RESUMO
Thyroid eye disease is an auto-immune mediated orbitopathy which can cause dysthyroid compressive optic neuropathy. Traditional management of active thyroid eye disease includes temporizing high-dose steroids, orbital radiation and surgical decompression, which each possess significant limitations and/or side effects. Teprotumumab is an IGF-IR inhibitor recently FDA-approved for active thyroid eye disease. The authors report reversal of bilateral dysthyroid compressive optic neuropathy managed medically utilizing teprotumumab.
Assuntos
Oftalmopatia de Graves , Doenças do Nervo Óptico , Anticorpos Monoclonais Humanizados/uso terapêutico , Descompressão Cirúrgica , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/cirurgia , Humanos , Nervo Óptico , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/tratamento farmacológico , Doenças do Nervo Óptico/etiologiaAssuntos
Quimioterapia Adjuvante/métodos , Melanoma/tratamento farmacológico , Melanoma/patologia , Metástase Neoplásica/prevenção & controle , Micrometástase de Neoplasia , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/patologia , Terapia Combinada , Humanos , Terapia de Alvo MolecularRESUMO
Uveal melanoma is the most common intraocular malignancy in adults. Despite excellent rates of local control, half of all patients with uveal melanoma ultimately go on to develop fatal metastatic disease. This review focuses on disparities and differences in the underlying characteristics of the patients, and how these patient characteristics impact the development of metastasis and subsequent patient survival. Specifically, we detail disparities in epidemiology and risk factors as they relate to the development of primary uveal melanoma, to the development of metastasis, and to patient survival following metastasis.
Assuntos
Disparidades nos Níveis de Saúde , Melanoma/epidemiologia , Neoplasias Uveais/epidemiologia , Humanos , Metástase Neoplásica , Fatores de Risco , Taxa de SobrevidaRESUMO
Uveal melanoma is the most common intraocular malignancy in adults. Although rates of local control for uveal melanoma exceed 95% with radiotherapy or enucleation, as many as 50% of patients develop hematogenous metastases, which manifest in the decades following initial diagnosis and are uniformly and rapidly fatal. Recent compelling evidence suggests that not all uveal melanomas are themselves equivalent with respect to metastatic potential and patient survival. This review focuses on the mounting evidence of survival disparities based on intrinsic tumor clinical and histopathologic characteristics and based on tumor genetics and gene expression profiles.
Assuntos
Melanoma , Metástase Neoplásica , Neoplasias Uveais , Disparidades nos Níveis de Saúde , Humanos , Melanoma/epidemiologia , Melanoma/genética , Melanoma/patologia , Fatores de Risco , Taxa de Sobrevida , Neoplasias Uveais/epidemiologia , Neoplasias Uveais/genética , Neoplasias Uveais/patologiaRESUMO
Tregs play important roles in maintaining immune homeostasis, and thus, therapies based on Treg are promising candidates for the treatment for a variety of immune-mediated disorders. These therapies, however, face the significant challenge of obtaining adequate numbers of Tregs from peripheral blood that maintains suppressive function following extensive expansion. Inducing Tregs from non-Tregs offers a viable alternative. Different methods to induce Tregs have been proposed and involve mainly treating cells with TGF-ß-iTreg. However, use of TGF-ß alone is not sufficient to induce stable Tregs. ATRA or rapa has been shown to synergize with TGF-ß to induce stable Tregs. Whereas TGF-ß plus RA-iTregs have been well-described in the literature, the phenotype, function, and migratory characteristics of TGF-ß plus rapa-iTreg have yet to be elucidated. Herein, we describe the phenotype and function of mouse rapa-iTreg and reveal that these cells differ in their in vivo homing capacity when compared with mouse RA-iTreg and mouse TGF-ß-iTreg. This difference in migratory activity significantly affects the therapeutic capacity of each subset in a mouse model of colitis. We also describe the characteristics of iTreg generated in the presence of TGF-ß, RA, and rapa.
Assuntos
Sirolimo/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Tretinoína/farmacologia , Animais , Antígenos CD/análise , Movimento Celular/efeitos dos fármacos , Sinergismo Farmacológico , Cadeias alfa de Integrinas/análise , Camundongos , Camundongos Endogâmicos C57BL , Receptores CCR/análise , Linfócitos T Reguladores/fisiologiaRESUMO
The absence of regulatory T cells (Treg) is a hallmark for a wide variety of disorders such as autoimmunity, dermatitis, periodontitis and even transplant rejection. A potential treatment option for these disorders is to increase local Treg numbers. Enhancing local numbers of Treg through in situ Treg expansion or induction could be a potential treatment option for these disorders. Current methods for in vivo Treg expansion rely on biologic therapies, which are not Treg-specific and are associated with many adverse side-effects. Synthetic formulations capable of inducing Treg could be an alternative strategy to achieve in situ increase in Treg numbers. Here we report the development and in vitro testing of a Treg-inducing synthetic formulation that consists of controlled release vehicles for IL-2, TGF-ß and rapamycin (a combination of cytokines and drugs that have previously been reported to induce Treg). We demonstrate that IL-2, TGF-ß and rapamycin (rapa) are released over 3-4weeks from these formulations. Additionally, Treg induced in the presence of these formulations expressed the canonical markers for Treg (phenotype) and suppressed naïve T cell proliferation (function) at levels similar to soluble factor induced Treg as well as naturally occurring Treg. Most importantly, we show that these release formulations are capable of inducing FoxP3(+) Treg in human cells in vitro. In conclusion, our data suggest that controlled release formulations of IL-2, TGF-ß and rapa can induce functional Treg in vitro with the potential to be developed into an in vivo Treg induction and expansion therapy.