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      Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior Translated title: Glycosphingolipid expression in squamous cell carcinoma of the upper aerodigestive tract

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          Abstract

          Os glicoesfingolipídios (GSLs) são importantes componentes da membrana celular, organizados em microdomínios, relacionados a receptores de membrana e comportamento anti-social da célula neoplásica como crescimento descontrolado, invasão e ocorrência de metástases. OBJETIVO: Como a expressão de GSLs no carcinoma espinocelular (CEC) é tema pouquíssimo estudado decidiu-se realizar estudo prospectivo visando avaliar a expressão de GSLs no CEC do trato aerodigestivo superior. MÉTODO: Coletou-se 33 amostras de CEC e mucosa normal e GSLs extraídos e purificados por cromatografia de fase reversa em coluna de C-18 e hidrólise alcalina em metanol. Os GSLs foram quantificados por densitometria das placas de cromatografia de alta resolução em camada delgada coradas com orcinol. RESULTADOS: Observou-se aumento significativo de GSLs no CEC (3,57µg/mg) em comparação à mucosa normal (1,92µg/mg), principalmente do monosialogangliosídeo (GM3), trihexosilceramida (CTH), dihexosilceramida (CDH), globosídeo (Gb4). A expressão de monohexosilceramida (CMH) foi semelhante no CEC e na mucosa normal. O aumento do GM3 no CEC foi demonstrado por métodos imunoquímicos empregando-se MAb DH2 (anti-GM3). Analisando-se os carboidratos do CMH por cromatografia gasosa acoplado a espectrômetro de massa constatou-se que a mucosa normal expressa glucosilceramida e o CEC glucosilceramida e galactosilceramida. CONCLUSÃO: O aumento de GSLs no tecido tumoral pode representar alterações dos microdomínios da membrana celular resultantes do processo de transformação maligna, responsáveis por uma maior interação célula-célula e célula-matriz aumentando seu potencial de infiltração e metástase, possibilitando o emprego dos GSLs e de MAbs no diagnóstico e no tratamento do CEC, a exemplo do que ocorre no melanoma.

          Translated abstract

          Glycosphingolipids are integral constituents of cellular membrane, arranged in rafts, and with neoplasic cell anti-social behavior, like uncontrolled cell growth, invasiveness, and metastatic potential. AIM: However, there are few studies about glycosphingolipids (GSL) expression in squamous cell carcinoma (SCC). Since GSL are known to be tumor-associated markers we decided to perform a prospective study on the GSL profiles of SCC. METHOD: Specimens of 33 SCC and normal mucosa were obtained and GSLs were extracted and purified by reverse-phase chromatography on C18 column and alkaline hydrolysis in methanol. GSLs were quantified using densitometry of orcinol-stained HPTLC plates. RESULT: A significant increase of GSLs in SCC (3.57µg/mg) was observed as compared to normal mucosa (1.92µg/mg). In SCC, an increase of 2 to 3 times in the amounts of CDH, CTH, Globoside, and GM3 was observed in comparison to normal mucosa. The identification of GM3 as well as its increased expression in SCC was confirmed unequivocally by HPTLC immunostaining and indirect immunofluorescence using MAb DH2 (anti-GM3). BY analyzing SCC and normal mucosa CMHs by GC/MS, normal mucosa expresses only glucosylceramide whereas SCC cells express both glucosylceramide and galactosylceramide. CONCLUSION: The increase in the amount of GSLs in tumor tissue may represent changes of cell membrane microdomains resulting from the malignant transformation process, which is responsible for greater cell-cell or cell-matrix interaction thereby increasing their potential for infiltration and metastasis.

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          Most cited references31

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          Glycosylation defining cancer malignancy: new wine in an old bottle.

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            Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer.

            Mucin glycoproteins are major secretory products of the colon and contain O-linked oligosaccharides synthesized on a polypeptide backbone. The initial step in the synthesis of O-linked oligosaccharides is the addition of N-acetylgalactosamine to serine or threonine residues forming the Tn antigen. This substance can then receive additional carbohydrate residues such as sialic acid to form sialosyl-Tn antigen, or galactose to form T antigen. In the colon, the T antigen is an oncodevelopmental cancer-associated antigen but little is known about Tn and sialosyl-Tn expression. The present comparative immunohistochemical study was performed to analyze the expression of these antigens in fetal, normal adult, and malignant colorectal tissues with an aim toward elucidating whether Tn and sialosyl-Tn are also oncodevelopmental colon cancer-associated antigens and to gain insight into the earliest steps of mucin glycosylation in colonocytes. We used three reagents to detect Tn antigen (two monoclonal antibodies ETn1.01 and CU-1, and one lectin Vicia villosa), two reagents to detect sialosyl-Tn (monoclonal antibodies TKH2 and B72.3) and one to detect T antigen (monoclonal antibody AH9-16). Except for occasional reactivity with VVA and CU-1, cells of normal colonic mucosa did not express Tn, sialosyl-Tn, or T antigens. However, in the transitional mucosa immediately adjacent to cancer, all three antigens were expressed (ranging from 35 to 67% of cases depending upon the reagent). In colon cancers, the percentage of cases expressing each antigen were as follows: Tn 72-81%, sialosyl-Tn 93-96%, and T 71%. Unlike T antigen, which was preferentially expressed by moderately well- and well-differentiated adenocarcinomas, both Tn and sialosyl-Tn antigens were expressed by most histological subsets of colon cancers, including poorly differentiated adenocarcinomas and mucinous (colloid and signet ring cell type) carcinomas. The majority of cancers expressed both Tn and sialosyl-Tn, usually in association with T antigen. Only one cancer lacked all three antigens. Fetal colonic mucosal cells expressed all three antigens, particularly in goblet cell mucin. These results indicate that like T antigen, Tn and sialosyl-Tn are oncodevelopmental cancer-associated antigens in the colon. Moreover, Tn and sialosyl-Tn antigens appear to be useful markers of poorly differentiated adenocarcinomas and mucinous carcinomas: two histological subsets that often fail to express other cancer-associated antigens and that are often associated with a poor clinical outcome.(ABSTRACT TRUNCATED AT 400 WORDS)
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              Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control.

              The ability to metabolise carcinogens or pro-carcinogens, repair DNA damage, and control cell signalling and the cell cycle are fundamental to homeostasis. Oral squamous cell carcinoma (oral cancer) and many squamous cell carcinomas of the head and neck (SCCHN) may, under appropriate exposure to mutagens, arise if these mechanisms are defective. SCCHN arise as a consequence of multiple molecular events induced by the effects of various carcinogens from habits such as tobacco use, influenced by environmental factors, possibly viruses in some instances, against a background of heritable resistance or susceptibility. Consequent genetic damage affects many chromosomes and genes, and it is the accumulation of these changes that appears to lead to carcinoma in some instances, sometimes via a clinically evident pre-malignant, or potentially malignant, lesion. Although lifestyle factors play a prominent role in aetiology, some patients appear susceptible because of an inherited trait in their ability or inability to metabolise carcinogens or pro-carcinogens, possibly along with an impaired ability to repair the DNA damage. This is the first of a series of three papers reviewing the advances in the understanding of this area of research since our last review [Scully C, Field JK. Genetic aberrations in squamous cell carcinoma of the head and neck (SCCHN), with reference to oral carcinoma (Review). Int J Oncol 1977;10:5-21] and discusses mainly oral carcinoma in the context of SCCHN.
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                Author and article information

                Journal
                rboto
                Revista Brasileira de Otorrinolaringologia
                Rev. Bras. Otorrinolaringol.
                ABORL-CCF Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial (São Paulo, SP, Brazil )
                0034-7299
                February 2006
                : 72
                : 1
                : 25-31
                Affiliations
                [05] orgnameUniversidade Federal de São Paulo orgdiv1Escola Paulista de Medicina orgdiv2Departamento de Bioquímica
                [03] orgnameUSP orgdiv1Faculdade de Medicina
                [02] orgnameSanta Casa de Misericórdia de Itabuna orgdiv1Serviço de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço
                [04] orgnameUniversidade Federal de São Paulo orgdiv1Departamento de Bioquímica
                [01] orgnameUniversidade Federal de São Paulo
                Article
                S0034-72992006000100005 S0034-7299(06)07200105
                10.1590/S0034-72992006000100005
                a3f4faed-c6f2-4579-98d3-ac7f1563b107

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 06 September 2005
                : 06 September 2005
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 31, Pages: 7
                Product

                SciELO Brazil

                Categories
                Artigos Originais

                neoplasias de cabeça e pescoço,carcinoma de células escamosas,glicoesfingolipídios,head and neck neoplasms,gangliosides,squamous cell carcinoma,glycosphingolipids,gangliosídeos

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