Rare presentation of mandibular intraosseous cell Lipoma

Lipomas may be located in all parts of the body and may be confused clinically with other soft tissue masses. They infrequently occur in the head and neck. Surgical excision of a lipoma is often used as the definitive treatment modality, and alternative treatments described for lipomas range from liposuction to steroid injections. In the present study, a 38-year-old woman who was initially referred by her dentist due to a myofascial pain is described. An incidental finding (8*5mm mass) was successfully removed and diagnosed as intraosseous cell lipoma. The surgery produced excellent painless results and no functional or neural impairment. Clinically and radiographically, the tumor demonstrated inferior alveolar canal involvement. Such unique tumor characteristics never been previously reported, invalidating prior theories suggested for the etiological factors of this rare tumor. The current case report suggests a clear etiology for this tumor as a true primary benign neoplasm. Keywords: Lipoma, Adipose tissue, Mass, Mandibl

Clinical and Prognostic Significance of the Eighth Edition Oral Cancer Staging System

Objectives: The most notable changes in the eighth edition of the AJCC Cancer Staging System include incorporating the depth of invasion (DOI) into T staging and extranodal extension (ENE) into N staging. In this study, we retrospectively assessed the prognostic and clinical implications of the eighth TNM staging system. Materials and Methods: Patients with Oral Squamous Cell Carcinoma (OSCC) who were treated surgically between 2010 and 2017 were retrospectively reviewed. Tumors were first staged according to the seventh edition and restaged using the eighth edition. The prognostic value of the resultant upstaging was evaluated. Results: Integrating the DOI into the T classification resulted in the upstaging of 65 patients, whereas incorporating ENE into the N staging resulted in the upstaging of 18 patients (p p > 0.05). Conclusion: Our results demonstrate the importance of incorporating ENE into nodal staging and considering adjuvant therapy when ENE is present

Dopaminergic-Like Neurons Derived from Oral Mucosa Stem Cells by Developmental Cues Improve Symptoms in the Hemi-Parkinsonian Rat Model

<div><p>Achieving safe and readily accessible sources for cell replacement therapy in Parkinson’s disease (PD) is still a challenging unresolved issue. Recently, a primitive neural crest stem cell population (hOMSC) was isolated from the adult human oral mucosa and characterized <i>in vitro</i> and <i>in vivo</i>. In this study we assessed hOMSC ability to differentiate into dopamine-secreting cells with a neuronal-dopaminergic phenotype <i>in vitro</i> in response to dopaminergic developmental cues and tested their therapeutic potential in the hemi-Parkinsonian rat model. We found that hOMSC express constitutively a repertoire of neuronal and dopaminergic markers and pivotal transcription factors. Soluble developmental factors induced a reproducible neuronal-like morphology in the majority of hOMSC, downregulated stem cells markers, upregulated the expression of the neuronal and dopaminergic markers that resulted in dopamine release capabilities. Transplantation of these dopaminergic-induced hOMSC into the striatum of hemi-Parkinsonian rats improved their behavioral deficits as determined by amphetamine-induced rotational behavior, motor asymmetry and motor coordination tests. Human TH expressing cells and increased levels of dopamine in the transplanted hemispheres were observed 10 weeks after transplantation. These results demonstrate for the first time that soluble factors involved in the development of DA neurons, induced a DA phenotype in hOMSC <i>in vitro</i> that significantly improved the motor function of hemiparkinsonian rats. Based on their neural-related origin, their niche accessibility by minimal-invasive procedures and their propensity for DA differentiation, hOMSC emerge as an attractive tool for autologous cell replacement therapy in PD.</p></div

Naive hOMSC express constitutively neuronal and dopaminergic markers.

<p>Immunofluorescence of neuronal (A–C) and dopaminergic (D–F) markers in naïve hOMSC, scale bars 100 µM.</p

hOMSC developed neuronal-like morphology and gene expression after DA differentiation protocol.

<p>Bright field microscopy of hOMSC cultured in serum free medium for 17 days and of hOMSC-DA (A–B), scale bar 200 µM. Real time PCR analysis of differentiated hOMSC-DA from four different donors (C), showing a reduction in the expression of Nanog, Oct4 and Sox2 and a concomitant increased expression of the neuronal markers β-III tubulin and NCAM1 compared to the naïve hOMSC which served as baseline (relative value = 1). Differentiated hOMSC also showed increased expression of genes related to dopaminergic differentiation and mature dopaminergic neurons. Data is expressed as Mean ± SEM. Significance levels: *p<0.05, **p<0.01, ***p<0.001.</p

Induced hOMSC show a mature dopaminergic-like phenotype <i>in vitro</i>.

<p>Immunofluorescence analysis and cell positive counts of neuronal and DA markers in naïve, DA-hOMSC and fibroblasts before and after differentiation, scale bar = 50 µM (A). Complete evaluation of naïve, differentiated hOMSC and fibroblasts marker expression can be seen in supplemental <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100445#pone.0100445.s002" target="_blank">figure S2</a>. Evaluation of Pitx3 and Tyrosine hydroxylase (TH) expression levels by western blot and band densitography, showing increased protein expression after differentiation (B). Medium dopamine content evaluation in naïve or hOMSC-DA in presence or absence of the non-specific membrane depolarizer agent KCl, showing increased levels of dopamine after membrane depolarization of differentiated hOMSC (C). Data is presented as Mean±SEM. Significance levels: *p<0.05, **p<0.01, ***p<0.001.</p

Increased expression and nuclear translocation of dopaminergic transcription factors was observed in hOMSC-DA.

<p> Immunofluorescent detection of Pitx3, Lmx1A and Nurr1 evaluated in naïve and differentiated hOMSC, midbrain primary culture, hOMSC-derived osteoblast-like cells and mouse embryonic fibroblasts (A). Arrows point to the nuclear localization of these transcription factors in the hOMSC-differentiated and midbrain DA cells. Scale bar = 50 µM. Quantification of cells expressing the evaluated transcription factors in the whole cell (nuclei+cytoplasm) or only in the nuclei before and after DA-differentiation (B).</p

Transplanted cells engrafted the injured hemisphere and increased dopamine levels.

<p>Ten weeks post-transplantation TH immunostaining (A) show decreased levels of TH in injured striatum and <i>substantia nigra</i> compared to healthy ones. TH striatal expression, analyzed by TH-DAB immunochemistry was detected in hOMSC-DA transplanted hemispheres, while saline or naïve hOMSC transplanted hemispheres showed significant reduced levels (black arrows indicate TH expressing cells). Injured hemispheres transplantated with hOMSC contain PKH26 (red) labeled cells. In hOMSC-DA transplanted hemispheres analyzed by immunofluorescence, TH expression (green) and PKH26 were found in the same cell clusters. Scale bar = 50 µm. (B) Whole hemisphere dopamine and serotonin HPLC quantification from healthy, and 6-OHDA rats treated with saline, naive and hOMSC-DA. Data is presented as Mean±SEM. Significance levels: *p<0.05, **p<0.01, ***p<0.001.</p

Induced hOMSC-DA show sustained therapeutic effect in a PD rat model after transplantation.

<p>Amphetamine-induced rotations (A), rotorod (B) and cylinder (C) test evaluation of 6-OHDA affected rats, following intra-striatal transplantation of saline, naive and hOMSC-DA. Data is presented as Mean±SEM. Significance levels: *p<0.05, **p<0.01, ***p<0.001.</p