Materiały źródłowe

• #1 Pathology Outlines – Schwannoma

  https://www.pathologyoutlines.com/topic/softtissueschwannoma.html

  Benign nerve sheath tumor arising from differentiated Schwann cells […] May occur spontaneously […] Can occur in familial tumor syndromes, such as neurofibromatosis type 2 (NF2), schwannomatosis or Carney complex […] Loss of function of the tumor suppressor gene merlin (schwannomin) […] Direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation […] Can occur in NF2 and spontaneous schwannomas […] Can cause other neoplasms including meningioma, mesothelioma, glioma multiforme and carcinomas of breast, colon and rectum, kidney (clear cell type), liver, prostate and skin […] Can be caused by loss of function of the tumor suppressor gene, merlin (schwannomin) […] Merlin acts as a tumor suppressor gene […] Overexpression can hinder cell proliferation and the changes induced by oncogenes […] Its downregulation leads to neoplastic transformation […] Mutations affecting SMARCB1 have a role in the pathogenesis of a small subset of spinal schwannomas and biallelic inactivation of SMARCB1 may cooperate with deficiency of NF2 function.

• #2 Schwannoma: Anatomy, Clinical Characteristics, & Management

  https://www.theplasticsfella.com/schwannoma/

  Schwannomas are benign tumors originating from Schwann cells, which form the myelin sheath around axons. […] A Schwannoma is a benign, isolated peripheral nerve lesion with no malignant potential. These benign tumors develop from Schwann cells, which form the myelin sheath around axons and are crucial for effective nerve signal transmission. […] Schwannomas originate from Schwann cells, their growth patterns, and the symptoms they cause due to nerve compression.

• #3 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF 2 gene on chromosome 22 or secondarily to merlin inactivation. […] This review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Following the identification of the NF2 gene, and its product merlin (schwannomin) on chromosome 22 in 1993, a better understanding of the disease pathogenesis has developed. […] The risk of offspring inheriting NF2 in mosaic patients is difficult to quantify, but may be considerably less than 50%.

• #4 Schwannomas and their pathogenesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/24450866/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. […] this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Merlin loss leads to increased growth factor expression and activation of the Ras and phosphatidylinositol 3-kinase (PI3K) pathways. A central mechanism is the loss of merlin-induced inhibition of the CRL4DCAF1 complex within the nucleus, resulting in increased transcription of a number of genes, including integrins and growth factor receptors. Merlin also interacts with cell surface proteins, including CD44 and adhesion junction proteins, so that merlin deficiency leads to reduced contact-dependent cell cycle arrest.

• #5 Schwannomas and their pathogenesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/24450866/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. […] this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Merlin loss leads to increased growth factor expression and activation of the Ras and phosphatidylinositol 3-kinase (PI3K) pathways. A central mechanism is the loss of merlin-induced inhibition of the CRL4DCAF1 complex within the nucleus, resulting in increased transcription of a number of genes, including integrins and growth factor receptors. Merlin also interacts with cell surface proteins, including CD44 and adhesion junction proteins, so that merlin deficiency leads to reduced contact-dependent cell cycle arrest.

• #6 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF 2 gene on chromosome 22 or secondarily to merlin inactivation. […] This review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Following the identification of the NF2 gene, and its product merlin (schwannomin) on chromosome 22 in 1993, a better understanding of the disease pathogenesis has developed. […] The risk of offspring inheriting NF2 in mosaic patients is difficult to quantify, but may be considerably less than 50%.

• #7 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Merlin functions as a tumor suppressor and regulates tumor growth in its open state, while phosphorylation converts it to a less active, more closed state. […] Merlin is involved in multiple oncogenic signaling pathways, including Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 signaling, which are downstream of receptor tyrosine kinases. […] Given that merlin inhibits this Ras-mediated signaling pathway, merlin dysfunction allows for enhanced Ras signaling and an accelerated tumor growth in schwannomas. […] The PI3K/Akt/mTORC1 signaling pathway similarly contributes to cell growth, differentiation, and apoptosis inhibition, and is upregulated in schwannomas. […] The activation of the Wnt/-catenin signaling has also been observed in human schwannoma cells, demonstrated by the upregulated expression of Wnt target genes c-myc and cyclin D1.

• #8 Molecular biology of sporadic vestibular schwannomas i…

  https://otorhinolaryngologypl.com/seo/article/01.3001.0014.4201/en

  The closed form of merlin represents its active form, which acts as a tumor suppressor protein. […] The evidence suggests that merlin has the ability to suppress this signaling pathway therefore an activation loop between merlin and PAK was suggested, although this mechanism may be limited to epithelial cells [16, 17]. […] The inactivation of merlin inhibits this mechanism and, as a result, accelerates the cell cycle [9, 18]. […] Merlin has been proposed to limit proliferation by inhibiting receptor tyrosine kinases, including receptors for many growth factors – PDGF, IGFR1, VEGF, EGF. […] Merlin also affects the Hippo signaling pathway. […] The major obstacles in conducting research are: lack of appropriate comparative material, contamination of tumor specimen by stromal and infiltrating inflammatory cells, which leads to a number of different results.

• #9 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] Merlin loss thus leads to increase integrin expression, resulting in increased cell spreading on the extracellular matrix in vitro and pseudomesaxon formation in vivo. […] Merlin loss also leads to increased expression and signaling of growth factors, resulting in increased proliferation in vitro and in vivo. […] Driven by the fact that growth factor receptors have been investigated intensively in oncology as potential therapeutic targets, growth factor receptors have been studied in some detail in schwannomas. […] Overexpression of platelet-derived growth factor receptor (PDGFR) and insulin-like growth factor receptor (IGF 1R) are also seen, and these seem to be functional in schwannomas, offering further potential sites for therapeutic drug targeting.

• #10 Schwannomas and their pathogenesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/24450866/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. […] this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Merlin loss leads to increased growth factor expression and activation of the Ras and phosphatidylinositol 3-kinase (PI3K) pathways. A central mechanism is the loss of merlin-induced inhibition of the CRL4DCAF1 complex within the nucleus, resulting in increased transcription of a number of genes, including integrins and growth factor receptors. Merlin also interacts with cell surface proteins, including CD44 and adhesion junction proteins, so that merlin deficiency leads to reduced contact-dependent cell cycle arrest.

• #11 Schwannomas and their pathogenesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/24450866/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. […] this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Merlin loss leads to increased growth factor expression and activation of the Ras and phosphatidylinositol 3-kinase (PI3K) pathways. A central mechanism is the loss of merlin-induced inhibition of the CRL4DCAF1 complex within the nucleus, resulting in increased transcription of a number of genes, including integrins and growth factor receptors. Merlin also interacts with cell surface proteins, including CD44 and adhesion junction proteins, so that merlin deficiency leads to reduced contact-dependent cell cycle arrest.

• #12 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] Merlin loss thus leads to increase integrin expression, resulting in increased cell spreading on the extracellular matrix in vitro and pseudomesaxon formation in vivo. […] Merlin loss also leads to increased expression and signaling of growth factors, resulting in increased proliferation in vitro and in vivo. […] Driven by the fact that growth factor receptors have been investigated intensively in oncology as potential therapeutic targets, growth factor receptors have been studied in some detail in schwannomas. […] Overexpression of platelet-derived growth factor receptor (PDGFR) and insulin-like growth factor receptor (IGF 1R) are also seen, and these seem to be functional in schwannomas, offering further potential sites for therapeutic drug targeting.

• #13 Schwannomas and their pathogenesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/24450866/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. […] this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Merlin loss leads to increased growth factor expression and activation of the Ras and phosphatidylinositol 3-kinase (PI3K) pathways. A central mechanism is the loss of merlin-induced inhibition of the CRL4DCAF1 complex within the nucleus, resulting in increased transcription of a number of genes, including integrins and growth factor receptors. Merlin also interacts with cell surface proteins, including CD44 and adhesion junction proteins, so that merlin deficiency leads to reduced contact-dependent cell cycle arrest.

• #14 Schwannomas and their pathogenesis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/24450866/

  Schwannomas may occur spontaneously, or in the context of a familial tumor syndrome such as neurofibromatosis type 2 (NF2), schwannomatosis and Carney’s complex. […] Central to the pathogenesis of these tumors is loss of function of merlin, either by direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation. […] this review summarizes our current understanding of the mechanisms by which merlin loss is involved in schwannoma pathogenesis, highlighting potential areas for therapeutic intervention. […] Merlin loss leads to increased growth factor expression and activation of the Ras and phosphatidylinositol 3-kinase (PI3K) pathways. A central mechanism is the loss of merlin-induced inhibition of the CRL4DCAF1 complex within the nucleus, resulting in increased transcription of a number of genes, including integrins and growth factor receptors. Merlin also interacts with cell surface proteins, including CD44 and adhesion junction proteins, so that merlin deficiency leads to reduced contact-dependent cell cycle arrest.

• #15 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Merlin functions as a tumor suppressor and regulates tumor growth in its open state, while phosphorylation converts it to a less active, more closed state. […] Merlin is involved in multiple oncogenic signaling pathways, including Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 signaling, which are downstream of receptor tyrosine kinases. […] Given that merlin inhibits this Ras-mediated signaling pathway, merlin dysfunction allows for enhanced Ras signaling and an accelerated tumor growth in schwannomas. […] The PI3K/Akt/mTORC1 signaling pathway similarly contributes to cell growth, differentiation, and apoptosis inhibition, and is upregulated in schwannomas. […] The activation of the Wnt/-catenin signaling has also been observed in human schwannoma cells, demonstrated by the upregulated expression of Wnt target genes c-myc and cyclin D1.

• #16

  https://link.springer.com/article/10.1007/s12105-020-01155-x

  Mutations to NF2, a tumour suppressor gene on chromosome 22, play a vital role in the development of both sporadic and NF2-related disease. Inactivation of the NF2 protein product, Merlin (schwannomin), leads to deregulation of various intracellular signalling pathways such as Rac1, Ras, PAK1, and mTORC1. Inactivation of other tumour suppressor genes including LZTR1, SMARCB1, and COQ6 are also linked to schwannoma development. […] Although the role of NF2 mutations was reinforced by recent large-scale sequencing studies, there are data to suggest that NF2-associated VS has a different, polyclonal mutation pattern. This has been postulated to account for variance in treatment outcomes as compared to sporadic VS.

• #17 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Merlin functions as a tumor suppressor and regulates tumor growth in its open state, while phosphorylation converts it to a less active, more closed state. […] Merlin is involved in multiple oncogenic signaling pathways, including Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 signaling, which are downstream of receptor tyrosine kinases. […] Given that merlin inhibits this Ras-mediated signaling pathway, merlin dysfunction allows for enhanced Ras signaling and an accelerated tumor growth in schwannomas. […] The PI3K/Akt/mTORC1 signaling pathway similarly contributes to cell growth, differentiation, and apoptosis inhibition, and is upregulated in schwannomas. […] The activation of the Wnt/-catenin signaling has also been observed in human schwannoma cells, demonstrated by the upregulated expression of Wnt target genes c-myc and cyclin D1.

• #18 A Review of Drug Therapy in Vestibular Schwannoma | DDDT

  https://www.dovepress.com/a-review-of-drug-therapy-in-vestibular-schwannoma-peer-reviewed-fulltext-article-DDDT

  Vestibular schwannomas (VSs, also known as acoustic neuromas) are benign intracranial tumors commonly managed with observation, surgery, and radiotherapy. […] Conventional chemotherapeutic agents are characterized by neurotoxicity or ototoxicity, poor effect on slow-growing tumors, and may induce new mutations in patients who have lost tumor suppressor function, and therefore are unsuitable for treating VSs. […] The growing understanding of the mechanisms by which merlin dysregulation induces disease, as well as of signal pathways related to VS growth, has raised hopes for the application of targeted therapies. […] Recent studies have suggested that merlin can regulate multiple pathways implicated in tumorigenesis including retrovirus-associated DNA sequences (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen extracellular signal-regulated kinase (MEK)/extracellular-signal-regulated kinases (ERK), mammalian target of rapamycin complex 1 (mTORC1), Rac/p21-activated kinase (PAK)/C-Jun kinase, phosphoinositide 3-kinase (PI3K)/Akt and the intranuclear E3 ubiquitin ligase CRL4 (DCAF1).

• #19 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Merlin functions as a tumor suppressor and regulates tumor growth in its open state, while phosphorylation converts it to a less active, more closed state. […] Merlin is involved in multiple oncogenic signaling pathways, including Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 signaling, which are downstream of receptor tyrosine kinases. […] Given that merlin inhibits this Ras-mediated signaling pathway, merlin dysfunction allows for enhanced Ras signaling and an accelerated tumor growth in schwannomas. […] The PI3K/Akt/mTORC1 signaling pathway similarly contributes to cell growth, differentiation, and apoptosis inhibition, and is upregulated in schwannomas. […] The activation of the Wnt/-catenin signaling has also been observed in human schwannoma cells, demonstrated by the upregulated expression of Wnt target genes c-myc and cyclin D1.

• #20 ADAM9: A novel player in vestibular schwannoma pathogenesis

  https://www.spandidos-publications.com/10.3892/ol.2020.11299?text=fulltext

  ADAM9 is expressed in different types of solid cancer and promotes tumor invasiveness. […] The main known pathomechanism for vestibular schwannoma is the loss of function by Merlin. Merlin’s loss of function is the main known mechanism for the development of VS and results in the activation of two signaling pathways. These are the Ras/Raf/MEK pathway and the PI3K/Akt/mTOR pathway, which inhibit apoptosis and result in higher cell survival or proliferation rates. […] ADAM9 may be a prognostic marker for VS, and ADAM9 inhibition might have the potential as a systemic approach for the treatment of VS. […] The present investigation demonstrates for the first time that ADAM9 is expressed in VS by neoplastic Schwann cells, and thus, could play a significant role in the pathogenesis of these tumors.

• #21 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Merlin functions as a tumor suppressor and regulates tumor growth in its open state, while phosphorylation converts it to a less active, more closed state. […] Merlin is involved in multiple oncogenic signaling pathways, including Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 signaling, which are downstream of receptor tyrosine kinases. […] Given that merlin inhibits this Ras-mediated signaling pathway, merlin dysfunction allows for enhanced Ras signaling and an accelerated tumor growth in schwannomas. […] The PI3K/Akt/mTORC1 signaling pathway similarly contributes to cell growth, differentiation, and apoptosis inhibition, and is upregulated in schwannomas. […] The activation of the Wnt/-catenin signaling has also been observed in human schwannoma cells, demonstrated by the upregulated expression of Wnt target genes c-myc and cyclin D1.

• #22 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Merlin functions as a tumor suppressor and regulates tumor growth in its open state, while phosphorylation converts it to a less active, more closed state. […] Merlin is involved in multiple oncogenic signaling pathways, including Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 signaling, which are downstream of receptor tyrosine kinases. […] Given that merlin inhibits this Ras-mediated signaling pathway, merlin dysfunction allows for enhanced Ras signaling and an accelerated tumor growth in schwannomas. […] The PI3K/Akt/mTORC1 signaling pathway similarly contributes to cell growth, differentiation, and apoptosis inhibition, and is upregulated in schwannomas. […] The activation of the Wnt/-catenin signaling has also been observed in human schwannoma cells, demonstrated by the upregulated expression of Wnt target genes c-myc and cyclin D1.

• #23

  https://insight.jci.org/articles/view/141514/figure/4

  Schwannoma development is mediated by Hippo pathway dysregulation and modified by RAS/MAPK signaling. […] Despite the identification of causative genes, including NF2 (Merlin), INI1/SMARCB1, and LZTR1, the exact molecular mechanism of schwannoma development is still poorly understood. […] Here, we provide direct genetic evidence that dysregulation of the Hippo pathway in the Schwann cell lineage causes development of multiple schwannomas in mice. […] We found that canonical Hippo signaling through the effectors YAP/TAZ is required for schwannomagenesis and that MAPK signaling modifies schwannoma formation. […] Our new model provides a tractable platform to dissect the molecular mechanisms underpinning schwannoma formation and the role of combinatorial targeted therapy in schwannoma treatment.

• #24 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  However, abnormalities in this signaling cause various types of tumors. […] The Hippo pathway plays a role in regulating cell number, influencing processes such as cell proliferation, cell death, and cell differentiation. […] Similarly, the Hippo pathway is inactivated by the downregulation of merlin in schwannomas. […] Merlin initiates the Hippo pathway and promotes the degradation of YAP and its homologous protein transcription coactivator (TAZ). […] In the inactivated state of merlin, YAP/TAZ translocate into the nucleus, where they bind to TEA domain family members (TEAD) and stimulate the transcription of growth-promoting and antiapoptotic genes, thus contributing to VS cell proliferation. […] The most prevalent mutations of the NF2, located on chromosome 22q12.2, account for 5376% of sporadic VS cases.

• #25 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Previous studies have demonstrated that somatic mutations affecting both alleles of NF2 result in the inactivation of this tumor suppressor gene, triggering tumorigenesis in sporadic VS. […] This phenomenon is encapsulated in the two-hit theory, also known as the Knudson hypothesis: the tumorigenesis of sporadic schwannomas is attributed not only to somatic mutations in NF2 but also to a second hit loss of heterozygosity (LOH) due to partial or complete loss of 22q which further contributes to NF2 inactivation and tumorigenesis. […] The occurrence of schwannomas with somatic SOX10 mutations is exceedingly scarce. […] Although a tendency for postoperative recurrence has been indicated in SOX10-mutant schwannomas, further investigation into the clinical features and mechanism of pathogenesis associated with SOX10 mutations is necessary, particularly in non-vestibular cranial nerve schwannomas.

• #26 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Previous studies have demonstrated that somatic mutations affecting both alleles of NF2 result in the inactivation of this tumor suppressor gene, triggering tumorigenesis in sporadic VS. […] This phenomenon is encapsulated in the two-hit theory, also known as the Knudson hypothesis: the tumorigenesis of sporadic schwannomas is attributed not only to somatic mutations in NF2 but also to a second hit loss of heterozygosity (LOH) due to partial or complete loss of 22q which further contributes to NF2 inactivation and tumorigenesis. […] The occurrence of schwannomas with somatic SOX10 mutations is exceedingly scarce. […] Although a tendency for postoperative recurrence has been indicated in SOX10-mutant schwannomas, further investigation into the clinical features and mechanism of pathogenesis associated with SOX10 mutations is necessary, particularly in non-vestibular cranial nerve schwannomas.

• #27 Molecular biology of sporadic vestibular schwannomas i…

  https://otorhinolaryngologypl.com/seo/article/01.3001.0014.4201/en

  Inactivation of the NF2 tumor suppressor gene is recognized as the prime cause of the development of sporadic (not related to NF2) schwannomas of the vestibular nerve (sVS) [5]. […] Most mutations in the NF2 gene occur in the region of exons 2 to 10 [14, 15]. […] The studies by Carlson et al. [15] imply that in small, slow-growing tumors mutations were localized within exons 1–10, while those with more aggressive course had mutations within exons 11–15. […] In addition to the expected changes in NF2, Agnihotri et al. [13] found repeated mutations in chromatin modifying genes ARID1A and ARID1B in 28% of tumors, and DDR1 (discoidin domain receptor tyrosine kinase 1 gene) in 11%. […] Merlin has long been considered a tumor suppressor protein, regulating signaling at the membrane and cortex of cell.

• #28 Molecular biology of sporadic vestibular schwannomas i…

  https://otorhinolaryngologypl.com/seo/article/01.3001.0014.4201/en

  Inactivation of the NF2 tumor suppressor gene is recognized as the prime cause of the development of sporadic (not related to NF2) schwannomas of the vestibular nerve (sVS) [5]. […] Most mutations in the NF2 gene occur in the region of exons 2 to 10 [14, 15]. […] The studies by Carlson et al. [15] imply that in small, slow-growing tumors mutations were localized within exons 1–10, while those with more aggressive course had mutations within exons 11–15. […] In addition to the expected changes in NF2, Agnihotri et al. [13] found repeated mutations in chromatin modifying genes ARID1A and ARID1B in 28% of tumors, and DDR1 (discoidin domain receptor tyrosine kinase 1 gene) in 11%. […] Merlin has long been considered a tumor suppressor protein, regulating signaling at the membrane and cortex of cell.

• #29

  https://link.springer.com/article/10.1007/s12105-020-01155-x

  Mutations to NF2, a tumour suppressor gene on chromosome 22, play a vital role in the development of both sporadic and NF2-related disease. Inactivation of the NF2 protein product, Merlin (schwannomin), leads to deregulation of various intracellular signalling pathways such as Rac1, Ras, PAK1, and mTORC1. Inactivation of other tumour suppressor genes including LZTR1, SMARCB1, and COQ6 are also linked to schwannoma development. […] Although the role of NF2 mutations was reinforced by recent large-scale sequencing studies, there are data to suggest that NF2-associated VS has a different, polyclonal mutation pattern. This has been postulated to account for variance in treatment outcomes as compared to sporadic VS.

• #30

  https://scite.ai/reports/10.1007/s00106-016-0201-3

  Inactivation of other tumour suppressor genes including LZTR1, SMARCB1, and COQ6 are also linked to schwannoma development. […] NF2 gene mutations lead to merlin deficient cells, causing Rac activation leading to intercellular adhesion and cell proliferation. […] Merlin deficient cells also deregulate various intracellular pathways causing cell proliferation. […] Mutations to NF2 also affect other pathways, seen in schwannomatosis, leading to eventual cell proliferation-although this is poorly understood. […] Collectively, loss of functional merlin expression precipitates schwannoma and other forms of neoplasia via dysregulation of cellular proliferation. […] Studies have also demonstrated that vestibular schwannomas express high levels of VEGFR1.

• #31 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Previous studies have demonstrated that somatic mutations affecting both alleles of NF2 result in the inactivation of this tumor suppressor gene, triggering tumorigenesis in sporadic VS. […] This phenomenon is encapsulated in the two-hit theory, also known as the Knudson hypothesis: the tumorigenesis of sporadic schwannomas is attributed not only to somatic mutations in NF2 but also to a second hit loss of heterozygosity (LOH) due to partial or complete loss of 22q which further contributes to NF2 inactivation and tumorigenesis. […] The occurrence of schwannomas with somatic SOX10 mutations is exceedingly scarce. […] Although a tendency for postoperative recurrence has been indicated in SOX10-mutant schwannomas, further investigation into the clinical features and mechanism of pathogenesis associated with SOX10 mutations is necessary, particularly in non-vestibular cranial nerve schwannomas.

• #32 Schwannomatosis – Wikipedia

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

  The candidate schwannomatosis gene, named SMARCB1, is a tumor suppressor gene that regulates cell cycle, growth and differentiation. An inactivating germline mutation in exon 1 of the tumor suppressor gene SMARCB1 has been reported in patients with schwannomatosis. […] A mechanism involving both the SMARCB1 and NF2 genes may be responsible for the development of the disease because tumor analysis of schwannomas indicates the presence of inactivating mutations in both the SMARCB1 and NF2 genes. […] Ultimately, the tumorigenesis of schwannomas is not solely dependent on one gene locus alone. […] In regards to the SMARCB1 and NF2 genes, it is important to understand constitutional mutations and somatic mutations. […] Schwannomas from one patient share the same constitutional mutations but have distinct somatic mutations.

• #33 Schwannomatosis – Wikipedia

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

  The candidate schwannomatosis gene, named SMARCB1, is a tumor suppressor gene that regulates cell cycle, growth and differentiation. An inactivating germline mutation in exon 1 of the tumor suppressor gene SMARCB1 has been reported in patients with schwannomatosis. […] A mechanism involving both the SMARCB1 and NF2 genes may be responsible for the development of the disease because tumor analysis of schwannomas indicates the presence of inactivating mutations in both the SMARCB1 and NF2 genes. […] Ultimately, the tumorigenesis of schwannomas is not solely dependent on one gene locus alone. […] In regards to the SMARCB1 and NF2 genes, it is important to understand constitutional mutations and somatic mutations. […] Schwannomas from one patient share the same constitutional mutations but have distinct somatic mutations.

• #34 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  Schwannomas are tumors of the peripheral nervous system, consisting of different cell types. These include tumorigenic Schwann cells, axons, macrophages, T cells, fibroblasts, blood vessels, and an extracellular matrix. All cell types involved constitute an intricate tumor microenvironment and play relevant roles in the development and progression of schwannomas. […] Although Nf2 tumor suppressor gene-deficient Schwann cells are the primary tumorigenic element and principle focus of current research efforts, evidence is accumulating regarding the contributory roles of other cell types in schwannoma pathology. In this review, we aim to provide an overview of intra- and intercellular mechanisms contributing to schwannoma formation. […] Schwannomas derive from tumorigenic Schwann cells, caused by loss-of-function mutations of the Nf2 tumor suppressor gene.

• #35 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  Schwannomas are tumors of the peripheral nervous system, consisting of different cell types. These include tumorigenic Schwann cells, axons, macrophages, T cells, fibroblasts, blood vessels, and an extracellular matrix. All cell types involved constitute an intricate tumor microenvironment and play relevant roles in the development and progression of schwannomas. […] Although Nf2 tumor suppressor gene-deficient Schwann cells are the primary tumorigenic element and principle focus of current research efforts, evidence is accumulating regarding the contributory roles of other cell types in schwannoma pathology. In this review, we aim to provide an overview of intra- and intercellular mechanisms contributing to schwannoma formation. […] Schwannomas derive from tumorigenic Schwann cells, caused by loss-of-function mutations of the Nf2 tumor suppressor gene.

• #36 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  The TME is a complex ecosystem comprising various cell types, including immune cells, vascular system cells, fibroblasts, and cancer stem cells, in addition to tumor cells. […] Tumor-associated macrophages (TAMs) are involved in the regulation of proliferation and immune responses. […] Recent studies using scRNA-seq have emerged as reliable methodologies for uncovering the association between schwannomas and TME. […] The findings from scRNA-seq studies illustrate that schwannomas are heterogeneous tumors involving multiple cell types.

• #37 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Schwann cell differentiation is regulated not only by Schwann cell-intrinsic programs but also by instructive signals from adjacent axons and the surrounding inflammatory environment, which controls the growth behavior of schwannomas. […] According to the Injury-like VS model proposed by Barrett et al., the initiation of VS tumor growth occurs through oncogenic events, followed by critical stressors such as nerve injury, prompting VS-associated tumor Schwann cells to adopt states reminiscent of repair process and antigen presentation. […] In addition, Liu et al. employed scRNA-seq to demonstrate that schwannomas comprise two distinct cell group populations, distinguished by their activation of neural crest or nerve injury pathways, which delineate the tumor cell state and the construction of the TME, thereby implicating TME in schwannoma progression.

• #38 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  These different cell types influence each other through a variety of paracrine and juxtracrine mechanisms, which are discussed in this review. […] Evidence for this hypothesis is provided by the observation of a transition zone at the borders between Antoni A and B tissue. […] It has been shown that these transition zones display the highest proliferation indices compared with the pure A- or B-type areas, as well as a marked infiltration of phagocytic macrophages. […] Macrophages are known to show high proliferation rates following activation and are, together with Schwann cells, mainly responsible for the clearance of debris during peripheral nervous system (PNS) degeneration. […] It is therefore reasonable to assume that macrophages contribute to the proliferative activity seen in the transition zone of schwannomas.

• #39 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  These different cell types influence each other through a variety of paracrine and juxtracrine mechanisms, which are discussed in this review. […] Evidence for this hypothesis is provided by the observation of a transition zone at the borders between Antoni A and B tissue. […] It has been shown that these transition zones display the highest proliferation indices compared with the pure A- or B-type areas, as well as a marked infiltration of phagocytic macrophages. […] Macrophages are known to show high proliferation rates following activation and are, together with Schwann cells, mainly responsible for the clearance of debris during peripheral nervous system (PNS) degeneration. […] It is therefore reasonable to assume that macrophages contribute to the proliferative activity seen in the transition zone of schwannomas.

• #40 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  A recent study from our research group might give some hints about the underlying pathogenesis. […] One reason proposed for the development of schwannomas in this mouse model is a failure of Schwann cell re-differentiation into myelinating cells, due to absent signals from nf2-deficient neurons. […] Schwann cells utilize autophagy and receptor-mediated phagocytosis to clear myelin from the degenerating distal nerve. […] The effectiveness of myelin clearance is critical for successful nerve regeneration in the PNS. […] Existing evidence suggests that a multi-leveled nerve microenvironment needs to be considered in schwannoma biology, as instructive cues from axons, inflammatory signals from macrophages and failed regenerative processes contribute to their formation and progression. […] The action of macrophages is crucial for Wallerian degeneration and peripheral nerve regeneration in general.

• #41 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  The significance of macrophages for schwannoma formation and progression is further underlined by a positive correlation between macrophage infiltration and tumor growth. […] Therefore, VEGF, which is also produced by schwannoma cells, is an attractive target for therapeutic intervention since it has been shown that its expression correlates with the tumor growth rate. […] According to one hypothesis, for which we tried to compile the available evidence in this paper, schwannomas can be regarded as chronic wounds of peripheral nerves. […] A lack of Schwann cell re-differentiation results in sustained cell proliferation and eventually tumor formation.

• #42 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  The significance of macrophages for schwannoma formation and progression is further underlined by a positive correlation between macrophage infiltration and tumor growth. […] Therefore, VEGF, which is also produced by schwannoma cells, is an attractive target for therapeutic intervention since it has been shown that its expression correlates with the tumor growth rate. […] According to one hypothesis, for which we tried to compile the available evidence in this paper, schwannomas can be regarded as chronic wounds of peripheral nerves. […] A lack of Schwann cell re-differentiation results in sustained cell proliferation and eventually tumor formation.

• #43 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Schwannomas are tumors that originate from myelinating Schwann cells and can occur in cranial, spinal, and peripheral nerves. […] The development of these tumors is primarily linked to mutations in the NF2 gene. Merlin, the protein encoded by NF2, is integral to several signaling pathways, including Ras/Raf/MEK/ERK, PI3K/Akt/mTORC1, Wnt/-catenin, and the Hippo pathway. […] The initial tumorigenic transformation of Schwann cells is primarily triggered by loss-of-function mutations in merlin due to biallelic inactivation of NF2. […] Following various types of nerve damage, such as compression, physical trauma, and chronic noise exposure, affected Schwann cells often undergo dedifferentiation, becoming immature and tumorigenic due to a failure to re-differentiate. […] This is supported by single-cell RNA sequencing (scRNA-seq) analysis, suggesting that various nerve injury factors and subsequent nerve repair processes may promote schwannoma development.

• #44 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Schwannomas are tumors that originate from myelinating Schwann cells and can occur in cranial, spinal, and peripheral nerves. […] The development of these tumors is primarily linked to mutations in the NF2 gene. Merlin, the protein encoded by NF2, is integral to several signaling pathways, including Ras/Raf/MEK/ERK, PI3K/Akt/mTORC1, Wnt/-catenin, and the Hippo pathway. […] The initial tumorigenic transformation of Schwann cells is primarily triggered by loss-of-function mutations in merlin due to biallelic inactivation of NF2. […] Following various types of nerve damage, such as compression, physical trauma, and chronic noise exposure, affected Schwann cells often undergo dedifferentiation, becoming immature and tumorigenic due to a failure to re-differentiate. […] This is supported by single-cell RNA sequencing (scRNA-seq) analysis, suggesting that various nerve injury factors and subsequent nerve repair processes may promote schwannoma development.

• #45 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Schwann cell differentiation is regulated not only by Schwann cell-intrinsic programs but also by instructive signals from adjacent axons and the surrounding inflammatory environment, which controls the growth behavior of schwannomas. […] According to the Injury-like VS model proposed by Barrett et al., the initiation of VS tumor growth occurs through oncogenic events, followed by critical stressors such as nerve injury, prompting VS-associated tumor Schwann cells to adopt states reminiscent of repair process and antigen presentation. […] In addition, Liu et al. employed scRNA-seq to demonstrate that schwannomas comprise two distinct cell group populations, distinguished by their activation of neural crest or nerve injury pathways, which delineate the tumor cell state and the construction of the TME, thereby implicating TME in schwannoma progression.

• #46 Current molecular understanding of central nervous system schwannomas | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-025-01937-w

  Schwann cell differentiation is regulated not only by Schwann cell-intrinsic programs but also by instructive signals from adjacent axons and the surrounding inflammatory environment, which controls the growth behavior of schwannomas. […] According to the Injury-like VS model proposed by Barrett et al., the initiation of VS tumor growth occurs through oncogenic events, followed by critical stressors such as nerve injury, prompting VS-associated tumor Schwann cells to adopt states reminiscent of repair process and antigen presentation. […] In addition, Liu et al. employed scRNA-seq to demonstrate that schwannomas comprise two distinct cell group populations, distinguished by their activation of neural crest or nerve injury pathways, which delineate the tumor cell state and the construction of the TME, thereby implicating TME in schwannoma progression.

• #47 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  A recent study from our research group might give some hints about the underlying pathogenesis. […] One reason proposed for the development of schwannomas in this mouse model is a failure of Schwann cell re-differentiation into myelinating cells, due to absent signals from nf2-deficient neurons. […] Schwann cells utilize autophagy and receptor-mediated phagocytosis to clear myelin from the degenerating distal nerve. […] The effectiveness of myelin clearance is critical for successful nerve regeneration in the PNS. […] Existing evidence suggests that a multi-leveled nerve microenvironment needs to be considered in schwannoma biology, as instructive cues from axons, inflammatory signals from macrophages and failed regenerative processes contribute to their formation and progression. […] The action of macrophages is crucial for Wallerian degeneration and peripheral nerve regeneration in general.

• #48 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] Merlin loss thus leads to increase integrin expression, resulting in increased cell spreading on the extracellular matrix in vitro and pseudomesaxon formation in vivo. […] Merlin loss also leads to increased expression and signaling of growth factors, resulting in increased proliferation in vitro and in vivo. […] Driven by the fact that growth factor receptors have been investigated intensively in oncology as potential therapeutic targets, growth factor receptors have been studied in some detail in schwannomas. […] Overexpression of platelet-derived growth factor receptor (PDGFR) and insulin-like growth factor receptor (IGF 1R) are also seen, and these seem to be functional in schwannomas, offering further potential sites for therapeutic drug targeting.

• #49 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] Merlin loss thus leads to increase integrin expression, resulting in increased cell spreading on the extracellular matrix in vitro and pseudomesaxon formation in vivo. […] Merlin loss also leads to increased expression and signaling of growth factors, resulting in increased proliferation in vitro and in vivo. […] Driven by the fact that growth factor receptors have been investigated intensively in oncology as potential therapeutic targets, growth factor receptors have been studied in some detail in schwannomas. […] Overexpression of platelet-derived growth factor receptor (PDGFR) and insulin-like growth factor receptor (IGF 1R) are also seen, and these seem to be functional in schwannomas, offering further potential sites for therapeutic drug targeting.

• #50 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] Merlin loss thus leads to increase integrin expression, resulting in increased cell spreading on the extracellular matrix in vitro and pseudomesaxon formation in vivo. […] Merlin loss also leads to increased expression and signaling of growth factors, resulting in increased proliferation in vitro and in vivo. […] Driven by the fact that growth factor receptors have been investigated intensively in oncology as potential therapeutic targets, growth factor receptors have been studied in some detail in schwannomas. […] Overexpression of platelet-derived growth factor receptor (PDGFR) and insulin-like growth factor receptor (IGF 1R) are also seen, and these seem to be functional in schwannomas, offering further potential sites for therapeutic drug targeting.

• #51 Schwannomas and Their Pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8029073/

  Vascular endothelial growth factor (VEGF) and its receptor expression are elevated in schwannomas, correlating with tumor growth and volume. […] Recent advances in our understanding of the pathogenesis of these tumors have indicated that defects in merlin are responsible for both sporadic and genetically acquired schwannomas, and the mechanisms by which merlin loss triggers tumor development are being unraveled.

• #52 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  The significance of macrophages for schwannoma formation and progression is further underlined by a positive correlation between macrophage infiltration and tumor growth. […] Therefore, VEGF, which is also produced by schwannoma cells, is an attractive target for therapeutic intervention since it has been shown that its expression correlates with the tumor growth rate. […] According to one hypothesis, for which we tried to compile the available evidence in this paper, schwannomas can be regarded as chronic wounds of peripheral nerves. […] A lack of Schwann cell re-differentiation results in sustained cell proliferation and eventually tumor formation.

• #53 CXCR4: A new player in vestibular schwannoma pathogenesis | Oncotarget

  https://www.oncotarget.com/article/24119/text/

  CXCR4 is a chemokine receptor that recruits blood stem cells and increases tumor cell growth and invasiveness. […] The aim was to determine whether CXCR4 can be used as a prognostic marker and as a target for systemic therapy. […] CXCR4 mRNA was overexpressed in VS relative to healthy vestibular nerves, and there was a trend towards higher CXCR4 expression levels being correlated with greater functional impairment. Thus, CXCR4 may be a prognostic marker of VS, and CXCR4 inhibition has potential as a systemic approach for the treatment of VS. […] The present investigation demonstrates for the first time in a larger cohort that CXCR4 is overexpressed in pure vestibular schwannomas with and without NF2 and could therefore play a role in the pathogenesis of these tumors. […] CXCR4 expression was not significantly different in NF2-associated vestibular schwannomas than in sporadic vestibular schwannoma.

• #54 CXCR4: A new player in vestibular schwannoma pathogenesis | Oncotarget

  https://www.oncotarget.com/article/24119/

  CXCR4 is a chemokine receptor that recruits blood stem cells and increases tumor cell growth and invasiveness. […] Overall, CXCR4 mRNA levels were 4.6-fold higher in VS versus control; the levels were 4.9-fold higher in NF2 patients and 4.2-fold higher in sporadic VS patients. […] CXCR4 mRNA was overexpressed in VS relative to healthy vestibular nerves, and there was a trend towards higher CXCR4 expression levels being correlated with greater functional impairment. Thus, CXCR4 may be a prognostic marker of VS, and CXCR4 inhibition has potential as a systemic approach for the treatment of VS.

• #55 ADAM9: A novel player in vestibular schwannoma pathogenesis

  https://www.spandidos-publications.com/10.3892/ol.2020.11299

  ADAM9 is a member of the transmembrane ADAM family. It is expressed in different types of solid cancer and promotes tumor invasiveness. The aim of the present study was to evaluate if ADAM9 could be used as prognostic marker or therapeutic target. The main known pathomechanism for vestibular schwannoma is the loss of function by Merlin. Merlin’s loss of function is the main known mechanism for the development of VS and results in the activation of two signaling pathways. These are the Ras/Raf/MEK pathway and the PI3K/Akt/mTOR pathway, which inhibit apoptosis and result in higher cell survival or proliferation rates. Furthermore, the Hippo pathway and the VEGF-mediated signaling pathway, are also activated by Merlin’s loss of function. Recently, we demonstrated that CXCR4 is of relevance for VS pathogenesis. Therefore, we assumed that other proteins beside Merlin and CXCR4 also might be involved. We hypothesized that ADAM9 could be overexpressed in VS because of its role in other solid cancers and its similarity to the function of Merlin. Therefore, we evaluated its potential role as a prognostic marker for VS by examining its expression and distribution in sporadic and NF2-associated VS tissue and its correlation to clinical parameters of the patients, especially their hearing-loss. The present investigation demonstrates for the first time that ADAM9 is expressed in VS by neoplastic Schwann cells, and thus, could play a significant role in the pathogenesis of these tumors. ADAM9 is involved in cell-cell and cell-matrix interaction by binding to several integrins and it promotes cell migration in tumor cells. In the current study, ADAM9 overexpression in VS could be demonstrated by qPCR for the first time with a difference between NF2 and sporadic cases. ADAM9 showed its highest expression in slow growing sporadic VS, medium expression in rapidly growing tumors with and without NF2 and the lowest expression in slow growing VS with NF2. ADAM9 overexpression did not correlate with the growth velocity or tumor extension, but with the functional impairment and therefore could be a marker for tumor invasiveness. ADAM9 was overexpressed specifically by Schwann cells of VS, but not of normal nerves. Its expression was higher in sporadic cases compared to NF2-associated VS. ADAM9 expression levels, especially of the secreted isoform, significantly correlated with hearing loss of the patients and therefore could be a marker for invasiveness of the tumor growth.

• #56 ADAM9: A novel player in vestibular schwannoma pathogenesis. – Document – Gale OneFile: Health and Medicine

  https://go.gale.com/ps/i.do?id=GALE%7CA619313986&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=17921074&p=HRCA&sw=w

  ADAM9 is a member of the transmembrane ADAM family. It is expressed in different types of solid cancer and promotes tumor invasiveness. To the best of our knowledge, the present study was the first to examine ADAM9 expression in vestibular schwannomas (VS) from patients with and without neurofibromatosis type 2 (NF2) and to associate the data with clinical parameters of the patients. The aim of the present study was to evaluate if ADAM9 could be used as prognostic marker or therapeutic target. ADAM9 mRNA levels were 8.8-fold higher in VS compared with in controls. The levels were 5.6-fold higher in patients with NF2 and 12-fold higher in patients with sporadic VS. There was a strong correlation between ADAM9 mRNA expression and the level of functional impairment (r~1, p=0.01). Particularly, the secreted isoform of ADAM9 was expressed in patients with higher hearing impairment. ADAM9 mRNA was overexpressed in the tumor samples relative to healthy vestibular nerves, and there was an association between higher ADAM9 expression levels and greater hearing impairment. Therefore, ADAM9 may be a prognostic marker for VS, and ADAM9 inhibition might have the potential as a systemic approach for the treatment of VS. […] ADAM9 mRNA and protein levels were measured in VS samples (n=60). A total of 30 of them were from patients with neurofibromatosis.

• #57 Cellular mechanisms of heterogeneity in NF2-mutant schwannoma | Nature Communications

  https://www.nature.com/articles/s41467-023-37226-0

  Schwannomas are common sporadic tumors and hallmarks of familial neurofibromatosis type 2 (NF2) that develop predominantly on cranial and spinal nerves. Virtually all schwannomas result from inactivation of the NF2 tumor suppressor gene with few, if any, cooperating mutations. […] How heterogeneity develops in NF2-mutant schwannomas is unknown. We have found that loss of the membrane:cytoskeleton-associated NF2 tumor suppressor, merlin, yields unstable intrinsic polarity and enables Nf2/ Schwann cells to adopt distinct programs of ErbB ligand production and polarized signaling, suggesting a self-generated model of schwannoma heterogeneity. […] Our studies highlight the importance of intrinsic mechanisms of heterogeneity across human cancers. […] We have found that NF2-deficient SCs exhibit unstable polarity and can adopt distinct phenotypic states featuring coordinated auto/paracrine ErbB ligand and polarity gene expression and polarized cytoskeletal organization, suggesting a model of self-generated heterogeneity that could explain the notoriously variable clinical and therapeutic behaviors of schwannomas.

• #58 Cellular mechanisms of heterogeneity in NF2-mutant schwannoma | Nature Communications

  https://www.nature.com/articles/s41467-023-37226-0

  Schwannomas are common sporadic tumors and hallmarks of familial neurofibromatosis type 2 (NF2) that develop predominantly on cranial and spinal nerves. Virtually all schwannomas result from inactivation of the NF2 tumor suppressor gene with few, if any, cooperating mutations. […] How heterogeneity develops in NF2-mutant schwannomas is unknown. We have found that loss of the membrane:cytoskeleton-associated NF2 tumor suppressor, merlin, yields unstable intrinsic polarity and enables Nf2/ Schwann cells to adopt distinct programs of ErbB ligand production and polarized signaling, suggesting a self-generated model of schwannoma heterogeneity. […] Our studies highlight the importance of intrinsic mechanisms of heterogeneity across human cancers. […] We have found that NF2-deficient SCs exhibit unstable polarity and can adopt distinct phenotypic states featuring coordinated auto/paracrine ErbB ligand and polarity gene expression and polarized cytoskeletal organization, suggesting a model of self-generated heterogeneity that could explain the notoriously variable clinical and therapeutic behaviors of schwannomas.

• #59 Cellular mechanisms of heterogeneity in NF2-mutant schwannoma | Nature Communications

  https://www.nature.com/articles/s41467-023-37226-0

  Our findings provide mechanistic insight into the adaptive biology of SCs, new biomarkers, and a quantitative imaging platform that can be developed to guide the treatment of human schwannoma; they also inform studies of intrinsic heterogeneity in other tumor types. […] Our studies suggest that the ability of Nf2/ SCs to variably enact distinct programs of ErbB ligand production and cytoskeletal polarity upon loss of axonally provided nutrients is a key intrinsic driver of schwannoma heterogeneity. […] Variability in the contribution of these states and their distinct auto/paracrine signaling and metabolic programs to each tumor could underlie the heterogeneous clinical behavior and therapeutic response of schwannomas. […] Our discovery that pS6 is a biomarker of Nrg1 expression but not of mTORC1i sensitivity in cultured Nf2/ SCs, together with the observation that mTORC1i does not block Nrg1 expression itself while ErbBi does, speaks to the complex clinically relevant circuitry that drives the development of these genetically simple tumors.

• #60 Cellular mechanisms of heterogeneity in NF2-mutant schwannoma | Nature Communications

  https://www.nature.com/articles/s41467-023-37226-0

  Our findings provide mechanistic insight into the adaptive biology of SCs, new biomarkers, and a quantitative imaging platform that can be developed to guide the treatment of human schwannoma; they also inform studies of intrinsic heterogeneity in other tumor types. […] Our studies suggest that the ability of Nf2/ SCs to variably enact distinct programs of ErbB ligand production and cytoskeletal polarity upon loss of axonally provided nutrients is a key intrinsic driver of schwannoma heterogeneity. […] Variability in the contribution of these states and their distinct auto/paracrine signaling and metabolic programs to each tumor could underlie the heterogeneous clinical behavior and therapeutic response of schwannomas. […] Our discovery that pS6 is a biomarker of Nrg1 expression but not of mTORC1i sensitivity in cultured Nf2/ SCs, together with the observation that mTORC1i does not block Nrg1 expression itself while ErbBi does, speaks to the complex clinically relevant circuitry that drives the development of these genetically simple tumors.

• #61 Cellular Schwannoma

  https://www.webpathology.com/images/soft-tissue/peripheral-nerve/schwannoma/44799

  Cellular schwannoma is a variant that is highly cellular and shows increased mitotic activity. […] The biologic behavior of cellular schwannomas is benign. Recurrences are rare when completely excised and metastases have not been reported. […] Schwannomas are composed of cellular Antoni A areas alternating with hypocellular Antoni B areas. Schwann cells in Antoni A areas show nuclear palisading, whorling patterns, and Verocay bodies. […] Cellular schwannoma is composed of mainly Antoni A areas and shows increased mitotic activity (usually 4 mitoses/10 HPF). They are usually found in deep-seated locations and behave in a benign fashion.

• #62 Pathology of vestibular schwannoma – Louis Hofmeyr

  https://lmhofmeyr.co.za/conditions/conditions-we-specialise-in/pathology-of-vestibular-schwannoma/

  A vestibular schwannoma, also known as an acoustic neuroma, is a benign tumour that typically arises from the Schwann cells of the vestibular portion of the eighth cranial nerve (1). […] Antoni A areas are histological patterns commonly found in vestibular schwannomas and benign vestibular nerve tumours (5). These areas are characterised by highly cellular zones with compactly arranged Schwann cells and densely packed collagen fibres. These areas are often associated with rapid tumour growth and increased cell proliferation (more aggressive growth). […] The presence of Antoni B areas in vestibular schwannomas is also associated with decreased cellularity, degeneration, and cyst formation within the tumour. […] SOX10 is a protein (transcription factor) expressed by Schwann cells. In the case of vestibular schwannoma, the SOX10 immunohistochemical stain is used to help differentiate Schwann cells from other cell types (7). […] Over time, microscopic ancient change of vestibular schwannoma can occur where the tumour becomes more fibrous and less cellular. This can lead to the formation of areas of calcification, cystic degeneration, and hyalinisation within the tumour (8,9,10)).

• #63 Pathology of vestibular schwannoma – Louis Hofmeyr

  https://lmhofmeyr.co.za/conditions/conditions-we-specialise-in/pathology-of-vestibular-schwannoma/

  A vestibular schwannoma, also known as an acoustic neuroma, is a benign tumour that typically arises from the Schwann cells of the vestibular portion of the eighth cranial nerve (1). […] Antoni A areas are histological patterns commonly found in vestibular schwannomas and benign vestibular nerve tumours (5). These areas are characterised by highly cellular zones with compactly arranged Schwann cells and densely packed collagen fibres. These areas are often associated with rapid tumour growth and increased cell proliferation (more aggressive growth). […] The presence of Antoni B areas in vestibular schwannomas is also associated with decreased cellularity, degeneration, and cyst formation within the tumour. […] SOX10 is a protein (transcription factor) expressed by Schwann cells. In the case of vestibular schwannoma, the SOX10 immunohistochemical stain is used to help differentiate Schwann cells from other cell types (7). […] Over time, microscopic ancient change of vestibular schwannoma can occur where the tumour becomes more fibrous and less cellular. This can lead to the formation of areas of calcification, cystic degeneration, and hyalinisation within the tumour (8,9,10)).

• #64 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  These different cell types influence each other through a variety of paracrine and juxtracrine mechanisms, which are discussed in this review. […] Evidence for this hypothesis is provided by the observation of a transition zone at the borders between Antoni A and B tissue. […] It has been shown that these transition zones display the highest proliferation indices compared with the pure A- or B-type areas, as well as a marked infiltration of phagocytic macrophages. […] Macrophages are known to show high proliferation rates following activation and are, together with Schwann cells, mainly responsible for the clearance of debris during peripheral nervous system (PNS) degeneration. […] It is therefore reasonable to assume that macrophages contribute to the proliferative activity seen in the transition zone of schwannomas.

• #65 Pathology of vestibular schwannoma – Louis Hofmeyr

  https://lmhofmeyr.co.za/conditions/conditions-we-specialise-in/pathology-of-vestibular-schwannoma/

  A vestibular schwannoma, also known as an acoustic neuroma, is a benign tumour that typically arises from the Schwann cells of the vestibular portion of the eighth cranial nerve (1). […] Antoni A areas are histological patterns commonly found in vestibular schwannomas and benign vestibular nerve tumours (5). These areas are characterised by highly cellular zones with compactly arranged Schwann cells and densely packed collagen fibres. These areas are often associated with rapid tumour growth and increased cell proliferation (more aggressive growth). […] The presence of Antoni B areas in vestibular schwannomas is also associated with decreased cellularity, degeneration, and cyst formation within the tumour. […] SOX10 is a protein (transcription factor) expressed by Schwann cells. In the case of vestibular schwannoma, the SOX10 immunohistochemical stain is used to help differentiate Schwann cells from other cell types (7). […] Over time, microscopic ancient change of vestibular schwannoma can occur where the tumour becomes more fibrous and less cellular. This can lead to the formation of areas of calcification, cystic degeneration, and hyalinisation within the tumour (8,9,10)).

• #66 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/cauda-equina-schwannoma-presenting-with-subarachnoid-and-subdural-hemorrhage-its-underlying-mechanism/

  A patient presented with a spinal subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) attributed to a spinal schwannoma at the T12-L1 level. […] This case demonstrates the rare acute presentation of a T12-L1 schwannoma with an accompanying intratumoral hemorrhage resulting in both a SDH/SAH. […] The hyalinized enlarged vessels of spinal schwannomas may become occluded by thrombosis, resulting in intrinsic tumor necrosis and intratumoral hemorrhage. The histological examination also revealed the presence of numerous degenerated blood vessels in the tumor with inflammatory cells clustered around them, suggesting that disruption of the degenerated blood caused the intratumoral hemorrhage.

• #67 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/cauda-equina-schwannoma-presenting-with-subarachnoid-and-subdural-hemorrhage-its-underlying-mechanism/

  A patient presented with a spinal subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) attributed to a spinal schwannoma at the T12-L1 level. […] This case demonstrates the rare acute presentation of a T12-L1 schwannoma with an accompanying intratumoral hemorrhage resulting in both a SDH/SAH. […] The hyalinized enlarged vessels of spinal schwannomas may become occluded by thrombosis, resulting in intrinsic tumor necrosis and intratumoral hemorrhage. The histological examination also revealed the presence of numerous degenerated blood vessels in the tumor with inflammatory cells clustered around them, suggesting that disruption of the degenerated blood caused the intratumoral hemorrhage.

• #68 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/cauda-equina-schwannoma-presenting-with-subarachnoid-and-subdural-hemorrhage-its-underlying-mechanism/

  A patient presented with a spinal subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) attributed to a spinal schwannoma at the T12-L1 level. […] This case demonstrates the rare acute presentation of a T12-L1 schwannoma with an accompanying intratumoral hemorrhage resulting in both a SDH/SAH. […] The hyalinized enlarged vessels of spinal schwannomas may become occluded by thrombosis, resulting in intrinsic tumor necrosis and intratumoral hemorrhage. The histological examination also revealed the presence of numerous degenerated blood vessels in the tumor with inflammatory cells clustered around them, suggesting that disruption of the degenerated blood caused the intratumoral hemorrhage.

• #69 Peritumoral Signal on Postcontrast FLAIR Images: Description and Proposed Biomechanism in Vestibular Schwannomas | American Journal of Neuroradiology

  http://www.ajnr.org/content/44/10/1171

  Anecdotally, postcontrast FLAIR images of vestibular schwannomas can show peritumoral hyperintense signal, hypothesized to represent gadolinium extravasation. […] Although its mechanism is unknown, this signal is hypothesized to represent gadolinium extravasation, given an ipsilateral increased signal in the adjacent internal auditory canal fundus and cochlea. […] The most logical explanation for the observed findings is that the hyperintense halo represents extratumoral leakage of gadolinium, because it was not demonstrated on any precontrast FLAIR images. […] It is also possible that the FLAIR images better depicted gadolinium leakage because they were acquired later in the imaging protocol, allowing interval leaching of contrast into the peritumoral space. […] As seen during microsurgical tumor dissection, VSs are surrounded by a thin, irregular, arachnoid layer that is variably adherent to the tumor surface.

• #70 Peritumoral Signal on Postcontrast FLAIR Images: Description and Proposed Biomechanism in Vestibular Schwannomas | American Journal of Neuroradiology

  http://www.ajnr.org/content/44/10/1171

  Anecdotally, postcontrast FLAIR images of vestibular schwannomas can show peritumoral hyperintense signal, hypothesized to represent gadolinium extravasation. […] Although its mechanism is unknown, this signal is hypothesized to represent gadolinium extravasation, given an ipsilateral increased signal in the adjacent internal auditory canal fundus and cochlea. […] The most logical explanation for the observed findings is that the hyperintense halo represents extratumoral leakage of gadolinium, because it was not demonstrated on any precontrast FLAIR images. […] It is also possible that the FLAIR images better depicted gadolinium leakage because they were acquired later in the imaging protocol, allowing interval leaching of contrast into the peritumoral space. […] As seen during microsurgical tumor dissection, VSs are surrounded by a thin, irregular, arachnoid layer that is variably adherent to the tumor surface.

• #71 STUDY OF PHYSIO-PATHOLOGICAL MECHANISMS AT THE BASE OF SCHWANNOMA DEVELOPMENT

  https://air.unimi.it/handle/2434/947449

  Schwannomas are the most common type of peripheral nerve tumor. […] The tumor suppressor merlin is a cytoskeleton-associated protein, which loss of function is the main cause for transformation of SCs into schwannomas. […] However, a large amount of VSs is sporadic and unilateral suggesting the presence of unknown pathogenic mechanisms beside NF2 gene mutation. […] Therefore, it is not excluded that mutations in other genes, may be responsible for the appearance of schwannomas presenting a characteristic clinical phenotype. […] The SCs from peripheral schwannoma were then immortalized using the LtAg-SV40, in order to obtain a continuous cell line for future studies addressed to better understand the schwannoma pathogenesis. […] Notably, the onset of schwannoma may be influenced by the exposure to environmental challenges, likely the electromagnetic fields (EMF), such as those generated by mobile phones or electronic devices.

• #72 Sporting Injuries – An Unusual Case of a Traumatic Schwannoma Presenting on the Upper Lip of a Professional Footballer, a Case Report | Hania | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/2761/2193

  Schwannomas are benign tumors that typically arise from the perineural Schwann cells responsible for the production of the insulating sheath called myelin with only 1% occurring intraorally. […] Schwannomas are benign tumors that typically arise from the perineural Schwann cells responsible for the production of the insulating sheath called myelin. They may develop at any age but are most common in younger to middle aged adults but unclear gender predisposition. […] Though the majority of schwannomas are idiopathic, trauma is suggested as a factor in papers written by Wilkinson et al and Brody et al in vertebral fracture and thyroidectomy, respectively. […] The treatment for benign schwannoma consists of total surgical excision. Ultrasonography, CT, and MRI may be helpful diagnostic and treatment tools, for the estimation of tumor margins, the lesion composition, and the determination of whether there is infiltration to surrounding structures. The recurrences as well as the malignant transformation are rare events. […] A better understanding of trauma-induced schwannoma, especially intraorally, may add to the clinical care of patients with this rare disorder as this is a lesion not encountered often in practice.

• #73 STUDY OF PHYSIO-PATHOLOGICAL MECHANISMS AT THE BASE OF SCHWANNOMA DEVELOPMENT

  https://air.unimi.it/handle/2434/947449

  In fact, it was suggested that EMFs can induce cellular changes towards non-physiological behavior, that may be pathologically relevant to the development of schwannoma. […] Overall, in this work of thesis we focused our attention on the investigation of putative genes, pathways, and molecular targets responsible for the oncotrasformation of SCs, studying the possible factors, also environmental, that could induce the development of schwannomas. […] The data are promising but further confirmatory studies will be needed for a more direct causeeffect correlation between EMF and SCs oncotransformation and finally to arrive at definitive conclusions widely accepted by the international scientific community.

• #74 Vestibular schwannoma | MedLink Neurology

  https://www.medlink.com/articles/vestibular-schwannoma

  Concern has risen in recent years about the potential role of microwave radiation from cellular telephones in the genesis of brain tumors, including vestibular schwannomas. […] Some studies have implicated long-term cellular phone use with an increased risk of vestibular schwannomas or other cranial tumors, especially with long latency and onset of use before the age of 20. […] Kundi reviewed 33 published studies and concluded that, although methodological flaws were found in every study, the weight of the evidence favored an increased risk for ipsilateral vestibular schwannomas with increasing duration of cellular phone usage, but the magnitude of that risk could not be assessed. […] A similar conclusion was reached in a meta-analysis by Hardell in 2008 for ipsilateral glioma and vestibular schwannomas.

• #75 Vestibular schwannoma | MedLink Neurology

  https://www.medlink.com/articles/vestibular-schwannoma

  Studies in rats and mice suggest a carcinogenic effect of whole body exposure to radiofrequency radiation. […] Cell cultures of human Schwann cells exposed to electromagnetic fields showed alterations in proliferation, intracellular signaling, metabolic pathways, and in the expression of genes related to hearing loss. […] In 2013 and 2019, Hardell and Carlberg concluded that emissions from wireless phones should be regarded as group 1 carcinogens. […] Some are skeptical of this interpretation, citing the fact that cell phone emissions are not energetic enough to break molecular bonds within cells, a necessary step toward oncogenesis. […] Additionally, some epidemiologic evidence does not appear to implicate cellular telephone use in the etiology of vestibular schwannomas or other brain tumors.

• #76 Vestibular schwannoma | MedLink Neurology

  https://www.medlink.com/articles/vestibular-schwannoma

  Studies in rats and mice suggest a carcinogenic effect of whole body exposure to radiofrequency radiation. […] Cell cultures of human Schwann cells exposed to electromagnetic fields showed alterations in proliferation, intracellular signaling, metabolic pathways, and in the expression of genes related to hearing loss. […] In 2013 and 2019, Hardell and Carlberg concluded that emissions from wireless phones should be regarded as group 1 carcinogens. […] Some are skeptical of this interpretation, citing the fact that cell phone emissions are not energetic enough to break molecular bonds within cells, a necessary step toward oncogenesis. […] Additionally, some epidemiologic evidence does not appear to implicate cellular telephone use in the etiology of vestibular schwannomas or other brain tumors.

• #77 Vestibular schwannoma | MedLink Neurology

  https://www.medlink.com/articles/vestibular-schwannoma

  At least two studies have implicated loud noise exposure in the genesis of vestibular schwannoma, but others have shown no increased risk or an indeterminate risk. […] Inactivating mutations in the NF2 gene were found more commonly in the tumor specimens of smokers than in never smokers. […] At this time there is no definitive evidence for a genetic/molecular signature suggestive of radiation-related vestibular schwannoma. […] An inherited but nonsyndromic contribution to sporadic vestibular schwannoma has been suggested by genealogic studies in veterans and residents of Utah. […] The distal location of the glia to Schwann cell transition in the vestibular nerves distinguishes them from other cranial nerves and has been thought to predispose them to neoplastic transformation. […] This theory has been questioned, and the incidence of vestibular tumors remains unexplained.

• #78 A Review of Drug Therapy in Vestibular Schwannoma | DDDT

  https://www.dovepress.com/a-review-of-drug-therapy-in-vestibular-schwannoma-peer-reviewed-fulltext-article-DDDT

  Vestibular schwannomas (VSs, also known as acoustic neuromas) are benign intracranial tumors commonly managed with observation, surgery, and radiotherapy. […] Conventional chemotherapeutic agents are characterized by neurotoxicity or ototoxicity, poor effect on slow-growing tumors, and may induce new mutations in patients who have lost tumor suppressor function, and therefore are unsuitable for treating VSs. […] The growing understanding of the mechanisms by which merlin dysregulation induces disease, as well as of signal pathways related to VS growth, has raised hopes for the application of targeted therapies. […] Recent studies have suggested that merlin can regulate multiple pathways implicated in tumorigenesis including retrovirus-associated DNA sequences (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen extracellular signal-regulated kinase (MEK)/extracellular-signal-regulated kinases (ERK), mammalian target of rapamycin complex 1 (mTORC1), Rac/p21-activated kinase (PAK)/C-Jun kinase, phosphoinositide 3-kinase (PI3K)/Akt and the intranuclear E3 ubiquitin ligase CRL4 (DCAF1).

• #79 A Review of Drug Therapy in Vestibular Schwannoma | DDDT

  https://www.dovepress.com/a-review-of-drug-therapy-in-vestibular-schwannoma-peer-reviewed-fulltext-article-DDDT

  All of these proposed sites are potential therapeutic targets of VS. […] The research on the pathways in which the NF2 gene product interacts provides a pharmacological basis for the development of VS targeted drugs. […] The loss of merlin results in the activation of a variety of signals related to cell survival, growth, and proliferation, and these abnormally expressed molecules are also potential drug therapeutic targets, of which VEGF has made the most progress. […] The complex interlinked signaling pathways in the pathogenesis of VS suggest that a combination therapy may provide an ideal therapeutic effect.

• #80 A Review of Drug Therapy in Vestibular Schwannoma | DDDT

  https://www.dovepress.com/a-review-of-drug-therapy-in-vestibular-schwannoma-peer-reviewed-fulltext-article-DDDT

  All of these proposed sites are potential therapeutic targets of VS. […] The research on the pathways in which the NF2 gene product interacts provides a pharmacological basis for the development of VS targeted drugs. […] The loss of merlin results in the activation of a variety of signals related to cell survival, growth, and proliferation, and these abnormally expressed molecules are also potential drug therapeutic targets, of which VEGF has made the most progress. […] The complex interlinked signaling pathways in the pathogenesis of VS suggest that a combination therapy may provide an ideal therapeutic effect.

• #81 New experimental treatment can stop the growth of schwannoma tumours – University of Plymouth

  https://www.plymouth.ac.uk/news/new-experimental-treatment-can-stop-the-growth-of-schwannoma-tumours

  Two novel and orally administered drugs can not only block the growth, but also shrink the size, of a tumour type found in the nervous system, new research has shown. […] Schwannomas are the most common nerve sheath tumour, and can occur in anyone but are also linked to a hereditary condition known as Neurofibromatosis Type II (NF2). […] With an urgent need for new treatments, an international team of scientists focused on the Hippo signalling pathway, which normally controls organ size in human tissues and cells, but is dysregulated in multiple types of cancer. […] Using a combination of patient-donor tumour cells from surgical resections and mouse models of schwannoma, the researchers showed that after just 21 days of the drugs being administered, tumour growth can be strongly and significantly reduced.

• #82 New experimental treatment can stop the growth of schwannoma tumours – University of Plymouth

  https://www.plymouth.ac.uk/news/new-experimental-treatment-can-stop-the-growth-of-schwannoma-tumours

  In addition, treatment with the Hippo pathway inhibitors (named VT1 and VT2 in the study) actually caused the death of tumour cells and an overall shrinkage of the tumour size. […] Dr Laraba, who completed the work as part of his PhD research, said: We are really excited to show that blocking the Hippo pathway is highly effective in preventing schwannoma and meningioma growth. […] Professor Parkinson, the studys senior author, added: Our current study gives an early indication that we can potentially provide schwannoma patients with a successful alternative treatment to manage their condition. […] For those patients, the prospect of a single drug that could treat both tumour types without the need for intrusive and risky surgery is clearly an exciting prospect.

• #83 New experimental treatment can stop the growth of schwannoma tumours – University of Plymouth

  https://www.plymouth.ac.uk/news/new-experimental-treatment-can-stop-the-growth-of-schwannoma-tumours

  In addition, treatment with the Hippo pathway inhibitors (named VT1 and VT2 in the study) actually caused the death of tumour cells and an overall shrinkage of the tumour size. […] Dr Laraba, who completed the work as part of his PhD research, said: We are really excited to show that blocking the Hippo pathway is highly effective in preventing schwannoma and meningioma growth. […] Professor Parkinson, the studys senior author, added: Our current study gives an early indication that we can potentially provide schwannoma patients with a successful alternative treatment to manage their condition. […] For those patients, the prospect of a single drug that could treat both tumour types without the need for intrusive and risky surgery is clearly an exciting prospect.

• #84 CXCR4: A new player in vestibular schwannoma pathogenesis | Oncotarget

  https://www.oncotarget.com/article/24119/text/

  An invasive growth pattern due to CXCR4 overexpression could explain why hearing impairment does not always correlate with tumor size. […] We conclude that CXCR4 is not a marker for the tumor extension but may be relevant for tumor invasiveness, as reflected by hearing impairment. […] Known mechanisms are Calcium release, ERK1/2 phosphorylation, IP3/Akt activation, and MAP signaling activation are all downstream of CXCR4 activation and lead to greater invasiveness and to the proliferation of diverse tumor cells. […] CXCR4 inhibition could be a promising new option with the use of AMD3100 or other more specific CXCR4 inhibitors with fewer side effects, like BL8040.

• #85 Pathomechanisms in schwannoma development and progression | Oncogene

  https://www.nature.com/articles/s41388-020-1374-5

  The significance of macrophages for schwannoma formation and progression is further underlined by a positive correlation between macrophage infiltration and tumor growth. […] Therefore, VEGF, which is also produced by schwannoma cells, is an attractive target for therapeutic intervention since it has been shown that its expression correlates with the tumor growth rate. […] According to one hypothesis, for which we tried to compile the available evidence in this paper, schwannomas can be regarded as chronic wounds of peripheral nerves. […] A lack of Schwann cell re-differentiation results in sustained cell proliferation and eventually tumor formation.

• #86 ADAM9: A novel player in vestibular schwannoma pathogenesis

  https://www.spandidos-publications.com/10.3892/ol.2020.11299?text=fulltext

  ADAM9 overexpression in VS could be demonstrated by qPCR for the first time with a difference between NF2 and sporadic cases. […] ADAM9 expression levels, especially of the secreted isoform, significantly correlated with hearing loss of the patients and therefore could be a marker for invasiveness of the tumor growth.

• #87

  https://link.springer.com/article/10.1007/s11060-023-04458-5

  These findings suggest different tumor immune environments in TMM subtypes, highlighting the need for personalized treatment of patients with vestibular schwannomas (VS) from a precision medicine standpoint. […] Our findings confirmed that among various cell types, microglia are the predominant users of telomerase, with greater APC activity seen in cells with greater stemness. […] These findings can provide valuable insights for implementing precision medicine and personalized patient care.

Zobacz więcej