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: Journal of Investigative Dermatology; August 2023, Vol. 143 Issue: 8 p1388-1396, 9p

مستخلص: 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.

المؤلفون: Rhodes, Steven D., McCormick, Frank, Cagan, Ross L., Bakker, Annette, Staedtke, Verena, Ly, Ina, Steensma, Matthew R., Lee, Sang Y., Romo, Carlos G., Blakeley, Jaishri O., Sarin, Kavita Y.

المصدر: Journal of Investigative Dermatology; August 2023, Vol. 143 Issue: 8 p1358-1368, 11p

مستخلص: Cutaneous neurofibromas (cNFs) are the most common tumor in people with the rasopathy neurofibromatosis type 1. They number in hundreds or even thousands throughout the body, and currently, there are no effective interventions to prevent or treat these skin tumors. To facilitate the identification of novel and effective therapies, essential studies including a more refined understanding of cNF biology and the role of RAS signaling and downstream effector pathways responsible for cNF initiation, growth, and maintenance are needed. This review highlights the current state of knowledge of RAS signaling in cNF pathogenesis and therapeutic development for cNF treatment.

المؤلفون: Jiang, Chunhui, McKay, Renée M., Lee, Sang Y., Romo, Carlos G., Blakeley, Jaishri O., Haniffa, Muzlifah, Serra, Eduard, Steensma, Matthew R., Largaespada, David, Le, Lu Q.

المصدر: Journal of Investigative Dermatology; August 2023, Vol. 143 Issue: 8 p1369-1377, 9p

مستخلص: Neurofibromatosis type 1 is one of the most common genetic disorders of the nervous system and predisposes patients to develop benign and malignant tumors. Cutaneous neurofibromas (cNFs) are NF1-associated benign tumors that affect nearly 100% of patients with NF1. cNFs dramatically reduce patients’ QOL owing to their unaesthetic appearance, physical discomfort, and corresponding psychological burden. There is currently no effective drug therapy option, and treatment is restricted to surgical removal. One of the greatest hurdles for cNF management is the variability of clinical expressivity in NF1, resulting in intrapatient and interpatient cNF tumor burden heterogeneity, that is, the variability in the presentation and evolution of these tumors. There is growing evidence that a wide array of factors are involved in the regulation of cNF heterogeneity. Understanding the mechanisms underlying this heterogeneity of cNF at the molecular, cellular, and environmental levels can facilitate the development of innovative and personalized treatment regimens.

المؤلفون: Staedtke, Verena, Topilko, Piotr, Le, Lu Q., Grimes, Kevin, Largaespada, David A., Cagan, Ross L., Steensma, Matthew R., Stemmer-Rachamimov, Anat, Blakeley, Jaishri O., Rhodes, Steven D., Ly, Ina, Romo, Carlos G., Lee, Sang Y., Serra, Eduard

المصدر: Journal of Investigative Dermatology; August 2023, Vol. 143 Issue: 8 p1378-1387, 10p

مستخلص: Neurofibromatosis type 1 (NF1) is caused by a nonfunctional copy of the NF1tumor suppressor gene that predisposes patients to the development of cutaneous neurofibromas (cNFs), the skin tumor that is the hallmark of this condition. Innumerable benign cNFs, each appearing by an independent somatic inactivation of the remaining functional NF1allele, form in nearly all patients with NF1. One of the limitations in developing a treatment for cNFs is an incomplete understanding of the underlying pathophysiology and limitations in experimental modeling. Recent advances in preclinical in vitro and in vivo modeling have substantially enhanced our understanding of cNF biology and created unprecedented opportunities for therapeutic discovery. We discuss the current state of cNF preclinical in vitro and in vivo model systems, including two- and three-dimensional cell cultures, organoids, genetically engineered mice, patient-derived xenografts, and porcine models. We highlight the models’ relationship to human cNFs and how they can be used to gain insight into cNF development and therapeutic discovery.

المؤلفون: Fertitta, Laura, Sarin, Kavita Y., Bergqvist, Christina, Patel, Ekshika, Peiffer, Bastien, Moryousef, Sabine, Armand, Marie-Laure, Jannic, Arnaud, Ferkal, Salah, Ravaud, Philippe, Tran, Viet-Thi, Blakeley, Jaishri O., Romo, Carlos G., Ezzedine, Khaled, Wolkenstein, Pierre

المصدر: Journal of Investigative Dermatology; November 2023, Vol. 143 Issue: 11 p2226-2232.e1

مستخلص: Cutaneous neurofibromas (cNF) contribute to the impairment of QOL in individuals with neurofibromatosis 1. The cNF-Skindex, validated in a French population, specifically assesses the cNF-related QOL. In this study, we first defined severity strata using an anchoring approach on the basis of patient’s burden. In total, 209 patients answered the anchor question and the cNF-Skindex. We tested the agreement among the three strata, generated by all potential couples of cut-off values of the cNF-Skindex and the three strata defined in the anchor question. The cut-off values 12 and 49 provided the highest Kappa value (κ = 0.685, 95% confidence interval = 0.604−0.765). Second, we validated the score and the strata in a United States population using the answers provided by 220 French and 148 United States adults. In the multivariable linear regression analysis, the country of origin was not a factor associated with the score (P = 0.297). The number of cNF along the different severity strata was similar between the French and the United States populations. In conclusion, stratification constitutes a powerful tool to better interpret the cNF-Skindex in daily practice and in clinical trials. This study validates its use in two populations that together constitute a large cohort of patients willing to participate in clinical research.