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Journal of Oral Pathology & Medicine :... May 2024Ameloblastoma (AM) is a benign, although aggressive, epithelial odontogenic tumour originating from tooth-forming tissues or remnants. Its aetiopathogenesis remains... (Review)
Review
Ameloblastoma (AM) is a benign, although aggressive, epithelial odontogenic tumour originating from tooth-forming tissues or remnants. Its aetiopathogenesis remains unclear; however, molecular analysis techniques have allowed researchers to progress in understanding its genetic basis. The high frequency of BRAF p.V600E as a main driver mutation in AM is well established; nevertheless, it is insufficient to explain its tumourigenesis. In this review, we aimed to integrate the current knowledge about the biology of AM and to describe the main genetic alterations reported, focusing on the findings of large-scale sequencing and gene expression profiling techniques. Current evidence shows that besides BRAF mutation and activation of the MAPK pathway, alterations in Hedgehog and Wnt/β-catenin pathway-related genes are also involved in AM pathogenesis. Recently, a tumour suppressor gene, KMT2D, has been reported as mutated by different research groups. The biological impact of these mutations in the pathogenesis of AM has yet to be elucidated. Further studies are needed to clarify the impact of these findings in the identification of novel biomarkers that could be useful for diagnosing, classifying, and molecular targeting this neoplasm.
Topics: Ameloblastoma; Humans; Mutation; Proto-Oncogene Proteins B-raf; Jaw Neoplasms; Wnt Signaling Pathway; Hedgehog Proteins; Gene Expression Profiling
PubMed: 38664938
DOI: 10.1111/jop.13538 -
Hormones (Athens, Greece) Mar 2024Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH)... (Review)
Review
Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH) concentrations, may occur as part of a hereditary syndromic disorder or as a non-syndromic disease. The associated syndromic disorders include multiple endocrine neoplasia types 1-5 (MEN1-5) and hyperparathyroidism with jaw tumor (HPT-JT) syndromes, and the non-syndromic forms include familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), familial isolated hyperparathyroidism (FIHP), and neonatal severe hyperparathyroidism (NS-HPT). Such hereditary forms may occur in > 10% of patients with PHPT, and their recognition is important for implementation of gene-specific screening protocols and investigations for other associated tumors. Syndromic PHPT tends to be multifocal and multiglandular with most patients requiring parathyroidectomy with the aim of limiting end-organ damage associated with hypercalcemia, particularly osteoporosis, nephrolithiasis, and renal failure. Some patients with non-syndromic PHPT may have mutations of the MEN1 gene or the calcium-sensing receptor (CASR), whose loss of function mutations usually cause FHH1, a disorder associated with mild hypercalcemia and may follow a benign clinical course. Measurement of the urinary calcium-to-creatinine ratio clearance (UCCR) may help to distinguish patients with FHH from those with PHPT, as the majority of FHH patients have low urinary calcium excretion (UCCR < 0.01). Once genetic testing confirms a hereditary cause of PHPT, further genetic testing can be offered to the patients' relatives and subsequent screening can be carried out in these affected family members, which prevents inappropriate testing in normal individuals.
Topics: Infant, Newborn; Humans; Hyperparathyroidism, Primary; Calcium; Hypercalcemia; Adenoma; Fibroma; Hyperparathyroidism; Jaw Neoplasms
PubMed: 38038882
DOI: 10.1007/s42000-023-00508-9 -
Oral and Maxillofacial Surgery Clinics... Aug 2024Pediatric odontogenic cysts and tumors are rare and often associated with developing or impacted teeth. Odontogenic cysts are broadly categorized as inflammatory or... (Review)
Review
Pediatric odontogenic cysts and tumors are rare and often associated with developing or impacted teeth. Odontogenic cysts are broadly categorized as inflammatory or developmental while odontogenic tumors are classified histologically as epithelial, mesenchymal, or mixed tumors. This article will discuss the presentation, diagnosis, and treatment of odontogenic cysts and tumors in the pediatric population.
Topics: Humans; Odontogenic Cysts; Child; Odontogenic Tumors; Diagnosis, Differential; Jaw Neoplasms
PubMed: 38462396
DOI: 10.1016/j.coms.2024.01.006 -
Journal of Cranio-maxillo-facial... Oct 2023The 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... (Review)
Review
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.
Topics: Humans; Jaw Neoplasms; Cherubism; Quality of Life; Odontogenic Tumors; Ameloblastoma
PubMed: 37852890
DOI: 10.1016/j.jcms.2023.10.003 -
Oral and Maxillofacial Surgery Clinics... Nov 2019Benign cysts and neoplasms of the maxillofacial region can vary in behavior, with some growing rapidly and resulting in destruction of surrounding structures. Despite... (Review)
Review
Benign cysts and neoplasms of the maxillofacial region can vary in behavior, with some growing rapidly and resulting in destruction of surrounding structures. Despite their benign histology, many require often-morbid treatment to prevent recurrence of these lesions. Several less invasive and adjunctive medical treatments have been developed to lessen the morbidity of surgical treatment. As the molecular and genomic pathogenesis of these lesions is better understood, more directed treatments may lessen the burden for patients.
Topics: Ameloblastoma; Humans; Jaw Neoplasms; Neoplasm Recurrence, Local; Odontogenic Cysts; Pathology, Oral
PubMed: 31427192
DOI: 10.1016/j.coms.2019.07.002 -
Journal of Stomatology, Oral and... Feb 2023
Topics: Humans; Palatal Neoplasms
PubMed: 36241159
DOI: 10.1016/j.jormas.2022.10.005 -
Journal of Surgical Oncology Aug 2019Sarcomas of the mandible are extremely rare tumors, with osteosarcoma being the most common, followed by Ewing's sarcoma MATERIALS AND METHODS: A retrospective review of...
INTRODUCTION
Sarcomas of the mandible are extremely rare tumors, with osteosarcoma being the most common, followed by Ewing's sarcoma MATERIALS AND METHODS: A retrospective review of the clinical records, imaging studies, and pathology slides of patients with sarcoma of the mandible at a Tertiary Care Cancer Center from 1998 to 2014 was undertaken. The impact of neoadjuvant chemotherapy and postoperative radiotherapy with or without chemotherapy was studied, and factors impacting upon local control and disease-specific survival were analyzed.
RESULTS
Twenty-two patients were treated over the study period, comprising of 15 males and seven females. External swelling, intraoral growth, or facial numbness were the presenting symptoms. Eighteen patients had osteosarcoma and four had the Ewing's sarcoma. Nine patients received neoadjuvant chemotherapy. All but one patient underwent surgery. Eleven had negative margins, with 90% recurrence-free survival at 3 years, compared to 10 with positive or close margins, leading to 67% recurrence-free survival. None of the patients receiving neoadjuvant chemotherapy developed recurrence and all were alive at 3 years. The impact of postoperative radiotherapy or adjuvant chemotherapy was not statistically significant.
CONCLUSIONS
Wide surgical resection with negative margins remains the hallmark of surgical treatment.
Topics: Adolescent; Adult; Aged; Child; Combined Modality Therapy; Female; Humans; Male; Mandibular Neoplasms; Margins of Excision; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Sarcoma; Survival Rate; Young Adult
PubMed: 30993699
DOI: 10.1002/jso.25477 -
La Revue Du Praticien May 2024
Topics: Humans; Ameloblastoma; Jaw Neoplasms
PubMed: 38833232
DOI: No ID Found -
Journal of the College of Physicians... Jan 2020
Topics: Adult; Humans; Male; Mandibular Neoplasms; Odontogenic Cysts; Radiography, Panoramic; Treatment Outcome
PubMed: 31931946
DOI: 10.29271/jcpsp.2020.01.104 -
International Journal of Molecular... Jun 2022The gene, a defect which causes hyperparathyroidism-jaw tumor (HPT-JT) syndrome, encodes CDC73/parafibromin. We aimed to investigate whether CDC73 would be a target for...
The gene, a defect which causes hyperparathyroidism-jaw tumor (HPT-JT) syndrome, encodes CDC73/parafibromin. We aimed to investigate whether CDC73 would be a target for ubiquitin-proteasome degradation. We cloned full-length cDNAs encoding a family of 58 ubiquitin-specific deubiquitinating enzymes (DUBs), also known as ubiquitin-specific proteases (USPs). Use of the yeast two-hybrid system then enabled us to identify USP37 as interacting with CDC73. The biochemical interaction between the USP37 and CDC73 and their reciprocal binding domains were studied. Co-localization of CDC73 and USP37 was observed in cells. CDC73 was found to be polyubiquitinated, and polyubiquitination of CDC73 was prominent in mutants. CDC73 was deubiquitinated via K48-specific ubiquitin chains by USP37, but not by the catalytically inactive USP37 mutant. Observation of the binding between deletion mutants of CDC73 and USP37 revealed that the β-catenin binding site of CDC73 and the ubiquitin-interacting motifs 2 and 3 (UIM2 and 3) of USP37 were responsible for the interaction between the two proteins. Moreover, these two enzymes co-existed within the nucleus of COS7 cells. We conclude that USP37 is a DUB for CDC73 and that the two proteins interact through specific domains, suggesting that USP37 is responsible for the stability of CDC73 in HPT-JT syndrome.
Topics: Adenoma; Endopeptidases; Fibroma; Humans; Hyperparathyroidism; Jaw Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Ubiquitins
PubMed: 35742816
DOI: 10.3390/ijms23126364