Navegando por Palavras-chave "metastatic melanoma"
Agora exibindo 1 - 4 de 4
Resultados por página
Opções de Ordenação
- ItemSomente MetadadadosAvaliação da heterogeneidade intratumoral e intermetástases do éxon 15 do gene braf (7q34) em amostras de melanoma metastático(Universidade Federal de São Paulo (UNIFESP), 2015-06-05) Guimaraes, Daiane Pereira [UNIFESP]; Landman, Gilles Landman [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Approximately a half of cutaneous melanoma has a BRAF V600E mutation and benefits from treatment with BRAF and MEK inhibitors, showing rapid tumor regression. However, most of these patients had progression of disease within 6 to 12 months after initiation of treatment. The intratumoral heterogeneity has been demonstrated and may contribute to the failure to treatment and drug resistance and may have important consequences to personalized cancer therapy Objective: To study the heterogeneity of mutations in genes belonging to the MAPK pathway in metastatic melanoma, in different areas of the same tumor and among tumors of the same patient. Methods: Analysis of mutations in exon 15 of BRAF, by Sanger sequencing, in metastatic melanoma paraffin samples stored in the Department of Pathology, from 1996 to 2012. Results: 86 samples of metastatic melanoma were analyzed from 54 patients. 17 (31.5%) patients had at least one mutation in exon 15 and ten patients (18.5%) had V600E mutation. 22.2% (12) of the cases, at least one sample presented intratumoral heterogeneity related to the expression of exon 15. When just codon V600 was observed, 7 (13%) patients had at least one sample with intratumoral heterogeneity related to V600E mutation. Twelve (22.2%) patients had at least two samples of metastasis and among them, nine (75%) was exon 15 mutaded and all of them presented both intratumoral and intermetastatic heterogeneity. Conclusion: Intratumoral and intermetastatic heterogeneity of the expression of exon 15 of BRAF was observed in metastatic melanoma samples.
- ItemAcesso aberto (Open Access)Blockade of MIF-CD74 Signalling on Macrophages and Dendritic Cells Restores the Antitumour Immune Response Against Metastatic Melanoma(Frontiers Media Sa, 2018) Figueiredo, Carlos Rogerio [UNIFESP]; Azevedo, Ricardo Alexandre de [UNIFESP]; Mousdell, Sasha; Resende-Lara, Pedro T.; Ireland, Lucy; Santos, Almudena; Girola, Natalia [UNIFESP]; Cunha, Rodrigo L. O. R.; Schmid, Michael C.; Polonelli, Luciano; Travassos, Luiz Rodolpho [UNIFESP]; Mielgo, AinhoaMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. While immunotherapies have shown a remarkable success in melanoma treatment, patients develop resistance by mechanisms that include the establishment of an immune suppressive tumor microenvironment. Thus, understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that macrophages (MOs) and dendritic cells (DCs) are suppressed in metastatic melanoma and that the Ig-CDR-based peptide C36L1 is able to restore MOs and DCs' antitumorigenic and immunogenic functions and to inhibit metastatic growth in lungs. Specifically, C36L1 treatment is able to repolarize M2-like immunosuppressive MOs into M1-like antitumorigenic MOs, and increase the number of immunogenic DCs, and activated cytotoxic T cells, while reducing the number of regulatory T cells and monocytic myeloid-derived suppressor cells in metastatic lungs. Mechanistically, we find that C36L1 directly binds to the MIF receptor CD74 which is expressed on MOs and DCs, disturbing CD74 structural dynamics and inhibiting MIF signaling on these cells. Interfering with MIF-CD74 signaling on MOs and DCs leads to a decrease in the expression of immunosuppressive factors from MOs and an increase in the capacity of DCs to activate cytotoxic T cells. Our findings suggest that interfering with MIF-CD74 immunosuppressive signaling in MOs and DCs, using peptide-based immunotherapy can restore the antitumor immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the antitumor immune response in metastatic melanoma.
- ItemSomente MetadadadosInhibition of melanoma metastasis by dual-peptlde PLGA NPS(Wiley, 2017) Arruda, Denise Costa; de Oliveira, Thais Dolzany; Fukuda Cursino, Patricia Harume [UNIFESP]; Carneiro Maia, Vera Susana; Berzaghi, Rodrigo [UNIFESP]; Travassos, Luiz R. [UNIFESP]; Tada, Dayane Batista [UNIFESP]Despite the positive results observed in vitro and in vivo, clinical trials with bioactive peptides are generally hampered by their fast degradation in the biological system. Two bioactive peptides, P20 (CSSRTMHHC and the combined peptide C (CVNHPAFACGYGHTMYYHHYQHHL) have been identified as anticancer therapeutics. Combined peptide C consists of peptide C (CVNHPAFAC), a tumor-homing peptide, conjugated to the antiangiogenic peptide HTMYYHHYQHHL with a GYG. In this work, PLGA NPs with peptide C were applied as a dual-peptide carrier for application in cancer therapy. Peptide P20 was loaded into the NPs and combined peptide C was conjugated to the NPs surface. These NPs were evaluated as a therapeutic system to treat metastatic melanoma. in vivo assays showed that P20 encapsulation in PLGA NPs enhanced its antitumor activity. The inhibitory activity of P20-PLGANPs was similar to the activity of non-encapsulated P20 in a dose fivefold higher. The inhibitory activity was even higher when P20PLGA NPs were functionalized with combined peptide C. P20PLGAPepC NPs reduced in 28% the number of lung nodules in a syngeneic model of metastatic melanoma as compared to untreated animals. Additionally to the better tumor targeting and the in situ release of P20, it is expected that the therapeutic efficiency of the dual-peptide PLGA NPs was further enhanced by a synergistic effect between P20 and combined peptide C. Our encouraging results showed that by enabling the co-delivery of two peptides and promoting tumor targeting, PLGA NPs coupled with peptide C is a promising platform for peptide-based cancer therapy.
- ItemSomente MetadadadosMetastatic melanoma positively influences pregnancy outcome in a mouse model: could a deadly tumor support embryo life?(Springer, 2008-03-01) Bollos, Rubens Harb [UNIFESP]; Nakamura, Mary Uchiyama [UNIFESP]; Valero-Lapchick, Valderez Bastos [UNIFESP]; Bevilacqua, Estela Maris Andrade Forell; Correa, Mariangela [UNIFESP]; Daher, Silvia [UNIFESP]; Ishigai, Marcia Marcelino de Souza [UNIFESP]; Jasiulionis, Miriam Galvonas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)The incidence of melanoma is increasing worldwide. It is one of the leading cancers in pregnancy and the most common malignancy to metastasize to placenta and fetus. There are no publications about experimental models of melanoma and pregnancy. We propose a new experimental murine model to study the effects of melanoma on pregnancy and its metastatic process. We tested several doses of melanoma cells until we arrived at the optimal dose, which produced tumor growth and allowed animal survival to the end of pregnancy. Two control groups were used: control (C) and stress control (SC) and three different routes of inoculation: intravenous (IV), intraperitoneal (IP) and subcutaneous (SC). All the fetuses and placentas were examined macroscopically and microscopically. the results suggest that melanoma is a risk factor for intrauterine growth restriction but does not affect placental weight. When inoculated by the SC route, the tumor grew only in the site of implantation. the IP route produced peritoneal tumoral growth and also ovarian and uterine metastases in 60% of the cases. the IV route produced pulmonary tumors. No placental or fetal metastases were obtained, regardless of the inoculation route. the injection of melanoma cells by any route did not increase the rate of fetal resorptions. Surprisingly, animals in the IV groups had no resorptions and a significantly higher number of fetuses. This finding may indicate that tumoral factors released in the host organism to favor tumor survival may also have a pro-gestational action and consequently improve the reproductive performance of these animals.