Periodontal disease affects oral cancer progression in a surrogate animal model for tobacco exposure.

For decades, the link between poor oral hygiene and the increased prevalence of oral cancer has been suggested. Most recently, emerging evidence has suggested that chronic inflammatory diseases from the oral cavity (e.g., periodontal disease), to some extent, play a role in the development of oral squamous cell carcinoma (OSCC). The present study aimed to explore the direct impact of biofilm­induced periodontitis in the carcinogenesis process using a tobacco surrogate animal model for oral cancer. A total of 42 Wistar rats were distributed into four experimental groups: Control group, periodontitis (Perio) group, 4­nitroquinoline 1­oxide (4­NQO) group and 4NQO/Perio group. Periodontitis was stimulated by placing a ligature subgingivally, while oral carcinogenesis was induced by systemic administration of 4NQO in the drinking water for 20 weeks. It was observed that the Perio, 4NQO and 4NQO/Perio groups presented with significantly higher alveolar bone loss compared with that in the control group. Furthermore, all groups receiving 4NQO developed lesions on the dorsal surface of the tongue; however, the 4NQO/Perio group presented larger lesions compared with the 4NQO group. There was also a modest overall increase in the number of epithelial dysplasia and OSCC lesions in the 4NQO/Perio group. Notably, abnormal focal activation of cellular differentiation (cytokeratin 10­positive cells) that extended near the basal cell layer of the mucosa was observed in rats receiving 4NQO alone, but was absent in rats receiving 4NQO and presenting with periodontal disease. Altogether, the presence of periodontitis combined with 4NQO administration augmented tumor size in the current rat model and tampered with the protective mechanisms of the cellular differentiation of epithelial cells.

Propolis reduces the stemness of head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the effect of Brazilian propolis on head and neck cancer stem cells in vitro. METHODS: Head and neck squamous cell carcinoma (HNSCC) cell lines (UM-SCC-17B and UM-SCC-74A), human keratinocytes (HK), and primary human dermal microvascular endothelial cells (HDMEC) were treated with 0.5, 5.0, or 50 µg/mL green, brown or red Brazilian propolis or vehicle control for 24, 36, and 72 h. Cell viability was evaluated by Sulforhodamine B assay. Western blots evaluated expression of cancer stem cell (CSC) markers (i.e. ALDH, CD44, Oct-4, Bmi-1) and flow cytometry was performed to determine the impact of propolis in the fraction of CSC, defined as ALDHhighCD44high cells. RESULTS: propolis significantly reduced cell viability of HNSCC and HDMEC cells, but not HK. Notably, red propolis caused a significant reduction in the percentage of CSC, reduced the number of orospheres, and downregulated the expression of stem cell markers. CONCLUSIONS: Collectively, our data demonstrate an anti-CSC effect of propolis, and suggest that propolis (i.e. red propolis) might be beneficial for patients with head and neck cancer.

Clinicopathological analysis of salivary gland tumors over a 15-year period.

Salivary gland tumors (SGT) are rare neoplasms that generate interest due to their histopathological diversity and clinical behavior. The aims of the present study were to investigate clinicopathological aspects of SGTs diagnosed at a tertiary health center and compare the findings with epidemiological data from different geographic locations. Cases of tumor in the head and neck region at a single health center in the period between 1995 and 2010 were reviewed. Patient gender, age and ethnic group as well as anatomic location, histological type and clinical behavior of the tumor were recorded. Availability of complete information about these aspects was considered the inclusion criteria. Descriptive statistical analysis of the data was performed using the frequencies of categorical variables. Among the 2168 cases of tumors in the head and neck region, 243 (11.20%) cases were diagnosed in the salivary glands, 109 of which met the inclusion criteria: 85 (78%) benign tumors and 24 (22%) malignant tumors. Mean patient age was 46.47 years. The female gender accounted for 56 cases (51.4%) and the male gender accounted for 53 (48.3%). The major salivary glands were affected more (75.2%) than the minor glands. The most frequent benign and malignant SGTs were pleomorphic adenoma (81.2%) and adenoid cystic carcinoma (58.3%), respectively. In conclusion, pleomorphic adenoma and adenoid cystic carcinoma are the most frequent benign and malignant lesions, respectively. Comparing the present data with previous studies on SGTs, one may infer that some demographic characteristics and the predominance of malignant tumors vary in different geographic regions.

BH3-mimetic small molecule inhibits the growth and recurrence of adenoid cystic carcinoma.

OBJECTIVES: To evaluate the anti-tumor effect of BM-1197, a new potent and highly specific small molecule inhibitor of Bcl-2/Bcl-xL, in preclinical models of human adenoid cystic carcinoma (ACC). METHODS: Low passage primary human adenoid cystic carcinoma cells (UM-HACC-2A,-2B,-5,-6) and patient-derived xenograft (PDX) models (UM-PDX-HACC) were developed from surgical specimens obtained from 4 patients. The effect of BM-1197 on cell viability and cell cycle were evaluated in vitro using this panel of low passage ACC cells. The effect of BM-1197 on tumor growth, recurrence and tumor cell apoptosis in vivo was evaluated with the PDX model of ACC (UM-PDX-HACC-5). RESULTS: Exposure of low passage primary human ACC cells to BM-1197 mediated an IC50 of 0.92-2.82 µM. This correlated with an increase in the fraction of apoptotic cells (p<0.0001) and an increase in caspase-3 activity (p<0.0001), but no noticeable differences in cell cycle (p>0.05). In vivo, BM-1197 inhibited tumor growth (p=0.0256) and induced tumor cell apoptosis (p=0.0165) without causing significant systemic toxicities, as determined by mouse weight over time. Surprisingly, weekly BM-1197 decreased the incidence of tumor recurrence (p=0.0297), as determined by Kaplan-Meier analysis. CONCLUSION: These data demonstrated that single agent BM-1197 induces apoptosis and inhibits tumor growth in preclinical models of adenoid cystic carcinoma. Notably, single agent BM-1197 inhibited tumor recurrence, which is considered a major clinical challenge in the clinical management of adenoid cystic carcinoma. Collectively, these results suggest that patients with adenoid cystic carcinoma might benefit from therapy with a BH3-mimetic small molecule.

The importance of histopathologic analysis of pericoronal follicles for the early identification of ameloblastomas.

The objective of this study was to discuss the importance of performing histopathological examination of pericoronal follicles as a routine procedure, so as to enable the early identification of odontogenic lesions. We describe two clinical cases with histopathological diagnoses of ameloblastomas who did not show clinical or radiographic signs of disease before microscopic examination.

Chronic alcohol consumption promotes alterations on salivary gland regeneration process.

The aim of this study is to investigate the histological effect of alcohol ingestion on the regeneration of the submandibular gland (SMG) in rats. Twelve 60-day-old male Wistar rats were randomized into two experimental groups. Test group (TG) animals ingested 40° GL of alcohol for 45 days before surgery, being its concentration gradually increased 10° GL/week for 4 weeks to achieve the final concentration of 40° GL. The control group (CG) received water during the whole experimental period. One-third of the left SMG lobe was removed. Three and seven days after, the whole gland was excised and analyzed. In the TG, the inflammatory process was pronounced when comparing the CG on day 3. The inverse aspect was observed on day 7, associated with an advanced parenchyma development. Changes in laminin expression and glycoproteins production were observed in the TG, causing advanced morphogenesis and delay in cytodifferentiation during the salivary gland regeneration, probably due to alcohol effects. Animals who received ethanol showed alterations in the pattern of glandular regeneration.

Differential diagnosis between oral fibroma and inflammatory hyperplasia: a proposal for histopathological criteria / Diagnóstico diferencial entre fibroma oral e hiperplasia fibrosa inflamatória: uma proposta para critério histopatológico

Aim: The present study proposed histopathological criteria for thedifferential diagnosis between those pathological entities. Materialsand methods: Histological sections of lesions histopathologicallydiagnosed as Oral Fibroma (n=61) and Inflammatory Hyperplasia(n=75) and were submitted to different techniques (HematoxylinEosin;Masson Trichrome and Phosphomolybdic acid - Picrosirius red)to allow quantitative and qualitative analysis. The qualitative analysisof collagen density was based on sections stained by HematoxylinEosinand focused in the center and periphery of each lesion.Results: Wound and collagen fibers were more frequent and higher inOral Fibroma, while parallel fibers were more frequent in InflammatoryHyperplasia (Fisher’s exact test, p<0.05). The percentage of parallelcollagen fibers beneath the epithelium was 72.22% and 92.3% in OralFibroma and Inflammatory Hyperplasia, respectively (Mann Whitney Utest, p<0.05). The parallel collagen fibers in the center of the lesionwas found in 84.6% of Inflammatory Hyperplasia cases and wasabsent in 88.88% of Oral Fibroma. The central portion of Oral Fibromahad characteristically a dense and wound arrangement of collagenfibers. Conclusion: Oral Fibroma and Inflammatory Hyperplasia havedistinctive features that may be useful in routine histopathologicalanalysis, supporting the differential diagnosis.

Objetivos: O presente estudo propôs critérios histopatológicos para odiagnóstico diferencial entre as entidades patológicas. Materiais emétodos: Cortes histológicos de lesões diagnosticadasmicroscopicamente como Fibroma Oral (n=61) e Hiperplasia FibrosaInflamatória (n=75) foram submetidos a diferentes técnicas decoloração (Hematoxilina-eosina, Tricrômio de Masson e ÁcidoFosfomolibidico- Vermelho de Picrosírius) para permitir análisesquantitativa e qualitativa. A análise qualitativa da densidade docolágeno foi baseada nas lâminas coradas em Hematoxilina- eosinae observada no centro e periferia de cada lesão. Resultados: Fibrascolágenas enoveladas eram mais frequentes e mais densas noFibroma Oral, enquanto as fibras paralelas e ram observadas naHiperplasia Fibrosa Inflamatória (teste exato de Fisher, p<0,05). Nocentro da lesão, fibras colágenas paralelas foram encontradas em84,6% dos casos de Hiperplasias Fibrosas Inflamatórias e ausentesem 88,88% dos Fibromas Orais. A porção central do Fibroma Oral eracaracterizado por um arranjo denso e frouxo das fibras colágenas.Conclusão: o Fibroma Oral e a Hiperplasia Fibrosa Inflamatóriapossuem características bem distintas que pode ser útil na rotina daanálise histopatológica, auxiliando no diagnóstico diferencial.