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There is a wide spectrum of craniofacial bone disorders and dysplasias because embryological development of the craniofacial region is complex. Classification of craniofacial bone disorders and dysplasias is also complex because they exhibit complex clinical, pathological, and molecular heterogeneity. Most craniofacial disorders and dysplasias are rare but they present an array of phenotypes that functionally impact the orofacial complex. Management of craniofacial disorders is a multidisciplinary approach that involves the collaborative efforts of multiple professionals. This review provides an overview of the complexity of craniofacial disorders and dysplasias from molecular, clinical, and management perspectives.
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Ameloblastoma is a highly recurrent odontogenic neoplasm with variable global distribution. However, impact of race and ethnicity on ameloblastoma recurrence are still unclear. The primary aim of this study was to assess duration of time between primary and recurrent ameloblastomas in a predominantly Black multi-institutional patient cohort and secondarily to determine whether recurrent ameloblastomas are more readily discovered when clinically-symptomatic rather than by radiographic surveillance. A retrospective cross-sectional design was used to evaluate demographic, clinical, and pathological information on recurrent ameloblastomas patients. Outcome variable was time to recurrence, determined as period between the diagnosis of primary and recurrent ameloblastomas. We assessed associations between outcome variable and race, time lapse between primary and recurrent ameloblastomas and clinical symptoms of recurrent ameloblastomas at time of diagnosis. Among 115 recurrent ameloblastomas identified, 90.5% occurred in adults, 91.3% in Blacks, and similarly, 91.3% were conventional ameloblastomas. About 41% affected the posterior mandible. 93.9% were clinically symptomatic at time of presentation while 6.1% non-symptomatic lesions were discovered by routine diagnostic radiology. Median time to presentation of recurrent tumor was significantly longer in females (90 months, p = 0.016) and clinically symptomatic group of ameloblastoma patients (75 months, p = 0.023). Ameloblastoma recurrence was distinctively high in Black patients, occurred faster in males than females and was located mostly in the posterior mandible. Concomitant with delayed access to healthcare of Black individuals, routine post-surgical follow-up is essential because time lag between primary and recurrence tumors was longer in clinically symptomatic ameloblastomas at the time of diagnosis.
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BACKGROUND: Ameloblastoma is an aggressively growing, highly recurrent odontogenic jaw tumor. Its association with BRAFV600E mutation is an indication for BRAFV00E-inhibitor therapy The study objective was to identify a sensitive low-cost test for BRAFV600E-positive ameloblastoma. We hypothesized that immunohistochemical staining of formalin-fixed paraffin-embedded tissues for BRAFV600E mutation is a low-cost surrogate for BRAFV600E gene sequencing when laboratory resources are inadequate for molecular testing. METHODS: Tissues from 40 ameloblastoma samples were retrieved from either formalin-fixed paraffin-embedded blocks, RNAlater™ stabilization solution or samples inadvertently pre-fixed in formalin before transfer to RNAlater™. BRAFV600E mutation was assessed by Direct Sanger sequencing, Amplification Refractory Mutation System-PCR and immunohistochemistry (IHC). RESULTS: BRAFV600E mutation was detected by IHC, Amplification Refractory Mutation System-PCR and Direct Sanger sequencing in 93.33%, 52.5% and 30% of samples respectively. Considering Direct Sanger sequencing as standard BRAFV600E detection method, there was significant difference between the three detection methods (ð2 (2) = 31.34, p < 0.0001). Sensitivity and specificity of IHC were 0.8 (95% CI: 0.64-0.90) and 0.9 (95% CI: 0.75-0.99) respectively, while positive predictive value and negative predictive value (NPV) were 0.9 and 0.8 (Fischer's test, p < 0.0001) respectively. Sensitivity and specificity of Amplification Refractory Mutation System-PCR detection method were 0.7 (95% CI: 0.53-0.80) and 0.9 (95% CI = 0.67-0.98) respectively, while PPV and NPV were 0.9 and 0.6 respectively (Fischer's test, p < 0.0001). CONCLUSION: Low-cost and less vulnerability of IHC to tissue quality make it a viable surrogate test for BRAFV600E detection in ameloblastoma. Sequential dual IHC and molecular testing for BRAFV600E will reduce equivocal results that could exclude some patients from BRAFV600E-inhibitor therapies.
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Ameloblastoma , Tumores Odontogénicos , Humanos , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Ameloblastoma/patología , Proteínas Proto-Oncogénicas B-raf/genética , Mutación , Tumores Odontogénicos/genética , FormaldehídoRESUMEN
Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.
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Ameloblastoma , Neoplasias Maxilomandibulares , Humanos , Ameloblastoma/genética , Ameloblastoma/patología , Ameloblastoma/terapia , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Maxilomandibulares/genética , Neoplasias Maxilomandibulares/patología , Neoplasias Maxilomandibulares/terapia , Resultado del Tratamiento , MutaciónRESUMEN
Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including "metabolic" (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4+ cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. Our group designed and implemented a prospective observational longitudinal study to address this gap. We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We described here the processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management. We also highlighted the rigors and challenges associated with participant recruitment and retention.
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The aim of our study was to review current concepts in targeted therapies for benign tumors of the jaw. Benign odontogenic and maxillofacial bone tumors often require radical surgery, with consequent morbidity that impacts patients' postsurgical quality of life. Currently, targeted therapies and novel nonsurgical therapeutics are being explored for management of non-resectable tumors, with the aim of avoiding surgery or minimizing surgical scope. However, data on clinical applications of targeted therapies for benign tumors of the jaw remain sparse. Therefore, a literature review was conducted, based on the PubMed database, which included in vivo human clinical studies describing clinical application of targeted therapy for benign tumor of the jaw. The review assessed the outcomes of BRAF and MEK inhibitors for treatment of ameloblastoma, RANKL monoclonal antibody for treatment of giant cell tumor, cherubism, aneurysmal bone cyst, and fibrous dysplasia, and tyrosine kinase inhibitor for treatment of odontogenic myxoma and cherubism. Targeted therapies decreased tumor size, slowed down tumor progression, and reduced bone pain. Surgery remains the gold standard, but targeted therapies are promising adjuvant or alternative treatment options for reducing tumor progression and morbidity of tumor surgery.
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Ameloblastoma , Querubismo , Neoplasias Maxilomandibulares , Tumores Odontogénicos , Humanos , Neoplasias Maxilomandibulares/tratamiento farmacológico , Neoplasias Maxilomandibulares/cirugía , Querubismo/tratamiento farmacológico , Calidad de Vida , Tumores Odontogénicos/patología , Ameloblastoma/patologíaRESUMEN
BACKGROUND: Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including "metabolic" (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4+ cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. METHODS: We describe here the study design, including processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management and statistical plan. DISCUSSION: We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We also highlight the rigors and challenges associated with our ongoing participant recruitment and retention. A rigorous prospective longitudinal study requires proper planning and execution. A great benefit is that large data sets are collected and biospecimen repository can be used to answer more questions in future studies including genetic, microbiome and metabolome-based studies. TRIAL REGISTRATION: National Institute of Health Clinical Trials Registration (NCT) #: NCT04645693.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Estudios Longitudinales , Estudios Prospectivos , Carga Viral , Evaluación de Resultado en la Atención de SaludRESUMEN
PURPOSE OF REVIEW: Osteoporosis ranks high among morbidities in the elderly as it is a natural process to lose bone, making them susceptible to fractures from minor falls. The cost of managing these patients is staggering. The fractures can be prevented with better care of the elderly, and by treating the major predisposing factor, osteoporosis. Clinicians and scientists, in general, constantly look for early diagnostic and prognostic indicators for osteopenia and osteoporosis to proactively prevent fractures. Dental panoramic radiography (DPR) is a rotational pantomography used for identifying dental pathology in patients. Early signs of osteopenia and osteoporosis can be identified in DPR. The usefulness of notable jaw changes in DPR to predict osteopenia and osteoporosis is still evolving as more studies continue to delve into this concept. The purpose of this review is to present advances made in the practical application of DPR for predicting early onset of osteopenia and osteoporosis. RECENT FINDINGS: Dental panoramic radiography, a form of tomography commonly used by dental practitioners, has been the standard of care for decades for detecting dento-alveolar pathology. Several technological advancements have taken place with respect to the use of DPR. These include conversion from plain film to digital radiography, advancements in the manufacture of flat panel detectors, and accurate imaging of the layers of mandible and maxilla that has become possible with appropriate patient positioning within the focal trough of the machine. Improvements in the software infrastructure make it easier to view, enhance, and save the radiographic images. The radiographic appearance of the trabecular bone within the mandible and indices measured from the dental panoramic radiographs focusing on the inferior cortex of the mandible are considered useful tools for identifying asymptomatic individuals with osteoporosis or at risk for developing osteoporosis. These indices apparently correlate with risks of fragility fractures of osteoporosis in other parts of the body. Dental panoramic radiography (DPR) is a commonly used radiographic procedure in dentistry for evaluation of teeth and associated maxillofacial structures. The evaluation of the inferior border of the mandible for reduction or loss of cortical thickness and evaluation of the trabecular bone within the mandible are helpful markers for early signs of osteopenia to identify patients at risk for osteoporosis. This review focused on research advancements on practical application of DPR in early identification of osteopenia and osteoporosis.
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Enfermedades Óseas Metabólicas , Fracturas Óseas , Osteoporosis , Anciano , Humanos , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Odontólogos , Osteoporosis/diagnóstico por imagen , Rol Profesional , Radiografía PanorámicaRESUMEN
OBJECTIVE: The objective of this systematic review was to evaluate the risks of medication-related osteonecrosis of the jaw (MRONJ) in fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) patients treated with bisphosphonates. METHOD AND MATERIALS: A systematic review of the literature was performed by searching PubMed and Embase databases using MeSH terms (fibrous dysplasia of bone, "fibrous dysplasia, polyostotic," osteonecrosis, jaw, therapeutics, diphosphonates, denosumab, teriparatide, estrogens, hormones, raloxifene hydrochloride, calcitonin, cathepsin K) and non-MeSH terms (antiresorptive therapy, antiresorptives, bisphosphonate, estrogen therapy, hormone therapy, bazedoxifene, cathepsin K inhibitor). Articles were limited to human studies, in English language, in which patients were on antiresorptives for at least 1 year. PRISMA statement guidelines were used to eliminate non-relevant studies. The PICOT question asked was, "Does exposure to bisphosphonates and other antiresorptives cause occurrence of MRONJ in fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients followed up for at least 1 year?" RESULTS: Eight eligible articles were included in the quantitative synthesis after articles were screened using a PRISMA flowchart. There were 12 reported occurrences of MRONJ among a combined total of 312 fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients (3.85%). CONCLUSION: Patients with fibrous dysplasia or fibrous dysplasia/McCune-Albright syndrome have a low incidence of MRONJ and may apparently have low susceptibility to spontaneous development of MRONJ.
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Conservadores de la Densidad Ósea , Displasia Fibrosa Ósea , Displasia Fibrosa Poliostótica , Osteonecrosis , Conservadores de la Densidad Ósea/efectos adversos , Catepsina K , Difosfonatos/efectos adversos , Displasia Fibrosa Ósea/inducido químicamente , Displasia Fibrosa Poliostótica/complicaciones , Displasia Fibrosa Poliostótica/tratamiento farmacológico , Displasia Fibrosa Poliostótica/epidemiología , HumanosRESUMEN
Ameloblastoma is a locally aggressive odontogenic tumor. Etiopathogenesis and locally aggressive growth properties of ameloblastoma can be attributed to a hypoxic microenvironment conducive to tumor cell survival. Epithelial-derived follicular ameloblastoma cells (EP-AMCs) display enhanced basal autophagy, but the interplay of hypoxia and autophagy in EP-AMCs survival and ameloblastoma recurrence is unclear. We evaluated differential expression of autophagic markers in primary and recurrent ameloblastomas and hypothesized that hypoxia-induced autophagy supports EP-AMC survival. Primary and recurrent ameloblastomas were comparatively assessed for expression levels of pan-cytokeratin, Vimentin, and autophagic markers SQSTM1/p62, LC3, and pS6. EP-AMCs compared with human odontoma-derived cells (HODCs) were subjected to severe hypoxia to determine the interplay of hypoxia and autophagic process in posthypoxia survival. Pan-cytokeratin and SQSTM1/p62 were expressed by both primary and recurrent ameloblastoma epithelial cells while the ameloblastoma connective tissues displayed weak reactivity to vimentin. Under hypoxia, EP-AMC expression levels of hypoxia-inducible factor (HIF)-1α, p62, and LC3 were increased while pS6 was decreased posthypoxia. The combined decrease in pS6 and enhanced LC3 in EP-AMCs under hypoxia indicate that EP-AMCs re-establish basal autophagy under hypoxia. Taken together, these suggest a possible role of LC3-associated phagocytosis (LAP) in ameloblastoma cell survival.
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Ameloblastoma , Ameloblastoma/patología , Autofagia , Hipoxia de la Célula , Línea Celular Tumoral , Células Epiteliales/metabolismo , Humanos , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Queratinas/metabolismo , Proteína Sequestosoma-1/metabolismo , Microambiente Tumoral , Vimentina/metabolismoRESUMEN
PURPOSE: Primary cilia play a significant role in mesenchymal stem cell (MSC) lineage commitment, skeletal development, and bone homeostasis. MSC responsiveness to metabolic stress is associated with radiation and drug-induced jaw osteonecrosis. Therefore, we hypothesize that orofacial MSCs (OFMSCs) osteogenic commitment in response to cellular stressors hypoxia and bisphosphonates is a survival response coupled to primary cilia biogenesis. MATERIALS AND METHODS: Human OFMSCs were subjected to cellular stress using severe hypoxia, nitrogen-containing bisphosphonate (pamidronate) and low serum starvation. OFMSC primary cilia formation, as well as cell survival and proliferation, were detected using immunofluorescence, CellTitre-Glo, and WST-1 assays respectively. OFMSC differentiation was tested using Alizarin Red S staining. OFMSCs survival and osteogenic markers were assessed by western blotting relative to primary cilia number and associated acetylated tubulin levels. RESULTS: Baseline OFMSC proliferation was stable under short-term severe hypoxia and pamidronate treatments whether combined with or without serum starvation. Hypoxia and pamidronate decreased the number of OFMSCs positive for primary cilia that was consistent with increased HIF-1α and caspase 3 but decreased cyclin D1. Combined effects of hypoxia and pamidronate on OFMSCs significantly reduced ciliation but did not completely abrogate it. Combination of serum deprivation, hypoxia, and pamidronate promoted OFMSCs osteogenic differentiation that was consistent with upregulated HIF-1α levels. CONCLUSIONS: Partial rather than complete loss of OFMSC ciliation and enhanced osteogenic commitment represent adaptive survival response of OFMSCs to severe hypoxia and pamidronate-induced metabolic stress. Hypoxia and drug-induced OFMSC stress may be significant events governing the pathogenesis and clinical outcomes of jaw osteonecrosis.
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Células Madre Mesenquimatosas , Osteogénesis , Diferenciación Celular , Cilios , Difosfonatos/farmacología , Humanos , Hipoxia , Subunidad alfa del Factor 1 Inducible por HipoxiaRESUMEN
Radiographic changes of the oral and maxillofacial hard tissues can be an indication of an underlying systemic disease. In this article, the range of individual disease entities that have both systemic and dental manifestations are reviewed. Images for many conditions are provided to illustrate the radiographic changes. A summary of the most common jaw affected, radiographic and pathognomonic findings, and management aspects is listed in a table format within this article for quick reference.
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Maxilares , Humanos , Maxilares/diagnóstico por imagen , RadiografíaRESUMEN
Oral multifocal epithelial hyperplasia (MEH), or Heck's disease, is a rare benign proliferation of the oral mucosa associated with human papillomavirus (HPV). It clinically presents as multiple asymptomatic papules and nodules that mostly affect the lips, buccal mucosa, and tongue. MEH is predominantly found in children and young adults while relatively few cases have been reported in the elderly population. Here, we report a case of oral MEH in a 65-year-old man with history of lung transplantation. This case highlights the potential susceptibility of organ transplant recipients to the development of MEH. Since MEH that does not require treatment unless the lesion bothers the patient, clinicians should promptly establish a definitive diagnosis to rule out other HPV-related precancerous lesions.
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Hiperplasia Epitelial Focal , Trasplante de Pulmón , Negro o Afroamericano , Anciano , Humanos , Hiperplasia , Masculino , PapillomaviridaeRESUMEN
Clinicians should be knowledgeable about the anatomy of the oral cavity and variations of normal because of oral and systemic health connections. This article presents an overview of normal and variations of normal anatomy of the oral cavity.
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Enfermedades de la Boca/diagnóstico , Boca/anatomía & histología , Examen Físico/métodos , Variación Anatómica , Exostosis/patología , Encía , Humanos , Labio/anatomía & histología , Mandíbula/patología , Mucosa Bucal , Hueso Paladar , Glándulas Salivales , Lengua , DienteRESUMEN
Ameloblastoma is an odontogenic tumor with a slow, locally aggressive growth pattern and multiple clinico-histologic types. The number of stromal myofibroblasts within ameloblastoma often is correlated with growth and aggressiveness. Color-deconvolution to separate different colors of immunostained tissues is a promising approach to quantifying myofibroblasts in tumors such as ameloblastoma. We investigated the reliability of the color-deconvolution method using cross-sectional design to evaluate alpha-smooth muscle actin (α-SMA)-positive myofibroblasts in solid multicystic ameloblastoma. Formalin fixed tissues of eight cases of solid multicystic ameloblastoma were immunostained for α-SMA using the horseradish peroxidase-diaminobenzidine (HRP-DAB) method. Color-deconvolution using ImageJ software was used to quantify the staining intensity of brown DAB α-SMA stained myofibroblasts. Color-deconvoluted images of brown DAB stained tissues exhibited distinct morphological features of solid multicystic ameloblastoma with α-SMA stained myofibroblasts distributed abundantly adjacent to the ameloblastoma epithelial islands. The computed image intensity of α-SMA stained myofibroblasts was quantitatively similar among the different ameloblastoma samples. A combination of color-deconvolution and α-SMA staining of myofibroblasts is a useful diagnostic tool for evaluating histologic differentiation and growth pattern of ameloblastoma.
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Actinas/metabolismo , Ameloblastoma/patología , Músculo Liso/patología , Miofibroblastos/patología , Estudios Transversales , Humanos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: Drug reference databases provide information on potential drug-related medical complications in a dental patient. It is important that database entries and recommendations are supported by evidence-based original studies focused on drug-related dental management complications. The aim of this study was to review and identify database drug categories associated with evidence-based drug-related medical complications during dental treatment. DATA SOURCES: Relevant publications on adverse drug reactions and dental management complications were thoroughly reviewed from the literature published between July 1975 and July 2019. METHOD AND MATERIALS: The drug reference database "Lexicomp Online for Dentistry" was reviewed to identify medications associated with the highest propensity to trigger drug-related dental management complications, and these were correlated with published original studies in PubMed, Embase, and Scopus databases that associated drug actions with dental treatment complications. RESULTS: Fifty-four publications (1.2% of all full-text articles) reported original studies that directly tested drug associations with dental management complications. The cautions in the drug reference database on drug-related dental treatment mainly focused on local anesthetic precaution (P < .001), xerostomia (P < .001), bleeding (P < .001), and a combination of xerostomia and bleeding (P < .001). Antipsychotics/antidepressants were mostly associated with local anesthetic complications (80.95%), xerostomia (81.93%), and a combination of xerostomia and bleeding (22.89%). Bleeding complication was associated with anticoagulants (80.00%) and cancer chemotherapeutic agents (59.21%). CONCLUSIONS: Similarities exist within and across different drug categories in the database entries on drug-related medical complications in a dental patient. There were a relatively limited number of publications that directly tested the association between drug-related medical complications and dental therapies. CLINICAL RELEVANCE: The most common drug cautions during dental treatment reported in Lexicomp Online for Dentistry were limited to drug-drug interactions with local anesthetic actions, excessive bleeding, xerostomia, or a combination of any of these. These recommendations were supported by limited evidence-based studies.
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Xerostomía , Anticoagulantes , Atención Odontológica , HumanosRESUMEN
OBJECTIVES: Ameloblastoma is an aggressive odontogenic jaw neoplasm. Its unlimited growth confers high potential for malignant transformation and recurrence. It is unclear why ameloblastoma is highly recurrent despite surgical resection with a wide margin of normal tissue. While canonical autophagy can be used to degrade and eliminate damaged cellular components, it is also a protective mechanism that provides energy and vital metabolites for cell survival. We used ameloblastoma-derived cells to test the hypothesis that autophagic processes play a role in survival and reactivation of ameloblastoma. METHODS: Primary epithelial (EP-AMCs) and mesenchymal (MS-AMCs) ameloblastoma-derived cells were established from tissue samples of solid multicystic ameloblastoma. Clonogenic capacity and basal autophagic capacity were assessed in ameloblastoma-derived cells relative to human odontoma-derived cells (HODCs) and maxilla-mesenchymal stem cells (MX-MSCs). Ability of ameloblastoma-derived cells to survive and form new ameloblastoma was assessed in mouse tumor xenografts. RESULTS: EP-AMCs were highly clonogenic (p < 0.0001) and demonstrated enhanced basal levels of autophagic proteins microtubule-associated protein 1-light chain 3 (LC3) (p < 0.01), p62 (Sequestosome 1, SQSTM1) (p < 0.01), and the LC3-adapter, melanoregulin (MREG) (p < 0.05) relative to controls. EP-AMCs xenografts regenerated solid ameloblastoma-like tumor with histological features of columnar ameloblast-like cells, loose stellate reticulum-like cells and regions of cystic degeneration characteristic of follicular variant of solid multicystic ameloblastoma. The xenografts also displayed stromal epithelial invaginations strongly reactive to LC3 and p62 suggestive of epithelial-mesenchymal transition and neoplastic odontogenic epithelium. CONCLUSIONS: EP-AMCs exhibit altered autophagic processes that can support survival and recurrence of post-surgical ameloblastoma cells.
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Ameloblastoma , Autofagia/fisiología , Supervivencia Celular , Tumores Odontogénicos , Proteínas Adaptadoras del Transporte Vesicular , Ameloblastoma/patología , Ameloblastos/metabolismo , Ameloblastos/patología , Animales , Proteínas Portadoras/metabolismo , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , Epitelio/metabolismo , Femenino , Xenoinjertos , Humanos , Péptidos y Proteínas de Señalización Intracelular , Células Madre Mesenquimatosas , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Recurrencia Local de Neoplasia , Proteína Sequestosoma-1/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Oral cancer therapies are associated with orofacial complications that could result in dose-limiting cancer treatment and consequent suboptimal tumor control. Oral cancer treatment complications include oral mucositis, salivary gland hypofunction, odontogenic infections, pain, dermatitis, neurotoxicity, soft tissue fibrosis, trismus, osteoradionecrosis, and potential cancer recurrence. These complications significantly affect cancer survivorship, quality of life, and psychosocial status. Effective dental management of patients with oral cancer involves the coordination of care among several health care professionals before, during, and after cancer therapy. The goal is to minimize complications, and establish optimal quality of life for survivors.
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Antineoplásicos/efectos adversos , Atención Dental para Enfermos Crónicos , Neoplasias de la Boca/terapia , Enfermedades Estomatognáticas/terapia , Caries Dental/etiología , Caries Dental/terapia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Recurrencia Local de Neoplasia , Osteorradionecrosis/etiología , Osteorradionecrosis/terapia , Calidad de Vida , Radioterapia/efectos adversos , Estomatitis/etiología , Estomatitis/terapia , Enfermedades Estomatognáticas/etiología , Trismo/etiología , Trismo/terapia , Xerostomía/etiología , Xerostomía/terapiaRESUMEN
OBJECTIVES: Mesenchymal stem cells (MSCs) offer a promising therapy in dentistry because of their multipotent properties. Selecting donor MSCs is crucial because Beagle dogs (canines) commonly used in preclinical studies have shown variable outcomes, and it is unclear whether canine MSCs (cMSCs) are skeletal site specific. This study tested whether jaw and long bone cMSCs have disparate in vitro and in vivo multilineage differentiation capabilities. STUDY DESIGN: Primary cMSCs were isolated from the mandible (M-cMSCs) and femur (F-cMSCs) of four healthy Beagle dogs. The femur served as the non-oral control. Clonogenic and proliferative abilities were assessed. In vitro osteogenic, chondrogenic, adipogenic, and neural multilineage differentiation were correlated with in vivo bone regeneration and potential for clinical applications. RESULTS: M-cMSCs displayed two-fold increase in clonogenic and proliferative capacities relative to F-cMSCs (P = .006). M-cMSCs in vitro osteogenesis based on alkaline phosphatase (P = .04), bone sialoprotein (P = .05), and osteocalcin (P = .03), as well as adipogenesis (P = .007) and chondrogenesis (P = .009), were relatively higher and correlated with enhanced M-cMSC bone regenerative capacity. Neural expression markers, nestin and ßIII-tubulin, were not significantly different. CONCLUSIONS: The enhanced differentiation and bone regenerative capacity of mandible MSCs may make them favorable donor graft materials for site-specific jaw bone regeneration.
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Regeneración Ósea/fisiología , Diferenciación Celular/fisiología , Células Madre Mesenquimatosas/fisiología , Adipogénesis/fisiología , Fosfatasa Alcalina/metabolismo , Animales , Western Blotting , Células Cultivadas , Condrogénesis/fisiología , Perros , Fémur/citología , Sialoproteína de Unión a Integrina/metabolismo , Mandíbula/citología , Nestina/metabolismo , Osteocalcina/metabolismo , Osteogénesis/fisiología , Tubulina (Proteína)/metabolismoRESUMEN
In this report, we describe the incidental finding of an oropharyngeal mass in a patient who presented with a chief complaint of temporomandibular pain. The patient was initially evaluated by an otorhinolaryngologist for complaints of headaches, earache, and sinus congestion. Due to worsening headaches and trismus, he was further referred for the management of temporomandibular disorder. The clinical evaluation was uneventful except for limited mouth opening (trismus). An advanced radiological evaluation using magnetic resonance imaging revealed a mass in the nasopharyngeal/oropharyngeal region. The mass occupied the masticatory space and extended superioinferiorly from the skull base to the mandible. A diagnostic biopsy of the lesion revealed a long-standing human papilloma virus (HPV-16)-positive squamous cell carcinoma of the oropharynx. This case illustrates the need for the timely radiological evaluation of seemingly innocuous orofacial pain.