Summary Recently. apoptosis has been implicated as one of the end points of cells exposed to chemotherapeutic agents. The p53 and Bcl-2 family of proteins are involved in chemotherapy-induced apoptosis. but in a cell type-dependent manner. We sought to determine the roles played by the p53 and Bcl-2 family of proteins in 5-fluorouracil (5-FU)-induced apoptosis of human colon cancer cell lines. We first studied the p53 genetic and functional status, and then 5-FU, at inhibitory concentration of 50% (ICj)
in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer. © 1999 Cancer Research Campaign Keywords: COX-2; colon cancer; metastasis; apoptosis; MMP; selective COX-2 inhibitor 1274British Journal of Cancer (1999) 81(8), 1274-1279 © 1999 Cancer Research Campaign Article no. bjoc.1999 Received 3 November 1998 Revised 18 March 1999 Accepted 19 April 1999 Correspondence to: S Tomozawa Inhibition of colon cancer metastasis by a selective COX-2 inhibitor 1275
Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.
BackgroundSer-249 TP53 mutation (249Ser) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249Ser mutation in HCC from patients in Brazil.MethodsWe studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249Ser mutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR.Results249Ser mutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249Ser mutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249Ser mutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249Ser mutation (OR = 2.415, 95% CI = 1.001 – 5.824, p = 0.05). The mean size of 249Ser HCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249Ser mutation.ConclusionOur results indicate that 249Ser mutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.
INTRODuÇÃOO advento de novas tecnologias de saúde como fármacos (p.ex. imunobiológicos), equipamentos médicos (p.ex. grampeadores para cirurgia), exames diagnósticos, entre outros, causaram impacto nos indicadores clínicos e econômicos. Nesse cenário, a importância de estudos que conjuguem estes elementos provém não de justificativas acadêmicas ou políticas, mas sobretudo, da constatação de que os gastos com saúde vêm crescendo em ritmo acelerado, podendo afetar a sustentabilidade dos sistemas de saúde (17) .Em âmbito mundial, os sistemas de saúde, na tentativa de melhorar a eficiência, a expansão da oferta e cobertura, e incorporar novas tecnologias que sejam comprovadamente eficazes e seguras, vêm adotando estratégias de monitoramento e avaliação da assistência, utilizando-se de instrumentos oriundos da economia da saúde e da epidemiologia clinica (15) .Considerando o jargão técnico da área, a eficácia considera o benefício no contexto artificial dos experimentos clínicos, a efetividade diz respeito ao benefício observado no mundo real do dia-a-dia do indivíduo, enquanto a eficiência se refere ao benefício ponderado pelo custo frente às opções terapêuticas existentes.A eficiência avaliada pelo estudo de custo-efetividade é um instrumento de análise de valor das intervenções em saúde. O método busca preencher a lacuna existente entre as preferências (subjetividade) e a ciência (objetividade, validade, reprodutibilidade). Nesse contexto, o conceito de "valor" deve ser compreendido numa concepção ampla, referindo-se às preferências que um indivíduo ou sociedade apresentam face a escolhas mutuamente excludentes, não apenas a quantia em dinheiro trocada na aquisição de bens ou serviços. Traduzir valor para uma dimensão apenas financeira não constitui bom caminho para as sociedades e muito menos para as ações de saúde. Oscar Wilde, no século XIV já mencionava: "O que é um cínico? Um homem que conhece o preço de qualquer coisa, mas não sabe o valor de nada". Em contrapartida, não se pode deixar de considerar que o custo das novas tecnologias tem que ser gerenciado, sob o risco de penalizar o próprio segmento e outras áreas de interesse social (8) .A seleção de uma opção terapêutica é problema cientifico e deve guiar-se pelo estado de arte e nível de conhecimento profissional, embora na tomada da decisão de utilização do uso de uma tecnologia estejam envolvidos aspectos políticos, sociais, éticos e mesmo culturais. E, hoje, os aspectos econômicos são absolutamente fundamentais. Ademais, à medida que a demanda no Sistema Único de Saúde (SUS) aumenta e os recursos tornam-se cada vez mais escassos, o próprio sistema de saúde, bem como os profissionais da saúde têm de reexaminar os benefícios e custos de suas ações para assegurar que haja uma implementação efetiva das intervenções (8) .Tendo em vista a importância de investigações acerca do "valor" das intervenções de saúde, da
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