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INTRODUCTION: Revised guidelines for Tobacco-Free Educational Institutes (ToEFI) were laid down in 2019 and they provide for tobacco free environment leading to a healthy life, implementation of legal provisions, and recognition about various approaches available for tobacco cessation. OBJECTIVE: To assess Madhyamik Vidyalays (MVs) for their compliance to the guidelines for ToFEI at the baseline using self-evaluation score card as part of operational research. MATERIAL AND METHOD: A cross sectional study was carried out during March 2021 among 19 MVs of Pimpri-Chinchwad block in Pune District, Maharashtra using census sampling. Trained data collectors scored for all 9 ToFEI criteria including the mandatory one's and their weightage points were calculated. RESULTS AND DISCUSSION: Eight {42%(0.21-0.64)} MVs had displays on tobacco-free area and awareness on the harms of tobacco displayed inside the premises and another three (16%(0.04-0.37)} had only the display of ToFEI signage at their boundary wall. No MV met with 4 or more criteria out of the total 9 criteria. The highest weightage of 29-30 out of 100 was achieved by only 2 {11%(0.01-0.30)} MVs and 5 {26%(0.10-0.49)} MVs achieved 0 points. No significance was given to tobacco free school probably because of untrained teachers and unawareness of the guidelines. CONCLUSION: This study demonstrates that minimal importance has been given to the revised ToEFI guidelines in making MVs tobacco-free. Hence, none of the them could attain the tobacco-free status.
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Fidelidade a Diretrizes , Humanos , Estudos Transversais , Índia , Política Antifumo/legislação & jurisprudência , Instituições AcadêmicasRESUMO
Odontogenic keratocysts (OKCs) are locally aggressive cysts that exhibit typical histopathological features and have a propensity for recurrence. Though histological variations are observed in OKCs, hard tissue formation and metaplastic changes are rare, and the underlying pathogenesis is not well understood. This study aimed to characterize stromal calcifications and analyze their association with odontogenic components in non-syndromic and syndrome-associated cases of OKCs. We analyzed 153 cases of OKCs from healthcare institutes in India and Japan. The epithelial and stromal features were evaluated, and the relationship of calcifications with odontogenic rests was determined. Immunohistochemistry for cytokeratin-19 and special stains including Masson Trichrome and Van Gieson, were used for identification of odontogenic rests and calcifications respectively. Stromal calcifications were observed in 29.41% OKCs. The calcification patterns included irregular dystrophic, dentinoid with linear or calcospherite-type mineralization, and psammoma calcifications. Psammoma and dentinoid calcifications were found in the proximity of cytokeratin-19-positive odontogenic rests or satellite cysts, whereas majority cases with dystrophic calcifications did not exhibit co-localization with stromal odontogenic components. Distinct patterns of calcifications were observed in OKCs. Calcifications found in proximity of the odontogenic rests were possibly indicative of an inductive or host-mediated response.
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Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but significant adverse event primarily associated with the intake of antiresorptive and antiangiogenic medications. Although antiresorptive and antiangiogenic the-rapies improve life expectancy, particularly in cancer patients, MRONJ may hamper the patient's quality of life due to pain, discomfort, anxiety, depression, speech impairment, difficulty in swallowing and eating, frequent medical and dental evaluations and treatments, and the possibility of treatment discontinuation. Leukocyte and Platelet-rich Fibrin (L-PRF) is an autologous platelet aggregate that promotes wound healing by stimulating re-epithelialization, angiogenesis, and extracellular matrix production. Aim: The present systematic review aimed to compare the results in the published literature on whether L-PRF is an effective and predictable adjuvant to surgical debridement of necrotic bone for improving the healing efficacy in patients with MRONJ. Materials and Methods: The PubMed, Scopus, Cochrane, Science Direct, LILACS, and Web of Science databases were searched using the predetermined MeSH terms and eligibility criteria, and the search yielded a total of five articles. Two studies were retrospective, and three studies were case series. Results: Seventeen participants received a combination of surgical debridement, L-PRF membrane, and antibiotics. Complete wound healing was observed in 70% of the participants, and most of them healed without any complications. Conclusions: L-PRF as an adjuvant to surgical debridement of necrosed bone appears to have a positive association with the healing outcome in patients with MRONJ.
Introducción: La osteonecrosis mandibular relacionada con medicamentos (ONMRM) es un evento adverso raro pero significativo asociado principalmente con la ingesta de medicamentos antirresortivos y antiangiogénicos. Aunque las terapias antirresortivas y antiangiogénicas mejoran la esperanza de vida, particularmente en pacientes con cáncer, la ONMRM puede obstaculizar la calidad de vida del paciente debido a dolor, incomodidad, ansiedad, depresión, discapacidad del habla, dificultad para tragar y comer, evaluaciones y tratamientos médicos y dentales frecuentes, y la posibilidad de interrupción del tratamiento. La fibrina rica en plaquetas y leucocitos (L-PRF) es un agregado de plaquetas autólogo que promueve la curación de heridas al estimular la reepitelización, la angiogénesis y la producción de la matriz extracelular. Objetivo: La presente revisión sistemática tuvo como objetivo comparar los resultados en la literatura publicada sobre si L-PRF es un adyuvante efectivo y predecible al desbridamiento quirúrgico del hueso necrótico para mejorar la eficacia curativa en pacientes con ONMRM. Materiales y Métodos: Las bases de datos de PubMed, Scopus, Cochrane, ScienceDirect, LILACS y Web of Science se registraron utilizando los términos DeCS/MeSH predeterminados y los criterios de elegibilidad, y la búsqueda arrojó un total de cinco artículos. Dos estudios fueron retrospectivos, y tres estudios fueron series de casos. Resultado: Diecisiete participantes recibieron una combinación de desbridamiento quirúrgico, membrana L-PRF y antibióticos. Se observó curación completa de heridas en el 70% de los participantes, y la mayoría de ellos se curaron sin ninguna complicación. Conclusión: L-PRF como adyuvante para el desbridamiento quirúrgico del hueso necrótico parece tener una asociación positiva con el resultado de curación en pacientes con ONMRM.
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Humanos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Baicalin is a flavonoid obtained from the Chinese herb Scutellaria baicalensis, which has a wide varieties of health benefits and scope to be studied for its therapeutic potential in oral fibrosis. AIM: The aim of the study was to investigate the antifibrotic effect of a Baicalin in arecoline induced human oral fibroblast in vitro setting. MATERIAL AND METHODS: Arecoline and ethanolic extracts of Baicalin were commercially purchased from Sigma-Aldrich. Human oral fibroblasts were cultured and characterized with specific fibroblast markers, and cells were stimulated with arecoline. An MTT assay (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) was executed to determine the half-maximal inhibitory concentration of arecoline and Baicalin. Arecoline-induced cells (25µg/ml) were treated with a non-toxic dose of Baicalin (proliferative dose of 25µg/ml). Cytokine (CCL2, CXCL-8, IL17, IL-beta, and IL-6) and fibrotic marker genes were studied by reverse transcription-polymerase chain reaction (RT-PCR). The inhibitory effect of Baicalin was studied to prove its antifibrotic properties. RESULTS: Arecoline significantly upregulated all inflammatory and fibrotic markers. On treatment with 25µg/ml of Baicalin, all inflammatory and fibrotic markers were inhibited. Arecoline affects fibroblast morphology, supporting the fact that arecoline is cytotoxic to cells. CONCLUSION: Baicalin can be used as an antifibrotic herb to treat OSMF.
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Arecolina , Fibroblastos , Flavonoides , Flavonoides/farmacologia , Humanos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Arecolina/farmacologia , Células Cultivadas , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Fibrose/tratamento farmacológico , Técnicas In Vitro , Scutellaria baicalensis/química , Antifibróticos/farmacologiaRESUMO
OBJECTIVES: Interplay of Factor XIIIa (FXIIIa), a transglutaminase, responsible for cross-linking of matrix proteins, Matrix Metalloproteinase-9 (MMP-9), a gelatinase, and Vascular Endothelial Growth Factor (VEGF), an angiogenic inducer, were studied in relation to fibrogenesis and disease progression in oral submucous fibrosis (OSMF). MATERIAL AND METHODS: Immunohistochemical expression of markers was studied in 60 formalin-fixed paraffin-embedded tissue blocks of OSMF and 20 normal oral mucosal tissues. FXIIIa was studied quantitatively while MMP-9 and VEGF were assessed semi-quantitatively. Expression was compared with histopathological grades of OSMF. RESULTS: FXIIIa expression significantly increased in OSMF (p-value 0.000). However, expression decreased and cells became quiescent with increasing grades (p-value 0.000). MMP-9 (p-value epithelium 0.011, p-value connective tissue 0.000) and VEGF expression (p-value epithelium 0.000, connective tissue 0.000) increased in OSMF. A negative correlation between FXIIIa and MMP-9 (-0.653) in early grade (p-value of 0.021) and a positive correlation between FXIIIa and VEGF (0.595) (p-value of 0.032) was found in the moderate grade OSMF. Regression analysis showed a significant association (p<0.01) of FXIIIa in OSMF and with increasing grades of OSMF. CONCLUSION: FXIIIa may play a crucial role in initiation of fibrosis in OSMF. MMP-9 may have a diverse role to play in OSMF as a regulator of fibrosis. VEGF may show an angio-fibrotic switch and contribute to fibrosis in OSMF. These cytokines may show altered function and can contribute to fibrosis and chronicity of disease due to changes in the microenvironment. Tissue stiffness in OSMF itself creates an environment that enhances the chronicity of the disease.
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Metaloproteinase 9 da Matriz , Fibrose Oral Submucosa , Humanos , Angiogênese , Fibrose , Fator A de Crescimento do Endotélio Vascular , Fator XIIIaRESUMO
Stem cells obtained from the body tissue, such as adipose tissue, dental pulp and gingival tissue. Fresh tissue is often used to isolate and culture for regenerative medicine. However, availability of tissue as and when required is one of the measure issue in regenerative medicine. Cryopreservation of tissue provides benefit over tissue availability, storage for significant amount of period and helps preserve the original cell structures. The effects of cryopreservation of gingival tissue for mesenchymal stem cell (MSC) are not well documented; however this process is of increasing importance for regenerative therapies. This study examined the effect of cryopreservation on the long term survival the whole gingival biopsy tissue. We studied cell outgrowth, cell morphology, MSC surface-markers and differentiation of mesenchymal stem cells derived from cryopreserved gingiva. In this study, gingival tissue was cryopreserved for 3, 6, 9 months. Cryopreserved tissue has been thawed and cells were isolated by using explant culture method. The fresh and cryopreserved gingival tissue cells were cultured and characterized for surface marker analysis, CFU-f, population doubling time, and osteogenic, chondrogenic and adipogenic differentiation. The fresh and cryopreserved tissue has similar stem cell properties. Results indicate that cryopreservation of the entire gingival tissue does not affect the properties of stem cells. This opens door for gingival tissue banking for future use in periodontology and regenerative medicine.
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The mesenchymal Stem Cells (MSCs) is one of the leading contender in therapeutic management of cytokine storm implicated in the COVID-19 and other inflammatory conditions. This study was aimed to investigate the effect of Interferon gamma (IFN-γ) and Ascorbic Acid (AA) preconditioning on the secretome of the human Umbilical Cord Derived MSCs (UCMSCs) and their potential to ameliorate the lipopolysaccharide (LPS) induced cytokine storm in the human peripheral blood mononuclear cells (PBMCs). UCMSCs were preconditioned with IFN-γ, AA and secretome (UCMSCs-S, IFNγ-UCMSCs-S and AA-UCSMCs-S) was analysed for the levels of growth factors and cytokines by flow cytometry. The potential of secretome to ameliorate cytokine storm and augment angiogenesis was assessed in the LPS induced PBMCs and yolk sac membrane (YSM) assay respectively. The mRNA transcript and protein levels of IL-6, IL-1ß and TNF-α was analysed by RT-PCR and flow cytometry respectively. IFNγ-UCMSCs-S and AA-UCSMCs-S ameliorated the LPS induced cytokine storm as revealed by the decreased mRNA and protein expression of IL-6, IL-1ß and TNF-α as compared to the UCMSCs-S. IFNγ-UCMSCs-S and AA-UCSMCs-S augmented angiogenesis in YSM assay. Furthermore, IFNγ and AA preconditioning of UCMSCs exhibited distinct growth factors and cytokine profile in the secretome. Our results unequivocally show that IFNγ and AA preconditioning of MSCs could give better therapeutic outcomes in the cell mediated therapies for COVID-19 and other inflammatory conditions.
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COVID-19 , Células-Tronco Mesenquimais , Humanos , Lipopolissacarídeos/farmacologia , Interferon gama/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Síndrome da Liberação de Citocina/metabolismo , COVID-19/terapia , COVID-19/metabolismo , Fatores Imunológicos/farmacologia , Células-Tronco Mesenquimais/metabolismo , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: The immune interaction between host immunity and the tumor microenvironment is complex, and a thorough understanding of tumor-infiltrating lymphocyte selection in oral cancer, including T and B cells, is urgently required. Within the tumor microenvironment, tumor cells escape immune surveillance and grow uncontrollably. The study examined the relationship and distribution of tumor-infiltrating T and B lymphocytes. STUDY DESIGN: Retrospective data of paraffin-embedded tissue samples of 47 primary oral squamous cell carcinoma (OSCC) cases were retrieved. Hematoxylin and eosin evaluation, along with all clinicopathologic data, were collected. Immunohistochemical CD3 and CD20 markers were used and evaluated for association and distribution in given OSCC cases. RESULTS: The intermediate type of inflammatory infiltrate was seen primarily in Well DIfferentiated Squamous cell Carcinoma grade and positive and negative lymph nodes. Compared with T-cell density, B-cell density showed an aggregate pattern rather than a scattered pattern, indicating a statistically significant association between T-cell and B-cell infiltrate. B-cell infiltrates were also found to have a statistically significant relationship with tertiary lymphoid structure. CONCLUSIONS: A strong, positive association and correlation exists between B- and T-lymphocyte infiltration in both the stroma and the invasive front. When compared with T-cell density, B-cell density is more predominantly in aggregates.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/patologia , Estudos Retrospectivos , Linfócitos B/patologia , Prognóstico , Microambiente TumoralRESUMO
BACKGROUND: Due to many uses of cell culture in cell biology, biotechnology, and medical research, this technique has evolved into a widely used and accepted methodology. The isolation of primary cells from primary cancer tissue is a crucial step in cell culture technology since it offers a trustworthy source for studying the biology, morphology, and molecular evaluation of cancer cells, just like in the oral cavity tissue of patients. Therefore, the technique used for the isolation, culture, and evaluation of these cells is crucial. AIM: The aim of the present study is to isolate and culture the cells from human primary Oral Squamous Cell Carcinoma [OSCC] tissue and evaluate them for morphological variations using an explant method. MATERIALS AND METHODS: The patients with OSCC who were undergoing surgery provided the tissue samples. An explant technique was used to achieve the isolation of cells from tissue samples. Following that, the cells were maintained, subcultured, and stored in accordance with the standard American Type Culture Collection [ATCC] protocol. Routine Hematoxylin & Eosin and crystal violet stains were used. These cells were morphologically studied, and the results were assessed for further studies. RESULTS: We were able to successfully isolate and culture cells from 4 different tissue samples using the explant method. Morphological analysis revealed that one tissue had a significantly distinct presentation of epithelial and stromal cells, whereas the other three tissues had only minor morphological differences predominantly stromal cells. Two tissues were discarded after showing contamination. CONCLUSION: Tissue culture should be done very meticulously specially when oral cavity tissue is used as it is house for millions of microorganisms. The technique must also be thoroughly followed and adjusted accordingly. Using common, inexpensive stains like Hematoxylin and Eosin and crystal violet, which are of great help for examining the morphology of cells routinely.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/patologia , Hematoxilina , Amarelo de Eosina-(YS) , Violeta Genciana , Corantes , Linhagem CelularRESUMO
OBJECTIVE: Fine needle aspiration cytology (FNAC) is a valuable, noninvasive technique for head and neck pathology diagnosis. The objective of case images was to highlight the utility of FNAC for diagnosing suspected cases of ameloblastoma. METHOD: FNAC smears of suspected cases of ameloblastoma were evaluated using their cellular and stromal features. RESULTS: Cellular features and background of smears exhibited characteristics of ameloblastoma. Predominant features included clusters of ameloblast-like cells and spindle cells in a myxoid background. CONCLUSION: Careful evaluation of FNAC helps diagnose ameloblastomas and must be considered a vital diagnostic tool.
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Ameloblastoma , Humanos , Biópsia por Agulha Fina/métodos , Ameloblastoma/diagnóstico , Ameloblastoma/patologia , CitodiagnósticoRESUMO
BACKGROUND: The human gingiva-derived mesenchymal stem cells (hGMSCs) possess a great potential to develop the cell-based therapy for diabetes due to its unscarred healing capacity and reparative potential. In this current study, we isolated, cultured and characterised the GMSCs and explored their potential to differentiate into Insulin Producing Cell Clusters (IPCCs). METHODS: The cells derived from gingival tissues exhibited fibroblast-like morphology. The flow cytometric analysis revealed positive expression of CD73(97.43%), CD90(95.05%), and CD105(93.17%) and negative expression of CD34(0.05%), CD45(0.09%), and HLA-DR (0.025) surface markers. We then converted this adherent fibroblast-like GMSCs into floating IPCCs using a sequential three-step protocol containing a different combination of differentiating agents. Initially, the presence of insulin in IPCCs was confirmed by dithizone staining. Glucose-stimulated insulin secretion (GSIS) assay confirmed that IPCCs secrete insulin in response to glucose. RESULTS: Generated IPCCs express pancreatic markers such as insulin, pdx1, glucagon, GLUT4 and GLUT2 as evidenced by RT-PCR analysis. Our results unequivocally showed that IPCCs can be generated from gingiva which is a potential source of postnatal MSCs. Our results offer the IPCCs generated from hGMSCs a platform for screening anti-diabetic drugs and a new autologous source of tissue for islet transplantation for the treatment of diabetes. CONCLUSIONS: Our results unequivocally demonstrate for the first time that hGMSCs can be used as an attractive non-invasive tissue source for generating IPCCs, which can be employed in diabetes research for screening antidiabetic agents and also for transplantation in type 1 diabetic patients as autologous source without the need of immunosuppression.
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Diabetes Mellitus , Células Secretoras de Insulina , Células-Tronco Mesenquimais , Humanos , Gengiva/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular , Diabetes Mellitus/terapia , Diabetes Mellitus/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Glucose/metabolismoRESUMO
OBJECTIVES: Several studies suggest that Glycyrrhiza glabra (GG) extract could be a useful supplemental source for various cancer treatments. However, very few studies on oral cancer (OC) have been conducted. The present study was aimed at exploring the bioactive compounds (bioactives) along with the mode of action of GG against OC using network pharmacology. METHODS: Liquid chromatography-mass spectrometry/mass spectrometry was used to identify and analyze compounds from GG. Public databases were used to identify genes associated with the selected bioactives and OC. With the help of Cytoscape software, the association between bioactive and common genes was built, visualized, and investigated. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to investigate protein-protein interactions for intergenic interactions. Finally, the pathway enrichment analysis of common genes was done using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. RESULTS: Overall, 378 bioactives were identified in GG. Using public databases, an entire 254 bioactive-related genes and 734 OC-related genes were recognized, with 48 common genes. Cytoscape analysis showed wortmannin as the key bioactive and androgen receptor as the hub gene. The DAVID results revealed that the significant mechanism of action of GG against OC may be to induce apoptosis of cancer cells by deactivating the PI3K-AKT signaling pathway. CONCLUSION: The key active components and mechanisms of action of GG against OC were investigated. The present study provides scientific suggestions to support the clinical outcome of GG for OC along with a research foundation for additional elaboration on the important bioactives and mechanisms of GG against OC.
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Glycyrrhiza , Neoplasias Bucais , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Extratos Vegetais/farmacologia , Neoplasias Bucais/tratamento farmacológicoRESUMO
Epidemiological data have proved the association of consumption of areca nut with the causation of oral submucous fibrosis (OSF). OSF is a chronic inflammatory disease with the potential for malignant transformation from 7 to 13%. The establishment of animal models makes it easier for researchers to focus on the therapeutic options to combat this disease further. We developed and compared two areca nut extract (ANE) administration methods in Swiss albino mice to establish OSF. This study compared an invasive intrabuccal injection technique with a non-invasive intraoral droplet administration. The duration of induction was around 12 weeks. Histopathology (H&E, Masson's trichrome staining) and gene expression analysis (COL-I, COL-II, and α-SMA) were performed using RT-PCR to confirm the OSF in animals. Our study showed that ANE administration through the intraoral droplet method exhibited significantly higher fibrosis than the intrabuccal injections, as evidenced by the H&E and Masson's trichrome staining. Furthermore, intraoral administration of ANE significantly upregulated the mRNA expression of COL-I, COL-II, and α-SMA, as revealed by the RT-PCR analysis. The non-invasive droplet method could simulate the absorption of areca nut seen in humans through daily dosing. This study establishes the intraoral droplet method as an efficient and non-invasive method to administer the ANE to develop OSF. These findings will aid in the efficient development of OSF animal models for interventional studies, including screening novel drugs in the reversal of the OSF.
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Fibrose Oral Submucosa , Animais , Areca , Modelos Animais de Doenças , Humanos , Camundongos , Fibrose Oral Submucosa/induzido quimicamente , Fibrose Oral Submucosa/tratamento farmacológicoRESUMO
To assess the protective role of the secretome of dental pulp mesenchymal stem cells on arecoline-induced epithelial-mesenchymal transition and senescence on epithelial cells of the oral mucosa. Effect of varying concentrations of arecoline extract and dental pulp mesenchymal stem cell condition media (DPSC-CM) were noted on oral mucosal epithelial cells. MTT assay, Annexin V-FITC/PI assay, and the quantitative gene expressions of BCL2, PUMA, BAD, BAX, CASP3, CASP9, CASP12, TGFB1, CST3, COL1A2, COL3A1, TIMP1, TIMP2, CDH1, and CDH2 were assessed. Oral mucosal epithelial cells exposed only to the arecoline were the control. 50% and 100% DPSC-CM decreased apoptosis-related gene expression in the cells exposed with 25 µM arecoline compared to the control. 50% DPSC-CM attenuated the expression of all fibrotic genes and EMT-related genes. 20% and 100% DPSC-CM showed differential effects on fibrotic and EMT-related genes. DPSC-CM inhibited apoptosis, and attenuated expression of fibrotic and EMT-related genes on arecoline treated human oral epithelial cells.
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Senescência Celular/fisiologia , Polpa Dentária/citologia , Transição Epitelial-Mesenquimal/fisiologia , Células-Tronco Mesenquimais/fisiologia , Apoptose/genética , Arecolina/farmacologia , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose/prevenção & controle , Humanos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Regulação para CimaRESUMO
BACKGROUND: The secretome of the dental pulp mesenchymal stem cells (DPMSCS-S) have an array of regenerative potential and could aid in the rehabilitation of cancer patients post-therapeutic interventions, although caution is required as DPMSC-S have shown to augment prostate cancer cells. Thus, it is vital to assess if these pro-carcinogenic effects extend to other cancer types. OBJECTIVE: To assess if DPMSC-S has any pro-carcinogenic effect on oral cancer, breast cancer, and melanoma cell lines. MATERIALS AND METHODS: Conditioned media obtained from the isolated and characterized DPMSC (DPMSC-CM) were profiled using bead-based multiplex assay. AW13515 (oral cancer), MDA-MB-231 (breast cancer), and A-375 (melanoma) cell lines were exposed to 20%, 50%, and 100% DPMSC-CM for 24, 48, and 72 h. DPMSC-CM effect on the cancer cell properties and secretome were assessed. RESULTS: DPMSC-CM augmented invasion, adhesion, multi-drug resistance, DNA repair, and mitochondrial repair in AW13516 through upregulation of growth factors Ang-2, EGF, M-CSF, PDGF-AA, PDGF-BB, pro-inflammatory cytokines TNF-α, IL-2, downregulation of anti-inflammatory cytokine TGF-ß1, and pro-inflammatory cytokine IL-4. In MDA-MB-231, invasion, and multi-drug resistance were augmented through upregulation of growth factors EGF, EPO, G-CSF, HGF, M-CSF, PDGF-AA, and pro-inflammatory cytokine TNF-α, CXCL10, IL-12p70. EMT, invasion, migration, and adhesion were augmented in A-375 through upregulation of growth factors Ang-2, EGF, PDGF-BB, TGF-α, pro-inflammatory cytokines TNF-α, and IL-17A. CONCLUSION: DPMSC-CM can augment the carcinogenic properties of oral cancer, breast cancer, and melanoma cells, further animal model studies are required to validate our in-vitro findings.
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BACKGROUND: Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients. OBJECTIVE: We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation. MATERIALS AND METHODS: DPMSCs were isolated from patients with healthy teeth (n = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells (AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control. RESULTS: VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-ß1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control. CONCLUSIONS: The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.
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Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Polpa Dentária/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neoplasias Bucais/metabolismo , Adolescente , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Separação Celular , Meios de Cultivo Condicionados/análise , Citocinas/análise , Polpa Dentária/citologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Células-Tronco Mesenquimais/citologia , Neoplasias Bucais/patologia , Cultura Primária de Células , Adulto JovemRESUMO
INTRODUCTION: Tobacco contains several genotoxic agents including N-nitrosamine which has the potential to cause significant nuclear damage. Nuclear blebbing is a form of protrusion on the nuclear membrane and could potentially be caused by tobacco-induced genotoxicity and is closely associated with malignancy. Thus, the present study aimed to assess if tobacco-associated oral potentially malignant disorders including oral submucous fibrosis (OSF) and oral leukoplakia have a higher nuclear blebbing frequency than patients with normal oral mucosa with no history of tobacco use. METHODS: The sample consisted of patients with OSF (n = 30) and oral leukoplakia (n = 10) and normal oral mucosa (n = 10). Exfoliated cells collected from the study groups were smeared on a clean microscopic slide and stained by May-Grunwald-Giemsa stain. A baseline frequency of nuclear blebbing was evaluated using a bright-field microscope with a ×100 objective. The number of nuclear blebbing per 1,000 epithelial cells was recorded and expressed in percentage. ANOVA, the Mann-Whitney U test, and Spearman's correlation were used to analyze the data. RESULTS: The mean rank of distribution of nuclear blebbing showed significant difference between all 3 groups, with the highest frequency noted in leukoplakia, followed by oral submucous and normal oral mucosa. Within OSF, the frequency of nuclear blebbing significantly increased from early stage to advanced stage. In OSF, a statistically significant positive linear correlation was noted between duration (in years), frequency (per day) of tobacco use, clinical grading, and nuclear blebbing. DISCUSSION/CONCLUSIONS: The frequency of nuclear blebbing was significantly higher in oral potentially malignant disorders than normal mucosa. Nuclear blebbing also exhibited a strong dose- and time-dependent correlation with tobacco usage and clinical staging in OSF. The nuclear blebbing frequency could be a noninvasive, economic tool to assess malignant risk in tobacco-induced oral potentially malignant disorders.
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Transformação Celular Neoplásica/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/etiologia , Fibrose Oral Submucosa/etiologia , Uso de Tabaco/efeitos adversos , Adulto , Núcleo Celular/patologia , Humanos , Leucoplasia Oral/patologia , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Fibrose Oral Submucosa/patologia , NicotianaRESUMO
Dear Editor, We thank Dr. Jian Xie for the valuable inputs on our paper titled 'Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis [1].' The first concern of Dr. Xie was that we had included two studies that were based on the same population. We re-examined these papers, one was published in 2010 [2] and the other in 2017 [3] by the same group of authors. Given the significant time difference between the two papers, we did not want to presume they were from the same sample population. There is no clear evidence that they are from the same sample population. Read more in PDF.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/epidemiologia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
The objective of the present article was to qualitatively and quantitatively review the association between chronic mechanical irritation and oral squamous cell carcinoma (OSCC). PubMed, SCOPUS, and Web of Science databases were searched using the keyword combinations "chronic trauma and oral squamous cell carcinoma; chronic irritation and oral squamous cell carcinoma; chronic irritation and oral cancer; and chronic trauma and oral cancer." Duplicates and irrelevant articles were excluded after the title and abstract screening. The full texts of the remaining articles were assessed using selection criteria. A total of 375 (PubMed-126; SCOPUS-152; WOS-97) articles were screened, and 343 duplicates and irrelevant articles were excluded from the study. Only 9 of the remaining 32 articles met the selection criteria and were included in the qualitative analysis. Buccal mucosa and tongue, being highly prone to chronic irritation through the dental prosthesis, were the common sites for OSCC. Edentulous subjects with ill-fitting dentures were at a high risk of developing chronic irritation associated-OSCC. According to the Joanna Briggs Institute of risk assessment, eight of the nine included studies had a low risk of bias. The quantitative analysis showed a significant association (p < 0.00001) between the chronic oral mucosal irritation and OSCC with an overall risk ratio of 2.56 at a confidence interval of 1.96-3.35. Chronic oral mucosa irritation has a significant association with OSCC, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.