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Genes Jul 2023Cell proliferation and invasion are characteristic of many tumors, including ameloblastoma, and are important features to target in possible future therapeutic...
UNLABELLED
Cell proliferation and invasion are characteristic of many tumors, including ameloblastoma, and are important features to target in possible future therapeutic applications.
OBJECTIVE
The objective of this study was the identification of key genes and inhibitory drugs related to the cell proliferation and invasion of ameloblastoma using bioinformatic analysis.
METHODS
The H10KA_07_38 gene profile database was analyzed by Rstudio and ShinyGO Gene Ontology enrichment. String, Cytoscape-MCODE, and Kaplan-Meier plots were generated, which were subsequently validated by RT-qPCR relative expression and immunoexpression analyses. To propose specific inhibitory drugs, a bioinformatic search using Drug Gene Budger and DrugBank was performed.
RESULTS
A total of 204 significantly upregulated genes were identified. Gene ontology enrichment analysis identified four pathways related to cell proliferation and cell invasion. A total of 37 genes were involved in these pathways, and 11 genes showed an MCODE score of ≥0.4; however, only SLC6A3, SOX10, and LRP5 were negatively associated with overall survival (HR = 1.49 ( = 0.0072), HR = 1.55 ( = 0.0018), and HR = 1.38 ( = 0.025), respectively). The RT-qPCR results confirmed the significant differences in expression, with overexpression of >2 for SLC6A3 and SOX10. The immunoexpression analysis indicated positive LRP5 and SLC6A3 expression. The inhibitory drugs bioinformatically obtained for the above three genes were parthenolide and vorinostat.
CONCLUSIONS
We identify LRP5, SLC6A3, and SOX10 as potentially important genes related to cell proliferation and invasion in the pathogenesis of ameloblastomas, along with both parthenolide and vorinostat as inhibitory drugs that could be further investigated for the development of novel therapeutic approaches against ameloblastoma.
Topics: Humans; Ameloblastoma; Vorinostat; Cell Proliferation; Computational Biology; SOXE Transcription Factors; Low Density Lipoprotein Receptor-Related Protein-5; Dopamine Plasma Membrane Transport Proteins
PubMed: 37628576
DOI: 10.3390/genes14081524 -
Maxillary Ameloblastoma with Orbital Involvement: An Institutional Experience and Literature Review.Ophthalmic Plastic and Reconstructive... 2016To describe 8 patients with orbital involvement by ameloblastoma and to review the literature on this topic. (Review)
Review
PURPOSE
To describe 8 patients with orbital involvement by ameloblastoma and to review the literature on this topic.
METHODS
The electronic medical records and pathology databases of the Hospital of the University of Pennsylvania were searched to identify all patients with histopathologically confirmed ameloblastoma diagnosed between 1990 and 2015. PubMed database was searched for all well-documented cases of maxillary ameloblastoma and ameloblastic carcinoma ex-ameloblastoma with orbital involvement published in the English literature. The information collected on the compiled 23 patients included age, sex, clinical presentation, imaging findings, management, tumor histopathologic features, and follow up.
RESULTS
Review of medical records identified 8 patients with orbital involvement by ameloblastoma. Literature search yielded 15 patients with well-documented orbital involvement by ameloblastoma. Most tumors occurred in men (19 of 23, M:F = 4-5:1) with an average age of 56 years. The overall rates of recurrence, visual compromise, death, and confirmed disease-related mortality were 70% (16/23), 26% (6/23), 39% (9/23), and 22% (5/23), respectively. The initial surgical approach correlated with prognosis. The rates of recurrence, orbital exenteration, and mortality in the cohort managed with conservative surgery or partial maxillectomy were 57% (8/14), 29% (4/14), and 50% (7/14), respectively. In contrast, the patients initially managed with a radical resection had substantially lower frequencies of tumor recurrence (2/7, 29%), exenteration (1/7, 14%), and death (1/7, 14%). Malignant transformation to ameloblastic carcinoma occurred in the setting of recurrent disease in 3 patients and in 1 patient with prolonged duration of symptoms, suggestive of a long-standing tumor.
CONCLUSIONS
Maxillary ameloblastoma can rarely involve the orbit, leading to significant ocular morbidity and occasional mortality. Prompt radical resection of the tumor has the potential to decrease the likelihood of recurrence and visual compromise, and can improve survival.
Topics: Ameloblastoma; Humans; Maxillary Neoplasms; Neoplasm Invasiveness; Orbit; Orbital Neoplasms; Tomography, X-Ray Computed
PubMed: 26505234
DOI: 10.1097/IOP.0000000000000580 -
Brazilian Dental Journal 2021The aim of this study was to assess and compare RANK, RANKL, and OPG immunoexpression in dentigerous cyst, odontogenic keratocyst, and ameloblastoma. The protocol was... (Meta-Analysis)
Meta-Analysis
The aim of this study was to assess and compare RANK, RANKL, and OPG immunoexpression in dentigerous cyst, odontogenic keratocyst, and ameloblastoma. The protocol was registered in PROSPERO (CRD42018105543). Seven databases (Embase, Lilacs, LIVIVO, PubMed, Scopus, SciELO, and Web of Science) were the primary search sources and two databases (Open Grey and Open Thesis) partially captured the "grey literature". Only cross sectional studies were included. The JBI Checklist assessed the risk of bias. A meta-analysis with random effects model estimated the values from the OPG and RANKL ratio reported by the individual studies and respective 95% confidence intervals. The heterogeneity among studies was assessed with I2 statistics. Only nine studies met the inclusion criteria and were considered in the analyses. The studies were published from 2008 to 2018. Two studies presented low risk of bias, while seven studies presented moderate risk. The meta-analysis showed the highest OPG>RANKL ratio for dentigerous cyst (ES=43.3%; 95% CI=14.3-74.8) and odontogenic keratocyst (ES=36.8%; 95% CI=18.8-56.7). In contrast, the highest OPG
ameloblastoma (ES=73.4%; 95% CI=55.4-88.4) and it was higher in the stromal region compared to the odontogenic epithelial region. The results may explain the aggressive potential of ameloblastoma from the higher OPG Topics: Ameloblastoma; Cross-Sectional Studies; Dentigerous Cyst; Humans; Odontogenic Cysts; Odontogenic Tumors
PubMed: 33913997
DOI: 10.1590/0103-6440202103387 -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2020The purpose of this experimental study was to compare the immunohistochemical expression of SOX2 and BCL-2 in Odontogenic Keratocyst (OKC) and Ameloblastoma (AB)...
BACKGROUND
The purpose of this experimental study was to compare the immunohistochemical expression of SOX2 and BCL-2 in Odontogenic Keratocyst (OKC) and Ameloblastoma (AB) specimens, and to identify a possible correlation in their expression.
MATERIAL AND METHODS
Immunohistochemical analysis was performed to evaluate SOX2 and BCL-2 expression in OKC (n = 20) and AB (n = 20). The immunoexpression was analyzed by a quantitative and qualitative scoring system. The comparison between the immunoexpression of SOX 2 and BCL-2 was assessed by the Mann-Whitney U-test. Spearman's correlation coefficient evaluated the correlation between SOX2 and BCL-2 expressions.
RESULTS
SOX2 and BCL-2 expression was observed in all specimens of OKC in the full thickness of the epithelium lining. SOX2 immunostaining was higher in OKC, in comparison with AB samples (P<0.05). BCL-2 immunostaining between OKC and AB was not statistically significant. There was no significant correlation between SOX2 and BCL-2 in OKC and AB specimens.
CONCLUSIONS
SOX2 and BCL-2 expressions in OKC may suggest their relationship with the biological behavior of this lesion, and the higher expression of SOX2 might be an upstream influence on the Hh signaling pathway.
Topics: Ameloblastoma; Humans; Odontogenic Cysts; Odontogenic Tumors; Proto-Oncogene Proteins c-bcl-2; SOXB1 Transcription Factors
PubMed: 31967981
DOI: 10.4317/medoral.23348 -
International Journal of Molecular and... 2016Odontogenic tumors constitute a group of heterogeneous lesions of benign and malignant neoplasms with variable aggressiveness. Ameloblastomas are a group of benign but...
Odontogenic tumors constitute a group of heterogeneous lesions of benign and malignant neoplasms with variable aggressiveness. Ameloblastomas are a group of benign but locally invasive neoplasms that occur in the jaws and are derived from epithelial elements of the tooth-forming apparatus. We previously described orosomucoid-1 protein expression in odontogenic myxomas. However, whether orosomucoid-1 is expressed in other odontogenic tumors remains unknown. Since orosomucoid-1 belongs to a group of acute-phase proteins and has many functions in health and disease, we identified and analyzed orosomucoid-1 expression in ameloblastoma variants and ameloblastic carcinoma using western blot and immunohistochemical techniques. Thirty cases of ameloblastoma were analyzed for orsomucoid-1; five specimens were fresh for western blot study (four benign ameloblastomas and one ameloblastic carcinoma), and 25 cases of benign ameloblastoma for immunohistochemical assays. Orosomucoid-1 was widely expressed in each tumor variant analyzed in this study, and differential orosomucoid-1 expression was observed between benign and malignant tumor. Orosomucoid-1 may play an important role in the behavior of ameloblastomas and influence the biology and development of the variants of this tumor.
PubMed: 27386438
DOI: No ID Found -
Head and Neck Pathology Mar 2023Cystic lesions of the gnathic bones present challenges in differential diagnosis. This category includes a smorgasbord of odontogenic and non-odontogenic entities that... (Review)
Review
BACKGROUND
Cystic lesions of the gnathic bones present challenges in differential diagnosis. This category includes a smorgasbord of odontogenic and non-odontogenic entities that may be reactive or neoplastic in nature. While most cystic jaw lesions are benign, variability in biologic behavior makes distinction between these entities absolutely crucial.
METHODS
Review.
RESULTS
Two clinical cases are presented in parallel and are followed by an illustrated discussion of the ten most likely differential diagnoses that should be considered when confronted with a cystic jaw lesion. Strong emphasis is placed on the histologic differences between these entities, empowering readers to diagnose them with confidence. Perhaps even more importantly, the more common diagnostic pitfalls in gnathic pathology are discussed, recognizing that a definitive diagnosis cannot be rendered in every situation. The histologic diagnoses for the two clinical cases are finally revealed.
CONCLUSION
Cystic lesions of the maxilla and mandible may be odontogenic or non-odontogenic. The most common cystic lesions are the reactive periapical cyst, and the dentigerous cyst (which is developmental in nature). It is important to note that cystic neoplasms also occur in the jaws, and that the presence of inflammation may obscure the diagnostic histologic features of lesions like odontogenic keratocyst and unicystic ameloblastoma. Ancillary testing is of limited diagnostic value in most scenarios. However, both clinical and radiographic information (such as the location, size, duration, associated symptoms, and morphology of the lesion in its natural habitat) are significantly useful.
Topics: Humans; Diagnosis, Differential; Jaw Neoplasms; Odontogenic Cysts; Odontogenic Tumors; Ameloblastoma; Maxilla
PubMed: 36928736
DOI: 10.1007/s12105-023-01525-1 -
International Journal of Oral Science Feb 2024Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms...
Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.
Topics: Humans; Ameloblastoma; Neoplasm Recurrence, Local; Phenotype; Cell Transformation, Neoplastic; Gene Expression Profiling
PubMed: 38424060
DOI: 10.1038/s41368-024-00281-4 -
Ear, Nose, & Throat Journal May 2023Ameloblastic carcinoma (AC) is a rare and aggressive malignant epithelial odontogenic tumor making up less than 1% of malignant head and neck tumors. The majority of...
Ameloblastic carcinoma (AC) is a rare and aggressive malignant epithelial odontogenic tumor making up less than 1% of malignant head and neck tumors. The majority of cases occur in the mandible with a minority occurring in the maxilla. Most occur de novo, while rare cases of AC have resulted from transformation from ameloblastoma. Here, we present a case in which a 30-year-old man presented with proptosis and a recurrent right temporal mass, which had been previously diagnosed as ameloblastoma on surgical pathology. CT findings demonstrated local invasion, and he was subsequently taken to the operating room for right craniotomy, infratemporal and middle cranial fossa tumor resection, and right modified radical neck dissection with reconstruction. Final pathology, which included areas of early focal necrosis, loss of peripheral palisading, and hyperchromatism, confirmed the diagnosis of ameloblastoma with transformation to AC. We further discuss radiologic and histopathological signs of this rare tumor, as well as recommended treatment modalities.
PubMed: 37158333
DOI: 10.1177/01455613231172857 -
Archives of Oral Biology Oct 2022Primary cilium is a cellular organelle with growing significance confirmed in tumour biology. Primary cilia have been associated with fine tuning of numerous cell...
OBJECTIVES
Primary cilium is a cellular organelle with growing significance confirmed in tumour biology. Primary cilia have been associated with fine tuning of numerous cell signalling pathways and the role of this structure in cancer initiation and progression is recently at the forefront of attention. Here, we investigated possible alterations in the occurrence of primary cilia and changes of associated signalling in ameloblastoma, which represents the most common odontogenic tumour.
METHODS
We performed immunohistochemistry to assess the number and morphology of primary cilia in ameloblastoma tissues. The gene expression of key SHH pathway members was analysed by qPCR. As a functional experiment, we treated a primary ameloblastoma cell line by a SHH pathway inhibitor Sonidegib (LDE225).
RESULTS
We uncovered differences in primary cilia distribution and appearance in histological subtypes of ameloblastoma with the highest number of ciliated cells in plexiform and follicular subtypes. SHH protein was located close to primary cilia in ameloblastoma epithelial cells and the expression of molecules downstream of SHH signalling was upregulated. Moreover, the inhibition of SHH pathway by Sonidegib caused downregulation of SHH effector gene GLI1 and cell cycle regulator CCND1 in ameloblastoma primary cell line. The inhibition of SHH signalling also altered the expression of molecules involved in intraflagellar transport.
CONCLUSIONS
In conclusion, our study uncovered alterations in number of ciliated cells and associated signalling in ameloblastoma, which indicate SHH inhibitors as potential therapeutic target to treat this disease.
Topics: Ameloblastoma; Cilia; Hedgehog Proteins; Humans; Odontogenic Tumors; Signal Transduction
PubMed: 35863182
DOI: 10.1016/j.archoralbio.2022.105499 -
Journal of Advanced Veterinary and... Sep 2023The escalating prevalence of canine oral tumors has emerged as a considerable health concern. This study examined the prevalence, types, and distributions of lesions...
OBJECTIVE
The escalating prevalence of canine oral tumors has emerged as a considerable health concern. This study examined the prevalence, types, and distributions of lesions linked to canine oral tumors.
MATERIAL AND METHODS
The medical records of 526 dogs diagnosed with oral tumors were analyzed to determine the prevalence, types, and distributions. Tumor stages were classified into four categories using the tumor node metastasis system.
RESULTS
Among the 526 dogs, there were 118 cases of benign tumors and 408 cases of malignant tumors. Acanthomatous ameloblastoma was the most common benign tumor (43.22%), while melanoma was the most common malignant tumor (51.23%). The gingiva was the most common site for both benign and malignant lesions, accounting for 89.83% and 63.73% of cases, respectively. Melanoma, squamous cell carcinoma, and fibrosarcoma were primarily located in the gingiva, whereas osteosarcoma was commonly found in the mandible. Most tumors were classified as stage III (ranging from 46.84% to 74.58%). Of the reported cases, 56.08% were males and 43.92% were females, and the most common breed was mixed at 30.41%, followed by Poodle at 14.25% and Shih Tzu at 11.40%. Moreover, patients with malignant oral tumors (11.6 ± 3.1 years) were significantly older than those with benign tumors (8.9 ± 3.4 years, < 0.0001).
CONCLUSION
Gingiva was the primary site for oral tumors, and mainly classified as stage III. These findings emphasize the increasing occurrence of oral tumors in senior and geriatric dogs and provide insights into the prevalent types and distribution.
PubMed: 37969809
DOI: 10.5455/javar.2023.j709