Reduced Apaf-1 expression in human cutaneous melanomas

Malignant melanoma is a life-threatening skin cancer due to its highly metastatic character and resistance to radio- and chemotherapy. It is believed that the ability to evade apoptosis is the key mechanism for the rapid growth of cancer cells. However, the exact mechanism for failure in the apoptotic pathway in melanoma cells is unclear. p53, the most frequently mutated tumour suppressor gene in human cancers, is a key apoptosis inducer. However, p53 mutation is only found in 15–20% of melanoma biopsies. Recently, it was found that Apaf-1, a downstream target of p53, is inactivated in metastatic melanoma. Specifically, loss of heterozygosity (LOH) of the Apaf-1 gene was found in 40% of metastatic melanoma. To determine if loss of Apaf-1 expression is indeed involved in melanoma progression, we employed the tissue microarray technology and examined Apaf-1 expression in 70 human primary malignant melanoma biopsies by immunohistochemistry. Our data showed that Apaf-1 expression is significantly reduced in melanoma cells compared with normal nevi (χ2=6.02, P=0.014). Our results also revealed that loss of Apaf-1 was not associated with the tumour thickness, ulceration or subtype, patient's gender, age and 5-year survival. In addition, our in vitro apoptosis assay revealed that overexpression of Apaf-1 can sensitise melanoma cells to anticancer drug treatment. Taken together, our data indicate that Apaf-1 expression is significantly reduced in human melanoma and that Apaf-1 may serve as a therapeutic target in melanoma

Garantia literária: elementos para uma revisão crítica após um século

This study contributes to a critical synthesis of the principle of literary warrant, initially formulated by Hulme in 1911. Hulme proposed that the terms of a classification system should be derived from the literature to be classified, rather than based on purely theoretical considerations. Founding literary warrant on literature which is actually documented rather than on scientific or philosophical classifications or on the supposed authority of the first classificationists implied a clear departure from the conceptions of Harris and Dewey, who had used the classifications of Bacon and Leibniz as models. The validity of this principle over the past century is studied by means of diverse documental data (entries in dictionaries, retrieval by Google, etc.), as it is recognized as a main methodological element for classification standards and systems. This study also discusses the situation with respect to the top-down or bottom-up methodologies of system design. Three traditional applications of literary warrant are described as well as three new applications are suggested, in light of its methodological potential. It is possible to conclude that this principle will find increasing applications in other contexts, within and beyond Information Science.Univ Estadual Paulista, Dept Ciência Informação, BR-17525900 Marilia, SP, BrazilUniv Republica, Montevideo, UruguayUniv Granada, Fac Comunicacao & Documentacao, Granada, SpainUniv Estadual Paulista, Dept Ciência Informação, BR-17525900 Marilia, SP, Brazi

Ontogeny and postnatal persistence of a strong suppressor activity in man.

Abstract We report here on the ontogeny and postnatal persistence of an inhibited human immune response in which lymphocytes from human newborns strongly suppress the proliferation of adults' lymphocytes stimulated by phytohemagglutinin (PHA) or alloantigens in vitro. For this research we used a 2-way mixed lymphocyte culture (MLC) supplemented with PHA, with sex chromosomes acting as markers for dividing male and female cells, or alternatively a double chamber system. The proliferation of maternal lymphocytes was significantly suppressed by fetal lymphoid cells from the liver as early as the 8th week of gestation and by those from fetal blood at the 14th week or later during gestation. This strong suppressor activity persisted in 11-mo-old infants but usually disappeared after that time.</jats:p