Materiały źródłowe

• #1 Schwannoma – Symptoms, Causes, TreatmentsSecond Opinion IconGroup 9Group 49

  https://www.barrowneuro.org/condition/schwannoma/

  A schwannoma is a rare type of tumor that develops from cells called Schwann cells. […] The exact cause of schwannomas is not fully understood. They can sometimes be associated with genetic conditions called neurofibromatosis type 2 (NF2) and schwannomatosis. […] Schwannomas are rare, with less than 200,000 diagnosed cases yearly in the United States. […] Schwannoma can occur in people of all ages. However, they are more common in people with the genetic disorders neurofibromatosis type 2 (NF2) and schwannomatosis. […] These tumors are often associated with genetic conditions, such as neurofibromatosis type 1 (NF1), which significantly increases the risk of developing MPNSTs.

• #1 Schwannoma: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17877-schwannoma

  Schwannomas usually develop randomly in otherwise healthy people. […] In some cases, a schwannoma is caused by a genetic condition, such as neurofibromatosis 2 (NF2), schwannomatosis or Carney complex. People with these genetic conditions usually have more than one schwannoma. […] The cause of schwannomas isn’t known in most cases. Approximately 90% of cases occur sporadically (randomly). […] Genetic disorders such as Carney complex, neurofibromatosis 2 (NF2) and schwannomatosis can cause schwannomas. Genetic studies show that the NF2 gene on chromosome 22 plays an essential role in schwannoma development.

• #1 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. […] The genetic pathways and morphological features of schwannomas associated with different genetic syndromes will be discussed. […] Most cases are sporadic; however, some are associated with NF2, schwannomatosis or Carney’s complex, and they may rarely occur following radiation. […] 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.

• #1 Vestibular Schwannoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562312/

  Approximately 90% of the schwannomas are sporadic. Schwannomas occurring in specific syndromes (neurofibromatosis type 2, schwannomatosis, and Carney complex) may have a possible genetic etiology, not only in the syndromic schwannoma but in sporadic cases. Neurofibromatosis type 2 accounts for 3% of the syndromic schwannomas, while schwannomatosis for 2%, and meningiomatosis with or without neurofibromatosis type 2 in 5%. […] Genetic studies show that the NF2 gene on chromosome 22 plays an essential role in sporadic and syndromic schwannoma development. The NF2 gene encodes for the merlin protein (schwannomin). Specific gene mutations in the NF2 gene cause the inactivation of the gene, thus preventing the formation of the merlin protein. Inactivation of both alleles of the NF2 gene is observed in most schwannomas. Carney complex may have a loss of PRKAR1A expression. […] Spinal schwannomas can have SMARCB1 mutations and inactivation.

• #1 Acoustic Neuroma Symptoms & Causes (Vestibular Schwannoma)

  https://health.ucsd.edu/care/ent/acoustic-neuroma/causes-and-symptoms/

  Radiation exposure to the head is the only environmental influence that has been definitively linked with an increased incidence of acoustic neuroma. […] No evidence currently exists for an association between cell phone use and the development of these tumors. […] Acoustic neuroma is not generally considered an inherited disease; however, 5% of cases are associated with a genetic disorder called neurofibromatosis type 2 (NF2). These individuals show two-sided vestibular tumors often associated with other tumors around the brain and/or in the spine. […] Most acoustic neuromas are sporadic (nonhereditary).

• #1 Causes of vestibular schwannoma – Louis Hofmeyr

  https://lmhofmeyr.co.za/conditions/conditions-we-specialise-in/acoustic-neuroma/elementor-21665/

  Numerous studies have investigated the potential connection between cell phones and VS, but the results have been inconclusive. The World Health Organizations International Agency for Research on Cancer conducted a comprehensive study on this topic. It concluded that there is no clear evidence to suggest that cell phone use causes vestibular schwannomas. […] While exposure to loud noises can cause damage to the inner ear and potentially lead to hearing loss, there is no scientific evidence to support the claim that it can cause vestibular schwannoma. […] Studies have shown that the majority of VS occur sporadically, with only a tiny percentage being associated with a genetic predisposition or exposure to high-dose radiation, such as that used in specific medical treatments. Low-dose radiation, such as that received during routine medical imaging or from environmental sources, is not believed to impact VS development significantly.

• #1 Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology | Journal of Experimental & Clinical Cancer Research | Full Text

  https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02473-4

  Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. […] The drivers of sporadic VS associated with progression have never been characterized previously, although electron microscopical studies of bovine schwannomas have revealed viral particles in the tumors, suggesting a potential viral etiology. […] Our findings show that in rapidly progressing VS, virus-inducible cellular gene networks, such as interferon gamma signaling, are enriched. […] Interestingly, we found that rapidly progressing VS cases exhibited activation of several pathways linked to viral infection, such as the canonical pathway NF-B Activation by Viruses, and others highlighted in Fig. 3C. These findings may indicate that fast progressing VS are associated with an underlying viral infection, which is associated with the dramatic upregulation of stress-related and proliferation/survival signaling pathways, as well as the significant downregulation of immune signaling.

• #1 Hearing loss and vestibular schwannoma: new insights into Schwann cells implication | Cell Death & Disease

  https://www.nature.com/articles/s41419-023-06141-z

  Noteworthy, the VS compresses mechanically the auditory nerve or the labyrinthine artery, producing a mechanical damage and leading to the unilateral SNHL. […] In accordance to the failure-of-nerve regeneration theory, the VS preferentially develops in a location prone to the nerve injury, given by compression or physical trauma. […] HL has been observed even in non-growing tumors anyhow, so great that the correlation between tumor size and HL suggested that mechanical compression could not be the unique cause of SNHL. […] The tumor microenvironment sustained by infiltrated immune cells leads to intratumoral inflammation, playing a key role in VS growth.

• #2 Schwannoma – NCI

  https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-soft-tissue-tumors/schwannoma

  Schwannoma forms when Schwann cells, a type of cell that protects nerve cells in the nervous system, grows and divides more than normal. […] There are some genetic conditions which may run in families that may increase the risk of schwannoma, such as neurofibromatosis type 2 (NF2), schwannomatosis, and Carney Complex. […] Scientists are always working to understand how tumors form, but it can be hard to prove.

• #2 Vestibular Schwannoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562312/

  Approximately 90% of the schwannomas are sporadic. Schwannomas occurring in specific syndromes (neurofibromatosis type 2, schwannomatosis, and Carney complex) may have a possible genetic etiology, not only in the syndromic schwannoma but in sporadic cases. Neurofibromatosis type 2 accounts for 3% of the syndromic schwannomas, while schwannomatosis for 2%, and meningiomatosis with or without neurofibromatosis type 2 in 5%. […] Genetic studies show that the NF2 gene on chromosome 22 plays an essential role in sporadic and syndromic schwannoma development. The NF2 gene encodes for the merlin protein (schwannomin). Specific gene mutations in the NF2 gene cause the inactivation of the gene, thus preventing the formation of the merlin protein. Inactivation of both alleles of the NF2 gene is observed in most schwannomas. Carney complex may have a loss of PRKAR1A expression. […] Spinal schwannomas can have SMARCB1 mutations and inactivation.

• #2 Acoustic Neuroma Symptoms & Causes (Vestibular Schwannoma)

  https://health.ucsd.edu/care/ent/acoustic-neuroma/causes-and-symptoms/

  Radiation exposure to the head is the only environmental influence that has been definitively linked with an increased incidence of acoustic neuroma. […] No evidence currently exists for an association between cell phone use and the development of these tumors. […] Acoustic neuroma is not generally considered an inherited disease; however, 5% of cases are associated with a genetic disorder called neurofibromatosis type 2 (NF2). These individuals show two-sided vestibular tumors often associated with other tumors around the brain and/or in the spine. […] Most acoustic neuromas are sporadic (nonhereditary).

• #2 Schwannoma | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/schwannoma?lang=us

  Schwannomas, less commonly called neurinomas or neurilemmomas, are benign tumors of Schwann cell origin and are the most common tumor of peripheral nerves, including cranial nerves. […] The vast majority of schwannomas are sporadic, with a peak presentation in the 5th to 6th decades. There is no sex predilection. […] Most schwannomas are solitary (90%) and sporadic, however, there is an association with neurofibromatosis type 2 (NF2) (abnormality of chromosome 22). Multiple schwannomas are characteristic of neurofibromatosis type 2. Approximately 18% of solitary schwannomas occur in patients with neurofibromatosis type 2. […] There is also schwannomatosis, which consists of multiple schwannomas without the concomitant involvement of cranial nerve VIII.

• #2 Schwannomas and Their Pathogenesis

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

  Thus, schwannomas in schwannomatosis have merlin loss, like schwannomas in NF2 or spontaneous schwannomas, but the initial mutation is different. […] PRKAR1a appears to act as a tumor suppressor gene, and inactivation results in increased cyclic adenosine monophosphate (cAMP) activity and Rac 1 activation, leading to suppression of merlin activity and the development of Schwann cell tumors.

• #2 Schwannomas and Their Pathogenesis

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

  The risk of offspring inheriting NF2 in mosaic patients is difficult to quantify, but may be considerably less than 50%. […] Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] In addition, the tumors may show patchy loss of SMARCB1 (INI1) immunoreactivity and the presence of intratumoral nerve fibers. […] 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. […] In addition to affecting these mostly mitogenic and survival pathways, merlin uncouples Ras/Rac growth factor receptor interactions and has a negative feedback loop with PAK, so that loss of merlin leads to Rac activation, which in turn leads to sustained and nonlocalized GTPase activation.

• #2 Schwannoma: Causes, Symptoms & Treatment

  https://mnamd.com/schwannoma/

  Radiation Exposure: Some studies suggest that exposure to high levels of radiation may increase the risk of developing Schwannomas. However, this is relatively rare and occurs primarily in cases of high-dose therapeutic radiation or occupational exposure to radiation. […] Environmental Factors: While not definitively proven, some environmental factors, such as exposure to certain chemicals or toxins, have been proposed as possible contributors to Schwannoma development. Research in this area is still ongoing. […] Sporadic Cases: In many instances, Schwannomas may develop sporadically without any identifiable genetic or environmental factors. These cases are often considered random occurrences. […] It is essential to recognize that Schwannomas are generally non-cancerous and do not result from lifestyle choices or behaviors. While understanding the causes of Schwannomas remains a subject of ongoing research, early detection and timely treatment are vital for optimal outcomes.

• #2 Causes of vestibular schwannoma – Louis Hofmeyr

  https://lmhofmeyr.co.za/conditions/conditions-we-specialise-in/acoustic-neuroma/elementor-21665/

  Some studies have suggested a possible association between hyperparathyroidism and an increased risk of developing VS, but further research is needed to confirm this link. […] Several studies have suggested that cigarette smoking may have a protective effect against the development of VS. However, the increased risk of developing other malignancies associated with smoking, such as lung cancer and heart disease, far outweighs any potential benefits for VS. […] Aspirin has been suggested to have a potential protective effect against the development of VS. While there is not enough evidence to recommend aspirin as a therapy for patients with VS currently, studies have shown that aspirin may act as a negative risk factor for the development of sporadic VS. […] While viruses have been shown to be a cause of approximately 15% of all cancers, no direct relationship has been established between viruses and VS. […] There is currently not enough evidence to support pregnancy and hormonal contraceptives as a cause of the formation of vestibular schwannoma.

• #2 Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology | Journal of Experimental & Clinical Cancer Research | Full Text

  https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02473-4

  Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. […] The drivers of sporadic VS associated with progression have never been characterized previously, although electron microscopical studies of bovine schwannomas have revealed viral particles in the tumors, suggesting a potential viral etiology. […] Our findings show that in rapidly progressing VS, virus-inducible cellular gene networks, such as interferon gamma signaling, are enriched. […] Interestingly, we found that rapidly progressing VS cases exhibited activation of several pathways linked to viral infection, such as the canonical pathway NF-B Activation by Viruses, and others highlighted in Fig. 3C. These findings may indicate that fast progressing VS are associated with an underlying viral infection, which is associated with the dramatic upregulation of stress-related and proliferation/survival signaling pathways, as well as the significant downregulation of immune signaling.

• #2 Hearing loss and vestibular schwannoma: new insights into Schwann cells implication | Cell Death & Disease

  https://www.nature.com/articles/s41419-023-06141-z

  Noteworthy, the VS compresses mechanically the auditory nerve or the labyrinthine artery, producing a mechanical damage and leading to the unilateral SNHL. […] In accordance to the failure-of-nerve regeneration theory, the VS preferentially develops in a location prone to the nerve injury, given by compression or physical trauma. […] HL has been observed even in non-growing tumors anyhow, so great that the correlation between tumor size and HL suggested that mechanical compression could not be the unique cause of SNHL. […] The tumor microenvironment sustained by infiltrated immune cells leads to intratumoral inflammation, playing a key role in VS growth.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-a-Vestibular-Schwannoma.aspx

  Unilateral acoustic neuromas which affect a single ear are more common, and may occur in any age group. However, people between 30 and 60 are most frequently affected. The tumor may develop because of environment-induced damage to the nerve, but the exact risk factors are unclear. […] Bilateral acoustic neuromas are rarer, are genetic in origin, and affect both ears. The underlying defect is in the gene on chromosome 22 that causes neurofibromatosis-2 (NF2). This is an autosomal dominant disorder, and the offspring of an affected parent have a 50% chance of getting this gene. […] Some scientists think that both types are caused by defects in the same gene which causes Schwann cells to function. In the case of unilateral vestibular schwannomas, the mutation is acquired, whereas it is inherited in the case of bilateral tumors. […] Vestibular schwannoma is associated with long-term exposure to noise including loud music or workplace noise. Radiation to the neck or face is also linked to vestibular schwannoma, though after many years. NF2, which may run in families, is another risk factor.

• #2 Schwannoma

  https://www.mymlc.com/health-information/diseases-and-conditions/s/schwannoma/

  It’s not clear why most peripheral nerve tumors develop. Some are linked to known inherited syndromes, such as neurofibromatosis (types 1 and 2) and schwannomatosis. Others may be caused by a malfunctioning gene or triggered by injury or surgery. […] Peripheral nerve tumors are more common in people who have: Neurofibromatosis (types 1 and 2) and schwannomatosis. In these disorders, tumors develop on or near the nerves throughout the body. These tumors, which are frequently multiple, can lead to a variety of symptoms and signs depending on their location. These tumors are usually noncancerous. […] A history of radiation treatment. If you were exposed to radiation, you are at increased risk of peripheral nerve tumors years later.

• #2 Schwannoma: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17877-schwannoma

  Schwannomas usually develop randomly in otherwise healthy people. […] In some cases, a schwannoma is caused by a genetic condition, such as neurofibromatosis 2 (NF2), schwannomatosis or Carney complex. People with these genetic conditions usually have more than one schwannoma. […] The cause of schwannomas isn’t known in most cases. Approximately 90% of cases occur sporadically (randomly). […] Genetic disorders such as Carney complex, neurofibromatosis 2 (NF2) and schwannomatosis can cause schwannomas. Genetic studies show that the NF2 gene on chromosome 22 plays an essential role in schwannoma development.

• #3 Schwannoma – Symptoms, Causes, TreatmentsSecond Opinion IconGroup 9Group 49

  https://www.barrowneuro.org/condition/schwannoma/

  A schwannoma is a rare type of tumor that develops from cells called Schwann cells. […] The exact cause of schwannomas is not fully understood. They can sometimes be associated with genetic conditions called neurofibromatosis type 2 (NF2) and schwannomatosis. […] Schwannomas are rare, with less than 200,000 diagnosed cases yearly in the United States. […] Schwannoma can occur in people of all ages. However, they are more common in people with the genetic disorders neurofibromatosis type 2 (NF2) and schwannomatosis. […] These tumors are often associated with genetic conditions, such as neurofibromatosis type 1 (NF1), which significantly increases the risk of developing MPNSTs.

• #3

  https://braintumourresearch.org/pages/types-of-brain-tumours-schwannoma?srsltid=AfmBOoo8NqqXiWSbsakpC1gdU0iCclFPRCK51OHo5DqvDfQtBly7wFPH

  Most schwannomas occur spontaneously. The cause of a schwannoma brain tumour is, in the majority of cases, the development of fault in a gene called NF2 (which is a gene on chromosome 22 in our DNA). […] The NF2 gene provides instructions for the body to make a protein called merlin. This protein is also known as schwannomin because it is produced in schwann cells within the nervous system. The merlin protein acts as a tumour suppressor. In other words, it prevents cells from growing and dividing in an uncontrolled way. When it fails to carry out this function, tumours form from the schwann cells that surround the nerves. […] Researchers also suspect that merlin helps to control cell movement, cell shape and communication between cells. The NF2 fault can lead to the genetic disease called neurofibromatosis 2.

• #3 Schwannomas and Their Pathogenesis

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

  The risk of offspring inheriting NF2 in mosaic patients is difficult to quantify, but may be considerably less than 50%. […] Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] In addition, the tumors may show patchy loss of SMARCB1 (INI1) immunoreactivity and the presence of intratumoral nerve fibers. […] 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. […] In addition to affecting these mostly mitogenic and survival pathways, merlin uncouples Ras/Rac growth factor receptor interactions and has a negative feedback loop with PAK, so that loss of merlin leads to Rac activation, which in turn leads to sustained and nonlocalized GTPase activation.

• #3

  https://braintumourresearch.org/pages/types-of-brain-tumours-schwannoma?srsltid=AfmBOoo8NqqXiWSbsakpC1gdU0iCclFPRCK51OHo5DqvDfQtBly7wFPH

  Schwannomatosis is another genetic disease that can lead to a schwannoma brain tumour. Schwannomatosis tends to be diagnosed in early adulthood. It can be preceded by chronic pain, sometimes in areas where there are no tumours, due to the fact that pain signals originating from nerves where tumours are causing pressure can sometimes be felt at distant sites within the body.

• #3 Schwannomas and Their Pathogenesis

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

  Thus, schwannomas in schwannomatosis have merlin loss, like schwannomas in NF2 or spontaneous schwannomas, but the initial mutation is different. […] PRKAR1a appears to act as a tumor suppressor gene, and inactivation results in increased cyclic adenosine monophosphate (cAMP) activity and Rac 1 activation, leading to suppression of merlin activity and the development of Schwann cell tumors.

• #3 Schwannomatosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/schwannomatosis/

  Schwannomatosis is a disorder characterized by multiple noncancerous (benign) tumors called schwannomas, which are a type of tumor that grows on nerves. Schwannomas develop when Schwann cells, which are specialized cells that normally form an insulating layer around the nerve, grow uncontrollably to form a tumor. […] Mutations in at least two genes, SMARCB1 and LZTR1, can cause schwannomatosis. The proteins produced from both genes are thought to act as tumor suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in either of these genes may help cells grow and divide without control or order to form a tumor. […] It appears that mutations in the SMARCB1 or LZTR1 gene alone are not enough to trigger the development of schwannomas. Additional genetic changes (somatic mutations) that are acquired during a person’s lifetime and are present only in certain cells may also be required for schwannomas to form. The most common somatic mutations in schwannomas are mutations in the NF2 gene and a loss of chromosome 22 (which is the chromosome on which the SMARCB1, LZTR1, and NF2 genes are found). […] Some people with schwannomatosis do not have an identified mutation in the SMARCB1 or LZTR1 gene. In these cases, the cause of the disorder is unknown. Researchers suspect that mutations in other as-yet-unidentified genes, most likely on chromosome 22, also contribute to this condition.

• #3 Acoustic Neuroma Symptoms & Causes (Vestibular Schwannoma)

  https://health.ucsd.edu/care/ent/acoustic-neuroma/causes-and-symptoms/

  Radiation exposure to the head is the only environmental influence that has been definitively linked with an increased incidence of acoustic neuroma. […] No evidence currently exists for an association between cell phone use and the development of these tumors. […] Acoustic neuroma is not generally considered an inherited disease; however, 5% of cases are associated with a genetic disorder called neurofibromatosis type 2 (NF2). These individuals show two-sided vestibular tumors often associated with other tumors around the brain and/or in the spine. […] Most acoustic neuromas are sporadic (nonhereditary).

• #3 Causes of vestibular schwannoma – Louis Hofmeyr

  https://lmhofmeyr.co.za/conditions/conditions-we-specialise-in/acoustic-neuroma/elementor-21665/

  Some studies have suggested a possible association between hyperparathyroidism and an increased risk of developing VS, but further research is needed to confirm this link. […] Several studies have suggested that cigarette smoking may have a protective effect against the development of VS. However, the increased risk of developing other malignancies associated with smoking, such as lung cancer and heart disease, far outweighs any potential benefits for VS. […] Aspirin has been suggested to have a potential protective effect against the development of VS. While there is not enough evidence to recommend aspirin as a therapy for patients with VS currently, studies have shown that aspirin may act as a negative risk factor for the development of sporadic VS. […] While viruses have been shown to be a cause of approximately 15% of all cancers, no direct relationship has been established between viruses and VS. […] There is currently not enough evidence to support pregnancy and hormonal contraceptives as a cause of the formation of vestibular schwannoma.

• #3 Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology | Journal of Experimental & Clinical Cancer Research | Full Text

  https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02473-4

  Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. […] The drivers of sporadic VS associated with progression have never been characterized previously, although electron microscopical studies of bovine schwannomas have revealed viral particles in the tumors, suggesting a potential viral etiology. […] Our findings show that in rapidly progressing VS, virus-inducible cellular gene networks, such as interferon gamma signaling, are enriched. […] Interestingly, we found that rapidly progressing VS cases exhibited activation of several pathways linked to viral infection, such as the canonical pathway NF-B Activation by Viruses, and others highlighted in Fig. 3C. These findings may indicate that fast progressing VS are associated with an underlying viral infection, which is associated with the dramatic upregulation of stress-related and proliferation/survival signaling pathways, as well as the significant downregulation of immune signaling.

• #3 Hearing loss and vestibular schwannoma: new insights into Schwann cells implication | Cell Death & Disease

  https://www.nature.com/articles/s41419-023-06141-z

  Noteworthy, the VS compresses mechanically the auditory nerve or the labyrinthine artery, producing a mechanical damage and leading to the unilateral SNHL. […] In accordance to the failure-of-nerve regeneration theory, the VS preferentially develops in a location prone to the nerve injury, given by compression or physical trauma. […] HL has been observed even in non-growing tumors anyhow, so great that the correlation between tumor size and HL suggested that mechanical compression could not be the unique cause of SNHL. […] The tumor microenvironment sustained by infiltrated immune cells leads to intratumoral inflammation, playing a key role in VS growth.

• #3 Schwannoma: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17877-schwannoma

  Schwannomas usually develop randomly in otherwise healthy people. […] In some cases, a schwannoma is caused by a genetic condition, such as neurofibromatosis 2 (NF2), schwannomatosis or Carney complex. People with these genetic conditions usually have more than one schwannoma. […] The cause of schwannomas isn’t known in most cases. Approximately 90% of cases occur sporadically (randomly). […] Genetic disorders such as Carney complex, neurofibromatosis 2 (NF2) and schwannomatosis can cause schwannomas. Genetic studies show that the NF2 gene on chromosome 22 plays an essential role in schwannoma development.

• #3 Schwannoma: Causes, Symptoms & Treatment

  https://mnamd.com/schwannoma/

  Radiation Exposure: Some studies suggest that exposure to high levels of radiation may increase the risk of developing Schwannomas. However, this is relatively rare and occurs primarily in cases of high-dose therapeutic radiation or occupational exposure to radiation. […] Environmental Factors: While not definitively proven, some environmental factors, such as exposure to certain chemicals or toxins, have been proposed as possible contributors to Schwannoma development. Research in this area is still ongoing. […] Sporadic Cases: In many instances, Schwannomas may develop sporadically without any identifiable genetic or environmental factors. These cases are often considered random occurrences. […] It is essential to recognize that Schwannomas are generally non-cancerous and do not result from lifestyle choices or behaviors. While understanding the causes of Schwannomas remains a subject of ongoing research, early detection and timely treatment are vital for optimal outcomes.

• #3 Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252048

  Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting in multiple schwannomas and meningiomas. […] There are no approved drug therapies for these common and relentlessly progressive tumors. […] Importantly, we established the FDA approved, multi-tyrosine kinase inhibitor (TKI), brigatinib, as a potent inhibitor of Merlin-deficient schwannoma and meningioma growth, both in vitro and in preclinical animal models. […] Interestingly, neither Merlin-deficient schwannoma nor meningioma cells express the primary published target of brigatinib, anaplastic lymphoma kinase (ALK). […] Our findings underscore the importance of kinome profiling in disease models of interest to identify potentially relevant but unanticipated drug targets. […] Based on the data presented here, brigatinib possesses potent anti-tumor activity against NF2-deficient tumors via inhibition of multiple RTKs frequently activated in these tumors as well as blockade of several non-RTKs and serine-threonine kinases, but not ALK.

• #4 Vagal Schwannoma | Otolaryngology | Loyola MedicineLearn more about Reinke’s edema, including the symptoms, causes, diagnosis and treatment at Loyola Medicine

  https://www.loyolamedicine.org/services/otolaryngology-ent/otolaryngology-conditions/vagal-schwannoma

  Vagal schwannomas typically occur in patients between 30 and 60 years of age but can be found at any age. […] The exact cause of these rare tumors is unknown. Researchers are investigating if underlying genetic disorders may play a role.

• #4 Vestibular Schwannoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562312/

  Approximately 90% of the schwannomas are sporadic. Schwannomas occurring in specific syndromes (neurofibromatosis type 2, schwannomatosis, and Carney complex) may have a possible genetic etiology, not only in the syndromic schwannoma but in sporadic cases. Neurofibromatosis type 2 accounts for 3% of the syndromic schwannomas, while schwannomatosis for 2%, and meningiomatosis with or without neurofibromatosis type 2 in 5%. […] Genetic studies show that the NF2 gene on chromosome 22 plays an essential role in sporadic and syndromic schwannoma development. The NF2 gene encodes for the merlin protein (schwannomin). Specific gene mutations in the NF2 gene cause the inactivation of the gene, thus preventing the formation of the merlin protein. Inactivation of both alleles of the NF2 gene is observed in most schwannomas. Carney complex may have a loss of PRKAR1A expression. […] Spinal schwannomas can have SMARCB1 mutations and inactivation.

• #4 Schwannomas and Their Pathogenesis

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

  The risk of offspring inheriting NF2 in mosaic patients is difficult to quantify, but may be considerably less than 50%. […] Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] In addition, the tumors may show patchy loss of SMARCB1 (INI1) immunoreactivity and the presence of intratumoral nerve fibers. […] 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. […] In addition to affecting these mostly mitogenic and survival pathways, merlin uncouples Ras/Rac growth factor receptor interactions and has a negative feedback loop with PAK, so that loss of merlin leads to Rac activation, which in turn leads to sustained and nonlocalized GTPase activation.

• #4 Schwannomas and Their Pathogenesis

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

  Thus, schwannomas in schwannomatosis have merlin loss, like schwannomas in NF2 or spontaneous schwannomas, but the initial mutation is different. […] PRKAR1a appears to act as a tumor suppressor gene, and inactivation results in increased cyclic adenosine monophosphate (cAMP) activity and Rac 1 activation, leading to suppression of merlin activity and the development of Schwann cell tumors.

• #4 Schwannomatosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/schwannomatosis/

  Schwannomatosis is a disorder characterized by multiple noncancerous (benign) tumors called schwannomas, which are a type of tumor that grows on nerves. Schwannomas develop when Schwann cells, which are specialized cells that normally form an insulating layer around the nerve, grow uncontrollably to form a tumor. […] Mutations in at least two genes, SMARCB1 and LZTR1, can cause schwannomatosis. The proteins produced from both genes are thought to act as tumor suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in either of these genes may help cells grow and divide without control or order to form a tumor. […] It appears that mutations in the SMARCB1 or LZTR1 gene alone are not enough to trigger the development of schwannomas. Additional genetic changes (somatic mutations) that are acquired during a person’s lifetime and are present only in certain cells may also be required for schwannomas to form. The most common somatic mutations in schwannomas are mutations in the NF2 gene and a loss of chromosome 22 (which is the chromosome on which the SMARCB1, LZTR1, and NF2 genes are found). […] Some people with schwannomatosis do not have an identified mutation in the SMARCB1 or LZTR1 gene. In these cases, the cause of the disorder is unknown. Researchers suspect that mutations in other as-yet-unidentified genes, most likely on chromosome 22, also contribute to this condition.

• #4 Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology | Journal of Experimental & Clinical Cancer Research | Full Text

  https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02473-4

  Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. […] The drivers of sporadic VS associated with progression have never been characterized previously, although electron microscopical studies of bovine schwannomas have revealed viral particles in the tumors, suggesting a potential viral etiology. […] Our findings show that in rapidly progressing VS, virus-inducible cellular gene networks, such as interferon gamma signaling, are enriched. […] Interestingly, we found that rapidly progressing VS cases exhibited activation of several pathways linked to viral infection, such as the canonical pathway NF-B Activation by Viruses, and others highlighted in Fig. 3C. These findings may indicate that fast progressing VS are associated with an underlying viral infection, which is associated with the dramatic upregulation of stress-related and proliferation/survival signaling pathways, as well as the significant downregulation of immune signaling.

• #4 Hearing loss and vestibular schwannoma: new insights into Schwann cells implication | Cell Death & Disease

  https://www.nature.com/articles/s41419-023-06141-z

  Overall, the causative genes are classified as presynaptic, synaptic, and postsynaptic. […] In addition, a variety of nervous neoplasms can cause HL, including the vestibular schwannoma (VS), described below. […] The first step of the pathologic process leading to SNHL, with SGN degeneration, entails a rapid and extensive loss of the unmyelinated axonal processes within the organ of Corti, followed by a gradual degeneration of the myelinated portion of the peripheral axons (within the osseous spiral lamina), and of the SGN soma inside the Rosenthals canal. […] The resulting SCs demyelination determines an increase of the neural membrane capacitance, reducing the capability of a neuron in initiating and propagating action potentials in response to electrical stimuli, and leading to a delayed nerve excitation.

• #4 Schwannoma: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17877-schwannoma

  Schwannomas usually develop randomly in otherwise healthy people. […] In some cases, a schwannoma is caused by a genetic condition, such as neurofibromatosis 2 (NF2), schwannomatosis or Carney complex. People with these genetic conditions usually have more than one schwannoma. […] The cause of schwannomas isn’t known in most cases. Approximately 90% of cases occur sporadically (randomly). […] Genetic disorders such as Carney complex, neurofibromatosis 2 (NF2) and schwannomatosis can cause schwannomas. Genetic studies show that the NF2 gene on chromosome 22 plays an essential role in schwannoma development.

• #4 Schwannoma: Causes, Symptoms & Treatment

  https://mnamd.com/schwannoma/

  Radiation Exposure: Some studies suggest that exposure to high levels of radiation may increase the risk of developing Schwannomas. However, this is relatively rare and occurs primarily in cases of high-dose therapeutic radiation or occupational exposure to radiation. […] Environmental Factors: While not definitively proven, some environmental factors, such as exposure to certain chemicals or toxins, have been proposed as possible contributors to Schwannoma development. Research in this area is still ongoing. […] Sporadic Cases: In many instances, Schwannomas may develop sporadically without any identifiable genetic or environmental factors. These cases are often considered random occurrences. […] It is essential to recognize that Schwannomas are generally non-cancerous and do not result from lifestyle choices or behaviors. While understanding the causes of Schwannomas remains a subject of ongoing research, early detection and timely treatment are vital for optimal outcomes.

• #4 Mifepristone may halt growth of intracranial tumor that causes hearing loss | Mass. Eye and Ear

  https://masseyeandear.org/news/press-releases/2018/04/mifepristone-may-halt-growth-of-intracranial-tumor-that-causes-hearing-loss

  Mifepristone, an FDA-approved drug for chemical abortion, is identified as a promising candidate for the treatment of vestibular schwannoma, a sometimes-lethal tumor associated with neurofibromatosis 2 (NF2) or occurring sporadically. […] Vestibular schwannomas are dangerous due to their location. Arising from the Schwann cells of the vestibular (balance) nerve, these tumors can grow to the point of damaging nearby structures — and can lead to death by compressing the brainstem. […] Though vestibular schwannomas affecting both sides are the hallmark of neurofibromatosis type 2 (NF2), a genetic disorder causing tumors to grow at multiple sites throughout a person’s life, vestibular schwannomas may also occur sporadically, and on one side only. […] Currently, patients with symptomatic or growing vestibular schwannomas can undergo surgical resection (through craniotomy) or radiation therapy; however, both of these procedures come with significant risks. […] Based on the findings described in Scientific Reports, the study authors are cautiously optimistic about the therapeutic potential of mifepristone for patients with vestibular schwannomas, either from NF2 or those arising sporadically.

• #5 Schwannoma | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/schwannoma?lang=us

  Schwannomas, less commonly called neurinomas or neurilemmomas, are benign tumors of Schwann cell origin and are the most common tumor of peripheral nerves, including cranial nerves. […] The vast majority of schwannomas are sporadic, with a peak presentation in the 5th to 6th decades. There is no sex predilection. […] Most schwannomas are solitary (90%) and sporadic, however, there is an association with neurofibromatosis type 2 (NF2) (abnormality of chromosome 22). Multiple schwannomas are characteristic of neurofibromatosis type 2. Approximately 18% of solitary schwannomas occur in patients with neurofibromatosis type 2. […] There is also schwannomatosis, which consists of multiple schwannomas without the concomitant involvement of cranial nerve VIII.

• #5 Schwannomas and Their Pathogenesis

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

  The risk of offspring inheriting NF2 in mosaic patients is difficult to quantify, but may be considerably less than 50%. […] Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] In addition, the tumors may show patchy loss of SMARCB1 (INI1) immunoreactivity and the presence of intratumoral nerve fibers. […] 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. […] In addition to affecting these mostly mitogenic and survival pathways, merlin uncouples Ras/Rac growth factor receptor interactions and has a negative feedback loop with PAK, so that loss of merlin leads to Rac activation, which in turn leads to sustained and nonlocalized GTPase activation.

• #5 Schwannoma: Symptoms, Causes, Treatment, and More

  https://www.healthline.com/health/schwannoma

  Aside from NF2 and schwannomatosis, researchers dont know what causes schwannomas. People with a family history of spinal cancer are more likely to have a spinal schwannoma, which suggests they could be genetic. Exposure to radiation is another possible cause. […] Malignant schwannomas do exist, but theyre very rare. They usually appear in the legs, lower back, and upper arms. They also sometimes occur in the nerves between your legs. When this happens, you might feel pain or discomfort in your bowels or bladder.

• #5 Vestibular schwannoma – Wikipedia

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

  The complexity of the molecular biology research involved is truly challenging. […] A key step forward in 1993 was the identification of the NF2 gene and its protein product Merlin, which modulates the complex molecular signaling pathways that control cell proliferation. These pathways that drive VS formation (tumorigenesis) and growth are currently under investigation. […] The development of a new generation of drugs may become a secondary therapy in view of advances in genome editing during the 1990s that led to the invention of CRISPR in 2009.

• #6 Schwannomas and Their Pathogenesis

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

  The risk of offspring inheriting NF2 in mosaic patients is difficult to quantify, but may be considerably less than 50%. […] Schwannomas in patients with NF2 have a similar morphology to sporadic tumors, but multifocal nerve involvement and whorl formation are more frequent. […] In addition, the tumors may show patchy loss of SMARCB1 (INI1) immunoreactivity and the presence of intratumoral nerve fibers. […] 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. […] In addition to affecting these mostly mitogenic and survival pathways, merlin uncouples Ras/Rac growth factor receptor interactions and has a negative feedback loop with PAK, so that loss of merlin leads to Rac activation, which in turn leads to sustained and nonlocalized GTPase activation.

Zobacz więcej