Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 315
Filtrar
1.
Clin Trials ; 21(1): 73-84, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37962219

RESUMO

BACKGROUND/AIMS: Individuals with neurofibromatosis, including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2)-related schwannomatosis (SWN), and other forms of SWN, often experience disease manifestations and mental health difficulties for which psychosocial interventions may help. An anonymous online survey of adults with neurofibromatosis assessed their physical, social, and emotional well-being and preferences about psychosocial interventions to inform clinical trial design. METHODS: Neurofibromatosis clinical researchers and patient representatives from the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration developed the survey. Eligibility criteria included age ≥ 18 years, self-reported diagnosis of NF1, NF2, or SWN, and ability to read and understand English. The online survey was distributed internationally by the Neurofibromatosis Registry and other neurofibromatosis foundations from June to August 2020. RESULTS: Surveys were completed by 630 adults (18-81 years of age; M = 45.5) with NF1 (78%), NF2 (14%), and SWN (8%) who were mostly White, not Hispanic/Latino, female, and from the United States. The majority (91%) reported that their neurofibromatosis symptoms had at least some impact on daily life. In the total sample, 51% endorsed a mental health diagnosis, and 27% without a diagnosis believed they had an undiagnosed mental health condition. Participants indicated that neurofibromatosis affected their emotional (44%), physical (38%), and social (35%) functioning to a high degree. Few reported ever having participated in a drug (6%) or psychosocial (7%) clinical trial, yet 68% reported they "probably" or "definitely" would want to participate in a psychosocial trial if it targeted a relevant concern. Top treatment targets were anxiety, healthier lifestyle, and daily stress. Top barriers to participating in psychosocial trials were distance to clinic, costs, and time commitment. Respondents preferred interventions delivered by clinicians via individual sessions or a combination of group and individual sessions, with limited in-person and mostly remote participation. There were no significant group differences by neurofibromatosis type in willingness to participate in psychosocial trials (p = 0.27). Regarding interest in intervention targets, adults with SWN were more likely to prefer psychosocial trials for pain support compared to those with NF1 (p < 0.001) and NF2 (p < 0.001). CONCLUSION: This study conducted the largest survey assessing physical symptoms, mental health needs, and preferences for psychosocial trials in adults with neurofibromatosis. Results indicate a high prevalence of disease manifestations, psychosocial difficulties, and untreated mental health problems in adults with neurofibromatosis and a high degree of willingness to participate in psychosocial clinical trials. Patient preferences should be considered when designing and implementing psychosocial interventions to develop the most feasible and meaningful studies.


Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 1 , Neurofibromatose 2 , Neoplasias Cutâneas , Adulto , Feminino , Humanos , Estados Unidos , Adolescente , Neurofibromatoses/terapia , Neurofibromatoses/diagnóstico , Neurofibromatoses/psicologia , Neurilemoma/diagnóstico , Neurilemoma/psicologia , Neurilemoma/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/psicologia , Neoplasias Cutâneas/terapia , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/psicologia , Neurofibromatose 2/terapia , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/psicologia , Neurofibromatose 1/terapia , Inquéritos e Questionários
2.
Clin Trials ; 21(1): 51-66, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37937606

RESUMO

Numerous successful gene-targeted therapies are arising for the treatment of a variety of rare diseases. At the same time, current treatment options for neurofibromatosis 1 and schwannomatosis are limited and do not directly address loss of gene/protein function. In addition, treatments have mostly focused on symptomatic tumors, but have failed to address multisystem involvement in these conditions. Gene-targeted therapies hold promise to address these limitations. However, despite intense interest over decades, multiple preclinical and clinical issues need to be resolved before they become a reality. The optimal approaches to gene-, mRNA-, or protein restoration and to delivery to the appropriate cell types remain elusive. Preclinical models that recapitulate manifestations of neurofibromatosis 1 and schwannomatosis need to be refined. The development of validated assays for measuring neurofibromin and merlin activity in animal and human tissues will be critical for early-stage trials, as will the selection of appropriate patients, based on their individual genotypes and risk/benefit balance. Once the safety of gene-targeted therapy for symptomatic tumors has been established, the possibility of addressing a wide range of symptoms, including non-tumor manifestations, should be explored. As preclinical efforts are underway, it will be essential to educate both clinicians and those affected by neurofibromatosis 1/schwannomatosis about the risks and benefits of gene-targeted therapy for these conditions.


Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 1 , Neurofibromatose 2 , Neoplasias Cutâneas , Animais , Humanos , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/genética , Neurofibromatose 2/patologia , Neurofibromatoses/genética , Neurofibromatoses/terapia , Neurofibromatoses/diagnóstico , Neurilemoma/genética , Neurilemoma/terapia , Neurilemoma/diagnóstico
3.
Prensa méd. argent ; 109(5): 215-218, 20230000. fig
Artigo em Inglês | LILACS, BINACIS | ID: biblio-1523807

RESUMO

El Schwannoma se origina de la vaina perineural de Schwannoma, se detecta con frecuencia incidentalmente en estudios imagenológicos siendo el principal método diagnóstico la Tomografía Computada. El tratamiento es la resección quirúrgica con márgenes libres. Se presenta una paciente femenina de 49 años, en control por oncología por enfermedad de base, cáncer de mama izquierda, se identifica por TAC y PECT/TC imagen voluminosa en retroperitoneo situación lateroaórtica izquierda de configuración no quística e hipermetabólica, solicita biopsia percutánea, ante la falta de ventana, se decide exeresis completa de masa. Diagnóstico definitivo patológico Schwannoma. Sin indicación de tratamiento adyuvante, cursa buena evolución postoperatoria sin recidiva.


Schwannoma, a benign tumor that arises from Schwann cells of the perineural nerve sheath, is often incidentally detected in imaging tests and mainly diagnosed by CT scan. Treatment consists of surgical resection with clear margins. We present the case of a 49-year-old female patient subject to Oncology Department follow-up due to an underlying disease, left breast cancer. A large, hypermetabolic, noncystic mass in the retroperitoneal region is identified by CT and PECT/CT scan in the left lateral aortic area. A percutaneous biopsy is requested. Due to the limited acoustic window, complete resection of the mass is decided. Final histopathology diagnosis of Schwannoma. No adjuvant treatment indication; undergoing favorable postoperative progress, without recurrence


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/cirurgia , Diagnóstico Diferencial , Neurilemoma/terapia
4.
Hum Vaccin Immunother ; 19(2): 2262639, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37786375

RESUMO

Schwannomas are slow-growing benign peripheral nerve sheath tumors derived from Schwann-lineage cells that develop in association with NF2-related schwannomatosis (NF2) and schwannomatosis (NF3), as well as spontaneously. Individuals affected with NF2 and NF3 have multiple schwannomas with tumors arising throughout life. Surgical resection, the standard management, is limited in scope and efficacy and is itself associated with significant morbidity. We have previously shown that direct intratumoral injection of attenuated Salmonella Typhimurium (S. Typhimurium), strain VNP20009, showed a potent anti-tumor effect in preclinical NF-2 schwannoma models. The United States Federal Drug Administration (FDA) requires that bacterial products utilized in clinical trials be produced without exposure to animal-derived-products. In this context, we developed, characterized, and tested the antitumor efficacy of an attenuated S. Typhimurium serially passaged in animal-product-free media, naming it VNP20009-AF for "VNP20009-animal-product-free." Our in vitro data did not indicate any significant changes in the viability, motility, or morphology of VNP20009-AF, compared to its parental strain. In vivo efficacy data demonstrated that VNP20009-AF and VNP20009 controlled tumor growth to the same degree in both human NF2-schwannoma xenograft and murine-NF2 schwannoma allograft models. Together, these data support the use of VNP20009-AF for the translation of bacterial schwannoma therapy into clinical trials.


Assuntos
Neurilemoma , Neoplasias Cutâneas , Humanos , Camundongos , Animais , Salmonella typhimurium , Neurilemoma/terapia
5.
Zh Vopr Neirokhir Im N N Burdenko ; 87(5): 104-109, 2023.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-37830475

RESUMO

Schwannomatoses is a new classification unit for all the hereditary diseases caused by chromosome 22 damage followed by multiple benign neoplasms of the peripheral and central nervous system. Schwannomatosis occurs as a result of damage to different genes: NF2, SMARCB1, LZRT1, loss of heterozygosity of the long arm of chromosome 22. Nevertheless, clinical manifestations are similar. Molecular diagnostics not only confirms the diagnosis, but also predicts the course of disease. Thus, the most severe clinical manifestations are observed in patients with violation of semantic sequences and reading frame shift in exons 2-13 of the NF2 gene. A more favorable course with less number of tumors is observed in patients with somatic mosaicism. Stereotactic irradiation and surgery are the main treatment options for schwannomatosis. However, there is evidence of effective targeted therapy with bevacizumab (inhibitor of vascular endothelial growth factor). Bevacizumab is used in patients with bilateral vestibular schwannomas and high risk of hearing loss, as well as for intramedullary tumor growth control.


Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 2 , Humanos , Bevacizumab , Fator A de Crescimento do Endotélio Vascular , Neurilemoma/genética , Neurilemoma/terapia , Neurofibromatoses/genética , Neurofibromatoses/terapia , Neurofibromatoses/diagnóstico , Neurofibromatose 2/genética , Neurofibromatose 2/terapia , Neurofibromatose 2/diagnóstico
6.
Curr Opin Oncol ; 35(6): 550-557, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37820090

RESUMO

PURPOSE OF REVIEW: In 2022, an international consensus recommendation revised the nomenclature for neurofibromatosis type 2 ( NF2 ) and Schwannomatosis (SWN), now grouped under the umbrella term Schwannomatosis, and defined new diagnostic criteria. RECENT FINDINGS: This review describes the molecular criteria for diagnosis of schwannomatosis and the subsequent diagnosis strategy, while setting out the most recent advances in our understanding of the natural history, pathology, molecular biology and treatment of schwannomatosis-associated tumors, including schwannomas, meningiomas and ependymomas. SUMMARY: Somatic mutation screening should become a new standard for the diagnosis of NF2 -, LTZTR1 -, SMARCB1 - and 22q-schwannomatosis to discriminate those conditions. Constitutional events in NF2 -Schwannomatosis have a major influence on disease severity and justifiably motivate ongoing efforts on gene replacement therapy research. On the other hand, underlying mechanisms of disease severity and associated pain remain largely unknown in non- NF2 -SWN and independent of germline mutation. Research efforts therefore focus on pain relief in ongoing trials and the discovery of new molecular mechanisms underlying schwannoma tumorigenesis/pain/neuropathies.


Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 2 , Neoplasias Cutâneas , Humanos , Neurilemoma/diagnóstico , Neurilemoma/genética , Neurilemoma/terapia , Neurofibromatoses/diagnóstico , Neurofibromatoses/genética , Neurofibromatoses/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/genética , Neurofibromatose 2/terapia , Dor
8.
Proc Natl Acad Sci U S A ; 119(24): e2202719119, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35675425

RESUMO

Schwannomas are slow-growing benign neoplasms that develop throughout the body causing pain, sensory/motor dysfunction, and death. Because bacterial immunotherapy has been used in the treatment of some malignant neoplasms, we evaluated attenuated Salmonella typhimurium strains as immunotherapies for benign murine schwannomas. Several bacterial strains were tested, including VNP20009, a highly attenuated strain that was previously shown to be safe in human subjects with advanced malignant neoplasms, and a VNP20009 mutant that was altered in motility and other properties that included adherence and invasion of cultured mammalian cells. VNP20009 controlled tumor growth in two murine schwannoma models and induced changes in cytokine and immune effector cell profiles that were consistent with induction of enhanced innate and adaptive host immune responses compared with controls. Intratumoral (i.t.) injection of S. typhimurium led to tumor cell apoptosis, decreased tumor angiogenesis, and lower growth of the injected schwannoma tumors. Invasive VNP20009 was significantly more efficacious than was a noninvasive derivative in controlling the growth of injected tumors. Bacterial treatment apparently induced systemic antitumor immunity in that the growth of rechallenge schwannomas implanted following primary bacterial treatment was also reduced. Checkpoint programmed death-1 (PD-1) blockade induced by systemic administration of anti-PD-1 antibodies controlled tumor growth to the same degree as i.t. injection of S. typhimurium, and together, these two therapies had an additive effect on suppressing schwannoma growth. These experiments represent validation of a bacterial therapy for a benign neoplasm and support development of S. typhimurium VNP20009, potentially in combination with PD-1 inhibition, as a schwannoma immunotherapy.


Assuntos
Imunoterapia , Neurilemoma , Salmonella typhimurium , Animais , Apoptose , Humanos , Imunoterapia/métodos , Injeções Intralesionais , Camundongos , Neoplasias Experimentais/terapia , Neurilemoma/terapia , Receptor de Morte Celular Programada 1 , Salmonella typhimurium/genética
9.
Pediatr Neurol ; 134: 1-6, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35759947

RESUMO

INTRODUCTION: The neurofibromatoses comprise three different genetic conditions causing considerable morbidity and mortality: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). This review summarizes recent and ongoing clinical trials involving patients with neurofibromatoses to better understand the current state of clinical trial research centered around these conditions and inform areas of need. METHODS: A search was conducted using the Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases. Inclusion and exclusion criteria were designed to identify clinical trials focused on patients with NF1, NF2, or SWN completed in or after 2010 and in process as of December 31, 2021. Information was collected using standardized guidelines. RESULTS: A total of 134 clinical trials were included, with 75 (56%) completed and 59 (44%) in process. For completed trials, 74% (n = 56) involved patients with NF1, and of those based on specific tumors (n = 26, 46%), the majority focused on plexiform neurofibromas (PNs) (n = 12, 46%). For ongoing trials, 79% (n = 47) involve patients with NF1, and of those based on specific tumors (n = 29, 61%), the majority are focused on PNs (n = 13, 45%). CONCLUSION: Both recent and ongoing clinical trials have primarily focused on patients with NF1 and the treatment of PNs. This research has led to the first FDA-approved drug for NF1-PN and has changed management of these tumors, allowing for systemic therapy rather than reliance on only a surgical modality. Trials evaluating comorbid psychiatric conditions and quality of life among patients with any of the neurofibromatoses appear less common. These areas may warrant focus in future studies to improve clinical management.


Assuntos
Neurilemoma , Neurofibroma Plexiforme , Neurofibromatoses , Neurofibromatose 1 , Neurofibromatose 2 , Humanos , Neurilemoma/terapia , Neurofibromatoses/terapia , Neurofibromatose 1/complicações , Neurofibromatose 1/terapia , Neurofibromatose 2/genética , Qualidade de Vida , Neoplasias Cutâneas
10.
Eur J Hum Genet ; 30(7): 812-817, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35361920

RESUMO

A Guideline Group (GG) was convened from multiple specialties and patients to develop the first comprehensive schwannomatosis guideline. The GG undertook thorough literature review and wrote recommendations for treatment and surveillance. A modified Delphi process was used to gain approval for recommendations which were further altered for maximal consensus. Schwannomatosis is a tumour predisposition syndrome leading to development of multiple benign nerve-sheath non-intra-cutaneous schwannomas that infrequently affect the vestibulocochlear nerves. Two definitive genes (SMARCB1/LZTR1) have been identified on chromosome 22q centromeric to NF2 that cause schwannoma development by a 3-event, 4-hit mechanism leading to complete inactivation of each gene plus NF2. These genes together account for 70-85% of familial schwannomatosis and 30-40% of isolated cases in which there is considerable overlap with mosaic NF2. Craniospinal MRI is generally recommended from symptomatic diagnosis or from age 12-14 if molecularly confirmed in asymptomatic individuals whose relative has schwannomas. Whole-body MRI may also be deployed and can alternate with craniospinal MRI. Ultrasound scans are useful in limbs where typical pain is not associated with palpable lumps. Malignant-Peripheral-Nerve-Sheath-Tumour-MPNST should be suspected in anyone with rapidly growing tumours and/or functional loss especially with SMARCB1-related schwannomatosis. Pain (often intractable to medication) is the most frequent symptom. Surgical removal, the most effective treatment, must be balanced against potential loss of function of adjacent nerves. Assessment of patients' psychosocial needs should be assessed annually as well as review of pain/pain medication. Genetic diagnosis and counselling should be guided ideally by both blood and tumour molecular testing.


Assuntos
Neurilemoma , Neurofibromatoses , Neoplasias Cutâneas , Adolescente , Criança , Humanos , Neurilemoma/diagnóstico , Neurilemoma/genética , Neurilemoma/terapia , Neurofibromatoses/diagnóstico , Neurofibromatoses/genética , Neurofibromatoses/terapia , Dor , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Fatores de Transcrição/genética
11.
No Shinkei Geka ; 50(1): 162-170, 2022 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-35169096

RESUMO

Schwannoma is a tumor that develops from the Schwann cells in the peripheral nervous system or cranial nerves. Gamma Knife radiosurgery has become an accepted treatment for schwannoma, with a high rate of tumor control. For sporadic or neurofibromatosis type 2-associated schwannoma resistant to radiotherapy, vascular endothelial growth factor(VEGF)-A/VEGF receptor(VEGFR)-targeted therapy(e.g., bevacizumab)may become the first-line therapy. However, some aspects of treatment with bevacizumab are problematic, such as the need for frequent parenteral administration, side effects, apparent drug resistance, and rebound tumor progression after cessation. In these situations, the gene product of the SH3PXD2A-HTRA1 fusion and several protein tyrosine kinase inhibitors may be supportive in preventing tumor progression because merlin inhibits signaling by tyrosine receptor kinases and there is activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Although the tumor-microenvironment(TME)plays a key role in tumor growth, this physiological state is unclear in schwannoma. Tumor-associated macrophages may be a major component of the immunosuppressive cells in the TME of schwannoma. To impede tumor growth, the TME is also explored as a potential therapeutic target. Multimodal therapy is required to manage patients with refractory schwannoma. Furthermore, basic scientific research may be essential in achieving a novel treatment strategy.


Assuntos
Neurilemoma , Neurofibromatose 2 , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Neurilemoma/genética , Neurilemoma/terapia , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular
12.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35055004

RESUMO

Schwannomas are tumors derived from Schwann-lineage cells, cells that protect and support myelinated nerves in the peripheral nervous system. They are typically slow-growing, encapsulated and benign. These tumors develop along peripheral, spinal and cranial nerves causing pain, sensory-motor dysfunction and death. Primary treatment for schwannoma is operative resection which can be associated with significant morbidity. Pharmacotherapy is largely restricted to bevacizumab, which has minimal or no efficacy for many patients and can be associated with treatment-limiting adverse effects. Given the suffering and morbidity associated with schwannoma and the paucity of therapeutic options, there is an urgent need for safe and effective therapies for schwannomas. We previously demonstrated that adeno-associated virus serotype 1 (AAV1) vector mediated delivery of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) under the control of the P0 promoter, produced a prolonged reduction in tumor volume and tumor-associated pain in human xenograft and mouse syngeneic schwannoma models. Here, we present data essential for the translation of our AAV1-P0-ASC schwannoma gene therapy to clinical trials. We determine the minimum effective dose of AAV1-P0-hASC required to induce an anti-tumor effect in the xenograft human-schwannoma model. We also show that the presence of preexisting AAV1 immunity does not alter the antitumor efficacy of AAV-P0-mASC in a syngeneic mouse schwannoma model. Furthermore, the maximum deliverable intratumoral dose of AAV1-P0-ASC was not associated with neuronal toxicity in immunocompetent mice. Taken together, these safety and efficacy data support the translation of the AAV1-P0-ASC schwannoma gene therapy strategy to clinical trials.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Dependovirus/genética , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos/genética , Neurilemoma/genética , Neurilemoma/terapia , Animais , Modelos Animais de Doenças , Imunofluorescência , Expressão Gênica , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Humanos , Imuno-Histoquímica , Camundongos , Transdução Genética , Transgenes , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Br J Neurosurg ; 36(2): 171-174, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33263426

RESUMO

BACKGROUND: Schwannomatosis is a relatively rare disorder and is related to neurofibromatosis type 2. Although there is clinical overlap between schwannomatosis and neurofibromatosis type 2, these diseases have to be regarded as separate entities due to the genetic origin and course of the disease. METHODS: A comprehensive review of the literature was conducted for relevant studies using Pubmed and Cochrane databases to discuss the epidemiology, clinical presentation, diagnostic criteria, pathological and imaging features, treatment and genetics of schwannomatosis. RESULTS: Germline mutations SMARCB1 and LZTRI together with the NF2 gene play a role in the pathophysiology of schwannomatosis. The most common symptom is pain with affection of the spine and peripheral nerves in the majority of patients. High quality contrast enhanced MRI scan is the imaging modality of choice. Treatment is conservative if asymptomatic and surgical if symptomatic. The goal is symptom control with preservation of neurological function. CONCLUSION: Schwannomatosis is a relatively rare disorder in which the main goal is to preserve neurological function.


Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 2 , Neoplasias Cutâneas , Humanos , Neurilemoma/diagnóstico , Neurilemoma/genética , Neurilemoma/terapia , Neurofibromatoses/diagnóstico , Neurofibromatoses/genética , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/genética , Neurofibromatose 2/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia
14.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360664

RESUMO

Peripheral nerve injuries are a common condition in which a nerve is damaged, affecting more than one million people every year. There are still no efficient therapeutic treatments for these injuries. Artificial scaffolds can offer new opportunities for nerve regeneration applications; in this framework, chitosan is emerging as a promising biomaterial. Here, we set up a simple and effective method for the production of micro-structured chitosan films by solvent casting, with high fidelity in the micro-pattern reproducibility. Three types of chitosan directional micro-grooved patterns, presenting different levels of symmetricity, were developed for application in nerve regenerative medicine: gratings (GR), isosceles triangles (ISO) and scalene triangles (SCA). The directional patterns were tested with a Schwann cell line. The most asymmetric topography (SCA), although it polarized the cell shaping less efficiently, promoted higher cell proliferation and a faster cell migration, both individually and collectively, with a higher directional persistence of motion. Overall, the use of micro-structured asymmetrical directional topographies may be exploited to enhance the nerve regeneration process mediated by chitosan scaffolds.


Assuntos
Quitosana/química , Membranas/química , Regeneração Nervosa , Neurilemoma/terapia , Células de Schwann/citologia , Cicatrização , Movimento Celular , Proliferação de Células , Humanos , Neurilemoma/patologia
15.
Neurology ; 97(7 Suppl 1): S15-S24, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34230202

RESUMO

OBJECTIVE: To assess the perspectives of adults with neurofibromatosis 1 (NF1) regarding cutaneous neurofibroma (cNF) morbidity, treatment options, and acceptable risk-benefit ratio to facilitate the design of patient-centered clinical trials. METHODS: An online survey developed by multidisciplinary experts and patient representatives of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) cNF Working Group was distributed to adults with NF1 (n = 3,734) in the largest international database of individuals with any form of NF. Eligibility criteria included self-reported NF1 diagnosis, age ≥18 years, ≥1 cNF, and ability to read English. RESULTS: A total of 548 adults with NF1 responded to the survey. Respondents ranked appearance, number, and then location as the most bothersome features of raised cNF. Seventy-five percent of respondents considered a partial decrease of 33%-66% in the number or size of cNF as a meaningful response to experimental treatments. Most respondents (48%-58%) were willing to try available cNF treatments but were not aware of options outside of surgical removal. Regarding experimental agents, respondents favored topical, then oral medications. Most individuals (>65%) reported being "very much" or "extremely willing" to try experimental treatments, especially those with the highest cNF burden. Many respondents were not willing to tolerate side effects like nausea/vomiting (51%) and rash (46%). The greatest barriers to participation in cNF clinical trials were cost of participation and need to take time off work. CONCLUSIONS: Most adults with NF1 are willing to consider experimental therapies for treatment of cNF. These data will guide the design of patient-centered clinical trials for adults with cNF.


Assuntos
Ensaios Clínicos como Assunto , Neurofibroma/terapia , Neurofibromatoses/terapia , Neurofibromatose 1/metabolismo , Adolescente , Adulto , Doenças do Tecido Conjuntivo/terapia , Humanos , Neurilemoma/terapia , Neoplasias Cutâneas/terapia , Inquéritos e Questionários
16.
Neurology ; 97(7 Suppl 1): S4-S14, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34230208

RESUMO

OBJECTIVE: As part of an evaluation of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration patient representative program, we surveyed REiNS members to (1) identify facilitators and barriers to involving patient representatives and (2) understand whether and how involving patient representatives affected recommendations for clinical trial outcomes. METHODS: We administered an anonymous online survey to all REiNS members. Facilitators and barriers to patient representative involvement were solicited using a modified free listing technique; responses were inductively grouped into higher-order categories and ranked based on saliency score (Smith s). Open-ended questions assessed patient representative expectations for engagement, perceived benefits/costs of patient engagement, and patient representative contributions; responses were analyzed using conventional content analysis. RESULTS: A total of 63/172 (37%) members responded, including 18/30 (60%) patient representatives. Providing sufficient opportunities to meaningfully engage in research tasks and cultivating a respectful, inclusive atmosphere were key facilitators to patient representatives' satisfaction and ability to make an impact. Respondents perceived that patient representatives directly (through their input on research tasks) and indirectly (through effects on other stakeholders' knowledge and communication style) improved the organization's research, leading to selection of more meaningful, relevant, and feasible clinical trial outcome measures. Ongoing challenges to patient engagement include difficulty scheduling meetings and concerns about the level of scientific knowledge patient representatives needed to effectively engage. CONCLUSIONS: Involving patient representatives in REiNS improved perceived quality of neurofibromatosis clinical trial outcome measures. Negotiating sufficient opportunities to engage, fostering an inclusive atmosphere, and navigating time pressures are key to effective patient engagement.


Assuntos
Neurilemoma/metabolismo , Neurilemoma/terapia , Neurofibromatoses/metabolismo , Neurofibromatoses/terapia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/terapia , Ensaios Clínicos como Assunto , Comunicação , Humanos , Neurofibromatose 1/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Participação do Paciente/métodos
17.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072574

RESUMO

Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of NF: NF1 accounting for 96% of all cases, NF2 in 3%, and schwannomatosis (SWN) in <1%. The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras/MAPK and PI3K/mTOR signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to ezrin-radixin-moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of SWN remain unclear. Inactivating mutations in the tumor suppressor genes SMARCB1 and LZTR1 are considered responsible for a majority of cases. Recently, treatment strategies to target specific genetic or molecular events involved in their tumorigenesis are developed. This study discusses molecular pathways and related targeted therapies for NF1, NF2, and SWN and reviews recent clinical trials which involve NF patients.


Assuntos
Suscetibilidade a Doenças , Neurilemoma/etiologia , Neurofibromatoses/etiologia , Neurofibromatose 1/etiologia , Neurofibromatose 2/etiologia , Neoplasias Cutâneas/etiologia , Animais , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Genes da Neurofibromatose 1 , Genes da Neurofibromatose 2 , Predisposição Genética para Doença , Humanos , Modelos Biológicos , Terapia de Alvo Molecular , Mutação , Neurilemoma/diagnóstico , Neurilemoma/terapia , Neurofibromatoses/diagnóstico , Neurofibromatoses/terapia , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/terapia , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/terapia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Resultado do Tratamento
18.
Galicia clin ; 82(1): 41-42, Enero-Febrero-Marzo 2021. ilus
Artigo em Inglês | IBECS | ID: ibc-221105

RESUMO

Urinary tract infection (UTI) affects mostly women. Any condition that allows stasis or urinary obstruction predisposes to the development of UTI. The authors report the case of a 37-year-old woman with a recurrent UTI who presented with right lumbar pain irradiating to homolateral inguinal regionand genito-urinary symptoms, and a pelvic extensive lesion was shown in the abdominal-pelvic CT in apparent relationship with L5 nerve root compatible with a Schwannoma. Schwannomas are usually benign tumors that rarely present malignant transformation. Repetitive UTIs may be a consequence of the mass effect or of neurological cause secondary to intraspinal schwannomas that cause urinary retention. Local recurrence or malignant change is possible, so complete tumor resection is important. (AU)


Assuntos
Humanos , Feminino , Adulto , Infecções Urinárias/diagnóstico por imagem , Infecções Urinárias/terapia , Achados Incidentais , Neurilemoma/diagnóstico , Neurilemoma/terapia
20.
Medicine (Baltimore) ; 99(38): e22307, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957393

RESUMO

RATIONALE: Schwannoma is a benign peripheral nerve sheath tumor composed of Schwann cells and caused by genetic mutation or deletion. It rarely occurs in seminal vesicles. The optimal therapic strategy for asymptomatic cases is still unclear. PATIENT CONCERNS: A 42-year-old man presented no clinical symptoms. A mass in his left seminal vesicle was found incidentally in a computed tomography scan and transrectal ultrasound-guided biopsy revealed the mass was schwannoma. DIAGNOSIS: The patient was diagnosed as schwannoma of the seminal vesicle with no significant extension to the surrounding tissues. INTERVENTIONS: The patient underwent computed tomography or magnetic resonance imaging scans periodically to estimate the alteration of the lesion and further strategy. OUTCOMES: After 20-month follow-up, computed tomography scans showed no significant alteration to the lesion and no clinical symptoms were reported by the patient. LESSONS: Conservative strategy might be an effective treatment option for asymptomatic patients with seminal vesical schwannoma. The period of follow-up depends on the size of the tumor.


Assuntos
Tratamento Conservador/métodos , Neoplasias dos Genitais Masculinos/terapia , Neurilemoma/terapia , Adulto , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Neoplasias dos Genitais Masculinos/patologia , Humanos , Achados Incidentais , Imageamento por Ressonância Magnética , Masculino , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Glândulas Seminais/diagnóstico por imagem , Glândulas Seminais/patologia , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...