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3.
BMC Med Genomics ; 3: 14, 2010 May 04.
Article in English | MEDLINE | ID: mdl-20441585

ABSTRACT

BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.


Subject(s)
Gene Expression Regulation, Neoplastic , Mouth Neoplasms/metabolism , Proteome/metabolism , Annexin A5/metabolism , Apoptosis , Cell Proliferation , Down-Regulation , Electrophoresis, Gel, Two-Dimensional , Fibroblasts/metabolism , Genomics , Hep G2 Cells , Humans , Keratins/metabolism , Mouth Neoplasms/genetics , Nucleic Acid Hybridization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Stromal Cells/metabolism , Vimentin/metabolism
4.
Histopathology ; 53(6): 715-27, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19076685

ABSTRACT

AIMS: Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. METHODS AND RESULTS: Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. CONCLUSIONS: ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.


Subject(s)
Annexin A1/metabolism , Carcinoma, Squamous Cell/metabolism , Laryngeal Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Annexin A1/analysis , Annexin A1/genetics , Blotting, Western , Carcinoma, Squamous Cell/pathology , Female , Gene Expression , Humans , Immunohistochemistry , Laryngeal Neoplasms/pathology , Male , Middle Aged
5.
Rev Assoc Med Bras (1992) ; 47(3): 208-14, 2001.
Article in Portuguese | MEDLINE | ID: mdl-11723500

ABSTRACT

BACKGROUND: Squamous cell carcinoma (SCC) of the oral cavity occurs mainly in the male population. The objective of the study is to identify the main clinical and epidemiological differences of the oral SCC between men and women. METHODS: Retrospective analysis of the charts of 228 cases of SCC of the oral cavity in women treated at the Head & Neck Surgery Service, Heliopolis Hospital, São Paulo, Brazil from 1977 to 1996. The clinical and epidemiological characteristics of these cases were compared with those of 849 male patients. RESULTS: The mean age of women was 60.7 years (ranging 2 to 100 years) and in the male group was 55.6 years (p<0.00001). In cases where the alcohol intake and tobacco use were absent, the tumors ocurred in older patients. The isolated tobacco use didn't affect the distribuction by age but for the alcohol intake (alone or combined with tobacco) the patients were younger. On the alcohol intake, 71% of the women and 8% of the man used no alcohol. The most common sites of tumors were tongue and floor of the mouth but in the women group the incidence of tumors in these sites were 43% compared with 61% in the men. CONCLUSIONS: The highest incidence of SCC the of oral cavity occurs later in women, than in men. This could be explained by a lesser exposure to alcohol and tobacco in women. Other factors seem to be involved in this issue.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Mouth Neoplasms/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Alcoholism/complications , Brazil/epidemiology , Carcinoma, Squamous Cell/etiology , Child , Child, Preschool , Female , Humans , Incidence , Male , Middle Aged , Mouth Neoplasms/etiology , Retrospective Studies , Risk Factors , Sex Distribution , Smoking/adverse effects
6.
Rev. Assoc. Med. Bras. (1992) ; 47(3): 208-214, jul.-set. 2001. tab
Article in Portuguese | LILACS, Sec. Est. Saúde SP | ID: lil-306102

ABSTRACT

OBJETIVO: Este trabalho tem como objetivo identificar as principais diferenças clínico-epidemiológicas do carcinoma epidermóide de cavidade oral no sexo feminino quando comparado ao sexo masculino. MÉTODOS: Foram estudados retrospectivamente os prontuários de 228 pacientes do sexo feminino portadoras de carcinoma epidermóide de cavidade oral, atendidos no Serviço de Cirurgia de Cabeça e Pescoço do Hospital Heliópolis, no período entre 1977 e 1996. As características clínico-epidemiológicas destas pacientes foram comparadas com aquelas de 849 pacientes do sexo masculino. RESULTADOS: A idade das pacientes das mulheres variou de 2 a 100 anos, com uma média de 60,7 anos. Nos homens encontramos idade entre 17 e 88 anos com uma média de 55,6 (p<0,00001). Quando o etilismo e o tabagismo estavam ausentes, a incidência do carcinoma epidermóide de boca ocorreu em uma faixa etária mais tardia. A presença do tabaco isoladamente näo afetou a distribuiçäo por faixa etária, enquanto que o álcool isoladamente ou em associaçäo com o tabaco leva a uma incidência mais precoce do câncer de boca. Os dois principais sítios de incidência säo a língua e o soalho. As mulheres têm uma menor incidência de lesöes de língua e soalho (43 por cento) quando comparado aos homens (61 por cento). Aproximadamente 50 por cento das mulheres eram estadio III e IV no momento do diagnóstico. Entre os homens este índice atinge 53 por cento. CONCLUSÖES: O carcinoma epidermóide de cavidade oral nas mulheres tem características clínico-epidemiológicas peculiares que justificam o desenvolvimento de protocolos de diagnóstico e tratamento específico para ele


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Mouth Neoplasms , Carcinoma, Squamous Cell , Aged, 80 and over , Brazil , Mouth Neoplasms , Carcinoma, Squamous Cell , Smoking , Incidence , Retrospective Studies , Risk Factors , Sex Distribution , Age Distribution , Alcoholism
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