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Radiology Case Reports Aug 2021Plexiform neurofibroma(PNF) is a rare benign tumor of the peripheral nerve, belonging to a subtype of neurofibroma. PNF is common in the head, neck and trunk. It is...
Plexiform neurofibroma(PNF) is a rare benign tumor of the peripheral nerve, belonging to a subtype of neurofibroma. PNF is common in the head, neck and trunk. It is uncommonly observed in the mesentery. We report a case of mesenteric PNF in a 64-year-old man history of neurofibromatosis type I(NF1), which caused abdomen pain. In addition, the computer tomography(CT) and endoscopic ultrasonography(EUS) manifestations of mesenteric PNF were analyzed. The imaging appearance of a mesenteric plexiform neurofibroma is that many low-density (CT) /mixed echo (EUS) soft tissue masses surrounding the superior mesenteric artery, but not surrounding the superior mesenteric vein. Our case adds to the limited literature regarding NF1 presenting with mesenteric PNF. The computer tomography and endoscopic ultrasonography may facilitate confirma diagnosis of mesenteric PNF.
PubMed: 34158903
DOI: 10.1016/j.radcr.2021.04.071 -
Ophthalmology Jan 2017Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas... (Review)
Review
TOPIC
Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem.
CLINICAL RELEVANCE
Although NF1 is a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. Although medical and surgical interventions have been reported, there are no agreed-on criteria for when OPPNs require therapy and which treatment produces the best outcome.
METHODS
Because a multidisciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics, and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual or aesthetic sequelae complicates the design of evidence-based studies and feasible clinical trials.
RESULTS
In September 2013, a multidisciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN.
CONCLUSIONS
This consensus statement provides recommendations for ophthalmologic monitoring, outlines treatment indications and forthcoming biologic therapy, and discusses challenges to performing clinical trials in this complicated condition.
Topics: Child; Consensus; Delivery of Health Care, Integrated; Disease Management; Eyelid Neoplasms; Humans; Interdisciplinary Communication; Neurofibroma, Plexiform; Neurofibromatosis 1; Orbital Neoplasms; Practice Guidelines as Topic
PubMed: 27817916
DOI: 10.1016/j.ophtha.2016.09.020 -
Oncogene Jul 2007The human disease von Recklinghausen's neurofibromatosis (Nf1) is one of the most common genetic disorders. It is caused by mutations in the NF1 tumor suppressor gene,... (Review)
Review
The human disease von Recklinghausen's neurofibromatosis (Nf1) is one of the most common genetic disorders. It is caused by mutations in the NF1 tumor suppressor gene, which encodes a GTPase activating protein (GAP) that negatively regulates p21-RAS signaling. Dermal and plexiform neurofibromas as well as malignant peripheral nerve sheath tumors and other malignant tumors, are significant complications in Nf1. Neurofibromas are complex tumors and composed mainly of abnormal local cells including Schwann cells, endothelial cells, fibroblasts and additionally a large number of infiltrating inflammatory mast cells. Recent work has indicated a role for the microenvironment in plexiform neurofibroma genesis. The emerging evidence points to mast cells as crucial contributors to neurofibroma tumorigenesis. Therefore, further understanding of the molecular interactions between Schwann cells and their environment will provide tools to develop new therapies aimed at delaying or preventing tumor formation in Nf1 patients.
Topics: Animals; Genes, Neurofibromatosis 1; Humans; Mast Cells; Mice; Neurofibromatosis 1; Neurofibromin 1
PubMed: 17297459
DOI: 10.1038/sj.onc.1210261 -
Molecules (Basel, Switzerland) Sep 2018Investigating protein-protein interactions (PPIs) holds great potential for therapeutic applications, since they mediate intricate cell signaling networks in... (Review)
Review
Investigating protein-protein interactions (PPIs) holds great potential for therapeutic applications, since they mediate intricate cell signaling networks in physiological and disease states. However, their complex and multifaceted nature poses a major challenge for biochemistry and medicinal chemistry, thereby limiting the druggability of biological partners participating in PPIs. Molecular Dynamics (MD) provides a solid framework to study the reciprocal shaping of proteins' interacting surfaces. Here, we review successful applications of MD-based methods developed in our group to predict interfacial areas involved in PPIs of pharmaceutical interest. We report two interesting examples of how structural, dynamic and energetic information can be combined into efficient strategies which, complemented by experiments, can lead to the design of new small molecules with promising activities against cancer and infections. Our advances in targeting key PPIs in angiogenic pathways and antigen-antibody recognition events will be discussed for their role in drug discovery and chemical biology.
Topics: Antineoplastic Agents; Computational Biology; Humans; Molecular Dynamics Simulation; Peptides; Protein Interaction Mapping
PubMed: 30181519
DOI: 10.3390/molecules23092256 -
Pediatric Neurology Sep 2022The neurofibromatoses comprise three different genetic conditions causing considerable morbidity and mortality: neurofibromatosis type 1 (NF1), neurofibromatosis type 2... (Review)
Review
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.
Topics: Humans; Neurilemmoma; Neurofibroma, Plexiform; Neurofibromatoses; Neurofibromatosis 1; Neurofibromatosis 2; Quality of Life; Skin Neoplasms
PubMed: 35759947
DOI: 10.1016/j.pediatrneurol.2022.06.003 -
European Journal of Paediatric... May 2022To provide a comprehensive characterization of verbal learning and memory (VLM) abilities in youth with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs)...
AIM
To provide a comprehensive characterization of verbal learning and memory (VLM) abilities in youth with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) and to evaluate disease severity as a predictor of VLM functioning over time.
METHOD
As part of a longitudinal natural history study, youth with NF1 and PNs were administered repeat neuropsychological assessments, including measures of VLM and ratings of NF1 disease severity completed by a medical professional. This sub-study analyzed data from 89 patients (M age = 13.1, SD = 4.3 years, range 6-24 years) who had completed tests of VLM abilities and verbal attention at either baseline and/or 36 months.
RESULTS
VLM scores across the sample fell predominantly within the average range of functioning at both time points. However, relative to peers with mild NF1 disease severity, youth with moderate/severe NF1 disease showed lower functioning across multiple VLM domains at 36 months, even after controlling for the effects of verbal attention.
INTERPRETATION
Exclusive use of overall domain scores does not fully characterize VLM functioning in youth with NF1 and PNs. Additionally, children and adolescents with more severe NF1 disease should be monitored more closely for verbal memory challenges and targeted for interventions.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Neurofibroma, Plexiform; Neurofibromatosis 1; Neuropsychological Tests; Severity of Illness Index; Verbal Learning
PubMed: 35334353
DOI: 10.1016/j.ejpn.2022.03.004 -
Annals of Dermatology Jun 2019Segmental neurofibromatosis (SN) is rare form of neurofibromatosis characterized that cutaneous or neural changes are limited to one region of the body. SN present...
Segmental neurofibromatosis (SN) is rare form of neurofibromatosis characterized that cutaneous or neural changes are limited to one region of the body. SN present neurofibroma and less frequently, café au lait macules (CALMs) on usually unilateral or rarely bilateral of the body region. SN seems to have fewer systemic complications than neurofibromatosis type I or II, except patients with plexiform neurofibromas (PNFs). PNFs are rare benign peripheral nerve sheath tumors which arise from single or multiple nerves. PNFs can easily become aggressive growth particularly during puberty or pregnancy and leading to disfigurement and functional impairment. Also, PNFs can transform to malignant peripheral nerve sheath tumor, higher rate than classic neurofibroma. So, it is important to decide appropriate treatment modalities and time to intervention.
PubMed: 33911600
DOI: 10.5021/ad.2019.31.3.331 -
Journal of the National Cancer Institute Aug 2017Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma for which the only effective therapy is surgery. In 2016, an international meeting... (Review)
Review
Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma for which the only effective therapy is surgery. In 2016, an international meeting entitled "MPNST State of the Science: Outlining a Research Agenda for the Future" was convened to establish short- and long-term research priorities. Key recommendations included the: 1) development of standardized, cost-efficient fluorodeoxyglucose positron emission tomography and whole-body magnetic resonance imaging guidelines to evaluate masses concerning for MPNST; 2) development of better understanding and histologic criteria for the transformation of a plexiform neurofibroma to MPNST; 3) establishment of a centralized database to collect genetic, genomic, histologic, immunohistochemical, molecular, radiographic, treatment, and related clinical data from MPNST subspecialty centers in a standardized manner; 4) creation of accurate mouse models to study the plexiform neurofibroma-to-MPNST transition, MPNST metastasis, and drug resistance; 5) use of trial designs that minimize regulatory requirements, maximize availability to patients, consider novel secondary end points, and study patients with newly diagnosed disease. Lastly, in order to minimize delays in developing novel therapies and promote the most efficient use of research resources and patient samples, data sharing should be incentivized.
Topics: Biomedical Research; Consensus; Humans; Nerve Sheath Neoplasms; Neurilemmoma; Neurofibromatosis 1; Practice Guidelines as Topic; Therapies, Investigational
PubMed: 29117388
DOI: 10.1093/jnci/djx124 -
Oncogene Feb 2021MicroRNAs (miRs) are small non-coding RNAs that can have large impacts on oncogenic pathways. Possible functions of dysregulated miRs have not been studied in...
MicroRNAs (miRs) are small non-coding RNAs that can have large impacts on oncogenic pathways. Possible functions of dysregulated miRs have not been studied in neurofibromatosis type 1 (NF1) plexiform neurofibromas (PNFs). In PNFs, Schwann cells (SCs) have biallelic NF1 mutations necessary for tumorigenesis. We analyzed a miR microarray comparing with normal and PNF SCs and identified differences in miR expression, and we validated in mouse PNFs versus normal mouse SCs by qRT-PCR. Among these, miR-155 was a top overexpressed miR, and its expression was regulated by RAS/MAPK signaling. Overexpression of miR-155 increased mature Nf1 mouse SC proliferation. In SC precursors, which model tumor-initiating cells, pharmacological and genetic inhibition of miR-155 decreased PNF-derived sphere numbers in vitro, and we identified Maf as a miR-155 target. In vivo, global deletion of miR-155 significantly decreased tumor number and volume, increasing mouse survival. Fluorescent nanoparticles entered PNFs, suggesting that an anti-miR might have therapeutic potential. However, treatment of established PNFs using anti-miR-155 peptide nucleic acid-loaded nanoparticles marginally decreased tumor numbers and did not reduce tumor growth. These results suggest that miR-155 plays a functional role in PNF growth and/or SC proliferation, and that targeting neurofibroma miRs is feasible, and might provide novel therapeutic opportunities.
Topics: Animals; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Humans; Mice; Mice, Knockout; MicroRNAs; Mitogen-Activated Protein Kinase Kinases; Neurofibroma; Neurofibromin 1; Schwann Cells
PubMed: 33293695
DOI: 10.1038/s41388-020-01581-9 -
Orphanet Journal of Rare Diseases Sep 2022Neurofibromatosis 1 (NF1) is a common autosomal dominant syndrome with complete penetrance and highly variable expressivity. The cutaneous neurofibroma (Cnf) and...
Head circumference and anthropometric changes and their relation to plexiform and skin neurofibromas in sporadic and familial neurofibromatosis 1 Brazilian adults: a cross-sectional study.
BACKGROUND
Neurofibromatosis 1 (NF1) is a common autosomal dominant syndrome with complete penetrance and highly variable expressivity. The cutaneous neurofibroma (Cnf) and plexiform neurofibroma (Pnf), café-au-lait spots, and freckle-like lesions are common in NF1, but many other manifestations can occur. We aimed to evaluate head circumference, height, weight, body mass index (BMI), head circumference-to-height ratio (HCHR) and waist-hip ratio (WHR) in adult NF1 Brazilian individuals versus a paired control group and investigate their correlation with the presence of clinically visible Pnfs, and number of "skin neurofibromas" (Snf), which include both cutaneous and subcutaneous neurofibromas.
METHODS
A case-control study was conducted with 168 individuals, 84 with NF1 and 84 without NF1, paired by sex and age. Head circumference and anthropometric measurements, Snf quantification, evaluation of clinically visible Pnf and familial inheritance were accessed.
RESULTS
Prevalence of macrocephaly was significantly higher in NF1 women. Height and weight were significantly lower in both males and females with NF1. HCHR was higher in the NF1 group than in the control group for both sexes. BMI was significantly lower in men with NF1. Waist and hip circumferences were significantly reduced in NF compared with the controls, but the mean WHR was significantly lower only in NF1 women. No correlation was found between the Snf and head circumference and anthropometric measurements, sex or family history. The presence and larger size of clinically visible plexiform neurofibromas were associated with normal stature (p = 0.037 and p = 0.003, respectively).
CONCLUSIONS
NF1 individuals have increased prevalence of macrocephaly, short stature, low BMI, and reduced abdominal fat. There is no relation between head circumference and anthropometric data with family history, or neurofibromas.
Topics: Adult; Brazil; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Male; Megalencephaly; Neurofibroma; Neurofibroma, Plexiform; Neurofibromatoses; Neurofibromatosis 1; Skin Neoplasms
PubMed: 36064430
DOI: 10.1186/s13023-022-02482-8