Ana Bela Sarmento Ribeiro

Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine fused chlorins as very active photodynamic agents for melanoma cells.

The development of new stable 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins with high absorption properties at 650 nm, and their impressive photosensitizer ability against melanotic and amelanotic cancer cells is described. Comparison between a diester-substituted chlorin with the corresponding dihydroxymethyl derivative demonstrated that the increased hydrophilicity of the latter is crucial to ensure nanomolar activity against melanoma cells. The new photosensitizer leads to death of human melanoma cells being both apoptosis and necrosis in equal parts involved in the treatment response. The dihydroxymethyl-chlorin was particularly active against human melanocytic melanoma A375 cells, which can be viewed as a solution to overcome the resistance of melanotic melanoma to photodynamic therapy.

Microenvironment influence on human colon adenocarcinoma phenotypes and matrix metalloproteinase-2, p53 and β-catenin tumor expressions from identical monoclonal cell tumor in the orthotopic model in athymic nude rats

Abstract The present study aims to identify differences between left and right colon adenocarcinoma arising from identical clonal cell and to find out if microenvironment has any influence on matrix metalloproteinase-2 (MMP2), p53 and β-catenin tumor expressions. Material and methods. Rats (RNU) were submitted to cecostomy to obtain the orthotopic model of right colon tumor (n = 10), while for the left colon model (n = 10), a colon diversion and distal mucous fistula in the descending colon was used. Cultivated human colon adenocarcinoma cells (WiDr) were inoculated in stomas submucosa. Histopathological analysis, real-time reverse transcription-PCR for β-catenin, p53 and MMP2, as well as immunohistochemical analysis for p53 and β-catenin expression were conducted. Central tendency, variance analysis and the Livak delta-delta–CT method were used for statistical analysis, adopting a 5% significance level. Results. All tumors from the left colon exhibited infiltrative ulceration, while in the right colon tumor growth was predominantly exophytic (67%). In the left colon, tumor growth was undifferentiated (100%), while it was moderately differentiated in the right colon (83%). In right colon tumors, MMP2, p53, and β-catenin gene expressions were higher than compared to left colon (p = 4.59354E-05, p = 0.0035179, p = 0.00093798, respectively, for MMP2, p53 and β-catenin). β-catenin and p53 results obtained by real-time polymerase chain reaction were confirmed by immunohistochemistry assay (p = 0.01 and p = 0.001, respectively, for β-catenin and p53). Conclusion. Left and right human colon adenocarcinomas developed in animal models have distinct phenotypes even when they have the same clonal origin. Microenvironment has influenced p53, β-catenin, and MMP2 expression in animal models of colon cancer.

Modelos experimentais em oncologia: O contributo da cultura de células para o conhecimento da biologia do cancro

Resumo A cultura de tecidos surgiu no seculo xx (Harrison, 1907) para estudar o comportamento das celulas animais em ambiente homeostatico e em situacoes de stress. A capacidade de estudar as celulas a nivel molecular relaciona-se com a forma como as celulas podem crescer e ser manipuladas em laboratorio. A cultura de celulas in vitro permitiu estudar crescimento, diferenciacao e morte celular e efectuar manipulacoes geneticas necessarias ao perfeito conhecimento da estrutura e funcoes dos genes. A cultura de celulas estaminais humanas veio colmatar algumas limitacoes inerentes aos restantes modelos de cultura. Ao que parece, as celulas estaminais cancerigenas mantem-se quiescentes nos locais metastaticos ate serem activadas por sinais apropriados do microambiente. Varios estudos revelaram que diferentes tipos de cancros podem surgir da transformacao maligna de celulas estaminais. A eliminacao destas celulas progenitoras tumorais e essencial para o desenvolvimento de novas abordagens terapeuticas mais eficazes em cancros agressivos. Por outro lado, a utilizacao de celulas dendriticas modificadas em cultura podera contribuir para a producao de uma potencial vacina terapeutica eficaz para obter a regressao tumoral. Rev Port Pneumol 2009; XV (4): 669-682

Epithelial-mesenchymal transition and microRNAs: Challenges and future perspectives in oral cancer

Head and neck cancer is the sixth most common cancer worldwide, with oral squamous cell carcinoma (OSCC) being the most representative type. OSCC is a public health problem with high morbidity and poor survival rate. Epithelial‐mesenchymal transition is emerging as a hallmark in OSCC.