In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy. In this article, we will review the molecular bases for these new metastatic melanoma therapeutic agents cited above and also analyze new molecular discoveries in melanoma study, as Cancer-Testis antigens (CT). They are capable of induce humoral and cellular immune responses in cancer patients and because of this immunogenicity and their restrict expression in normal tissues, they are considered an ideal candidate for vaccine development against cancer. Among CT antigens, NY-ESO-1 is the best characterized in terms of expression patterns and immunogenicity. It is expressed in 20-40% of all melanomas, more in metastatic lesions than in primary ones, and it is very heterogeneous inter and intratumoral. Breslow index is associate with NY-ESO-1 expression in primary cutaneous melanomas, but its relation to patient survival remains controversial.

Case report of a patient with severe atopic dermatitis who showed a good response to dupilumab. She had already used two immunosuppressive agents, cyclosporine A and mycophenolate mofetil, for the treatment of atopic dermatitis with no proper control of the disease. She had also been taking all measures to control severe cases of the disease: bath and environmental controls, topical potent corticosteroids and emollients. She presented constant pruritus and skin lesions, frequent skin infections e poor quality of life. She also developed depression due to her disease. Recently, dupilumab, a new biological agent, was approved for the treatment of moderate/severe atopic dermatitis in many countries, including Brazil. Dupilumab is a monoclonal antibody with a common alpha chain of interleukin (IL) 4 and IL-13 receptors, two cytokines involved in the Th2 profile immune response that promote atopic inflammation. In a pioneer way in Brazil, the patient initiated the treatment with an attack dose of 600mg subcutaneous of dupilumab and 300mg subcutaneous every other week. Up to now, she has taken four applications, presenting a great improvement of the disease and her quality of life. There were no adverse effects, nor in the injection site nor of other kind. Patient and her family are very satisfied, and the medical team evaluates that the treatment is being well succeed. The case report described here subsidizes the use of dupilumab in the treatment of severe atopic dermatitis refractory to use of immunosuppressive agents.

Prieto-Lastra et al 1 described three patients who developed adverse reactions after receiving codeine. It is known that codeine can induce direct mast cell degranulation and therefore non-IgE mediated reactions 2. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequent cause of urticaria and patients with chronic urticaria can present worsening of symptoms with their use. One alternative for these patients is the use of paracetamol, which sometimes is associated with codeine for treatment of more severe pain. We performed 25 controlled oral challenges with 30 mg codeine in patients with chronic urticaria who reported exacerbation with multiple NSAIDs. Neither patient presented adverse reactions. A week later the same patients were submitted to oral challenge with 30 mg codeine associated with 500mg paracetamol. One patient (4 %) developed urticaria 24 hours after drugs intake. Although the present study shows some degree of safety, it is not possible to state that these chronic urticaria patients will not present adverse reactions to codeine in the future. Large and long-term studies are necessary before widespread utilization of codeine in chronic urticaria.

diseases. Nevertheless, many of them demonstrate willingness to acquire more knowledge in this subject. The implementations of strategies to improve students' skills seem to be essential for both their professional development and allergic patients' well-being.

Ao Laboratório Diagnóstika, na pessoa do Dr. Roberto El Ibrahim, que se dispôs a padronizar e realizar o estudo imunohistoquímico com o NY-ESO-1. À Luciane Kanashiro, técnica em imunohistoquímica do Laboratório Diagnóstika, pela presteza, paciência e, principalmente, competência na realização dos exames imunohistoquímicos. Ao Professor José Antonio Sanches e à Fundação SEADE pelas informações sobre os pacientes. À Dra. Alice Lobo, que me apresentou à Prof. Lyn Duncan e me incentivou a realizar a parte do projeto nos Estados Unidos. Aos colegas médicos do Ambulatório de Melanoma da Dermatologia da FMUSP, Caio Lamunier de Abreu Camargo, Dilci Franco e Helena Olegário da Costa, atual coordenadora. Aos integrantes da banca da aula de qualificação do doutorado:

Melanoma is a serious public health problem that affects the population of Latin America and is increasing rapidly compared to other types of tumors. The growth or change in this type of tumor is progressive and is in the horizontal and/or vertical direction. Breslow thickness (vertical staging) is the tumor thickness in the dermis where patients with lesion thickness less than 0.75 mm have good prognosis, unlike lesion thickness larger than 3 mm. This stage is classified into T (primary tumor): T0 (with no evidence of primary tumor); Tis (in situ melanoma); T1 (1 mm); T2 (1.01 to 2 mm); T3 (2.01 to 4 mm); and T4 (above 4 mm). Knowing some molecular markers of melanoma is essential for the identification of genetically predisposed individuals, as well as early detection of the disease. Recent works has demonstrated that microRNAs may be involved in modulation of melanoma. Dicer is an essential member of the RNase III family which controls maturation of miRNAs in the cytoplasm from microRNA precursors (pre-miRNAs). The upregulation of Dicer is associated with aggressive features and proliferation of melanoma and no other skin tumors such as carcinomas and sarcoma. In our present study, we found that the knockdown expression of Dicer using the CRISPR/CAS9 in melanoma cell line induced more chemosensitivity to cisplatin and these changes correlated with the downregulation of Dicer. We examined the consequence of Dicer knockdown on melanoma cell proliferation, clonogenic assays, and overall survival. We also compared Dicer in tissue from patients diagnosed with melanoma in different stages with the prognosis of these patients, suggesting that the reduction in Dicer expression is associated with melanoma progression. Considering the fundamental and multiple biologic roles of Dicer in various cellular processes, our results suggest that modulation of Dicer in melanoma should become a promising therapeutic candidate for further clinical application. Note: This abstract was not presented at the conference. Citation Format: Nathalia Cruz de Victo, Sandy Adjemian, Romulo dos Santos Sobreira Nunes, Rildo Aparecido Volpini, Mara Huffenbaecher Giavina-Bianchi, Cyro Festa Neto, Niels Olsen Saraiva Câmara, Gustavo Pessini Amarante-Mendes, Jacqueline de Fátima Jacysyn. Role of Dicer on human melanoma progression and resistance [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B59.