المؤلفون: Nguyen, Huyen, Kohl, Emily, Bade, Jessica, Eng, Stefan, Tosevska, Anela, Al Shihabi, Ahmad, Tebon, Peyton, Hong, Jenny, Dry, Sarah, Boutros, Paul, Panossian, Andre, Gosline, Sara, Soragni, Alice

المصدر: Cell Reports: Methods. 4(5)

مصطلحات موضوعية: CP: Cancer biology, CP: Stem cell, HTS screening, benign tumor, cNF tumor organoids, cutaneous neurofibroma, neurofibroma, neurofibromatosis type 1, organoids, Humans, Organoids, Skin Neoplasms, Neurofibroma, Neurofibromatosis 1

الوصف: Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, they can cover a significant proportion of the body, with some individuals developing hundreds to thousands of lesions. cNFs can cause pain, itching, and disfigurement resulting in substantial socio-emotional repercussions. Currently, surgery and laser desiccation are the sole treatment options but may result in scarring and potential regrowth from incomplete removal. To identify effective systemic therapies, we introduce an approach to establish and screen cNF organoids. We optimized conditions to support the ex vivo growth of genomically diverse cNFs. Patient-derived cNF organoids closely recapitulate cellular and molecular features of parental tumors as measured by immunohistopathology, methylation, RNA sequencing, and flow cytometry. Our cNF organoid platform enables rapid screening of hundreds of compounds in a patient- and tumor-specific manner.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2hh0z0rhTest
https://escholarship.org/content/qt2hh0z0rh/qt2hh0z0rh.pdfTest

المؤلفون: Blakeley, Jaishri O, Le, Lu Q, Lee, Sang Y, Ly, Ina, Rhodes, Steven D, Romo, Carlos G, Sarin, Kavita Y, Staedtke, Verena, Steensma, Matthew R, Wolkenstein, Pierre, Participants, 2022 NTAP Cutaneous Neurofibroma Symposium, Largaespada, David, Serra, Eduard, Haniffa, Muzlifah, Bakker, Annette, McCormick, Frank, Cagan, Ross L, Ju, William, Stemmer-Rachamimov, Anat, Grimes, Kevin, Topilko, Piotr, Kornacki, Deanna, Kelly, Kristen M, Gottesman, Sally, York, Zachary, Epps, Roselyn

المصدر: Journal of Investigative Dermatology. 143(8)

مصطلحات موضوعية: Humans, Neurofibroma, Neurofibromatosis 1, Skin Neoplasms, Connective Tissue Diseases, NTAP Cutaneous Neurofibroma Symposium Participants, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7cs8b3d4Test

المؤلفون: Li, Yingjoy, Blakeley, Jaishri O, Ly, Ina, Berman, Yemima, Lau, Jonathan, Wolkenstein, Pierre, Bergqvist, Christina, Jia, Wangcun, Milner, Thomas E, Katta, Nitesh, Durkin, Anthony J, Kennedy, Gordon T, Rowland, Rebecca, Romo, Carlos G, Fleming, Jane, Kelly, Kristen M

المصدر: Journal of Investigative Dermatology. 143(8)

مصطلحات موضوعية: Cancer, Rare Diseases, Biomedical Imaging, Neurosciences, Neurofibromatosis, Pediatric, Humans, Neurofibromatosis 1, Neurofibroma, Skin Neoplasms, Ultrasonography, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases

الوصف: A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4qg8h655Test

المؤلفون: Ly, Ina, Romo, Carlos G, Gottesman, Sally, Kelly, Kristen M, Kornacki, Deanna, York, Zachary, Lee, Sang Y, Rhodes, Steven D, Staedtke, Verena, Steensma, Matthew R, Blakeley, Jaishri O, Wolkenstein, Pierre

المصدر: The Journal of investigative dermatology. 143(8)

مصطلحات موضوعية: Humans, Neurofibroma, Neurofibromatosis 1, Skin Neoplasms, Pruritus, Quality of Life, Adult, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Rare Diseases, Clinical Sciences, Oncology and Carcinogenesis, Dermatology & Venereal Diseases

الوصف: Cutaneous neurofibromas (cNFs) are benign tumors of the skin that affect >95% of adults with neurofibromatosis type 1. Despite their benign histology, cNFs can significantly impact QOL due to disfigurement, pain, and pruritus. There are no approved therapies for cNFs. Existing treatments are limited to surgery or laser-based treatments that have had mixed success and cannot be readily applied to a large number of tumors. We review cNF treatment options that are currently available and under investigation, discuss the regulatory considerations specific to cNFs, and propose strategies to improve cNF clinical trial design and standardize clinical trial endpoints.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2j02s0htTest

المؤلفون: Fisher, Michael J, Belzberg, Allan J, de Blank, Peter, De Raedt, Thomas, Elefteriou, Florent, Ferner, Rosalie E, Giovannini, Marco, Harris, Gordon J, Kalamarides, Michel, Karajannis, Matthias A, Kim, AeRang, Lázaro, Conxi, Le, Lu Q, Li, Wei, Listernick, Robert, Martin, Staci, Morrison, Helen, Pasmant, Eric, Ratner, Nancy, Schorry, Elisabeth, Ullrich, Nicole J, Viskochil, David, Weiss, Brian, Widemann, Brigitte C, Zhu, Yuan, Bakker, Annette, Serra, Eduard

المصدر: American Journal of Medical Genetics Part A. 176(5)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Cancer, Neurosciences, Biotechnology, Pediatric, Brain Cancer, Neurofibromatosis, Brain Disorders, Animals, Disease Management, Disease Models, Animal, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Molecular Diagnostic Techniques, Neurilemmoma, Neurofibromatoses, Neurofibromatosis 1, Neurofibromatosis 2, Skin Neoplasms, Translational Research, Biomedical, autism, conference, ependymoma, glioma, malignant peripheral nerve sheath tumor, meningioma, merlin, neurofibroma, neurofibromatosis, neurofibromin, schwannoma, schwannomatosis, pseudoarthrosis, Genetics, Clinical sciences

الوصف: Organized and hosted by the Children's Tumor Foundation (CTF), the Neurofibromatosis (NF) conference is the premier annual gathering for clinicians and researchers interested in neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). The 2016 edition constituted a blend of clinical and basic aspects of NF research that helped in clarifying different advances in the field. The incorporation of next generation sequencing is changing the way genetic diagnostics is performed for NF and related disorders, providing solutions to problems like genetic heterogeneity, overlapping clinical manifestations, or the presence of mosaicism. The transformation from plexiform neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) is being clarified, along with new management and treatments for benign and premalignant tumors. Promising new cellular and in vivo models for understanding the musculoskeletal abnormalities in NF1, the development of NF2 or SWN associated schwannomas, and clarifying the cells that give rise to NF1-associated optic pathway glioma were presented. The interaction of neurofibromin and SPRED1 was described comprehensively, providing functional insight that will help in the interpretation of pathogenicity of certain missense variants identified in NF1 and Legius syndrome patients. Novel promising imaging techniques are being developed, as well as new integrative and holistic management models for patients that take into account psychological, social, and biological factors. Importantly, new therapeutic approaches for schwannomas, meningiomas, ependymomas, PNF, and MPNST are being pursued. This report highlights the major advances that were presented at the 2016 CTF NF conference.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5hd217gpTest

المؤلفون: Diogo Lisbôa Basto, Gustavo de Souza Vieira, Raquel M. Andrade-Losso, Paula Nascimento Almeida, Vincent M. Riccardi, Rafaela Elvira Rozza-de-Menezes, Karin Soares Cunha

المصدر: Orphanet Journal of Rare Diseases. 17

مصطلحات موضوعية: Adult, Male, Neurofibroma, Plexiform, Neurofibroma, Neurofibromatosis 1, Skin Neoplasms, Neurofibromatoses, General Medicine, Megalencephaly, Cross-Sectional Studies, Case-Control Studies, Humans, Female, Pharmacology (medical), Brazil, Genetics (clinical)

الوصف: 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::322160761a15b54ac6f3e0875e63e54cTest
https://doi.org/10.1186/s13023-022-02482-8Test

المؤلفون: L. Fertitta, C. Bergqvist, M.L. Armand, S. Moryousef, S. Ferkal, A. Jannic, P. Ravaud, V.T. Tran, K. Ezzedine, P. Wolkenstein

المصدر: Journal of the European Academy of Dermatology and Venereology. 36:1359-1366

مصطلحات موضوعية: Adult, Neurofibroma, Neurofibromatosis 1, Skin Neoplasms, Infectious Diseases, Psychometrics, Surveys and Questionnaires, Quality of Life, Humans, Reproducibility of Results, Translations, Dermatology

الوصف: Cutaneous neurofibromas (cNF), present in 95% of individuals with neurofibromatosis 1 (NF1), are considered as one of the greatest medical burden because of physical disfigurement. No specific score evaluates their impact on quality of life (QoL).To develop a specific score assessing cNF-related QoL.Through a multidisciplinary workshop including 10 patients, 3 expert-in-NF1 physicians, 3 health care workers (nurses and psychologist) and 1 methodologist, the French version of the Skindex-16 was modified by adding 3 items. The new cNF-Skindex was validated among patients with NF1 recruited in the ComPaRe online cohort, in France (N = 284). Construct validity was assessed by comparing it with the EQ-5D-5L, its visual analogue scale and the MYMOP2 and by assessing its association with patients' characteristics. Reliability was assessed by a test-retest. An English version of the tool was developed using a back-forward translation.A total of 228 individuals with NF1, with cNF answered the 19-item questionnaire. These items fitted into 3 domains: emotions, symptoms, functioning. One was dropped during analysis because90% responders were not concerned. The cNF-Skindex significantly correlated with the EQ-5D-5L (N = 193) and MYMOP2 (N = 210) indicating good external validity: rs 0.38 (P 0.001), and 0.58 (P 0.001), respectively. Having50 cNF was the only independent variable associated with the total score cNF-Skindex (β = 15.88, 95%CI 6.96-24.81, P = 0.001), and with the 3 sub-scores: 'functioning' (β = 2.65, 95%CI 0.71-4.59, P = 0.008), 'emotions' (β = 17.03, 95%CI 4.11-29.96, P = 0.010) and 'symptoms' (β = 3.90, 95%CI 1.95-5.85, P 0.001). Test-retest reliability (N = 133) found an ICC at 0.96 demonstrating good reproducibility.The cNF-Skindex demonstrated excellent psychometric properties. The global and sub-scores were increased with higher number of cNF arguing for its use in further trials aiming to reduce their number or prevent their development. Cross-cultural validation and evaluation of its responsiveness are the next steps.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c7ec6a3f2cd745828bd6e2b4a309f9fTest
https://doi.org/10.1111/jdv.18140Test

المؤلفون: Francisco Javier García-Martínez, Angela Hernández-Martín, Anna Duat-Rodríguez, Daniel Azorín

المصدر: JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 19:73-80

مصطلحات موضوعية: Hypertrichosis, Pathology, medicine.medical_specialty, Neurofibromatosis 1, Skin Neoplasms, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Plexiform neurofibroma, Biopsy, medicine, Humans, Neurofibromatosis, Child, Retrospective Studies, Neurofibroma, medicine.diagnostic_test, CD68, business.industry, Cafe-au-Lait Spots, Diffuse Neurofibroma, Infant, medicine.disease, Clinicopathological features, business, Immunostaining

الوصف: Background and objective Clinicopathological features of cutaneous neurofibromas presenting as large irregularly shaped congenital cafe-au-lait macules (CALM) in Neurofibromatosis type 1 (NF1) patients have not been well characterized. We aimed to analyze the histopathological findings of large "atypical" CALM in children with NF1. Patients and methods In this retrospective observational study we analyzed histopathological and immunostaining features of 21 biopsy specimens from 18 large hyperpigmented macules with irregular borders with or without hypertrichosis present during the first months of life in NF1 diagnosed children. Results Of the 21 biopsies, ten showed a diffuse neurofibroma pattern and four exhibited characteristics of plexiform neurofibroma (PNF). In twelve specimens we observed groups of fusiform cells arranged linearly mimicking a small caliber nerve trunk with abnormal morphology. Repeated biopsies from two of these lesions performed at different ages showed transformation to a plexiform pattern. An increased interstitial cellularity was observed in 17 samples that was more evident around eccrine glands in 16 or accompanying hair follicles and vascular structures in twelve samples. All these cells had immunoreactivity for S100-protein, CD68 and were Melan-A positive in 15 samples. Conclusion Clinicopathological findings of congenital cutaneous neurofibromas provide early diagnostic clues of NF1 with high relevance for monitoring of these patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63dcf317690d7e4c46cd2c01bc27ec97Test
https://doi.org/10.1111/ddg.14322Test

المؤلفون: Johannes Salamon, Dale J. Berg, Shivani Ahlawat, Michael Fisher, Dusica Babovic-Vuksanovic, Jaishri O. Blakeley, K. Ina Ly, Gordon J. Harris, Andrés J. Lessing, Laura M. Fayad, Scott R. Plotkin, Eva Dombi, Victor-Felix Mautner

المصدر: Neurology

مصطلحات موضوعية: Adult, Male, Pediatrics, medicine.medical_specialty, Neurofibromatosis 1, Skin Neoplasms, Adolescent, Neurofibromatoses, MEDLINE, Asymptomatic, Imaging, Young Adult, Surveys and Questionnaires, Humans, Medicine, Clinical care, Neurofibromatosis, Child, Schwannomatosis, Neurofibroma, Plexiform, High prevalence, business.industry, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Clinical trial, Patient population, Neurology (clinical), medicine.symptom, business, Neurilemmoma

الوصف: ObjectiveTo assess imaging utilization practices across clinical specialists in neurofibromatosis type 1 (NF1) for the evaluation of symptomatic and asymptomatic children and adults with or without plexiform neurofibromas (PN).MethodsAn institutional review board–exempt survey was administered to medical practitioners caring for individuals with NF1 at the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) meeting in September 2019. The survey included questions on respondent demographic data (9 questions), type of imaging obtained for asymptomatic (4 questions) and symptomatic (4 questions) people with and without PN, and utilization of diffusion-weighted imaging (2 questions).ResultsThirty practitioners participated in the survey. Most were academic neuro-oncologists at high-volume (>10 patients/week) NF1 centers. Of 30 respondents, 26 had access to whole-body MRI (WB-MRI). The most common approach to an asymptomatic person without PN was no imaging (adults: 57% [17/30]; children: 50% [15/30]), followed by a screening WB-MRI (adults: 20% [6/30]; children: 26.7% [8/30]). The most common approach to a person with symptoms or known PN was regional MRI (adults: 90% [27/30]; children: 93% [28/30]), followed by WB-MRI (adults: 20% [6/30]; children: 36.7% [11/30]). WB-MRI was most often obtained to evaluate a symptomatic child with PN (37% [11/30]).ConclusionsMore than 90% of practitioners indicated they would obtain a regional MRI in a symptomatic patient without known or visible PN. Otherwise, there was little consensus on imaging practices. Given the high prevalence of PN and risk of malignant conversion in this patient population, there is a need to define imaging-based guidelines for optimal clinical care and the design of future clinical trials.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::116688cecd5566b543eaadae3baaac75Test
https://doi.org/10.1212/wnl.0000000000012437Test

المؤلفون: Christian Hagel, Reinhard E Friedrich, Martin Zenker, Ina Schanze, Ilse Wieland, Felix K Kohlrusch

المصدر: Anticancer Research. 40:3423-3427

مصطلحات موضوعية: congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, Pathology, medicine.medical_specialty, Neurofibromatosis 1, Skin Neoplasms, Somatic cell, Biopsy, Gene mutation, Germline, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Plexiform neurofibroma, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Neurofibromatosis, neoplasms, Genetic Association Studies, Neurofibroma, Plexiform, Leg, integumentary system, Mosaicism, business.industry, General Medicine, Middle Aged, medicine.disease, Penetrance, Phenotype, nervous system diseases, Oncology, 030220 oncology & carcinogenesis, Female, business

الوصف: Background Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease with complete penetrance and a very variable phenotype. Recent research has shown that postzygotic NF1 gene mutations occur to a far greater extent than previously thought. The phenotype of affected individuals reflects the time of somatic mutation and the phenotype is correspondingly diverse. This report describes histological and genetic findings in a case of mosaic NF1, the clinical control of which documents almost stationary skin findings over a period of 9 years. Case report The 55-year-old female first presented for advice on a strip of nodular skin tumours of the calf skin. She had no hallmarks of NF1. It was only 9 years later that she had the skin tumours removed, all of which were partially diffuse and partially plexiform neurofibroma. The genetic examination showed an atypical large deletion of the NF1 gene in the skin tumours, but not in overlying skin or blood. Conclusion Segmental NF1 is a distinct type of mosaic/somatic NF1 mutation. The phenotype of diffuse and plexiform skin neurofibromas can resemble cutaneous neurofibroma. Surgical therapy for segmental neurofibromatosis does not differ from the concepts for treating nerve sheath tumours in NF1 patients with a germline NF1 mutation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47a0502782ca1219dfcf530b4d508692Test
https://doi.org/10.21873/anticanres.14327Test