ABSTRACT
Uveal melanoma is the most common primary intraocular tumor in adults. It can arise from melanocytes in the anterior (iris) or posterior uveal tract (choroid and ciliary body). Uveal melanoma has a particular molecular pathogenesis, being characterized by specific chromosome alterations and gene mutations (e.g., GNAQ/GNA11; BAP1), which are considered promising targets for molecular therapy. Primary treatment of uveal melanoma includes radiotherapy (brachytherapy and charged-particle therapy), phototherapy (photocoagulation, transpupillary thermal therapy, and photodynamic therapy) and surgery (local resection, enucleation and exenteration). Approximately half of patients with uveal melanoma will, however, develop metastasis, especially in the liver. The treatment of metastatic uveal melanoma includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, chemoembolization, immunoembolization, radioembolization, isolated hepatic perfusion and percutaneous hepatic perfusion, are also available to treat metastatic uveal melanoma. Several clinical trials are being developed to study new therapeutic options to treat uveal melanoma, mainly for those with identified liver metastases. The present work discusses the physiopathology and new in situ-specific therapies for the treatment of uveal melanoma.
Subject(s)
Liver Neoplasms/therapy , Melanoma/pathology , Uveal Neoplasms/pathology , Adult , Chromosome Aberrations , GTP-Binding Protein alpha Subunits/genetics , GTP-Binding Protein alpha Subunits, Gq-G11/genetics , Humans , Liver Neoplasms/secondary , Melanoma/genetics , Melanoma/therapy , Mutation , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Uveal Neoplasms/genetics , Uveal Neoplasms/therapyABSTRACT
Cushing's disease is a rare condition which may present with a variety of signs and symptoms. In this report, we present a case of a 37-year-old man referred to our department due to osteoporosis complicated with vertebral and rib fractures and loss of six centimeters in height within the previous year. Study of secondary causes of osteoporosis led to the diagnosis of Cushing's disease. The patient was submitted to transsphenoidal surgery and histological findings confirmed the diagnosis. After surgery, the symptoms improved. Glucocorticoid induced osteoporosis may be reversible, but recovery of bone loss is gradual and may continue for as long as 10 years before bone mineral density normalizes. This case illustrates the need to consider secondary causes of osteoporosis in a young man with bone fractures, namely Cushing's syndrome.
Subject(s)
Cushing Syndrome/complications , Osteoporotic Fractures/etiology , Spinal Fractures/etiology , Adult , Body Height , Humans , MaleABSTRACT
A novel nanocarrier based on solid lipid nanoparticles (SLNs) was developed for insulin delivery using a novel double emulsion method. Physical stability of particles was assessed by size analysis using dynamic light scattering (DLS), matrix crystallinity by differential scanning calorimetry (DSC) and toxicity analysis by Drosophila melanogaster testing. Insulin-SLNs were composed of Softisan®100 1.25% wt, Lutrol®F68 1% wt, soybean lecithin 0.125% wt, and loaded with 0.73-0.58 mg/mL peptide. Placebo-SLNs (insulin-free) also contained 0.025% wt Tween®80. Mean particle sizes of placebo-SLN and insulin-SLN were 958 ± 9.5 and 978 ± 8.3 nm, respectively. The polydispersity index (PI) was 0.28 ± 0.018 and 0.29 ± 0.013, respectively. Polarized light microscopy analysis depicted no aggregation of developed particles. DSC analysis allowed characterizing SLN with 43-51% matrix crystallinity. Using Drosophila melanogaster test, no toxicity was reported for SLN and for the bulk lipid. This study shows that SLNs are promising and helpful to overcome conventional insulin therapy, in particular for their lack of toxicity for oral delivery.
