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Histology and Histopathology Feb 2024Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest.... (Review)
Review
Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest. Tumors frequently encounter areas with inadequate oxygen supply, resulting in a hypoxic microenvironment. Ameloblastoma is one of the most common benign odontogenic tumors of the maxillofacial region. It is a slow-growing but locally invasive tumor with a high recurrence rate. The literature has demonstrated the correlation between hypoxia and ameloblastoma, revealing a discernible link between the heightened expression of hypoxic markers in low oxygen conditions. This association is intricately tied to the tumoral potential for invasion, progression, and malignant transformation. Hypoxia profoundly influences the molecular and cellular landscape within ameloblastic lesions. The present review sheds light on the mechanisms, implications, and emerging perspectives in understanding this intriguing association to clarify the dynamic relationship between hypoxia and ameloblastoma.
PubMed: 38362601
DOI: 10.14670/HH-18-718 -
Malawi Medical Journal : the Journal of... Dec 2023Odontogenic keratocyst is a benign intraosseous lesion of odontogenic origin which is characterized by its aggressive nature. It is usually present in the mandibular...
Odontogenic keratocyst is a benign intraosseous lesion of odontogenic origin which is characterized by its aggressive nature. It is usually present in the mandibular posterior area, although it can also be found in the maxilla, particularly in the canine region. We discuss a unique example of OKC in the maxillary sinus involving the 27&28 region. Due to comparable clinical signs, this lesion is more prone to be mistaken for other lesions of the maxillary sinus, such as sinusitis or polyps. On the other side, this benign disease has the potential to develop into Ameloblastoma or squamous cell carcinoma. A favorable prognosis thus depends on early identification, precise diagnosis, appropriate treatment, and follow-ups.
Topics: Humans; Animals; Dogs; Maxillary Sinus; Odontogenic Cysts; Carcinoma, Squamous Cell
PubMed: 38362567
DOI: 10.4314/mmj.v35i4.6 -
Scientific Reports Feb 2024The aim of this study was to verify whether the expression of cell proliferation and apoptosis markers in different types of unicystic ameloblastoma (UA) is associated...
The aim of this study was to verify whether the expression of cell proliferation and apoptosis markers in different types of unicystic ameloblastoma (UA) is associated with the location of neoplastic cells. Immunohistochemical study with a sample of 32 cases of UA, 11 cases of conventional ameloblastoma (CAM) and ten dental follicles (DF) cases was performed. Cell proliferation was assessed using Ki-67 status, and apoptosis by caspase-3 expression. Mural UA (MUA) showed a higher immunostaining of Ki-67 (p < 0.05) and a lower immunostaining of Caspase-3 (p < 0.05) compared with luminal and intraluminal subtypes of UA and CAM. The neoplastic cells of the MUA's cystic capsule showed a higher expression of Ki-67 protein (p < 0.0001) and a lower expression of Caspase-3 (p < 0.0001) compared with the lumen. DF showed lower Ki-67 and Caspase-3 immunostaining (p < 0.05) than neoplasms. The higher immunoexpression of Ki-67 and the lower immunoexpression of Caspase-3 in MUA, in the parenchyma cells within the cystic capsule, suggest an association between the biological behaviour and location of neoplastic cells in a tumour.
Topics: Humans; Ameloblastoma; Ki-67 Antigen; Caspase 3; Prognosis; Cell Proliferation; Apoptosis
PubMed: 38360984
DOI: 10.1038/s41598-024-54132-7 -
Journal of Maxillofacial and Oral... Feb 2024Clear cell odontogenic carcinoma (CCOC) is a rare epithelial malignant odontogenic tumor of the jaw with a distinct histology and deceptive behavior. As the clinical...
Clear cell odontogenic carcinoma (CCOC) is a rare epithelial malignant odontogenic tumor of the jaw with a distinct histology and deceptive behavior. As the clinical presentation is often misleading, the contribution of biopsy, molecular biology, immunohistochemistry and cytogenetics are essential in the diagnostic process. This article describes the presentation of an aymptomatic, painless swelling in the lower jaw of a 63 yrs old female, who was initially diagnosed as an ameloblastoma, taken up for segmental resection, subsequently histopathologically diagnosed as a case of clear cell odontogenic carcinoma and later managed with chemotherapy. Current management protocols and presentation of CCOC have also been reviewed.
PubMed: 38312974
DOI: 10.1007/s12663-023-01904-9 -
Gene May 2024Ameloblastoma (AM), a common odontogenic epithelial tumor, exhibits aggressive growth due to incomplete encapsulation within the jawbone. Postoperative recurrence is a...
OBJECTIVES
Ameloblastoma (AM), a common odontogenic epithelial tumor, exhibits aggressive growth due to incomplete encapsulation within the jawbone. Postoperative recurrence is a significant concern, closely associated with its invasive nature. We investigate the role of tRNA N-7 methylguanosine (mG) modification mediated by Methyltransferase-like 1 (METTL1) in AM's invasive growth and prognosis.
MATERIALS AND METHODS
METTL1 expression was analyzed in diverse cell lines and clinical AM tissues. Its association with postoperative AM recurrence was examined. Functional experiments included METTL1 gene silencing using shRNA in hTERT-AM cells, assessing cell proliferation, migration, and invasion. Xenograft tumor model was constructed to investigate tumor growth. Molecular mechanisms behind METTL1's role in AM invasiveness were elucidated using Ribosome nascent-chain complex-bound mRNA sequencing (RNC-seq) and experimental analysis.
RESULTS
High METTL1 expression was significantly associated with postoperative recurrence in AM. The inhibition of AM development following METTL1 knockdown has been corroborated by experiments conducted both in vitro and in vivo. Analysis of RNC-seq data revealed that downregulated genes were predominantly enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, suggesting that METTL1 may promote AM's invasive growth through the MAPK signaling pathway.
CONCLUSION
Our study elucidates the functional role of METTL1 in AM's invasive development and prognosis. High METTL1 expression is linked to postoperative recurrence, and METTL1 appears to promote AM invasiveness through the MAPK signaling pathway. These findings contribute to a better understanding of AM pathogenesis and may guide future therapeutic strategies.
Topics: Humans; Ameloblastoma; Cell Line; Cell Proliferation; MAP Kinase Signaling System; Methyltransferases
PubMed: 38309318
DOI: 10.1016/j.gene.2024.148234 -
Molecular Medicine Reports Mar 2024Keratoameloblastoma (KA) and solid variant of odontogenic keratocyst (SOKC) are rare odontogenic lesions, and their relationship and differences are unclear. The present...
Keratoameloblastoma (KA) and solid variant of odontogenic keratocyst (SOKC) are rare odontogenic lesions, and their relationship and differences are unclear. The present study described a case that started as an odontogenic keratocyst (OKC) and transformed to SOKC/KA upon recurrence. Briefly, a 26‑year‑old man presented with swelling in the right cheek and was referred to the Department of Oral and Maxillofacial surgery, Hiroshima University Hospital (Hiroshima, Japan). At the initial visit, unicystic bone permeation was observed extending from the right canine to the molar, maxillary sinus and nasal cavity. After the biopsy, the patient underwent excisional surgery and was diagnosed with OKC. Thereafter, the lesion recurred six times over a period of 13 years and showed different histopathological features from those of the primary lesion, all consisting of numerous cysts with keratinization, which were diagnosed as SOKC/KA. The Ki‑67 positivity rate was ~10%, which was higher than that of the primary lesion, but there was no atypia. Genetic analysis of the recurrent lesion revealed mutations in adenomatous polyposis coli and Kirsten rat sarcoma viral oncogene homolog. This case originated from OKC, and the morphological features of OKC and KA were mixed upon recurrence, supporting the commonality and association between the two. However, multiple mutations different from those of OKC and ameloblastoma were detected, suggesting an association of SOKC/KA with increased proliferative activity and a high recurrence rate.
Topics: Male; Humans; Adult; Ameloblastoma; Odontogenic Cysts; Mutation; Biopsy; Bone and Bones
PubMed: 38275130
DOI: 10.3892/mmr.2024.13168 -
Oral Oncology Mar 2024
Topics: Humans; Ameloblastoma; Odontogenic Tumors; Mandibular Neoplasms; Carcinoma
PubMed: 38271776
DOI: 10.1016/j.oraloncology.2024.106704 -
Medicina (Kaunas, Lithuania) Dec 2023Ameloblastoma is a benign epithelial tumor that has aggressive, destructive and unlimited growth potential, having the capacity for recurrence and malignant...
Ameloblastoma is a benign epithelial tumor that has aggressive, destructive and unlimited growth potential, having the capacity for recurrence and malignant transformation. Regarding the symptoms and clinical signs, the presentation of ameloblastoma is poor. In children and young people, ameloblastoma can be difficult to diagnose, because it mimics other benign lesions. Its diagnosis requires a combination of imaging data, histopathological analysis and molecular tests. The methods of treatment consist of radical surgery (segmental resection) and conservative treatments (enucleation with bone curettage). The particularity of the presented case is represented by the late request for medical consultation, a direct consequence of the measures implemented to prevent and control the spread of COVID-19.
Topics: Child; Female; Humans; Adolescent; Ameloblastoma; Mandible; Aggression; COVID-19; Conservative Treatment
PubMed: 38256328
DOI: 10.3390/medicina60010066 -
International Journal of Molecular... Jan 2024Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates... (Review)
Review
Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.
Topics: Humans; Ameloblastoma; Craniopharyngioma; Imidazoles; Oximes; Pituitary Neoplasms
PubMed: 38255797
DOI: 10.3390/ijms25020723 -
Calcified Tissue International Apr 2024Ameloblastoma is a rare odontogenic tumor which may be complicated by hypercalcemia in advanced disease. Tumoral parathyroid hormone-related peptide (PTHrP) production...
Ameloblastoma is a rare odontogenic tumor which may be complicated by hypercalcemia in advanced disease. Tumoral parathyroid hormone-related peptide (PTHrP) production and local osteolysis from paracrine factors have been proposed as mechanisms. Mitogen-activated protein kinase (MAPK) inhibitors have been successfully used in ameloblastomas with BRAF V600E mutation to reduce symptoms and decrease tumor burden. Serum calcium has been observed to normalize following treatment with MAPK inhibitors; however, the response of PTHrP and markers of bone turnover has not been reported. We describe a case of a 55-year-old female with PTHrP-mediated hypercalcemia secondary to BRAF V600E-positive ameloblastoma with pulmonary metastases. Following treatment with dabrafenib and trametinib, the patient experienced the regression of pulmonary lesions and normalization of serum calcium, PTHrP, and markers of bone turnover. Tissue samples of ameloblastoma carrying BRAF V600E mutation are more likely to express PTHrP than tissue samples carrying wild-type BRAF. In our case, resolution of PTHrP-mediated hypercalcemia following initiation of BRAF/MEK inhibition provides additional evidence that the MAPK pathway contributes to PTHrP synthesis. It also raises the question of whether MAPK inhibitors would be effective in treating PTHrP-mediated hypercalcemia associated with other malignancies harboring BRAF V600E mutation.
Topics: Female; Humans; Middle Aged; Parathyroid Hormone-Related Protein; Hypercalcemia; Ameloblastoma; Proto-Oncogene Proteins B-raf; Calcium; Mitogen-Activated Protein Kinase Kinases; Mutation
PubMed: 38252285
DOI: 10.1007/s00223-023-01177-x