Materiały źródłowe

• #1 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  Ameloblastoma is the second most common benign epithelial odontogenic tumor and though it is of a benign nature, it is locally invasive, has a high recurrence rate and could potentially become malignant. […] Many theories have been proposed to explain the pathogenesis of ameloblastoma. Proper understanding of the pathogenic mechanism involved in ameloblastoma and its proliferation aids in constituting proper treatment of choice at an early stage, preventing morbidity associated with extensive therapy. […] Numerous studies have been found to explain the molecular pathogenesis of ameloblastoma. Every cellular change, including proliferation, differentiation and tumorigenesis occurs through the activation or inactivation of the related molecular signaling pathways. The important signaling molecules are either overexpressed or underexpressed during tumorigenesis of ameloblastomas.

• #2

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Ameloblastomas are usually benign, locally aggressive neoplasms derived from the epithelial odontogenic tissues. […] Different mechanisms have been proposed to explain the mechanism behind the pathogenesis of ameloblastoma. The proper understanding of the pathogenetic mechanism involved in ameloblastoma and its proliferation, aids in constituting proper treatment. […] The molecular and genetic characteristics of ameloblastomas are poorly understood and the origin of the tumor is still unclear. The cloning and characterization of expression of the ameloblastin and amelogenin genes in these tumors suggests that ameloblastoma arise from the odontogenic apparatus or cells that are potentially capable of forming dental tissue. […] In the pathogenesis of ameloblastoma different factors have been found to play a role and they potentiate their action through different mechanisms.

• #3 Ameloblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545165/

  The cause of ameloblastoma is not well understood. There is recent evidence that genetic mutations that activate a specific signaling pathway (MAPK) play a role in the pathogenesis of ameloblastoma. […] Further understanding of the molecular basis of tumorigenesis will have implications for diagnosis and therapy.

• #4 Ameloblastoma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Ameloblastoma_pathophysiology

  Ameloblastoma arise from remnants of ameloblast or dental lamina, dentigerous cysts, or basal layer of oral mucosa. […] There is evidence that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro. […] There is also some research suggesting that 51 integrin may participate in the local invasiveness of ameloblastomas. […] The ameloblastoma is an ectodermal odontogenic tumor of the jaw which apparently originates from the Malassez rests in the periodontium, from the gingival epithelium, from the enamel organs, or from ordinary dental cysts (dentigerous cysts, follicular cysts, or radicular cysts). […] Genes involved in the pathogenesis of ameloblastoma include BRAF V600E.

• #5 Ameloblastoma | PPT

  https://www.slideshare.net/slideshow/ameloblastoma-69909552/69909552

  1) Ameloblastoma is believed to be derived from a) Cell rest of enamel organ, either remnants of dental lamina or Hertwigs sheath, the epithelial rest of Malassez. b) Epithelium of odontogenic cysts, particularly the Dentigerous cyst odontomas. c) Disturbance to developing enamel organ. d) Basal cells of the surface epithelium of the jaws. e) Heteropic epithelium in other parts of body especially the pituitary gland. PATHOGENESIS […] 10) Ameloblastoma is believed to be derived from a) Cell rest of enamel organ, either remnants of dental lamina or Hertwigs sheath, the epithelial rest of Malassez. b) Epithelium of odontogenic cysts, particularly the Dentigerous cyst odontomas. c) Disturbance to developing enamel organ. d) Basal cells of the surface epithelium of the jaws. e) Heteropic epithelium in other parts of body especially the pituitary gland. PATHOGENESIS

• #6 Ameloblastoma | SpringerLink

  https://link.springer.com/10.1007/978-3-319-28085-1_653

  The ameloblastoma is believed to originate from the remnants of dental lamina, the developing enamel organ, the epithelial lining of odontogenic cysts, or the basilar epithelial cells of the gingival surface epithelium. […] The tumor exhibits a microscopic resemblance to the enamel organ of a developing tooth. Specifically, the tumor epithelial cells may mimic the inner enamel epithelium and stellate reticulum of the enamel organ. […] Expression and alterations of the PTEN/AKT/mTOR pathway in ameloblastomas. […] Aberrant beta-catenin expression and adenomatous polyposis coli gene mutation in ameloblastoma and odontogenic carcinoma.

• #7 Contemporary Treatment of Ameloblastoma | Pocket Dentistry

  https://pocketdentistry.com/contemporary-treatment-of-ameloblastoma/

  Ameloblastoma is the most common benign tumor of the jaws, comprising approximately 10% of odontogenic tumors and 1% of all cysts and tumors. […] Due to the historically high recurrence rates and potential for local destruction and locally uncontrollable disease, a thorough understanding of the pathogenesis and clinical behavior of ameloblastoma is imperative for the oral and maxillofacial surgeon. […] The ameloblastoma arises from odontogenic ectoderm. Malassez suggested that it arose from epithelial remnants of the developing root sheath. However, the causes of ameloblastoma are largely unknown. […] Presumptive factors causing local inflammation, such as tooth extraction, caries, infection, calculus, developing teeth, trauma, nutritional deficiencies, and viruses, have been investigated; however, no direct causative correlation exists.

• #8

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Ameloblastomas are usually benign, locally aggressive neoplasms derived from the epithelial odontogenic tissues. […] Different mechanisms have been proposed to explain the mechanism behind the pathogenesis of ameloblastoma. The proper understanding of the pathogenetic mechanism involved in ameloblastoma and its proliferation, aids in constituting proper treatment. […] The molecular and genetic characteristics of ameloblastomas are poorly understood and the origin of the tumor is still unclear. The cloning and characterization of expression of the ameloblastin and amelogenin genes in these tumors suggests that ameloblastoma arise from the odontogenic apparatus or cells that are potentially capable of forming dental tissue. […] In the pathogenesis of ameloblastoma different factors have been found to play a role and they potentiate their action through different mechanisms.

• #9 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  The molecular and genetic alterations that occur in ameloblastoma would be discussed in this review which is helpful for better treatment and prognosis. […] Various signaling pathways have been identified to explain the pathogenesis of ameloblastoma. Sonic Hedgehog (SHH), a mammalian homolog of drosophila segment polarity gene Hedgehog, encodes a secreted protein that activates a membrane receptor complex formed by patched 1 (PCTH 1) and smoothened (SMO). […] High expression of SHH, SMO and GLi 1 was reported in ameloblastoma. […] Studies suggested that SHH signaling molecules may play a role in epithelial-mesenchymal interaction and cell proliferation in ameloblastoma. […] WNT genes encode a family of glycoproteins, first identified in mammals as proto-oncogenic integration site for mouse mammary tumor virus. These proteins activate a number of signaling pathways that are divided into two categories: Canonical -catenin pathway and noncanonical -catenin independent pathway.

• #10 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Ameloblastomas are benign odontogenic tumors of epithelial origin, uncommon, locally aggressive and being able to reach large sizes. […] In 2014 important studies on the genetics of ameloblastomas were published. Crucial to its etiopathogenesis and understanding, these studies identified highly recurrent mutations in mitogen-activated protein kinase (MAPK) and Hedgehog (SHH) signaling pathways. […] The etiologic factors described relate to the onset of the lesion after a local trauma, inflammation, nutritional deficiencies, mutations and/or molecular alterations, where different signaling pathways participate. More recent theories indicate the existence of genetic anomalies related to the appearance of ameloblastomas, enabling less aggressive treatments. […] Currently, there are targeted therapies due to recent advances in the understanding of the molecular signaling pathways associated with ameloblastoma pathogenesis. MAPK-specific drugs (Mitogen-Activated Protein Kinases) selectively inhibit the functions of BRAF (B-Raf proto-oncogene) and MEK mutants to stop the deregulated proliferation and differentiation of ameloblastic cells.

• #11 Frontiers | Genetic Profile of Adenomatoid Odontogenic Tumor and Ameloblastoma. A Systematic Review

  https://www.frontiersin.org/journals/oral-health/articles/10.3389/froh.2021.767474/full

  The available genetic data reports that AOTs and AM harbor somatic mutations in well-known oncogenes, being KRAS G12V/R and BRAFV600E mutations the most common, respectively. […] Different genomic alterations, which includes chromosomal imbalances and genetic mutations, have been reported to be present in ameloblastomas. Mutations in genes that belong to the mitogen-activated protein kinase (MAPK) pathway are present in almost 90% of ameloblastomas, with BRAF V600E, being the most described mutation. […] The relatively high frequency of ameloblastoma compared to other odontogenic tumors, such as AOT, has facilitated the performance of different sequencing techniques, allowing the discovery of different mutational signatures. […] The presence of other mutational signatures with clinical impact, co-occurring with background KRAS mutations or in wild-type KRAS cases, cannot be ruled out.

• #12 Anti-MAPK Targeted Therapy for Ameloblastoma: Case Report with a Systematic Review

  https://www.mdpi.com/2072-6694/16/12/2174

  Ameloblastoma is a benign odontogenic tumor that originates from odontogenic epithelium. Although benign, it is a locally aggressive neoplasm that has a strong tendency to recur and may metastasize to distant sites. In 2014, three independent studies were published about the genetic profiling of ameloblastomas via DNA sequencing and all three studies showed a high incidence of somatic mutations impacting the mitogen-activated protein kinase (MAPK) that controls cell proliferation. A specific mutation, BRAF V600E, was reported at high frequencies. BRAF is a serine–threonine kinase within the MAPK pathway. This mutation constitutively initiates the mitogen-activated kinase pathway and thus enhances cell proliferation and survival activity in a ligand-independent manner. More interestingly, if a BRAF mutation is present, it tends to be exclusive regarding other mutations also present in ameloblastoma, making BRAF the most frequent genetic alteration and closely associated with its pathogenesis. 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. The MAPK pathway seems to be the keystone to targeting.

• #13 Perspective Chapter: Ameloblastoma – Present and Future Concepts of Managing | IntechOpen

  https://www.intechopen.com/chapters/83748

  Ameloblastomas belong to benign odontogenic tumors with locally aggressive behavior. […] In addition, recent literature has provided us with breakthrough in the understanding of genetic mutations and signaling pathways crucial in ameloblastoma pathogenesis. […] As the genetic understanding increased, valuable findings have been brought to light regarding molecular pathogenesis of ameloblastoma. In 2014, it was confirmed that recurrent somatic and activating mutations in the mitogen-activated protein kinase (MAPK) plays a prominent role in the pathogenesis of the disease. […] Together, all the mentioned mutations are present in vast majority of ameloblastomas, suggesting that activation of the MAPK signaling pathway represents a critical event in the pathogenesis of ameloblastoma. […] Several non-MAPK mutations have also been associated with ameloblastoma. The most important is nonclassical G protein-coupled receptor, the smoothened (SMO) gene. […] The main identified mutations are found in MAPK and SHH signaling pathways. These include BRAF, RAS and FGFR2 genes from MAPK pathway and SMO gene from SHH signaling pathway.

• #14 Ameloblastoma: brief review of molecular pathogenesis and history

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=115385

  Ameloblastoma is a progressively growing benign intraosseous epithelial odontogenic odontogenic neoplasm characterized by local invasion and a tendency to recur if not adequately removed. […] Although the pathogenesis of ameloblastoma is controversial, several authors have invoked numerous theories to elucidate the development and behavior of these tumors. […] Recently, studies have increasingly focused on the molecular aspects of ameloblastoma pathogenesis to identify potential therapeutic targets. […] However, the molecular background of ameloblastoma development remains unclear. […] The presence or absence of mutations correlates with several clinicopathologic features, including location, age at diagnosis, histology, and prognosis. […] Further studies are needed to verify these theories.

• #15 Anti-MAPK Targeted Therapy for Ameloblastoma: Case Report with a Systematic Review

  https://www.mdpi.com/2072-6694/16/12/2174

  Ameloblastoma is a benign odontogenic tumor that originates from odontogenic epithelium. Although benign, it is a locally aggressive neoplasm that has a strong tendency to recur and may metastasize to distant sites. In 2014, three independent studies were published about the genetic profiling of ameloblastomas via DNA sequencing and all three studies showed a high incidence of somatic mutations impacting the mitogen-activated protein kinase (MAPK) that controls cell proliferation. A specific mutation, BRAF V600E, was reported at high frequencies. BRAF is a serine–threonine kinase within the MAPK pathway. This mutation constitutively initiates the mitogen-activated kinase pathway and thus enhances cell proliferation and survival activity in a ligand-independent manner. More interestingly, if a BRAF mutation is present, it tends to be exclusive regarding other mutations also present in ameloblastoma, making BRAF the most frequent genetic alteration and closely associated with its pathogenesis. 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. The MAPK pathway seems to be the keystone to targeting.

• #16 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  The molecular and genetic alterations that occur in ameloblastoma would be discussed in this review which is helpful for better treatment and prognosis. […] Various signaling pathways have been identified to explain the pathogenesis of ameloblastoma. Sonic Hedgehog (SHH), a mammalian homolog of drosophila segment polarity gene Hedgehog, encodes a secreted protein that activates a membrane receptor complex formed by patched 1 (PCTH 1) and smoothened (SMO). […] High expression of SHH, SMO and GLi 1 was reported in ameloblastoma. […] Studies suggested that SHH signaling molecules may play a role in epithelial-mesenchymal interaction and cell proliferation in ameloblastoma. […] WNT genes encode a family of glycoproteins, first identified in mammals as proto-oncogenic integration site for mouse mammary tumor virus. These proteins activate a number of signaling pathways that are divided into two categories: Canonical -catenin pathway and noncanonical -catenin independent pathway.

• #17 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  The molecular and genetic alterations that occur in ameloblastoma would be discussed in this review which is helpful for better treatment and prognosis. […] Various signaling pathways have been identified to explain the pathogenesis of ameloblastoma. Sonic Hedgehog (SHH), a mammalian homolog of drosophila segment polarity gene Hedgehog, encodes a secreted protein that activates a membrane receptor complex formed by patched 1 (PCTH 1) and smoothened (SMO). […] High expression of SHH, SMO and GLi 1 was reported in ameloblastoma. […] Studies suggested that SHH signaling molecules may play a role in epithelial-mesenchymal interaction and cell proliferation in ameloblastoma. […] WNT genes encode a family of glycoproteins, first identified in mammals as proto-oncogenic integration site for mouse mammary tumor virus. These proteins activate a number of signaling pathways that are divided into two categories: Canonical -catenin pathway and noncanonical -catenin independent pathway.

• #18

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Genes involved in the initiation of tooth development, morphogenesis, and cytodifferentiation and tooth patterning include, sonic hedgehog (SHH), patched (PTCH), WNT, activin A, bone morphogenetic proteins (BMP2 and BMP4), fibroblast-growth-factor (FGF), PAX9, BARX1, LEF1, DLX1, DLX2, MSX1, and MSX2. […] The transmembrane receptor for Sonic Hedgehog (SHH) and other Hedgehog proteins (HH) is coded by the PTCH1 gene. […] A high expression of SHH, SMO and GLI protein was reported in ameloblastoma. […] Nuclear accumulation of catenin was demonstrated in ameloblastomas. […] The loss of Syndecan-1 indicates unfavorable prognosis in epithelial tumors. The decreased expression of Syndecan-1 was seen in ameloblastomas which could attribute to the aggressive behavior of the tumor. […] PTEN protein functions as an inhibitor of Akt signaling pathway, leading to cell cycle arrest and apoptosis. Its expression was reduced in ameloblastomas compared with teeth germs.

• #19 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  The molecular and genetic alterations that occur in ameloblastoma would be discussed in this review which is helpful for better treatment and prognosis. […] Various signaling pathways have been identified to explain the pathogenesis of ameloblastoma. Sonic Hedgehog (SHH), a mammalian homolog of drosophila segment polarity gene Hedgehog, encodes a secreted protein that activates a membrane receptor complex formed by patched 1 (PCTH 1) and smoothened (SMO). […] High expression of SHH, SMO and GLi 1 was reported in ameloblastoma. […] Studies suggested that SHH signaling molecules may play a role in epithelial-mesenchymal interaction and cell proliferation in ameloblastoma. […] WNT genes encode a family of glycoproteins, first identified in mammals as proto-oncogenic integration site for mouse mammary tumor virus. These proteins activate a number of signaling pathways that are divided into two categories: Canonical -catenin pathway and noncanonical -catenin independent pathway.

• #20 Sonic Hedgehog Flagging Pathway and Ameloblastoma

  https://www.longdom.org/open-access/sonic-hedgehog-flagging-pathway-and-ameloblastoma-77105.html

  Various examinations have been found to clarify the sub-atomic pathogenesis of ameloblastoma. Cell changes jak expansion, separation, senescence, tumourigenesis i tak dalej happen through the actywacja or inactivation of related atomic signalling pathways. […] Clonality, cell cycle expansion, apoptosis, tumor silencer qualities, osteoclastic komponenty i system metalloproteinases i różne flagging pathways are the proposes used to clarify the pathogenesis of ameloblastoma. […] Articulation of SHH flagging pathway has been reported in various odontogenic pimples and tumors. […] They proposed that SHH flagging atoms may assume a part in epithelial-mesenchymal collaboration i cell multiplication in ameloblastoma. […] Pathogenesis of ameloblastoma is multifactorial and includes various cell pathways. SHH pathway, which assumes a definitive part in the turn of events i designing of różnych organs, is fundamental in odontogenesis i również assumes an essential part in the pathogenesis of ameloblastoma.

• #21 Sonic Hedgehog Flagging Pathway and Ameloblastoma

  https://www.longdom.org/open-access/sonic-hedgehog-flagging-pathway-and-ameloblastoma-77105.html

  Various examinations have been found to clarify the sub-atomic pathogenesis of ameloblastoma. Cell changes jak expansion, separation, senescence, tumourigenesis i tak dalej happen through the actywacja or inactivation of related atomic signalling pathways. […] Clonality, cell cycle expansion, apoptosis, tumor silencer qualities, osteoclastic komponenty i system metalloproteinases i różne flagging pathways are the proposes used to clarify the pathogenesis of ameloblastoma. […] Articulation of SHH flagging pathway has been reported in various odontogenic pimples and tumors. […] They proposed that SHH flagging atoms may assume a part in epithelial-mesenchymal collaboration i cell multiplication in ameloblastoma. […] Pathogenesis of ameloblastoma is multifactorial and includes various cell pathways. SHH pathway, which assumes a definitive part in the turn of events i designing of różnych organs, is fundamental in odontogenesis i również assumes an essential part in the pathogenesis of ameloblastoma.

• #22 Perspective Chapter: Ameloblastoma – Present and Future Concepts of Managing | IntechOpen

  https://www.intechopen.com/chapters/83748

  Ameloblastomas belong to benign odontogenic tumors with locally aggressive behavior. […] In addition, recent literature has provided us with breakthrough in the understanding of genetic mutations and signaling pathways crucial in ameloblastoma pathogenesis. […] As the genetic understanding increased, valuable findings have been brought to light regarding molecular pathogenesis of ameloblastoma. In 2014, it was confirmed that recurrent somatic and activating mutations in the mitogen-activated protein kinase (MAPK) plays a prominent role in the pathogenesis of the disease. […] Together, all the mentioned mutations are present in vast majority of ameloblastomas, suggesting that activation of the MAPK signaling pathway represents a critical event in the pathogenesis of ameloblastoma. […] Several non-MAPK mutations have also been associated with ameloblastoma. The most important is nonclassical G protein-coupled receptor, the smoothened (SMO) gene. […] The main identified mutations are found in MAPK and SHH signaling pathways. These include BRAF, RAS and FGFR2 genes from MAPK pathway and SMO gene from SHH signaling pathway.

• #23 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Similarly, targeted therapies have been developed to control the effect of the SMO mutation associated with ameloblastoma pathogenesis. […] As the expression of SHH is high in ameloblastomas, several drugs already used to antagonize SHH signaling offer other non-surgical targeted therapeutic options for patients with this type of tumor.

• #24 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  The molecular and genetic alterations that occur in ameloblastoma would be discussed in this review which is helpful for better treatment and prognosis. […] Various signaling pathways have been identified to explain the pathogenesis of ameloblastoma. Sonic Hedgehog (SHH), a mammalian homolog of drosophila segment polarity gene Hedgehog, encodes a secreted protein that activates a membrane receptor complex formed by patched 1 (PCTH 1) and smoothened (SMO). […] High expression of SHH, SMO and GLi 1 was reported in ameloblastoma. […] Studies suggested that SHH signaling molecules may play a role in epithelial-mesenchymal interaction and cell proliferation in ameloblastoma. […] WNT genes encode a family of glycoproteins, first identified in mammals as proto-oncogenic integration site for mouse mammary tumor virus. These proteins activate a number of signaling pathways that are divided into two categories: Canonical -catenin pathway and noncanonical -catenin independent pathway.

• #25 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  Overexpression of WNT 5a increases enamel epithelial cell migration while suppression impairs their migration and fails to form actin re-organization. […] The TGF /SMAD signaling pathway has an important role in the invasiveness of ameloblastoma, especially in later stages. […] Pathogenesis of ameloblastoma is multifactorial and involves numerous cellular pathways. Diverse type of molecules and gene alterations affect the development and progression of odontogenic epithelium and these characteristics appear to depend on diverse molecular mechanisms. Proper understanding of the pathogenic mechanism involved in ameloblastoma and its proliferation will help in the development of new therapeutic approaches such as molecular-targeted treatment for odontogenic tumors.

• #26

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Genes involved in the initiation of tooth development, morphogenesis, and cytodifferentiation and tooth patterning include, sonic hedgehog (SHH), patched (PTCH), WNT, activin A, bone morphogenetic proteins (BMP2 and BMP4), fibroblast-growth-factor (FGF), PAX9, BARX1, LEF1, DLX1, DLX2, MSX1, and MSX2. […] The transmembrane receptor for Sonic Hedgehog (SHH) and other Hedgehog proteins (HH) is coded by the PTCH1 gene. […] A high expression of SHH, SMO and GLI protein was reported in ameloblastoma. […] Nuclear accumulation of catenin was demonstrated in ameloblastomas. […] The loss of Syndecan-1 indicates unfavorable prognosis in epithelial tumors. The decreased expression of Syndecan-1 was seen in ameloblastomas which could attribute to the aggressive behavior of the tumor. […] PTEN protein functions as an inhibitor of Akt signaling pathway, leading to cell cycle arrest and apoptosis. Its expression was reduced in ameloblastomas compared with teeth germs.

• #27 Ameloblastoma: Current Etiopathological Concepts and Management

  https://repository.upenn.edu/items/113033ac-d15a-4b1a-a710-1e9c2332e50a

  Ameloblastoma is a benign odontogenic tumor of epithelial origin. It is locally aggressive with unlimited growth capacity and has a high potential for malignant transformation as well as metastasis. […] Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen-activated protein kinase, sonic hedgehog, and WNT/β-catenin signaling pathways. […] It is expected that further elucidation of molecular factors that orchestrate pathogenesis and recurrence of ameloblastoma will lead to new diagnostic markers and targeted drug therapies for ameloblastoma.

• #28 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  Overexpression of WNT 5a increases enamel epithelial cell migration while suppression impairs their migration and fails to form actin re-organization. […] The TGF /SMAD signaling pathway has an important role in the invasiveness of ameloblastoma, especially in later stages. […] Pathogenesis of ameloblastoma is multifactorial and involves numerous cellular pathways. Diverse type of molecules and gene alterations affect the development and progression of odontogenic epithelium and these characteristics appear to depend on diverse molecular mechanisms. Proper understanding of the pathogenic mechanism involved in ameloblastoma and its proliferation will help in the development of new therapeutic approaches such as molecular-targeted treatment for odontogenic tumors.

• #29

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Overexpression of FOS and TNFR1A have been significant in the oncogenic transformation pathway of ameloblastoma. […] The tumor cells do not attain functional maturation as secretory phase ameloblasts thereby not expressing the enamel proteins. […] Other mechanisms which have been studied and quoted in the literature are listed. Epigenetics is an event in the pathogenesis of ameloblastoma where the P21 gene undergoes methylation along with alterations in P16 and RB1. […] The invasive ability of ameloblastoma is related to the release of molecules like matrix metalloproteinases, which trigger mitogens to be released, leading to proliferation of ameloblastoma cells. […] Bone Morphogenetic Protein (BMP), member of the transforming growth factor (TGF) super family, is a mesenchymal cell differentiation factor and a morphogen.

• #30 Mechanism and Potential Therapy in Ameloblastoma: Akt Signaling Pathway | Hadi | The Indonesian Biomedical Journal

  https://inabj.org/index.php/ibj/article/view/1824

  Ameloblastoma can arise at any age, however it most usually affect patients between the ages of 20 and 40. […] Akt signaling pathway in ameloblastoma has been implicated in the formation and progression of tumors. […] The present review highlights various Akt signaling involved in ameloblastoma and its potential pathways for treatments, while the gold standard of ameloblastoma treatment is still surgery to remove the tumor, there are many potential agents through various means of inhibition for ameloblastoma. […] Therefore, understanding the underlying signaling on ameloblastoma is necessary to induce inhibition on ameloblastoma. […] More research in potential ways to inhibit Akt signaling in ameloblastoma will lead to a better management of ameloblastoma in the future.

• #31

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Genes involved in the initiation of tooth development, morphogenesis, and cytodifferentiation and tooth patterning include, sonic hedgehog (SHH), patched (PTCH), WNT, activin A, bone morphogenetic proteins (BMP2 and BMP4), fibroblast-growth-factor (FGF), PAX9, BARX1, LEF1, DLX1, DLX2, MSX1, and MSX2. […] The transmembrane receptor for Sonic Hedgehog (SHH) and other Hedgehog proteins (HH) is coded by the PTCH1 gene. […] A high expression of SHH, SMO and GLI protein was reported in ameloblastoma. […] Nuclear accumulation of catenin was demonstrated in ameloblastomas. […] The loss of Syndecan-1 indicates unfavorable prognosis in epithelial tumors. The decreased expression of Syndecan-1 was seen in ameloblastomas which could attribute to the aggressive behavior of the tumor. […] PTEN protein functions as an inhibitor of Akt signaling pathway, leading to cell cycle arrest and apoptosis. Its expression was reduced in ameloblastomas compared with teeth germs.

• #32 Mechanism and Potential Therapy in Ameloblastoma: Akt Signaling Pathway | Hadi | The Indonesian Biomedical Journal

  https://inabj.org/index.php/ibj/article/view/1824

  Ameloblastoma can arise at any age, however it most usually affect patients between the ages of 20 and 40. […] Akt signaling pathway in ameloblastoma has been implicated in the formation and progression of tumors. […] The present review highlights various Akt signaling involved in ameloblastoma and its potential pathways for treatments, while the gold standard of ameloblastoma treatment is still surgery to remove the tumor, there are many potential agents through various means of inhibition for ameloblastoma. […] Therefore, understanding the underlying signaling on ameloblastoma is necessary to induce inhibition on ameloblastoma. […] More research in potential ways to inhibit Akt signaling in ameloblastoma will lead to a better management of ameloblastoma in the future.

• #33 Bioinformatic Analysis of Genes Involved In The Pathogenesis Of Ameloblastoma And Human Tooth Germ | Journal of Population Therapeutics and Clinical Pharmacology

  https://jptcp.com/index.php/jptcp/article/view/1808

  Background: Pathogenesis of most odontogenic tumors is not well established. It is important to identify various genetic deregulations and molecular alterations. Common signaling pathways between ameloblastoma and human tooth germ is yet to be well established. […] This study aimed to investigate, through bioinformatic analysis, the possible genes involved in the pathogenesis of ameloblastoma (AM) and human tooth germ. […] To analyze the genes commonly expressed in human tooth germ and ameloblastoma for better understanding the molecular pathogenesis of ameloblastoma. […] GeneCards and STRING analysis showed a final count of 10 genes that were commonly expressed in ameloblastoma and human tooth germ were included. These were: IGF1, STAT1, TLR2, BRAF, IGF2, ERK2, ERK1, NFkappaB, MEK2 and MEK1.

• #34 Bioinformatic Analysis of Genes Involved In The Pathogenesis Of Ameloblastoma And Human Tooth Germ | Journal of Population Therapeutics and Clinical Pharmacology

  https://jptcp.com/index.php/jptcp/article/view/1808

  From the WNL analysis, ameloblastoma, the highest WNL values were identified in genes BRAF V600E, MAPK, STAT1 and NFKappaB. […] Conclusion: STAT 1 and NFKappaB together help in tumor cell proliferation and cell survival. Numerous targeted therapies have been produced against these genes. Further in vitro molecular analysis such as microarray are needed for proper application of these therapies.

• #35

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Genes involved in the initiation of tooth development, morphogenesis, and cytodifferentiation and tooth patterning include, sonic hedgehog (SHH), patched (PTCH), WNT, activin A, bone morphogenetic proteins (BMP2 and BMP4), fibroblast-growth-factor (FGF), PAX9, BARX1, LEF1, DLX1, DLX2, MSX1, and MSX2. […] The transmembrane receptor for Sonic Hedgehog (SHH) and other Hedgehog proteins (HH) is coded by the PTCH1 gene. […] A high expression of SHH, SMO and GLI protein was reported in ameloblastoma. […] Nuclear accumulation of catenin was demonstrated in ameloblastomas. […] The loss of Syndecan-1 indicates unfavorable prognosis in epithelial tumors. The decreased expression of Syndecan-1 was seen in ameloblastomas which could attribute to the aggressive behavior of the tumor. […] PTEN protein functions as an inhibitor of Akt signaling pathway, leading to cell cycle arrest and apoptosis. Its expression was reduced in ameloblastomas compared with teeth germs.

• #36

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Genes involved in the initiation of tooth development, morphogenesis, and cytodifferentiation and tooth patterning include, sonic hedgehog (SHH), patched (PTCH), WNT, activin A, bone morphogenetic proteins (BMP2 and BMP4), fibroblast-growth-factor (FGF), PAX9, BARX1, LEF1, DLX1, DLX2, MSX1, and MSX2. […] The transmembrane receptor for Sonic Hedgehog (SHH) and other Hedgehog proteins (HH) is coded by the PTCH1 gene. […] A high expression of SHH, SMO and GLI protein was reported in ameloblastoma. […] Nuclear accumulation of catenin was demonstrated in ameloblastomas. […] The loss of Syndecan-1 indicates unfavorable prognosis in epithelial tumors. The decreased expression of Syndecan-1 was seen in ameloblastomas which could attribute to the aggressive behavior of the tumor. […] PTEN protein functions as an inhibitor of Akt signaling pathway, leading to cell cycle arrest and apoptosis. Its expression was reduced in ameloblastomas compared with teeth germs.

• #37 Bioinformatic Analysis of Genes Involved In The Pathogenesis Of Ameloblastoma And Human Tooth Germ | Journal of Population Therapeutics and Clinical Pharmacology

  https://jptcp.com/index.php/jptcp/article/view/1808

  Background: Pathogenesis of most odontogenic tumors is not well established. It is important to identify various genetic deregulations and molecular alterations. Common signaling pathways between ameloblastoma and human tooth germ is yet to be well established. […] This study aimed to investigate, through bioinformatic analysis, the possible genes involved in the pathogenesis of ameloblastoma (AM) and human tooth germ. […] To analyze the genes commonly expressed in human tooth germ and ameloblastoma for better understanding the molecular pathogenesis of ameloblastoma. […] GeneCards and STRING analysis showed a final count of 10 genes that were commonly expressed in ameloblastoma and human tooth germ were included. These were: IGF1, STAT1, TLR2, BRAF, IGF2, ERK2, ERK1, NFkappaB, MEK2 and MEK1.

• #38 Bioinformatic Analysis of Genes Involved In The Pathogenesis Of Ameloblastoma And Human Tooth Germ | Journal of Population Therapeutics and Clinical Pharmacology

  https://jptcp.com/index.php/jptcp/article/view/1808

  From the WNL analysis, ameloblastoma, the highest WNL values were identified in genes BRAF V600E, MAPK, STAT1 and NFKappaB. […] Conclusion: STAT 1 and NFKappaB together help in tumor cell proliferation and cell survival. Numerous targeted therapies have been produced against these genes. Further in vitro molecular analysis such as microarray are needed for proper application of these therapies.

• #39

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Overexpression of FOS and TNFR1A have been significant in the oncogenic transformation pathway of ameloblastoma. […] The tumor cells do not attain functional maturation as secretory phase ameloblasts thereby not expressing the enamel proteins. […] Other mechanisms which have been studied and quoted in the literature are listed. Epigenetics is an event in the pathogenesis of ameloblastoma where the P21 gene undergoes methylation along with alterations in P16 and RB1. […] The invasive ability of ameloblastoma is related to the release of molecules like matrix metalloproteinases, which trigger mitogens to be released, leading to proliferation of ameloblastoma cells. […] Bone Morphogenetic Protein (BMP), member of the transforming growth factor (TGF) super family, is a mesenchymal cell differentiation factor and a morphogen.

• #40 SciELO Brazil – Microarray and bioinformatic analysis of conventional ameloblastoma: an observational analysis Microarray and bioinformatic analysis of conventional ameloblastoma: an observational analysis

  https://www.scielo.br/j/jaos/a/sSBGMRP7XyMWsdJjfrbMqBm/?lang=en

  PDGF is an important factor in ameloblastoma pathogenesis and the expression of the PDGF chain is higher in ameloblastic tumors than in tooth germs, and alongside its cognate receptor (PDGFRA) it is expressed at a variable level in ameloblastomas. […] Cytokines are major mediators of the immune response. […] The interleukin-2 receptor is involved in the regulation of immune tolerance by controlling regulatory T cell (TREG) activity. […] This is the first report to identify IL2RA as a possible participant in the mechanism underlying the development of ameloblastoma. […] Taken together, our bioinformatic analysis identified two hub genes (PDGFA and IL2RA) between CAm and normal dental follicles. The results suggested that these genes play key roles in the pathogenesis, progression, and prognosis of CAm.

• #41

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Overexpression of FOS and TNFR1A have been significant in the oncogenic transformation pathway of ameloblastoma. […] The tumor cells do not attain functional maturation as secretory phase ameloblasts thereby not expressing the enamel proteins. […] Other mechanisms which have been studied and quoted in the literature are listed. Epigenetics is an event in the pathogenesis of ameloblastoma where the P21 gene undergoes methylation along with alterations in P16 and RB1. […] The invasive ability of ameloblastoma is related to the release of molecules like matrix metalloproteinases, which trigger mitogens to be released, leading to proliferation of ameloblastoma cells. […] Bone Morphogenetic Protein (BMP), member of the transforming growth factor (TGF) super family, is a mesenchymal cell differentiation factor and a morphogen.

• #42

  https://journals.lww.com/jpbs/fulltext/2015/07001/ameloblastoma.46.aspx

  Ameloblastoma is a neoplasm of odontogenic epithelium, principally of enamel organ-type tissue that has not undergone differentiation to the point of hard tissue formation. […] Signaling pathway such as WNT, Akt and growth factors like fibroblast growth factor play a pivotal role in the pathogenesis of solid type of ameloblastoma. Proteins mainly bone morphogenic protein ameloblastin, enamel matrix proteins calretinin, syndecan-1 and matrix metalloproteinases also play an important contribution in the etiopathogenesis. Tumor suppressor genes p53, p63 and p73 bring about molecular changes in the pathogenesis of ameloblastoma. p53 plays an important role in the differentiation and proliferation of odontogenic epithelial cells. Matrix metalloproteinases, triggers mitogens to be released, leading to the proliferation of ameloblastoma cells. […] Three pathogenic mechanisms for the evolution of UA: Reduced enamel epithelium, from dentigerous cyst and due to cystic degeneration of solid ameloblastoma.

• #43

  https://journals.lww.com/jpbs/fulltext/2015/07001/ameloblastoma.46.aspx

  Ameloblastoma is a neoplasm of odontogenic epithelium, principally of enamel organ-type tissue that has not undergone differentiation to the point of hard tissue formation. […] Signaling pathway such as WNT, Akt and growth factors like fibroblast growth factor play a pivotal role in the pathogenesis of solid type of ameloblastoma. Proteins mainly bone morphogenic protein ameloblastin, enamel matrix proteins calretinin, syndecan-1 and matrix metalloproteinases also play an important contribution in the etiopathogenesis. Tumor suppressor genes p53, p63 and p73 bring about molecular changes in the pathogenesis of ameloblastoma. p53 plays an important role in the differentiation and proliferation of odontogenic epithelial cells. Matrix metalloproteinases, triggers mitogens to be released, leading to the proliferation of ameloblastoma cells. […] Three pathogenic mechanisms for the evolution of UA: Reduced enamel epithelium, from dentigerous cyst and due to cystic degeneration of solid ameloblastoma.

• #44

  https://journals.lww.com/jpbs/fulltext/2015/07001/ameloblastoma.46.aspx

  Ameloblastoma is a neoplasm of odontogenic epithelium, principally of enamel organ-type tissue that has not undergone differentiation to the point of hard tissue formation. […] Signaling pathway such as WNT, Akt and growth factors like fibroblast growth factor play a pivotal role in the pathogenesis of solid type of ameloblastoma. Proteins mainly bone morphogenic protein ameloblastin, enamel matrix proteins calretinin, syndecan-1 and matrix metalloproteinases also play an important contribution in the etiopathogenesis. Tumor suppressor genes p53, p63 and p73 bring about molecular changes in the pathogenesis of ameloblastoma. p53 plays an important role in the differentiation and proliferation of odontogenic epithelial cells. Matrix metalloproteinases, triggers mitogens to be released, leading to the proliferation of ameloblastoma cells. […] Three pathogenic mechanisms for the evolution of UA: Reduced enamel epithelium, from dentigerous cyst and due to cystic degeneration of solid ameloblastoma.

• #45

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Genes involved in the initiation of tooth development, morphogenesis, and cytodifferentiation and tooth patterning include, sonic hedgehog (SHH), patched (PTCH), WNT, activin A, bone morphogenetic proteins (BMP2 and BMP4), fibroblast-growth-factor (FGF), PAX9, BARX1, LEF1, DLX1, DLX2, MSX1, and MSX2. […] The transmembrane receptor for Sonic Hedgehog (SHH) and other Hedgehog proteins (HH) is coded by the PTCH1 gene. […] A high expression of SHH, SMO and GLI protein was reported in ameloblastoma. […] Nuclear accumulation of catenin was demonstrated in ameloblastomas. […] The loss of Syndecan-1 indicates unfavorable prognosis in epithelial tumors. The decreased expression of Syndecan-1 was seen in ameloblastomas which could attribute to the aggressive behavior of the tumor. […] PTEN protein functions as an inhibitor of Akt signaling pathway, leading to cell cycle arrest and apoptosis. Its expression was reduced in ameloblastomas compared with teeth germs.

• #46 Bone Resorption in Ameloblastoma and Its Underlying Mechanism | Jackson | Indonesian Journal of Cancer Chemoprevention

  https://ijcc.chemoprev.org/index.php/ijcc/article/view/356

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed. […] The role of RANKL and MMP-9 in the bone resorption caused by ameloblastoma. […] Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone. […] The role of RANK/RANKL/OPG signaling pathways in osteoclastogenesis in odontogenic keratocysts, radicular cysts, and ameloblastomas.

• #47 DOAJ Logotype

  https://doaj.org/article/8d01dbcef2f143b3bd8e1e7d42e0d068

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed.

• #48 Bone Resorption in Ameloblastoma and Its Underlying Mechanism | Jackson | Indonesian Journal of Cancer Chemoprevention

  https://ijcc.chemoprev.org/index.php/ijcc/article/view/356

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed. […] The role of RANKL and MMP-9 in the bone resorption caused by ameloblastoma. […] Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone. […] The role of RANK/RANKL/OPG signaling pathways in osteoclastogenesis in odontogenic keratocysts, radicular cysts, and ameloblastomas.

• #49 Bone Resorption in Ameloblastoma and Its Underlying Mechanism | Jackson | Indonesian Journal of Cancer Chemoprevention

  https://ijcc.chemoprev.org/index.php/ijcc/article/view/356

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed. […] The role of RANKL and MMP-9 in the bone resorption caused by ameloblastoma. […] Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone. […] The role of RANK/RANKL/OPG signaling pathways in osteoclastogenesis in odontogenic keratocysts, radicular cysts, and ameloblastomas.

• #50 DOAJ Logotype

  https://doaj.org/article/8d01dbcef2f143b3bd8e1e7d42e0d068

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed.

• #51 Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation | Scientific Reports

  https://www.nature.com/articles/s41598-021-03484-5

  We bio-engineered an active bone-forming stroma with live osteoblasts, to study the interaction between ameloblastoma and native bone stroma. […] We showed direct inhibition of bone nodule formation by osteoblasts when ameloblastoma is present. […] Ameloblastoma cells caused osteoblasts to increase their TNFSF11 (RANKL) expression. This finding deepens our understanding of the mechanism by which ameloblastoma cells indirectly activate osteoclasts through osteoblasts, ultimately leading to bone resorption.

• #52 Bone Resorption in Ameloblastoma and Its Underlying Mechanism | Jackson | Indonesian Journal of Cancer Chemoprevention

  https://ijcc.chemoprev.org/index.php/ijcc/article/view/356

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed. […] The role of RANKL and MMP-9 in the bone resorption caused by ameloblastoma. […] Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone. […] The role of RANK/RANKL/OPG signaling pathways in osteoclastogenesis in odontogenic keratocysts, radicular cysts, and ameloblastomas.

• #53 Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation | Scientific Reports

  https://www.nature.com/articles/s41598-021-03484-5

  A range of gene mutations and copy number alterations have been identified and suggested as potential drivers of AM pathogenesis, mostly within the MAPK cascade pathway such as BRAF V600E, FGF2 and RAS. Notably less research has been conducted concerning the mechanisms driving bone remodelling in the microenvironment surrounding the neoplastic cells, even though AM growth typically causes bone resorption. […] The current theory is that AM increases RANKL, which then binds to its receptor RANK on the surface of osteoclasts and causes osteoclast activation and thereby, bone resorption. Strong PTHrP expression in AM is also involved in the activation of osteoclasts. The matrix metalloproteinases (MMPs) in particular MMP-2 and -9 found in AM epithelium cause further osteoclasts activation as well as degradation of fibrillar collagen (collagen type IV).

• #54 (PDF) REVIEW ARTICLE: Current concepts of ameloblastoma pathogenesis

  https://www.academia.edu/61448760/REVIEW_ARTICLE_Current_concepts_of_ameloblastoma_pathogenesis

  However, as mutations of ameloblastin gene were also detected in other epithelial odontogenic tumours, this alteration is not a specific molecular signature of ameloblastoma development. […] RT-PCR reactions in ameloblastomas and dental follicles pointed to a contribution of a high expression of MMP-2, TIMP-2 and MMP-14 mRNA to the local invasive characteristics of ameloblastoma. […] Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen-activated protein kinase, sonic hedgehog, and WNT/b-catenin signaling pathways. […] Our results suggest an interdependent mechanism involving MMPs and proliferation of ameloblastoma cells, which may contribute to the local invasiveness of this tumour.

• #55 Ameloblastoma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Ameloblastoma_pathophysiology

  Ameloblastoma arise from remnants of ameloblast or dental lamina, dentigerous cysts, or basal layer of oral mucosa. […] There is evidence that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro. […] There is also some research suggesting that 51 integrin may participate in the local invasiveness of ameloblastomas. […] The ameloblastoma is an ectodermal odontogenic tumor of the jaw which apparently originates from the Malassez rests in the periodontium, from the gingival epithelium, from the enamel organs, or from ordinary dental cysts (dentigerous cysts, follicular cysts, or radicular cysts). […] Genes involved in the pathogenesis of ameloblastoma include BRAF V600E.

• #56 Ameloblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Ameloblastoma

  Ameloblastoma is a rare, benign or cancerous tumor of odontogenic epithelium (ameloblasts, or outside portion, of the teeth during development) much more commonly appearing in the lower jaw than the upper jaw. […] BRAF V600E gene and SMO gene mutations have been found in ameloblastomas. V600E mutation is also seen in other malignant and benign neoplasms, which activate the MAP kinase pathway required for cell division and differentiation but is the most commonly seen mutation in ameloblastoma. […] Evidence shows that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro. […] There is also some research suggesting that 51 integrin may participate in the local invasiveness of ameloblastomas.

• #57 Ameloblastoma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Ameloblastoma_pathophysiology

  Ameloblastoma arise from remnants of ameloblast or dental lamina, dentigerous cysts, or basal layer of oral mucosa. […] There is evidence that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro. […] There is also some research suggesting that 51 integrin may participate in the local invasiveness of ameloblastomas. […] The ameloblastoma is an ectodermal odontogenic tumor of the jaw which apparently originates from the Malassez rests in the periodontium, from the gingival epithelium, from the enamel organs, or from ordinary dental cysts (dentigerous cysts, follicular cysts, or radicular cysts). […] Genes involved in the pathogenesis of ameloblastoma include BRAF V600E.

• #58 Ameloblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Ameloblastoma

  Ameloblastoma is a rare, benign or cancerous tumor of odontogenic epithelium (ameloblasts, or outside portion, of the teeth during development) much more commonly appearing in the lower jaw than the upper jaw. […] BRAF V600E gene and SMO gene mutations have been found in ameloblastomas. V600E mutation is also seen in other malignant and benign neoplasms, which activate the MAP kinase pathway required for cell division and differentiation but is the most commonly seen mutation in ameloblastoma. […] Evidence shows that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro. […] There is also some research suggesting that 51 integrin may participate in the local invasiveness of ameloblastomas.

• #59 Bone Resorption in Ameloblastoma and Its Underlying Mechanism | Jackson | Indonesian Journal of Cancer Chemoprevention

  https://ijcc.chemoprev.org/index.php/ijcc/article/view/356

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed. […] The role of RANKL and MMP-9 in the bone resorption caused by ameloblastoma. […] Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone. […] The role of RANK/RANKL/OPG signaling pathways in osteoclastogenesis in odontogenic keratocysts, radicular cysts, and ameloblastomas.

• #60 DOAJ Logotype

  https://doaj.org/article/8d01dbcef2f143b3bd8e1e7d42e0d068

  Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. […] To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-B (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-. […] RANKL plays an important role in generating osteoclastogenesis. […] MMPs degrade the extracellular matrix. […] TNF- can induce the formation of osteoclast and modulate the MMPs. […] In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed.

• #61 SciELO Brazil – The mechanism: how dental resorptions occur in ameloblastoma The mechanism: how dental resorptions occur in ameloblastoma

  https://www.scielo.br/j/dpjo/a/JnBzjdWBVcxzdvSd9QprpWh/?lang=en

  Knife-edge or blunt root resorptions characterize ameloblastomas and are pathognomonic for this tumor, because they differentiate ameloblastomas from simple bone cysts, odontogenic keratocysts and nasopalatine duct cysts, which do not lead to resorption of involved teeth. […] This paper describes a six-step hypothesis to explain the mechanism by which ameloblastomas promote the characteristic root resorptions found in association with these benign epithelial tumors, which have a fibrous capsule formed by islands and epithelial cords that mimic the dental lamina, invade neighboring tissues and release mediators (IL-1, EGF) of tooth and root resorption. […] The following hypothesis has been made to explain the mechanism of root resorption in ameloblastomas: 1) The epithelial islands and cords in the neoplastic mass of the ameloblastoma move towards the roots and compress the vessels in the periodontal ligament. 2) Hypoxia, later followed by anoxia, leads to the death of cementoblasts, the cells responsible for preserving root integrity, because of the lack of receptors for local and systemic mediators of bone resorption on their cell membranes. 3) The death of odontoblasts exposes the mineralized structure of the root, which, because the periodontal ligament is 0.25-mm thick in average, induces chemotaxis of the abundant clasts in the periodontal region. 4) Clasts on the exposed root surface are juxtaposed to the neoplastic epithelial islands and cords in a parallel or palisade pattern and initiate root resorption. 5) Resorption tends to be uniform or regular, parallel to the interface with neoplastic epithelial islands closer to the root, and the set of clasts generates a regular surface, which appears as a knife-edge root resorption on imaging studies. 6) Resorption continues because of the release of bone or tooth resorption mediators by the ameloblastoma, such as epidermal growth factor (EGF) and interleukin-1 (IL-1). Ameloblastomas are epithelial odontogenic tumors that release EGF and other mediators that induce resorption, such as interleukins.

• #62 SciELO Brazil – The mechanism: how dental resorptions occur in ameloblastoma The mechanism: how dental resorptions occur in ameloblastoma

  https://www.scielo.br/j/dpjo/a/JnBzjdWBVcxzdvSd9QprpWh/?lang=en

  Knife-edge or blunt root resorptions characterize ameloblastomas and are pathognomonic for this tumor, because they differentiate ameloblastomas from simple bone cysts, odontogenic keratocysts and nasopalatine duct cysts, which do not lead to resorption of involved teeth. […] This paper describes a six-step hypothesis to explain the mechanism by which ameloblastomas promote the characteristic root resorptions found in association with these benign epithelial tumors, which have a fibrous capsule formed by islands and epithelial cords that mimic the dental lamina, invade neighboring tissues and release mediators (IL-1, EGF) of tooth and root resorption. […] The following hypothesis has been made to explain the mechanism of root resorption in ameloblastomas: 1) The epithelial islands and cords in the neoplastic mass of the ameloblastoma move towards the roots and compress the vessels in the periodontal ligament. 2) Hypoxia, later followed by anoxia, leads to the death of cementoblasts, the cells responsible for preserving root integrity, because of the lack of receptors for local and systemic mediators of bone resorption on their cell membranes. 3) The death of odontoblasts exposes the mineralized structure of the root, which, because the periodontal ligament is 0.25-mm thick in average, induces chemotaxis of the abundant clasts in the periodontal region. 4) Clasts on the exposed root surface are juxtaposed to the neoplastic epithelial islands and cords in a parallel or palisade pattern and initiate root resorption. 5) Resorption tends to be uniform or regular, parallel to the interface with neoplastic epithelial islands closer to the root, and the set of clasts generates a regular surface, which appears as a knife-edge root resorption on imaging studies. 6) Resorption continues because of the release of bone or tooth resorption mediators by the ameloblastoma, such as epidermal growth factor (EGF) and interleukin-1 (IL-1). Ameloblastomas are epithelial odontogenic tumors that release EGF and other mediators that induce resorption, such as interleukins.

• #63 SciELO Brazil – The mechanism: how dental resorptions occur in ameloblastoma The mechanism: how dental resorptions occur in ameloblastoma

  https://www.scielo.br/j/dpjo/a/JnBzjdWBVcxzdvSd9QprpWh/?lang=en

  Knife-edge or blunt root resorptions characterize ameloblastomas and are pathognomonic for this tumor, because they differentiate ameloblastomas from simple bone cysts, odontogenic keratocysts and nasopalatine duct cysts, which do not lead to resorption of involved teeth. […] This paper describes a six-step hypothesis to explain the mechanism by which ameloblastomas promote the characteristic root resorptions found in association with these benign epithelial tumors, which have a fibrous capsule formed by islands and epithelial cords that mimic the dental lamina, invade neighboring tissues and release mediators (IL-1, EGF) of tooth and root resorption. […] The following hypothesis has been made to explain the mechanism of root resorption in ameloblastomas: 1) The epithelial islands and cords in the neoplastic mass of the ameloblastoma move towards the roots and compress the vessels in the periodontal ligament. 2) Hypoxia, later followed by anoxia, leads to the death of cementoblasts, the cells responsible for preserving root integrity, because of the lack of receptors for local and systemic mediators of bone resorption on their cell membranes. 3) The death of odontoblasts exposes the mineralized structure of the root, which, because the periodontal ligament is 0.25-mm thick in average, induces chemotaxis of the abundant clasts in the periodontal region. 4) Clasts on the exposed root surface are juxtaposed to the neoplastic epithelial islands and cords in a parallel or palisade pattern and initiate root resorption. 5) Resorption tends to be uniform or regular, parallel to the interface with neoplastic epithelial islands closer to the root, and the set of clasts generates a regular surface, which appears as a knife-edge root resorption on imaging studies. 6) Resorption continues because of the release of bone or tooth resorption mediators by the ameloblastoma, such as epidermal growth factor (EGF) and interleukin-1 (IL-1). Ameloblastomas are epithelial odontogenic tumors that release EGF and other mediators that induce resorption, such as interleukins.

• #64 THE ROLE OF LGR5+ EPITHELIAL STEM-LIKE CELLS IN 3D-ORGANOID MODELING AND PATHOGENESIS OF AMELOBLASTOMA

  https://repository.upenn.edu/entities/publication/2f6e0092-8fd8-4e35-9ab4-c5a4624f4ce9

  Ameloblastoma (AM) is a benign yet locally aggressive tumor with high recurrences. Currently, the underlying pathophysiology remains elusive and radical surgery remains the most definitive treatment with severe morbidities. […] Herein, this study further explored whether LGR5+ epithelial cells in AM possess unique stem-like cell properties and their potential contribution to the pathogenesis and recurrence of AM. […] Our findings demonstrated that LGR5 and stem cell-related genes were simultaneously expressed in a subpopulation of AM epithelial cells, both in vivo and in vitro, which were markedly enriched under the 3D-spheroid culture condition. […] As compared to LGR5- counterparts, LGR5+ AM epithelial cells showed increased expression of several critical genes involved in the regulation of epithelial-mesenchymal transition (EMT) and stem cell pluripotency, and functionally, exhibited enhanced capacity to form 3D-spheroids and generate human tumor 3D-organoids, which recapitulated characteristic histopathologic features of distinct subtypes of solid AM.

• #65 THE ROLE OF LGR5+ EPITHELIAL STEM-LIKE CELLS IN 3D-ORGANOID MODELING AND PATHOGENESIS OF AMELOBLASTOMA

  https://repository.upenn.edu/entities/publication/2f6e0092-8fd8-4e35-9ab4-c5a4624f4ce9

  Ameloblastoma (AM) is a benign yet locally aggressive tumor with high recurrences. Currently, the underlying pathophysiology remains elusive and radical surgery remains the most definitive treatment with severe morbidities. […] Herein, this study further explored whether LGR5+ epithelial cells in AM possess unique stem-like cell properties and their potential contribution to the pathogenesis and recurrence of AM. […] Our findings demonstrated that LGR5 and stem cell-related genes were simultaneously expressed in a subpopulation of AM epithelial cells, both in vivo and in vitro, which were markedly enriched under the 3D-spheroid culture condition. […] As compared to LGR5- counterparts, LGR5+ AM epithelial cells showed increased expression of several critical genes involved in the regulation of epithelial-mesenchymal transition (EMT) and stem cell pluripotency, and functionally, exhibited enhanced capacity to form 3D-spheroids and generate human tumor 3D-organoids, which recapitulated characteristic histopathologic features of distinct subtypes of solid AM.

• #66 THE ROLE OF LGR5+ EPITHELIAL STEM-LIKE CELLS IN 3D-ORGANOID MODELING AND PATHOGENESIS OF AMELOBLASTOMA

  https://repository.upenn.edu/entities/publication/2f6e0092-8fd8-4e35-9ab4-c5a4624f4ce9

  Ameloblastoma (AM) is a benign yet locally aggressive tumor with high recurrences. Currently, the underlying pathophysiology remains elusive and radical surgery remains the most definitive treatment with severe morbidities. […] Herein, this study further explored whether LGR5+ epithelial cells in AM possess unique stem-like cell properties and their potential contribution to the pathogenesis and recurrence of AM. […] Our findings demonstrated that LGR5 and stem cell-related genes were simultaneously expressed in a subpopulation of AM epithelial cells, both in vivo and in vitro, which were markedly enriched under the 3D-spheroid culture condition. […] As compared to LGR5- counterparts, LGR5+ AM epithelial cells showed increased expression of several critical genes involved in the regulation of epithelial-mesenchymal transition (EMT) and stem cell pluripotency, and functionally, exhibited enhanced capacity to form 3D-spheroids and generate human tumor 3D-organoids, which recapitulated characteristic histopathologic features of distinct subtypes of solid AM.

• #67 THE ROLE OF LGR5+ EPITHELIAL STEM-LIKE CELLS IN 3D-ORGANOID MODELING AND PATHOGENESIS OF AMELOBLASTOMA

  https://repository.upenn.edu/entities/publication/2f6e0092-8fd8-4e35-9ab4-c5a4624f4ce9

  Interestingly, AM derived mesenchymal stromal cells (AM-MSCs) and their secretomes or extracellular vesicles (EVs) significantly promoted the generation of LGR5+ AM-EpiSCs both in vitro and in vivo. […] Furthermore, treatment with a selective BRAFV600E inhibitor, Vemurafenib, unexpectedly enriched the proportion of LGR5+ AM-EpiSCs in AM 3D-organoids, which may explain the therapeutic resistant and recurrent properties of AM conferred by this unique subpopulation of AM-EpiSCs. […] Therefore, the tumor 3D-organoids generated by LGR5+ AM-EpiSCs provided a novel ex vivo platform for mechanistic studies of human AM and high throughput screening of targeted therapeutic drugs. […] These findings suggest that LGR5+ AM-EpiSCs play a pivotal role in pathogenesis and progression of AM and targeted inhibition of both BRAF and LGR5 potentially serves a novel non-surgical adjuvant therapeutic approach for this benign yet aggressively destructive jaw tumor.

• #68 Establishing the Natural History and Growth Rate of Ameloblastoma with Implications for Management: Systematic Review and Meta-Analysis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117241

  Ameloblastoma is the second most common odontogenic tumor, known to be slow-growing, persistent, and locally aggressive. […] An understanding of the growth rate and natural history of ameloblastoma has been notably lacking from the literature. […] The growth rate of ameloblastoma has been demonstrated, offering prognostic and management information, particularly in cases where a delay in management is envisaged. […] The calculated growth rates as above are based on averages from the reported series. This is clearly not a reflection of the tumor biology nor the intrinsic growth of ameloblastoma and its subtypes, but of the average calculated rates. […] Notwithstanding, in the literature, there are other factors that have established a clear correlation with more rapid growth and a poorer outcome. These include maxillary ameloblastoma when compared to the mandible, the solid, multicystic histological subtype, unicystic subtype invading the fibrous wall, older age, malignant ameloblastoma, and suboptimal treatment. […] Current meta-analysis has produced a mean SGR of 87.84% growth per year for benign ameloblastoma, after removing outliers, which offers prognostic and management information, particularly in cases where a delay in management is envisaged.

• #69 Contemporary Treatment of Ameloblastoma | Pocket Dentistry

  https://pocketdentistry.com/contemporary-treatment-of-ameloblastoma/

  Ameloblastoma is a slow-growing tumor that may take years before clinical presentation. […] The majority of ameloblastomas, approximately 80%, arise in the mandible versus 20% in the maxilla. […] There are three classic varieties of ameloblastoma: solid/multicystic, unicystic, and peripheral. […] The solid/multicystic and unicystic types have several histologic variants that can have different biologic behavior. […] Although there are many histologic subtypes of ameloblastoma, there does not appear to be a significant difference in clinical behavior. […] However, Hong et al suggested that the follicular, granular cell, and acanthomatous subtypes showed a higher recurrence rate, whereas the plexiform and desmoplastic patterns showed a lower rate of recurrence. […] The desmoplastic type is the most recently identified form, first described by Eversole. […] The clinical presentation of unicystic ameloblastomas varies from the solid/multicystic types. […] The mural type of unicystic ameloblastoma is characterized by infiltration of the tumor islands into the fibrous connective tissue wall of the cyst.

• #70 Ameloblastoma | PPT

  https://www.slideshare.net/slideshow/ameloblastoma-69909552/69909552

  11) Age: 20-50 years Sex: no significant sex predilection Race: more common in blacks than in white race. Site: mandible maxilla(more than 80% mandible) with in mandible molar ramus area is affected three times more commonly than premolars anteriors. CLINICAL FEATURES […] 33) MALIGNANT AMELOBLASTOMA Malignant transformation of ameloblastoma Rare lesion Almost exclusively in mandible Mean age: 28-32 yrs Common sites for metastasis; Lungs, spleen, kidney, ileum […] 40) SEGMENTAL RESECTION Means removal of segment of the maxilla/mandible up to including hemisection or more. Includes hemimaxillectomy hemimandibulectomy. Most Commonly used treatment. Least chance of recurrence. It is noted that the lesion most likely to recur after segmental resection are those over 5cm.

• #71 Establishing the Natural History and Growth Rate of Ameloblastoma with Implications for Management: Systematic Review and Meta-Analysis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117241

  Ameloblastoma is the second most common odontogenic tumor, known to be slow-growing, persistent, and locally aggressive. […] An understanding of the growth rate and natural history of ameloblastoma has been notably lacking from the literature. […] The growth rate of ameloblastoma has been demonstrated, offering prognostic and management information, particularly in cases where a delay in management is envisaged. […] The calculated growth rates as above are based on averages from the reported series. This is clearly not a reflection of the tumor biology nor the intrinsic growth of ameloblastoma and its subtypes, but of the average calculated rates. […] Notwithstanding, in the literature, there are other factors that have established a clear correlation with more rapid growth and a poorer outcome. These include maxillary ameloblastoma when compared to the mandible, the solid, multicystic histological subtype, unicystic subtype invading the fibrous wall, older age, malignant ameloblastoma, and suboptimal treatment. […] Current meta-analysis has produced a mean SGR of 87.84% growth per year for benign ameloblastoma, after removing outliers, which offers prognostic and management information, particularly in cases where a delay in management is envisaged.

• #72

  https://bibliomed.org/?mno=109815

  Ameloblastoma are benign epithelial odontogenic tumors affecting the jaws. […] The main objective of this article is to review the pathogenesis, clinical and radiological features, classification, and management of ameloblastoma. […] In 2017, ameloblastomas were classified by W.H.O into three categories: a) unicystic, b) conventional, and c) extraosseous/peripheral. […] Clinically, they are slow-growing, localized, aggressive neoplasms. […] Radologically, they mainly present as extensive, radiolucent, multilocular images, with a typical soap bubble-like appearance with a thinner, expanded, and eroded cortical plate. […] Because of their late signs and symptoms, ameloblastomas are usually identified at an advanced stage. […] Their management typically includes a large resection with safety margins and immediate reconstruction when possible. […] Regular long-term postoperative follow-ups are mandatory for optimum treatment outcome and recurrence prevention.

• #73 Ameloblastoma: Pathogenesis, Clinical and Radiological Features, Classification, and Management – IJBH

  https://ijbh.org/article/ameloblastoma-pathogenesis-clinical-and-radiological-features-classification-and-management/

  Background: Ameloblastoma are benign epithelial odontogenic tumors affecting the jaws. […] Objective: The main objective of this article is to review the pathogenesis, clinical and radiological features, classification, and management of ameloblastoma. […] Results: In 2017, ameloblastomas were classified by W.H.O into three categories: a) unicystic, b) conventional, and c) extraosseous/peripheral. […] Clinically, they are slow-growing, localized, aggressive neoplasms. […] Radologically, they mainly present as extensive, radiolucent, multilocular images, with a typical „soap bubble-like” appearance with a thinner, expanded, and eroded cortical plate. […] Conclusion: Because of their late signs and symptoms, ameloblastomas are usually identified at an advanced stage.

• #74 Contemporary Treatment of Ameloblastoma | Pocket Dentistry

  https://pocketdentistry.com/contemporary-treatment-of-ameloblastoma/

  Ameloblastoma is a slow-growing tumor that may take years before clinical presentation. […] The majority of ameloblastomas, approximately 80%, arise in the mandible versus 20% in the maxilla. […] There are three classic varieties of ameloblastoma: solid/multicystic, unicystic, and peripheral. […] The solid/multicystic and unicystic types have several histologic variants that can have different biologic behavior. […] Although there are many histologic subtypes of ameloblastoma, there does not appear to be a significant difference in clinical behavior. […] However, Hong et al suggested that the follicular, granular cell, and acanthomatous subtypes showed a higher recurrence rate, whereas the plexiform and desmoplastic patterns showed a lower rate of recurrence. […] The desmoplastic type is the most recently identified form, first described by Eversole. […] The clinical presentation of unicystic ameloblastomas varies from the solid/multicystic types. […] The mural type of unicystic ameloblastoma is characterized by infiltration of the tumor islands into the fibrous connective tissue wall of the cyst.

• #75 Contemporary Treatment of Ameloblastoma | Pocket Dentistry

  https://pocketdentistry.com/contemporary-treatment-of-ameloblastoma/

  Ameloblastoma is a slow-growing tumor that may take years before clinical presentation. […] The majority of ameloblastomas, approximately 80%, arise in the mandible versus 20% in the maxilla. […] There are three classic varieties of ameloblastoma: solid/multicystic, unicystic, and peripheral. […] The solid/multicystic and unicystic types have several histologic variants that can have different biologic behavior. […] Although there are many histologic subtypes of ameloblastoma, there does not appear to be a significant difference in clinical behavior. […] However, Hong et al suggested that the follicular, granular cell, and acanthomatous subtypes showed a higher recurrence rate, whereas the plexiform and desmoplastic patterns showed a lower rate of recurrence. […] The desmoplastic type is the most recently identified form, first described by Eversole. […] The clinical presentation of unicystic ameloblastomas varies from the solid/multicystic types. […] The mural type of unicystic ameloblastoma is characterized by infiltration of the tumor islands into the fibrous connective tissue wall of the cyst.

• #76 Establishing the Natural History and Growth Rate of Ameloblastoma with Implications for Management: Systematic Review and Meta-Analysis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117241

  Ameloblastoma is the second most common odontogenic tumor, known to be slow-growing, persistent, and locally aggressive. […] An understanding of the growth rate and natural history of ameloblastoma has been notably lacking from the literature. […] The growth rate of ameloblastoma has been demonstrated, offering prognostic and management information, particularly in cases where a delay in management is envisaged. […] The calculated growth rates as above are based on averages from the reported series. This is clearly not a reflection of the tumor biology nor the intrinsic growth of ameloblastoma and its subtypes, but of the average calculated rates. […] Notwithstanding, in the literature, there are other factors that have established a clear correlation with more rapid growth and a poorer outcome. These include maxillary ameloblastoma when compared to the mandible, the solid, multicystic histological subtype, unicystic subtype invading the fibrous wall, older age, malignant ameloblastoma, and suboptimal treatment. […] Current meta-analysis has produced a mean SGR of 87.84% growth per year for benign ameloblastoma, after removing outliers, which offers prognostic and management information, particularly in cases where a delay in management is envisaged.

• #77

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Overexpression of FOS and TNFR1A have been significant in the oncogenic transformation pathway of ameloblastoma. […] The tumor cells do not attain functional maturation as secretory phase ameloblasts thereby not expressing the enamel proteins. […] Other mechanisms which have been studied and quoted in the literature are listed. Epigenetics is an event in the pathogenesis of ameloblastoma where the P21 gene undergoes methylation along with alterations in P16 and RB1. […] The invasive ability of ameloblastoma is related to the release of molecules like matrix metalloproteinases, which trigger mitogens to be released, leading to proliferation of ameloblastoma cells. […] Bone Morphogenetic Protein (BMP), member of the transforming growth factor (TGF) super family, is a mesenchymal cell differentiation factor and a morphogen.

• #78

  https://journals.lww.com/jpbs/fulltext/2015/07001/ameloblastoma.46.aspx

  Ameloblastoma is a neoplasm of odontogenic epithelium, principally of enamel organ-type tissue that has not undergone differentiation to the point of hard tissue formation. […] Signaling pathway such as WNT, Akt and growth factors like fibroblast growth factor play a pivotal role in the pathogenesis of solid type of ameloblastoma. Proteins mainly bone morphogenic protein ameloblastin, enamel matrix proteins calretinin, syndecan-1 and matrix metalloproteinases also play an important contribution in the etiopathogenesis. Tumor suppressor genes p53, p63 and p73 bring about molecular changes in the pathogenesis of ameloblastoma. p53 plays an important role in the differentiation and proliferation of odontogenic epithelial cells. Matrix metalloproteinases, triggers mitogens to be released, leading to the proliferation of ameloblastoma cells. […] Three pathogenic mechanisms for the evolution of UA: Reduced enamel epithelium, from dentigerous cyst and due to cystic degeneration of solid ameloblastoma.

• #79

  https://journals.lww.com/jpbs/fulltext/2015/07001/ameloblastoma.46.aspx

  Ameloblastoma is a neoplasm of odontogenic epithelium, principally of enamel organ-type tissue that has not undergone differentiation to the point of hard tissue formation. […] Signaling pathway such as WNT, Akt and growth factors like fibroblast growth factor play a pivotal role in the pathogenesis of solid type of ameloblastoma. Proteins mainly bone morphogenic protein ameloblastin, enamel matrix proteins calretinin, syndecan-1 and matrix metalloproteinases also play an important contribution in the etiopathogenesis. Tumor suppressor genes p53, p63 and p73 bring about molecular changes in the pathogenesis of ameloblastoma. p53 plays an important role in the differentiation and proliferation of odontogenic epithelial cells. Matrix metalloproteinases, triggers mitogens to be released, leading to the proliferation of ameloblastoma cells. […] Three pathogenic mechanisms for the evolution of UA: Reduced enamel epithelium, from dentigerous cyst and due to cystic degeneration of solid ameloblastoma.

• #80

  http://jurnal.pdgi.or.id/index.php/jida/article/view/1022

  Unicystic ameloblastoma can occur due to neoplastic transformation from an odontogenic cyst to an odontogenic tumor, ameloblastic transformation of reduced enamel epithelium from developing teeth, or cystic degeneration of solid ameloblastoma. […] However, there is no convincing evidence has yet been found for each proposed pathogenesis. […] Etiology of the unicystic ameloblastoma has not undergone renewal, and the currently known pathogenesis of the unicystic ameloblastoma is molecular pathogenesis, namely where the development of odontogenic lesions occurs due to pathogenic gene mutations that affect the signaling pathway. […] The mutation that often occurs is the BRAF V600E mutation which is included in the MAPK signaling pathway.

• #81

  http://jurnal.pdgi.or.id/index.php/jida/article/view/1022

  Unicystic ameloblastoma can occur due to neoplastic transformation from an odontogenic cyst to an odontogenic tumor, ameloblastic transformation of reduced enamel epithelium from developing teeth, or cystic degeneration of solid ameloblastoma. […] However, there is no convincing evidence has yet been found for each proposed pathogenesis. […] Etiology of the unicystic ameloblastoma has not undergone renewal, and the currently known pathogenesis of the unicystic ameloblastoma is molecular pathogenesis, namely where the development of odontogenic lesions occurs due to pathogenic gene mutations that affect the signaling pathway. […] The mutation that often occurs is the BRAF V600E mutation which is included in the MAPK signaling pathway.

• #82 Ameloblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK545165/

  The cause of ameloblastoma is not well understood. There is recent evidence that genetic mutations that activate a specific signaling pathway (MAPK) play a role in the pathogenesis of ameloblastoma. […] Further understanding of the molecular basis of tumorigenesis will have implications for diagnosis and therapy.

• #83 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Ameloblastomas are benign odontogenic tumors of epithelial origin, uncommon, locally aggressive and being able to reach large sizes. […] In 2014 important studies on the genetics of ameloblastomas were published. Crucial to its etiopathogenesis and understanding, these studies identified highly recurrent mutations in mitogen-activated protein kinase (MAPK) and Hedgehog (SHH) signaling pathways. […] The etiologic factors described relate to the onset of the lesion after a local trauma, inflammation, nutritional deficiencies, mutations and/or molecular alterations, where different signaling pathways participate. More recent theories indicate the existence of genetic anomalies related to the appearance of ameloblastomas, enabling less aggressive treatments. […] Currently, there are targeted therapies due to recent advances in the understanding of the molecular signaling pathways associated with ameloblastoma pathogenesis. MAPK-specific drugs (Mitogen-Activated Protein Kinases) selectively inhibit the functions of BRAF (B-Raf proto-oncogene) and MEK mutants to stop the deregulated proliferation and differentiation of ameloblastic cells.

• #84 (PDF) REVIEW ARTICLE: Current concepts of ameloblastoma pathogenesis

  https://www.academia.edu/61448760/REVIEW_ARTICLE_Current_concepts_of_ameloblastoma_pathogenesis

  Ameloblastoma is a locally destructive and invasive tumour that can recur despite adequate surgical removal. Molecular studies have offered interesting findings regarding ameloblastoma pathogenesis. In the present review, the following topics are discussed regarding its molecular nature: clonality, cell cycle proliferation, apoptosis, tumour suppressor genes, ameloblastin and other enamel matrix proteins, osteoclastic mechanism and matrix metalloproteinases and other signalling molecules. […] It is clear from the literature reviewed that translational studies are necessary to identify prognostic markers of ameloblastoma behaviour and to establish new diagnostic tools to the differential diagnosis of unicystic from multicystic ameloblastoma. […] Finally, molecular biology studies are also important to develop more effective alternative approaches to the treatment of this aggressive odontogenic tumour.

• #85 Ameloblastoma: brief review of molecular pathogenesis and history

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=115385

  Ameloblastoma is a progressively growing benign intraosseous epithelial odontogenic odontogenic neoplasm characterized by local invasion and a tendency to recur if not adequately removed. […] Although the pathogenesis of ameloblastoma is controversial, several authors have invoked numerous theories to elucidate the development and behavior of these tumors. […] Recently, studies have increasingly focused on the molecular aspects of ameloblastoma pathogenesis to identify potential therapeutic targets. […] However, the molecular background of ameloblastoma development remains unclear. […] The presence or absence of mutations correlates with several clinicopathologic features, including location, age at diagnosis, histology, and prognosis. […] Further studies are needed to verify these theories.

• #86

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Though numerous markers are mentioned in pathogenesis, aggressiveness and malignant potential of the tumor, no specific marker has been illustrated for different histopathological variants of ameloblastoma. […] The proper understanding of the pathogenetic mechanism involved in ameloblastoma and its proliferation aids in constituting proper treatment of choice at an early stage thereby preventing morbidity associated with extensive therapy.

• #87 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Ameloblastomas are benign odontogenic tumors of epithelial origin, uncommon, locally aggressive and being able to reach large sizes. […] In 2014 important studies on the genetics of ameloblastomas were published. Crucial to its etiopathogenesis and understanding, these studies identified highly recurrent mutations in mitogen-activated protein kinase (MAPK) and Hedgehog (SHH) signaling pathways. […] The etiologic factors described relate to the onset of the lesion after a local trauma, inflammation, nutritional deficiencies, mutations and/or molecular alterations, where different signaling pathways participate. More recent theories indicate the existence of genetic anomalies related to the appearance of ameloblastomas, enabling less aggressive treatments. […] Currently, there are targeted therapies due to recent advances in the understanding of the molecular signaling pathways associated with ameloblastoma pathogenesis. MAPK-specific drugs (Mitogen-Activated Protein Kinases) selectively inhibit the functions of BRAF (B-Raf proto-oncogene) and MEK mutants to stop the deregulated proliferation and differentiation of ameloblastic cells.

• #88 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Ameloblastomas are benign odontogenic tumors of epithelial origin, uncommon, locally aggressive and being able to reach large sizes. […] In 2014 important studies on the genetics of ameloblastomas were published. Crucial to its etiopathogenesis and understanding, these studies identified highly recurrent mutations in mitogen-activated protein kinase (MAPK) and Hedgehog (SHH) signaling pathways. […] The etiologic factors described relate to the onset of the lesion after a local trauma, inflammation, nutritional deficiencies, mutations and/or molecular alterations, where different signaling pathways participate. More recent theories indicate the existence of genetic anomalies related to the appearance of ameloblastomas, enabling less aggressive treatments. […] Currently, there are targeted therapies due to recent advances in the understanding of the molecular signaling pathways associated with ameloblastoma pathogenesis. MAPK-specific drugs (Mitogen-Activated Protein Kinases) selectively inhibit the functions of BRAF (B-Raf proto-oncogene) and MEK mutants to stop the deregulated proliferation and differentiation of ameloblastic cells.

• #89 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Ameloblastomas are benign odontogenic tumors of epithelial origin, uncommon, locally aggressive and being able to reach large sizes. […] In 2014 important studies on the genetics of ameloblastomas were published. Crucial to its etiopathogenesis and understanding, these studies identified highly recurrent mutations in mitogen-activated protein kinase (MAPK) and Hedgehog (SHH) signaling pathways. […] The etiologic factors described relate to the onset of the lesion after a local trauma, inflammation, nutritional deficiencies, mutations and/or molecular alterations, where different signaling pathways participate. More recent theories indicate the existence of genetic anomalies related to the appearance of ameloblastomas, enabling less aggressive treatments. […] Currently, there are targeted therapies due to recent advances in the understanding of the molecular signaling pathways associated with ameloblastoma pathogenesis. MAPK-specific drugs (Mitogen-Activated Protein Kinases) selectively inhibit the functions of BRAF (B-Raf proto-oncogene) and MEK mutants to stop the deregulated proliferation and differentiation of ameloblastic cells.

• #90 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Similarly, targeted therapies have been developed to control the effect of the SMO mutation associated with ameloblastoma pathogenesis. […] As the expression of SHH is high in ameloblastomas, several drugs already used to antagonize SHH signaling offer other non-surgical targeted therapeutic options for patients with this type of tumor.

• #91 Ameloblastomas: current aspects of the new WHO classification in an analysis of 136 cases | Surgical and Experimental Pathology | Full Text

  https://surgexppathol.biomedcentral.com/articles/10.1186/s42047-019-0041-z

  Similarly, targeted therapies have been developed to control the effect of the SMO mutation associated with ameloblastoma pathogenesis. […] As the expression of SHH is high in ameloblastomas, several drugs already used to antagonize SHH signaling offer other non-surgical targeted therapeutic options for patients with this type of tumor.

• #92 Anti-MAPK Targeted Therapy for Ameloblastoma: Case Report with a Systematic Review

  https://www.mdpi.com/2072-6694/16/12/2174

  Ameloblastoma is a benign odontogenic tumor that originates from odontogenic epithelium. Although benign, it is a locally aggressive neoplasm that has a strong tendency to recur and may metastasize to distant sites. In 2014, three independent studies were published about the genetic profiling of ameloblastomas via DNA sequencing and all three studies showed a high incidence of somatic mutations impacting the mitogen-activated protein kinase (MAPK) that controls cell proliferation. A specific mutation, BRAF V600E, was reported at high frequencies. BRAF is a serine–threonine kinase within the MAPK pathway. This mutation constitutively initiates the mitogen-activated kinase pathway and thus enhances cell proliferation and survival activity in a ligand-independent manner. More interestingly, if a BRAF mutation is present, it tends to be exclusive regarding other mutations also present in ameloblastoma, making BRAF the most frequent genetic alteration and closely associated with its pathogenesis. 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. The MAPK pathway seems to be the keystone to targeting.

• #93

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Though numerous markers are mentioned in pathogenesis, aggressiveness and malignant potential of the tumor, no specific marker has been illustrated for different histopathological variants of ameloblastoma. […] The proper understanding of the pathogenetic mechanism involved in ameloblastoma and its proliferation aids in constituting proper treatment of choice at an early stage thereby preventing morbidity associated with extensive therapy.

• #94 Establishing the Natural History and Growth Rate of Ameloblastoma with Implications for Management: Systematic Review and Meta-Analysis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117241

  Ameloblastoma is the second most common odontogenic tumor, known to be slow-growing, persistent, and locally aggressive. […] An understanding of the growth rate and natural history of ameloblastoma has been notably lacking from the literature. […] The growth rate of ameloblastoma has been demonstrated, offering prognostic and management information, particularly in cases where a delay in management is envisaged. […] The calculated growth rates as above are based on averages from the reported series. This is clearly not a reflection of the tumor biology nor the intrinsic growth of ameloblastoma and its subtypes, but of the average calculated rates. […] Notwithstanding, in the literature, there are other factors that have established a clear correlation with more rapid growth and a poorer outcome. These include maxillary ameloblastoma when compared to the mandible, the solid, multicystic histological subtype, unicystic subtype invading the fibrous wall, older age, malignant ameloblastoma, and suboptimal treatment. […] Current meta-analysis has produced a mean SGR of 87.84% growth per year for benign ameloblastoma, after removing outliers, which offers prognostic and management information, particularly in cases where a delay in management is envisaged.

• #95

  https://journals.lww.com/jdyu/fulltext/2013/02030/the_molecular_and_genetic_aspects_in_the.1.aspx

  Though numerous markers are mentioned in pathogenesis, aggressiveness and malignant potential of the tumor, no specific marker has been illustrated for different histopathological variants of ameloblastoma. […] The proper understanding of the pathogenetic mechanism involved in ameloblastoma and its proliferation aids in constituting proper treatment of choice at an early stage thereby preventing morbidity associated with extensive therapy.

• #96 Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5051300/

  Overexpression of WNT 5a increases enamel epithelial cell migration while suppression impairs their migration and fails to form actin re-organization. […] The TGF /SMAD signaling pathway has an important role in the invasiveness of ameloblastoma, especially in later stages. […] Pathogenesis of ameloblastoma is multifactorial and involves numerous cellular pathways. Diverse type of molecules and gene alterations affect the development and progression of odontogenic epithelium and these characteristics appear to depend on diverse molecular mechanisms. Proper understanding of the pathogenic mechanism involved in ameloblastoma and its proliferation will help in the development of new therapeutic approaches such as molecular-targeted treatment for odontogenic tumors.

• #97 Ameloblastoma: Current Etiopathological Concepts and Management

  https://repository.upenn.edu/items/113033ac-d15a-4b1a-a710-1e9c2332e50a

  Ameloblastoma is a benign odontogenic tumor of epithelial origin. It is locally aggressive with unlimited growth capacity and has a high potential for malignant transformation as well as metastasis. […] Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen-activated protein kinase, sonic hedgehog, and WNT/β-catenin signaling pathways. […] It is expected that further elucidation of molecular factors that orchestrate pathogenesis and recurrence of ameloblastoma will lead to new diagnostic markers and targeted drug therapies for ameloblastoma.

• #98 (PDF) REVIEW ARTICLE: Current concepts of ameloblastoma pathogenesis

  https://www.academia.edu/61448760/REVIEW_ARTICLE_Current_concepts_of_ameloblastoma_pathogenesis

  Ameloblastoma is a locally destructive and invasive tumour that can recur despite adequate surgical removal. Molecular studies have offered interesting findings regarding ameloblastoma pathogenesis. In the present review, the following topics are discussed regarding its molecular nature: clonality, cell cycle proliferation, apoptosis, tumour suppressor genes, ameloblastin and other enamel matrix proteins, osteoclastic mechanism and matrix metalloproteinases and other signalling molecules. […] It is clear from the literature reviewed that translational studies are necessary to identify prognostic markers of ameloblastoma behaviour and to establish new diagnostic tools to the differential diagnosis of unicystic from multicystic ameloblastoma. […] Finally, molecular biology studies are also important to develop more effective alternative approaches to the treatment of this aggressive odontogenic tumour.

• #99 Ameloblastoma: Current Etiopathological Concepts and Management

  https://repository.upenn.edu/items/113033ac-d15a-4b1a-a710-1e9c2332e50a

  Ameloblastoma is a benign odontogenic tumor of epithelial origin. It is locally aggressive with unlimited growth capacity and has a high potential for malignant transformation as well as metastasis. […] Molecular and genetic factors that promote oncogenic transformation of odontogenic epithelium to ameloblastoma are strongly linked to dysregulation of multiple genes associated with mitogen-activated protein kinase, sonic hedgehog, and WNT/β-catenin signaling pathways. […] It is expected that further elucidation of molecular factors that orchestrate pathogenesis and recurrence of ameloblastoma will lead to new diagnostic markers and targeted drug therapies for ameloblastoma.

• #100 Ameloblastoma of the Mandible in a 16-Year-Old Female—Case Report

  https://www.mdpi.com/1648-9144/60/1/66

  Ameloblastoma arises from remnants of the odontogenic epithelium, more specifically the remnants of the dental lamina. […] The pathogenesis of ameloblastoma has been found to be related to the deregulation of the SHH, WNT/β-catenin and MAPK signaling pathways, and the detection of the BRAF V600E mutation has been found to be associated with more aggressive clinical forms. […] There are data in the literature that indicate LRP5, SLC6A3 and SOX10 are potentially important genes whose presence is related to cell proliferation and invasion of ameloblastomas, and a possible inhibitory treatment is indicated subject to clarification of the molecular pathways of these genes in relation to ameloblastoma tumorigenesis.

• #101 Mechanism and Potential Therapy in Ameloblastoma: Akt Signaling Pathway | Hadi | The Indonesian Biomedical Journal

  https://inabj.org/index.php/ibj/article/view/1824

  Ameloblastoma can arise at any age, however it most usually affect patients between the ages of 20 and 40. […] Akt signaling pathway in ameloblastoma has been implicated in the formation and progression of tumors. […] The present review highlights various Akt signaling involved in ameloblastoma and its potential pathways for treatments, while the gold standard of ameloblastoma treatment is still surgery to remove the tumor, there are many potential agents through various means of inhibition for ameloblastoma. […] Therefore, understanding the underlying signaling on ameloblastoma is necessary to induce inhibition on ameloblastoma. […] More research in potential ways to inhibit Akt signaling in ameloblastoma will lead to a better management of ameloblastoma in the future.

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