Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies.

UNASSIGNED: Various stemness markers (SOX2, OCT4, and NANOG) have been studied in odontogenic cysts and tumors. However, studies on SALL4 having similar properties of stemness has not been documented. Additionally, insight into fascin as a migratory molecule is less explored. In this study, the expression of SALL4 and fascin were evaluated in ameloblastoma, adenomatoid odontogenic tumor (AOT), odontogenic keratocyst (OKC), dentigerous cyst (DC), radicular cyst (RC), and calcifying odontogenic cyst (COC).
UNASSIGNED: Semi-quantitative analysis of fascin and SALL4 immuno-positive cells was done in a total of 40 cases of ameloblastoma (11 plexiform, 12 follicular, 12 unicystic, and 5 desmoplastic) variants, 6 cases of AOT, 15 each of OKC, DC, RC and 5 of COC. Chi-square test was applied to evaluate the association between SALL4 and fascin expression in odontogenic cysts and tumors.
UNASSIGNED: Fascin immunopositivity was observed in peripheral ameloblast-like cells, and weak or absent in stellate reticulum-like cells. A moderate to weak immune-reactivity to SALL4 was observed in the cytoplasm of ameloblastoma, epithelial cells of dentigerous and radicular cysts, having a marked inflammatory infiltrate, which is an interesting observation. COC and AOT had negative to weak expressions. No recurrence has been reported.
UNASSIGNED: Expression of fascin in ameloblastomas elucidate their role in motility and localized invasion. Its expression in less aggressive lesions like DC, COC, AOT will incite to explore the other functional properties of fascin. SALL4 expression in the cytoplasm of odontogenic cysts and tumors may represent inactive or mutant forms which requires further validation.

Ameloblastic carcinoma is a rare malignant odontogenic tumor that is further classified into being primary or secondary arising from a preexisting benign ameloblastoma. It affects the mandible in two thirds of the patients. There is no standard treatment protocol for this lesion but radicalsurgical excision with or without radiotherapy is reported in the majority of cases. In this paper, we present a case of a 22 year old male diagnosed with Ameloblastic carcinoma of the mandible with a clinical course of typical aggressiveness and extensive destruction. Histopathological examination of the incised biopsy showed a parakeratinized stratified squamous epithelium with underlying fibrous connective tissue stroma. The stroma is highly myxomatous and exhibits islands of odontogenic epithelium and chronic inflammatory cell infiltrates. Interlacing strands of odontogenic epithelium shows stellate reticulum-like cells and occasional areas of squamous metaplasia with cellular and nuclear pleomorphism. In addition, mitotic figures were noted. With the correlation of clinical, radiographic, and histological features, the lesion is diagnosed as ameloblastic carcinoma. The lesion was surgical excised and post-treatment follow-up for 6 months revealed no recurrence of the malignancy.

Ameloblastoma is a non-cancerous but aggressive oral tumor emerging from odontogenic epithelial tissue involved during odontogenesis. Since there is lack in unravelling the complete molecular pathogenesis of ameloblastoma, chemotherapy is less attempted and a lot of disagreement over the optimal treatment option. Hence, till date, wide surgical resection is considered to be the reliable treatment for ameloblastoma. The Neurotrophin Signaling pathway plays an important role in neuron signaling and it is closely related with the MAPK pathway, which on the other hand regulated cell differentiation, apoptosis, proliferation, plasticity and survival. Protein- Protein Interaction analysis was analysed with STRING tool using WNL value, identified that CTNNB1, HRAS, NGFR, NGFR, and SORT1 having high interacting with BDNF, NT4, p75NTR, NGF, and NT3. The results of ontology analysis revealed that Neurotrophin signaling pathway is associated with Cell surface receptor signaling pathway, regulation of cell differentiation, regulation of development process, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, PI3K-Akt signaling pathway and Ras signaling pathway leading to pathogenesis involving genes. Further, clustering coefficient values of proteins BDNF, NT4, p75NTR, NGF & NT3 were identified as 0.627, 0.708, 0.367, 0.644 & 0.415. The results of molecular docking studies revealed among the selected ligands Methyl-ɣ-oresellinate, N-(4-Hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, Atranorin and Oresellinate exhibited high binding affinity with selected protein. The key genes involved in Neurotrophin signaling pathway leading to ameloblastoma pathogenesis is revealed, which are closely associated with cell differentiation, cell proliferation, pro-apoptosis, and pro-survival regulations. Further it can be concluded that Neurotrophin signaling pathway could be one of the promising pathway to tailor the targeted drug therapy for Ameloblastoma treatment.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00223-2.

UNASSIGNED: Ameloblastoma (AM) is a benign tumor locally originated from odontogenic epithelium that is commonly found in the jaw. This tumor makes aggressive invasions and has a high recurrence rate. This study aimed to investigate the differentially expressed genes (DEGs), biological function alterations, disease targets, and existing drugs for AM using bioinformatics analysis.
UNASSIGNED: The data set of AM was retrieved from the GEO database (GSE132474) and identified the DEGs using bioinformatics analysis. The biological alteration analysis was applied to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-protein interaction (PPI) network analysis and hub gene identification were screened through NetworkAnalyst. The transcription factor-protein network was constructed via OmicsNet. We also identified candidate compounds from L1000CDS2 database. The target of AM and candidate compounds were verified using docking simulation.
UNASSIGNED: Totally, 611 DEGs were identified. The biological function enrichment analysis revealed glycosaminoglycan and GABA (γ-aminobutyric acid) signaling were most significantly up-regulated and down-regulated in AM, respectively. Subsequently, hub genes and transcription factors were screened via the network and showed FOS protein was found in both networks. Furthermore, we evaluated FOS protein to be a therapeutic target in AMs. Candidate compounds were screened and verified using docking simulation. Tanespimycin showed the greatest affinity binding value to bind FOS protein.
UNASSIGNED: This study presented the underlying molecular mechanisms of disease pathogenesis, biological alteration, and important pathways of AMs and provided a candidate compound, Tanespimycin, targeting FOS protein for the treatment of AMs.

UNASSIGNED: Ameloblastoma is one of the major odontogenic neoplasms with an invasive and recurrence potential. Its tumourigenesis and proliferative capacity can be attributed to the activation or inactivation of certain molecular signalling pathways. Hippo signalling pathway is known to regulate diverse physiological processes related to mitosis and organ growth and is an emerging tumour suppressor pathway, the dysfunction of which is implicated in various diseases including cancers. Yes-associated protein1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the downstream effectors in the Hippo cascade, which on nuclear activation leads to cellular proliferation in various tumours.
UNASSIGNED: The current study was undertaken to evaluate the expression of YAP in various histopathological variants of ameloblastoma and unicystic ameloblastoma.
UNASSIGNED: Fifty formalin-fixed paraffin-embedded tissue samples of histopathologically diagnosed cases of ameloblastoma, and 10 histopathologically diagnosed cases of unicystic ameloblastoma were obtained from the departmental archives to evaluate the immunohistochemical expression of YAP both manually and by software analysis.
UNASSIGNED: More than 90% of cases of conventional ameloblastoma and unicystic ameloblastoma elicited positive expression of YAP. No statistical difference was found among different histopathological variants of conventional ameloblastoma. Significant difference between the means of all four quantitative score groups was observed.
UNASSIGNED: In view of the modulating effect of YAP in tumourigenesis and its higher expression in ameloblastoma, further exploration of this molecule appears to be a promising area of research.

UNASSIGNED: Glucose uptake may be considered the rate-limiting step for the growth and metabolism of the cancer cell. Studies on GLUT1 have shown that GLUT1 is involved in cell survival and proliferation in both healthy and pathological circumstances. GLUT1 expression is regarded as one of the crucial elements in the development of local aggressiveness, tumour invasiveness, and metastasis, particularly in malignant tumours. The role of glut1 in odontogenic cysts and tumours has remained uncertain.
UNASSIGNED: The aim of the study is to assess the expression of Glut1 in dentigerous cysts, odontogenic keratocysts, and ameloblastoma.
UNASSIGNED: The study was conducted in GSL Dental College. The study design was a resprospective immunohistochemical study.
UNASSIGNED: Formalin-fixed, paraffin-embedded blocks of histologically confirmed cases (n = 50), 10 cases of odontogenic keratocysts, dentigerous cysts, ameloblastomas solid, ameloblastomas unicystic, and dental follicles each. Brown colour staining was considered as positive staining for GLUT1. Quantitative analysis was performed by counting the number of labelled cells, and semi-quantitative analysis was conducted by assigning immunostaining intensity scores.
UNASSIGNED: Chi-square test was used to compare differences between the groups. A P value of ≤0.05 was considered as statistically significant.
UNASSIGNED: Odontogenic keratocysts and unicystic ameloblastoma showed ≥50% of label cells with strong intensity of staining. Odontogenic keratocysts and solid ameloblastoma showed sub-cellular localisation of staining in the cytoplasm and membrane. Dentigerous cysts exhibited combined nucleus, cytoplasm, and membrane sub-cellular localisation of staining.
UNASSIGNED: The development of ameloblastomas, odontogenic keratocysts, and dentigerous cysts appears to be influenced by GLUT-1. Variation in its expression may aid in explanation of some of the differences in biological activity of these lesions.

UNASSIGNED: To explore the feasibility and effectiveness of mixed reality technology for localizing perforator vessels in the repair of mandibular defects using free fibular flap.
UNASSIGNED: Between June 2020 and June 2023, 12 patients with mandibular defects were repaired with free fibular flap. There were 8 males and 4 females, with an average age of 61 years (range, 35-78 years). There were 9 cases of ameloblastomas and 3 cases of squamous cell carcinomas involving the mandible. The disease duration ranged from 15 days to 2 years (median, 14.2 months). The length of mandibular defects ranged from 5 to 14 cm (mean, 8.5 cm). The area of soft tissue defects ranged from 5 cm×4 cm to 8 cm×6 cm. Preoperative enhanced CT scans of the maxillofacial region and CT angiography of the lower limbs were performed, and the data was used to create three-dimensional models of the mandible and lower limb perforator vessels. During operation, the mixed reality technology was used to overlay the three-dimensional model of perforator vessels onto the body surface for harvesting the free fibular flap. The length of the fibula harvested ranged from 6 to 15 cm, with a mean of 9.5 cm; the size of the flap ranged from 6 cm×5 cm to 10 cm×8 cm. The donor sites were sutured directly in 7 cases and repaired with free skin grafting in 5 cases.
UNASSIGNED: Thirty perforator vessels were located by mixed reality technology before operation, with an average of 2.5 vessels per case; the distance between the exit point of the perforator vessels located before operation and the actual exit point ranged from 1 to 4 mm, with a mean of 2.8 mm. All fibular flaps survived; 1 case had necrosis at the distal end of flap, which healed after dressing changes. One donor site had infection, which healed after anti-inflammatory dressing changes; the remaining incisions healed by first intention, and the grafts survived smoothly. All patients were followed up 8-36 months (median, 21 months). The repaired facial appearance was satisfactory, with no flap swelling. Among the patients underwent postoperative radiotherapy, 2 patients had normal bone healing and 1 had delayed healing at 6 months.
UNASSIGNED: In free fibular flap reconstruction of mandibular defects, the use of mixed reality technology for perforator vessel localization can achieve three-dimensional visualization, simplify surgical procedures, and reduce errors.
UNASSIGNED: 探讨在游离腓骨皮瓣修复下颌骨缺损中，使用混合现实技术定位穿支血管的可行性和效果。.
UNASSIGNED: 2020年6月—2023年6月，采用游离腓骨皮瓣修复12例下颌骨缺损患者。男8例，女4例；年龄35～78岁，平均61岁。下颌骨成釉细胞瘤9例，侵犯下颌骨口腔鳞癌3例。病程15 d～2年，中位病程14.2个月。下颌骨缺损长度5～14 cm，平均8.5 cm；软组织缺损范围为5 cm×4 cm～8 cm×6 cm。术前均行颌面部增强CT和下肢CT血管造影检查，将所得数据制成下颌骨、下肢穿支血管三维模型。术中使用混合现实技术将穿支血管三维模型重叠于患者体表，制取游离腓骨皮瓣修复缺损。腓骨切取长度为6～15 cm，平均9.5 cm；皮瓣切取范围6 cm×5 cm～10 cm×8 cm，供区拉拢缝合（7例）或游离植皮修复（5例）。.
UNASSIGNED: 12例患者术前使用混合现实技术定位穿支血管30支，每例平均2.5支；术中测量术前定位穿支血管穿出点与实际穿出点距离为1～4 mm，平均2.8 mm。术后12例腓骨瓣顺利成活；1例皮瓣远端边缘坏死，换药后延期愈合。供区发生感染1例，经抗炎换药治疗后愈合；其余患者切口Ⅰ期愈合，植皮顺利成活。患者均获随访，随访时间8～36个月，中位时间21个月。修复面部外形好，皮瓣无臃肿。3例术后接受放化疗患者中，随访6个月时2例正常骨愈合、1例延迟愈合。.
UNASSIGNED: 在游离腓骨皮瓣修复下颌骨缺损手术中使用混合现实技术，可以实现穿支血管三维可视化，手术操作简便，误差较小。.

Odontogenic tumors (OTs) are distinct conditions that develop in the jawbones, exhibiting diverse histopathological features and variable clinical behaviors. Unfortunately, the literature on this subject in Saudi Arabia remains sparse, indicating a pressing need for more comprehensive data concerning the frequency, demographics, treatment modalities, and outcomes of OTs.
OBJECTIVE: The study aims to evaluate the frequency, demographic features, treatment, and outcomes of OTs across three tertiary medical centers.
METHODS: OT cases were identified in King Abdulaziz Medical City (KAMC), King Fahad Medical City (KFMC), and Prince Sultan Military Medical City (PSMMC) from January 2010 to December 2021.
RESULTS: Ninety-two OT cases were identified from the anatomical pathology laboratories of three tertiary hospitals. KFMC contributed the highest number of cases (43.5%), followed by KAMC (30.4%) and PSMMC (26.1%). The median age of OT patients was 29 years (range: 5-83), with males representing more than half of the patients (56.5%). The mandible was the most frequent site of OT occurrence (72.5%), with ameloblastoma being the predominant OT (63.0%), followed by odontoma (19.5%). Among the treatment modalities, bone resection was employed the most (51.0%), followed by enucleation (25.6%). Notably, 11.5% of OT cases with available follow-up data exhibited recurrence, with ameloblastoma accounting for eight recurrent cases.
CONCLUSIONS: Although OTs are relatively common in the jaws, they are rare in anatomical pathology laboratories and the general population. This study contributes valuable insights into the epidemiology characteristics, treatment trends, and recurrence rates of OTs in Saudi Arabia.

BACKGROUND: Odontogenic lesions constitute a heterogeneous group of lesions. CLIC4 protein regulates different cellular processes, including epithelial-mesenchymal transition and fibroblast-myofibroblast transdifferentiation. This study analyzed CLIC4, E-cadherin, Vimentin, and α-SMA immunoexpression in epithelial odontogenic lesions that exhibit different biological behavior.
METHODS: It analyzed the immunoexpression of CLIC4, E-cadherin, and Vimentin in the epithelial cells, as well as CLIC4 and α-SMA in the mesenchymal cells, of ameloblastoma (AM) (n = 16), odontogenic keratocyst (OKC) (n = 20), and adenomatoid odontogenic tumor (AOT) (n = 8). Immunoexpressions were categorized as score 0 (0% positive cells), 1 (< 25%), 2 (≥ 25% - < 50%), 3 (≥ 50% - < 75%), or 4 (≥ 75%).
RESULTS: Cytoplasmic CLIC4 immunoexpression was higher in AM and AOT (p < 0.001) epithelial cells. Nuclear-cytoplasmic CLIC4 was higher in OKC\'s epithelial lining (p < 0.001). Membrane (p = 0.012) and membrane-cytoplasmic (p < 0.001) E-cadherin immunoexpression were higher in OKC, while cytoplasmic E-cadherin expression was higher in AM and AOT (p < 0.001). Vimentin immunoexpression was higher in AM and AOT (p < 0.001). Stromal CLIC4 was higher in AM and OKC (p = 0.008). Similarly, α-SMA immunoexpression was higher in AM and OKC (p = 0.037). Correlations in these proteins\' immunoexpression were observed in AM and OKC (p < 0.05).
CONCLUSIONS: CLIC4 seems to regulate the epithelial-mesenchymal transition, modifying E-cadherin and Vimentin expression. In mesenchymal cells, CLIC4 may play a role in fibroblast-myofibroblast transdifferentiation. CLIC4 may be associated with epithelial odontogenic lesions with aggressive biological behavior.