Oral Mucosal Epithelium Research Articles

ORAL LYMPHOEPITHELIAL CYST IN FLOOR OF MOUTH: A CASE REPORT

Oral lymphoepithelial cyst (OLC) is a rare developmental cyst of soft tissue. Clinically, OLC exhibits as a small and asymptomatic mass, with color ranging from rose to yellowish. OLC develops manly in floor of mouth and lateral and ventral surfaces of tongue. Based on this, we aimed to report a case of OLC in a young patient. A 17-year-old male patient presented a painless nodular aspect located in floor of mouth with a history of evolution of 2 months. Clinical hypothesis was ranula. Excisional biopsy was performed, and histopathologic analysis revealed a cystic cavity lined by keratinized stratified epithelium; cystic lumen showed desquamated epithelial cells. Cystic capsule was composed of connective tissue exhibiting numerous lymphocytes, sometimes arranged in germinal centers. Superficially, epithelium of oral mucosa was observed. Based on pathologic findings, final diagnosis was OLC. After 12 months of follow-up, no sign of recurrence was observed. Oral lymphoepithelial cyst (OLC) is a rare developmental cyst of soft tissue. Clinically, OLC exhibits as a small and asymptomatic mass, with color ranging from rose to yellowish. OLC develops manly in floor of mouth and lateral and ventral surfaces of tongue. Based on this, we aimed to report a case of OLC in a young patient. A 17-year-old male patient presented a painless nodular aspect located in floor of mouth with a history of evolution of 2 months. Clinical hypothesis was ranula. Excisional biopsy was performed, and histopathologic analysis revealed a cystic cavity lined by keratinized stratified epithelium; cystic lumen showed desquamated epithelial cells. Cystic capsule was composed of connective tissue exhibiting numerous lymphocytes, sometimes arranged in germinal centers. Superficially, epithelium of oral mucosa was observed. Based on pathologic findings, final diagnosis was OLC. After 12 months of follow-up, no sign of recurrence was observed.

Human immunodeficiency virus interaction with oral and genital mucosal epithelia may lead to epithelial-mesenchymal transition and sequestration of virions in the endosomal compartments.

Oral and genital mucosal epithelia are multistratified epithelial barriers with well-developed tight and adherens junctions. These barriers serve as the first line of defense against many pathogens, including human immunodeficiency virus (HIV). HIV interaction with the surface of mucosal epithelial cells, however, may activate transforming growth factor-beta (TGF-β) and mitogen-activated protein kinase signaling pathways. When activated, these pathways may lead to the disruption of epithelial junctions and epithelial-mesenchymal transition (EMT). HIV-induced impairment of the mucosal barrier may facilitate the spread of pathogenic viral, bacterial, fungal, and other infectious agents. HIV-induced EMT promotes highly motile/migratory cells. In oral and genital mucosa, if EMT occurs within a human papillomavirus (HPV)-infected premalignant or malignant cell environment, the HPV-associated neoplastic process could be accelerated by promoting viral invasion of malignant cells. HIV also internalizes into oral and genital mucosal epithelial cells. The majority (90%) of internalized virions do not cross the epithelium, but are retained in endosomal compartments for several days. These sequestered virions are infectious. Upon interaction with activated peripheral blood mononuclear cells and CD4+ T lymphocytes, epithelial cells containing the virus can be transferred. The induction of HIV-1 release and the cell-to-cell spread of virus from epithelial cells to lymphocytes is mediated by interaction of lymphocyte receptor function-associated antigen-1 with the epithelial cell receptor intercellular adhesion molecule-1. Thus, mucosal epithelial cells may serve as a transient reservoir for HIV, which could play a critical role in viral transmission.

Abstract 3813: Activation of EGFR induces loss of primary cilia in oral mucosa carcinogenesis

Abstract Objective: Primary cilia are evolutionally conserved cell structures involving multiple cell functions by sensing extracellular signals. Loss of primary cilia is frequently observed in various cancer types, suggesting that the absence of this organelle may promote tumorigenesis. However, little is known about the role of primary cilia in oral premalignant lesions and oral squamous cell carcinoma (OSCC). Materials and Methods: Immunofluosense staining was carried out to detect the incidence of primary cilia in every stages of oral carcinogenesis from normal to OSCC. Immunohistochemical analysis was used for validating the correlation between the ciliary incidence and the expression level of EGFR in the oral carcinogenesis. Furthermore, the change of primary cilia was detected by activating and inhibiting the EGFR pathway activity in vitro. Results: A significant decrease in the percentage of ciliated cells was found on both oral leukoplakia (OLK), as well as OSCC tissues, compared to normal oral mucosa epithelium, and this loss of cilia was independent of the increased proliferative index. A parallel increase of EGFR activity was observed in OLK and OSCC tissues. In addition, EGF stimulation induced obvious primary cilia absorption, whereas inhibition of EGFR by gefitinib significantly restored cilia formation in vitro. We further found that the activation of EGFR resulted in the phosphorylation of AURKA, a pivotal kinase promoting disassembly of primary cilia. Conclusion: EGFR-AURKA pathway might be a critical regulator of ciliary loss in the carcinogenesis of oral mucosa. This may provide insight into the development of new therapeutic strategies to prevent oral premalignant lesions from becoming malignant. Citation Format: Fengg yin, Zihao Wei, Jing Li, Liang Xie, Qianming Chen. Activation of EGFR induces loss of primary cilia in oral mucosa carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3813.

Liquen plano oral. Reporte de un caso y revisión de la literatura

El liquen plano oral (LPO) es una enfermedad mucocutánea crónica, de carácter inflamatorio, etiología desconocida y naturaleza autoinmune, en la que se produce una agresión por parte de los linfocitos T dirigida frente a las células basales del epitelio de la mucosa oral. El diagnóstico del LPO debe basarse en la observación clínica y confirmarse con la descripción de las características histopatológicas. Se presenta caso clínico de paciente femenina de 39 años de edad que acudió a consulta odontológica al Servicio de Estomatología de la Escuela de Odontología, de la Facultad de Ciencias de la Salud, Universidad Católica de Córdoba, por presentar múltiples lesiones blancas en la cavidad bucal de 1 año de evolución. La paciente manifiesta episodios de stress. Se realizó biopsia de tipo incisional y se envió a anatomía patológica donde se confirmó el diagnóstico de Liquen Plano Oral.

Can wearing face masks in public affect transmission route and viral load in COVID-19?

The mandatory face mask wearing was implemented in the Czech Republic and Slovakia shortly after the COVID-19 outbreak in Central Europe. So far, the number of COVID-19-associated deaths per 100,000 individuals is far lower in these countries as compared with other neighbouring or close countries. The use of face masks in public may not protect the general public from contracting the virus, however, presumptively decreases the viral load and contributes to a favourable clinical outcome in COVID-19 disease. A certain time is required for antigen-specific T cells and B cells to fully develop. Obligatory face mask wearing in public favours the virus transmission through oral mucosa and/or conjunctival epithelium, which enables the adaptive immune responses to evolve. In the case of inhalation of high loads of SARS-CoV-2, the time for the development of fully protective adaptive immune responses seems to be insufficient. Then, a less specific and more damaging innate immune response prevails.

Histological Study on the Effect o fMethotrexate on the Oral Tissues of Aadult Male Rabbits

Aims: The objective of this study is to evaluate the effects of oral methotrexate on the oral tissues of rabbits. Materials and Methods: In the present study nine adults' male rabbits, aged 3 months were used, and divided into three main groups. Group 1: served as a control and received normal saline only. Group II: given a single dose of 0.5mg/kg per week methotrexate orally by cavage needle for 8 weeks. Group III: given 0.5mg/kg of methotrexate orally twice/weekly for 8 weeks. The animals were scarified and the floor of the mouth, check and tongue, were excised and processed for histological study. Results: The epithelium of oral mucosa in the treated groups is thinner than that of the control group with vacuolation in the cytoplasm, fewer and shorter slender papillae ,congestion of the blood vessels in the lamina propria , fatty infiltration and distortion of attachments of mucosa to underlying muscle .The minor salivary glands show loss of normal architecture ,inflammatory cellular infiltration, disarrangements of acini, and vacuolation in the acinar cells .The dorsal surface of the tongue showed an epithelial atrophy, with loss of the lingual papillae . The lamina propria showed short papillae, inflammatory cellular infiltration and congestion of blood vessels, as well as considerable distortion of arrangements in the musculature of the tongue. Conclusion: weekly administrations of methotrexate produce dramatize histological changes in the oral tissues.

Noncoding RNAs in oral premalignant disorders and oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) has the highest mortality rate among all head and neck cancers and a relatively low five-year survival rate. Generally, the development of an oral mucosal malignancy represents a multistep process beginning with normal oral mucosa epithelium and culminating in OSCC after transitioning through intermediary oral premalignant disorders (OPMDs), during which dysplasia is often observed. Noncoding RNAs (ncRNAs) are RNAs that are not translated into proteins, but still can participate in regulating neoplastic cell behavior. Recently, data have emerged on the role of ncRNAs in the progression of oral mucosal malignant diseases, but the exact mechanisms through which ncRNAs are involved remain to be elucidated. Knowledge on ncRNAs has added an extra layer of complexity to our understanding of the malignant progression of oral mucosal diseases. The identification of ncRNAs in multiple body fluids as biomarkers may provide new diagnostic options that can be used for the diagnosis and prognosis of OPMDs and OSCC, respectively. Despite overall advances that have been made in cancer treatment, the treatment options for OPMDs and OSCC are still limited. Several studies have shown that ncRNA-based treatment regimens may hold promise as alternative methods for treating OPMDs and OSCC. The use of ncRNAs as therapeutic agents, including miR-155, miR-34 and lncRNA HOTAIR, appear promising.

Oral manifestations associated with antimalarial therapy in patients with systemic lupus erythematosus

Lupus erythematosus (LE) is an autoimmune disease often treated with antimalarial drugs. The prolonged use of chloroquine and hydroxychloroquine can cause hyperpigmentation in the skin, oral mucosa and retinal pigment epithelium, which in turn can trigger toxicity in this epithelium, which in some cases causes vision loss. The objective of the present work was to establish the association between the presence of oral pigmented macules by antimalarial and secondary retinal toxicity. A total of 105 patients diagnosed with LE being treated with chloroquine/hydroxychloroquine were evaluated. All patients were ophthalmologically evaluated for retinopathy screening. When the patient showed oral hyperpigmented maculae, an incisional biopsy was performed with the corresponding histopathological study with informed consent. The variables were compared using the chi-square test for quantitative variables and the non-parametric Mann-Whitney U-test for categorical variables. The confidence level was established at 95%, and p-values of ≤0.005 were considered statistically significant. Only 9.5% of the patients showed oral brown spots. Histopathologically, 100% of the oral macules showed characteristics of oral pigmentation by drug and 100% ophthalmological parameters of normality. Two patients presented with a diagnosis of pre-retinopathy, but none showed oral lesions. Hyperpigmented macules in the buccal mucosa in lupus patients receiving antimalarial treatment are not frequent and do not represent a predictive finding of toxicity of the drug.

Optimization of an oral mucosa in vitro model based on cell line TR146

ABSTRACT During the last years, the popularity of saliva has been increasing for its applicability as a diagnostic fluid. Blood biomarker molecules have to cross the blood-saliva barrier (BSB) in order to appear in saliva. The BSB consists of all oral and salivary gland epithelial barriers. Within this context, the optimization of in vitro models for mechanistic studies about the transport of molecules across the oral mucosa is an important task. Here, we describe the optimization and comprehensive characterization of a Transwell model of the oral mucosa based on the epithelial cell line TR146. Through systematic media optimization investigating 12 different set-ups, a significant increase of barrier integrity upon airlift cultivation was achieved for TR146 cell layers. The distinct improvement of the paracellular barrier was shown by measurements of transepithelial electrical resistance (TEER) and carboxyfluorescein permeability assays. Histological characterization supported TEER data and showed a stratified, non-keratinized multilayer of the optimized TR146 model. High-Throughput qPCR using 96 selected markers for keratinization, cornification, epithelial–mesenchymal transition, aquaporins, mucins, tight junctions, receptors, and transporter proteins was applied to comprehensively characterize the systematic optimization of the cellular model and validate against human biopsy samples. Data revealed the expression of several genes in the oral mucosa epithelium for the first time and elucidated novel regulations dependent on culture conditions. Moreover, functional activity of ABC transporters ABCB1 and ABCC4 was shown indicating the applicability of the model for drug transport studies. In conclusion, a Transwell model of the oral mucosa epithelium was optimized being suitable for transport studies.

Nucleolar organizer regions in human oral verrucous carcinoma and adjacent lining epithelium

ABSTRACT The epithelium adjacent to an oral squamous cell carcinoma is at risk of undergoing precancerous changes. Even after such changes occur, however, the adjacent epithelium remains histologically similar to normal mucosa. We investigated five argyrophilic nucleolar organizer region (AgNOR)-related features in samples of oral verrucous carcinoma (VeCa) and their corresponding adjacent lining epithelium (adj. VeCa). Morphometric characteristics of AgNORs in oral adj. VeCa and oral VeCa were compared to normal mucosa epithelium, squamous cell carcinoma and oral mucosa epithelium adjacent to squamous cell carcinoma findings that we published earlier. Although adj. VeCa and normal oral mucosa were histologically similar, total AgNOR volume differentiated adj. VeCa from normal oral mucosa, but revealed no significant difference between VeCa and adj. VeCa. Total AgNOR volume/nuclear volume discriminated VeCa from adj. VeCa and normal oral mucosa. Certain AgNOR parameters provide a complementary tool for discriminating VeCa from adj. VeCa and normal oral mucosa, and also for detecting incipient malignant changes in epithelium adjacent to VeCa. Use of the AgNOR technique is cost-effective, because it can be performed on paraffin sections.

Squamous differentiation requires G2/mitosis slippage to avoid apoptosis

The cellular mechanisms controlling cell fate in self-renewal tissues remain unclear. Cell cycle failure often leads to an apoptosis anti-oncogenic response. We have inactivated Cdk1 or Polo-like-1 kinases, essential targets of the mitotic checkpoints, in the epithelia of skin and oral mucosa. Here, we show that inactivation of the mitotic kinases leading to polyploidy in vivo, produces a fully differentiated epithelium. Cells within the basal layer aberrantly differentiate and contain large or various nuclei. Freshly isolated KO cells were also differentiated and polyploid. However, sustained metaphase arrest downstream of the spindle anaphase checkpoint (SAC) due to abrogation of CDC20 (essential cofactor of anaphase-promoting complex), impaired squamous differentiation and resulted in apoptosis. Therefore, upon prolonged arrest keratinocytes need to slip beyond G2 or mitosis in order to initiate differentiation. The results altogether demonstrate that mitotic checkpoints drive squamous cell fate towards differentiation or apoptosis in response to genetic damage.

IL-2 regulates oral mucosa inflammation through inducing endoplasmic reticulum stress and activating the NF-ĸB pathway

Objective: The molecular mechanism underlying oral mucosa inflammation remains unknown.Aim: The aim of our study is to explore the influence of interleukin-2 (IL-2) in regulating oral mucosa viability and inflammation response.Methods: Oral mucosa epithelium was treated with IL-2. Cell viability and death were determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefo (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Inflammation response was measured via enzyme-linked immunosorbent assay (ELISA), and quantitative polymerase chain reaction (qPCR). Western blot and immunofluorescence were used to verify the alterations of nuclear factor-κB (NF-κB) pathway.Results: IL-2 treatment induced a loss of cell viability in oral mucosa. Besides, inflammatory factors transcription and expression were significantly elevated in response to IL-2 treatment. In addition, oxidative stress and cell apoptosis were also augmented by IL-2 treatment. Mechanistically, IL-2 treatment was associated with an activation of the NF-ĸB pathway. Inhibition of NF-ĸB pathway could abolish the promotive effects exerted by IL-2 on oral mucosa death and inflammation response.Conclusion: Taken together, our results demonstrated that IL-2 treatment activated NF-ĸB pathway and then promoted oral mucosa inflammation, leading to intracellular oxidative stress and cell apoptosis.

The reduced susceptibility of mouse keratinocytes to retinoic acid may be involved in the keratinization of oral and esophageal mucosal epithelium.

Keratinocytes take up serum-derived retinol (vitamin A) and metabolize it to all-trans-retinoic acid (atRA), which binds to the nuclear retinoic acid receptor (RAR). We previously reported that serum-affected keratinocyte differentiation and function; namely, it inhibited keratinization, decreased loricrin (LOR) and claudin (CLDN) 1 expression, increased keratin (K) 4 and CLDN4 levels, and reduced paracellular permeability in three-dimensional (3D) cultures of mouse keratinocytes (COCA). Contrarily, RAR inhibition reversed these changes. Here, we aimed to examine whether atRA exerted the same effects as serum, and whether it was involved in the differential oral mucosa keratinization among animal species. Porcine oral mucosal keratinocytes, which form non-keratinized epithelium in vivo, established keratinized epithelium in 3D cultures. Both mouse and porcine sera induced non-keratinized epithelium at 0.1% in COCA 3D cultures. Although atRA caused the same changes as serum, its effective concentration differed. atRA inhibited keratinization at 0.1nM and 1nM in porcine or human keratinocytes and COCA, respectively. Furthermore, atRA upregulated CLDN7 in the cytoplasm but not in cell-cell contacts. These atRA-induced changes were reverted by RAR inhibition. The results indicate that serum-induced changes are probably due to the effect of serum-derived atRA, and that mouse keratinocytes require higher atRA concentrations to suppress keratinization than porcine and human keratinocytes. We propose that the lower susceptibility of mouse keratinocytes to atRA, rather than a lower retinol concentration, is a possible reason for the keratinization of mouse oral mucosal epithelium.

Site-Specific Expression Pattern of PIWI-Interacting RNA in Skin and Oral Mucosal Wound Healing

The oral mucosa exhibits exceptional healing capability when compared to skin. Recent studies suggest that intrinsic differences in coding genes and regulatory small non-coding RNA (sncRNA) genes (e.g., microRNAs) may underlie the exceptional healing that occurs in the oral mucosa. Here, we investigate the role of a novel class of sncRNA—Piwi-interacting RNA (piRNA)—in the tissue-specific differential response to injury. An abundance of piRNAs was detected in both skin and oral mucosal epithelium during wound healing. The expression of PIWI genes (the obligate binding partners of piRNAs) was also detected in skin and oral wound healing. This data suggested that PIWI-piRNA machinery may serve an unknown function in the highly orchestrated wound healing process. Furthermore, unique tissue-specific piRNA profiles were obtained in the skin and oral mucosal epithelium, and substantially more changes in piRNA expression were observed during skin wound healing than oral mucosal wound healing. Thus, we present the first clue suggesting a role of piRNA in wound healing, and provide the first site-specific piRNA profile of skin and oral mucosal wound healing. These results serve as a foundation for the future investigation of the functional contribution(s) of piRNA in wound repair and tissue regeneration.

The Current Understanding on Langerhans' Cells and Its Role in Oral Lesions.

Objective:Description of Langerhans' cells (LCs) as an important antigen-presenting cells responsible for detecting the antigens, recruiting T-cells, and thereby initiating the immune response. An adequate response of the mucosal immune system is essential to protect the mucosa against pathological conditions. Hence, a detailed review was planned about this unique antigen-presenting cell.Methods:A literature search of the electronic databases included the MEDLINE, EBSCOHOST, PUBMED, and hand searches of references retrieved were undertaken using the following MeSH terms “Langerhans cells,” “LCs in Oral Lichen Planus,” “Langerhans cell histiocytosis,” “LCs and HIV,” “LCs in Periodontitis.”Results:LCs are present suprabasally in the epithelium of oral mucosa and in the epidermis of the skin. The role played by LCs though not fully elucidated, but several research studies indicate that these cells are involved in the pathogenesis of many oral diseases. In this article, the historical perspective, structure, function, origin, and phenotypic expressions of LCs are discussed in detail. The current understanding on the role of LCs in various oral lesions and its immunological characteristics are discussed.Conclusion:LCs act as immune mediator cells, tumor cells, vectors of infected cells, and phagocytic cells. Further studies could bolster the knowledge about the role of Langerhans cells in the immune response of various oral diseases and thereby provide diagnostic tools and help for prognostic evaluation. This review illuminates the pivotal role of Langerhans cells and its immune surveillance as a “Sentinels” of the oral mucosa.

Expression of Survivin in Oral Potentially Malignant Disorders: An Immunohistochemical Study.

ABSTRACTAim:The aim of this study was to compare the immunohistochemical expression of survivin in oral potentially malignant disorders (OPMDs) and evaluate its prognostic significance among oral leukoplakia (OL), oral submucous fibrosis (OSMF), and oral lichen planus (OLP).Materials and Methods:The study material consisted of 60 formalin-fixed paraffin-embedded tissue samples: 15 cases each of OL, OSMF, OLP, and normal oral mucosal epithelium as control. Survivin expression was analyzed immunohistochemically, and data analysis was accomplished using Statistical Package for Social Sciences, version 22.0 (SPSS Inc., Chicago, IL). Fisher’s chi-square test was opted to compare the study groups.Results:Survivin was expressed in all the OPMDs including OL, OSMF, and OLP, but was absent in normal oral tissue samples. Higher immunoreactivity and survivin staining was observed in OLP compared to OL and OSMF whereas OL showed a significant difference in the distribution of survivin immunoexpression against OLP. An increased nuclear expression of survivin along with distribution in the basal and parabasal layers was evident in all OPMDs.Conclusion:Survivin was expressed more in OLP in comparison to OSMF and OLP, indicating unfavorable prognosis. OL showed increased expression in comparison to OSMF, showing unfavorable prognosis. On the basis of this study, it was concluded that survivin may be used as an important diagnostic and prognostic marker for OPMDs.

STATE CHARACTERISTICS OF THE PROBLEM OF ORAL CAVITY ENVIRONMENTAL SYSTEM

The aim: Analysis of literary sources with the study of modern views on the problem of the immune status of the oral mucosa. Materials and methods: The review and analysis of scientific and medical literature for the years 2013-2019, based on Scopus databases, Web of Science, Med Line, The Cochrane Library, EMBASE, Global Health, CyberLeninka, RIC. Conclusions: Bacterial wall antigens are able to affect the local immune response of the oral mucosa. In particular, suppression of lymphocytes and macrophages proliferation, alteration of adhesion molecules expression and homing of the immune system cells to the inflammation site, inhibition of cytokine secretion by contact of the immune system cells with gram-positive bacteria is revealed. Therefore, studying the changes in the differentiation of the oral mucosa epithelium and periodontal tissues under the influence of environmental factors is of relevance. The conception of the oral cavity as a complex ecological system has not only theoretical but also practical value. Summarizing the data, we can say that at the current stage of science development the interaction of all structures should be considered, focusing on epitheliocytes of the oral mucosa, as a closing chain, which initiates changes that can affect the condition of the oral cavity and the results of pathological processes treatment of the oral cavity mucous membrane and periodontal tissues.

Simple oral mucosal epithelial transplantation in a rabbit model

This study investigated a rabbit model of autologous simple oral mucosal epithelium transplantation (SOMET) for limbal stem cell deficiency (LSCD). LSCD was created in the SOMET group and the Control group. In the SOMET group, oral mucosa harvested from the buccal region was treated with dispase, cut into small pieces, and placed on the exposed corneal stroma without using graft sutures, amniotic membrane, and/or glue. A soft contact lens was positioned and tarsorrhaphy was performed in both groups. Postoperative corneal neovascularization and fluorescein staining scores were evaluated by slit lamp microscopy in both groups. At 2 weeks postoperatively, eyes were excised and subjected to immunohistochemical staining for CK3, CK13, CK15, and p63. In the SOMET group, transplantation of oral mucosa led to complete recovery of LSCD, as indicated by low neovascularization scores, low fluorescein staining scores, and detection of stratified K3/K13-positive cells on the stroma at 2 weeks after surgery. In contrast, corneal epithelial defects persisted in the Control group at 2 weeks. SOMET achieved re-epithelialization of the corneal surface in this rabbit LSCD model. It is a simple technique that does not require culture and could be a promising option for ocular surface reconstruction in bilateral LSCD.

Hyperplasia of Wistar rat tongue mucosa due to exposure to cigarette side-stream smoke

Background: Hyperplasia, a condition whereby an excessive number of cells are produced due to their uncontrolled division, represents a common symptom of carcinogenesis. Cancer is a physical manifestation of cell malignancy resulting from abnormal proliferation. Globally, oral cancer currently constitutes the sixth largest lethal form of the condition. The most common etiology of oral cancer is tobacco of which cigarettes are the most popular related product. The health risks associated with cigarette smoke not only affect active smokers but also individuals who ingest it passively. Sidestream smoke comes from the lighted end of a burning tobacco product such as a cigarette, pipe or cigar and contains nicotine and many harmful cancer-causing chemicals. Inhaling sidestream smoke increases the risk of lung and other types of cancer. Purpose: The purpose of this study was to understand how sidestream cigarette smoke initiates precancerous changes, in this case hyperplasia, in the oral mucosa epithelium of Wistar rats. Methods: The subjects were divided into three groups, a 4-week treatment group (P1), an 8-week treatment group (P2), and a control group (K), each consisting of ten subjects. The subjects were exposed to a daily two-cigarette dose of smoke. The experiment used a post-test only control group design. All samples were sacrificed during the fourth and eighth weeks. Haematoxylin-eosin staining was performed on the tongues of the Wistar rats to establish the presence of hyperplasia. Data was analyzed using a one-way ANOVA test. Results: After the Wistar rats had been exposed to cigarette smoke, an increased degree of epithelial cell proliferation (hyperplasia) showed a significant difference with a p-value <0.05 during the eighth week. Conclusion: Exposure to cigarette sidestream smoke induces increased epithelial cell proliferation (hyperplasia) in Wistar rats.

Preclinical study for treatment of hypospadias by advanced therapy medicinal products.

This paper explores the feasibility of a new therapy for the treatment of hypospadias patients. Hypospadias is a very common congenital malformation of male genitals, with very high rate of recurrences after surgery. The field of regenerative medicine, which offers innovative solutions for many pathologies, still does not offer reliable solution for this pathology. Here, we propose quality, safety, and clinical feasibility assessment for an oral mucosa advanced therapy medicinal product (ATMP) grown on a biocompatible scaffold for a clinical study on urethral reconstruction of hypospadias patients. Urethral and oral mucosal epithelia from donor biopsies were cultivated between two fibrin layers, under clinical-grade conditions for cell and tissue characterization and comparison, aimed at tissue engineering. In addition, single-clone analyses were performed to analyze gene expression profiles of the two epithelia by microarray technology. Oral mucosa appeared suitable for urethral reconstruction. The resulting ATMP was proven to maintain stem cells and regenerative potency. The preclinical safety studies were performed on human tissues to assess abnormalities and tumorigenicity, and confirmed the safety of the ATMP. Finally, the patient selection and the clinical protocol for the upcoming clinical trial were defined. Against this backdrop, in this paper, we are proposing a new reproducible and reliable ATMP for the treatment of hypospadias.