Repositório Institucional - Unifesp :: Navegando por Palavras-chave "melanoma"

Navegando por Palavras-chave "melanoma"

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AC-1001 H3 CDR peptide induces apoptosis and signs of autophagy in vitro and exhibits antimetastatic activity in a syngeneic melanoma model
(Wiley, 2016) Rabaca, Aline N. [UNIFESP]; Arruda, Denise C. [UNIFESP]; Figueiredo, Carlos R. [UNIFESP]; Massaoka, Mariana H. [UNIFESP]; Farias, Camyla F. [UNIFESP]; Tada, Dayane B. [UNIFESP]; Maia, Vera C.; Silva Junior, Pedro I.; Girola, Natalia [UNIFESP]; Real, Fernando [UNIFESP]; Mortara, Renato A. [UNIFESP]; Polonelli, Luciano; Travassos, Luiz R. [UNIFESP]
Antibody-derived peptides modulate functions of the immune system and are a source of anti-infective and antitumor substances. Recent studies have shown that they comprise amino acid sequences of immunoglobulin complementarity-determining regions, but also fragments of constant regions. V-H CDR3 of murine mAb AC-1001 displays antimetastatic activities using B16F10-Nex2 murine melanoma cells in a syngeneic model. The peptide was cytotoxic in vitro in murine and human melanoma cells inducing reactive oxygen species (ROS) and apoptosis by the intrinsic pathway. Signs of autophagy were also suggested by the increased expression of LC3/LC3II and Beclin 1 and by ultrastructural evidence. AC-1001 H3 bound to both G- and F-actin and inhibited tumor cell migration. These results are important evidence of the antitumor activity of Ig CDR-derived peptides.
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Antagonista do receptor b1 de bradicinina inibe a nefrotoxicidade induzida por cisplatina em modelo de melanoma murino
(Universidade Federal de São Paulo (UNIFESP), 2015-12-31) Monteiro, Ana Paula Fernandes da Silva [UNIFESP]; Keller, Alexandre de Castro Keller [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
A cisplatina ainda é um dos tratamentos mais utilizados contra diferentes tumores sólidos, sendo seu uso limitado pela nefrotoxicidade e o risco do desenvolvimento de lesão renal aguda (LRA). Tendo em vista que o receptor de bradicinina B1R já foi associado tanto com a nefrotoxicidade pela cisplatina quanto com o controle da agressividade de tumores, nosso objetivo foi estudar a influência do seu antagonista Lys-(Des-Arg9,Leu8)-bradykinin (LDALBK) em um modelo experimental de quimioterapia com cisplatina. No modelo clássico de LRA por cisplatina, o pré-condicionamento dos animais com LDALBK inibiu tanto a morte das células tubulares quanto a expressão, no tecido renal, de moléculas pró-inflamatórias como o TNF-?, preservando a função renal dos animais. Essa mesma abordagem durante um protocolo de quimioterapia, em animais inoculados com o melanoma murino B16F10, foi capaz de inibir a nefrotoxicidade inerente à cisplatina sem influenciar sua atividade antineoplásica. O tratamento com cisplatina estabilizou o crescimento tumoral, inibindo tanto a mitose celular quanto a formação de vasos, sendo esse mesmo fenômeno observado nos animais pré-condicionados com LDALBK, mostrando que o antagonismo do receptor B1R não influencia o controle tumoral pela quimioterapia. Além da nefrotoxicidade, a cisplatina também age sobre o sistema imunológico, sendo associada com o desenvolvimento de um quadro de imunossupressão. Nesse sentido, observamos que o pré-condicionamento dos animais com o LDALBK preserva a capacidade dos linfócitos T e dos macrófagos de responder in vitro a estimulação via TCR e receptor TLR-4. Portanto, nossos dados indicam que o antagonismo do receptor B1R durante um protocolo de quimioterapia pode ser uma alternativa para melhorar o prognóstico do tratamento.
Acesso aberto (Open Access)
Antifungal and antitumor models of bioactive protective peptides
(Academia Brasileira de Ciências, 2009-09-01) Rodrigues, Elaine Guadelupe [UNIFESP]; Dobroff, Andrey Sergee [UNIFESP]; Taborda, Carlos Pelleschi [UNIFESP]; Travassos, Luiz Rodolpho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
Peptides are remarkably reactive molecules produced by a great variety of species and able to display a number of functions in uni-and multicellular organisms as mediators, agonists and regulating substances. Some of them exert cytotoxic effects on cells other than those that produced them, and may have a role in controlling subpopulations and protecting certain species or cell types. Presently, we focus on antifungal and antitumor peptides and discuss a few models in which specific sequences and structures exerted direct inhibitory effects or stimulated a protective immune response. The killer peptide, deduced from an antiidiotypic antibody, with several antimicrobial activities and other Ig-derived peptides with cytotoxic activities including antitumor effects, are models studied in vitro and in vivo. Peptide 10 from gp43 of P. brasiliensis (P10) and the vaccine perspective against paracoccidioidomycosis is another topic illustrating the protective effect in vivo against a pathogenic fungus. The cationic antimicrobial peptides with antitumor activities are mostly reviewed here. Local treatment of murine melanoma by the peptide gomesin is another model studied at the Experimental Oncology Unit of UNIFESP.
Acesso aberto (Open Access)
Avaliação da aplicação de complexos de ferro-fenantrolina em terapia fotodinâmica de câncer de melanoma metastático
(Universidade Federal de São Paulo, 2023-01-09) Plaça, Alex Rodrigues [UNIFESP]; Campos, Hugo de Braga [UNIFESP]; Tada, Dayane Bastista [UNIFESP]; http://lattes.cnpq.br/2894306023783490; http://lattes.cnpq.br/7925606825143497; http://lattes.cnpq.br/5716495210309125
A terapia fotodinâmica (TFD) surgiu como uma vantajosa alternativa para o tratamento de câncer e infecções ao usar fotossensibilizadores para causar danos menos severos nas células e tecidos saudáveis. Apesar de diversos fotossensibilizadores terem sido desenvolvidos nas últimas décadas em busca de maior eficiência e menores efeitos colaterais, a grande maioria ainda atua por mecanismos dependentes de oxigênio. Esse fator configura em uma das principais limitações para o avanço translacional da TFD uma vez que em muitos tecidos o transporte de oxigênio é limitado ou se torna limitado após as primeiras sessões de tratamento. Desta forma, a concentração de oxigênio no local tornar-se insuficiente para garantir o sucesso do tratamento. Recentemente, complexos de ferro-fenantrolina foram apontados como eficientes fotossensibilizadores responsáveis por causar lise em DNA bacteriano sob irradiação UV ainda que na ausência de oxigênio. Assim, o presente projeto propõe a avaliação da fotoatividade dos complexos de ferro fenantrolínicos, Fe(Phen)3 e seu derivado organocalcogênio Fe(TDZP)3, em células tumorais de melanoma metastático B16-F10Nex2 sob diferentes condições como comprimento de onda da luz de irradiação, dose de luz e concentração de complexo. O complexo Fe(TDZP)3 teve maior fotoatividade e atingiu o maior efeito citotóxico na concentração de 17,5 μM sob irradiação de comprimento de onda de 254 nm por 10 min com irradiância de 0,053 W/cm2. Acredita-se que o comprimento de onda de 254 nm forma preferencialmente radicais independentes de oxigênio com maior tempo de vida concomitantemente a produção de radicais via dependente de oxigênio – com os radicais superóxidos que possuem um tempo de vida longo produzidos em maior quantidade – classificando o complexo Fe(TDZP)3 como um potencial candidato para aplicação na TFD.
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Avaliação 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.
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Avaliação do anticorpo monoclonal g12f2 para reação de imuno-histoquímica do melanoma murino b16f10
(Universidade Federal de São Paulo (UNIFESP), 2015-02-25) Grillo, Carlos Alberto [UNIFESP]; Lopes, Jose Daniel Lopes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
In 2006, at the Department of Microbiology, Immunology and Parasitology of Federal University of São Paulo - UNIFESP, was developed a new monoclonal antibody (mAb), type IgM, designated G12F2, which recognized a single band of approximately 230 kDa in total protein extract of melanoma murine B16F10. Interactions between antigenantibody represent the reaction principle of immunohistochemistry (IHC) performed in the laboratory. Therefore, the capacity of monoclonal antibody G12F2 to recognize a molecule of murine melanoma B16F10 can help the study and diagnosis of murine melanoma by IHC reaction. Objectives: Evaluation of the efficiency of monoclonal antibody G12F2 in the IHC reaction to identify the melanoma murine B16F10. Materials and Methods: The monoclonal antibody G12F2 was studied by IHC reaction in 02 groups of female mice C57BL6. Initially, B16F10 cells were maintained in culture and used to induce the melanoma in vivo. A group of five mice received subcutaneous injection of B16F10 cells in the left flank, in order to induce subcutaneous nodule. Another group of five mice received intravenous injection of B16F10 cells in the tail, in order to induce pulmonary metastases. After 15 to 21 days, skin and pulmonary tissues containing tumor nodules, as well as lymph node with tumor cells were collected for IHC analysis. Samples were collected, fixed and forwarded to the pathology laboratory. Blocks of paraffin containing the samples were stained by hematoxylin and eosin (HE) and after evaluated by IHC. Immunohistochemical reactions were performed in accordance with procedures previously established at the Department of Pathology for use of the monoclonal antibody G12F2. Results: All mice (n = 10) developed melanoma after injection of B16F10 cells; which 5 mice developed subcutaneous nodule in the left flank and 5 mice developed pulmonary nodules. Also was collected a subcutaneous lymph node with metastasis. After the procedures of fixation, preparation of the paraffin block and stained with HE, slides containing samples of nodules were used in the IHC reaction using monoclonal antibody G12F2. Positive reaction was observed by brown staining in the cell membrane of tumor cells present in subcutaneous and pulmonary nodules and lymph node containing B16F10 cells. However, monoclonal antibody G12F2 also labeled other non-tumor tissues as: normal alveolar epithelium, subcutaneous and adipose tissues and the secretory portion of the sebaceous gland. There was no labeling in lymphoid tissue, blood vessels wall, bronchi, melanocytes or other components of the epidermis and basal membrane. This fact shows that the cell membrane protein recognized by the monoclonal antibody G12F2 in B16F10 cells, is also present on the cell membrane of non-tumor tissues. Conclusion: Due to the fact of monoclonal antibody G12F2 recognize an antigen present in the cell membrane not only of B16F10 murine melanoma cells, but also in pulmonary alveoli, adipocytes and sebaceous glands, it is possible to conclude that this antibody is not a melanoma specific marker and as recommended for using with other tumor markers, both positive labeling and morphological analysis are necessary to definitive diagnosis of melanoma
Acesso aberto (Open Access)
Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma
(Nature Publishing Group, 2016) Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles [UNIFESP]; Soares de Sa, Bianca Costa; Rezze, Gisele Gargantini; Facure, Luciana; Ribeiro de Avila, Alexandre Leon; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, Joao Pedreira; Grazziotin, Thais C.; Bonamigo, Renan R.; Rey, Maria Carolina W.; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Borges, Alejandra Larre; Barquet, Virginia; Perez, Javiera; Martinez, Miguel; Cabo, Horacio; Sabban, Emilia Cohen; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C.; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia
Purpose: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. Methods: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Results: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. Conclusion: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first-or second-degree relatives.
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Cyclopalladated compounds containing 2,6-dimethylpyridine: Synthesis and cytotoxicity against human melanoma cell lines
(Springer, 2017) Netto, Adelino V. G.; Cunha, Gislaine A.; Mauro, Antonio E.; Garcia, Daniel M. [UNIFESP]; Spindola, Daniel G. [UNIFESP]; Michelin, Luis F.G. [UNIFESP]; Bincoletto, Claudia [UNIFESP]; Deflon, Victor
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Depression and quality of life during treatment of ocular bulb removal in individuals with uveal melanoma
(Wiley-Blackwell, 2010-07-01) Amaro, T. A. C. [UNIFESP]; Yazigi, L. [UNIFESP]; Erwenne, C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
The objective of this study is to asses the emotional repercussions in individuals with uveal melanoma referred for surgery, during the diagnosis and preoperative, post-surgery and late post-surgery phases. the clinical qualitative assessment used the Beck Depression Inventory and the Medical Outcomes Study 36-Item Short-Form Health Survey. Twenty patients were individually assessed, 13 men and 7 women, with an average age of 52. Before surgery, patients appeared fragile and impacted by the diagnosis and treatment, showing a minimum to mild state of depression and a quality of life affected by emotional and physical concepts. Three months after surgery, the patients showed a mild to severe state of depression. This depression had an effect on the physical, vitality, emotional, mental health and social life concepts, the emotional concept being the most affected. One year after the surgery, patients presented a minimum state of depression and quality of life had most health concepts in balance. It was concluded that the worst moment for the patient is 3 months after the surgery, when they appear more fragile with difficulties of adaptation, anxiety and depression. One year after the surgery, they appear more structured and with a more balanced quality of life.
Acesso aberto (Open Access)
Dermatoscopia na pele negra: estudo comparativo dos nevos melanocíticos adquiridos em pacientes com fototipos v e vi versus i e ii
(Universidade Federal de São Paulo (UNIFESP), 2015-03-31) Tuma, Bruna [UNIFESP]; Hirata, Sergio Henrique [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
BLACKGROUND: The identification of "normal" dermoscopic pattern of acquired melanocytic nevi (AMN) provides a better diagnostic accuracy of melanoma in people with black skin. OBJECTIVE: Describe melanocytic lesions (number and anatomical distribution) in skin types V and VI (ST V/VI) compared to skin types I and II (ST I/II) according to Fitzpatrick's classification. Identify differences in dermoscopic findings of acquired melanocytic nevi (global pattern, pigment and color distribution) between the groups. METHODS: Cross-sectional, prospective and consecutive data collection in two dermatological outpatient clinic, between October 8, 2010, and March 20, 2013. From the 501 volunteers, 480 participants fullfilled the eligibility criteria. A total of 460 acquired melanocytic nevi were selected for dermoscopy analysis. RESULTS: The individuals with ST V/VI had less melanocytic lesions than those with ST I/II (15,08 vs 7,90, p=0,032), and the anatomical distribution in the first group was predominantly in the face and acral sites (p<0,001). The AMN in the group ST V/VI were associated with reticular pattern (p<0.0001), tendency to central hyperpigmentation (p=0.0025). LIMITATIONS: Choice of a single representative nevus per patient. CONCLUSION: The AMN in the individuals with ST V/VI has a distinct dermoscopic pattern from those with ST I/II.
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Dermoscopic examination of the nail bed and matrix
(Blackwell Publishing, 2006-01-01) Hirata, Sergio Henrique [UNIFESP]; Yamada, S. [UNIFESP]; Almeida, F. A. [UNIFESP]; Enokihara, Mauro Y. [UNIFESP]; Rosa, I. P.; Enokihara, Milvia MS [UNIFESP]; Michalany, Nilceo S. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Background Dermoscopy has furthered advances in the differential diagnosis of longitudinal melanonychia; however, fewer details observed in the nail, as compared to skin lesions, make interpretation difficult.Methods Ten cases of longitudinal melancholia, from several etiologies, were submitted to direct dermoscopic examination of the nail bed and matrix.Results We observed the presence of globules, streaks, and pigment network in the nail bed and matrix, which are dermoscopic features not seen in the nail plate.Conclusions This procedure enables visualization of dermascopic features not seen in the nail plate, making the diagnosis of melanocytic lesions easier.
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Determinação de vias de sinalização ativadas por timp1 ao longo da genese do melanoma
(Universidade Federal de São Paulo (UNIFESP), 2015-07-31) Pinto, Mariana Toricelli [UNIFESP]; Leon, Miriam Galvonas Jasiulionis Leon [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Embora o melanoma maligno seja o câncer de pele menos incidente, ele é o que apresenta pior prognóstico, sendo que esta característica está relacionada ao seu alto poder de formar metástases e por ser altamente quimioresistente. Em nosso laboratório, foi desenvolvido um modelo linear de gênese do melanoma, que nos permite estudar diferentes etapas da progressão do melanoma. Melanócitos murinos melana foram submetidos a 1, 2, 3 e 4 ciclos de impedimento de adesão ao substrato e estas células apresentaram morfologia diferente e crescimento independente de PMA e foram chamadas de 1C, 2C, 3C e 4C, respectivamente. Diferentes linhagens de melanoma foram estabelecidas após submeter esferóides dos pelo bloqueio de adesão da linhagem 4C à diluição limitante (entre elas, células de melanoma não metastático 4C11- e células de melanoma metastático 4C11+). Uma das características de células transformadas é a resistência ao anoikis e esta característica está relacionada à formação de metástases. Dados prévios do nosso grupo mostraram aumento da expressão de Timp1 nas células derivadas dos bloqueios de ancoragem dos melanócitos melan-a. O aumento de expressão de Timp1 nestas células está correlacionado com a resistência ao anoikis. Embora tenha sido demonstrada a interação de CD63, Timp1 e ?1-integrinas somente em células de melanoma em nosso modelo, o mecanismo de sinalização envolvido nesse processo ainda não está claro. Portanto, neste trabalho analisamos o papel de Timp1 na progressão do melanoma e as vias de sinalização envolvidas no processo de resistência ao anoikis. Através da análise dos resultados, podemos concluir que Timp1 modula a via de sinalização PI3K. Essa modulação parece ser através de PDK1 nas linhagens de melanoma 4C11- e 4C11+. Essa modulação confere, ao longo da progressão maligna, maior resistência ao anoikis e fenótipo mais agressivo in vivo na linhagem de melanoma metastático 4C11+. Assim, o presente trabalho contribui com o entendimento de como Timp1 regula resistência ao anoikis ao longo da transformação maligna de melanócitos.
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Enzyme and integrin expression by high and low metastatic melanoma cell lines
(Lippincott Williams & Wilkins, 2003-02-01) Staquicini, F. I.; Moreira, C. R.; Nascimento, F. D.; Tersariol, ILS; Nader, H. B.; Dietrich, C. P.; Lopes, J. D.; Universidade Federal de São Paulo (UNIFESP); Univ Mogi Cruzes
Dissemination of a malignant tumour is the result of a cascade of events beginning with detachment of cells from primary tumour followed by extravasation and growth at secondary sites. the differences in metastatic ability could be attributed to properties intrinsic to the various tumour types. Thus the clonal selection of tumour cells from successive metastases apparently results in cells better equipped for survival and formation of colonies in secondary sites, indicating that survival is not a random phenomenon. Many studies of malignant cells have correlated the overexpression of adhesion receptors such as integrins and the production of cysteine proteases and glycosidases with the progression of malignancy. the interaction of cysteine proteases with basement membrane components has been implicated in tumour invasion, activation of hormones and growth factors. On the other hand, the expression of the heparanase gene and its protein has been associated with the metastatic potential of several human and mouse tumour cell lines. This study aimed to investigate the correlations between the metastatic properties of clones with high and low metastatic potential and their ability to adhere to the extracellular matrix and to degrade proteins and sulphated glycosaminoglycans present there. Clonal selection of the B16F10 cell line was performed, and the clones were examined for the expression of an integrin-type laminin receptor. A significantly higher level was detected in a high metastatic clone. Enzymatic assays showed higher activity for alpha-D-N-acetylglucosaminidase, beta-D-N-acetylgalactosaminidase and beta-D-glucuronidase in conditioned medium from low metastatic clones compared with that from high metastatic clones. However, higher endopeptidase activity was observed in conditioned medium from high metastatic clones. in summary, these results showed a positive correlation between high metastatic potential and endopeptidase secretion. Similarly, a positive correlation was observed between low metastatic cells and the secretion of glycosaminoglycan-degrading glycosidases.
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Evaluation of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: Results from the International Melanoma Pathology Study Group
(Mosby-Elsevier, 2016) Lott, Jason P.; Elmore, Joann G.; Zhao, Ge A.; Knezevich, Stevan R.; Frederick, Paul D.; Reisch, Lisa M.; Chu, Emily Y.; Cook, Martin G.; Duncan, Lyn M.; Elenitsas, Rosalie; Gerami, Pedram; Landman, Gilles [UNIFESP]; Lowe, Lori; Messina, Jane L.; Mihm, Martin C.; van den Oord, Joost J.; Rabkin, Michael S.; Schmidt, Birgitta; Shea, Christopher R.; Yun, Sook Jung; Xu, George X.; Piepkorn, Michael W.; Elder, David E.; Barnhill, Raymond L.
Background: Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. Objective: We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. Methods: Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. Results: Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. Limitations: This was a small sample size of experienced pathologists in a testing situation. Conclusion: Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care.
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Expressão e regulação epigenética de y-sinucleina e seu papel na progressão do melanoma
(Universidade Federal de São Paulo (UNIFESP), 2013-02-27) Monteiro, Ana Carolina [UNIFESP]; Leon, Miriam Galvonas Jasiulionis Leon [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Epigenética é o estudo de padrões de expressão gênica transmitidos que não incluem alterações na sequência de nucleotídeos do DNA. Trata-se de um mecanismo essencial para a preservação da identidade celular. Os mecanismos epigenéticos mais estudados são a metilação do DNA e modificações em histonas. O estabelecimento de padrões epigenéticos aberrantes está relacionado com diversas patologias, incluindo o câncer. A correlação positiva entre a superexpressão do gene da γ-sinucleína humana (SNCG) e o aumento de proliferação celular, invasão e metástase tem sido observada em estágios avançados de diversos tipos de tumores. Assim, a proteína γ-sinucleína apresenta-se como potencial indicador de agressividade. Um dos cânceres mais agressivos, de alta incidência mundial e que possui poucos tratamentos eficientes disponíveis é o melanoma metastático, que resulta na mortalidade de cerca de 90% dos pacientes. Até o momento não há dados sobre o papel biológico de γ-sinucleína em melanomas. Neste estudo observamos a superexpressão do transcrito e da proteína γ-sinucleína na linhagem murina de melanoma metastático 4C11+ em comparação com as linhagens melan-a (melanócitos imortalizados, porém não tumorigênicos), 4C (melanócitos pré-malignos) e 4C11- (melanoma não-metastático). O tratamento do DNA genômico com bissulfito de sódio seguido por sequenciamento nos permitiu observar a desmetilação do éxon 1 do gene murino Sncg na linhagem de melanoma metastático 4C11+ em relação às demais linhagens murinas. Nesse contexto, identificamos a desmetilação do DNA como potencial mecanismo da superexpressão do gene Sncg e marcador específico do estágio metastático. Esse achado correlacionou-se positivamente com o aumento da proteína γ-sinucleína, bem como com o fenótipo migratório, invasivo e metastático exibido pela linhagem de melanoma 4C11+. Elevada expressão de SNCG foi observada também em amostras de melanoma humano comparado a melanócitos primários. O presente estudo demonstra a regulação epigenética do gene Sncg, além de sugerir o papel da γ-sinucleína na progressão do melanoma, o que deverá ser confirmado futuramente por estudos de knockdown.
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Incidence of Melanocytic Lesions of the Conjunctiva in a Review of 10 675 Ophthalmic Specimens
(Sage Publications Inc, 2010-02-01) Novais, Gustavo A.; Fernandes, Bruno F.; Belfort, Rubens N. [UNIFESP]; Castiglione, Enzo; Cheema, Devinder P.; Burnier, Miguel N.; McGill Univ; Henry C Witelson Ocular Pathol Lab; Universidade Federal de São Paulo (UNIFESP)
During the study period, 10 675 human ophthalmic specimens were received at the Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University, Montreal, Canada. of those, 271 were conjunctival lesions (2.5%), with 101 being classified as melanocytic: 50 (49.5%) nevi, 36 (35.6%) primary acquired melanoses, and 15 (14.9%) melanomas. After exclusion of referred cases, 85 lesions were included in the study: 44 (51.7%) nevi, 33 (38.8%) primary acquired melanoses, and 8 (9.4%) melanomas. the most prevalent location was the bulbar conjunctiva. Conjunctival melanomas were most commonly found in an older age group than primary acquired melanosis or nevi. Conjunctival nevi were subdivided into compound (32.9%), subepithelial (16.4%), and junctional (2.3%). Primary acquired melanosis were further classified into primary acquired melanosis with atypia (8.2%) and primary acquired melanosis without atypia (30.5%). Primary acquired melanoses was the predisposing lesion in 75% of the cases of melanoma. in our sample, referral bias could alter the distribution of conjunctival pigmented lesions, with a shift toward the malignant end.
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Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth
(Wiley-Blackwell, 2007-01-01) Jasiulionis, Miriam G.; Luchessi, Augusto D.; Moreira, Andreia G.; Souza, Pedro P. C.; Suenaga, Ana P. M.; Correa, Mariangeta; Costa, Carlos A. S.; Curi, Rui; Costa-Neto, Claudio M.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); UNESP
The eukaryotic translation initiation factor 5A (eIF5A) undergoes a specific post-translational modification called hypusination. This modification is required for the functionality of this protein. the compound N1-guanyl-1,7-diaminoheptane (GC7) is a potent and selective inhibitor of deoxyhypusine synthase, which catalyses the first step of eIF5A hypusination process. in the present study, the effects of GC7 on cell death were investigated using two cell lines: melan-a murine melanocytes and Tm5 murine melanoma. in vitro treatment with GC7 increased by 3-fold the number of cells presenting DNA fragmentation in Tm5 cells. Exposure to GC7 also decreased viability to both cell lines. This study also describes, for the first time, the in vivo antitumour effect of GC7, as indicated by impaired melanoma growth in C57BL/6 mice. Copyright (c) 2006 John Wiley & Sons, Ltd.
Somente Metadadados
Investigação da expressão dos marcadores de células tronco em linhagem celular de melanoma murino e sua reprogramação em células pluripotentes induzidas
(Universidade Federal de São Paulo (UNIFESP), 2015-02-26) Camara, Diana Aparecida Dias [UNIFESP]; Kerkis, Irina Kerkis [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Malignant melanoma is a heterogeneous tumor that originates from melanocytes that have suffered genetic and epigenetic mutations. Some studies have shown reversal of the phenotype of human metastatic melanoma cells at the embryonic microenvironment via a cellular reprogramming. The use of reprogramming is a good starting point, which can significantly contribute to the understanding of the main molecular mechanism related to the pathogenesis of this aggressive tumor and develop new biological strategies based on anticancer therapies. Objective: The objectives of this paper were to study the expression of stem cell markers in a murine melanoma cell line and establish a model for studying the possible cellular mechanisms of loss of malignancy through reprogramming of tumor cells in ?normal? IPS. Materials and Methods: Seven clones were isolated using the limiting dilution assay from the cell line B16F10. These clones were characterized by flow cytometry with surface markers (CD271, CD146 and CD44, CD24) by qPCR for pluripotency markers. Cell cycle analysis was performed and some proteins were analyzed by Western blot, such as cyclin D and cyclin DNMT1. Each clone was tested for the UFC, sphere formation and tumorigenic ability in vivo. The individual sensitivity of each clone and the parent strain in the presence of antitumor drugs was evaluated in vitro. One clone was chosen and transfection was performed using circular plasmid DNA containing -2 Sox genes, Oct4, Nanog, Lin28 and GFP. Results: the clones showed different patterns of cell proliferation, expression of surface markers, tumorigenicity, metastatic capacity and drug resistance. This heterogeneous and divergent character between clones occurred spontaneously under the same culture conditions showing tumor plasticity. Clone 7, which was used for the reprogramming assays, obtained high efficiency in transfection when compared to the fibroblasts used for control, however reprogramming showed low efficiency as evidenced by the appearance of a small number of colonies morphologically similar to melanospheres. Conclusions: We conclude that heterogeneity is an intrinsic characteristic of melanomas that contributes to the wide phenotypic diversity found in these tumors. An interesting way to modulate this phenomenon is the reprogramming of these tumor cells and the verification of what it entails in terms of expression of tumor markers and also of CTT.
Acesso aberto (Open Access)
Linfonodo sentinela em melanoma de criança: relato de caso
(Sociedade Brasileira de Pediatria, 2002-10-01) Oliveira Filho, Renato Santos de [UNIFESP]; Paiva, Geruza Rezende; Ferreira, Lydia Masako [UNIFESP]; Alves, Marcos Chaves de Arruda [UNIFESP]; Santos, Ivan Dunshee de Abranches Oliveira [UNIFESP]; Enokihara, Mílvia Maria Simões e Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Objective: to present a case of a child who was subjected to sentinel lymph node biopsy for cutaneous melanoma. Description: a 12 year-old child with Dysplastic Nevus Syndrome developed melanoma on the lumbar region. The excision biopsy revealed a melanoma with depth of 1.5 mm. The patient was submitted to amplification of the margins 2 cm in all directions and the sentinel node was also excised. The histopathological exam did not show residual disease. Sentinel on exam did not show metastases either under hematoxylin-eosin stain or immunohistochemistry (S-100 and HMB45). Therefore, RT-PCR for tyrosinase mRNA was positive. The patient has been followed for twelve months without evidence of recurrence. Comments: childhood melanoma is rare, corresponding to less than 1% of malignant tumors in children. Data point to a worldwide increase in its incidence. Melanoma occurs in melanocytic lesions in 70% and in the remaining 30% it occurs de novo. Melanoma is very aggressive, so the survival depends on an early diagnosis. Sentinel lymph node biopsy has selected patients to complete lymphadenectomy. Some authors have been using this technique in childhood melanoma.
Acesso aberto (Open Access)
Manifestações sistêmicas adversas em medicina intensiva após realização de perfusão isolada de membro com melfalan e hipertermia: relato de caso
(Associação de Medicina Intensiva Brasileira - AMIB, 2006-12-01) Arruda, Fernando Oetterer [UNIFESP]; Guimarães, Hélio Penna [UNIFESP]; Falcão, Luiz Fernando dos Reis [UNIFESP]; Leal, Patrícia Helena Rocha [UNIFESP]; Lopes, Renato Delascio [UNIFESP]; Santos, Ivan Dunshee de Abranches Oliveira [UNIFESP]; Amaral, José Luiz Gomes do [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
BACKGROUND AND OBJECTIVES: The presence of adverse reactions, inherent to all treatments, justifies the necessity of deep knowledge, by the medical team of the prevention and treatment of occasional organic dysfunctions, reducing its impact. The purpose of this paper is to report a case comprising the several systemic adverse reactions after perfusion of limb with melphalan and hyperthermia. CASE REPORT: A white female, 64-years old patient with diagnosis of melanoma in the medial malleoli region of the left lower limb. Six months after surgical removal of wound, an isolated perfusion of limb was carried out with melphalan and hyperthermia in order to curb the possible metastatic process in evolution. At admission in the ICU, the patient presented systemic inflammatory response syndrome (SIRS) with refractary hemodynamic instability to volemic expansion. During internation the patient evolved to acute lung edema and myocardial dysfunction, all reverted successfully. CONCLUSIONS: The potential presence of adverse reactions, inherent to all treatments, justify the necessity of knowledge by the intensive care team in the prevention and treatment of occasional organic dysfunctions, reducing the impact of morbidity and mortality.

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