclitaxel) is an important approach in counteracting ATC or slowing its progression in tumors without known genetic aberrations or those which are unresponsive to other treatments. Unfortunately, resistance often develops and, for this reason, new therapies that overcome taxane resistance are needed. In this study, effects of inhibition of several bromodomain proteins in paclitaxel-resistant ATC cell lines were investigated. GSK2801, a specific inhibitor of BAZ2A, BAZ2B and BRD9, was effective in resensitizing cells to paclitaxel. In fact, when used in combination with paclitaxel, it was able to reduce cell viability, block the ability to form colonies in an anchor-independent manner, and strongly decrease cell motility. After RNA-seq following treatment with GSK2801, we focused our attention on MYCN. Based on the hypothesis that MYCN was a major downstream player in the biological effects of GSK2801, we tested a specific inhibitor, VPC-70619, which showed effective biological effects when used in association with paclitaxel. This suggests that the functional deficiency of MYCN determines a partial resensitization of the cells examined and, ultimately, that a substantial part of the effect of GSK2801 results from inhibition of MYCN expression

Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report

Background We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD). Case presentation A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects. Conclusions This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway

The Onset of a Peripheral Ameloblastoma

Incipient odontogenic tumors often display intermediate features between two or more lesions leading to diagnosis dilemma. We report the onset of a peripheral ameloblastoma fortuitously found subjacent to a nondysplastic leukoplakia in the region of missing 38 teeth of a 52-year-old man. The aim of this paper is the discussion of the microscopical features observed in the case reported which allowed the establishment of the final diagnosis of an early peripheral ameloblastoma

The Intracellular Localization of APE 1 /Ref-1: More than a Passive Phenomenon?

Human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a perfect paradigm of the functional complexity of a biological macromolecule. First, it plays a crucial role, by both redox-dependent and –independent mechanisms, as a transcriptional coactivator for different transcription factors, either ubiquitous (i.e., AP-1, Egr-1, NF-κB, p53, HIF) or tissue-specific (i.e., PEBP-2, Pax-5 and -8, TTF-1), in controlling different cellular processes such as apoptosis, proliferation, and differentiation. Second, it acts, as an apurinic/apyrimidinic endonuclease, during the second step of the DNA base excision repair pathway, which is responsible for the repair of cellular alkylation and oxidative DNA damages. Third, it controls the intracellular reactive oxygen species production by negatively regulating the activity of the Ras-related GTPase Rac1. Despite these known functions of APE1/Ref-1, information is still scanty about the molecular mechanisms responsible for the coordinated control of its several activities. Some evidence suggests that the expression and subcellular localization of APE1/Ref-1 are finely tuned. APE1/Ref-1 is a ubiquitous protein, but its expression pattern differs according to the different cell types. APE1/Ref-1 subcellular localization is mainly nuclear, but cytoplasmic staining has also been reported, the latter being associated with mitochondria and/or presence within the endoplasmic reticulum. It is not by chance that both expression and subcellular localization are altered in several metabolic and proliferative disorders, such as in tumors and aging. Moreover, a fundamental role played by different posttranslational modifications in modulating APE1/Ref-1 functional activity is becoming evident. In the present review, we tried to put together a growing body of information concerning APE1/Ref-1's different functions, shedding new light on present and future directions to understand fully this unique molecule

Effects of dihydrotanshinone I on proliferation and invasiveness of paclitaxel-resistant anaplastic thyroid cancer cells

ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono-or combined chemotherapy, which is often not fully effective for the appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches for this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel and investigated the characteristics of these cells by analyzing the profile of gene expression and comparing it with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-\u3baB compared to sensitive cells. DHT treatment resulted in a reduction of viability and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-\u3baB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro