A comparative study to evaluate the effects of antibiotics, plant extracts and fluoride-based toothpaste on the oral pathogens isolated from patients with gum diseases in Pakistan / Um estudo comparativo para avaliar os efeitos de antibióticos, extratos vegetais e creme dental à base de flúor sobre os patógenos orais isolados de pacientes com doenças gengivais no Paquistão

Oral diseases caused by various microorganisms are common around the world. Scientific research has now been focusing on novel medicines to overcome bacterial resistance and antibiotics side effects; therefore, the current study was designed to assess the efficacy of certain antibiotics, toothpaste, and medicinal plant extracts (Ajuga bracteosa and Curcuma longa) versus the bacterial pathogens isolated from the human oral cavity. A total of 130 samples were collected from Khyber Teaching Hospital Peshawar, Pakistan, among those 27 species isolated, and eight bacterial species were identified from the samples. Among all the bacterial species, Staphylococcus aureus (29.62%) and Proteus mirabilis (22.2%) were found to be more prevalent oral pathogens. In comparison, the least pervasive microbes were Proteus vulgaris, Shigella sonnei, Escherichia coli and Aeromonas hydrophila. The study also suggested that dental problems were more prevalent in males (41-50 years of age) than females. Among the eight antibiotics used in the study, the most promising results were shown by Foxicillin against A. hydrophila. The survey of TP1 revealed that it showed more potent antagonist activity against Proteus vulgaris as compared TP2 and TP3 that might be due to the high content of fluoride. The Curcuma longa showed more significant activity than Ajuga bracteosa (Stem, leaves and root) extracts. The data obtained through this study revealed that antibiotics were more effective for oral bacterial pathogens than toothpaste and plant extracts which showed moderate and low activity, respectively. Therefore, it is suggested that the active compounds in individual medicinal plants like Curcuma longa and Ajuga bracteosa could replace the antibiotics when used in daily routine as tooth cleansers or mouth rinses.

As doenças bucais causadas por vários microrganismos são comuns em todo o mundo. A pesquisa científica agora tem se concentrado em novos medicamentos para superar a resistência bacteriana e os efeitos colaterais dos antibióticos; portanto, o presente estudo foi desenhado para avaliar a eficácia de certos antibióticos, pasta de dente e extratos de plantas medicinais (Ajuga bracteosa e Curcuma longa) contra os patógenos bacterianos isolados da cavidade oral humana. No total, 130 amostras foram coletadas do Khyber Teaching Hospital Peshawar, Paquistão, entre essas, 27 espécies foram isoladas e oito espécies bacterianas foram identificadas a partir das amostras. Entre todas as espécies bacterianas, Staphylococcus aureus (29.62%) e Proteus mirabilis (22.2%) foram os patógenos orais mais prevalentes. Em comparação, os micróbios menos difundidos foram Proteus vulgaris, Shigella sonnei, Escherichia coli e Aeromonas hydrophila. O estudo também sugeriu que os problemas dentários eram mais prevalentes em homens (41-50 anos de idade) do que em mulheres. Entre os oito antibióticos usados no estudo, os resultados mais promissores foram mostrados pelo Foxicillin contra A. hydrophila. A pesquisa de TP1 revelou que ele mostrou atividade antagonista mais potente contra Proteus vulgaris em comparação a TP2 e TP3, o que pode ser devido ao alto teor de flúor. A Curcuma longa apresentou atividade mais significativa em relação aos extratos de Ajuga bracteosa (caule, folhas e raiz). Os dados obtidos neste estudo revelaram que os antibióticos foram mais eficazes para os patógenos bacterianos orais do que os dentifrícios e os extratos vegetais que apresentaram atividade moderada e baixa, respectivamente. Portanto, sugere-se que os compostos ativos em plantas medicinais individuais como Curcuma longa e Ajuga bracteosa possam substituir os antibióticos quando usados na rotina diária como limpadores de dentes ou enxaguatórios bucais.

High expression of aryl hydrocarbon receptor (AhR) plays an important role in the formation of fibrous epulis.

OBJECTIVES: Epulis is considered to be a massive reactive lesion rather than a true neoplasia. AhR is thought to be associated with inflammation and development of neoplasms. Here, we aimed to observe the expression of AhR in fibrous epulis and explore its role and possible mechanism in the pathogenesis of epulis. MATERIALS AND METHODS: Epulis and normal gingival tissues were collected, and AhR expression was detected at the mRNA and protein levels by quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. The expression levels of proinflammatory cytokines and apoptosis-related factor genes in human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (hGFs) transfected with AhR short interfering RNA (siRNA) or negative control siRNA, upon stimulation with lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS), were then examined. Finally, the expression levels of the proinflammatory cytokines and apoptosis-related factor genes in the epulis tissues were observed by qPCR. RESULTS: AhR expression in fibrous epulis was significantly increased at both the mRNA and protein levels. The expression of proinflammatory cytokines and apoptosis-related factor genes in hPDLCs transfected with AhR siRNA was significantly decreased when stimulated with Pg-LPS. The same trends were observed for hGFs. The opposite trend was detected in the epulis tissues. CONCLUSION: AhR may be a key factor in fibrous epulis pathogenesis that acts by regulating the expression of BCL2 family genes and inflammatory factor-related genes.

Concomitant endogenous and exogenous etiology for gingival pigmentation.

Oral pigmented lesions can be physiological or pathological, exogenous or endogenous, as well as focal, multifocal, or diffuse. Among them, the oral melanotic macule (OMM) is a small, well-delimited brown-to-black macule, often affecting the lip and gingiva. Amalgam tattoo (AT) is a grey or black area of discoloration on the oral mucosa as a result of entry of dental amalgam into the soft tissues, commonly gingiva and alveolar ridge. Herein, we present a patient with gingival pigmentation with features of both OMM and AT in the same location.

PCR array analysis identified hyperproliferation but not autophagy or apoptosis in fibrous epulis.

BACKGROUND: The pathogenesis of fibrous epulis is still quite unclear. Our recent genome-wide RNA sequencing analysis revealed that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway regulates the expression of Bcl-2 family and IAP family genes, leading to increased proliferation and the inhibition of apoptosis. The PI3K/AKT signaling pathway can promote autophagy in human gingival fibroblasts; therefore, the purpose of the present study was to identify whether autophagy is involved in the pathogenesis of fibrous epulis. METHODS: Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were identified using the PCR array. The expression levels of eighteen autophagy-related (ATG) family genes, twelve B-cell lymphoma 2 (Bcl-2) family genes, and eleven cysteine-dependent aspartate-directed protease (caspase) family genes were validated using quantitative real-time PCR (qRT-PCR). Autophagy induction was determined by measuring microtubule-associated protein light chain 3 (LC3) conversion (LC3-I to LC3-II) by immunoblot analysis. RESULTS: The PCR array identified six upregulated genes, whereas no genes were expressed at significantly lower levels. The upregulated genes were BCL2, BCL2L1, CXCR4, HSP90AA1, HSPA8, and IGF1, which all belong to the "regulation of autophagy" group but not the "autophagy machinery components" group. qRT-PCR verified that the expression levels of BCL2, BCL2L1 (also known as BCL-XL), and BCL2L2 (also known as BCL-W) were significantly increased in fibrous epulis. No LC3-I to LC3-II conversion was observed. CONCLUSIONS: The present study reveals that in fibrous epulis, Bcl-2 and Bcl-xL coordinately mediate gingival cell escape from apoptosis, leading to uncontrolled proliferation. Moreover, ATG family genes are not activated, and autophagy is not involved in this process.

Gingival Leukoplakia: Hyperkeratosis with Epithelial Atrophy Is A Frequent Histopathologic Finding.

White lesions on the gingiva and palatal mucosa may represent reactive keratoses, including specific diseases such as benign alveolar ridge keratosis, or nonreactive keratoses, such as true leukoplakia, the latter being associated with a high recurrence rate at this site. The aim of this study is to determine the histopathologic features of gingival keratoses. Hyperkeratotic lesions from the gingiva, palatal mucosa, and alveolar ridge mucosa were available for evaluation after excluding specific keratotic lesions such as candidiasis. There were 321 biopsies from 296 patients and approximately half of the cases (159/321, 49.5%) were reactive keratoses. The rest of the 162 biopsies from 149 patients (76 females; 51.0%) represented true leukoaplakias. The most common location was the gingiva (73.2%) followed by the palatal mucosa (17.0%). Hyperkeratosis/parakeratosis not reactive (HkNR) represented 43.8% of cases; 45.7% were dysplasia or carcinoma, and the rest were not readily classifiable as reactive or non-reactive keratoses. Histopathologic features commonly noted in the HkNR lesions include sharp demarcation (72.7%), corrugated surface (53.5%), and epithelial atrophy (48.1%). A lymphocytic band was noted in 8.5% of the cases, mostly associated with epithelial atrophy (5/6 cases). Seven patients with 17 biopsies from noncontiguous sites likely had proliferative leukoplakia; the most common location was the gingiva (88.2%) and the most common diagnosis was HkNR (52.9%). HkNR is a common histopathologic diagnosis for leukoplakias on the gingiva, and these lesions frequently exhibit thick hyperkeratosis, epithelial atrophy and a lymphocytic band at the interface.

An unusually large peripheral giant cell granuloma: a case report / Granuloma periférico de células gigantes inusualmente grande: reporte de un caso

Peripheral giant cell granuloma (PGCG) is a benign reactive lesion of the oral cavity. Although PGCG is classified as a tumor-like lesion, it does not represent a true neoplasm, however it is often associated with a response of local irritation and trauma. Clinically, it appears as an exophytic growth with either sessile or pedunculated base, it can be located in gingiva or edentulous alveolar mucosa and usually does not exceed two cm in diameter. The following report describes the case of a 64-year-old female diagnosed with a PGCG of a particularly large size and rapidly evolving, located in the upper jaw area. The lesion was completely excised, and the diagnosis was confirmed by histopathology, there is no apparent recurrence in the area after 12 months of follow-up. A few cases of PGCG greater than 5 cm in diameter have been reported. Furthermore, exceptional cases might present an abnormal rapid growth as well. An opportune diagnosis based on clinical examination, radiographic and histopathological study are fundamental for a prompt and efficient treatment

El granuloma periférico de células gigantes (GPCG) es una lesión reactiva benigna de la cavidad oral en respuesta a una irritación local o a un traumatismo crónico. Si bien es una lesión de aspecto tumoral, no constituye una verdadera neoplasia. Se manifiesta como un crecimiento exofítico de base sésil o pediculada, localizado en encía o procesos alveolares edéntulos y no suele sobrepasar los 2 cm de diámetro. El presente reporte describe el caso de un GPCG de tamaño anormalmente grande y rápida evolución localizado en la zona del maxilar superior en un paciente femenino de 64 años. La biopsia escisional de la lesión confirmó el diagnóstico de GPCG y a 12 meses de seguimiento no se ha presentado recidiva. Se han reportado algunos casos de GPCG de más de 5 cm de diámetro. Además, casos excepcionales también pueden presentar un crecimiento rápido anormal. Un diagnóstico oportuno basado en el examen clínico, radiográfico e histopatológico es fundamental para un tratamiento rápido y eficaz

Oral focal mucinosis of the palate: a rare disease entity.

Oral focal mucinosis (OFM) is an extremely rare, benign oral soft tissue condition; less than 10 documented cases have been reported in the literature in patients under 18 years old. OFM has an unknown aetiology and predominantly presents in the fourth and fifth decades. The pathogenesis of OFM may be due to fibroblast overproduction of hyaluronic acid. Clinically, it remains almost impossible to diagnose definitively, due to its lack of pathognomonic features, therefore such lesions may have multiple differential diagnoses and histological analysis is essential to confirm OFM. We present an unusual presentation of OFM in a 14-year-old female patient. Following excision, focal myxoid degeneration of the connective tissue was apparent. This case highlights this rare condition for consideration in differential diagnosis of clinically similar lesions.

Distinguishing bowenoid papulosis from Bowen disease in the mouth: A case report.

Bowenoid papulosis (BPap) is an uncommon skin disorder linked to human papillomavirus (HPV) infection and characterized clinically by the presence of scattered papules or small plaques, multiple and pigmented, that involve the stratified squamous epithelium. Bowen disease (BD) is recognized as the main differential diagnosis of BPap. An 80-year old white woman was referred for the evaluation of multiple, brown verrucous papules measuring 3 to 4 mm in diameter on the right maxillary gingiva. Histopathological analysis revealed disturbed epithelial maturation with papillary stratified squamous epithelium, koilocytic dysplasia, parakeratosis, acanthosis, basal double-layer, loss of cellular polarity, nuclear hyperchromatism and pleomorphism, scattered mitosoid bodies, and a high degree of cytologic atypia. An immunohistochemical investigation for p53 and Ki67 showed staining of the basal and suprabasal layer, while p16 was strongly expressed in the nuclei of epithelial cells and Bcl-2 was positive only in mitosoid bodies and the lymphocytic inflammatory infiltrate. In situ DNA hybridization was negative for HPV. Oral BPap is an uncommon lesion in which the diagnostic process includes clinical, histopathological, and molecular correlations due to the similarity to aggressive behavior lesions such as BD.

EXOME REPORT: Novel mutation in ATP6V1B2 segregating with autosomal dominant epilepsy, intellectual disability and mild gingival and nail abnormalities.

Mutations in ATP6V1B2, which encodes the B2 subunit of the vacuolar H + ATPase have previously been associated with Zimmermann-Laband syndrome 2 (ZLS2) and deafness-onychodystrophy (DDOD) syndrome. Recently epilepsy has also been described as a potentially associated phenotype. Here we further uncover the role of ATP61VB2 in epilepsy and report autosomal dominant inheritance of a novel missense variant in ATP6V1B2 in a large Polish family with relatively mild gingival and nail problems, no phalangeal hypoplasia and with generalized epilepsy. In light of our findings and review of the literature, we propose that the ATP6V1B2 gene should be considered in families with autosomal dominant epilepsy both with or without intellectual disability, and that presence of subtle gingival and nail problems may be another characteristic calling card of affected individuals with ATP6V1B2 mutations.

The RAS-PI3K-AKT-NF-κB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes and inhibits apoptosis in fibrous epulis.

BACKGROUND: Epulis has a tumor-like appearance but is considered to be a massive reactive lesion rather than a true neoplasia. Limited information about the pathogenesis of epulis is available. The purpose of our study was to identify potential signaling pathways in fibrous epulis through transcriptome profiling. METHODS: Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were detected using RNA sequencing (RNAseq). The expression levels of eighteen genes were validated using quantitative real-time PCR (qRT-PCR). RESULTS: RNAseq identified 533 upregulated genes and 732 downregulated genes. The top 10 upregulated genes were IL11, OSM, MMP3, KRT75, MMP1, IL6, IL1B, IL24, SP7, and ADGRG3. The top 10 downregulated genes were BCHE, TYR, DCT, KRT222, RP11-507K12.1, COL6A5, PMP2, GFRA1, SCN7A, and CDH19. KEGG pathway analysis further indicated that the DEGs were enriched in "Pathways in cancer" and the "Ras signaling pathway". quantitative real-time PCR verified that the expression levels of SOS1, HRAS, PIK3CA, AKT3, IKBKA, IKBKB, NFKB1, BCL2, BCL2L1, XIAP, BIRC2, and BIRC3 were increased significantly. CONCLUSIONS: The current transcriptomic profiling study reveals that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes, leading to increased proliferation and apoptosis inhibition.

Oral focal mucinosis of the mandible in an adolescent patient.

Oral focal mucinosis (OFM) is the rare oral manifestation of cutaneous focal mucinosis. It is a diagnosis made histopathologically, as OFM remains clinically similar to other more common oral lesions, and radiographs do not provide any diagnostic information. This case is a report of a teenage female with left mandibular involvement of an elevated, rounded, asymptomatic, mucosa-coloured lesion in the facial and lingual gingiva between her left first and second mandibular molars. The cause was unclear, although the patient stated that she may have sustained a laceration in that area several months prior. An incisional biopsy revealed histopathological findings consistent with OFM, and complete surgical excision of the lesion was performed under a general anaesthetic, with no signs of recurrence for 2 months. The histological, clinical and accepted treatment methods on OFM will be discussed. Clinicians, including those serving paediatric populations, should consider OFM in their differential diagnoses when evaluating gingival lesions.

Peri-implant peripheral giant cell lesions: report of 13 new cases and comparative histological and immunohistochemical analysis with peripheral and central giant cell lesions

BACKGROUND: Few cases or periimplant peripheral giant cell lesions (PGCL) have been reported in the literature. The aim of this study was to report 13 new cases of peri-implant PGCL and compare the expression of smooth muscle actin, Bcl-2 protein, GLUT-1, CD68, osteoprotegerin, receptor activator of nuclear factor kappa-B, Ki-67 and CD34 in these cases with PGCL and central giant cell lesions (CGCL). MATERIAL AND METHODS: Clinical data were retrieved from the laboratory records and histological analysis was performed using HE-stained slides. Immunohistochemical reactions for the above mentioned antibodies were performed and digitally scored. RESULTS: Peri-implant PGCL mostly affected the posterior mandible of adult females. CD68 and Bcl-2 expressions were higher in conventional PGCL and CGCL than in peri-implant PGCL (p = 0.033 for CD68 and p < 0.0001 for Bcl-2). Microvessel density was higher in conventional peripheral than in central and peri-implant PGCL (p = 0.002). Proliferative index of the mononuclear cells showed no statistically significant differences comparing the three groups but it was higher in peri-implant PGCL. CONCLUSIONS: The current study demonstrated that peri-implant PGCL is more common in the posterior mandible of adult females. There were some differences in microvessel density, proliferative activity and expression of CD68 and Bcl-2 among conventional PGCL, peri-implant and CGCL. Further studies are encouraged to better understand these early findings

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Granuloma Periférico de Células Gigantes e Hiperparatiroidismo. Presentación de un Caso / Peripheral Giant Cell Granuloma and Hyperparathyroidism. Case Report

RESUMEN: Se presenta el caso de un paciente sexo femenino 31 años, insuficienciente renal crónica en hemodiálisis, hipertensa secundaria, consulta por aumento de volumen oral en relación a encía marginal vestibular izquierda, 6 meses de evolución. Al examen se observa aumento de volumen de 15 mm en relación a piezas. 3.6 y 3.7. Radiografía muestra compromiso periodontal pieza 3.7. Se realiza biopsia excisional y exodoncia pieza 3.7. Histopatología informa granuloma periférico de células gigantes. Se solicitan exámenes de laboratorio para estudio de hiperparatiroidismo (PTH elevada, calcemia fosfatemia normales). Evoluciona favorablemente. Sin signos de recidiva a los 3 meses. El diagnóstico histopatológico de lesión de células gigantes debe ser complementado con la clínica, exámenes de laboratorio e imagenología, el objetivo final es definir si tal diagnóstico corresponde a un tumor pardo, a un granuloma central de células gigantes o a un granuloma periférico de células gigantes. En la literatura los reportes de asociación entre granuloma periférico de células gigantes e hiperparatiroidismo son escasos. Este caso corresponde a granuloma periférico células gigantes, asociado a hipersecreción de paratohormona.

ABSTRACT: A 31-year-old female patient with chronic renal insufficiency in hemodialysis and secondary hypertension consulted due to an enlarging intraoral lesion in relation to the left marginal vestibular gingival, with 6 months of evolution. A 15mm mass in relation to mandibular left molars was noted. Radiograph showed periodontal involvement of mandibular left second molar. Excisional biopsy and tooth 3.7 extraction were performed. Histopathology reported a peripheral giant cell granuloma. Laboratory tests were requested for suspected hyperparathyroidism (aiding in the diagnosis) (high PTH, normal phosphatemia and calcemia). Evolution was favorable, without signs of reappearance after 3 months. The histopathological diagnosis of giant cell lesions should be complemented with clinical, laboratory and imaging tests. The final objective is to make the differential diagnosis between brown tumor, central giant cell granuloma and peripheral giant cell granuloma because the treatment varies considerably. There are few reports in the literature about the association between peripheral giant cell granuloma and hyperparathyroidism. This case corresponds to peripheral giant cell granuloma, possibly associated with parathormone hypersecretion.

Hallazgos Histopatológicos del Tejido Pericoronario de Terceros Molares Incluidos Sanos / Histopathological Findings of Pericoronary Tissue in Healthy Third Molars

RESUMEN: Este estudio se realizó para evaluar la presentación de cambios histopatológicos tempranos en sacos pericoronarios de terceros molares incluidos sanos. Sesenta y un tejidos pericoronarios de terceros molares incluidos, clínicamente asintomáticos y sin evidencia radiográfica de anomalía del saco pericoronario, se extrajeron por diferentes razones. Las muestras se fijaron y procesaron de forma rutinaria y se tiñeron con hematoxilina-eosina antes de la evaluación. Se estandarizaron los diagnósticos concluyendo que toda muestra que presente metaplasia escamosa del epitelio reducido del órgano del esmalte (EEE) se considerará cambio quístico temprano. De las muestras presentadas, el 28 % mostró metaplasia escamosa sugerente de cambio quístico temprano. Esta variación histológica del tejido pericoronario fue significativamente mayor en los pacientes menores de 20 años de edad, sexo femenino, terceros molares mandibulares, en inclusión ósea y en pacientes que no informaron sintomatología local previa (P = 0,05). Estos hallazgos sugieren que la ausencia de semiología clínica y radiográfica en terceros molares incluidos no necesariamente indica ausencia de alteraciones en el tejido pericoronario de los mismos.

ABSTRACT: This study was performed to evaluate the presentation of early histopathological changes in pericoronal healthy third molars. Sixty-one pericororonitis tissues third molars, without radiographic evidence of abnormality in pericoronary sack, extracted for various reasons. The samples were fixed and processed routinely and stained with hematoxylin-eosin before evaluation. Diagnostic standardized concluding that all this shows that squamous metaplasia of the reduced enamel organ (EEE) is considered cystic epithelium were early change. Of the samples submitted, 28 % showed squamous metaplasia early suggestive of cystic change. This histological tissue pericoronary variation was significantly higher in patients under 20 years of age, female gender, mandibular third molars, including in bone and in patients who reported no previous local symptoms (P = 0.05). These findings suggest that the absence of clinical and radiographic semiology third molars does not necessarily indicate the absence of alterations in tissue pericoronary thereof.

Aggressive type of central giant cell granuloma in a woman on hormone replacement therapy: a histopathological insight.

Quite a few lesions of the oral cavity specifically of the gingiva have a greater inclination towards women and mostly occur during the first four decades of life, the cause of which may be credited to the changing levels of sex hormones. Out of all such lesions, one lesion whose aetiology is still unclear and which originats from the periosteum or periodontal ligament is central giant cell granuloma. Repeatedly, it is has been described as a reactive lesion, the cause of which may be secondary to local irritants or trauma, specifically plaque or calculus, which is not considered to be a true neoplasm. Here we present a case of a 51-year-old female patient with aggressive gingival growth within 10-13 months of hormonal replacement therapy. The aetiology, histological features and appropriate treatment are discussed in the light of current literature.

Inflammatory myofibroblastic tumor of the oral cavity: A case report and literature review.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor of unknown etiology and pathogenesis. The lesion has been recognized to occur at various sites but rarely affects the head and neck region. A 29-year-old male presented with a 13 months' history of a slow growing, painless growth in maxillary left posterior gingiva. An excisional biopsy was performed under local anesthesia. Microscopic examination revealed a compact cellular spindle cell proliferation with collagenous stroma having storiform architecture. Immunohistochemistry revealed that the tumor cells were positive for smooth muscle actin, CD-68 and negative for anaplastic lymphoma kinase. Oral IMT should be included in the differential diagnosis of localized gingival enlargement mimicking oral hyperplastic/reactive lesions.

Establishment and genomic characterization of gingivobuccal carcinoma cell lines with smokeless tobacco associated genetic alterations and oncogenic PIK3CA mutation.

Smokeless tobacco associated Gingivobuccal squamous cell carcinoma (GB-SCC) is a major public health problem but available oral cancer cell lines are mostly from smoking associated tongue SCC raising the need for pertinent GB-SCC cell line models. As part of the International Cancer Genome Consortium (ICGC) Project, 4 novel cell lines, namely, Indian Tata Memorial Centre Oral Cancer (ITOC) -01 to -04 were established and characterized with conventional methods, karyotyping, ultrastructure, in vivo tumourigenicity, Whole exome sequencing (WES) and RNA sequencing. These hyperploid cell lines form xenografts in mice and show metabolically active and necrotic areas on fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. WES of ITOC cell lines recapitulate the genomic tumor profile of ICGC GB-SCC database. We further identified smokeless tobacco associated genetic alterations (PCLO, FAT3 and SYNE2) and oncogenic PIK3CA mutation in GB-SCC cell lines. Transcriptome profiling identified deregulation of pathways commonly altered in cancer and down-regulation of arachidonic acid metabolism pathway, implying its possible role in GB-SCC. Clinical application of high throughput sequencing data depends on relevant cell line models to validate potential targets. Extensively characterized, these oral SCC cell lines are particularly suited for mechanistic studies and pre-clinical drug development for smokeless tobacco associated oral cancer.

Prevalence of p53 dysregulations in feline oral squamous cell carcinoma and non-neoplastic oral mucosa.

Squamous cell carcinoma is the most common malignant oral tumor in cats. The late presentation is one of the factors contributing to the detrimental prognosis of this disease. The immunohistochemical expression of the p53 tumor suppressor protein has been reported in 24% to 65% of feline oral squamous cell carcinomas, but no study has systematically evaluated in this tumor the presence of p53 encoding gene (TP53) mutations. The aim of this retrospective study was to determine whether p53 immunohistochemistry accurately reflects the mutational status of the TP53 gene in feline oral squamous cell carcinoma. Additionally, the prevalence of p53 dysregulation in feline oral squamous cell carcinoma was compared with that of feline non-neoplastic oral mucosa, in order to investigate the relevance of these dysregulations in cancer development. The association between p53 dysregulations and exposure to environmental tobacco smoke and tumor characteristics was further assessed. Twenty-six incisional biopsies of oral squamous cell carcinomas and 10 cases each of lingual eosinophilic granuloma, chronic gingivostomatitis and normal oral mucosa were included in the study. Eighteen squamous cell carcinomas (69%) expressed p53 and 18 had mutations in exons 5-8 of TP53. The agreement between immunohistochemistry and mutation analysis was 77%. None of non-neoplastic oral mucosa samples had a positive immunohistochemical staining, while one case each of eosinophilic granuloma and chronic gingivostomatitis harbored TP53 mutations. Unlike previously hypothesized, p53 dysregulations were not associated with exposure to environmental tobacco smoke. These results suggest an important role of p53 in feline oral tumorigenesis. Additionally, the immunohistochemical detection of p53 expression appears to reflect the presence of TP53 mutations in the majority of cases. It remains to be determined if the screening for p53 dysregulations, alone or in association with other markers, can eventually contribute to the early detection of this devastating disease.

Diagnosis and treatment of oral focal mucinosis: a case series.

BACKGROUND: Oral focal mucinosis, the oral counterpart of cutaneous focal mucinosis, is a rare disease. As it has no characteristic clinical or radiological features, diagnosis is established by histopathological and immunohistological examination. We present three cases of oral focal mucinosis occurring in the retromolar (which is extremely rare) and gingival regions. CASE PRESENTATION: Case 1 involved a 26-year-old Japanese man with radiolucency in the right retromolar region on panoramic radiograph and computed tomography; no obvious protrusion was observed in the region. This finding was clinically diagnosed as a tumor of the retromolar region. Case 2 involved a 60-year-old Japanese woman. A tumor-like mass of tissue was identified on the buccal gingiva at the maxillary right canine and first premolar region. The lesion measured 7 × 6 mm and exhibited elastic hardness and healthy-colored mucosa. The lesion was diagnosed as an epulis. Case 3 involved a 47-year-old Japanese woman. A tumor-like mass of tissue was identified on the buccal gingiva at the maxillary right canine and first premolar region. The lesion measured 10 × 10 mm and exhibited elastic hardness and redness of the surface mucosa. This lesion was also diagnosed as an epulis. Resection was performed in all three cases, and the lesions were histopathologically diagnosed as oral focal mucinosis. Postoperative courses were uneventful and, thus far, there have been no recurrences. CONCLUSIONS: Although it is difficult to diagnose oral focal mucinosis based on clinical symptoms and imaging findings, the disease should be considered a possibility when diagnosing benign oral tumors. We believe that an emphasis on histopathologic study is essential to confirm the clinical suspicion.