TSPY is a cancer testis antigen expressed in human hepatocellular carcinoma

In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that the transcription of TSPY, ‘testis-specific protein Y-encoded', was upregulated in HCC. Investigation of a broad spectrum of normal and malignant tissues by RT–PCR revealed the TSPY transcript selectively expressed in normal testis, different histological types of human neoplastic tissues, and tumour cell lines. The expression of TSPY in cancer cells was further confirmed by in situ hybridisation. Indirect immunofluorescence microscopy analysis showed that TSPY was localised mainly in the cytoplasm of transiently transfected cells. Testis-specific protein Y-encoded was detected in 50% (16 of 32) of well- and moderately differentiated HCC patients, in 16% (four of 25) of poorly differentiated HCC patients, and in 5% (one of 19) of renal cell cancer patients. A serological survey revealed that 6.6% (seven of 106) HCC patients had anti-TSPY antibody response, demonstrating the immunogenicity of TSPY in humans. In conclusion, these data suggest that TSPY is a novel cancer/testis (CT) antigen and may be a potential candidate in vaccine strategy for immunotherapy in HCC patients

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Comparison of Bothropoides jararaca bites with and without envenoming treated at the Vital Brazil Hospital of the Butantan Institute, State of São Paulo, Brazil Comparação dos acidentes causados por Bothropoides jararaca com e sem envenenamento atendidos no Hospital Vital Brazil do Instituto Butantan, Estado de São Paulo

INTRODUCTION: This study analyses the cases of all bites (including dry bites) caused by Bothropoides jararaca attended at the Vital Brazil Hospital of the Butantan Institute, State of São Paulo, Brazil. METHODS: A retrospective study was conducted of patients bitten by Bothropoides jararaca (n=792) from January 1990 to December 2004. The characteristics of the snake specimen, data related to the accident and clinical manifestations on admission were obtained from patient medical records. RESULTS: The majority of the cases in this study were caused by female and juvenile snakes. No stomach contents were found in 93.4% of the snake specimens after dissection. No statistical difference was observed between the occurrence of dry bites and the maturity or sex of the snake. The median SVL of snakes in mild and moderate cases was 40.5cm and in severe cases, SVL increased to 99cm. Necrosis was more common in the digits of the feet and hands (4.8%) compared to the other body regions (1.8%). A significant difference was verified between severity and a time interval greater than six hours from the bite to hospital admission. A significant association was verified between gingival bleeding and abnormal blood coagulability. In accidents caused by adult snakes, necrosis was more frequent (7.2%) compared to accidents caused by juvenile snakes (1%). CONCLUSIONS: In this work, the association between certain epidemiological data and the evolution of biological parameters in the clinical course of Bothrops sensu latu accidents were highlighted, contributing to the improvement of snake bite assistance.<br>INTRODUÇÃO: Neste estudo, analisou-se todos os casos de picadas (incluindo picadas secas) causadas por Bothropoides jararaca atendidos no Hospital Vital Brazil do Instituto Butantan, São Paulo, Brasil. MÉTODOS: Estudo retrospectivo em que foram incluídos pacientes atendidos no Hospital Vital Brazil do Instituto Butantan, picados por serpentes da espécie Bothropoides jararaca (nº=792) entre 1990 a 2004. Os dados foram obtidos através de prontuários médicos. RESULTADOS: No presente estudo, a maioria dos acidentes foi causada por serpentes fêmeas e filhotes. Não havia presença de conteúdo estomacal em 93,4% das serpentes dissecadas. Não houve diferença estatística entre a ocorrência de picada seca e o sexo da serpente. O comprimento rostro cloacal das serpentes nos casos leves e moderados foram 40,5cm e nos casos severos 99cm. Necrose foi mais comum nos dedos dos pés e das mãos (4,8%) em comparação com outras regiões do corpo (1,8%). Houve diferença estatística entre a gravidade e o intervalo de tempo entre a picada e a admissão hospitalar superior a seis horas. Encontramos uma associação significativa entre gengivorragia e incoagulabilidade sanguínea. Nos acidentes causados por serpentes adultas, a necrose foi mais frequente (7,2%) quando comparado aos acidentes causados por serpentes filhotes (1%). CONCLUSÕES: Neste estudo, destaca-se a associação entre os dados epidemiológicos e biológicos em relação à evolução do quadro clínico nos acidentes botrópicos, contribuindo para a melhoria da assistência nos acidentes ofídicos

Loss of PTEN selectively desensitizes upstream IGF1 and insulin signaling

Many tumours have chronically elevated activity of PI 3-kinase dependent signalling pathways, caused largely by oncogenic mutation of PI 3-kinase itself or loss of the opposing tumour suppressor lipid phosphatase, PTEN. Several PI 3-kinase dependent feedback mechanisms have been identified that may affect the sensitivity of upstream receptor signalling, but the events required to initiate an inhibited state have not been addressed. We show that in a variety of cell types, loss of PTEN via experimental knockdown or in tumour cell lines correlates with a block in IGF1/insulin signalling, without affecting the sensitivity of PDGF or EGF signalling. These effects on IGF/insulin signalling include a reduction of up to five to ten fold in IGF stimulated PI 3-kinase activation, a failure to activate the ERK kinases, and in some cells, reduced expression of IRS1, and both IGF1 and insulin receptors. These data indicate that chronically elevated PI 3-kinase dependent signalling to the degree seen in many tumours causes a selective loss of sensitivity in IGF1/insulin signalling that could significantly reduce the selective advantage of deregulated activation of IGF1/IGF1-R signalling in tumour development